deamino-arginine-vasopressin and Adenoma

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

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

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

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

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

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

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

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

Prolactin may reduce false-negative results in diagnosing Cushing's disease (CD) during inferior petrosal sinus sampling (IPSS). Prolactin normalization could improve the accuracy of IPSS in predicting adenoma lateralization in CD. However, none of the previous studies had involved the use of desmopressin during IPSS. Our objective was to examine the utility of prolactin measurement during IPSS with desmopressin stimulation. We conducted a retrospective analysis of 40 patients (including 31 females) with ACTH-dependent Cushing's syndrome who underwent IPSS between 2010 and 2013. Thirty-eight CD patients were partitioned into true positive (n = 35) and false negative (n = 3). The proportion of improper IPSS venous sampling defined by corresponding IPS:P (inferior petrosal sinus to peripheral) prolactin ratio <1.8 was significantly different between two groups (P = 0.004). Applying a prolactin-normalized ACTH IPS:P ratio >0.8 cutoff could increase the sensitivity of IPSS to 38/38 (100 %). Among the 31 patients with histopathologically proven adenoma localization, correct prediction of adenoma lateralization was obtained in 14/31 (45 %) patients by a peak intersinus ACTH gradient of ≥1.4 in baseline and was not improved by desmopressin stimulation. Left-right intersinus gradients of unilateral prolactin-adjusted ACTH IPS:P ratios could increase the correct prediction of adenoma lateralization to 20/31 (65 %) in baseline and 24/31 (77 %) (P = 0.006) after desmopressin stimulation, respectively. Prolactin is helpful to adjust negative results of IPSS with desmopressin stimulation. It may improve the accuracy in predicting adenoma lateralization in CD as well.

Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Adult; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Petrosal Sinus Sampling; Pituitary ACTH Hypersecretion; Prolactin

We herein present the case of a 53-year-old patient with adrenocorticotropin-independent macronodular adrenocortical hyperplasia (AIMAH), which is a rare form of Cushing syndrome. He had hypercortisolemia and bilateral macronodular adrenal glands with a left side predominance. The administration of vasopressin significantly increased the plasma cortisol level (1.9-fold). Following left adrenalectomy, the patient's hypercortisolemia significantly improved and vasopressin responsiveness was lost, suggesting that the responsiveness originated from the resected left adrenal gland. The marked difference in vasopressin responsiveness between the adrenals corresponded with their asymmetrical size and function. Evaluating the differences in the vasopressin sensitivity may therefore be helpful for understanding the progression of AIMAH.

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Neoplasms; Adrenalectomy; Adrenocorticotropic Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Dexamethasone; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Humans; Hydrocortisone; Hypertriglyceridemia; Laparoscopy; Male; Middle Aged; Organ Size; Receptors, Vasopressin; Thyrotropin-Releasing Hormone; Vasopressins

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

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

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

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

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

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

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

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

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

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

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

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

We evaluated the usefulness of a desmopressin (DDAVP) test in the diagnosis of ACTH-dependent Cushing's syndrome. After an intravenous injection of 5 microg DDAVP, plasma ACTH levels increased to more than 200% of the basal levels in 10 of 10 patients with Cushing's disease, but remained less than 150% in all of 11 normal subjects, 3 patients with Addison's disease, 5 cases of Cushing's disease in remission, and 3 patients with ectopic ACTH syndrome. Peak levels of plasma cortisol after the DDAVP stimulation were 159 +/- 14% in the patients with Cushing's disease, and less than 150% of the basal levels in the other 5 groups. We also found a case of Cushing's disease with periodicity which responded to DDAVP only in the active stage. In vitro studies revealed that DDAVP directly stimulates ACTH release from corticotropic adenoma cells through V1b but not V2 vasopressin receptors. In conclusion, the DDAVP stimulation test, i.e., determination of plasma ACTH levels after 5 microg DDAVP injection, seems useful for discriminating Cushing's disease from normality, and may serve to facilitate the differentiation between Cushing's disease and ectopic ACTH syndrome.

Topics: Adenoma; Adrenal Cortex Function Tests; Adrenocorticotropic Hormone; Adult; Cohort Studies; Cushing Syndrome; Cyclic AMP; Deamino Arginine Vasopressin; Female; Humans; Hydrocortisone; Injections, Intravenous; Kidney; Male; Middle Aged; Receptors, Vasopressin; Reference Values; Renal Agents; Sensitivity and Specificity; Time Factors

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 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

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

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