pituitrin and Adrenal-Insufficiency

Septic shock is a leading cause of mortality in intensive care units throughout the world. While this disease state represents a highly complex pathophysiology involving numerous organ systems, the early approach to care includes adequate hemodynamic support traditionally achieved via infusions of vasoactive medications after adequate fluid resuscitation. Relative adrenal and vasopressin deficiencies are a common feature of septic shock that contribute to impaired hemodynamics. Hydrocortisone and vasopressin are endocrine system hormone analogues that target the acute neuroendocrine imbalance associated with septic shock. This clinically focused annotated review describes the pathophysiological mechanisms behind their use and explores the potential clinical roles of early administration and synergy when combined.

Topics: Adrenal Insufficiency; Animals; Hemodynamics; Humans; Resuscitation; Shock, Septic; Vasopressins

Liver cirrhosis is a major cause of morbidity and mortality worldwide, mainly due to complications of portal hypertension. In this article, we review the current understanding on the pathophysiology, the diagnostic criteria and the available therapeutic options for patients with emerging hepatic syndromes in cirrhosis, namely the hepatorenal, hepato-adrenal and hepatopulmonary syndrome. The hepatorenal syndrome is a well-recognized complication of advanced cirrhosis and is usually associated with an accelerated course to death unless liver transplantation is performed. The hepatopulmonary syndrome is often missed in the evaluation of patients with cirrhosis; however, early recognition is essential for the efficient management of individual patients. The hepato-adrenal syndrome, although not fully characterized, offers an exciting field for research and potential therapeutic interventions.

Topics: Acute Kidney Injury; Adrenal Insufficiency; Ascites; Creatinine; Evidence-Based Medicine; Hepatorenal Syndrome; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Transplantation; Lypressin; Midodrine; Norepinephrine; Octreotide; Plasma Substitutes; Portasystemic Shunt, Transjugular Intrahepatic; Serum Albumin; Terlipressin; Vasodilator Agents; Vasopressins

Hyponatremia in virtually all patients results from water retention due to an inability to excrete ingested water. In most cases, this defect represents the persistent secretion of ADH (such as in effective circulating volume depletion, and in the syndrome of inappropriate ADH secretion), although free water excretion can also be limited in disorders in which ADH levels may be appropriately suppressed (such as in advanced renal failure, and in primary polydipsia). The symptoms of hyponatremia primarily reflect neurologic dysfunction induced by cerebral edema and are related both to the severity and to the rapidity of reductions in the plasma sodium concentration. The degree of cerebral edema which occurs in acute hyponatremia is much less with chronic hyponatremia, because the brain cells lose solutes, leading to the osmotic movement of water out the cells and less brain swelling. In general, hyponatremia is corrected acutely by giving Na+ to patients who are volume-depleted and by restricting water intake in patients who are normovolemic or edematous. The optimal rate of correction should be defined to prevent the risk of central demyelinating lesions.

Topics: Adrenal Insufficiency; Adult; Brain Edema; Edema; Female; Humans; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Kidney Failure, Chronic; Models, Biological; Osmolar Concentration; Potassium; Pregnancy; Syndrome; Vasopressins

Hyponatraemia is very common in AIDS patients. It is observed in about 40-50% of hospitalized patients. It may contribute to overall mortality in advanced disease. Vasopressin measurements in these patients basically present two distinct syndromes: hyponatraemia and 'normal' vasopressin levels (i.e. measurable vasopressin) and hyponatraemia with suppressed vasopressin. Hyponatraemia with suppressed vasopressin is very rare and has only been observed in AIDS patients with dementia and primary polydipsia. Hyponatraemia and measurable vasopressin can be also divided into two syndromes. In some patients vasopressin is 'appropriately' elevated, i.e. in those with body fluid losses (diarrhoea) or chronic hypovolaemia (adrenal failure); these patients also present with hyperuricaemia and other signs of low blood volume. In other patients vasopressin is 'inappropriately' elevated in those with no clinical evidence of hypovolaemia (typically characterized by low serum uric acid levels) such as in Pneumocystis carinii pneumonia and other opportunistic infections leading to SIADH. CSWS is a relatively frequent complication in some patients with cerebral infection or tumour. High-dose trimethoprim (for Pneumocystis carinii prevention) acts as an amiloride-like drug and induces a clinical state characterized by hyponatraemia and hyperkalaemia which is indistinguishable from hyporeninaemic hypoaldosteronism. The mechanism of the hyponatraemia caused by other drugs (miconazole, pentamidine, amphotericin, vidarabine) is not as yet known.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Insufficiency; Humans; Hyponatremia; Inappropriate ADH Syndrome; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Insufficiency; Diet, Sodium-Restricted; Diuretics; Humans; Hyponatremia; Neoplasms; Nephritis; Paraneoplastic Endocrine Syndromes; Sodium; Vasopressins

Topics: Adrenal Insufficiency; Carcinoma, Bronchogenic; Diagnosis, Differential; Hormones, Ectopic; Humans; Hyponatremia; Lung Neoplasms; Neurologic Manifestations; Phenytoin; Syndrome; Vasopressins

Topics: Adrenal Insufficiency; Diuresis; Glucocorticoids; Humans; Hypothyroidism; Kidney; Kidney Failure, Chronic; Osmolar Concentration; Urination Disorders; Vasopressins; Water; Water Intoxication

Topics: Adrenal Insufficiency; Animals; Congenital Hypothyroidism; Diabetes Insipidus; Heart Failure; Humans; Liver Cirrhosis; Osmolar Concentration; Pituitary Diseases; Vasopressins

Topics: Absorption; Adrenal Insufficiency; Adult; Blood Volume; Diuresis; Fludrocortisone; Glomerular Filtration Rate; Glucocorticoids; Humans; Kidney Tubules; Male; Methylprednisolone; Middle Aged; Osmolar Concentration; Placebos; Sodium; Vasopressins; Water

Patients with secondary adrenal insufficiency can present with impaired free water excretion and hyponatremia, which is due to the enhanced secretion of vasopressin (AVP) despite increased total body water. AVP is produced in magnocellular neurons in the paraventricular nucleus of the hypothalamus (PVH) and supraoptic nucleus and in parvocellular corticotropin-releasing factor (CRF) neurons in the PVH. This study aimed to elucidate whether magnocellular AVP neurons or parvocellular CRF neurons coexpressing AVP are responsible for the pathogenesis of hyponatremia in secondary adrenal insufficiency. The number of CRF neurons expressing copeptin, an AVP gene product, was significantly higher in adrenalectomized AVP-floxed mice (AVPfl/fl) than in sham-operated controls. Adrenalectomized AVPfl/fl mice supplemented with aldosterone showed impaired water diuresis under ad libitum access to water or after acute water loading. They became hyponatremic after acute water loading, and it was revealed under such conditions that aquaporin-2 (AQP2) protein levels were increased in the kidney. Furthermore, translocation of AQP2 to the apical membrane was markedly enhanced in renal collecting duct epithelial cells. Remarkably, all these abnormalities observed in the mouse model for secondary adrenal insufficiency were ameliorated in CRF-AVP-/- mice that lacked AVP in CRF neurons. Our study demonstrates that CRF neurons in the PVH are responsible for the pathogenesis of impaired water excretion in secondary adrenal insufficiency.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Animals; Aquaporin 2; Arginine Vasopressin; Corticotropin-Releasing Hormone; Diuresis; Hyponatremia; Hypothalamus; Mice; Neurons; Paraventricular Hypothalamic Nucleus; Pituitary Hormone-Releasing Hormones; Vasopressins

A 57-year-old woman with pre-dialysis chronic kidney disease (CKD) was hospitalized because of fever and fatigue. On admission, increased inflammatory response and pyuria with bacteriuria were observed. Pyelonephritis was successfully treated with antibiotics, whereas her fatigue continued and she developed progressive hypercalcemia and hyponatremia; serum sodium level, 116 mEq/L and corrected serum calcium level, 13.4 mg/dL. Plasma concentrations of adrenocorticotropic hormone and cortisol and serum luteinizing hormone were under the detection level. Although the reaction of other anterior pituitary hormones and the serum antidiuretic hormone (ADH) was preserved, the response of serum luteinizing hormone to administration of luteinizing hormone releasing hormone was impaired. Magnetic resonance imaging showed no structural abnormality in the thalamus, hypothalamus, and pituitary gland. She was diagnosed with adrenal insufficiency caused by partial hypopituitarism in concomitant with pyelonephritis. After starting hydrocortisone replacement, serum levels of sodium and calcium were rapidly normalized. This case highlights the importance of adrenal insufficiency as a differential diagnosis of hypercalcemia in patients with pre-dialysis CKD, especially when hyponatremia was concomitantly observed. Besides, infection should be considered as an important trigger for the development of latent adrenal insufficiency since it could increase the physiological demand of corticosteroid in the body. Also, CKD may enhance the magnitude of hypercalcemia since CKD patients have decreased capacity to increase urinary calcium excretion.

Topics: Acute Disease; Adrenal Insufficiency; Adrenocorticotropic Hormone; Diagnosis, Differential; Dialysis; Female; Humans; Hydrocortisone; Hypercalcemia; Hyponatremia; Hypopituitarism; Luteinizing Hormone; Magnetic Resonance Imaging; Middle Aged; Pyelonephritis; Renal Insufficiency, Chronic; Treatment Outcome; Vasopressins

A 78-year-old woman diagnosed with non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency had been under glucocorticoid replacement therapy since the age of 17 years. After several weeks of suffering from gastroenteritis with vomiting, she presented with disturbance of consciousness, hypotension, dehydration, and severe hyponatremia (108 mEq/L) and a markedly increased serum vasopressin concentration (45.5 pg/mL). She regained consciousness after correcting her body-fluid balance with hypertonic saline and intravenous hydrocortisone sodium therapy. Her hyponatremia was likely caused by extra-renal sodium loss and impaired water excretion induced by an increase of serum vasopressin due to volume depletion and glucocorticoid deficiency.

Topics: Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Aged; Female; Glucocorticoids; Humans; Hyponatremia; Saline Solution, Hypertonic; Sodium; Vasopressins

Hyponatremia is a serious, but often overlooked, electrolyte imbalance that has been independently associated with a wide range of deleterious changes involving many different body systems. Untreated acute hyponatremia can cause substantial morbidity and mortality as a result of osmotically induced cerebral edema, and excessively rapid correction of chronic hyponatremia can cause severe neurologic impairment and death as a result of osmotic demyelination. The diverse etiologies and comorbidities associated with hyponatremia pose substantial challenges in managing this disorder. In 2007, a panel of experts in hyponatremia convened to develop the Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations that defined strategies for clinicians caring for patients with hyponatremia. In the 6 years since the publication of that document, the field has seen several notable developments, including new evidence on morbidities and complications associated with hyponatremia, the importance of treating mild to moderate hyponatremia, and the efficacy and safety of vasopressin receptor antagonist therapy for hyponatremic patients. Therefore, additional guidance was deemed necessary and a panel of hyponatremia experts (which included all of the original panel members) was convened to update the previous recommendations for optimal current management of this disorder. The updated expert panel recommendations in this document represent recommended approaches for multiple etiologies of hyponatremia that are based on both consensus opinions of experts in hyponatremia and the most recent published data in this field.

Topics: Adrenal Insufficiency; Antidiuretic Hormone Receptor Antagonists; Clinical Trials as Topic; Diagnosis, Differential; Diuretics; Gastrointestinal Diseases; Genetic Diseases, X-Linked; Humans; Hyponatremia; Hypothyroidism; Hypovolemia; Inappropriate ADH Syndrome; Liver Cirrhosis; Polydipsia; Receptors, Vasopressin; Sodium Chloride; Vasopressins

Cardiac arrest is often fatal and can be extremely stressful to patients, even if spontaneous rhythm is returned. The purpose of this study was to analyze the hormonal response after return of spontaneous circulation (ROSC).. This is a retrospective review of the chart and laboratory findings in a single medical facility. The patients admitted to the intensive care unit after successful resuscitation after out-of-hospital cardiac arrest were retrospectively identified and evaluated. Patients with hormonal diseases, patients who received cortisol treatment, those experiencing trauma, and pregnant women were excluded. Serum cortisol, adrenocorticotropic hormone (ACTH), and anti-diuretic hormone (ADH (vasopressin)) were analyzed and a corticotropin-stimulation test was performed. Mortality at one week and one month after admission, and neurologic outcome (cerebral performance category (CPC)) one month after admission were evaluated.. A total of 117 patients, including 84 males (71.8%), were evaluated in this study. One week and one month after admission, 87 (74.4%) and 65 patients (55.6%) survived, respectively. Relative adrenal insufficiency, and higher plasma ACTH and ADH levels were associated with shock-related mortality (P = 0.046, 0.005, and 0.037, respectively), and ACTH and ADH levels were also associated with late mortality (P = 0.002 and 0.004, respectively). Patients with relative adrenal insufficiency, ACTH ≧5 pg/mL, and ADH ≧30 pg/mL, had a two-fold increased risk of a poor outcome (shock-related mortality): (odds ratio (OR), 2.601 and 95% confidence interval (CI), 1.015 to 6.664; OR, 2.759 and 95% CI, 1.060 to 7.185; OR, 2.576 and 95% CI, 1.051 to 6.313, respectively). Thirty-five patients (29.9%) had a good CPC (1 to 2), and 82 patients (70.1%) had a bad CPC (3 to 5). Age ≧50 years and an ADH ≧30 pg/mL were associated with a bad CPC (OR, 4.564 and 95% CI, 1.794 to 11.612; OR, 6.568 and 95% CI, 1.918 to 22.483, respectively).. The patients with relative adrenal insufficiency and higher blood levels of ACTH and ADH upon ROSC after cardiac arrest had a poor outcome. The effectiveness of administration of cortisol and ADH to patients upon ROSC after cardiac arrest is uncertain and additional studies are needed.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Biomarkers; Blood Circulation; Cardiopulmonary Resuscitation; Female; Hospital Mortality; Humans; Hydrocortisone; Intensive Care Units; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Retrospective Studies; Treatment Outcome; Vasopressins

Topics: Adrenal Insufficiency; Adult; Amputation, Surgical; Anti-Bacterial Agents; Disseminated Intravascular Coagulation; Epoprostenol; Escherichia coli; Escherichia coli Infections; Female; Gangrene; Humans; Hydrocortisone; Hypotension; Kidney Calculi; Leg; Metatarsus; Pain; Platelet Aggregation Inhibitors; Purpura Fulminans; Shock, Septic; Vasopressins

Up to 21% of severe cases of malaria tropica are associated with polyuria and are life-threatening. We describe a 39-yr-old man with malaria tropica who developed disseminated intravascular coagulation, polyuria, and a pituitary lesion. Empiric treatment with vasopressin improved the polyuria. This is the first case of malaria tropica in which central diabetes insipidus has been documented.

Topics: Adrenal Insufficiency; Adult; Diabetes Insipidus, Neurogenic; Disseminated Intravascular Coagulation; Humans; Hydrocortisone; Magnetic Resonance Imaging; Malaria, Falciparum; Male; Natriuresis; Pituitary Gland, Posterior; Polyuria; Pulmonary Embolism; Renal Insufficiency; Vasopressins

Traumatic hypopituitarism was diagnosed in an 11-month-old male neutered cat. The presenting complaints were polydipsia, polyuria and lethargy of three months' duration. Craniocerebral trauma, as a result of a road traffic accident, had preceded the onset of clinical signs by six weeks. Neurological examination revealed right-sided mydriasis, reduced visual and tactile left forelimb placing reflexes and decreased proprioception in both the left fore- and hindlimb. Initial laboratory findings included hypernatraemia, hyperchloraemia, mild azotaemia, eosinophilia and isosthenuria. Low basal cortisol, thyroxine, thyroid-stimulating hormone and insulin growth factor-1 were noted. Subsequent to treatment with prednisolone, a water deprivation test confirmed the presence of central diabetes insipidus and therapy with synthetic antidiuretic hormone successfully ameliorated the polydipsia.

Topics: Accidents, Traffic; Adrenal Insufficiency; Animals; Cat Diseases; Cats; Craniocerebral Trauma; Diabetes Insipidus; Diagnosis, Differential; Male; Vasopressins

Corticotropin-releasing hormone (CRH)-deficient (KO) mice provide a unique system to define the role of CRH in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Despite several manifestations of chronic glucocorticoid insufficiency, basal pituitary proopiomelanocortin (POMC) mRNA, adrenocorticotrophic hormone (ACTH) peptide content within the pituitary, and plasma ACTH concentrations are not elevated in CRH KO mice. The normal POMC mRNA content in KO mice is dependent upon residual glucocorticoid secretion, as it increases in both KO and WT mice after adrenalectomy; this increase is reversed by glucocorticoid, but not aldosterone, replacement. However, the normal plasma levels of ACTH in CRH KO mice are not dependent upon residual glucocorticoid secretion, because, after adrenalectomy, these levels do not undergo the normal increase seen in KO mice despite the increase in POMC mRNA content. Administration of CRH restores ACTH secretion to its expected high level in adrenalectomized CRH KO mice. Thus, in adrenal insufficiency, loss of glucocorticoid feedback by itself can increase POMC gene expression in the pituitary; but CRH action is essential for this to result in increased secretion of ACTH. This may explain why, after withdrawal of chronic glucocorticoid treatment, reactivation of CRH secretion is a necessary prerequisite for recovery from suppression of the HPA axis.

Topics: Adrenal Insufficiency; Adrenalectomy; Adrenocorticotropic Hormone; Animals; Corticotropin-Releasing Hormone; Female; Glucocorticoids; Hypothalamo-Hypophyseal System; Male; Mice; Mice, Knockout; Pituitary Gland; Pituitary-Adrenal System; Pro-Opiomelanocortin; Vasopressins

A case of isolated ACTH deficiency who developed autoimmune-mediated hypothyroidism and still showed impaired water diuresis during glucocorticoid replacement therapy is reported. A 45-year-old woman was initially admitted for nausea, vomiting, and general malaise. Her serum sodium and plasma osmolality, ACTH and cortisol values were low, but her urine osmolality was high. Other pituitary hormone levels, thyroid hormone levels, and a computed tomogram of the pituitary gland were normal. The patient was treated with hydrocortisone and followed in the outpatient clinic; however, she was lost to follow up 18 months after admission. Three years later she presented with hypoglycemia and hyponatremia. Her serum or plasma ACTH, FT3, FT4, cortisol levels were low and her serum TSH level was high. Pituitary stimulation tests revealed a blunted response of ACTH to CRH and an exaggerated response of TSH to TRH. Plasma ADH was inappropriately high, and a water-loading test revealed impaired water diuresis and poor suppression of ADH. Although ADH was suppressed, impaired water diuresis was observed in the water loading test after hydrocortisone supplementation. Thyroxine supplementation completely normalized the water diuresis. Her outpatient clinic medical records revealed a gradual increase in TSH levels during follow up, indicating that she had developed hypothyroidism during glucocorticoid replacement therapy. The hyponatremia on the first admission was due to glucocorticoid deficiency, whereas the hyponatremia on the second admission was due to combined deficiencies of glucocorticoid and thyroid hormones.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Autoimmune Diseases; Blood; Diuresis; Female; Hormone Replacement Therapy; Humans; Hydrocortisone; Hyponatremia; Hypothyroidism; Middle Aged; Osmolar Concentration; Thyrotropin; Thyroxine; Triiodothyronine; Urine; Vasopressins

Topics: Adrenal Insufficiency; Humans; Hyponatremia; Hypothalamo-Hypophyseal System; Inappropriate ADH Syndrome; Pituitary-Adrenal System; Practice Guidelines as Topic; Vasopressins

A 60-year-old woman was admitted with severe hyponatremia. Basal values of adrenocorticotropic hormone (ACTH), thyroid hormone and cortisol were normal on admission. Impairment of water diuresis was observed by water loading test. Initially, we diagnosed her condition as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). By provocation test, we finally confirmed that the hyponatremia was caused by hypothalamic adrenal insufficiency. The basal values of ACTH and cortisol might not be sufficient to exclude the possibility of adrenal insufficiency. Therefore, it is necessary to evaluate adrenal function by provocation test or to re-evaluate it after recovery from hyponatremia.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Female; Humans; Hydrocortisone; Hyponatremia; Hypothalamo-Hypophyseal System; Inappropriate ADH Syndrome; Middle Aged; Pituitary-Adrenal System; Thyrotropin; 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

A 70-year-old woman was admitted because of disturbance of her consciousness. Physical examinations and laboratory data suggested hypothyroidism. Primary hypothyroidism was subsequently confirmed with endocrinological examinations. Antidiuretic hormone (ADH) levels were elevated despite severe hyponatremia. On admission, urinary sodium concentration was 10mEq/l. The patient was treated with saline intravenously; serum sodium level increased from 120 to 125mEq/l and urinary sodium concentration increased from 10 to 54mEq/l. Mental confusion developed and serum sodium level dropped with urinary sodium concentration above 20mEq/l when thyroid replacement was started with the cessation of saline infusion. The patient's state of consciousness, elevated ADH levels, decreased serum sodium level and urinary sodium concentration were improved by thyroid replacement together with hydrocortisone therapy. Effects of acute water loading were abnormal with the administration of iodothyronine (T3) alone but were normalized with the administration of hydrocortisone together with T3. On discharge she was treated with the oral administration of levothyroxine alone. Pituitary hormones were normal. These results suggest that the patient was in a state of hypoadrenocorticism. Impaired water excretion in a state of hypoadrenocorticism due to hypothyroidism may give rise to an inappropriate secretion of ADH thereby resulting in hyponatremia, which in turn leads to hypotonic dehydration induced by water intoxication.

Topics: Adrenal Cortex; Adrenal Insufficiency; Aged; Dehydration; Female; Humans; Hyponatremia; Hypothyroidism; Vasopressins; Water Intoxication

Topics: Adrenal Cortex; Adrenal Insufficiency; Animals; Median Eminence; Neurophysins; Neurosecretory Systems; Pituitary Gland, Posterior; Pituitary-Adrenal System; Vasopressins

The effect of adrenal insufficiency on the plasma concentrations of two vasoactive hormones, vasopressin and angiotensin II, was studied in conscious dogs. In addition the role of vasopressin in the maintenance of blood pressure during adrenal insufficiency was studied using [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]arginine vasopressin, a specific antagonist of the vasoconstrictor action of vasopressin. Dogs were bilaterally adrenalectomized and maintained on daily cortisol and deoxycorticosterone acetate injections. Withdrawal of steroids for 4 days resulted in a 4-fold increase in plasma vasopressin concentration (P less than 0.05) and a 3-fold increase in plasma angiotensin II concentration (P less than 0.001); mean arterial pressure did not change significantly. Administration of the vasopressin antagonist in adrenalectomized dogs maintained on steroids had no effect on blood pressure. In marked contrast, vasopressin blockade in dogs with adrenal insufficiency decreased mean arterial pressure by 22 +/- 5 mm Hg (P less than 0.001). These results demonstrate the plasma angiotensin II and vasopressin concentrations increase during adrenal insufficiency in conscious dogs, and that vasopressin plays an important role in blood pressure regulation in this hypovolemic state.

Topics: Adrenal Insufficiency; Angiotensin II; Animals; Blood Pressure; Dogs; Female; Heart Rate; Male; Vasoconstriction; Vasopressins

The pathophysiology of hyponatremia in adrenal insufficiency has been a subject of intense controversy. The controversy centers on whether the inability of the kidney to maximally dilute the urine is secondary to increased levels of antidiuretic hormone (ADH) or is independent of ADH. Review of the pertinent studies allows us to conclude that (1) in prolonged glucocorticoid deficiency, plasma ADH levels are elevated because of decreased effective circulating blood volume; (2) in mineralocorticoid deficiency, plasma ADH levels may also be elevated, but in this case because of decreased absolute circulating blood volume; (3) in both instances the elevated ADH levels impair the ability to dilute the urine; and (4) in both glucocorticoid and mineralocorticoid deficiency hemodynamic changes may also contribute, independently of ADH, by limiting delivery of tubular fluid to the diluting site.

Topics: Adrenal Insufficiency; Glucocorticoids; Hemodynamics; Humans; Hyponatremia; Kidney; Mineralocorticoids; Vasopressins

Topics: Adrenal Insufficiency; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Vasopressins

Mineralo- and glucocorticoid-deficient states, such as Addison's disease, are partly characterized by an inability to generate a maximally concentrated urine. The purpose of the present study was to develop a model of adrenal insufficiency and to determine whether changes in the intrinsic function of the collecting duct could partly account for this concentrating defect. Two kinds of experiments were performed: an assessment of the in vivo ability of adrenal-ectomized rabbits to concentrate their urine, and an examination of the intrinsic hydroosmotic responsiveness of in vitro perfused collecting ducts isolated from normal and adrenalectomized rabbits. The present study demonstrates that adrenalectomized rabbits are unable to concentrate their urine maximally, and that the in vivo administration of either deoxycorticosterone, 250 mug/kg, or dexamethasone, 50 mug/kg, restored to or toward normal their concentrating ability. When cortical collecting tubules from adrenalectomized rabbits were perfused in vitro, they demonstrated a markedly blunted hydroosmotic response to antidiuretic hormone (ADH), which was corrected by the in vitro addition of either aldosterone (50 pM) or dexamethasone (50 pM), but not progesterone (50 pM). The steroids by themselves, in the absence of ADH, had no intrinsic effect on the water permeability of the collecting duct. The blunted hydroosmotic response across cortical collecting tubules from adrenal-ectomized rabbits was corrected by the addition of either 8-bromo cyclic AMP or a potent phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine. The present studies show that the cortical collecting tubules obtained from adrenalectomized rabbits do not respond normally to ADH. The poor hydroosmotic response to ADH was corrected by exogenous aldosterone, dexamethasone, an analog of cyclic AMP, or a phosphodiesterase inhibitor. In conclusion, the present studies are consistent with the view that the concentrating defect seen in adrenal insufficiency is at least partly the result of the absence of the permissive effect that adrenal steroids exert on the ADH-induced reabsorption of water across the collecting duct. The absence of adrenal steroids results in a diminished rate of cyclic AMP accumulation in the cells of the collecting duct, either as a result of an augmented activity of cyclic AMP phosphodiesterase or a diminished rate of cyclic AMP generation.

Topics: 1-Methyl-3-isobutylxanthine; Adrenal Insufficiency; Adrenalectomy; Animals; Cyclic AMP; Glucocorticoids; Kidney Concentrating Ability; Kidney Tubules; Mineralocorticoids; Rabbits; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Catecholamines; Child; Child, Preschool; Diabetes Insipidus; Emotions; Endocrine System Diseases; Growth Disorders; Hormones; Humans; Hyperthyroidism; Hypopituitarism; Hypothyroidism; Infant; Infant, Newborn; Protein-Energy Malnutrition; Vasopressins

Plasma and urinary arginine vasopressin (AVP) in normal subjects and in patients with various water metabolism disorders was measured using a sensitive, specific radioimmunoassay. The AVP plasma levels in normal subjects were 3.1 +/- 1.2 pg/ml. The parallel changes in plasma osmolality, plasma AVP concentration, and urinary osmolality were observed after water load. In patients with various kinds of hyponatremia and impaired water excretion, plasma AVP concentrations were within or over normal levels, suggesting that persistent secretion of AVP may play an important role in the pathogenesis of hyponatremia. Variable levels of plasma AVP were observed in patients with essential hypernatremia, which in turn suggested that osmoreceptors may be selectively damaged in some patients, and that ADH-secreting neurons are also involved in others. Our radioimmunoassay facility made it possible for us to measure plasma and urinary DDAVP in the treatment of diabetes insipidus.

Topics: Adrenal Insufficiency; Adult; Animals; Arginine Vasopressin; Ascites; Diabetes Insipidus; Dogs; Edema; Humans; Hypernatremia; Hyponatremia; Hypotension, Orthostatic; Infant; Neoplasms; Osmolar Concentration; Radioimmunoassay; Vasopressins; Water

Three cases of septo-optic dysplasia are related in infants. A neurogenic diabetes insipidus and an central adrenocortical insufficiency is proved. An growth hormone deficiency is founded in one case. The other anterior pituitary functions are normal. The pneumo-encephalography with congenital absence of septum lucidum and the ophtalmologic anomalies are typical. The treatment is envisaged. In one case an autopsy sustains the radiologic aspect.

Topics: Adrenal Insufficiency; Child, Preschool; Diabetes Insipidus; Female; Humans; Hypopituitarism; Infant; Infant, Newborn; Male; Optic Nerve; Septum Pellucidum; Vasopressins

Topics: Adrenal Insufficiency; Humans; Hyperglycemia; Hyperlipidemias; Hyponatremia; Pituitary Gland, Posterior; Syndrome; Vasopressins; Water Intoxication; Water-Electrolyte Balance

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Child; Child, Preschool; Depression, Chemical; Female; Humans; Hydrocortisone; Infant; Male; Nephrotic Syndrome; Prednisone; Spectrometry, Fluorescence; Stimulation, Chemical; Time Factors; Vasopressins

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Circadian Rhythm; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Stress, Physiological; Vasopressins

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aldosterone; Dehydroepiandrosterone; Estriol; Female; Humans; Hydroxycorticosteroids; Hypopituitarism; Lysine; Pregnancy; Pregnancy Complications; Vasopressins

Topics: Adrenal Glands; Adrenal Insufficiency; Blindness; Bradycardia; Brain; Electrolytes; Female; Glucagon; Glucose; Glucose Tolerance Test; Growth Hormone; Humans; Hypoglycemia; Hypopituitarism; Infant; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Intellectual Disability; Male; Pituitary Gland; Seizures; Vasopressins

Topics: 17-Hydroxycorticosteroids; Adolescent; Adrenal Gland Neoplasms; Adrenal Glands; Adrenal Insufficiency; Adrenalectomy; Adrenocorticotropic Hormone; Adult; Child; Cortisone; Cushing Syndrome; Female; Humans; Hydrocortisone; Hypothalamus; Male; Metyrapone; Middle Aged; Pituitary Gland; Pituitary-Adrenal Function Tests; Postoperative Complications; Prednisone; Stress, Physiological; Time Factors; Vasopressins

Topics: Adolescent; Adrenal Insufficiency; Arachnoid; Arachnoiditis; Brain Diseases; Carbamazepine; Diabetes Insipidus; Drinking; Growth Hormone; Humans; Hydrocortisone; Hypogonadism; Hypothalamo-Hypophyseal System; Male; Osmolar Concentration; Pituitary Diseases; Thirst; Thyroid Hormones; Vasopressins

Topics: 11-Hydroxycorticosteroids; 17-Hydroxycorticosteroids; Adolescent; Adrenal Glands; Adrenal Insufficiency; Blood Glucose; Child; Child, Preschool; Dwarfism; Evaluation Studies as Topic; Female; Humans; Hypoglycemia; Hypopituitarism; Hypothalamus; Insulin; Lysine; Male; Metyrapone; Obesity; Pituitary Gland; Pituitary-Adrenal Function Tests; Time Factors; Vasopressins

Topics: Adrenal Insufficiency; Animals; Ascites; Diuresis; Edema; Heart Failure; Humans; Male; Methods; Rats; Vasopressins

The response of trained, conscious dogs to an acute water load was studied before adrenalectomy and under five conditions of hormonal replacement and sodium intake after adrenalectomy. Before adrenalectomy, with the dogs drinking isotonic saline, the minimal urinary osmolality (Uosm) was 47+/-7 (SEM) mOsm and free-water clearance (C(H2O)) was 8.6+/-1 ml/min. These values were not different after adrenalectomy with or without deoxycorticosterone (DOCA) if the animals continued to drink saline and receive dexamethasone. Moreover, after adrenalectomy in the presence of saline drinking both dexamethasone and DOCA could be withdrawn for up to 4 days without impairment of diluting ability (Uosm, 54+/-7 mOsm and C(H2O), 7.3+/-1 ml/min). In contrast, when the dogs drank tap water (Na intake 30 mEq/day), water loading in the absence of dexamethasone and DOCA was associated with a significantly higher Uosm (127+/-28 mOsm) and lower C(H2O) (2.7+/-0.3 ml/min). Replacing DOCA alone in the presence of this limited Na intake returned diluting ability to normal (Uosm 31+/-7 mOsm, C(H2O) 7.7+/-0.5 ml/min). Glomerular filtration rate for each animal was the same under each condition except for a significant diminution which occurred when dexamethasone and DOCA were withdrawn while the animals were on a 30 mEq sodium intake. In contrast to previous conclusions, the present results indicate that in the absence of adrenal hormones normal renal diluting ability may occur, indicating both maximal suppression of vasopressin release and maximal distal tubular impermeability to water. In the present study the diluting defect observed after adrenalectomy related to negative sodium balance and could be overcome by either replacement with DOCA or a high intake of sodium alone.

Topics: Adrenal Insufficiency; Adrenalectomy; Animals; Desoxycorticosterone; Dexamethasone; Diet; Dogs; Female; Glomerular Filtration Rate; Kidney Tubules; Osmolar Concentration; Sodium; Urine; Vasopressins

Topics: Adolescent; Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Circadian Rhythm; Desoxycorticosterone; Female; Humans; Hydrocortisone; Hypopituitarism; Male; Metyrapone; Middle Aged; Pituitary Diseases; Pituitary-Adrenal Function Tests; Vasopressins

Topics: Adrenal Insufficiency; Adrenalectomy; Aging; Animals; Cortisone; Female; Juxtaglomerular Apparatus; Male; Mineralocorticoids; Nephrectomy; Rats; Sex Factors; Sodium Chloride; Spironolactone; Stimulation, Chemical; Vasopressins

Topics: Adrenal Insufficiency; Adrenalectomy; Animals; Anxiety; Blood; Body Weight; Diuresis; Dogs; Handling, Psychological; Hematocrit; Humans; Hydrocortisone; Osmolar Concentration; Potassium; Renin; Sodium; Sodium Chloride; Vasopressins

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Cortex Hormones; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Cushing Syndrome; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal Function Tests; Prednisone; Stress, Physiological; Vasopressins

Topics: Adrenal Insufficiency; Adrenalectomy; Animals; Blood Pressure; Blood Volume; Body Weight; Cortisone; Dogs; Potassium; Sodium; Sodium Chloride; Vasopressins

In order to determine whether or not antidiuretic hormone (ADH) is essential to the inhibition of an acute water diuresis in adrenal insufficiency, the response to oral water loads was tested in rats with hereditary hypothalamic diabetes insipidus (DI) which lack ADH. It was found that 60 min after water loads of 3 or 5% of body weight urine flow was significantly lower and urine osmolality significantly higher in adrenalectomized DI rats than in the same DI rats before removal of their adrenal glands. The efficacy of gluco- and mineralocorticoids in reversing the inhibition was then determined in the same adrenalectomized DI rats. Prednisolone alone, administered either acutely or chronically, restored the response in urine flow to that seen in the same rats before adrenalectomy, but failed to correct the defect in urinary dilution. Aldosterone when given alone tended to correct the diluting ability but not the response in urine flow. When these two adrenal cortical hormones were given simultaneously, both the urine flow and urine osmolality were nearly identical to what they had been in the same DI rats before adrenalectomy. These studies strongly suggest (a) that ADH is not essential to the inhibition of an acute water diuresis in adrenal insufficiency, although it may abet the inhibition in individuals without diabetes insipidus, which can elaborate ADH; and (b) that both gluco- and mineralocorticoids are required in adrenal insufficiency in order to fully restore the water diuresis as judged by the dual criteria of urine flow and urine osmolality.

Topics: Adrenal Glands; Adrenal Insufficiency; Adrenalectomy; Aldosterone; Animals; Diabetes Insipidus; Diuresis; Female; Glomerular Filtration Rate; Kidney; Male; Osmolar Concentration; Prednisolone; Rats; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Insufficiency; Adrenocorticotropic Hormone; Dexamethasone; Diuresis; Ethanol; Extracellular Space; Female; Glucocorticoids; Growth Hormone; Humans; Hyponatremia; Hypopituitarism; Infusions, Parenteral; Metyrapone; Middle Aged; Natriuresis; Sodium Chloride; Vasopressins; Water-Electrolyte Balance

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Addison Disease; Adrenal Insufficiency; Humans; Vasopressins

Topics: 17-Hydroxycorticosteroids; Adenocarcinoma; Adrenal Gland Neoplasms; Adrenal Glands; Adrenal Insufficiency; Aldosterone; Body Weight; Female; Humans; Hyponatremia; Lung Neoplasms; Middle Aged; Neoplasm Metastasis; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: 17-Hydroxycorticosteroids; Adrenal Gland Diseases; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Arginine; Corticotropin-Releasing Hormone; Cushing Syndrome; Female; Humans; Hypothalamo-Hypophyseal System; Insulin; Lysine; Male; Metyrapone; Middle Aged; Pituitary Gland; Pituitary-Adrenal Function Tests; Pyrogens; Stimulation, Chemical; Vasopressins

Topics: Absorption; Adrenal Insufficiency; Adrenalectomy; Aldosterone; Animals; Cell Membrane Permeability; Cortisone; Dexamethasone; Diuresis; Glomerular Filtration Rate; Glucocorticoids; Kidney Tubules; Male; Osmolar Concentration; Perfusion; Rats; Vasopressins; Water

Topics: Adrenal Insufficiency; Ascites; Brain Injuries; Diabetes Insipidus; Eclampsia; Endocrine System Diseases; Female; Humans; Liver Cirrhosis; Oxytocin; Pregnancy; Vasopressins; Water-Electrolyte Balance

Trichloroacetic acid extracts of plasma were fractionated on a CG-50 resin column and the 50% acetic acid eluents chromatographed on silicic acid-impregnated glass paper in butanol-acetic acid-water. The specific arginine vasopressin (AVP) zone was eluted and assayed for antidiuretic activity in the diuretic rat. Thioglycolate inactivation was used to confirm AVP activity. Recovery of as little as 4 muU AVP per ml plasma ranged between 80 and 90%. In normal subjects after an overnight fast, plasma AVP ranged between 2.5 and 10.0 muU per ml. AVP secretion was inhibited by hemodilution and stimulated with nicotine and hypertonic saline. Plasma AVP was absent in patients with diabetes insipidus even after neurohypophyseal stimulation. Plasma AVP was abnormally elevated during mild dehydration and remained above the normal range despite hemodilution in patients with untreated adrenocortical insufficiency demonstrating a delayed water diuresis. Glucosteroid therapy lowered plasma AVP to normal in dehydrated patients. A normal diuretic response to hydration was accompanied by a fall in plasma AVP to zero in steroid-treated patients. These findings suggest that hypersecretion of AVP may play an important role in the abnormal water metabolism of adrenocortical insufficiency and that the glucosteroids promote normal water diuresis by inhibiting the secretion of AVP from the neurohypophysis.

Topics: Addison Disease; Adrenal Insufficiency; Adult; Animals; Arginine; Chromatography, Paper; Diuresis; Female; Glucose; Glycolates; Humans; Hydrocortisone; Hypopituitarism; Hypothalamo-Hypophyseal System; Male; Middle Aged; Nicotine; Rats; Sodium Chloride; Steroids; Thioglycolates; Trichloroacetic Acid; Vasopressins

Topics: Adrenal Insufficiency; Diabetes Insipidus; Humans; Injections, Intravenous; Kidney; Potassium; Sodium; Vasopressins

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Insufficiency; Adrenocorticotropic Hormone; Creatine; Creatinine; Diagnosis, Differential; Drug Therapy; Eosinophils; Follicle Stimulating Hormone; Humans; Hyponatremia; Hypothalamus; Pituitary Gland; Pituitary Gland, Posterior; Pituitary-Adrenal Function Tests; Prednisone; Sodium; Urine; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Insufficiency; Humans; Hypothyroidism; Male; Middle Aged; Vasopressins

Topics: Adrenal Insufficiency; Humans; Vasopressins

Topics: Adrenal Insufficiency; Adrenalectomy; Animals; Arginine; Blood; Creatine; Creatinine; Diuresis; Dogs; Hydrocortisone; Hypopituitarism; Permeability; Pharmacology; Physiology; Rats; Research; Urine; Vasopressins; Water

Topics: Addison Disease; Adrenal Cortex; Adrenal Insufficiency; Humans; Hypoadrenocorticism, Familial; Pituitary Gland; Pituitary Gland, Posterior; Vasopressins

Topics: Adrenal Insufficiency; Adrenalectomy; Liver; Sodium Chloride; Vasopressins; Water