deamino-arginine-vasopressin and Pituitary-Neoplasms

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy.

Topics: Acute Disease; Adenoma; Adrenocorticotropic Hormone; Chronic Disease; Deamino Arginine Vasopressin; Gonadal Steroid Hormones; Gonadotropins, Pituitary; Hormone Replacement Therapy; Human Growth Hormone; Humans; Hydrocortisone; Hypophysectomy; Hypopituitarism; Pituitary Gland; Pituitary Hormones, Anterior; Pituitary Irradiation; Pituitary Neoplasms; Prolactin; Radiotherapy; Thyrotropin; Thyroxine; Vasopressins

The aim of this study was to review the literature published and the most important papers presented to meetings on Cushing's disease from October 2011 to September 2012. The selection has been performed according to the authors' criteria. Articles have been classified into five groups: quality of life and perception of the disease, clinical features and pathophysiology, comorbidity conditions, diagnosis, and treatment. The results and conclusions of each publication are discussed.

Topics: ACTH-Secreting Pituitary Adenoma; Deamino Arginine Vasopressin; Endomyocardial Fibrosis; Humans; Hyperglycemia; Hypertension; Hypoglycemic Agents; Hypophysectomy; Neoplasm Proteins; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prognosis; Quality of Life; Somatostatin; Thrombophilia

Diabetes insipidus (DI) is a common complication following pituitary surgery and can be transient or permanent. Neurogenic DI occurs following injury to the magnocellular neurons in the hypothalamus that produce and transport arginine vasopressin (AVP) and form the hypothalamo-hypophyseal tract. DI is defined by a constellation of signs and symptoms resulting in dilute high-volume urine output and increasing serum osmolality. The body's inability to concentrate urine leaves the patient dehydrated and leads to metabolic abnormalities that can be life threatening if not recognized and treated in a timely manner with an exogenous AVP analog. The reported incidence of postsurgical central DI varies from 1 to 67%. This wide range likely reflects inconsistencies in the working definition of DI across the literature. Factors affecting the rate of DI include pituitary tumor size, adherence to surrounding structures, surgical approach, and histopathology of pituitary lesion. The likelihood of postoperative DI can be reduced by careful preservation of the neurovascular structures of the hypothalamus, infundibulum, and neurohypophysis. Vigilance and meticulous surgical technique are essential to minimize injury to these critical regions that can lead to postsurgical DI.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Endoscopy; Humans; Microsurgery; Neurosurgical Procedures; Pituitary Gland; Pituitary Neoplasms; Postoperative Complications; Vasopressins

Because of the variability in the clinical expression of Cushing's syndrome, different biochemical tests and imaging techniques must be used for effective diagnosis and treatment. The clinical history is important to assess the general impact of hypercortisolism on organs and systems, as well as to guide suspicion toward more aggressive entities such as overt ectopic ACTH syndrome or to detect an iatrogenic etiology of Cushing's syndrome. The screening phase relies on tests that are sensitive but not specific, such as urinary free cortisol, nocturnal salivary cortisol and 1 mg dexamethasone suppression, which still require established assessment criteria. Confirmation can be obtained by repeating urinary cortisol, 2 mg/day dexamethasone suppression, both alone and combined with corticotropin releasing hormone (CRH), to exclude pseudoCushing states. ACTH dependency can be easily explored by ACTH measurements, but the differential diagnosis between pituitary and ectopic Cushing's disease is difficult and may require invasive procedures such as inferior petrosal sinus sampling. Sophisticated imaging and isotopic techniques play a significant role in locating the source of ACTH in ectopic syndromes but are not always effective. In general, biochemical and imaging tests should be combined in order to assess different mechanisms and perspectives of the syndrome. Rigorous methodology is essential to obtain accurate results, allowing a correct diagnosis and improving therapeutic performance in this devastating disease.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Circadian Rhythm; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Dexamethasone; Diagnosis, Differential; Diagnostic Imaging; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Petrosal Sinus Sampling; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Pituitary-Adrenal System; Saliva

We report an uncommon case of an intrasellar plasmacytoma presenting as a non-functional invasive pituitary macro-adenoma as the first manifestation of multiple myeloma. A 57 year old woman was referred to our department with a presumed diagnosis of a non-functioning pituitary macro-adenoma. She reported a 3 month history of headaches and a 2 week history of sudden onset of right facial numbness. Preoperative endocrine evaluation was remarkable only for a modestly elevated serum prolactin. A magnetic resonance imaging (MRI) scan revealed 3.6 x 5 x 4 cm enhancing homogeneous intrasellar mass with extension into the sphenoid and cavernous sinuses bilaterally; the optic chiasm was not displaced. She underwent transphenoidal surgery of the sellar lesion. The surgical specimen was heavily infiltrated with abnormal plasma cells, which stained almost exclusively for Kappa light chain immunoglobulins. An extensive investigation was undertaken to look for occult myelomatous disease. A diagnosis of multiple myeloma was made 1 month later based on a combination of clinical, pathological and radiologic features. She underwent radiation therapy directed towards the residual sellar tumor, followed by chemotherapy and autologous stem cell transplantation. Review of the world literature revealed only 22 previous reports of patients in whom a solitary plasmacytoma or multiple myeloma first presented as a sellar mass; in all cases mimicking clinically and radiologically a non-functioning invasive pituitary adenoma however with additional cranial nerve involvement. Intrasellar plasma cell tumors are rare tumors which may mimic non-functioning invasive pituitary tumors. The diagnosis should be suspected in patients with well preserved anterior pituitary function and cranial nerve neuropathies in the presence of significant sellar destruction.

Topics: Adenoma; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Female; Humans; Middle Aged; Pituitary Neoplasms; Plasmacytoma; Postoperative Complications; Treatment Outcome

Topics: ACTH Syndrome, Ectopic; Adrenal Cortex Function Tests; Adrenocorticotropic Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; Humans; Hydrocortisone; Pituitary ACTH Hypersecretion; Pituitary Neoplasms

Hypothermia has been demonstrated to induce pancytopenia in animals, but whether this association exists in humans is unknown. The authors report the case of an 8-year-old girl in whom hypothermia (temperature 33 degrees C-35 degrees C) is the cause of pancytopenia. The patient developed thermoregulatory dysfunction subsequent to surgical resection of a craniopharyngioma. Her recurrent cytopenias could not be explained by any etiology except chronic hypothermia. The pancytopenia improved upon rewarming the patient to a temperature of 36 degrees C. This association between hypothermia and pancytopenia has rarely been reported in humans and may be underdiagnosed especially in cases of transient or milder presentations. The authors recommend careful hematologic monitoring of patients with thermoregulatory dysfunction.

Topics: Adrenal Insufficiency; Blood Cell Count; Cerebral Infarction; Child; Chronic Disease; Consciousness Disorders; Craniopharyngioma; Deamino Arginine Vasopressin; Dehydration; Diabetes Insipidus; Female; Frontal Lobe; Humans; Hyponatremia; Hypophysectomy; Hypopituitarism; Hypothalamus; Hypothermia; Hypothyroidism; Pancreatitis; Pancytopenia; Pituitary Neoplasms; Postoperative Complications; Seizures; Sleep Stages

The diagnosis and differential diagnosis of Cushing's syndrome remains a considerable challenge in clinical endocrinology. Investigation is a two-step process, involving first diagnosis followed by differential diagnosis. Traditionally diagnosis has relied upon urinary free cortisol (UFC) collection, low-dose dexamethasone-testing, and assessment of midnight cortisol. More recently, differentiation between mild disease and pseudo-Cushing's states has been achieved using dexamethasone-suppressed corticotropin releasing hormone (CRH) and desmopressin tests. Refinements of tests used for differential diagnosis have been made including optimized response criteria for ovine and human sequence CRH tests, desmopressin tests, GHBP-testing and testing with combinations of peptides. Despite improvements in these non-invasive tests use of inferior petrosal or cavernous sinus sampling is frequently required. Imaging is guided by biochemical assessment. MRI is the investigation of choice for Cushing's disease, but is often negative. Scintigraphic investigation using radionucleotide-labeled agonists for receptors commonly expressed by neuroendocrine tumors the investigation of occult ACTH-dependent disease remains disappointing. In this review we critically analyze the tests used for this most challenging of clinical conditions.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Circadian Rhythm; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Dexamethasone; Diagnosis, Differential; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Magnetic Resonance Imaging; Oligopeptides; Petrosal Sinus Sampling; Pituitary Neoplasms; Pituitary-Adrenal System; Radiography; Radionuclide Imaging; Sheep

The development of transsphenoidal microsurgery and the refinement of endocrinological and radiological diagnostic procedures have afforded therapeutic options appropriate for each individual case in patients with pituitary-dependent hypercortisolism. Compared with other secreting pituitary tumors, the corticotroph adenoma seems to be the most biologically active tumor. Clinical evidence of hypercortisolism mainly occurs at an early stage of tumor growth when the tumor is very small, below the detection threshold of modern imaging techniques. While the treatment of large tumors remains difficult due to the non-discrete boundary lines of the tumor and extension or invasion, surgical removal of very tiny tumors requires reliable preoperative or peroperative identification in order to achieve total tumor resection for clinical remission and pituitary preservation to prevent hypopituitarism. We reviewed all the current surgical techniques or clever surgical procedures used to achieve both goals with the lowest complication rate. We report here the state-of-the-art of surgical management of corticotroph pituitary adenoma focusing on preoperative radiological and biological data required for performing guided intrasellar surgical exploration and reliable tumor identification. Different technical aspects of the nasosphenoidal approaches are reported as well as the modified transdiaphragmatic or transtubercular transcisternal approaches to tumors in a suprasellar localization or lying along the pituitary stalk. The advantages of minimally invasive surgical techniques such as intrasellar endoscopic surgery are discussed. Adapted surgical techniques for second transnasal surgery indicated for recurrent tumors are described. Guidelines are given for peroperative tumor identification with macroscopic assessment or histological control with frozen section biopsies. Different techniques for tumor removal are discussed from selective microadenomectomy to enlarged pituitary resection and total hypophysectomy. Methods for preoperative guidance of total tumor removal are proposed including histological or biological assessment of normal adjacent pituitary tissue. the strategy of surgical intrasellar exploration and tumor resection is outlined using a set of algorithms. The first is devoted to positive preoperative documentation of the tumor. The second is proposed for the surgical scenario where there is no preoperative MRI evidence of the tumor. Special strategies are dis

Topics: ACTH Syndrome, Ectopic; Adenoma; Adrenocorticotropic Hormone; Anti-Bacterial Agents; Cortisone; Cushing Syndrome; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnostic Imaging; Endoscopy; Humans; Hypophysectomy; Magnetic Resonance Imaging; Petrosal Sinus Sampling; Pituitary Neoplasms; Postoperative Complications; Premedication; Reoperation

Hyponatremia following acute or chronic central nervous system injury which is due to excessive Na+ loss in the urine without an increase in the body fluid, has been described as Cerebral Salt Wasting Syndrome (CSWS). This syndrome is often confused with dilutional hyponatremia secondary to inappropriate ADH secretion. Accurate diagnosis and management are mandatory for to improve the course of the disease. In this study a patient with CSW Syndrome is presented and the treatment and diagnosis of this syndrome are discussed in view of the literature.

Topics: Adenoma; Adult; Deamino Arginine Vasopressin; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Pituitary Neoplasms; Postoperative Complications; Saline Solution, Hypertonic; Sodium

We describe a case of spontaneous muscle necrosis of the anterior tibial compartment occurring in a patient who had a hypophysectomy for a craniopharyngioma five years previously. We know of no other reported cases of spontaneous muscle necrosis in association with diabetes insipidus and feel that there should be increased awareness of the association between the two.

Topics: Adult; Biopsy; Compartment Syndromes; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hypophysectomy; Leg; Male; Pituitary Neoplasms; Postoperative Complications

The authors describe several useful surgical techniques from our experiences in transsphenoidal microsurgery for pituitary adenomas. Intentional two-staged transsphenoidal removal with open sella floor and intrasellar drainage is available for most of giant adenomas with suprasellar extension. The open sella floor method and intrasellar drainage after first transsphenoidal adenomectomy accelerate to decrease the suprasellar tumor extension. In four of six patients in our series, macroscopically total selective adenomectomy was achieved by a second transsphenoidal operation without complications. As for extremely small microadenomas, represented in patients with Cushing's disease, stepwise systemic search is required to identify a subcortical microadenoma, preserving postoperative pituitary function. Edge resection around the microadenoma is also necessary for normalization of hormonal hypersecretion and permanent cure.

Topics: Adenoma; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hydrocortisone; Hypophysectomy; Pituitary Neoplasms; Postoperative Care; Vasopressins

A 57-year-old man with pituitary metastasis from renal cell carcinoma is reported. He underwent right nephrectomy and total pancreatectomy for renal cell carcinoma and its pancreatic metastasis, respectively. Imaging studies showed an intrasellar mass lesion. The examination revealed panhypopituitarism, diabetes insipidus and bitemporal hemianospia. Metastatic renal cell carcinoma was diagnosed by the biopsy of the pituitary tumor. Metastatic renal cell carcinoma to the pituitary gland, which is extremely rare, appears to have unique features of presenting with hypopituitarism and visual disturbance more frequently than other metastatic pituitary tumors.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Renal Cell; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hypopituitarism; Kidney Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Pancreatic Neoplasms; Pituitary Gland; Pituitary Neoplasms; Tomography, X-Ray Computed

Bilateral inferior petrosal sinus sampling (BIPSS) is a useful investigative technique in the differential diagnosis of ACTH-dependent Cushing's syndrome (CS). The diagnostic sensitivity of this procedure is improved by the administration of CRH to stimulate ACTH secretion. It has been reported recently that the combined administration of CRH and desmopressin is a more potent stimulus for ACTH release from corticotroph adenomas. We therefore hypothesized that the combined stimulation of ACTH secretion with CRH plus desmopressin may further improve the diagnostic outcome of this procedure.. To report our experience of the application of combined stimulation with CRH and desmopressin during BIPSS in patients with ACTH-dependent Cushing's syndrome, and to compare these results to those obtained in patients who have undergone BIPSS with CRH stimulation alone.. We studied 34 patients with ACTH-dependent CS: 30 with Cushing's disease (CD) and four with occult ectopic ACTH syndrome (oEAS). A combined stimulation with CRH (100 micrograms i.v.) plus desmopressin (10 micrograms i.v.) during BIPSS was performed in 15 patients with CD, while in a different group of 15 patients with CD, BIPSS was performed with CRH stimulation alone (100 micrograms i.v.). In the patients with oEAS, BIPSS was performed with CRH stimulation in three and CRH plus desmopressin in one patient.. In patients with CD the mean peak ACTH levels from the dominant petrosal sinus samples were significantly higher in the group given a combined stimulus than in the group who had only CRH stimulation (mean +/- SD: 1649 +/- 938 vs. 692 +/- 561 ng/l, P < 0. 05). Dominant inferior petrosal sinus/peripheral (IPS/P) ACTH ratios greater than 2 were observed in 15/15 (100%) patients following the combined stimulation with CRH and desmopressin and 13/15 (87%) patients undergoing stimulation with CRH alone. No patient with oEAS had an IPS/P ratio greater than 2. It is of note that the single patient with oEAS studied following a combined stimulation during BIPSS had a IPS/P ratio of less than 2, despite a significant peripheral ACTH and cortisol response.. A combined stimulus using CRH and desmopressin appears to induce a higher ACTH output from pituitary corticotroph adenomas during BIPSS, which may improve the diagnostic sensitivity of this procedure.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Biomarkers, Tumor; Chi-Square Distribution; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Petrosal Sinus Sampling; Pituitary Neoplasms; Sensitivity and Specificity; Statistics, Nonparametric

A challenge in clinical endocrinology is the distinction between Cushing's disease (Cushing's syndrome dependent by adrenocorticotrophic hormone (ACTH)-secreting tumours of pituitary origin) and alcohol-dependent pseudo-Cushing's syndrome. Patients with Cushing's disease are known to have high ACTH/cortisol responses to desmopressin (DDAVP, a vasopressin analogue) and to hexarelin (HEX, a synthetic GH-releasing peptide).. To compare the ACTH/cortisol responses to desmopressin and to hexarelin of subjects with alcohol pseudo-Cushing's syndrome with those obtained in patients with Cushing's disease and in normal controls.. Randomized, single-blind study.. University medical centre.. Eight alcoholics with pseudo-Cushing's syndrome, six patients with Cushing's disease and nine age-matched normal controls.. Three tests at weekly intervals. The dexamethasone (1 mg) suppression test (DST) was carried out first. The desmopressin (10 microg intravenously at 09:00 h) test and hexarelin (2 microgram kg-1 intravenously at 09:00 h) test were carried out in random order.. Plasma ACTH and cortisol levels.. The basal plasma levels of ACTH and cortisol were significantly lower in normal subjects than in patients with Cushing's disease and in alcoholic subjects; these latter groups showed similar basal hormonal values. All normal controls, two patients with Cushing's disease and two alcoholics showed suppression of plasma cortisol levels (<5 microgram dL-1) after dexamethasone administration. Both desmopressin and hexarelin induced striking ACTH/cortisol responses in patients with Cushing's disease, whereas hexarelin, but not desmopressin, slightly increased ACTH/cortisol secretion in the normal controls. Neither desmopressin nor hexarelin administration induced any significant change in ACTH/cortisol secretion in alcoholics.. These data suggest that either the hexarelin or desmopressin test can be used to differentiate patients with Cushing's disease from subjects with alcohol-dependent pseudo-Cushing's syndrome.

Topics: Adrenocorticotropic Hormone; Adult; Alcoholism; Cushing Syndrome; Deamino Arginine Vasopressin; Ethanol; Female; Humans; Hydrocortisone; Male; Oligopeptides; Pituitary Neoplasms; Radioimmunoassay; Single-Blind Method

To assess the ability of desmopressin to differentiate between pituitary and ectopic ACTH-dependent Cushing's syndrome and to determine whether diagnostic accuracy could be improved by administering it together with human sequence CRH, we examined its effects on cortisol and ACTH secretion when given alone or in combination with CRH in patients with Cushing's syndrome of varied etiology and compared these data to the results of a standard CRH test in the same individuals. Each patient was studied on three occasions, in random order, separated by at least 48 h. At 0900 h, via an indwelling forearm cannula, 10 micrograms desmopressin, 100 micrograms CRH, or a combination of the two were given as an iv bolus; thereafter, blood was drawn every 15 min for 2 h. The responses to the individual agents were determined according to the timing and calculation criteria suggested by Nieman et al. (1993). A total of 25 patients with Cushing's syndrome were studied: 17 patients with pituitary-dependent Cushing's syndrome, Cushing's disease (CD); 5 patients with occult ectopic ACTH secretion (EC); and 3 patients with primary adrenal (ACTH-independent) Cushing's syndrome. In this series, the best discrimination among ACTH-dependent patient groups was achieved using the combined test. Using the responses of plasma cortisol, all 17 patients with CD showed a rise greater than any of the 5 patients with EC, whereas 1 patient with CD showed a plasma ACTH response within the range seen in the patients with EC. Plasma cortisol responses to desmopressin alone were seen in 14 of 17 patients with CD and 1 of 5 patients with EC and, after CRH alone, in 15 of 17 patients with CD but in no patient with EC. In contrast, plasma ACTH responses after CRH alone were seen in 14 of 17 patients with CD and 2 of 5 patients with EC and, after desmopressin alone, in 12 of 17 with CD and 3 of 5 with EC, thus indicating overlapping responses between the groups and poorer discrimination. No responses were seen in the ACTH-independent group. These data indicate that desmopressin causes the secretion of ACTH and cortisol in patients with ACTH-dependent Cushing's syndrome, and that in combination with CRH, it may provide an improvement over the standard CRH test in the differential diagnosis of ACTH-dependent Cushing's syndrome. Furthermore, these data suggest that there may be abnormalities in vasopressin receptor function or number in ACTH-secreting tumors.

Topics: ACTH Syndrome, Ectopic; Adolescent; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Adult; Aged; Child; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Humans; Hydrocortisone; Male; Middle Aged; Pituitary Neoplasms

The vasopressin analog desmopressin (DDAVP) is known to enhance memory in animals and man but its precise mechanism of action is uncertain. We report the case of a patient who experienced chronic memory dysfunction with impaired job performance following transsphenoidal resection of a pituitary adenoma. A prospective double-blind, placebo-controlled trial of the effects of DDAVP was performed. Memory storage and recall improved with DDAVP treatment and declined within 1 week after drug withdrawal both by subjective and objective criteria. The Buschke Selective Reminding Test was clearly the most responsive out of a battery of standard memory testing paradigms employed to track the presence or absence of DDAVP treatment.

Topics: Adenoma; Adult; Deamino Arginine Vasopressin; Double-Blind Method; Female; Humans; Memory Disorders; Pituitary Neoplasms; Postoperative Complications; Prospective Studies

This single-center retrospective cohort study aimed to describe the findings and validity of Bilateral inferior petrosal sinus sampling (BIPSS) in the differential diagnosis of patients with ACTH-dependent Cushing's syndrome (CS).. Eleven patients underwent BIPSS due to equivocal biochemical tests and imaging results. Blood samples were taken from the right inferior petrosal sinus (IPS), left IPS, and a peripheral vein before and after stimulation with desmopressin (DDAVP). ACTH and prolactin levels were measured. The diagnosis was based on the ACTH ratio between the IPS and the peripheral vein. Also, lateralization of pituitary adenoma in patients with Cushing's disease (CD) was predicted. No significant complications were observed with BIPSS.. Based on the pathology report, eight patients had CD, and three had ectopic ACTH syndrome (EAS). Unstimulated BIPSS resulted in a sensitivity of 87.5%, specificity of 100%, PPV of 100%, NPV of 75%, and accuracy of 91%. Stimulated BIPSS resulted in a sensitivity of 100%, specificity of 100%, PPV of 100%, NPV of 100%, and accuracy of 100%. However, pituitary magnetic resonance imaging (MRI) had a lower diagnostic accuracy (sensitivity:62.5%, specificity:33%, PPV:71%, NPV:25%, accuracy:54%). BIPSS accurately demonstrated pituitary adenoma lateralization in 75% of patients with CD.. This study suggests that BIPSS may be a reliable and low-complication technique in evaluating patients with ACTH-dependent CS who had inconclusive imaging and biochemical test results. The diagnostic accuracy is improved by DDAVP stimulation. Pituitary adenoma lateralization can be predicted with the aid of BIPSS.

Topics: Adenoma; Adrenocorticotropic Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; Humans; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Retrospective Studies

Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively.. Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate.. The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%.. This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.

Topics: Child; Craniopharyngioma; Deamino Arginine Vasopressin; Hormone Replacement Therapy; Humans; Hydrocortisone; Hypothalamic Diseases; Neoplasm Recurrence, Local; Pituitary Diseases; Pituitary Neoplasms; Quality of Life; Retrospective Studies; Thyroxine

Endocrinopathy can occur as a postoperative sequel in children treated for supratentorial tumors (STTs). We assessed prediction of a residual hypothalamic/pituitary insufficiency (HPI) in these patients and factors associated with prolonged length of hospital stay (LOS).. This is a retrospective cohort study of children who had surgery for STTs in two tertiary centers in Saudi Arabia (2009-2019). We assessed PICU postoperative management and risk of HPI. Data were analyzed using SPSS V24.0 and a logistic regression model for a prediction of a prolonged LOS.. Data included 55 children (1-18 years, mean 9.5 ± 4.9 years) who required STT surgeries, 32 (54%) females. Craniopharyngioma (27.3%) was the commonest STTs and 20% of patients had initial symptoms of HPI. PICU management included the use of different types of intravenous fluids (IVFs) and medications such as steroids and desmopressin (DDAVP). An early postoperative DI was reported in 21.8% (n=12/55). Residual HPI included 24 (43.6%) presumed cortisol deficient and 18 (32.7%) central DI patients. Risk factors for postoperative HPI were female gender, age <6 years, headache and preoperative pituitary symptoms. LOS (Median=25.5 ± 12.2 days) was significantly prolonged in patients who required two or more doses of DDAVP [B=13; 95% CI= (1.7-24.3) days] and reduced in patients who had suspected preoperative HPI [B=-19.6; 95% CI= (-31.1, -8.2) days].. Prediction of postoperative HPI in pediatric STTs enhances an early initiation of treatment in PICU and reduces LOS. A meticulous use of IVF and medications supervised by a multidisciplinary team is essential for a favorable outcome.

Topics: Child, Preschool; Critical Care; Deamino Arginine Vasopressin; Female; Humans; Length of Stay; Male; Pituitary Diseases; Pituitary Neoplasms; Retrospective Studies; Supratentorial Neoplasms

Water and electrolyte disturbances are common after pituitary surgery and can generally be classified into transient hypotonic polyuria and transient or permanent diabetes insipidus (DI). The prevalence varies in the literature between 31-51% for transient hypotonic polyuria, 5.1-25.2% for transient DI, and 1-8.8% for permanent DI.. The aim of this study was to identify the prevalence of water and electrolyte disturbances with polyuria and the preoperative and postoperative predictive factors in patients undergoing surgery with an extended endoscopic endonasal approach.. The overall prevalence of water and electrolyte disorders was 30.5% (62), and the prevalence of postoperative polyuria was 23.6% (48). The median number of desmopressin doses administered to patients with postoperative polyuria was one dose (interquartile range [IQR] 1-2), and thus the median duration of treatment was 0 days. The median initiation of desmopressin was the second day after surgery (IQR 1-2). The overall prevalence of DI was 6.89%. Among the patients with transient DI, the duration was less than 3 months in three patients (1.47%), and between 3 and 6 months in two (0.98%). Nine patients had permanent DI (4.43%). (4.43%).. The prevalence of electrolyte disturbances in our study was high, although similar to that found in the literature. Most of the cases were transient hypotonic polyuria that resolved within one day. The prevalence of transient DI in our cohort was lower than that described in the literature, while permanent DI was similar.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Pituitary Neoplasms; Polyuria; Postoperative Complications; Retrospective Studies; Water-Electrolyte Imbalance

Differentiating the etiology of ACTH-dependent Cushing's syndrome (CS) has remained challenging due to the limited accuracy of noninvasive assays. Nowadays, bilateral inferior petrosal sinus sampling (BIPSS) with corticotropin-releasing hormone (CRH) is the gold standard method in the diagnostic work-up of complex CS. However, this method is as yet far from being widespread. The limited utility of this method could be due to many factors such as limited availability of an experienced interventionist, limited availability of CRH, and cost of the procedure. So far, very few studies have been conducted using desmopressin instead of CRH. In this study, we report the use of BIPSS with desmopressin as a diagnostic tool in a series of patients with suspected Cushing's disease (CD) and equivocal imaging in a tertiary referral center in Iran.. A total of 13 patients with ACTH-dependent CS and no significant lesions in their pituitary MRI participated in this retrospective case series. All patients underwent BIPSS with desmopressin, and, following centralization of CS, transsphenoidal surgery (TSS) was carried out and diagnosis of CD was confirmed using standard methods.. Of the 13 patients with confirmed CD (by pathology or biochemical response after surgery), eight (61.5%) were female, with a median age of 32 years (IQR: 26-41). The median duration of disease was 24 months (IQR: 11-48). During BIPSS, all patients had a central-to-peripheral gradient greater than 2 under basal conditions. This central-to-peripheral gradient did not increase to > 3 after desmopressin administration in two of these patients. Based on the gradient after BIPSS, the sensitivity of this modality in the diagnosis of CD was 100%. Eight of the 13 patients had right lateralization in both BIPSS and TSS; therefore, the accuracy rate of lateralization by BIPSS was 61.5%. No complications occurred after BIPSS, the exception being the development of groin hematoma in one patient.. No significant benefits of adding desmopressin to BIPSS were observed. The sensitivity of BIPSS in the diagnosis of CD was high, whereas it has moderate accuracy in tumor lateralization.

Topics: Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Female; Humans; Iran; Petrosal Sinus Sampling; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Retrospective Studies

Rathke's cleft cyst (RCC) is a common incidental tumor in the hypothalamic-pituitary region. Some reports have shown that the clinical symptoms and endocrine functions of symptomatic RCCs are temporarily improved by glucocorticoid administration. However, it is still unknown whether glucocorticoid treatment is effective for symptomatic RCCs according to long-term observations. In this study, we describe the long-term clinical outcomes of two cases of glucocorticoid-treated biopsy-proven secondary hypophysitis caused by RCCs. We summarize the symptoms, imaging findings, and endocrine evaluations of two symptomatic RCC patients with concomitant hypophysitis before and after prednisolone treatment. In both evaluated cases, visual impairments and altered endocrine parameters were present due to chiasm and stalk compression; these outcomes improved after shrinkage of RCCs in response to prednisolone administration, and partial recovery of anterior pituitary hormone secretion was observed. However, in both cases, the deficits in anterior pituitary hormone secretion recurred, possibly due to persistent inflammatory infiltration in the RCCs and pituitary glands. After relapse of hypophysitis, anterior hormone secretion did not fully recover. In our cases of secondary hypophysitis caused by RCCs, prednisolone administration had an early effect of cyst shrinkage, followed by partial improvements in clinical symptoms and pituitary functions. However, long-term observation showed that prednisolone treatment did not contribute to complete improvement in anterior pituitary hormone dysfunction.

Topics: Antidiuretic Agents; Central Nervous System Cysts; Deamino Arginine Vasopressin; Female; Glucocorticoids; Hormone Replacement Therapy; Humans; Hydrocortisone; Hypophysitis; Hypopituitarism; Middle Aged; Pituitary Neoplasms; Prednisolone

Diabetes insipidus (DI) develops commonly after endoscopic transsphenoidal surgery (ETS). We retrospectively investigated the incidence, onset, duration and predictors of DI after ETS in patients with non-functioning pituitary adenoma (NFPA).. A total of 168 patients who underwent ETS to remove NFPAs were included. Various perioperative data on demographics, comorbidities, previous treatments, perioperative hormone deficiencies, tumor characteristics, surgery, anesthesia, intraoperative fluid balance, perioperative laboratory findings, postoperative complications, readmission and hospital length of stay were collected and analyzed. Patients were diagnosed with DI and treated with desmopressin when they showed urine output > 5 mL/kg/hr with a serum sodium concentration > 145 mmol/L or an increase ≥ 3 mmol/L in serum sodium concentration between two consecutive tests after surgery. DI was considered permanent when desmopressin was prescribed for > 6 months after surgery.. Seventy-seven (45.8%) patients experienced postoperative DI and 10 (6.0%) patients suffered from permanent DI. The median onset of DI and the median duration of transient DI were postoperative day 1 and 5 days, respectively. In multivariable logistic regression analysis, cephalocaudal tumor diameter (odds ratio [95% confidence interval] 2.59 [1.05-6.36], P = 0.038) was related to postoperative DI. In receiver operating characteristic analysis, its area under the curve was 0.68 (95% confidence interval 0.59-0.76, P < 0.001). Its optimal cutoff value that maximized the sum of sensitivity and specificity for postoperative DI was 2.7 cm.. Postoperative DI was observed in 45.8% of patients undergoing ETS to remove NFPAs. A large cephalocaudal tumor diameter was predictive of postoperative DI in such patients.

Topics: Adenoma; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Mellitus; Humans; Pituitary Neoplasms; Postoperative Complications; Retrospective Studies; Sodium

Topics: Adult; Craniopharyngioma; Deamino Arginine Vasopressin; Drug Administration Schedule; Female; Humans; Hypernatremia; Hypopituitarism; Neurologic Examination; Pituitary Neoplasms; Postoperative Complications; Sodium; Substance Withdrawal Syndrome

We report the case of a pituitary stalk germinoma initially misdiagnosed and treated as infundibuloneurohypophysitis (INH). A 27-year-old man presented with a 1-year history of polydipsia, polyuria, nycturia consistent with central diabetes insipidus and a hyperintense pituitary stalk lesion on MRI. A possible INH diagnosis was considered, after excluding other pathologies. Lesion biopsy was discarded at that time on the ground of a small target and the high risk of added morbidity. Oral desmopressin led to initial symptoms resolution but, in the following months, an anterior panhypopituitarism developed, in spite of appropriate treatment and, by that time, the brain MRI also revealed lesion growth, which prompted a biopsy recommendation. The pathology analysis revealed a germinoma. After chemotherapy and radiotherapy, there was complete disappearance of the pituitary lesion, but the panhypopituitarism persisted. In conclusion, this case highlights the importance and difficulty of precise diagnosis in the initial assessment of pituitary stalk lesions and the need for close monitoring of treatment response. Diagnostic reassessment and biopsy in atypical cases is the only path to achieve the correct diagnosis and treatment.

Topics: Adult; Autoimmune Hypophysitis; Biopsy; Chemoradiotherapy; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Drug Monitoring; Germinoma; Hormone Replacement Therapy; Hormones; Humans; Hydrocortisone; Hypopituitarism; Magnetic Resonance Imaging; Male; Pituitary Gland; Pituitary Neoplasms; Thyroxine; Treatment Outcome

Adipsic diabetes insipidus is an infrequent disease which may be associated with craniopharyngioma. It may be secondary to the tumour's extension, as well as to resection of the mass. We present the case of a 24-year-old woman with a history of delayed puberty and hypothyroidism, but no prior study reports. She consulted due to a headache with warning signs associated with altered visual acuity. Brain MRI was performed which showed signs of a non-adenomatous lesion with suprasellar and hypothalamic extension. Following transcranial surgery, she developed diabetes insipidus criteria, with absence of thirst documented during the hospitalisation. The histopathological findings confirmed the diagnosis of craniopharyngioma. The patient was treated with desmopressin and received recommendations regarding rehydration according to the quantification of losses, with electrolyte stabilisation.

Topics: Antidiuretic Agents; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Magnetic Resonance Imaging; Pituitary Neoplasms; Prednisolone; Sodium; Thirst; Thyroxine; Treatment Outcome; Young Adult

Pituitary stalk sectioning is only essential in cases of craniopharyngioma originating from the stalk or metastatic tumor to the stalk. Some patients can discontinue postoperative antidiuretic hormone (ADH) supplementation with special conditions.. Sixty-three patients with craniopharyngiomas who were treated by surgery with pituitary stalk sectioning were included in this study. Great care was taken to preserve the fine arteries running along the lateral walls of the third ventricle. Removal rates, change of endocrinologic status, and magnetic resonance imaging (MRI) findings were investigated.. Total removal was achieved in 52 of 54 patients in initial surgery (96.3%), and in 5 of 9 patients in retreatment (55.6%). ADH supplementation was required in all patients from the day of surgery, but was discontinued in 29 of 54 patients among the initial surgery group (53.7%) and in 2 of 9 patients among the retreatment group (22.2%). Preservation of thyroid hormone secretion was observed in 24 of 31 patients who could discontinue ADH (77.4%), but only in 12 of 32 patients who could not discontinue ADH (37.5%). Recovery from diabetes insipidus (DI) was significantly associated with preservation of thyroid function (P < 0.01). Postoperative MRI showed that part of the hypothalamus was enhanced in patients with recovery from DI.. Total removal was achieved in 91% of all cases. Half of the patients could discontinue ADH supplementation, which was associated with preservation of thyroid function. The findings of hypothalamic enhancement on postoperative MRI may be associated with recovery from DI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidiuretic Agents; Child; Child, Preschool; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Glucocorticoids; Hormone Replacement Therapy; Humans; Hypopituitarism; Hypothalamo-Hypophyseal System; Hypothyroidism; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Pituitary Gland; Pituitary Neoplasms; Postoperative Complications; Prognosis; Recovery of Function; Thyroid Hormones; Young Adult

During pregnancy, physiological changes in osmotic homeostasis cause water retention. If excessive, this can cause gestational diabetes insipidus (DI), particularly in patients with already impaired vasopressin secretion. We present the case of a 34-year-old patient with pre-existing hypopituitarism who experienced a transient exacerbation of her DI during a twin pregnancy. In contrast to typical gestational DI, polyuria and polydipsia occurred during the first trimester and remained stable thereafter. This case highlights a challenging clinical entity of which pathophysiology, diagnostic approach and treatment will be discussed.

Topics: Adenoma; Adult; Antidiuretic Agents; Deamino Arginine Vasopressin; Diabetes Insipidus; Disease Progression; Female; Humans; Hypopituitarism; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Pregnancy, Twin

To assess the utility of the desmopressin (DDAVP) test in the diagnosis and follow-up of a cyclical Cushing's disease (CCS) case.. Laboratory tests included morning and midnight serum cortisol levels, 24h urine free cortisol excretion, midnight salivary cortisol levels, serum cortisol levels after low (1 mg) and high (8 mg) dexamethasone, plasma ACTH and serum cortisol levels after DDAVP. Magnetic resonance imaging (MRI) was used to assess the presence of a pituitary adenoma. The resected tumor specimen was studied by histological, immunohistochemical and cell biology techniques.. A patient was referred to our unit with a diagnosis of Cushing's syndrome (CS) for further evaluation and treatment. However, no biochemical evidence of hypercortisolism was observed in the follow-up evaluations. Furthermore, the typical features of CS fluctuated throughout this period. A consistent positive response to the DDAVP stimulation test was observed during the diagnostic work-up, even when overt clinical features of CS were not apparent, raising suspicion for CCS. After two years of follow-up a definitive diagnosis of hypercortisolism was established. An MRI scan revealed a pituitary adenoma, as the source of ACTH production. After transphenoidal surgery, clinical signs of CS resolved and the response to DDAVP became negative. DDAVP induced a significant increase in ACTH levels in cultured pituitary adenoma cells, consistent with the in vivo DDAVP test results.. Our case illustrates the utility of the DDAVP test in the evaluation of patients with suspected CCS. The DDAVP test could facilitate the management of CCS by shortening the time of diagnosis.

Topics: ACTH-Secreting Pituitary Adenoma; Adrenocorticotropic Hormone; Adult; Circadian Rhythm; Deamino Arginine Vasopressin; Female; Humans; Hydrocortisone; Hypophysectomy; Magnetic Resonance Imaging; Periodicity; Phenotype; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured

Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs). The desmopressin stimulation test is used in the diagnosis and postsurgery prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in patients with CD are poorly understood.. The objectives of this study were to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release and to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD.. A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures derived from corticotropinomas, nonfunctioning pituitary adenomas, somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH secretion/expression, [Ca(2+)]i kinetics, and AVPR expression and/or proliferative response were evaluated. The relationship between AVPR expression and plasma adrenocorticotropin/cortisol levels obtained from desmopressin tests was assessed.. Desmopressin affects all functional parameters evaluated in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas.. The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our data indicate that AVPR1b is responsible for the direct/exclusive desmopressin stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b antagonists as potential therapeutic tools for CD treatment.

Topics: Adenoma; Adrenocorticotropic Hormone; Aged; Deamino Arginine Vasopressin; Humans; Male; Middle Aged; Pituitary ACTH Hypersecretion; Pituitary Function Tests; Pituitary Gland; Pituitary Neoplasms; Prognosis; Receptors, Vasopressin

Diabetes insipidus (DI) is common following surgery for a pituitary/sellar lesion. Postoperative DI persisting beyond a few weeks is usually regarded as permanent, requiring lifelong desmopressin therapy.. A 16-year-old girl underwent pituitary decompression following a pituitary tumour apoplexy. She developed DI with thirst and hypotonic polyuria in the immediate post-operative period, which was controlled with parenteral DDAVP. Her symptoms persisted and she was discharged on oral desmopressin. Subsequently, she commenced growth hormone replacement. A water deprivation test 6 weeks postoperatively confirmed persistent DI with failure to concentrate urine after 8 hours of dehydration. She was maintained on desmopressin and reported intense thirst and polyuria every time she delayed taking the medication up until 1 year postoperatively. After 1 year, she complained of bloating and stopped taking desmopressin but her symptoms did not recur. A repeat water deprivation test confirmed very late resolution of DI with normal urinary concentration. She has remained asymptomatic ever since.. Delayed recovery of normal posterior pituitary function is exceptionally rare. We hypothesise that the underlying mechanism may be the revascularisation and regeneration of the posterior pituitary tissues or of the axons terminating in the posterior pituitary.

Topics: Adolescent; Antidiuretic Agents; Deamino Arginine Vasopressin; Decompressive Craniectomy; Diabetes Insipidus, Neurogenic; Female; Humans; Pituitary Apoplexy; Pituitary Neoplasms; Postoperative Complications; Recovery of Function; Time Factors

In more than one third of patients with Cushing's disease, pituitary MRI does not identify a microadenoma. The diagnostic approach should be as rigorous as possible in patients with ACTH-dependent Cushing's syndrome, to obtain a definitive diagnosis. Improved pituitary MRI techniques, including dynamic sequences, optimal T1-weighted spin-echo MRI protocol, MRI technique of spoiled gradient recalled acquisition in the steady state, and using a 3-tesla magnet, improved the tumor detection rate, parallel to the performance of endocrine dynamic tests (CRH stimulation, desmopressin stimulation and high-dose dexamethasone suppression tests). When a pituitary tumor is not convincingly identified, inferior petrosal sinus sampling remains the gold standard for diagnosis, and recently, new approaches (simultaneous prolactin measurement) could improve its sensitivity and specificity. Transsphenoidal surgery is the first-line treatment, with remission rates similar to those of patients with preoperative positive MRI. However, medical therapies play an important role after surgical failure or in a search for the onset of a visible tumor, especially with development of new drugs targeting the pituitary gland.

Topics: Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Deamino Arginine Vasopressin; Dexamethasone; False Negative Reactions; Humans; Magnetic Resonance Imaging; Petrosal Sinus Sampling; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Remission Induction; Sensitivity and Specificity

Diabetes insipidus (DI) after endoscopic transsphenoidal surgery (ETSS) can lead to increased morbidity, longer hospital stays, and increased medication requirements. Predicting which patients are at high risk for developing DI can help direct services to ensure adequate care and follow-up. The objective of this study was to review our institution's experience with ETSS and determine which clinical/laboratory variables are associated with DI in this patient population. The authors wanted to see if there was an easily determined single value that would help predict which patients develop DI. This represents the largest North American series of this type. We retrospectively reviewed the charts of patients who had undergone ETSS for resection of sellar and parasellar pathology between 2006 and 2011. We examined patient and tumor characteristics and their relationship to postoperative DI. Out of 172 endoscopic transsphenoidal surgeries, there were 15 cases of transient DI (8.7%) and 14 cases of permanent DI (8.1%). Statistically significant predictors of postoperative DI (p < 0.05) included tumor volume and histopathology (Rathke's cleft cyst and craniopharyngioma). Significant indicators of development of DI were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of 1-deamino-8-D-arginine vasopressin. An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80% specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98% specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively. In this large series, we demonstrated that there were multiple perioperative risk factors for the development of DI. These findings, which are consistent with other reports from microscopic surgical series, will help identify patients at risk for diabetes insipidus, aid in planning treatment algorithms, and increase vigilance in high risk patients.

Topics: Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Neuroendoscopy; Pituitary Neoplasms; Retrospective Studies

There is no consensus on the remission criteria for Cushing's disease or on the definition of disease recurrence after transsphenoidal surgery, and comparison of the different published series is therefore difficult. A long-term recurrence rate of Cushing's disease ranging from 2%-25% has been reported. Predictors of long-term remission reported include: 1) adenoma-related factors (aggressiveness, size, preoperative identification in MRI), 2) surgery-related factors, mainly neurosurgeon experience, 3) clinical factors, of which dependence on and duration of glucocorticoid treatment are most important, and 4) biochemical factors. Among the latter, low postoperative cortisol levels, less than 2 mcg/dL predict for disease remission. However, even when undetectable plasma cortisol levels are present, long-term recurrence may still occur and lifetime follow-up is required. We report the preliminary results of the first 20 patients with Cushing's disease operated on at our hospital using nadir cortisol levels less than 2 mcg/dl as remission criterion.

Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Adolescent; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Circadian Rhythm; Combined Modality Therapy; Deamino Arginine Vasopressin; Dexamethasone; Female; Follow-Up Studies; Glucocorticoids; Hormone Replacement Therapy; Humans; Hydrocortisone; Hypophysectomy; Male; Metyrapone; Middle Aged; Neoplasm Recurrence, Local; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Postoperative Complications; Remission Induction; Retrospective Studies; Saliva; Secretory Rate; Young Adult

Most patients with Cushing's disease (CD) respond to corticotrophin-releasing hormone (CRH) or desmopressin with increased corticotrophin (ACTH) and cortisol levels. Although the vasopressin receptor subtype located on normal corticotrophs is the V3 receptor (V3R), desmopressin is a selective V2 receptor (V2R) agonist and it is unclear whether corticotrophinomas exhibit aberrant V2R expression. Furthermore, no studies have determined the relationship between the in vivo response of CD patients to desmopressin and vasopressin receptor expression, or between the response to CRH and CRH receptor (CRHR) expression. Therefore, the aim of this study was to investigate the expression of vasopressin receptors (V1R, V2R, and V3R) and CRHR on corticotroph tumours and its possible relation to the in vivo response.. A prospective study of 29 patients with CD.. Patients underwent desmopressin and CRH stimulation tests before surgery. The expression of vasopressin receptors and CRHR on corticotrophinomas was determined by immunocytochemistry.. Most of the corticotrophinomas exhibited abundant expression of V1R, V3R, and CRHR, whereas the expression of V2R varied greatly and was lower in macroadenomas than in microadenomas. Both the percentage increment of ACTH and net area under the curve (AUC) of ACTH in the desmopressin stimulation test were found to be correlated with tumour volume. After adjustment for tumour volume, a positive correlation was found between the percentage increment of ACTH and the degree of V2R expression, but not between that of V1R or V3R. No relationship between the level of expression of CRHR on tumour tissues and the percentage increment or netAUC of ACTH to CRH was observed in CD patients.. We concluded that V2R was expressed on corticotrophinomas and that the level of its expression correlated well with the ACTH response to desmopressin in CD patients, although abundant expression of V1R and V3R was also found in almost all corticotroph tumours. Further studies are needed to elucidate the role of these receptors in the pathogenesis of CD.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Corticotropin-Releasing Hormone; Deamino Arginine Vasopressin; Female; Fluorescent Antibody Technique; Humans; In Situ Hybridization; Male; Middle Aged; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prospective Studies; Receptors, Vasopressin

Pituitary apoplexy during pregnancy is so rare that only 15 cases (12 pituitary adenomas, 2 lymphocytic neurohypophysitis, and 1 normal pituitary gland) have been published to date. Here, we report the case of a pregnant woman presenting with pituitary apoplexy from a nonfunctioning pituitary adenoma and provide a possible mechanism and management option for postoperative diabetes insipidus (DI).. A 26-year-old woman presented with sudden onset of headache and bitemporal hemianopsia in the 26th week of her first pregnancy. Magnetic resonance imaging clearly revealed an 18 mm pituitary mass with a fluid-fluid level component displacing the optic chiasma upward. Endonasal endoscopic transsphenoidal surgery was successfully carried out 7 days after the onset of symptoms. DI became apparent immediately after the operation and was not controllable by arginine vasopressin (AVP) but by 1-desamino-8-D-arginine vasopressin (DDAVP) instead. This finding suggests an association between DI and vasopressinase secretion from the placenta, because vasopressinase can degrade AVP but not DDAVP. DI had diminished by the time the patient delivered a healthy girl at the 40th week of gestation.. Postoperative DI associated with pituitary apoplexy during pregnancy should be treated by DDAVP, which is not affected by placental vasopressinase secretion.

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Pituitary Apoplexy; Pituitary Neoplasms; Postoperative Complications; Pregnancy; Pregnancy Complications, Neoplastic

To clarify the outcome of all cases of Rathke's cleft cysts (RCC) treated surgically and followed up in Oxford during a long-term period.. The records of all patients with RCC seen in the Department of Endocrinology between January 1978 and June 2009 were reviewed.. A total of 33 patients (20 females, median age 43 years) were identified. At presentation, major visual field defects were detected in 58% of patients and gonadotrophin, ACTH and TSH deficiency in 60, 36 and 36% of patients respectively. Desmopressin treatment was required in 18% of patients. Treatment consisted of cyst evacuation combined with or without biopsy/removal of the wall. Post-operatively, visual fields improved in 83% of patients with impairment, whereas there was no reversal of ACTH or TSH deficiency or of diabetes insipidus. All but one subject had imaging follow-up during a mean period of 48 months (range 2-267). Cyst relapse was detected in 22% of patients at a mean interval of 29 months (range 3-48 months); in 57% of them, the recurrence was symptomatic. Relapse-free rates were 88% at 24-months and 52% at 48-months follow-up. At last assessment, at least quadrantanopia was reported in 19% of patients, gonadotrophin, ACTH and TSH deficiency in 50, 42 and 47% of patients respectively. Desmopressin treatment was required in 39% of patients.. In this study of patients with RCC and long-term follow-up, we showed a considerable relapse rate necessitating long-term monitoring. Surgical intervention is of major importance for the restoration of visual field defects, but it does not improve endocrine morbidity, which in the long-term affects a substantial number of patients.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Central Nervous System Cysts; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Neoplasm Recurrence, Local; Pituitary Neoplasms; Thyrotropin; Treatment Outcome; Visual Fields

GH-producing pituitary adenomas frequently co-produce other certain anterior pituitary hormones, such as prolactin (PRL). In contrast, GH-producing adenomas which express all of corticotropin-releasing factor (CRF), urocorin1 (Ucn1) and urocortin3 (Ucn3) have not been reported. A 39-year-old woman was admitted for evaluation of the pituitary tumor. The diagnosis of acromegaly was confirmed by elevated serum GH and IGF-I levels, and the absence of GH suppression by oral glucose tolerance test. ACTH response to desmopressin (DDAVP) was observed (plasma ACTH levels increased from 13.9 to 50.4 pg/ml at 90 min). Although it is known that ACTH response to DDAVP is considerably useful for the diagnosis of ACTH-dependent Cushing's syndrome, the diagnosis of Cushing's disease was not supported by the criteria. The patient underwent transsphenoidal resection of the pituitary tumor. Immunohistological examination confirmed a GH- and PRL-producing adenoma, whereas ACTH was negative. ACTH response to DDAVP disappeared after tumor removal. To determine the cause of preoperative ACTH response to DDAVP, we examined expression of CRF family peptides and vasopressin V1b receptor in the pituitary adenoma by immunohistochemistry. Immunohistochemistry revealed positive immunostaining for CRF, Ucn1, Ucn3 and vasopressin V1b receptor in the adenoma. These observations raised the possibility that DDAVP caused an ACTH response, perhaps via the paracrine effects of tumor-derived CRF and Ucn1. When ACTH response to DDAVP is observed in patients with pituitary tumor, not only the direct effect of DDAVP on ACTH secretion, but also a possible involvement of CRF and/or urocortins expressed in the pituitary adenoma, should be considered.

Topics: Acromegaly; Adenoma; Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Human Growth Hormone; Humans; Immunohistochemistry; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Receptors, Vasopressin; Urocortins

Patients requiring CSF shunts frequently have comorbidities that can influence water and electrolyte balances. The authors report on a case involving a ventriculoperitoneal shunt in a patient who underwent intravenous hyperhydration and withdrawal of vasopressin substitution prior to scheduled high-dose chemotherapy regimen for a metastatic suprasellar germinoma. After acute neurological deterioration, the patient underwent CT scanning that demonstrated ventriculomegaly. A shunt tap revealed no flow and negative opening pressure. Due to suspicion of proximal shunt malfunction, the comatose patient underwent immediate surgical exploration of the ventricle catheter, which was found to be patent. However, acute severe hypernatremia was diagnosed during the procedure. After correction of the electrolyte disturbances, the patient regained consciousness and made a good recovery. Although rare, the effects of acute severe hypernatremia on brain volume and ventricular size should be considered in the differential diagnosis of ventriculoperitoneal shunt failure.

Topics: Acute Disease; Adult; Antidiuretic Agents; Antineoplastic Agents; Astrocytoma; Brain Stem Neoplasms; Cerebral Ventricles; Chemotherapy, Adjuvant; Cranial Irradiation; Deamino Arginine Vasopressin; Diagnosis, Differential; Diagnostic Errors; Equipment Failure Analysis; Fluid Therapy; Humans; Hydrocephalus; Hypernatremia; Hypertrophy; Male; Neoplasms, Multiple Primary; Pituitary Neoplasms; Postoperative Complications; Substance Withdrawal Syndrome; Tectum Mesencephali; Tomography, X-Ray Computed; Ventriculoperitoneal Shunt

Desmopressin is a synthetic analogue of the hypothalamic peptide vasopressin and binds to specific pituitary vasopressin (V3) receptors. The V3-receptor is overexpressed in pituitary corticotrope tumors and the injection of desmopressin induces a marked ACTH and cortisol release in human patients with pituitary- (PDH), but not adrenal tumor (AT) dependent hyperadrenocorticism. In this prospective study, we investigated the effects of desmopressin on serum cortisol levels in 80 dogs suspected of Cushing's syndrome. The aim was to find a sensitive and specific test to exclude AT. According to standard tests the dogs were divided into 3 groups (group 1=other disease, n=27; group 2=PDH, n=46; group 3=AT, n=7). Desmopressin was injected as an i.v. bolus of 4microg and serial blood samples were collected before and after 30, 60 and 90min. Desmopressin significantly stimulated cortisol release in dogs with PDH (median 51%, range -24 to 563%; p<0.0001), whereas no increase was seen in dogs with AT (median -12%, range -44 to 5%; p=0.063) and in controls (median +7%, range -36 to 196%; p=0.131). Using a cut off value of 10% increase over baseline, it was possible to exclude AT in 75% of patients. The results of this study suggest that the desmopressin test could be a useful tool in differentiating pituitary from adrenal dependent Cushing's syndromes. Additional dogs with adrenocortical tumor must be tested in order to recommend its use in clinical practice.

Topics: Adrenal Gland Neoplasms; Animals; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; Dog Diseases; Dogs; Hydrocortisone; Pituitary Neoplasms; Prospective Studies; ROC Curve

Germinoma represents 7.8% of cerebral tumors in pediatric age and 50-65% of germ cell cerebral tumors. Generally it is a definite lesion of the pineal gland or suprasellar region, frequently occurring in the first three decades of life. Clinical presentation depends on tumor localization. Pineal lesions generally determine symptoms due to the compression of cerebral structures, causing Parinaud syndrome, while hypothalamic lesions are often characterized by diabetes insipidus, hypopituitarism and visual defects. In the absence of these classic signs and symptoms, however, the diagnosis of germinoma can be difficult. We presented the case of an 8-year-old boy, referred to our clinic for polyuria and polydipsia. Hormonal evaluations demonstrated central diabetes insipidus (CDI), with normal anterior pituitary function. Magnetic resonance imaging (MRI) showed a lack of posterior pituitary gland and partial pituitary stalk enlargement. The patient started therapy with desmopressin (Minirin) with good hydro-electrolytic balance. During follow-up the pituitary function became insufficient with low growth velocity. A second MRI demonstrated a bifocal lesion with dyshomogeneous and cystic appearance, suggesting the diagnosis of germinoma. On the basis of this case report we would like to point out the importance of an early diagnosis in order to improve the prognosis of the disease and the necessity of a careful follow-up of these patients.

Topics: Antidiuretic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Drug Therapy, Combination; Germinoma; Humans; Male; Pituitary Neoplasms; Treatment Outcome

Bilateral inferior petrosal sinus sampling (BIPSS) with corticotrophin-releasing hormone (CRH) stimulation is currently the gold standard test for the differential diagnosis of ACTH-dependent Cushing's syndrome. Reports on the use of desmopressin in this approach are limited. The aim of this study was to evaluate the use of desmopressin during BIPSS in a cohort of patients with ACTH-dependent Cushing's syndrome.. A retrospective case-record study.. Fifty-six patients with confirmed ACTH-dependent Cushing's syndrome underwent BIPSS with desmopressin stimulation when presenting negative pituitary tumour imaging.. Central to peripheral (CEN:PER) ACTH gradient, lateralization of the ACTH source and surgical tumour confirmation were evaluated.. A CEN:PER ACTH gradient was found in 40 patients under basal conditions (CEN:PER >or= 2) and in 47 patients after desmopressin stimulation (CEN:PER >or= 3). Ectopic ACTH-producing tumours (three lung carcinoid tumour, one thymus carcinoid tumour and one thymus hyperplasia) were confirmed in five out of nine patients without the CEN:PER ACTH gradient, and four cases were false negative for Cushing's disease. Lateralization (IPS:IPS >or= 1.4) was observed in 80.8% of patients under basal conditions (38/47) and in 97.8% after desmopressin (46/47), and it was surgically confirmed in 78.7%. There were no false-positive cases. Sensitivity and specificity were 92.1% and 100%, respectively.. Desmopressin improves the differential diagnosis of ACTH-dependent Cushing's syndrome by amplifying the CEN:PER and IPS:IPS ACTH gradients, and is therefore a useful ACTH secretagogue in BIPSS.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Humans; Hydrocortisone; Male; Middle Aged; Petrosal Sinus Sampling; Pituitary Neoplasms; Retrospective Studies; Statistics, Nonparametric; Stimulation, Chemical

The etiological diagnosis of ACTH-dependent Cushing's syndrome is often a problem. In fact, no endocrine or radiological examination can conclusively distinguish the ectopic from the pituitary source of disease. The aim of our study was to evaluate the role of stimulation and suppression endocrine tests in the diagnostic and therapeutic approach of patients with Cushing's disease (CD) and negative pituitary magnetic resonance imaging (MRI), considering their post-surgical outcome in comparison with patients with CD and positive MRI.. We retrospectively analyzed 31 patients (25 women and 6 men, median age 40 +/- 15 years) with a confirmed diagnosis of CD who underwent transsphenoidal pituitary surgery by the same neurosurgeon between 2001 and 2005. Preoperative endocrine assessment included corticotropin-releasing hormone (CRH), desmopressin (dDAVP), and overnight 8 mg dexamethasone suppression tests (8-DST) in all patients. Fifteen patients had a normal pituitary MRI and sixteen had a clearly evident pituitary microadenoma. Bilateral inferior petrosal sinus sampling (BIPSS) was performed in patients with discordant biochemical results or with signs and symptoms highly suggestive of an ectopic source of ACTH. Post-surgical median follow-up was 38.4 +/- 22.0 months.. Among patients with negative MRI, 60% had concordant positive endocrine tests and underwent neurosurgery without other examinations. BIPSS was performed in three other patients prompted by discordant endocrine tests (negative dDAVP) and in two patients with clinical suspicion of ectopic disease. Among patients with positive MRI, 87% underwent neurosurgery without BIPSS that was performed in two patients because of negative concomitant response to dDAVP and CRH tests. A pituitary adenoma, confirmed by pathological examination, was found in 40 and 81% of patients with negative and positive MRI respectively (P<0.05), corticotroph hyperplasia resulted more frequent in the group with negative MRI. Remission rate was not different between patients with negative and positive MRI (73 and 75% respectively; P=0.61) and between patients with negative MRI who did not undergo BIPSS and patients with positive MRI (P=0.56). The recurrence rate was also similar between groups (P=0.64), but higher, although not statistically different (P=0.07) in patients with corticotroph hyperplasia at histology.. An accurate evaluation of presurgical endocrine tests results enabled us to reduce the number of BIPSS in patients with a negative MRI without any fallout on their post-surgical outcome. In the hands of an expert pituitary surgeon, the outcome after surgeryand the subsequent recurrence rate are much the same in patients with negative or positive MRI.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Corticotropin-Releasing Hormone; Deamino Arginine Vasopressin; Decision Trees; Dexamethasone; Female; Follow-Up Studies; Glucocorticoids; Humans; Hydrocortisone; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Predictive Value of Tests; Preoperative Care; Remission Induction; Retrospective Studies; Treatment Outcome

Symptomatic metastases to the pituitary (MP) from renal cell carcinoma (RCC) are rare. In this largest case series reported, we describe the clinical features, treatment and outcome of 5 patients. Over a 6-year period (2000-2006), we treated 5 patients (3 males; mean age 61 years) with large sellar masses and RCC. Four patients had a history of RCC, while in one, RCC was diagnosed after surgery. RCC was diagnosed a median of 11 years prior to diagnosis of MP (range 0-27 years). Four patients had previously developed distant metastases. Clinical presentation included bitemporal hemianopia (3 patients), lethargy (3), headaches (2) and diabetes insipidus (DI) (2). Panhypopituitarism was present in 3 patients and the other two had deficiency of at least ACTH and gonadotropin axes. Elevated prolactin was seen in 3 patients. MRI showed an enhancing sellar mass with suprasellar extension and chiasmal compression in all; prominent vascular flow voids were seen in 2. Three patients underwent transsphenoidal surgery and radiation, while 2 underwent radiotherapy alone. Four patients are alive (follow up 6-46 months); 1 patient died due to systemic metastases at 12 months. Metastases to the pituitary from RCC cause more severe hypopituitarism and visual dysfunction compared to those from other primaries, whereas DI is less common. MRI shows contrast enhancement, stalk involvement, sclerosis and/or erosion of sella and presence of vascular flow voids. Combined treatment using decompressive surgery and stereotactic radiotherapy may result in better outcomes.

Topics: Aged; Carcinoma, Renal Cell; Combined Modality Therapy; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Headache; Hemianopsia; Hormones; Humans; Hydrocortisone; Kidney Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Nephrectomy; Pituitary Neoplasms; Thyroxine; Treatment Outcome

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Combined Modality Therapy; Cortisone; Cyclophosphamide; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Fluorouracil; Humans; Hypopituitarism; Mastectomy, Modified Radical; Methotrexate; Pituitary Neoplasms; Radiotherapy, Conformal; Tamoxifen; Thyroxine

A 39-year-old man with occult eutopic corticotropin microadenoma leading to Cushing's syndrome was presented. Magnetic resonance imaging was unable to identify the pituitary microadenoma. In another department bilateral adrenalectomy was justified. In our department to identify or exclude a pituitary source of autonomous corticotropin secretion desmopressin test was performed. Intravenous desmopressin administration enhanced both circulating concentrations ofACTH and cortisol by 217.36% (peak vs. baseline) and 67% respectively. The patient underwent a transsphenoidal adenomectomy. Immunostaining demonstrated ACTH in adenoma cells. After surgery cortisol levels returned to the normal range, moreover no ACTH and cortisol response was elicited by desmopressin administration. This clinical case represents the demonstration of the possibility to unmask an occult eutopic Cushing's syndrome with the desmopressin test.

Topics: ACTH Syndrome, Ectopic; Adrenal Gland Diseases; Adrenalectomy; Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; Follow-Up Studies; Humans; Hydrocortisone; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Treatment Outcome

Topics: Adenoma; Deamino Arginine Vasopressin; Electroencephalography; Female; Humans; Hypertensive Encephalopathy; Hypoglycemic Agents; Magnetic Resonance Imaging; Middle Aged; Pituitary Neoplasms; Postoperative Complications

The features of pituitary ACTH-dependent Cushing syndrome are often indistinguishable from those of occult ectopic ACTH-dependent Cushing syndrome (CS).. To assess the diagnostic accuracy of bilateral inferior petrosal sinus sampling (BIPSS) in the differential diagnosis of ACTH-dependent Cushing's syndrome as compared with ACTH levels and the overnight high dose dexamethasone suppression test (HDDST).. Retrospective review of medical records of 23 patients (aged 19 to 63 years, 16 women) with surgically proven CS, 20 pituitary microadenomas (CD) and 3 with occult ectopic ACTH secretion (EAS).. No tumor was identifiable by imaging techniques. Mean plasma ACTH values were higher in patients with EAS than in CD (103+/- 110.2 and 73.1+/-41.98 pg/mL respectively, p=NS). Three patients with EAS and 3 patients with CD did not suppress cortisol with the HDDST. The sensitivity of the test was 86% and the specificity 100%. To improve the diagnostic outcome of BIPSS, an stimulation with Desmopressin (9 fig i.v) was performed in 9 patients. The threshold for a pituitary source, was defined as an inferior petrosal sinus to peripheral ACTH basal and post Desmopression ratio >2. BIPSS was successfully carried out in 22 patients and no complications occurred. In 6 patients BIPSS failed to meet the threshold criteria. In 3 patients, bronchial carcinoid tumors which proved to synthesize ACTH, were removed. The diagnostic sensitivity of BIPSS greatly improved from 86% to 100% after Desmopressin stimulation. BIPSS accurately predicted the inverted exclamation markateralization of the microadenoma in 8 of 12 patients (66%).. The combination of Desmopressin stimulation with BIPSS was useful for the differential diagnosis of ACTH-dependent Cushing's Syndrome. However, the preoperative location of pituitary microadenomas was poorly predicted by BIPSS.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adrenocorticotropic Hormone; Adult; Antidiuretic Agents; Cushing Syndrome; Deamino Arginine Vasopressin; Dexamethasone; Diagnosis, Differential; Female; Glucocorticoids; Humans; Male; Middle Aged; Petrosal Sinus Sampling; Pituitary Neoplasms; Retrospective Studies; Sensitivity and Specificity

Tumor metastasis to the pituitary gland has been infrequently reported, and this is probably because only a small proportion of these patients are symptomatic. Most of the symptoms of this malady are related to diabetes insipidus. A 78-year-old man was diagnosed 2 years previously with stage IIIA adenocarcinoma of the lung and treated with sequential chemoradiation therapy and later with whole-brain radiation therapy because of newly developed brain metastasis; he was then admitted to our hospital with symptoms of polydipsia and polyuria. He was confirmed to have central diabetes insipidus that was caused by the pituitary metastasis from lung cancer. His symptoms resolved after treatment with desmopressin. Because of the rarity of this manifestation in lung cancer patients, we report on this case along with a brief review of the relevant literature.

Topics: Aged; Antidiuretic Agents; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Humans; Lung Neoplasms; Male; Pituitary Neoplasms; Polyuria; Radiography; Thirst

Disorders of fluid and sodium regulation, often termed "diabetes insipidus," are a frequent occurrence following surgery for pituitary adenomas. The present study was undertaken to identify the incidence of diabetes insipidus after pituitary surgery and its associated factors.. A retrospective review of the medical records 300 patients who underwent transsphenoidal surgery for pituitary adenoma was undertaken. Information regarding patient gender, perioperative serum sodium levels and urinary output volumes, tumor size, previous pituitary surgery, tumor subtype, and the use of DDAVP was gathered. A multivariate statistical analysis was performed.. Follow-up data were available on 288 patients. During the inpatient postoperative hospital stay, DDAVP was administered to 19% of all patients and 16% of patients not taking DDAVP preoperatively. Of patients with normal fluid/sodium regulation preoperatively, DDAVP was prescribed for 9% at discharge and 4% at 6 weeks postoperatively. Only 1.4% of patients were taking vasopressing replacement at the time of last follow-up. Significant correlations were found between gender, previous surgery, serum sodium levels, and urine volumes at various time points. Immunohistochemical type of tumor and tumor size were not related to DDAVP requirement.. Transient hypotonic polyuria is frequently encountered after pituitary surgery. However, only a small number of patients will develop a long-term requiring for ongoing medical treatment. Previous surgery, female gender, and elevated serum sodium and urine volumes in perioperative period were associated with DDAVP requirement.

Topics: Adenoma; Antidiuretic Agents; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Kidney Concentrating Ability; Male; Neoplasm Recurrence, Local; Neurosurgical Procedures; Pituitary Gland; Pituitary Neoplasms; Polyuria; Postoperative Complications; Reoperation; Retrospective Studies; Sex Factors; Sodium; Sphenoid Bone; Treatment Outcome; Water-Electrolyte Balance

Adipsic diabetes insipidus (ADI) is a rare condition in which thirst, an essential clinical feature for the prevention of hypernatraemic dehydration, is absent. We report the first case of adipsic diabetes insipidus to occur following surgery for a pituitary macroprolactinoma, with loss of both osmoregulated and baroregulated vasopressin release. Following extensive surgery for a vision threatening macroprolactinoma a 14-year-old boy developed profound hypernatraemia with absent thirst sensation. Detailed investigation, with hypertonic saline infusion and trimetaphan infusion, revealed absence of both osmoregulatory and baroregulatory release of vasopressin. We discuss the investigation and management of such patients and the physiology of hypothalamic-neurohypophyseal dysfunction in such patients.

Topics: Adolescent; Deamino Arginine Vasopressin; Diabetes Insipidus; Fluid Therapy; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Postoperative Complications; Prolactinoma; Treatment Outcome

Lymphocytic infundibuloneurohypophysitis is a rare disorder in which neurohypophyseal function is impaired by an autoimmune process. Although several etiologies for this rare entity have been suggested, its occurrence following transsphenoidal adenomectomy has not been reported. A 20-year-old man presented with diabetes insipidus - seven years after successful transsphenoidal microadenomectomy for Cushing's disease, first diagnosed at the age of 13. Seven years later, he developed fairly rapid onset of polydipsia and polyuria. Magnetic resonance imaging demonstrated swelling of the posterior pituitary gland with thickening of the pituitary stalk. Endocrinological evaluation revealed neurohypophyseal dysfunction without the adenohypophysis being affected. On the basis of these findings, a diagnosis of lymphocytic infundibuloneurohypophysitis was made. The mass lesion of the posterior pituitary resolved after the administration of corticosteroids for two months and no operation was required. Lymphocytic infundibuloneurohypophysitis should be considered in the differential diagnosis of pituitary mass lesions following transsphenoidal surgery, especially when the mass is confined to the posterior pituitary gland with neurohypophyseal function being compromised.

Topics: Adenoma; Adult; Anti-Inflammatory Agents; Cushing Syndrome; Deamino Arginine Vasopressin; Humans; Magnetic Resonance Imaging; Male; Neurosurgical Procedures; Pituitary Diseases; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Pituitary Neoplasms; Postoperative Complications; Prednisolone

We present a case of late recurrence of breast cancer manifested with diabetes insipidus caused by isolated intracranial metastases. A 57-year-old postmenopausal woman was diagnosed with breast cancer and underwent radical mastectomy, without any adjuvant therapy. Seventeen years later, she presented with polyuria, polydipsia, weight loss, weakness, diffuse bone pain, hoarseness and mild dyspnoea. Cranial CT revealed several dural masses in the frontal, parietal and occipital lobes and along the falx cerebri. The diagnosis of central diabetes insipidus without impairment of anterior pituitary function was based on the clinical symptoms, laboratory tests and imaging findings. The patient was successfully treated with desmopressin acetate and letrozole, and remained alive and ambulating 22 months after initial presentation with diabetes insipidus.

Topics: Antineoplastic Agents; Breast Neoplasms; Deamino Arginine Vasopressin; Diabetes Insipidus; Fatal Outcome; Female; Humans; Letrozole; Magnetic Resonance Imaging; Meningeal Neoplasms; Middle Aged; Nitriles; Pituitary Neoplasms; Renal Agents; Triazoles

A 71-year-old man was admitted with high fever, thirst, polyposia and polyuria. After examination, lung cancer (adenocarcinoma T1NOM1, Stage IV) and central diabitus insipidus caused by pituitary metastasis of lung cancer, were diagnosed. We gave him desmopressin acetate, gamma knife surgery for pituitary metastasis and chemotherapy with paclitaxel and carboplatin, and his symptoms improved. However, his lung cancer progressed. Diabitus insipidus caused by lung cancer is rare.

Topics: Adenocarcinoma; Aged; Antidiuretic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Combined Modality Therapy; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Docetaxel; Humans; Lung Neoplasms; Male; Paclitaxel; Pituitary Neoplasms; Radiosurgery; Taxoids

Von Willebrand factor (VWF) is synthesized in endothelial cells, where it is stored in Weibel-Palade bodies. Administration of 1-desamino-8-D-arginine-vasopressin (DDAVP) to patients with type 1 von Willebrand disease and to healthy individuals causes a rapid increase in plasma VWF levels. This increase is the result of stimulated release of VWF from Weibel-Palade bodies in certain beds of endothelial cells. The VWF propeptide (VWFpp) targets VWF to storage granules through a noncovalent association. The nature of the VWFpp/VWF interaction was investigated by using cross-species differences in VWF storage. While canine VWFpp traffics to storage granules and facilitates the multimerization of human VWF, it does not direct human VWF to storage granules. Since storage takes place after furin cleavage, this defect appears to be due to the defective interaction of canine VWFpp and human VWF. To determine the regions within VWFpp and VWF important for this VWFpp/VWF association and costorage, a series of human-canine chimeric VWFpp and propeptide-deleted VWF (Deltapro) constructs were produced and expressed in AtT-20 cells. The intracellular localization of coexpressed proteins was examined by confocal microscopy. Two amino acids, 416 in VWFpp and 869 in the mature VWF molecule, were identified as being critical for the association and granular storage of VWF.

Topics: Adrenocorticotropic Hormone; Amino Acid Sequence; Animals; Cell Line; Deamino Arginine Vasopressin; Dogs; Embryo, Mammalian; Endothelium; Humans; Kidney; Mice; Microscopy, Confocal; Molecular Sequence Data; Pituitary Neoplasms; Point Mutation; Protein Precursors; Recombinant Fusion Proteins; Species Specificity; Structure-Activity Relationship; Transfection; Tumor Cells, Cultured; von Willebrand Diseases; von Willebrand Factor; Weibel-Palade Bodies

Desmopressin (DDAVP), an arginine vasopressin analogue, markedly stimulates ACTH secretion in patients with Cushing's disease, in contrast to its minimal effect in normal subjects. However, little is known about the mechanisms underlying this action and it appeared to be of interest to evaluate the effect of DDAVP on ACTH-secreting pituitary adenomas in vitro, in comparison with its effect in the same patients in vivo. Pituitary adenomas from 14 patients with Cushing's disease were incubated with DDAVP, corticotrophin-releasing hormone (CRH) and DDAVP together with vasopressin receptor antagonists or CRH. Incubation with DDAVP induced a modest dose-dependent increase in ACTH concentrations which appeared maximal at 10 nM. CRH stimulated ACTH to a greater extent compared with DDAVP and potentiated the effect of DDAVP alone. The DDAVP-induced ACTH increase appeared blunted by vasopressin V(2) and V(3) receptor antagonists. V(3) receptor gene expression was detected by RT-PCR in all adenoma samples except for two which were not responsive to DDAVP in vitro but responsive to the peptide in vivo. Surprisingly, no difference in the in vitro ACTH secretory response was observed between in vivo DDAVP-responsive (ACTH peak>150% baseline) and -unresponsive (ACTH peak<120% baseline) patients, suggesting that the pituitary adenoma is not the sole mediator of the ACTH-releasing effect of DDAVP. In conclusion, the marked stimulatory effect of DDAVP observed in patients with Cushing's disease appears to be mainly dependent on an extrapituitary action, possibly the inhibition of a corticotrophin release-inhibitory factor.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Aged; Antidiuretic Hormone Receptor Antagonists; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Receptors, Vasopressin; Statistics, Nonparametric; Stimulation, Chemical; Tumor Cells, Cultured

A 41-year-old woman who had undergone transfrontal craniotomy for a pituitary tumor 4 months before presentation was admitted with confusion and orientation only to self. She had a fever of 40 degrees C. Serum sodium and chloride levels on admission were 180 and 139 mEq/L, respectively. Measured serum osmolality was 380 mOsmol/L with a urine osmolality of 360 mOsmol/L. Magnetic resonance imaging revealed a 1.5-cm mass in the sella turcica, which was nonfunctioning on endocrine evaluation. The "bright spot" of a normal posterior pituitary was absent. Central diabetes insipidus was confirmed by a 300% increase in urine osmolality with desmopressin. The patient survived her severe hypernatremia, which has 70% mortality with a serum sodium level of 160 mEq/L or above. However, she developed permanent (6 months) disorientation to time and place even when hypernatremia was corrected, which has not been described previously.

Topics: Adult; Confusion; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Humans; Hypernatremia; Magnetic Resonance Imaging; Pituitary Gland; Pituitary Neoplasms; Renal Agents; Sella Turcica

Topics: Adenoma; Cushing Syndrome; Deamino Arginine Vasopressin; Dexamethasone; Follow-Up Studies; Glucocorticoids; Humans; Hydrocortisone; Neoplasm Recurrence, Local; Pituitary Neoplasms; Predictive Value of Tests; Remission Induction; Treatment Outcome

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Deamino Arginine Vasopressin; Female; Humans; Hydrocortisone; Hypophysectomy; Pituitary Neoplasms

Central diabetes insipidus is clinically masked in dialysis patients. We report a 12-year-old girl receiving a living-related donor graft for renal failure from Alport syndrome, in whom a craniopharyngioma had been resected 6 months before transplantation. Pretransplant evaluation had documented central hypothyroidism, growth hormone deficiency, and presumptive hypogonadotropic hypogonadism. The corticotropin-releasing factor test had been normal. Four hours after transplantation, urine output exceeded 1,000 ml/h without diuretic therapy. Serum sodium concentration was 155 mmol/l, serum osmolality 333 mmol/kg, and plasma antidiuretic hormone 4.9 ng/l, while urine osmolality was 233 mmol/kg. Desmopressin acetate was started by continuous intravenous infusion at 1 microgram/day. Serum electrolytes rapidly normalized, urine output stabilized at 2 l/day. The patient was discharged 4 weeks after transplantation with good allograft function, receiving intranasal desmopressin acetate 10 micrograms twice daily. Pre-existing central diabetes insipidus is unmasked after successful kidney transplantation, leading to rapid dehydration and hypernatremia, which can be prevented by prompt institution of desmopressin therapy.

Topics: Child; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Magnetic Resonance Imaging; Pituitary Neoplasms; Renal Agents

The desmopressin test is generally regarded as an alternative to the CRH test but it is unclear whether desmopressin is as effective as CRH in the differential diagnosis of ACTH-dependent Cushing's syndrome. However, a precise assessment of the operating characteristics of the desmopressin test in comparison with the CRH test has not been reported. The aim of the present study was to make a comparative evaluation of desmopressin and CRH tests in a consecutive cohort of patients with ACTH-dependent Cushing's syndrome and in a group of healthy subjects.. We studied 34 patients with Cushing's disease (CD) and nine patients with ectopic ACTH syndrome (EAS). The control group included 30 healthy subjects. Estimates of sensitivity and specificity were determined for a value of ACTH percent increment (Delta%) > 35% and for a Delta % > 50%, following either desmopressin or CRH, to differentiate CD from EAS. The sensitivity and specificity of a composite rule requiring an ACTH net increment (Delta) > 4.5 pmol/l at both values of Delta % was also calculated. When evaluating cortisol responses, the criteria were Delta % > 20% and Delta > 193 nmol/l. Moreover, to allow comparison of individual end points of the desmopressin and CRH tests at multiple levels of Delta % or Delta either for ACTH or cortisol without the bias of predetermined criteria, univariate curves of the receiver operating characteristics (ROC) were constructed by plotting the sensitivity against 1 - specificity at each level.. In the patients with CD, the frequency of ACTH response was of 90% after both tests while the figures for cortisol were 73% after CRH and 77% after desmopressin, respectively. In the 15 patients who underwent both tests the magnitude of ACTH and cortisol responses induced by the 2 stimuli were fully comparable. In the patients with EAS a (false) positive ACTH response was found in 2/9 cases (22%) after the CRH test and in 2/5 patients (40%) after the desmopressin test. In the healthy subjects the CRH test was performed in 25 cases and the desmopressin test in 15 cases. The frequency of ACTH response was 52% following CRH and 13% following desmopressin. In the 10 healthy subjects who underwent both tests the ACTH response was significantly greater after CRH than desmopressin. The area under the ROC curve for the ACTH Delta % was significantly different than that occurring by chance following CRH but not desmopressin. The point on the ROC curve closest to 1 corresponded to an ACTH Delta % of 47% (sensitivity 87% and specificity 89%). However, a criterion of 100 % specificity would require an increase in the threshold for the ACTH Delta % to 259%. ROC analysis validated also the use of the ACTH Delta as a method to assess the response to CRH, but not after desmopressin. However, the diagnostic performance of this parameter was reduced in comparison to that of the ACTH Delta %, since the best cut-off for the Delta (6.2 pmol/l) had inferior specificity (79%). The operating characteristics of CRH and desmopressin were worse when considering cortisol responses.. The present data suggest that the CRH test is more reliable than the desmopressin test in determining the aetiology of Cushing's syndrome. The desmopressin test resulted in a high frequency of false positive results in patients with ectopic ACTH secondary to carcinoid tumours. This finding may be due to the capability of these tumours to express the V3 vasopressin receptor through which desmopressin acts. However, the clinical endocrinologist may be confronted with some disturbing cases which are misdiagnosed because it is almost impossible to set a diagnostic criterion providing complete specificity in the differentiation of (occult) ectopic Cushing's syndrome using either CRH or desmopressin tests.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adrenocorticotropic Hormone; Adult; Aged; Case-Control Studies; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Female; Humans; Hydrocortisone; Male; Middle Aged; Pituitary Neoplasms; Predictive Value of Tests; Renal Agents; ROC Curve

The treatment of choice in Cushing's disease is transsphenoidal adenomectomy with a recurrence rate ranging 9-23%. We investigated whether abnormal hormonal responses may predict the relapse in "operated" patients followed-up for a long period.. Sixty-eight surgically treated patients with Cushing's disease were followed-up for 12-252 months. Forty-eight patients underwent selective adenomectomy, 17 enlarged adenomectomy and 3 underwent total hypophysectomy. After surgery ACTH and cortisol levels were measured after stimulatory (desmopressin and CRH) and inhibitory tests (dexamethasone and loperamide).. After operation 46 patients were cured (group A), 15 patients only normalized cortisol levels (group B), 7 patients were surgical failures. During the follow-up, a disease-free condition was maintained in 48 of 61 cases (79%), while a recurrence occurred in 13 patients (21%, 5 of group A and 8 of group B). In 5/13 patients who relapsed an absent inhibition after dexamethasone and an exaggerated response to CRH test preceded the recurrence. In 5 other patients the relapse was suspected by loperamide test. In the 3 remaining cases, positive responses to desmopressin preceded the recurrence. In 7/13 patients who relapsed the pituitary tumour was visualized by MRI/CT imaging.. During the follow-up a careful assessment of ACTH dynamics is needed. Although no single test can reliably predict the late outcome, individual patients at risk for relapse may be identified by abnormal responses to desmopressin, CRH and loperamide tests; particularly, the persistent responsiveness to desmopressin may be a criterion of risk for recurrence in patients who only normalized cortisol levels after surgery.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Cushing Syndrome; Deamino Arginine Vasopressin; Female; Humans; Hydrocortisone; Male; Middle Aged; Neoplasm Recurrence, Local; Pituitary Neoplasms; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome

Four cases of hypothalamic-pituitary Langerhans cell histiocytosis (LCH) are reported, highlighting the expanding spectrum of clinical and magnetic resonance imaging (MRI) features in adults. The diagnostic challenge of hypothalamic-pituitary LCH is emphasized in cases revealed as supra-sellar tumors with panhypopituitarism or as isolated central diabetes insipidus. Diagnosis is confirmed by histological examination showing infiltration with CD1a positive histiocytes. General guidelines for diagnosis procedure are drawn out, including the neurosurgical biopsy in particular cases.

Topics: Adult; Aged; Blindness; Deamino Arginine Vasopressin; Fatal Outcome; Female; Histiocytosis, Langerhans-Cell; Humans; Lung Diseases; Magnetic Resonance Imaging; Male; Pituitary Diseases; Pituitary Neoplasms; Renal Agents

We observed the histopathological and physiological characteristics of adrenocorticotropic hormone (ACTH)-secreting adenoma cells derived from a rapidly growing pituitary adenoma, which have firm cell attachment and well-preserved hormonal function in a relatively longterm culture. Corticotrophs, obtained from a 43-year-old woman with Cushing's disease in whom plasma ACTH levels increased in response to 1-deamino-8-D-arginine vasopressin (DDAVP) stimulation and the proliferative potential was very high, were grown in tissue culture for up to 6 months. The morphological features were observed by phase contrast and electron microscopy. The cultured cells were incubated with corticotroph-releasing hormone (CRH), arginine vasopressin (AVP), or DDAVP, and ACTH in the medium was measured by radioimmunoassay (RIA). The morphology of the ACTH-secreting adenoma cells in culture revealed a mixed population of formed clusters and spindle-shaped fibroblast-like cells. The adenoma cells were immunohistochemically positive only for ACTH. On electron microscopic observation, pituitary tumor cells obtained 6 days after seeding demonstrated many secretory granules, well-developed rough endoplasmic reticulum, and mitochondria; fewer secretory granules were observed after cultivation for 24 days. ACTH levels in the incubation media were elevated with stimulation by DDAVP, AVP, or CRH. In this study, the establishment of relatively longterm culture of human pituitary adenoma cells seemed to be due to the high proliferative potential of this adenoma. This in vitro study may imply that DDAVP as well as AVP directly stimulates ACTH release from corticotropic adenoma cells.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Deamino Arginine Vasopressin; Female; Humans; Magnetic Resonance Imaging; Pituitary Neoplasms; Tumor Cells, Cultured

The clinical, biochemical, and radiological features of pituitary ACTH-dependent Cushing's syndrome (CS) [Cushing's disease (CD)] are often indistinguishable from those of occult ectopic ACTH-dependent CS (oEAS). We have evaluated, retrospectively, the results of simultaneous bilateral inferior petrosal sinus (IPS) ACTH sampling before and after CRH stimulation in 128 patients with ACTH-dependent CS: 107 patients with CD, 6 with oEAS, 1 with an adrenal adenoma, 1 with a pituitary gangliocytoma, and 1 with Nelson's syndrome; while, in the remaining 12, the source remains unclear. One hundred seven patients received human-sequence CRH (hCRH), and 11 received ovine CRH; another 6 patients underwent stimulation with desmopressin and hCRH, and 4 with desmopressin alone. A successful bilateral IPS catheterization and sampling (IPSCS) rate of 87.5% was obtained only after considerable experience had been gained. Sixty-nine patients with CD underwent successful bilateral IPSCS: the IPS-to-peripheral ratio of plasma ACTH value (IPS/P) rose from 9.5 +/- 1.4 to a maximum ratio of 55.8 +/- 7.5 in 67 patients, after CRH stimulation. The maximum ratio was obtained at 5 min in 60 of the 69 patients with CD; however, all 69 patients obtained a ratio of more than 2, at that time. In contrast, the 6 patients with occult ACTH-secreting neoplasms had a maximal IPS/P ratio of 1.3 +/- 0.16, and this did not change after CRH stimulation. A bilateral IPS/P ratio more than 2, obtained 5 min after CRH stimulation, had a sensitivity of 97% and a specificity of 100% in diagnosing CD. Two patients with proven active CD had an IPS/P ratio of less than 2. After successful bilateral IPSCS, the gradients between the IPS ACTH concentrations [IPS ACTH gradient (IPSG)] of more than 1.4, at 5 min after CRH stimulation, had a sensitivity of 83% in correctly lateralizing the pituitary microadenoma, compared with 72% sensitivity for magnetic resonance imaging (MRI) scanning. Furthermore, when IPSG and MRI findings were contradictory, IPSG was more often correct than MRI scanning. Although oEAS is a relatively uncommon cause of ACTH-dependent hypercortisolism (5.5% in our series), the accurate diagnosis of ACTH-dependent CS and localization of an intrapituitary microadenoma requires bilateral IPSCS with CRH stimulation, provided that the appropriate technical experience is available. hCRH is as effective a secretagogue as ovine CRH, and either may be used. The value of the combination of CRH and

Topics: ACTH Syndrome, Ectopic; Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Animals; Child; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Humans; Kinetics; Male; Middle Aged; Petrosal Sinus Sampling; Pituitary Neoplasms; Sheep

Disturbances of osmoregulation, leading to diabetes insipidus and hyponatraemia are well known complications after surgery in the sella region. This study was performed to examine the prevalence and predictors of polyuria and hyponatraemia after a complete and selective removal of pituitary adenomas was attempted via the transnasal-transsphenoidal approach.. 1571 patients with pituitary adenomas (238 Cushing's disease, 405 acromegaly, 534 hormonally inactive adenomas, 358 prolactinoma, 23 Nelson's syndrome, and 13 thyrotropinoma) were daily examined within a 10-day postoperative inpatient observation period. Prevalence of patterns of polyuria (> 2500 ml) and oliguria/hyponatraemia (< 132 mmol/l) were surveyed as well as predictors of postoperative morbidity.. 487 patients (31%) developed immediate postoperative hypotonic polyuria, 161 patients (10%) showed prolonged polyuria and 37 patients (2.4%) delayed hyponatraemia. A biphasic (polyuria-hyponatraemia) and triphasic (polyuria-hyponatraemia-polyuria) pattern was seen in 53 (3.4%) and 18 (1.1%) patients, respectively. Forty-one patients (2.6%) displayed immediate postoperative (day 1) hyponatraemia. Altogether, 8.4% of patients developed hyponatraemia at some time up to the 10th day postoperative, with symptomatic hyponatraemia in 32 patients (2.1%). Risk analysis showed that patients with Cushing's disease had a fourfold higher risk of polyuria than patients with acromegaly and a 2.8-fold higher risk for postoperative hyponatraemia. Younger age, male sex, and intrasellar expansion were associated with a higher risk of hypotonic polyuria, but this was not considered clinically relevant.. The analysis illustrates that disturbances in osmoregulation resulting in polyuria and pertubations of serum sodium concentration are of very high prevalence and need observation even after selective transsphenoidal surgery for pituitary adenomas, especially in patients with Cushing's disease.

Topics: Acromegaly; Adenoma; Adult; Cushing Syndrome; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Male; Middle Aged; Pituitary Neoplasms; Polyuria; Postoperative Complications; Prevalence; Prolactinoma; Renal Agents; Risk Factors; Water-Electrolyte Imbalance

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Craniotomy; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Etoposide; Female; Germinoma; Humans; Hypopituitarism; Pituitary Gland, Anterior; Pituitary Neoplasms; Renal Agents

In a retrospective study, the intra- and early postoperative data of 39 children with 46 operations for craniopharyngioma were analyzed. Diabetes insipidus (DI) occurred in 30 out of 32 cases without preoperative evidence of DI. We observed that all children who did not have a pituitary stalk preserved and 5 out of 7 patients with preserved pituitary stalk developed DI within 18 h of surgery. Short-term inappropriate secretion of antidiuretic hormone (SIADH) occurred in 2 children, but was quickly followed by DI. The time of onset of DI and SIADH did not correlate with sex, age, body weight, location of tumor, or duration or extent of surgery. Parenteral desmopressin was an effective treatment for intra- and postoperative DI. The duration of the clinical effect of desmopressin administration varied in different patients between 4 and 23 h. An approach to the immediate intra- and postoperative management of children with craniopharyngioma is presented.

Topics: Administration, Intranasal; Adolescent; Child; Child, Preschool; Combined Modality Therapy; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Fluid Therapy; Humans; Inappropriate ADH Syndrome; Infant; Infant, Newborn; Male; Perioperative Care; Pituitary Neoplasms; Postoperative Complications; Retrospective Studies; Water-Electrolyte Imbalance

ACTH secreting macroadenomas and pituitary apoplexy are unusual in Cushing disease. In the few cases reported in the literature, they have been found in long term hypercortisolism. We communicate a 43 yr old woman with a 4 year evolution Cushing syndrome, who developed sudden cephalea and oftalmoplejia. A Computed Tomography of the pituitary fossa disclosed a macroadenoma with intracapsular hemorrhage and suprasellar expansion. In the functional tests, serum cortisol was suppressed with dexamethasone in a dose of 1 and 8 mg and responded to the desmopressin stimulus. Nevertheless, cortisol levels were lower than those observed in Cushing syndrome of similar magnitude. The tumor was resected by transphenoidal surgery and immunohistochemistry to ACTH was positive. In this case, the laboratory results suggest a partial remission of the hypercortisolism after pituitary apoplexy.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Deamino Arginine Vasopressin; Dexamethasone; Female; Humans; Hydrocortisone; Pituitary Apoplexy; Pituitary Neoplasms; Tomography, X-Ray Computed

To assess the ability of desmopressin administration to stimulate ACTH/cortisol secretion in patients with Cushing's disease, either before or after surgery, and in patients with other states characterized by ACTH hypersecretion, and to compare the results with those obtained after CRH testing.. Plasma ACTH and serum cortisol levels were evaluated after the administration of desmopressin (10 micrograms i.v.), CRH (1 microgram/kg i.v.) and saline on different days in 17 patients with Cushing's disease, 1 with occult ectopic ACTH syndrome, 5 with Addison's disease, 3 who had been bilaterally adrenalectomized for Cushing's syndrome and 4 normal subjects. After pituitary adenomectomy desmopressin and CRH were administered again to 13 of the patients who had undergone pituitary surgery for their Cushing's disease.. In 16 patients with Cushing's disease with microadenoma a positive ACTH/cortisol rise occurred in 11 patients after both desmopressin and CRH, 2 other patients were responsive only to desmopressin and 2 only to CRH, while in 1 patient equivocal responses to both tests were found. The persistence of a hormonal response to desmopressin after pituitary adenomectomy for Cushing's disease correlated with unsuccessful surgery, while, contrary to CRH, absent ACTH/cortisol rises were found in cured patients 1 and 12 months after operation. In 1 patient suspected for ectopic ACTH hypersecretion, desmopressin and CRH administration did not cause any ACTH/cortisol rise. Significant ACTH rises occurred after both desmopressin and CRH testing in patients with Addison's disease. All the 3 patients adrenalectomized for Cushing's syndrome showed a rise of ACTH levels after CRH, while a similar response after desmopressin occurred in only one of them.. Desmopressin is able to stimulate ACTH and hence cortisol release in Cushing's disease. It may be a useful test in patients with doubtful responses to CRH test, in those exhibiting responses to CRH indistinguishable from those of normal subjects and in the postoperative follow-up of Cushing's disease. In some patients with abolished or reduced cortisol feed-back at hypothalamic-pituitary level the sensitivity of normal corticotrophs to desmopressin is enhanced.

Topics: ACTH Syndrome, Ectopic; Addison Disease; Adenoma; Adrenal Gland Diseases; Adrenalectomy; Adrenocorticotropic Hormone; Adult; Aged; Corticotropin-Releasing Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged; Pituitary Neoplasms; Renal Agents; Stimulation, Chemical; Treatment Outcome

A prospective observational study of the pathophysiology of sodium and water disorders in patients with pituitary region tumours after surgical excision was carried out in 20 patients. Serial pre-operative and post-operative fluid and sodium balance, plasma and urine elctrolyte biochemistry and their derived parameters, and circulating hormones associated with fluid balance, atrial natriureic peptide (ANP) and antidiuretic hormone (ADH) were documented to correlate with the patients' clinical conditions. Ten out of these twenty cases developed diabetes insipidus (DI) requiring ADH replacement therapy, although in the majority (6 cases), this way only a transient event. Of the nine patients who developed hyponatraemia, six had symptoms such as impaired consciousness and convulsions. Four patients developed alternating hypoatraemia and hypernatraemia, which constituted a difficult group, where appropriate sodium and fluid management, and ADH replacement therapy were based upon twice daily plasma and urine biochemistry and their derived parameters. Whilst DI in this group of patients was the result of a low circulating ADH level, hyponatraemia was not associated with an exaggerated ADH activity (6.0 +/- 2.3 vs 7.4 +/- 2.3 pmol/ml, mean +/- SEM). Rather, hyponatraemia was strongly associated with an elevated circulating ANP concentration (82.4 +/- 10.5 vs 30.0 +/- 3.1 pmol/ml, mean +/- SEM, p < 0.001), resulting in salt wasting and hypovolaemia.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Child; Creatinine; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Male; Middle Aged; Pituitary Neoplasms; Postoperative Complications; Prospective Studies; Sodium; Urea; Vasopressins; Water; Water-Electrolyte Balance

We describe a case of diabetes insipidus (DI) due to a pituitary tumor in a 33-year-old pregnant woman who developed a sudden onset of polyuria (over 8 l/day) and polydipsia at 30 weeks of gestation. Her plasma concentration of vasopressin (AVP) was low compared with high serum osmolality (298 mOsm/kg), and her urine output was well controlled by treatment with desmopressin acetate (DDAVP). Cranial magnetic resonance imaging (MRI) demonstrated a 1.8 x 1.2-cm pituitary tumor, but she did not have any disturbance in the release of anterior pituitary hormones. The serum concentration of cystine aminopeptidase (CAP) was within the normal range for a woman at 34 weeks of gestation. After an uncomplicated delivery of a healthy girl, her polyuria gradually resolved. The size of the pituitary tumor gradually decreased in parallel to a reduction in her urine output, but a silent hemorrhage was detected in her pituitary gland 4 weeks after the delivery. Although pregnancy is sometimes associated with central DI, the occurrence of DI due to pituitary tumor under pregnancy is rare. The basal AVP recovered to within the normal range, but the low response of AVP secretion to high osmolality persisted. In this case, pregnancy may affect the manifestation of subclinical DI. This case may therefore enhance our understanding of the mechanisms of DI during pregnancy.

Topics: Adenoma; Adult; Body Weight; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hypoglycemic Agents; Magnetic Resonance Imaging; Osmolar Concentration; Pituitary Function Tests; Pituitary Gland, Anterior; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Complications, Neoplastic; Pregnancy Trimester, Third; Time Factors; Urine; Vasopressins

A 46-year-old man who had a history of hypogonadism, bilateral hydronephrosis and huge residual urine volume during the past ten years was admitted complaining of fever and flank pain. Polyuria which was more than 4 liters per day and inability of urine concentration suggested diabetes insipidus. Magnetic resonance imaging (MRI) demonstrated a tumor which was compatible with craniopharyngioma. Tumor resection and administration of desmopressin improved polyuria and urinary tract dilatation with marked reduction of residual urine volume from 400 ml to 20 ml.

Topics: Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Dilatation, Pathologic; Humans; Hydronephrosis; Male; Middle Aged; Pituitary Neoplasms; Renal Agents; Urinary Tract

The postoperative course of children undergoing surgery for craniopharyngioma was reviewed. Typically they were below height at presentation. All had an attempt at radical surgical resection of the tumor. Most developed diabetes insipidus in the postoperative period, which was permanent in all but 1 child. 94% required thyroid replacement therapy, and sex steroids were administered in 100% when they reached the age of puberty. 91% required maintenance corticosteroids. 54% required growth hormone replacement, but some children showed continued growth despite apparent growth hormone deficiency. Postoperative obesity develops in one half of patients, and may be improved with administration of growth hormone; a controlled trial is underway.

Topics: Adolescent; Body Height; Body Weight; Child; Child, Preschool; Combined Modality Therapy; Craniopharyngioma; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Growth Hormone; Humans; Hypophysectomy; Hypopituitarism; Infant; Male; Pituitary Function Tests; Pituitary Hormones; Pituitary Neoplasms; Postoperative Complications; Thyroxine

1. We have studied the response of six patients with cranial diabetes insipidus and six age-matched control subjects to dietary sodium restriction during constant administration of the synthetic vasopressin analogue desamino-[8-D-arginine]vasopressin. 2. Urine flow increased on the first low salt day in the normal control subjects but not in the patients with cranial diabetes insipidus. Body weight fell 1.35 kg in the control subjects but was constant in the patients with cranial diabetes insipidus. 3. Urinary sodium excretion fell at the same rate in both groups. Diurnal variation of urinary sodium excretion and creatinine clearance was present in the control subjects but not in the patients with cranial diabetes insipidus. 4. Changes in plasma sodium concentration and osmolality were similar. Plasma protein concentration increased more in the control subjects (from 69.1 +/- 1.5 to 73 +/- 1.2 versus from 71.7 +/- 1 to 73.2 +/- 1.1 milligrams). The responses of plasma atrial natriuretic peptide, plasma renin activity and salivary aldosterone concentration were similar between the two groups. Salivary aldosterone concentration levels were consistently higher in the patients with cranial diabetes insipidus. 5. We confirm that the low salt diuresis is triggered by release from the antidiuretic activity of arginine vasopressin. In the patients with cranial diabetes insipidus extracellular fluid osmoregulation appeared to be achieved by the movement of water out of and sodium into the extracellular fluid. 6. Absent posterior pituitary function and hypothalamic disturbances did not alter renal sodium conservation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Pressure; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Heart Rate; Humans; Male; Middle Aged; Pituitary Neoplasms; Sodium; Sodium, Dietary

A rare case of a postmenopausal (60-year-old) female with lymphocytic adenohypophysitis manifesting as a sudden onset of diabetes insipidus is reported. Magnetic resonance imaging with gadolinium-diethylene-triaminepentaacetic acid enhancement showed a spherical lesion, approximately 1 cm in diameter, in the sella turcica and a thickened, deviated pituitary stalk. The abnormal tissue was totally removed. Histological examination showed marked infiltration of lymphocytes and plasma cells. Postoperatively, the pituitary stalk became normal. Preoperative differentiation of lymphocytic adenohypophysitis from pituitary adenoma is extremely difficult, and biopsy is essential.

Topics: Adenoma; Autoimmune Diseases; Biopsy; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Female; Humans; Lymphocytes; Magnetic Resonance Imaging; Menopause; Middle Aged; Pituitary Diseases; Pituitary Gland, Anterior; Pituitary Neoplasms; Plasma Cells

A case is presented of a pregnancy complicated by a suprasellar mass diagnosed at 27 weeks' gestation. This patient developed diabetes insipidus, which was successfully treated with 1-desamino-8-D-arginine vasopressin. Thyrotropin-releasing hormone and ACTH stimulation tests were also abnormal, requiring the institution of thyroid and cortisol replacement therapy. The patient was delivered at 34 weeks' gestation secondary to worsening visual field testing. A craniotomy was performed in the postpartum period with removal of a craniopharyngioma. With successful medical treatment and careful observation, surgical intervention may be postponed until postpartum or until a gestational age with lower neonatal morbidity and mortality is reached.

Topics: Adult; Combined Modality Therapy; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hydrocortisone; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Thyroxine

Pyoderma gangrenosum is a rare chronic and recurrent skin disease characterized by progressing lesions from papulopustules to large necrotic sterile ulcers. Its definite etiology remains unknown. In a 40-year-old woman with typical pyoderma gangrenosum an intrasellar mass with suprasellar extension was diagnosed and removed by transsphenoidal surgery. Histopathological features of the lesion were those of a nonspecific granulomatous hypophysitis. Five months postoperatively the patient experienced visual defects and hypopituitarism demonstrated by endocrine evaluation. Computerized tomography showed the recurrence of the intrasellar expanding mass. Extensive and repeated evaluation failed to find any evidence of sarcoidosis, tuberculosis or histiocytosis. Corticosteroid therapy was preferred to surgery and 80 mg daily prednisone produced a dramatic shrinkage of the pituitary pseudotumor. Long-term follow-up studies did not disclose any recurrence of the pituitary granulomatous process nor objective evidence of underlying disease even after steroid dosage has been tapered. The hypothesis of a pituitary localization of pyoderma gangrenosum is suggested by the similarity between the histopathologic findings of the two conditions and the excellent response to steroid therapy.

Topics: Adult; Deamino Arginine Vasopressin; Female; Gangrene; Granuloma; Humans; Hydrocortisone; Pituitary Neoplasms; Prednisone; Recurrence; Tomography, X-Ray Computed

Topics: Adenoma, Chromophobe; Deamino Arginine Vasopressin; Drug Administration Schedule; Humans; Hyponatremia; Male; Middle Aged; Pituitary Neoplasms; Postoperative Complications; Water Intoxication

Topics: Adolescent; Arginine Vasopressin; Chlorpropamide; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Therapy, Combination; Humans; Male; Pituitary Neoplasms; Thirst

Topics: Adenoma; Adolescent; Adult; Arginine Vasopressin; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Postoperative Period

Topics: Child; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Headache; Humans; Male; Pituitary Neoplasms; Postoperative Complications; Vision Disorders

The effect of DDAVP (1-deamino-8-D-arginine vasopressin), a synthetic analogue of vasopressin, was studied in twelve patients with acute postoperative cranial diabetes insipidus (D.I.). The most severe D.I. occurred in four cases following total removal of tumor (3 pituitary microadenoma, 1 dermoid cyst). The urinary volume over 1000 ml per hour in these four cases could not be controlled by DDAVP but could be controlled by drip infusion of aqueous pitressin (AP) and pitressin tannate in oil (PTO). DDAVP was effective when the urinary volume was decreased in under 500 ml per hour. The mild D.I. occurred in four cases after partial removal of tumor (3 craniopharyngioma, 1 pituitary microadenoma). These four cases could be controlled by drinking water only during one or two postoperative weeks. DDAVP was administered in doses of 10 to 30 microgram two times daily after 2 or 3 postoperative weeks and the urinary production was normalized. The four patients developed D.I. after removal of functioning pituitary microadenoma operated by transsphenoidal route. These four cases were treated with drip infusion of AP and PTO during one or two weeks after the operation and were effectively treated with 5 to 15 microgram of DDAVP intranasally every 8 to 12 hours one or two weeks after the operation. Nine cases in 12 cases with postoperative D.I. became chronic D.I. The maintenance dose of DDAVP gradually lessened in accordance with decreasing urinary volume except the two cases of craniopharyngioma. No side effect was experienced for 19 months of treatment.

Topics: Adenoma; Adult; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Postoperative Complications

A patient is described who developed diabetes insipidus during pregnancy. During a revised Carter test performed at 36 wk gestation using DDAVP (1-desamino-8-D-arginine-vasopressin), uterine activity was recorded with a maximum activity of 120 Montevideo Units. The induction of uterine activity by DDAVP in our patient might be related to the high endogenous oxytocin levels or to the far advanced state of amenorrhea. Post partum, the patient reported decreased vision, and the visual fields were found to be abnormal. A neurosurgical procedure followed, and the diagnosis of craniopharyngioma was made.

Topics: Adult; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Oxytocin; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Uterine Contraction

Topics: Adolescent; Adult; Child; Craniopharyngioma; Deamino Arginine Vasopressin; Female; Humans; Male; Neoplasm Recurrence, Local; Pituitary Gland; Pituitary Neoplasms; Tomography, X-Ray Computed