pituitrin and Pituitary-Neoplasms

Although transient diabetes insipidus (DI) is the most common complication of pituitary surgery, there is no consensus on its definition. Polyuria is the most overt symptoms of DI, but can also reflect several physiological adaptive mechanisms in the postoperative phase. These may be difficult to distinguish from and might coincide with DI. The difficulty to distinguish DI from other causes of postoperative polyuria might explain the high variation in incidence rates. This limits interpretation of outcomes, in particular complication rates between centers, and may lead to unnecessary treatment. Aim of this review is to determine a pathophysiologically sound and practical definition of DI for uniform outcome evaluations and treatment recommendations.. This study incorporates actual data and the experience of our center and combines this with a review of literature on pathophysiological mechanisms and definitions used in clinical studies reporting of postoperative DI.. The occurrence of excessive thirst and/or hyperosmolality or hypernatremia are the best indicators to discriminate between pathophysiological symptoms and signs of DI and other causes. Urine osmolality distinguishes DI from osmotic diuresis.. To improve reliability and comparability we propose the following definition for postoperative DI: polyuria (urine production > 300 ml/hour for 3 h) accompanied by a urine specific gravity (USG) < 1.005, and at least one of the following symptoms: excessive thirst, serum osmolality > 300 mosmol/kg, or serum sodium > 145 mmol/L. To prevent unnecessary treatment with desmopressin, we present an algorithm for the diagnosis and treatment of postoperative DI.

Topics: Diabetes Insipidus; Humans; Pituitary Neoplasms; Postoperative Period; Vasopressins

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

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

Pre-operative central diabetes insipidus has been reported in 8-35% of patients affected with craniopharyngioma, and in 70-90% after surgery. The management of postoperative polyuria and polydipsia can be challenging and fluid balance needs to be closely monitored. The classical triphasic pattern of endogenous vasopressin secretion--an initial phase of symptomatic diabetes insipidus occurring 24 hours after surgery; a second phase of inappropriate vasopressin secretion potentially causing hyponatraemia; and a third phase with a return to diabetes insipidus occurring up to 2 weeks later--is often complicated by cerebral salt wasting and thirst disorders. Inadequate adrenal replacement therapy and anticonvulsant agent treatment may increase the risk of life-threatening hyponatraemia in the course of desmopressin (DDAVP) treatment. Appropriate management, in order to avoid life-threatening or disabling electrolyte disturbances, requires a good grasp of the relevant pathophysiology. We review here the pathophysiology and management of the multiple fluid disorders encountered following surgery for craniopharyngiomas.

Topics: Child; Craniopharyngioma; Diabetes Insipidus; Humans; Hyponatremia; Neurosurgical Procedures; Pituitary Neoplasms; Postoperative Complications; Thirst; Vasopressins; Water-Electrolyte Imbalance

Despite a stuttering course, gene therapy continues to provide a potential treatment avenue for many human diseases, including cancer and various inherited disorders. Gene therapy is also attractive for the treatment of local, benign disorders, such as pituitary adenomas. Advances in technology have focused on modifying existing viral vectors and developing targeted expression of therapeutic genes in an effort to achieve efficacy with minimal toxicity. Gene therapy also offers innovative strategies for treating hypopituitarism by replacing hormones such as growth hormone (GH) and vasopressin.

Topics: Adenoma; Animals; Gene Targeting; Genetic Therapy; Genetic Vectors; Growth Hormone; Hormone Replacement Therapy; Humans; Hypopituitarism; Models, Animal; Pituitary Diseases; Pituitary Neoplasms; Vasopressins

Due to the proximity of craniopharyngiomas to the hypothalamus and pituitary gland, most children and adolescents presenting with these tumors will exhibit significant endocrine dysfunction. After treatment, these impairments can become a major cause of morbidity and mortality.. The postoperative course of children undergoing surgery for craniopharyngioma is reviewed.. Even if hormone levels seem to be adequate in the short term after treatment, deficiencies may develop over years and need to be monitored closely.

Topics: Adrenocorticotropic Hormone; Body Weight; Child; Child, Preschool; Craniopharyngioma; Endocrine System; Endocrine System Diseases; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Neurophysins; Pituitary Neoplasms; Postoperative Complications; Protein Precursors; Thyrotropin; Vasopressins

Cushing's disease remains a difficult diagnosis in spite of new technical procedures such as pituitary MRI, selective bilateral petrosal or cavernous sampling, (111)In pentreotide scan and 18 Flurodeoxyglucose pituitary PET scan. In this article, we review biological diagnostic procedures of Cushing's disease and corticotroph adenomas. According to our experience and the literature, we summarize the approach in medical treatment of Cushing's disease.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adrenal Cortex Neoplasms; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Adult; Algorithms; Carcinoid Tumor; Child; Corticotropin-Releasing Hormone; Cushing Syndrome; Dexamethasone; Diagnosis, Differential; Diagnostic Imaging; Dopamine Agonists; Female; Humans; Hypothalamo-Hypophyseal System; Magnetic Resonance Imaging; Male; Petrosal Sinus Sampling; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Pregnancy; Pregnancy Complications, Neoplastic; Vasopressins

The diagnosis of Cushing's syndrome remains one of the most challenging tasks in clinical neuroendocrinology. The diagnostic procedure can be divided into two distinct steps: diagnosis of the neuroendocrine disorder and differential diagnosis of the precise aetiology. The goal of the first laboratory tests is to obtain biochemical proof of Cushing's syndrome. Patients with Cushing's syndrome are relatively insensitive to glucocorticoid feedback and exhibit an oversecretion of cortisol devoid of a circadian cycle. In our experience, a low-dose dexamethasone suppression test provides the most reliable confirmation of steroid resistance, a cortisol level of<50 nmol/l at 9 a.m. having 98% sensitivity. A cortisol level below 50 nmol/l at midnight rules out active Cushing's syndrome with, in our experience, 100% sensitivity and a specificity depending on numerous other variables. A very high level of free urinary corticol can be a useful sign. After having established the diagnosis of Cushing's syndrome, a persistently low level of ACTH (<10 pg/ml), or preferentially an undetectable level unresponsive to CRH (100 microgram iv), is suggestive of an ACTH-independent disorder, and consequently of primary adrenal disease. The precise location of the lesion can identified with CT or MRI imaging, generally prior to surgical cure. If the ACTH level is detectable, patients with pituitary Cushing's syndrome, or Cushing's disease, should be differentiated from those with ectopic ACTH secretion. The secreting tumour may be difficult to localise and diagnosis is never 100% sure with dynamic tests. Catheterisation of the petrosal sinus with CRH stimulation provides the best sensitivity for differentiating the two aetiologies. We consider a central to peripheral gradient of>3 to confirm the pituitary origin of the disorder with a 98% sensitivity. Chest or abdominal CT can be helpful to identify an ectopic tumour but very small tumours may go undetected. MRI can detect 60 or 70% of all pituitary adenomas but is virtually non-contributive to the diagnosis of Cushing's disease in children.

Topics: Adenoma; Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Cushing Syndrome; Dexamethasone; Diagnosis, Differential; Diagnostic Imaging; Humans; Petrosal Sinus Sampling; Pituitary Neoplasms; Vasopressins

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

Although the majority of patients with pituitary tumor, undergoing transsphenoidal microsurgery, have a low incidence of hormonal deficiency after surgery, the endocrinological evaluations should be carefully done before and after surgery. Glucocorticoid replacement is necessary in patients with Cushing's disease during and after surgery as well as those with adrenal insufficiency. Repeated CRF test is useful to assess the secondary adrenal insufficiency of Cushing's disease after surgery. Patients with impaired secretion of both ACTH and TSH should receive glucocorticoid replacement before thyroid hormone replacement in order to avoid adrenal crisis. A combination of CRF, GRF, TRH and GnRH is a safer and more reliable test to evaluate pituitary function than the conventional triple test consisting of insulin, TRH and GnRH, especially in patients predicted to have pituitary-adrenal insufficiency. Diabetes insipidus(DI), immediately after pituitary surgery, should be treated with subcutaneous injection of Pitressin. Even if patients seem to have recovered from DI several days after surgery, they must be monitored closely because of the incidence of triphasic DI. Less attention has been given to replacement for GH deficiency in adults. Recent reports revealed that GH replacement in adults with GH deficiency decreases visceral fat tissue and increases plasma calcium, phosphorus, osteocalcin and procollagen III levels. GH replacement will become more popular even in adults. Many options and technological advantages in the diagnosis and treatment of pituitary tumors have developed in a decade. In the near future, post-operative patients with pituitary tumors must be cared for in view of the "quality of life".

Topics: Adenoma; Diabetes Insipidus; Female; Follow-Up Studies; Humans; Hydrocortisone; Hypophysectomy; Male; Pituitary Neoplasms; Postoperative Care; Vasopressins

Topics: Adenoma; Adrenocorticotropic Hormone; Bromocriptine; Growth Hormone; Humans; Hydrocortisone; Microsurgery; Pituitary Hormones; Pituitary Neoplasms; Prolactin; Sella Turcica; Thyrotropin; Tomography, X-Ray Computed; Vasopressins

A variety of cells found in the pituitary and pineal glands, sympathetic nervous system and adrenal glands, the gut, pancreas, thyroid (C-cells), chemoreceptors (type I-Cells), lungs (P-cells), skin (melanocytes) and the urogenital tract have a common origin from the neural crest. These cells are programmed for neuro-endocrine function and, as a group, can be regarded as one of the physiological control systems. They secrete a variety of amine and peptide hormones and have common cytochemical characteristics from which the term APUD cell is derived. Tumours of these cells are referred to as 'apudomas' and may synthesise not only their own hormones but also those which are normally produced by other APUD cells. The relevant physiological properties of some of the peptides which have been described relatively recently are discussed and the principal clinical syndromes produced by the APUDomas are described.

Topics: Adenoma, Islet Cell; APUD Cells; Apudoma; Cushing Syndrome; Endocrine System Diseases; Gastrointestinal Neoplasms; Hormones; Humans; Malignant Carcinoid Syndrome; Neoplasms, Nerve Tissue; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Pheochromocytoma; Pituitary Neoplasms; Thyroid Neoplasms; Vasopressins; Zollinger-Ellison Syndrome

Topics: Addison Disease; Adrenocorticotropic Hormone; Biological Assay; Blood Chemical Analysis; Circadian Rhythm; Cushing Syndrome; Hormones, Ectopic; Humans; Hyperplasia; Hypopituitarism; Insulin; Lysine; Metyrapone; Pituitary Neoplasms; Pyrogens; Radioimmunoassay; Vasopressins

Topics: Anencephaly; Cavernous Sinus; Cerebral Angiography; Diabetes Insipidus; Diabetic Retinopathy; Endocrine System Diseases; Feedback; Hemianopsia; Humans; Hypothalamo-Hypophyseal System; Nervous System Diseases; Neurosecretion; Phlebography; Pituitary Hormones, Posterior; Pituitary Neoplasms; Pneumoencephalography; Sella Turcica; Vasopressins; Water Deprivation

Arginine vasopressin (AVP) stimulates steroid secretion from the normal human adrenal gland and some cortisol-producing adrenocortical tumors or hyperplasia through activation of the V(1a) receptor.. The objective of the study was to investigate in vitro and in vivo the possible involvement of AVP in the physiopathology of primary aldosteronism.. The design of the study included immunohistochemical, pharmacological, and molecular studies on aldosterone-producing adenoma (APA), followed by a monocentric, crossover trial of the orally active V(1a) receptor antagonist, SR 49059, in a double blind, randomized, and placebo-controlled fashion.. The study was conducted at a university hospital and research laboratory.. The study population included eight untreated patients with primary aldosteronism, four with APA and four with idiopathic hyperaldosteronism.. Aldosterone secretion of APA cells in vitro and plasma aldosterone, renin, and ACTH were measured.. SR 49059 (200 mg once daily) or placebo was administered during two 1-wk treatment periods separated by a 2-wk washout.. We observed the occurrence of AVP-containing cells in APA tissues. Administration of AVP to perifused APA cells induced an increase in aldosterone production, which was inhibited by a specific V(1a) antagonist. RT-PCR analysis showed the expression of V(1a) receptor mRNA in most APAs studied. In APA patients, SR 49059 did not induce any effect on basal aldosterone secretion but provoked a plasma aldosterone response to orthostatism (P < 0.03) and strengthened the positive correlation between plasma aldosterone and ACTH.. The present study indicates that functional V(1a) receptors are present in APA and suggests that AVP may exert an autocrine/paracrine control of aldosterone secretion in APA tissues.

Topics: Adenoma; Adrenocorticotropic Hormone; Aldosterone; Cross-Over Studies; Double-Blind Method; Female; Fluorescent Antibody Technique; Hormone Antagonists; Humans; Hyperaldosteronism; Immunohistochemistry; Indoles; Male; Middle Aged; Pituitary Neoplasms; Pyrrolidines; Receptors, Vasopressin; Reverse Transcriptase Polymerase Chain Reaction; RNA; Vasopressins

Topics: 17-Hydroxycorticosteroids; Acromegaly; Adenoma, Chromophobe; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Brain Diseases; Central Nervous System Diseases; Clinical Trials as Topic; Craniocerebral Trauma; Diabetes Insipidus; Female; Humans; Hypothalamo-Hypophyseal System; Intracranial Pressure; Male; Metyrapone; Pituitary Diseases; Pituitary Function Tests; Pituitary Neoplasms; Pseudotumor Cerebri; Vasopressins

A macro pituitary tumour or giant pituitary tumour is regarded as a rare causal factor in syndrome of inappropriate antidiuretic hormone (SIADH) cases. Previous reports have presented findings showing that blood flow insufficiency related to stress caused by an obstructive mass may lead to inappropriate secretion of arginine vasopressin. On the other hand, prolactin is known to influence water metabolism, and several cases of a macroprolactinoma or giant prolactinoma (PRLoma) in patients with SIADH have been reported. Nevertheless, few studies have examined such a relationship with SIADH and discussion of pathophysiological factors has been limited. The present report provides details of an elderly patient with SIADH in a chronic giant PRLoma. Of note, exacerbation of prolactin level accompanied the occurrence of SIADH. Findings obtained in this case suggest the possibility of development of SIADH in PRLoma cases due to more than only the effect of the mass.

Topics: Aged; Cabergoline; Humans; Inappropriate ADH Syndrome; Pituitary Neoplasms; Prolactin; Prolactinoma; Vasopressins

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common problem during the postoperative course after pituitary surgery. Although treatment of this condition is well characterized, prevention strategies are less studied and reported. The authors sought to characterize outcomes and predictive factors of SIADH after implementation of routine postoperative fluid restriction for patients undergoing endoscopic transsphenoidal surgery for pituitary adenoma.. In March 2018, routine postoperative fluid restriction to 1000 ml/day for 7 days was instituted for all patients who underwent surgery for pituitary adenoma. These patients were compared with patients who underwent surgery for pituitary adenoma between March 2016 and March 2018, prior to implementation of routine fluid restriction. Patients with preoperative history of diabetes insipidus (DI) or concern for postsurgical DI were excluded. Patients were followed by neuroendocrinologists and neurosurgeons, and sodium levels were checked between 7 and 10 days postoperatively. SIADH was defined by a serum sodium level less than 136 mmol/L, with or without symptoms within 10 days after surgery. Thirty-day readmission was recorded and reviewed to determine underlying reasons.. In total, 82 patients in the fluid-unrestricted cohort and 135 patients in the fluid-restricted cohort were analyzed. The patients in the fluid-restricted cohort had a significantly lower rate of postoperative SIADH than patients in the fluid-unrestricted cohort (5% vs 15%, adjusted OR [95% CI] 0.1 [0.0-0.6], p = 0.01). Higher BMI was associated with lower rate of postoperative SIADH (adjusted OR [95%] 0.9 [0.9-1.0], p = 0.03), whereas female sex was associated with higher rate of SIADH (adjusted OR [95% CI] 3.1 [1.1-9.8], p = 0.03). There was no difference in the 30-day readmission rates between patients in the fluid-unrestricted and fluid-restricted cohorts (4% vs 7%, adjusted OR [95% CI] 0.5 [0-5.1], p = 0.56). Thirty-day readmission was more likely for patients with history of hypertension (adjusted OR [95% CI] 5.7 [1.3-26.3], p = 0.02) and less likely for White patients (adjusted OR [95% CI] 0.3 [0.1-0.9], p = 0.04).. Routine fluid restriction reduced the rate of SIADH in patients who underwent surgery for pituitary adenoma but was not associated with reduction in 30-day readmission rate.

Topics: Adenoma; Diabetes Insipidus; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Pituitary Neoplasms; Postoperative Complications; Retrospective Studies; Sodium; Vasopressins

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Diabetes Insipidus, Nephrogenic; Female; Humans; Intraoperative Complications; Pituitary Gland; Pituitary Neoplasms; Sodium Chloride Symporter Inhibitors; Trichlormethiazide; Vasopressins

At our institution, a total of 320 patients were operated on between 2000 and 2010 for a newly diagnosed pituitary adenoma. In an attempt to improve quality of tumor resection, the transsphenoidal microscopic technique was replaced by the endoscopic technique in June 2008. This retrospective single center study compares the outcomes after microscopic (n = 144) and endoscopic (n = 41) tumor surgery of all patients operated on for a nonfunctional pituitary adenoma.. Tumor size and location, Knosp grade, prevalence of anterior hypopituitarism, diabetes insipidus, visual acuity/fields, complication rates, and operation time were compared between the groups.. At the 3-month follow-up, hypopituitarism had improved in 7% of patients in the microscopic group and in 9% in the endoscopic group, and had further impaired in 13% and 9%, respectively. At the 3-month follow-up magnetic resonance imaging, a total tumor removal was achieved in 45% versus 56% of patients, respectively (P = not significant [NS]). Visual fields had normalized or improved in 90% versus 88% of patients, respectively (P = NS). Postoperative cerebrospinal fluid leak occurred in 3.5% versus 2.4% (P = NS), and diabetes insipidus (transient or permanent) in 7.6% versus 4.9% (P = NS) of cases, respectively. Larger tumor size (P < 0.0005) and endoscopic technique (P = 0.03) were independent predictors of increased mean operative time.. Initial results with the endoscopic technique were statistically similar to those achieved with the microscopic technique. However, there was a trend toward improved outcomes and fewer complications in the endoscopic group.

Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Hormone Replacement Therapy; Human Growth Hormone; Humans; Hydrocortisone; Magnetic Resonance Imaging; Male; Microsurgery; Middle Aged; Neoplasm, Residual; Neuroendoscopy; Pituitary Gland; Pituitary Neoplasms; Radiography; Retrospective Studies; Sphenoid Sinus; Testosterone; Thyroxine; Treatment Outcome; Vasopressins

Surgical manipulation of the pituitary stalk, neurohypophysis or the hypothalamus may disturb control of the plasma sodium level. The factors that might predict the risk of postoperative sodium imbalance are not clear, and were investigated in this study.. A retrospective survey of 129 surgical records for the occurrence of plasma sodium levels outside the normal range, following transsphenoidal procedures. Median patient age was 49 (range 20-78) years, 65 female. 73 of the operated lesions were non-functioning pituitary adenomas. Patients were considered to have impaired plasma sodium balance if the range of 135-145 mmol/L was not maintained.. Of all 129 surgical cases, 68 (53%) experienced an imbalance in sodium levels. Severe sodium imbalance (≥ 149 or ≤ 131 mmol/L) was observed in 28 patients (22%). 13 showed hypernatraemia (median day 1), and 15 hyponatraemia (median day 6). Tumour size was associated with an increased incidence of sodium imbalance, particularly in patients younger than 49 years; surgery resulted in sodium imbalance in 38% of young patients operated on for tumours < 22 mm and in 76% of young patients, operated on for tumours ≥ 22 mm. Overall, tumour size increased with patients' age, and tumour size was less predictive for sodium disturbances in elderly patients. Median time in hospital was 5 days for patients without sodium imbalance, 6 days for patients with hypernatraemia and 11 days for patients with hyponatraemia.. Following pituitary surgery, patients with large tumours, in particular those of young age, are at higher risk for losing control of their plasma sodium level. Increased ADH secretion (hyponatraemia), but not transient diabetes insipidus was associated with a prolonged hospital stay. Postoperative follow-up of patients with sellar tumours should include careful monitoring of plasma sodium levels within the first two postoperative weeks and clear patients' instructions.

Topics: Adenoma; Adult; Aged; Analysis of Variance; Diabetes Insipidus, Neurogenic; Female; Homeostasis; Humans; Hypernatremia; Hyponatremia; Male; Middle Aged; Pituitary Neoplasms; Postoperative Complications; Retrospective Studies; Sella Turcica; Sodium; Tumor Burden; Vasopressins; Young Adult

Topics: Adult; Blood Gas Analysis; Diabetes Insipidus; Female; Fluid Therapy; Humans; Osmolar Concentration; Perioperative Care; Pituitary Gland; Pituitary Neoplasms; Polyuria; Postoperative Complications; Sodium; Vasopressins; Water-Electrolyte Imbalance

Vasopressin was reported to stimulate secretion of both cortisol and aldosterone through eutopic V1a receptors in adrenal gland. Recently, adrenal hyper-responsiveness of plasma cortisol to vasopressin with eutopic overexpession of V1a receptors has been reported in Cushing's syndrome, such as a majority of cases of ACTH-independent macronodular adrenal hyperplasia and some cases of Cushing's adenomas. There were a few reports regarding the aldosterone response to vasopressin in aldosterone-producing adenoma. The aim of our study was to investigate the aldosterone response to vasopressin and its pathophysiological roles in the patients with aldosterone-producing adenoma. Vasopressin-loading test was performed in 10 patients with aldosterone-producing adenoma, and in 16 patients with non-functioning adrenal tumors. The roles of the aldosterone response to vasopressin were analyzed in terms of hormonal secretion and the expression of V1a receptor mRNA on the operated adrenal gland in aldosterone-producing adenoma. We found that (1) a varying aldosterone response to vasopressin was observed, (2) absolute response of plasma aldosterone in aldosterone-producing adenoma was significantly higher than that in non-functioning tumor, (3) aldosterone response rate to vasopressin was significantly and negatively correlated with the decline rate (%) in plasma aldosterone from morning to evening in aldosterone-producing adenoma, (4) V1a receptor mRNA was expressed at various values in aldosterone-producing adenoma, and (5) surgical removal of aldosterone-producing adenoma eliminated the aldosterone response to vasopressin observed in patients with aldosterone-producing adenoma. These findings indicated that vasopressin might be involved in the coordination of aldosterone secretion through eutopic expression of V1a receptor in aldosterone-producing adenoma.

Topics: Adenoma; Adrenal Glands; Aged; Aldosterone; Circadian Rhythm; Cushing Syndrome; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Prospective Studies; Receptors, Vasopressin; RNA, Messenger; Vasopressins

Diabetes insipidus (DI) is a rare clinical condition, which is usually caused by neurohypophyseal or pituitary stalk infiltration in cancer patients.. we present a 62-year old metastatic breast cancer woman with DI. She admitted to the hospital because of nausea, vomiting, polyuria and polydipsia, while she was on no cytotoxic medication. She had no electrolyte imbalance except mild hypernatremia. The CT scan of the brain yielded a suspicious area in pituitary gland. A pituitary stalk metastasis was found on magnetic resonance imaging (MRI) of pituitary. Water deprivation test was compatible with DI. A clinical response to nasal vasopressin was achieved.. Cancer patients who have symptoms such as nausea, vomiting, polyuria and polydipsia while they are not on chemotherapy should be evaluated for not only metabolic complications like hypercalcemia but also posterior pituitary or stalk metastasis MRI could be the choice of imaging for pituitary metastasis.

Topics: Administration, Intranasal; Breast Neoplasms; Diabetes Insipidus; Female; Humans; Magnetic Resonance Imaging; Nausea; Pituitary Neoplasms; Polyuria; Thirst; Vasopressins; Vomiting

We performed an analysis of early factors influencing the outcome of Cushing's disease treated by transsphenoidal pituitary surgery.. Prospective study of 29 patients who underwent transsphenoidal pituitary surgery for Cushing's disease. The prognostic value of preoperative and operative variables, histological findings and serum cortisol (measured at 8:00 a.m. the day after surgery) were analyzed.. Of the 29 patients included in this study, 26 achieved postoperative remission while in 3 patients treatment failed. Tumor was identified at histology in 92.3% patients in the remission group and in 33.3% in the failure group, this difference being significant (p = 0.03). Median postoperative cortisol levels were 95.8 nmol/l in the remission group and 676 nmol/l in the failure group, this difference being significant (p = 0.024). Serum cortisol of 600 nmol/l correctly classified the remission and failure groups with a sensitivity of 100% and a specificity of 96%.. In our experience, no identification of an adenoma at histology and an early postoperative cortisol level higher than 600 nmol/l after transsphenoidal pituitary surgery for Cushing's disease was associated with a high risk of failed treatment.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; Child; Female; Humans; Hydrocortisone; Male; Middle Aged; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Postoperative Period; Prognosis; Remission Induction; Risk Factors; Sensitivity and Specificity; Treatment Failure; Vasopressins

In this study we aimed to establish the frequency of postoperative diabetes insipidus and the incidence and characteristics of abnormalities of thirst in a cohort of patients with craniopharyngioma, in whom neurosurgery had been performed.. Diabetes insipidus was determined by either standard criteria for diagnosis in the immediate postoperative period, or by water deprivation test, in all craniopharyngioma and pituitary tumour patients who underwent surgery in Beaumont Hospital between the years 1986 and 1998. Osmoregulated thirst and vasopressin release were studied during a 2-h infusion of hypertonic (5%) saline followed by a 30-min period of free access to water.. Data on the incidence of postoperative diabetes insipidus was collected in 26 patients with craniopharyngioma and 154 patients with pituitary adenomata. We recruited 16 healthy control patients, 16 patients with cranial diabetes insipidus following pituitary tumour surgery and 16 patients with cranial diabetes insipidus following craniopharyngioma resection for the hypertonic saline infusion study.. Twenty-five patients out of 26 (96%) patients developed diabetes insipidus after surgery for craniopharyngioma, a much higher incidence than after surgery for suprasellar (26/88, 30%, P < 0.001) or intrasellar pituitary tumours (9/66, 14%, P < 0.001). Hypertonic saline infusion identified abnormal thirst responses in five of the 16 craniopharygioma patients studied; all of the pituitary tumour patients had a normal thirst response. Three of the craniopharyngioma patients had adipsic diabetes insipidus whilst two had polydipsic diabetes insipidus.. This study demonstrates following surgery for craniopharyngioma there is a high incidence of cranial diabetes insipidus and a significant incidence of abnormal thirst responses to osmotic stimuli.

Topics: Adult; Blood Pressure; Cohort Studies; Craniopharyngioma; Diabetes Insipidus; Drinking; Female; Humans; Male; Middle Aged; Neurosurgical Procedures; Osmolar Concentration; Pituitary Neoplasms; Postoperative Complications; Retrospective Studies; Saline Solution, Hypertonic; Thirst; Vasopressins

Hyponatremia can result from a wide range of causes. While hyponatremia is known to occur in patients with hypopituitarism, severe hyponatremia occurring as the presenting feature of hypopituitarism is very rare. We present two cases in which severe hyponatremia developed with weakness, light-headedness and seizure. The hyponatremia in these 2 cases mimicked the laboratory diagnostic criteria of a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). However, the hormone studies displayed hypopituitarism. Hyponatremia was completely corrected after administering a supplement of prednisolone and L-thyroxine. Computerized tomography of the brain revealed an adenoma of the pituitary gland. These two cases illustrate that severe hyponatremia may be the presenting feature of clinically non-functional pituitary adenoma with hypopituitarism, which should be kept in mind in the differential diagnosis of hyponatremia mimicking SIADH.

Topics: Adenoma; Aged; Anti-Inflammatory Agents; Diagnosis, Differential; Drug Therapy, Combination; Humans; Hyponatremia; Male; Middle Aged; Pituitary Neoplasms; Prednisolone; Thyroid Hormones; Thyroxine; Vasopressins

The purpose of this study was to determine the location of the pituitary bright spot in patients with pituitary macroadenomas before surgery.. A total of 54 patients with pituitary macroadenomas were retrospectively included in this study. Nonenhanced spin-echo T1-weighted MR images were reviewed to identify the location of the high-intensity-signal posterior pituitary lobe that indicates antidiuretic hormone (ADH) storage. Images were acquired with a 1.5-T machine by using 3-mm-thick contiguous sections in two or three orthogonal planes and a 300 x 512 matrix.. The bright spot corresponding to ADH storage was identified in 44 (81%) patients. Two groups of patients were defined by the height of the macroadenoma: Group A patients (n = 27) had pituitary macroadenomas less than 20 mm in height, and group B (n = 27) had macroadenomas 20 mm or larger. In group A, the bright spot was identified in 25 patients (93%); it was located in the sella in 24 of these cases (96%). In group B, the bright spot was identified in 19 patients (70%); it was in an ectopic location in 14 of these cases (74%).. MR imaging can be used to depict the pituitary bright spot in most patients with pituitary macroadenomas before surgery. The bright spot is usually identified at its expected location within the sella in patients with pituitary macroadenomas less than 20 mm in height, whereas an ectopic location is common when pituitary macroadenomas are larger more than 20 mm.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Gland, Posterior; Pituitary Neoplasms; Retrospective Studies; Vasopressins

Characteristic findings of the pituitary stalk on magnetic resonance (MR) imaging, which suggest a damming-up phenomenon of neurosecretory granules, were reported. Neurosecretory granules containing vasopressin influence the signal intensity on MR T1-weighted image (T1WI). The normal posterior lobe of the pituitary gland appears as a bright signal on T1WI. The bright signal of the posterior lobe represents the normal content of neurosecretory granules and disappears in patients with central diabetes insipidus. The normal pituitary stalk appears as a low-intermediate intensity signal on sagittal and coronal T1WIs with 3 mm-slice thickness. The pituitary stalk appeared as a bright signal in 20 patients; 13 with pituitary adenoma, 4 with an intrasellar cystic lesion, one with cavernous sinus mass, and 2 with no abnormal MR findings. The pituitary stalk was not severed in any of the cases. The normal bright signal of the posterior lobe disappeared in 17 patients. No patients suffered from symptoms of central diabetes insipidus when the bright pituitary stalk appeared. It is suggested that the origin of the bright signal in the pituitary stalk is the damming up and accumulation of neurosecretory granules in the nerve fibers of the hypothalamohypophyseal tract obstructed by adenoma, postoperative scarring, cystic mass and so on. Probably, the damming-up phenomenon on MR imaging represents the functional integrity of the hypothalamo-neurohypophyseal system, and should be distinguished from an ectopic posterior lobe formation which is caused by stalk transection.

Topics: Adenoma; Adolescent; Adult; Aged; Female; Humans; Hypothalamo-Hypophyseal System; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Secretory Vesicles; Vasopressins

Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant trait in which expression of a mutant vasopressin prohormone reduces vasopressin production. We investigated the NP85 Cys-->Gly mutant vasopressin prohormone in a large kindred in The Netherlands. We demonstrate that growth retardation is an important early sign in two children from this kindred, which recuperates by substitution therapy with 1-desamino-8-D-arginine vasopressin. To obtain clues about the basis for the dominant inheritance of FNDI, we analyzed the trafficking and processing of the mutant vasopressin prohormone in cell lines by metabolic labeling and immunoprecipitation. The mutant vasopressin prohormone was retained in the endoplasmic reticulum and thus was not processed to vasopressin. This defect was not caused by dimerization of the vasopressin prohormone via its unpaired cysteine residue. High level expression of the mutant vasopressin prohormone in cell lines resulted in strong accumulation in the endoplasmic reticulum and an altered morphology of this organelle. We hypothesize that disturbance of the endoplasmic reticulum results in dysfunction and ultimately cell death of the cells expressing the mutant prohormone. Our data support the hypothesis that FNDI is a progressive neurodegenerative disease with delayed onset of symptoms. Its treatment requires early detection of symptoms for which growth parameters are useful.

Topics: Adult; Animals; Cell Death; Child; Child, Preschool; Diabetes Insipidus; Dimerization; Endoplasmic Reticulum; Female; Fluorescent Antibody Technique; Growth Disorders; Humans; Immunosorbent Techniques; Male; Mice; Mutation; Netherlands; PC12 Cells; Pedigree; Pituitary Neoplasms; Protein Precursors; Rats; Transfection; Tumor Cells, Cultured; Vasopressins

We report an unusual case of inappropriate antidiuresis with undetectable vasopressin in an elderly man presenting with confusion due to severe hyponatremia. Further investigations led to the diagnosis of non-functional pituitary macroadenoma. The patient had normal thyroid and adrenal function. The abnormal water balance resolved promptly after transsphenoidal removal of the tumor, confirmed by a repeat water loading test. We conclude that inappropriate antidiuresis in the absence of excess vasopressin secretion may implicate mass effect from an underlying pituitary tumor.

Topics: Adenoma; Aged; Confusion; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Pituitary Neoplasms; Vasopressins

Over 20 mutations affecting the neurophysin moiety of the vasopressin prohormone, have been identified in families suffering from familial neurohypophysial diabetes insipidus (FNDI). Only one of these, NP87E-->stop, is located outside the central conserved domain implicated in sorting of the vasopressin prohormone. To obtain clues about the mechanism of induction of FNDI by this atypical mutant we stably expressed wild type and NP87E-->stop vasopressin prohormones in (neuro)endocrine cell lines. Metabolic labeling and immunoprecipitation demonstrated reduced processing of the mutant prohormone to neurophysin. In addition, evoked secretion of neurophysin and vasopressin was diminished, suggesting that part of the mutant is retained in another intracellular compartment than the secretory granules. Indeed, immunofluorescence demonstrated accumulation of the truncated vasopressin prohormone in the endoplasmic reticulum. We conclude that the presence of the vasopressin moiety and the central conserved core of the neurophysin domain suffices for sorting and processing, but not for efficient endoplasmic reticulum exit of the vasopressin-neurophysin molecule.

Topics: Animals; Diabetes Insipidus, Neurogenic; Electrophoresis, Polyacrylamide Gel; Endoplasmic Reticulum; Humans; Immunohistochemistry; Mice; Microscopy, Confocal; Mutation; Neurophysins; PC12 Cells; Pituitary Neoplasms; Plasmids; Protein Precursors; Protein Processing, Post-Translational; Protein Transport; Rats; Transfection; Tumor Cells, Cultured; Vasopressins

Topics: Child; Craniopharyngioma; Craniotomy; Dehydration; Diagnosis, Differential; Female; Humans; Hypernatremia; Hypothalamic Diseases; Pituitary Neoplasms; Syndrome; Vasopressins

Extrinsic factors such as hypothalamic hormones or intrapituitary growth factors may stimulate clonal expansion of a genomically altered cell and therefore play a role in pituitary tumorigenesis. Here we report on the effects of the hypophysiotrophic hormones corticotrophin-releasing hormone (CRH) and vasopressin (AVP) and the intrapituitary growth factor insulin-like growth factor-I (IGF-I) on the proliferation of, as measured by the bromodeoxyuridine labelling index, and ACTH secretion by normal canine pituitary cells and corticotrophic adenoma cells of dogs with pituitary-dependent hyperadrenocorticism. The sensitivity to inhibition by cortisol was analysed under various conditions. Under basal conditions, no significant differences were found in the bromodeoxyuridine labelling indices between control cells and tumour cells. CRH, AVP, IGF-I and cortisol had no effect on the proliferation of canine pituitary cells or canine corticotrophic adenoma cells. In contrast with normal pituitary cells, the proliferation of corticotrophic adenoma cells was stimulated by fetal calf serum (FCS). This FCS-induced proliferation was not inhibited by cortisol. The CRH-induced ACTH secretion by corticotrophic adenoma cells was significantly (P < 0.05) lower than that by normal pituitary cells after 4 h incubation with CRH. Incubation with cortisol for 24 h resulted in reduced ACTH secretion under basal and AVP- or IGF-I-stimulated conditions. The relative inhibition was, however, significantly (P < 0.05) lower in ACTH-producing tumour cells than in normal pituitary cells. Cortisol did not inhibit the CRH-induced ACTH secretion in normal pituitary cells after 24 h. In conclusion, canine corticotrophic adenomas are less sensitive to stimulation by CRH and less sensitive to inhibition by glucocorticoids. These tumours have an aberrant sensitivity to a growth-promoting factor present in FCS. This factor may have an important role in the growth promotion of canine corticotrophic tumours.

Topics: Adenoma; Adrenocorticotropic Hormone; Animals; Cell Division; Cells, Cultured; Corticotropin-Releasing Hormone; Dogs; Insulin-Like Growth Factor I; Pituitary Gland; Pituitary Neoplasms; Time Factors; Tumor Cells, Cultured; Vasopressins

A patient with a ganglioglioma of the neurohypophysis developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present the case and describe its microscopic and ultrastructural features. Malignant neoplasms were thought to be the main cause of ectopic production of vasopressin. Head trauma, infection, or drugs, however, can also induce hypersecretion of vasopressin. Mechanical compression of the pituitary stalk can lead to an excessive antidiuretic hormone (ADH) release by affecting the inhibitory system. Primary neuroendocrine tumors of the hypothalamic-neurohypophyseal system are extremely rare. We demonstrate the presence of vasopressin in the tumor cells by immunocytochemistry. This represents the first case of SIADH caused by a tumor of the neurohypophysis.

Topics: Aged; Cell Nucleus; Cytoplasm; Ganglioglioma; Humans; Immunohistochemistry; Inappropriate ADH Syndrome; Male; Microscopy, Electron; Pituitary Neoplasms; Vasopressins

Neurohypophyseal function was studied by hypertonic saline infusion with plasma vasopressin measurement in 3 patients with adrenal insufficiency before and after cortisol replacement. Although each patient had different causes of adrenal insufficiency, all showed impaired water excretion before replacement. The first patient with isolated adrenocorticotropin deficiency had marked hyponatremia and inappropriate vasopressin secretion which was normalized after replacement, indicating vasopressin hypersecretion during hypoadrenocorticism. The second patient had combined anterior and posterior pituitary deficiency due to postpartum hypopituitarism and showed completely absent vasopressin secretion, with her polyuria being masked before cortisol replacement, suggesting a vasopressin-independent intrarenal mechanism of antidiuresis. The third patient with panhypopituitarism due to a pituitary tumor also had preexisting diabetes insipidus with defective vasopressin secretion. In this case, however, plasma vasopressin was found to be elevated when adrenal insufficiency and hyponatremia subsequently developed. Together, these results indicate that vasopressin hypersecretion does occur during adrenal insufficiency, but that the accompanying urinary diluting defect may be attributable either to vasopressin-dependent or to vasopressin-independent mechanisms.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Diabetes Insipidus; Female; Humans; Hydrocortisone; Hyponatremia; Hypopituitarism; Male; Pituitary Neoplasms; Polyuria; Vasopressins; Water-Electrolyte Balance

Although the effects of the various secretagogues on corticotropin (ACTH) secretion have been well studied, their effects on the POMC gene expression have not been thoroughly characterized. In this study, we established a new model system using the AtT20 mouse corticotroph tumor cell line transfected stably with a plasmid containing 0.7 kb of the rat POMC 5' promoter-luciferase fusion gene. The responsiveness to exogenous CRH improved markedly when the cells were cultured with low serum medium (1% FBS) compared with serum rich medium (10%). Using this culture condition, we examined the effects of not only CRH but also other secretagogues such as catecholamines, vasopressin, and angiotensin II, upon the transcriptional activity of the POMC gene. CRH stimulated POMC promoter activity (3.5-fold increase) as well as cAMP generation and ACTH secretion in a dose- and time-dependent manner, with the maximal effect being observed 3-5 h after the start of incubation. Catecholamines, especially epinephrine (10 nM and above), also stimulated all parameters, although less potently than CRH, and the effect was mimicked by the beta-, but not alpha-adrenergic, agonist, suggesting the involvement of the beta-adrenergic receptor. The combined effects of epinephrine and CRH were greater in all parameters than those of CRH alone, and the effects of both hormones were completely blocked by H89, an inhibitor of protein kinase A. Vasopressin and angiotensin II showed minimal effects on POMC expression. Our results suggest that 1) catecholamines, as well as CRH, positively regulate the POMC gene at physiological concentrations; 2) the cAMP-PKA system is the common intracellular signaling pathway for CRH and catecholamines; and 3) vasopressin and angiotensin II also have weak but significant stimulatory effects on POMC promoter activity.

Topics: Adrenergic beta-Agonists; Adrenocorticotropic Hormone; Angiotensin II; Animals; Blood; Corticotropin-Releasing Hormone; Culture Media; Cyclic AMP; Epinephrine; Gene Expression Regulation; Isoproterenol; Kinetics; Mice; Norepinephrine; Pituitary Neoplasms; Pro-Opiomelanocortin; Rats; Transfection; Tumor Cells, Cultured; Vasopressins

Gangliocytomas or gangliogliomas of the sellar region are very rare tumors. In a great proportion of those cases an adenoma of the anterior pituitary develops from the cell type that is hyperstimulated by the releasing hormone produced from the gangliocytoma. Five GHRH secreting gangliocytomas are reported. Four of these were localized adjacent to a GH secreting adenoma. In one case, no adenoma tissue was found beside the ganglicytoma. As only the adenomas can secrete GH, the adenomas and not the gangliocytomas are directly responsible for acromegaly so that such an adenoma has to be present in cases of acromegaly. A CRH secreting gangliocytoma was combined with an ACTH cell adenoma that had induced Cushing's disease. A ganglioglioma of the posterior pituitary had led to an inappropriate secretion of Vasopressin. The morphology of the different tumors is presented.

Topics: Acromegaly; Adenoma; Adult; Aged; Child; Female; Ganglioneuroma; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Male; Middle Aged; Pituitary Neoplasms; Sella Turcica; Vasopressins

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

Familial hypothalamic diabetes insipidus is an autosomal dominant disorder characterized by deficient vasopressin synthesis. Different point mutations in the vasopressin-neurophysin (VP-NP) precursor gene have been found in affected families. In a Dutch kindred, a single G to T transversion in the NP-encoding exon B of one allele converts the highly conserved glycine 17 to a valine residue. In order to examine whether this point mutation affects the processing and transport of the VP-NP precursor, the normal (HV2) and mutant (MT6) vasopressin cDNAs were stably expressed in the mouse pituitary cell line AtT20. The normal precursor was correctly glycosylated and processed, and NP was detected in the culture medium. Secretion of NP was stimulated by 8-bromo-cAMP, indicating that the normal precursor was targeted to the regulated secretory pathway. In contrast, the mutant precursor was synthesized, but processing and secretion were dramatically reduced. The mutant precursor was core-glycosylated but remained endoglycosidase H-sensitive, suggesting that the protein did not reach the trans-Golgi network. These results were supported by immunocytochemical studies. In HV2 cells, NP derived from the precursor was concentrated in the tips of the cell processes where secretory granules accumulate. In MT6 cells, NP staining was restricted to the endoplasmic reticulum (ER) as determined by colocalization with an ER-resident protein, BiP. These results suggest that the mutation within the conserved part of NP alters the conformation of the precursor and thus triggers its retention in the ER.

Topics: Amino Acid Sequence; Animals; Arginine Vasopressin; Cell Line; Conserved Sequence; Cyclic GMP; Diabetes Insipidus; Fluorescent Antibody Technique; Glycine; Glycosylation; Humans; Mice; Netherlands; Neurophysins; Oxytocin; Pituitary Gland; Pituitary Neoplasms; Point Mutation; Protein Precursors; Recombinant Proteins; Transfection; Valine; Vasopressins

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

The action of arginine vasopressin (AVP) on cytosolic free calcium concentration ([Ca2+]i) was studied at the single-cell level in corticotrophs cultured from pituitary adenoma fragments removed from eight patients with Cushing's disease. AVP evoked distinct [Ca2+]i responses with regard to the tumor origin. In cells from two tumors, AVP consistently evoked a series of characteristic elevations of [Ca2+]i (transient pattern) that depended on Ca2+ entry. In cells from the other tumors, AVP triggered different patterns of [Ca2+]i rise, which consisted of low-amplitude slow monophasic increases at low AVP concentration and a high-amplitude spike increase followed by a sustained plateau (spike-plateau pattern) at higher concentration of AVP. Slow monophasic increases and the spike of spike-plateau responses were due to calcium release from internal stores, whereas the plateau was a consequence of calcium entry. These two patterns (transient vs. spike-plateau) resemble those observed in subpopulations of corticotrophs from healthy rat pituitary glands (Corcuff et al., J. Biol. Chem. 268: 22313-22321, 1993), suggesting that tumorigenesis can lead in pituitary tissues to a selection rather than alteration of AVP [Ca2+]i signals.

Topics: Adenoma; Adrenocorticotropic Hormone; Arginine Vasopressin; Calcium; Cells, Cultured; Corticotropin-Releasing Hormone; Cytosol; Electrophysiology; Humans; Osmolar Concentration; Pituitary Gland, Anterior; Pituitary Neoplasms; Signal Transduction; Vasopressins

Topics: Adolescent; Chlorides; Craniopharyngioma; Humans; Hyponatremia; Hypopituitarism; Male; Neoplasm Recurrence, Local; Pituitary Neoplasms; Postoperative Complications; Sodium; Syndrome; Vasopressins

A case of pulmonary embolism associated with diabetes insipidus is reported in an 18-year-old male. The patient, who had been treated with DDAVP for diabetes insipidus and hydrocortisone for hypocorticism for two years after first operation for the removal of craniopharyngioma, was admitted with recurrence of that tumor. Diabetes insipidus immediately after second operation was controlled with intermittent drip infusion of a small amount of aqueous pitressin under monitorings of body weight hourly using a patient weighing system to keep the weight changes within +/- one kilogram. Serum and urine electrolytes levels, osmolarity, and free water clearance were also monitored every three hours to maintain water-electrolytes balances appropriately. Postoperative course had been uneventful except that CSF rhinorrhea occurred 7 days after operation. The patient was, then, kept in bed with horizontal plane to avoid further leakage of CSF. Two days later, he developed chest pain suddenly with tachypnea, tachycardia, and general cyanosis. The arterial-BGA showed PaO2 of 53.5mmHg and PaCO2 of 35.3mmHg in room air. The definite diagnosis of pulmonary embolism was made by technetium microaggregate lung perfusion scans and by pulmonary angiograms. The patient was treated with heparin, 15000IU/day, and urokinase, 720000IU/day. The symptoms due to pulmonary embolism had improved gradually within a couple of weeks. Recent articles have shown an unexpected high incidence of deep vein thrombosis and pulmonary embolism in neurosurgical patients associated with the elevation of blood coagulability. Brain tumors, especially suprasellar mass with hypothalamic dysfunction have been suggested to cause thromboembolic disorders frequently. The clinical course was described and factors causing pulmonary embolism on this patient was discussed.

Topics: Adolescent; Craniopharyngioma; Diabetes Insipidus; Heparin; Humans; Lung; Male; Neoplasm Recurrence, Local; Pituitary Neoplasms; Postoperative Complications; Pulmonary Embolism; Radionuclide Imaging; Tomography, X-Ray Computed; Urokinase-Type Plasminogen Activator; Vasopressins

In order to investigate the production and secretion of hypothalamic factors by the prolactin and proopiomelanocortin (POMC)-derived, peptide-producing, transplantable rat pituitary tumor 7315a, we determined the concentrations of corticotropin-releasing factor (CRF)- and vasopressin (AVP)-like immunoreactivities (IR) in the tumor extracts [14.0 +/- 1.6 (SE) and 4.2 +/- 0.9 pmol/g, respectively] and incubation media (0.26 +/- 0.01 and 0.07 +/- 0.01 pmol/10(7) cells/h, respectively). Total peptide content correlated well with tumor weight. Moreover, there is a very good correlation between the CRF and AVP IR, but not as good between CRF or AVP IR and POMC peptide IR tumor contents. Tumor extracts were chromatographed on Sephadex G-75 and compared with chromatograms of stalk median eminence (SME) extracts from normal Buffalo rats. CRF IR in tumor chromatograms gave an unusual pattern of peaks. About 31% of the total CRF IR was eluted in the high molecular weight region. The major portion of CRF IR was located in a wide region of lower molecular weight. The AVP radioimmunoassay revealed a similar pattern of peaks in tumor and SME chromatograms. A propressophysin-like peak and a smaller peak coeluting with synthetic AVP were detected. Immunohistochemical staining of consecutive sections of the tumor indicated that AVP and CRF are often found in the same cell, but the CRF and AVP-producing cells are clearly distinct from the POMC peptide-producing cells.

Topics: Adrenocorticotropic Hormone; Animals; Corticotropin-Releasing Hormone; Immunohistochemistry; Pituitary Neoplasms; Pro-Opiomelanocortin; Rats; Rats, Inbred BUF; Vasopressins

Spontaneous pituitary adenomas are common in certain strains of the laboratory rat. Investigations of Wistar rats of two years chronic toxicity studies revealed pituitary tumors in 50% of the females and 26% of the males. The morphology of the spontaneous changes in the pituitary gland was investigated with immunohistochemical and histological methods. The peroxidase-antiperoxidase (PAP) technique was used to localize different hormones (LH, ACTH) in cells of the pars intermedia and pars distalis as well as neurophysin, oxytocin and vasopressin the terminals of the classic neurosecretory system of the pars nervosa. The results show that most of the neoplasms were endocrinologically inactive chromophobe adenomas of the pars distalis.

Topics: Adenoma; Adrenocorticotropic Hormone; Animals; Female; Immunoenzyme Techniques; Luteinizing Hormone; Male; Neurophysins; Oxytocin; Pituitary Gland; Pituitary Neoplasms; Rats; Rats, Inbred Strains; Vasopressins

Topics: Adenoma; Adult; Aged; Diabetes Insipidus; Hemodynamics; Humans; Male; Middle Aged; Pituitary Neoplasms; Postoperative Period; Vascular Resistance; Vasopressins

Pro-vasopressin mRNA, neurophysin and arginine vasopressin (AVP) were assayed in the mouse anterior pituitary gland, in mouse anterior pituitary cells in culture and in the AtT-20 corticotrophic tumour cell line. Northern blot analysis revealed the presence of an approximately 700 base pair pro-vasopressin mRNA in anterior pituitary and AtT-20 cells. Neurophysin, identified by immunoblots, and AVP, identified by high-performance liquid chromatography and cross-reactivity with AVP antiserum, were detected in anterior pituitary cells and AtT-20 cells. Immunocytochemical staining with anti-neurophysin showed that approximately 40-45% of the dissociated anterior pituitary cells in culture and greater than 95% of the AtT-20 cells were stained. Anterior pituitary cells in culture and AtT-20 cells had a basal level of release of AVP in the 0.01-0.1 nM range. These results indicate that anterior pituitary cells and AtT-20 cells have the ability to synthesize and process pro-vasopressin to AVP and neurophysin, endogenously.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Cell Line; Cells, Cultured; Corticotropin-Releasing Hormone; Immunoblotting; Immunohistochemistry; Male; Mice; Neurophysins; Oxytocin; Pituitary Gland, Anterior; Pituitary Neoplasms; Protein Precursors; Radioimmunoassay; RNA, Messenger; Tumor Cells, Cultured; Vasopressins

Topics: Atrial Natriuretic Factor; Clofibrate; Craniopharyngioma; Female; Humans; Hydrocortisone; Hypernatremia; Middle Aged; Pituitary Neoplasms; Postoperative Complications; Vasopressins

Topics: Adenoma; Female; Humans; Hyponatremia; Middle Aged; Osmolar Concentration; Pituitary Neoplasms; Polyuria; Thirst; Vasopressins

Preprovasopressin-neurophysin II (prepro-AVP-Np), the precursor of the cyclic, amidated nonapeptide, arginine vasopressin (AVP), is present in the central and peripheral nervous systems, adrenal glands, and gonads of rats. To study cell-specific processing of prepro-AVP-Np, a fusion gene consisting of the heavy metal-inducible promoter of the mouse metallothionein I gene and the rat prepro-AVP-Np gene was introduced by cellular transfection into several defined cell phenotypes: a fibroblast line (BHK), a pituitary growth hormone and prolactin-producing cell line (GH4), a pituitary cell line that produces several amidated peptides (AtT-20), and an insulin-producing pancreatic islet line (RIN- 1046-38). Clonal cell lines were isolated and prepro-AVP-Np-specific transcripts were detected by Northern blot hybridization analyses. Fibroblast BHK and pituitary GH4 cells transfected with the fusion gene synthesized a polypeptide (Mr = 18,000) characteristic of the glycosylated precursor, pro-AVP-Np; in metal -treated cells, this protein was the major secreted cysteine-labeled polypeptide. Extracts of RIN-1046-38 and AtT-20 cells transfected with the fusion gene contained predominantly processed neurophysin and amidated arginine vasopressin, whereas extracts of BHK and GH4 cells contained mainly precursors of AVP and neurophysin. These observations indicate that the pathways involving specific post-translational processing of pro-AVP-Np are more efficiently utilized in the prohormone-producing AtT-20 and RIN-1046-38 cells than in GH4 and BHK cells that do not synthesize any recognized prohormones.

Topics: Animals; Arginine Vasopressin; Cell Line; Cloning, Molecular; Genes; Genes, Synthetic; Metallothionein; Mice; Neurophysins; Oxytocin; Pituitary Neoplasms; Protein Biosynthesis; Protein Precursors; Transcription, Genetic; Vasopressins

Polyuria subsequent to pituitary surgery was studied in 64 cases. Most cases of postoperative polyuria were due to diabetes insipidus. These cases showed a triphasic pattern in daily urinary volume. Observation of hourly urinary volume in polyuria revealed four diurnal patterns of urinary excretion: rhythmic, continuous, transient, and unspecific. Clinical observation of diurnal patterns has an advantage, in terms of simplicity of procedure, in immediately determining the nature of the polyuria, prognosticating diabetes insipidus, and eliminating inappropriate procedures in treatment. Indomethacin suppository is considered to be a favorable agent in reducing polyuria without disturbing the diurnal pattern in diabetes insipidus.

Topics: Adenoma; Adolescent; Adult; Aged; Circadian Rhythm; Diabetes Insipidus; Female; Humans; Indomethacin; Male; Middle Aged; Pituitary Diseases; Pituitary Neoplasms; Polyuria; Postoperative Complications; Sodium; Vasopressins

Hyponatremia developing some days after transsphenoidal pituitary adenectomy is a treacherous complication of uncertain cause. Of 19 patients monitored in a pilot study at the Wessex Neurological Centre, plasma sodium fell below 125 mmol/liter in three patients at times ranging from 6 to 9 days postoperatively. One patient had evidence of inappropriate secretion of arginine vasopressin (AVP), and the other two probably had steroid insufficiency despite apparently adequate steroid cover. In a more detailed study, the fluid and sodium balance of a further 16 patients was monitored for 7 to 11 days following transsphenoidal surgery together with plasma cortisol, renin, and AVP concentrations. No patient became severely hyponatremic. Three developed partial diabetes insipidus. Two patients with Cushing's disease had evidence of postoperative corticosteroid insufficiency despite normal steroid protection. An inappropriately low plasma cortisol concentration was recorded in both. Plasma AVP concentrations did not show a delayed surge postoperatively. Delayed hyponatremia appears to occur most often in patients with hypoadrenalism, as glucocorticoid cover is decreased. It results from water retention combined with natriuresis, and is reversed by glucocorticoid treatment.

Topics: Adenoma; Adult; Arginine Vasopressin; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Pituitary Neoplasms; Vasopressins; Water-Electrolyte Imbalance

Posterior and anterior pituitary functions were assessed in 8 patients before, during, and after surgery for tumors in the suprasellar region. Preoperatively, all patients but one responded adequately to an osmotic stimulus with a rise in plasma vasopressin (AVP) and all but one showed adequate cortisol response to adrenocorticotropic hormone (ACTH) and hypoglycemia. During surgery a transient rise was seen in plasma levels of AVP (5 out of 8 patients), cortisol (7 out of 8 patients) and growth hormone (4 out of 8 patients). This response could be predicted from the preoperative stimulation tests. Postoperatively the AVP response to osmotic stimuli was impaired in 4 out of 5 patients, although urine volume had returned to normal after a transient polyuric phase. The response of plasma cortisol to ACTH was still adequate but lower than preoperatively.

Topics: Adenoma; Adult; Female; Growth Hormone; Humans; Hydrocortisone; Male; Meningioma; Middle Aged; Osmolar Concentration; Pituitary Neoplasms; Sella Turcica; Skull Neoplasms; Vasopressins

Eighteen patients aged between 14 and 60 years suffering from diabetes insipidus were studied. Diabetes insipidus was diagnosed by means of Robertson's test. All patients underwent C.T. scanning and evaluation of PRL basally and after TRH (200 mcg e.v.). Twelve patients (66%) showed neurological lesions (secondary central diabetes insipidus). Six of these patients had hyperprolactinaemia. Our data suggest that most of central diabetes insipidus are associated with central system nervous (S.N.C.) damage. In same cases the presence of hyperprolactinaemia suggests a brain damage. Therefore neuroradiological study is very important in all cases of neurohypophyseal diabetes insipidus.

Topics: Adolescent; Adult; Diabetes Insipidus; Female; Humans; Hypopituitarism; Male; Middle Aged; Pituitary Gland, Posterior; Pituitary Neoplasms; Prolactin; Vasopressins

The response of pituitary adenomas obtained surgically from patients with Cushing's disease of Nelson's syndrome to synthetic ovine corticotropin-releasing factor (CRF), vasopressins, somatostatin-28, dexamethasone, 3-isobutylmethylxanthine or high [K+] was examined in vitro by measuring the amount of pro-opiomelanocortin (POMC)-derived peptides secreted into the culture medium. CRF did not stimulate the secretion of adrenocorticotropin-, beta-endorphin-, or gamma 3-melanotropin-like peptides from the pituitary adenomas at concentrations ranging from 1 x 10(-13) M to 1 x 10(-7) M whereas vasopressins, 3-isobutyrl-methylxanthine and high [K+] increased, while somatostatin-28 and dexamethasone suppressed, the secretion of these POMC-derived peptides. These findings suggest that either the pituitary ACTH-producing tumors have lost their receptors to CRF or their post-receptor mechanism to CRF is not functional.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Cells, Cultured; Corticotropin-Releasing Hormone; Cushing Syndrome; Dexamethasone; Endorphins; Female; Humans; Male; Melanocyte-Stimulating Hormones; Nelson Syndrome; Pituitary Neoplasms; Somatostatin; Somatostatin-28; Vasopressins

Topics: Adolescent; Adult; Child; Child, Preschool; Craniopharyngioma; Diabetes Insipidus; Female; Follow-Up Studies; Humans; Hydrocortisone; Male; Pituitary Neoplasms; Postoperative Complications; Vasopressins

Topics: Adenoma, Chromophobe; Adrenocorticotropic Hormone; Aged; Humans; Hyponatremia; Male; Osmolar Concentration; Pituitary Neoplasms; Vasopressins

Topics: Aged; Humans; Hyponatremia; Hypopituitarism; Hypothalamic Neoplasms; Kidney Concentrating Ability; Lung Neoplasms; Male; Pituitary Neoplasms; Polyuria; Vasopressins

Topics: Acute Disease; Adenoma; Adult; Body Weight; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Postoperative Complications; Solubility; Vasopressins

Various clinical disorders of water and electrolytes metabolism were reported in relation to decrease or increase of the plasma anti-diuretic hormone (ADH), however, the estimated ADH value was not infrequently found inconsistent with clinical features. In order to determine the influence from surgical intervention to the hypophyseo-hypothalamic system, continuous estimation of the urinary secretion and specific gravity was performed with computerized analyzer, and it was found that there were at least 5 patterns of postoperative change in rhythmicity of ADH secretion. Most interesting finding was that the ADH was discharged in phasic pattern and irregularly intermingled oligo- and polyuric phases were observed quite in early stage of postoperative observation. Forty cases were examined and this method of examination was found useful in the prognostic view point for the postoperative water and electrolytes disorders.

Topics: Adenoma; Circadian Rhythm; Humans; Hydrocortisone; Hypophysectomy; Hypothalamus; Inappropriate ADH Syndrome; Pituitary Neoplasms; Postoperative Period; Vasopressins

Topics: Adolescent; Adult; Craniopharyngioma; Diabetes Mellitus; Humans; Pituitary Neoplasms; Postoperative Complications; Vasopressins

Topics: Humans; Hypothalamus; Pituitary Diseases; Pituitary Gland; Pituitary Hormones, Anterior; Pituitary Hormones, Posterior; Pituitary Neoplasms; Vasopressins

A systematic method for the perioperative management of routine cases of pituitary microadenoma treated by transsphenoidal microsurgery is presented. These methods have evolved over a 7-year period and have been utilized in the management of more than 750 patients with pituitary tumors and related problems treated by trans-sphenoidal surgery. The goals in this joint neurosurgical, endocrinological, and otorhinolaryngological team effort are to eliminate errors in patient management, to assure the safety of the patient in the perioperative period, and to make the therapy as efficient and as cost-effective as possible.

Topics: Adenoma; Female; Humans; Hypopituitarism; Male; Metyrapone; Microsurgery; Pituitary Neoplasms; Postoperative Care; Prednisone; Preoperative Care; Vasopressins

Topics: Blood Glucose; Child; Child, Preschool; Craniopharyngioma; Diabetes Insipidus; Diabetic Coma; Female; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Pituitary Neoplasms; Postoperative Complications; Vasopressins

A 50-yr-old woman with Addison's disease from the age of 14 yr was diagnosed as empty sella turcica in 1974 (Rev Clin Esp 139: 183, 1975). She subsequently continued with hyperpigmentation in spite of adequate hormone substitution therapy which permitted her to lead a normal life. When studied she showed an extreme elevation of plasma ACTH (1500--2000 pg/ml), and with dexamethasone (2 and 8 mg/day) continued to have levels of 900 pg/ml. With 60 mg hydrocortisone daily, effects of overdosage were observed (swelling and Cushingoid facies) associated with depigmentation. However, she continued to manifest levels of plasma ACTH of 700 pg/ml and an absence of circadian rhythm. It seems likely that this patient represents a case of pituitary ACTH secretory adenoma (corticotropinoma) secondary to the preexisting Addison's disease. The circulating levels of other pituitary hormones were normal.

Topics: Addison Disease; Adenoma; Adrenocorticotropic Hormone; Adult; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged; Pituitary Neoplasms; Somatostatin; Vasopressins

Topics: Activities of Daily Living; Diabetes Insipidus; Humans; Hydrocortisone; Hypophysectomy; Patient Education as Topic; Pituitary Gland; Pituitary Neoplasms; Self Administration; Vasopressins

Topics: Clofibrate; Craniopharyngioma; Diabetes Insipidus; Drinking; Humans; Neoplasm Recurrence, Local; Pituitary Neoplasms; Postoperative Complications; Sodium; Vasopressins

A 49-year-old man was submitted to neurosurgery for a cranio-pharyngioma. The lesion, which appeared to involve the antero-inferior wall of the third ventricle, caused lack of appropriate antidiuretic hormone (ADH) release in response to hypernatraemia and plasma hyperosmolality. The probable mechanism of this hypothalamic syndrome is suggested.

Topics: Craniopharyngioma; Humans; Hypernatremia; Hypothalamus; Male; Middle Aged; Osmolar Concentration; Pituitary Neoplasms; Postoperative Complications; Potassium; Sodium; Vasopressins

Diabetes insipidus, resulting from metastatic involvement of the neurohypophysial system, is a rare complication of breast cancer. This review examined the clinical features, metastatic pattern, and radiological and postmortem findings of 39 breast cancer patients with this complication. All patients had polyuria and polydipsia, and all had evidence of advanced metastatic breast cancer. A high incidence of meningeal carcinoma carcinomatosis and/or sellar metastases was observed. In view of the anatomical proximity of the posterior pituitary to the dura mater and the sella turcica, our findings suggest that metastases to the neurohypophysis can occur not only as a result of hematogenous dissemination of malignant cells, but also from direct tumor extension and/or invasion from adjacent structures. Although satisfactory symptomatic relief can be obtained with vasopressin tannate, complete resolution of the diabetic insipidus syndrome was evident only in those patients who had achieved control of the underlying breast disease.

Topics: Adult; Aged; Breast Neoplasms; Diabetes Insipidus; Female; Humans; Meningeal Neoplasms; Menopause; Middle Aged; Neoplasm Metastasis; Pituitary Neoplasms; Sella Turcica; Vasopressins

A cyclic excess of cortisol secretion was detected in a patient with diabetes insipidus and diabetes mellitus. The cycles of hypercortisolism were of 7 days' duration, but during the nadir of these cycles urinary excretion of corticosteroids and 17-ketosteroids was within the normal range. The radiological appearance of the sella turcica was normal; however, computerized axial tomography of the head revealed a small tumor immediately superior to the sella turcica. At operation a small chromophobe adenoma superior to the diaphragma sellae and involving the hypophysial stalk was partially resected. Postoperatively, the patient continued to have 7-day cycles of increased corticosteroid excretion, but the amounts excreted were less than they had been preoperatively. Other patients have been described in whom Cushing's disease has been due to cyclic hypercortisolism. These cycles have been remarkably regular in individual patients, but of variable duration in different patients. Furthermore, cyclic hormonogenesis probably occurs in a variety of endocrinopathies. (Neurosurgery, 5: 598--603, 1979).

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adenoma, Chromophobe; Adrenal Cortex; Adult; Cushing Syndrome; Dexamethasone; Diabetes Insipidus; Humans; Hydrocortisone; Male; Periodicity; Pituitary Neoplasms; Vasopressins

Topics: Child; Craniopharyngioma; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Infant; Male; Pituitary Neoplasms; Postoperative Care; Postoperative Complications; Sodium; Time Factors; Vasopressins; Water-Electrolyte Imbalance

While pituitary tumors are not as rare as was once thought, it is difficult to assess how many are of clinical significance. Trans-sphenoidal pituitary exploration is a technique which can be performed with low operative morbidity and mortality, and when instituted early can prevent subsequent visual and endocrine impairment from an expanding lesion. Thus early recognition has increased importance.

Topics: Acromegaly; Adenoma; Adenoma, Chromophobe; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Female; Follicle Stimulating Hormone; Growth Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Thyrotropin; Vasopressins

Topics: 17-Hydroxycorticosteroids; Adrenocorticotropic Hormone; Estradiol; Follicle Stimulating Hormone; Growth Hormone; Humans; Hydrocortisone; Luteinizing Hormone; Methods; Pituitary Neoplasms; Postoperative Care; Preoperative Care; Prolactin; Testosterone; Thyrotropin; Thyroxine; Vasopressins; Water-Electrolyte Balance

For the assessment of hypothalamo-pituitary-adrenal function in the presence of pituitary adenomas and craniopharyngiomas, insulin tests, lysine-vasopressin tests, and rapid ACTH tests were performed and plasma cortisol was assayed. Rapid ACTH test and lysine-vasopressin test, which examine adrenal and mainly pituitary function respectively, showed normal function in ten among 14 cases. But insulin test, which examines the whole hypothalamo-pituitary-adrenal function, showed various levels of abnormality in eight among 14 cases. Frequent association of functional disturbances of this axis in these diseases was stressed.

Topics: Adenoma, Chromophobe; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Child; Craniopharyngioma; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Lypressin; Male; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal System; Vasopressins

Topics: Adrenocorticotropic Hormone; Bromocriptine; Clomiphene; Diabetes Insipidus; Female; Growth Hormone; Humans; Hyperpituitarism; Hypogonadism; Hypopituitarism; Infertility, Female; Male; Pituitary Diseases; Pituitary Gland; Pituitary Neoplasms; Prolactin; Thyrotropin; Vasopressins

Plasma ACTH (normal value: 0.16 plus or minus mU/100 ml) was measured in 116 patients with Cushing's syndrome, using a bioassay including dynamic tests and sequential determinations. In 10 patients with adrenal tumors ACTH levels were nondetectable (ND) or low, and usually nonstimulatable. In 10 patients with ectopic ACTH secretion high levels (0.42 plus or minus 0.07 mU/100 ml) were measured. The extracts of 6 tumors yielded an ACTH-like substance. Forty-three patients with Cushing's disease (without pituitary tumor) had, before treatment, a mean ACTH level of 0.18 plus or minus 0.01 mU/100 ml, accompanied by high levels of plasma cortisol (32.1 plus or minus 1.9 mug/100 ml). Irregular nycthemeral variations occurred. ACTH rose to 0.30 mU/100 ml after incomplete adrenalectomy (20 patients) and to 1.14 mU/100 ml after total adrenalectomy (21 patients). Dexamethasone (8 mg per day) suppressed ACTH levels. Metyrapone induced a normal ACTH rise, but at abnormal times. Lysine-vasopressin (LVP) induced an ACTH mean relative increase of 120% before, and of 140% after adrenalectomy (i.e., within the normal range). Six nonadrenalectomized patients with pituitary tumors showed similar abnormalities of ACTH regulation. However, the ACTH rise after LVP was above 500%. When pituitary tumors occurred after adrenalectomy (12 patients) the mean basal ACTH level was 18 mU/100 ml. Dexamethasone induced a 90% decrease, and LVP a 416% increase in ACTH levels. In 6 patients with nodular adrenal hyperplasia, ACTH was undetectable before treatment. After adrenalectomy, ACTH rose to 0.4 mU/100 ml (11 patients) and the increase after LVP was 90%. Five additional patients developed pituitary tumors. These data confirm the abnormalities of ACTH feedback regulation in Cushing's disease. However, even when pituitary tumors occur, ACTH levels can be altered by metyrapone, dexamethasone and LVP. This last test is of particular interest for the detection of pituitary tumors. The follow-up pattern of treated nodular adrenal hyperplasia appears to be very similar to that of Cushing's disease.

Topics: Adrenal Gland Diseases; Adrenalectomy; Adrenocorticotropic Hormone; Animals; Biological Assay; Cushing Syndrome; Dexamethasone; Hormones, Ectopic; Humans; Hydrocortisone; Hyperplasia; Metyrapone; Pituitary Function Tests; Pituitary Gland; Pituitary Gland, Anterior; Pituitary Neoplasms; Rats; Vasopressins

In addition to progressive endocrine dysfunction and progressive visual loss, pituitary neoplasms may annouce their presence by the more catastrophic alternative of spontaneous tumor infarction. In two patients reported, illness due to the spontaneous infraction of pituitary tumors was heralded by sudden onset of focal headache associated with diplopia. Stupor, confusion, and evidence of increased intracranial pressure occurred without subarachnoid hemorrhage or massive extrasellar extension of tumor. One patient developed inappropriate antidiuretic hormone secretion with spontaneous infarction in a large but clinically silent chromophobe adenoma. In both patients, skull x-rays suggested a long-standing intrasella mass. Both underwent prompt treatment with endocrinologic replacement therapy and subsequent successful transsphenoidal removal of voluminous, infarcted, pituitary masses.

Topics: Adenoma, Chromophobe; Adult; Eye Manifestations; Female; Humans; Hypophysectomy; Male; Middle Aged; Necrosis; Pituitary Neoplasms; Sphenoid Sinus; Vasopressins

Topics: 11-Hydroxycorticosteroids; 17-Hydroxycorticosteroids; 17-Ketosteroids; Adenoma, Chromophobe; Cortisone; Drinking; Ethanol; Growth Hormone; Humans; Hyponatremia; Hypopituitarism; Male; Middle Aged; Osmolar Concentration; Pituitary Neoplasms; Urination; Vasopressins

Topics: Acute Disease; Anuria; Child; Craniopharyngioma; Depression, Chemical; Diabetes Insipidus; Female; Humans; Injections, Intravenous; Phenytoin; Pituitary Neoplasms; Postoperative Care; Postoperative Complications; Secretory Rate; Sodium; Stimulation, Chemical; Time Factors; Vasopressins

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adenoma, Chromophobe; Adrenocorticotropic Hormone; Adult; Arginine; Blood Glucose; Craniopharyngioma; Diagnosis, Differential; Female; Glucose; Glucose Tolerance Test; Gonadotropins, Pituitary; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Insulin; Male; Metyrapone; Middle Aged; Pituitary Gland; Pituitary Hormones, Anterior; Pituitary Neoplasms; Pituitary-Adrenal System; Sella Turcica; Thyroid Gland; Vasopressins

Topics: Acromegaly; Adenoma, Acidophil; Adenoma, Chromophobe; Adult; Brain Neoplasms; Craniopharyngioma; Diabetes Insipidus; Female; Humans; Luteinizing Hormone; Male; Meningioma; Metyrapone; Pinealoma; Pituitary Hormone-Releasing Hormones; Pituitary Neoplasms; Radioimmunoassay; Thyrotropin; Thyrotropin-Releasing Hormone; Vasopressins

Topics: Adenoma, Chromophobe; Adrenocorticotropic Hormone; Adult; Aged; Child; Craniopharyngioma; Female; Follicle Stimulating Hormone; Growth Hormone; Humans; Hypopituitarism; Hypothalamus; Hypothyroidism; Luteinizing Hormone; Male; Meningioma; Middle Aged; Pituitary Neoplasms; Radioimmunoassay; Thyrotropin; Thyrotropin-Releasing Hormone; Time Factors; Vasopressins

Topics: Autopsy; Brain Neoplasms; Bronchial Neoplasms; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Humans; Hypopituitarism; Hypothalamus; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Paraneoplastic Endocrine Syndromes; Pituitary Gland; Pituitary Neoplasms; Vasopressins

Topics: 17-Hydroxycorticosteroids; Acromegaly; Adenoma, Chromophobe; Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Child; Craniopharyngioma; Dexamethasone; Humans; Hypoglycemia; Hypothalamus; Insulin; Lysine; Metyrapone; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Pyrogens; Sella Turcica; Vasopressins

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Circadian Rhythm; Cushing Syndrome; Dexamethasone; Diagnosis, Differential; Humans; Hydrocortisone; Immune Sera; Injections, Intramuscular; Injections, Intravenous; Insulin; Iodine Radioisotopes; Lysine; Pituitary Neoplasms; Prognosis; Radioimmunoassay; Vasopressins

Topics: 11-Hydroxycorticosteroids; Adult; Brain Diseases; Circadian Rhythm; Female; Humans; Hydrocortisone; Male; Metyrapone; Middle Aged; Optic Atrophy; Pituitary Neoplasms; Vasopressins

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Circadian Rhythm; Endocrine System Diseases; Female; Humans; Hydroxycorticosteroids; Hypothalamus; Lysine; Male; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Vasopressins

Topics: Adrenocorticotropic Hormone; Adult; Arginine; Child; Female; Gonadotropins; Gonadotropins, Pituitary; Growth Hormone; Humans; Hypopituitarism; Male; Melanocyte-Stimulating Hormones; Pituitary Neoplasms; Prolactin; Thyrotropin; Vasopressins

Topics: Adenoma; Adolescent; Adult; Craniopharyngioma; Diabetes Insipidus; Diuresis; Female; Humans; Hypophysectomy; Kidney Concentrating Ability; Male; Middle Aged; Osmolar Concentration; Osmotic Pressure; Pituitary Neoplasms; Thirst; Vasopressins

Topics: Adult; Chorionic Gonadotropin; Cortisone; Craniopharyngioma; Desoxycorticosterone; Estrogens; Female; Gestational Age; Gonadotropins, Pituitary; Humans; Hypophysectomy; Hypopituitarism; Infertility, Female; Menopause; Ovulation; Pituitary Neoplasms; Pregnancy; Pregnanediol; Vasopressins

Topics: Acid-Base Equilibrium; Blood Cell Count; Cortisone; Depression; Diabetes Insipidus; Diuresis; Electrocardiography; Heart Failure; Hemorrhage; Humans; Hypophysectomy; Kidney Diseases; Methods; Pituitary Diseases; Pituitary Neoplasms; Postoperative Care; Postoperative Complications; Posture; Preoperative Care; Sodium; Time Factors; Vasopressins

Topics: 17-Hydroxycorticosteroids; Adenoma, Chromophobe; Adult; Biological Assay; Blood Pressure; Cerebral Angiography; Gonadotropins; Hemangioma; Humans; Hyperthyroidism; Insulin; Iodine; Iodine Isotopes; Lysine; Male; Methimazole; Middle Aged; Pituitary Neoplasms; Radioimmunoassay; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Vasopressins

Topics: Addison Disease; Adolescent; Adrenal Gland Diseases; Adrenal Glands; Adrenalectomy; Adrenocorticotropic Hormone; Adult; Aged; Child; Cushing Syndrome; Dexamethasone; Female; Fluorometry; Humans; Hydrocortisone; Hyperplasia; Hypopituitarism; Hypothalamo-Hypophyseal System; Injections, Intramuscular; Lysine; Male; Metyrapone; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Vasopressins

Topics: Diabetes Insipidus; Female; Humans; Hypothalamo-Hypophyseal System; Male; Pituitary Neoplasms; Vasopressins

Topics: Adult; Aged; Breast Neoplasms; Diabetes Insipidus; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Pituitary Neoplasms; Polyuria; Vasopressins

Topics: Aged; Humans; Hypopituitarism; Male; Multiple Myeloma; Pituitary Neoplasms; Prednisolone; Vasopressins

Topics: Acromegaly; Adenoma, Chromophobe; Craniopharyngioma; Female; Headache; Humans; Hypogonadism; Insulin; Iodine Radioisotopes; Male; Metyrapone; Optic Atrophy; Osteoporosis; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Skull Neoplasms; Thyroid Function Tests; Vasopressins; Vision Disorders

Topics: Adenoma; Cerebral Angiography; Female; Humans; Hyponatremia; Middle Aged; Pituitary Function Tests; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Vasopressins

Topics: Breast Neoplasms; Carcinoma; Deficiency Diseases; Diabetes Insipidus; Female; Humans; Injections, Subcutaneous; Male; Neoplasm Metastasis; Osmolar Concentration; Pituitary Function Tests; Pituitary Gland, Posterior; Pituitary Neoplasms; Polyuria; Vasopressins; Water Deprivation

Topics: Acetates; Acute Disease; Adult; Chlorides; Coma; Cortisone; Craniopharyngioma; Diabetes Insipidus; Diet Therapy; Electrocardiography; Humans; Hypernatremia; Hypokalemia; Male; Natriuresis; Osmolar Concentration; Paralysis; Pituitary Neoplasms; Postoperative Complications; Potassium; Sodium; Thirst; Thyroxine; Vasopressins

Topics: Adenoma, Acidophil; Adenoma, Chromophobe; Adrenocorticotropic Hormone; Adult; Aged; Diagnosis, Differential; Female; Humans; Hydrocortisone; Hypopituitarism; Hypothalamus; Male; Meningioma; Metyrapone; Middle Aged; Pituitary Neoplasms; Sella Turcica; Vasopressins

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; Aged; Cerebral Ventriculography; Female; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Metyrapone; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Pyrogens; Vasopressins

Topics: Animals; Chick Embryo; Diabetes Insipidus; Dogs; Hypothalamo-Hypophyseal System; Microscopy, Electron; Neurosecretion; Oxytocin; Pituitary Gland, Posterior; Pituitary Neoplasms; Vasopressins

Topics: 17-Hydroxycorticosteroids; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Brain Neoplasms; Circadian Rhythm; Dexamethasone; Diabetes Insipidus; Female; Hepatitis; Humans; Hydrocortisone; Injections, Intravenous; Lysine; Male; Metyrapone; Middle Aged; Pituitary Diseases; Pituitary Gland; Pituitary Neoplasms; Prednisolone; Vasopressins

Topics: Adolescent; Adrenocorticotropic Hormone; Blood Glucose; Body Height; Body Weight; Brain Neoplasms; Child; Craniopharyngioma; Exercise Test; Feeding and Eating Disorders; Female; Glucose Tolerance Test; Gonadotropins; Growth; Growth Hormone; Humans; Hypothalamus; Insulin; Male; Obesity; Pituitary Neoplasms; Postoperative Complications; Radioimmunoassay; Thirst; Thyrotropin; Vasopressins; Vision Disorders

Topics: Acromegaly; Adenoma; Adolescent; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Adult; Anorexia Nervosa; Brain Diseases; Brain Neoplasms; Cushing Syndrome; Endocrine System Diseases; Female; Humans; Hydrocortisone; Hypothalamus; Injections, Intramuscular; Lysine; Male; Metyrapone; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Vasopressins

Topics: Adrenocorticotropic Hormone; Growth Hormone; Humans; Hydrocortisone; Injections, Intramuscular; Lysine; Pituitary Neoplasms; Vasopressins

Topics: Adenoma; Adrenal Glands; Adult; Ethanol; Female; Humans; Hydrocortisone; Hypothalamus; Male; Middle Aged; Morphine; Pituitary Gland; Pituitary Neoplasms; Vasopressins

Topics: Acetylcholine; Adenoma; Animals; Cortisone; Estrone; Female; Neoplasms, Experimental; Nicotine; Oxytocin; Pituitary Neoplasms; Rats; Sodium Chloride; Vasopressins; Water-Electrolyte Balance

Topics: Adolescent; Adult; Aged; Dexamethasone; Diabetes Insipidus; Ethanol; Female; Glaucoma; Humans; Injections, Intravenous; Injections, Subcutaneous; Intraocular Pressure; Male; Middle Aged; Pituitary Gland, Posterior; Pituitary Neoplasms; Tonometry, Ocular; Vasopressins

Topics: Adenoma, Chromophobe; Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Craniopharyngioma; Female; Glucose Tolerance Test; Gonadotropins; Growth Hormone; Humans; Hydrocortisone; Hypopituitarism; Iodine; Male; Melanocyte-Stimulating Hormones; Middle Aged; Pituitary Neoplasms; Pituitary-Adrenal Function Tests; Thyroid Function Tests; Thyrotropin; Vasopressins; Water-Electrolyte Balance

Topics: Craniopharyngioma; Diabetes Insipidus; Estrogens; Humans; Hypogonadism; Medroxyprogesterone; North Carolina; Pituitary Neoplasms; Testosterone; Vasopressins

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Humans; Neoplasms; Pituitary Gland; Pituitary Neoplasms; Vasopressins