pituitrin and Hypothyroidism

Disturbances in sodium concentration are common in the critically ill patient and associated with increased mortality. The key principle in treatment and prevention is that plasma [Na+] (P-[Na+]) is determined by external water and cation balances. P-[Na+] determines plasma tonicity. An important exception is hyperglycaemia, where P-[Na+] may be reduced despite plasma hypertonicity. The patient is first treated to secure airway, breathing and circulation to diminish secondary organ damage. Symptoms are critical when handling a patient with hyponatraemia. Severe symptoms are treated with 2 ml/kg 3% NaCl bolus infusions irrespective of the supposed duration of hyponatraemia. The goal is to reduce cerebral symptoms. The bolus therapy ensures an immediate and controllable rise in P-[Na+]. A maximum of three boluses are given (increases P-[Na+] about 6 mmol/l). In all patients with hyponatraemia, correction above 10 mmol/l/day must be avoided to reduce the risk of osmotic demyelination. Practical measures for handling a rapid rise in P-[Na+] are discussed. The risk of overcorrection is associated with the mechanisms that cause hyponatraemia. Traditional classifications according to volume status are notoriously difficult to handle in clinical practice. Moreover, multiple combined mechanisms are common. More than one mechanism must therefore be considered for safe and lasting correction. Hypernatraemia is less common than hyponatraemia, but implies that the patient is more ill and has a worse prognosis. A practical approach includes treatment of the underlying diseases and restoration of the distorted water and salt balances. Multiple combined mechanisms are common and must be searched for. Importantly, hypernatraemia is not only a matter of water deficit, and treatment of the critically ill patient with an accumulated fluid balance of 20 litres and corresponding weight gain should not comprise more water, but measures to invoke a negative cation balance. Reduction of hypernatraemia/hypertonicity is critical, but should not exceed 12 mmol/l/day in order to reduce the risk of rebounding brain oedema.

Topics: Critical Illness; Decision Support Techniques; Diuresis; Diuretics; Humans; Hypernatremia; Hyponatremia; Hypothyroidism; Iatrogenic Disease; Inappropriate ADH Syndrome; Plasma Volume; Sodium Chloride Symporter Inhibitors; Vasopressins

Topics: Animals; Atrial Natriuretic Factor; Blood Volume; Cardiomegaly; Catecholamines; Humans; Hypertension; Hyperthyroidism; Hypothyroidism; Myocardial Contraction; Receptors, Thyroid Hormone; Renin-Angiotensin System; Thyroxine; Triiodothyronine; Vascular Resistance; Vasopressins

This discussion emphasizes two aspects of hyponatremia: classification according to effective osmolality of the body fluid, and distinction between appropriate and inappropriate ADH secretion. Assessment of the effective osmolality is important because the main deleterious effect of hyponatremia is cell overhydration, which occurs only when the effective osmolality is reduced. Since most cases of hyponatremia are associated with low effective osmolality, cell overhydration is a hallmark of acute hyponatremia. On the other hand, one must be aware of other types of hyponatremia in which effective osmolality is either normal or even increased. Inappropriateness of ADH secretion is defined as ADH secretion that occurs despite low effective osmolality and normal or expanded effective vascular volume. ADH secretion that occurs in hyponatremia is deemed appropriate if the effective vascular volume is low. The use of laboratory parameters is much more reliable in determining effective vascular volume than is careful physical examination.

Topics: Body Water; Extracellular Space; Glucocorticoids; Glucose; Homeostasis; Humans; Hyponatremia; Hypothyroidism; Neurophysins; Osmolar Concentration; Protein Precursors; Transurethral Resection of Prostate; 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

Topics: Atrial Natriuretic Factor; Biomarkers; Humans; Hyperaldosteronism; Hypothyroidism; Inappropriate ADH Syndrome; Vasopressins; Water-Electrolyte Balance

Topics: Adult; Animals; Congenital Hypothyroidism; Diseases in Twins; Female; Humans; Hyponatremia; Hypothyroidism; Infant; Infant, Newborn; Infant, Premature, Diseases; Male; Pregnancy; Thyroxine; Vasopressins

The osmoregulation of arginine-8-vasopressin (AVP) was investigated in 14 patients with primary hypothyroidism, in 6 with Addison's disease, and in 21 with central diabetes insipidus (CDI). In the latter disease the effect of histamine stimulus was also evaluated. Plasma AVP was measured by radioimmunoassay (RIA). Patients with primary hypothyroidism were classified into subgroups with elevated or normal basal levels of plasma AVP. A decreased osmotic threshold was found in hypothyroid patients with augmented basal AVP levels. Patients with Addison's disease exhibited an increased basal level of plasma AVP and a decreased osmotic threshold. CDI patients according to their AVP responses on osmotic stimulus fell into two groups: CDI I gave no response at all, while CDI II responded subnormally. CDI II exhibited blunted AVP release to histamine. The AVP reactions of the CDI I patients fell into two subgroups: CDI I/A had undetectable plasma AVP, whereas histamine evoked AVP release in CDI I/B. Patients with CDI II suffer from a partial CDI, while those with CDI I/A represent a complete form of the disease and CDI I/B presumably have an osmoreceptor failure.

Topics: Addison Disease; Adult; Arginine; Diabetes Insipidus; Female; Humans; Hypothyroidism; Male; Middle Aged; Saline Solution, Hypertonic; Vasopressins; Water-Electrolyte Balance

Topics: Adrenocorticotropic Hormone; Brain; Calcifediol; Calcium; Chronic Disease; Estradiol; Estrogens; Female; Follicle Stimulating Hormone; Glucose; Growth Hormone; Hormones; Humans; Hypothalamo-Hypophyseal System; Hypothyroidism; Insulin; Liver Cirrhosis, Alcoholic; Liver Diseases; Luteinizing Hormone; Male; Melatonin; Neurotransmitter Agents; Parathyroid Hormone; Phosphorus; Pituitary Gland; Prolactin; Renin-Angiotensin System; Somatomedins; Testosterone; Thyroid Hormones; Thyrotropin-Releasing Hormone; Vasopressins; Vitamin D

Vasopressin is capable of being stimulated by several nonosmotic factors such as hypovolemia, hypotension, pharmacologic agents and stress. Vasopressin levels of only 1-2 pg/ml are capable of decreasing substantially renal water excretion. If water is ingested or given intravenously in this setting, positive water balance with hypotonicity and hyponatremia of extracellular fluid (ECF) occur. Such dilution of the ECF results in water movement into cells and potential central nervous system complications [3]. Many disorders (see Tab. 1) may be associated with nonosmotic stimulation of vasopressin release. In these clinical settings, judicious administration of free water and monitoring of serum sodium concentration is necessary. A knowledge of clinical conditions associated with vasopressin-mediated water retention may have therapeutic implications as well. Thus, in recent years it has become appreciated that selected pharmacologic agents such as lithium and demeclocycline can impair the water retaining property of vasopressin [26]. Although lithium appears too toxic for routine usage, demeclocycline has proved to be efficacious therapy in some patients with high vasopressin levels and hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone who are unable to limit their water intake [9]. More recently, other compounds that selectively antagonize the hydro-osmotic effect of vasopressin are being tested and soon may be available [13].

Topics: Adrenal Cortex Diseases; Blood Volume; Diuresis; Extracellular Space; Humans; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Liver Cirrhosis; Osmosis; Respiratory Insufficiency; Vasopressins

Topics: Demeclocycline; Humans; Hypothyroidism; Inappropriate ADH Syndrome; Lithium; Neoplasms; Osmolar Concentration; Vasopressins

Topics: Chromatography, Ion Exchange; Cyclic AMP; Cyclic GMP; Diabetes Insipidus; Extracellular Space; Glucagon; Humans; Hyperthyroidism; Hypoparathyroidism; Hypothyroidism; Immune Sera; Inosine Nucleotides; Iodine Radioisotopes; Methods; Nucleotides, Cyclic; Phosphorus Radioisotopes; Protein Kinases; Tritium; Vasopressins

Topics: Amphetamine; Angiotensin II; Barbiturates; Brain Damage, Chronic; Cardiac Glycosides; Computers; Dehydration; Diuretics; Drinking; Drinking Behavior; Eating; Electric Stimulation; Electrolytes; Endocrine Glands; Hot Temperature; Humans; Hypothyroidism; Insulin; Kidney; Parasympatholytics; Parasympathomimetics; Renin; Serotonin; Thirst; Time Factors; Vasopressins

Topics: Adrenocorticotropic Hormone; Androgens; Animals; Catecholamines; Cushing Syndrome; Estrogens; Glucagon; Glucocorticoids; Growth Hormone; Humans; Hyperthyroidism; Hypothyroidism; Insulin; Insulin Secretion; Iodine; Pituitary Gland; Pituitary Hormone-Releasing Hormones; Progesterone; Rats; Stress, Physiological; Thyroid Gland; Thyroid Hormones; Thyroxine; Vasopressins

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

Topics: Acromegaly; Addison Disease; Adult; Central Nervous System Diseases; Diabetes Insipidus; Humans; Hyperthyroidism; Hypothyroidism; Kidney; Lung Diseases; Male; Neoplasms; Pituitary Diseases; Thyroid Diseases; Vasopressins

Topics: Acromegaly; Addison Disease; Adrenocortical Hyperfunction; Cushing Syndrome; Diabetes Insipidus; Endocrine System Diseases; Humans; Hyperaldosteronism; Hyperparathyroidism; Hypopituitarism; Hypothyroidism; Kidney; Vasopressins; Water-Electrolyte Balance

Topics: Adult; Creatinine; Diuresis; Humans; Hypothyroidism; Kidney Tubules; Male; Phosphates; Urea; Vasopressins

Topics: Adult; Blood Vessels; Clinical Trials as Topic; Constriction; Depression, Chemical; Humans; Hypothyroidism; Iodine; Iodine Radioisotopes; Male; Middle Aged; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Vasopressins

Topics: Humans; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Vasopressins

Linfoma B intravascular hipotalamico en una paciente inmunocompetente.

Topics: Aged; Combined Modality Therapy; Confusion; Cranial Irradiation; Female; Glucocorticoids; Humans; Hypothalamus; Hypothyroidism; Immunocompetence; Lymphoma, B-Cell; Neoplasm Invasiveness; Positron Emission Tomography Computed Tomography; Sleep Disorders, Circadian Rhythm; Vascular Neoplasms; Vasopressins; Weight Loss

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

This study was performed to investigate the effects of L-thyroxine treatment on plasma vasopressin (AVP) levels in rats with hypothyroidism induced by propylthiouracil (PTU). Animals were separated into three groups each having 6 rats: control, PTU, PTU+L-thyroxine groups. Then, the groups were further divided into 3 sub-groups including 6 rats (a; basal, b; hypertonic stimulated and c; hypovolemic stimulated). At the end of the experiments all rats were decapitated in order to obtain plasma samples for analysis in terms of Hct, osmolality, TT 3 , TT 4 and vasopressin. Haematocrit (Hct) levels were the highest in hypovolemic stimulated sub-group (P < 0.001). Osmolality levels were higher in hypertonic stimulated sub-groups (P < 0.001). Total T 3 and T 4 values were the lowest in the PTU group and the highest in the L-thyroxine treated group (P < 0.001). Plasma AVP levels were reduced by hypothyroidism. However, L-thyroxine treatment after the hypothyroidism prevented this reduction (P < 0.001). Vasopressin responses to basal, hypovolemic and hypertonic stimulations were the lowest in the PTU group (P < 0.001). The results of the present study show that basal and stimulated plasma vasopressin levels are reduced in PTU-induced hypothyroidism. However, L-thyroxine treatment following hypothyroidism prevents this reduction.

Topics: Animals; Antithyroid Agents; Body Weight; Dietary Supplements; Hypertonic Solutions; Hypothyroidism; Hypovolemia; Male; Propylthiouracil; Rats; Rats, Wistar; Thyroxine; Vasopressins

Neurological involvement of the central nervous system in brucellosis is uncommon. We describe a rare case of meningoencephalitis due to Brucella melitensis infection, associated with the syndrome of inappropriate antidiuretic hormone secretion and leading to diabetes insipidus and hypothyroidism. Neurobrucellosis, although rare, should be considered in cases of neurological disease of unknown etiology.

Topics: Adolescent; Brucella melitensis; Brucellosis; Diabetes Insipidus; Humans; Hypothyroidism; Male; Meningoencephalitis; Vasopressins

Hypophysiotropic thyrotropin-releasing hormone (TRH) neurons, the central regulators of the hypothalamic-pituitary-thyroid axis, are located in the hypothalamic paraventricular nucleus (PVN) in a partly overlapping distribution with non-hypophysiotropic TRH neurons. The distribution of hypophysiotropic TRH neurons in the rat PVN is well understood, but the localization of these neurons is unknown in mice. To determine the distribution and phenotype of hypophysiotropic TRH neurons in mice, double- and triple-labeling experiments were performed on sections of intact mice, and mice treated intravenously and intraperitoneally with the retrograde tracer Fluoro-Gold. TRH neurons were located in all parts of the PVN except the periventricular zone. Hypophysiotropic TRH neurons were observed only at the mid-level of the PVN, primarily in the compact part. In this part of the PVN, TRH neurons were intermingled with oxytocin and vasopressin neurons, but based on their size, the TRH neurons were parvocellular and did not contain magnocellular neuropeptides. Co-localization of TRH and cocaine- and amphetamine-regulated transcript (CART) were observed only in areas where hypophysiotropic TRH neurons were located. In accordance with the morphological observations, hypothyroidism increased TRH mRNA content of neurons only at the mid-level of the PVN. These data demonstrate that the distribution of hypophysiotropic TRH neurons in mice is vastly different from the pattern in rats, with a dominant occurrence of these neurosecretory cells in the compact part and adjacent regions at the mid-level of the PVN. Furthermore, our data demonstrate that the organization of the PVN is markedly different in mice and rats.

Topics: Animals; Hypothyroidism; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Thyrotropin-Releasing Hormone; Vasopressins

The purpose of this study was to examine protein expression of renal aquaporins (AQP) and ion transporters in hypothyroid (HT) rats in response to an oral water load compared with controls (CTL) and HT rats replaced with l-thyroxine (HT+T). Hypothyroidism was induced by aminotriazole administration for 10 wk. Body weight, water intake, urine output, solute and urea excretion, and serum and urine osmolality were comparable among the three groups at the conclusion of the 10-wk treatment period. One hour after oral gavage of water (50 ml/kg body wt), HT rats demonstrated significantly less water excretion, higher minimal urinary osmolality, and decreased serum osmolality compared with CTL and HT+T rats. Despite the hyposmolality, plasma vasopressin concentration was elevated in HT rats. These findings in HT rats were associated with an increase in protein abundance of renal cortex AQP1 and inner medulla AQP2. AQP3, AQP4, and the Na-K-2Cl cotransporter were also increased. Moreover, 1 h following the oral water load, HT rats demonstrated a significant increase in the membrane-to-vesicle fraction of AQP2 by Western blot analysis. The defect in urinary dilution in HT rats was reversed by the V(2) vasopressin antagonist OPC-31260. In conclusion, impaired urinary dilution in HT rats is primarily compatible with the nonosmotic release of vasopressin and increased protein expression of renal AQP2. The impairment of maximal solute-free water excretion in HT rats, however, appears also to involve diminished distal fluid delivery.

Topics: Amitrole; Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 1; Aquaporin 2; Aquaporin 4; Aquaporins; Biological Transport, Active; Blotting, Western; Echocardiography; Hemodynamics; Hypothyroidism; Kidney; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Sodium; Sodium-Potassium-Exchanging ATPase; Vasopressins

The aim of the present investigations was to examine the effects of the states of hypothyroidism or hyperthyroidism on vasopressin (AVP) and oxytocin (OT) release under conditions of equilibrated water metabolism as well as of osmotic stimulation, brought about by the dehydration or hypertonic saline administration. The euhydrated and simultaneously hypothyroid rats showed decreased hypothalamic AVP and OT content and somewhat higher but not significant neurohypophysial AVP content. In these animals the raised OT (but not AVP) plasma level has been observed. In hyperthyroid rats drinking tap water ad libitum the neurohypophysial AVP and OT content significantly diminished; plasma OT concentration (but not AVP) was then elevated. The state of osmotic stimulation was the reason of different response of the hypothalamo-neurohypohysial system function in hypo- or hyperthyroid rats. Significant decreases of neurohypophysial AVP and OT content were found in both hypothyroid dehydrated as well as hypothyroid hypertonic saline-treatment rats as compared with hypothyroid euhydrated ones. On the contrary, in the state of hyperthyroidism AVP content in the neurohypophysis distinctly raised in dehydrated and salt-loaded rats; in these last neurohypophysial OT content increased as well. Plasma OT (but not AVP) distinctly diminished in hyperthyroid and simultaneously dehydrated or hypertonic saline injected rats in relation to hyperthyroid control subgroup. Data from the present study suggest that: 1). altered thyroid gland function affects vasopressin and oxytocin release from the hypothalamo-neurohypophysial system in the state of equilibrated water metabolism; 2). the state of hypo- or hyperthyroidism modifies the response of AVP-ergic and OT-ergic neurons upon the osmoreceptors/osmodetectors stimulation. It may be supposed that OT-ergic neurons display greater than AVP-ergic neurons sensitivity upon the thyroid hormone influence.

Topics: Animals; Disease Models, Animal; Drinking; Hyperthyroidism; Hypothalamo-Hypophyseal System; Hypothyroidism; Male; Oxytocin; Pituitary-Adrenal System; Rats; Rats, Wistar; Vasopressins; Water; Water Deprivation

The importance of the sn-glycerol- 3-phosphate (G-3-P) electron transfer shuttle in hormonal regulation of gluconeogenesis was examined in hepatocytes from rats with decreased mitochondrial G-3-P dehydrogenase activity (thyroidectomized) or increased G-3-P dehydrogenase activity [triiodothyronine (T(3)) or dehydroepiandrosterone (DHEA) treated]. Rates of glucose formation from 10 mM lactate, 10 mM pyruvate, or 2.5 mM dihydroxyacetone were somewhat less in hypothyroid cells than in cells from normal rats but gluconeogenic responses to calcium addition and to norepinephrine (NE), glucagon (G), or vasopressin (VP) were similar to the responses observed in cells from normal rats. However, with 2. 5 mM glycerol or 2.5 mM sorbitol, substrates that must be oxidized in the cytosol before conversion to glucose, basal gluconeogenesis was not appreciably altered by hypothyroidism but responses to calcium and to the calcium-mobilizing hormones were abolished. Injecting thyroidectomized rats with T(3) 2 days before preparing the hepatocytes greatly enhanced gluconeogenesis from glyc erol and restored the response to Ca(2+) and gluconeogenic hormones. Feeding dehydroepiandrosterone for 6 days depressed gluconeogenesis from lactate or pyruvate but substantially increased glucose production from glycerol in euthyroid cells and restored responses to Ca(2+) in hypothyroid cells metabolizing glycerol. Euthyroid cells metabolizing glycerol or sorbitol use the G-3-P and malate/aspartate shuttles to oxidize excess NADH generated in the cytosol. The transaminase inhibitor aminooxyacetate (AOA) decreased gluconeogenesis from glycerol 40%, but had little effect on responses to Ca(2+) and NE. However, in hypothyroid cells, with minimal G-3-P dehydrogenase, AOA decreased gluconeogenesis from glycerol more than 90%. Thus, the basal rate of gluconeogenesis from glycerol in the euthyroid cells is only partly dependent on electron transport from cytosol to mitochondria via the malate/aspartate shuttle and almost completely dependent in the hypothyroid state, and the hormone enhancement of the rate in euthyroid cells involves primarily the G-3-P cycle. These data are consistent with Ca(2+) being mobilized by gluconeogenic hormones and G-3-P dehydrogenase being activated by Ca(2+) so as to permit it to transfer reducing equivalents from the cytosol to the mitochondria.

Topics: Aminooxyacetic Acid; Animals; Calcium; Cyclic AMP; Dehydroepiandrosterone; Glucagon; Gluconeogenesis; Glucose; Glycerol; Glycerol-3-Phosphate Dehydrogenase (NAD+); Glycerolphosphate Dehydrogenase; Glycerophosphates; Hypothyroidism; Lactic Acid; Liver; Male; Mitochondria, Liver; Norepinephrine; Pyruvic Acid; Rats; Rats, Sprague-Dawley; Thyroidectomy; Transaminases; Triiodothyronine; Vasopressins; Xylitol

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

We evaluated the causal role of glucocorticoid deficiency in the hyponatremia that developed in a 57-year-old Japanese man with hypothyroidism following the performance of a total thyroidectomy for laryngeal cancer. The plasma concentration of vasopressin (1.78 pg/ml) was not suppressed in the presence of hyponatremia (125 mEq/l). The urinary excretion of sodium was increased, and the plasma renin activity and plasma aldosterone concentration were suppressed. The infusion of hypertonic saline increased the plasma osmolality, but not the plasma concentration of vasopressin. An oral water load (20 ml/kg of body weight) did not suppress the plasma vasopressin level or induce diuresis. Pretreatment with hydrocortisone normalized the response of plasma vasopressin to the water load was well as the diuretic response during the hypothyroid state. The urinary excretion of 17-hydroxycorticosteroids was below normal in the hypothyroid state in the face of normal serum cortisol concentration. The correction of the hypothyroidism returned these abnormalities to normal. A disturbed metabolism of glucocorticoid may have been responsible for the hyponatremia and disturbance in plasma vasopressin regulation observed in this hypothyroid patient.

Topics: Diuresis; Glucocorticoids; Humans; Hydrocortisone; Hyponatremia; Hypothyroidism; Laryngeal Neoplasms; Male; Middle Aged; Postoperative Complications; Thyroidectomy; Vasopressins

The present work aimed to elucidate the influence of thyroid functional status on the alpha 1-adrenoreceptor-induced activation of hepatic metabolic functions. The experiments were performed in either a nonrecirculating liver perfusion system featuring continuous monitoring of portal pressure, PO2, pCa, and pH, or isolated hepatocytes from euthyroid, hyperthyroid, and hypothyroid rats. Hypothyroidism decreased the alpha 1-adrenergic stimulation of respiration, glycogen breakdown, and gluconeogenesis. These effects were accompanied by a decreased intracellular Ca2+ mobilization corroborating that those processes are regulated by the Ca(2+)-dependent branch of the alpha 1-adrenoreceptor signaling pathway. Moreover, in hyperthyroid rats the alpha 1-adrenergic-induced increase in cytosolic Ca2+ was enhanced, and glucose synthesis or mobilization was not altered. The thyroid status influenced neither the alpha 1-adrenergic stimulation of vascular smooth muscle contraction nor the alpha 1-agonist-induced intracellular alkalinization and protein kinase C (PKC) activation. Thus the distinct impairment of the Ca(2+)-dependent branch of the alpha 1-adrenoreceptor signaling pathway by thyroid status provides a useful tool to investigate the role played by each signaling pathway, Ca2+ or PKC, in controlling hepatic functions.

Topics: Angiotensin II; Animals; Calcium; Cytosol; Gluconeogenesis; Glucose; Hyperthyroidism; Hypothyroidism; Liver; Male; Muscle, Smooth, Vascular; Parathyroidectomy; Phenylephrine; Protein Kinase C; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1; Signal Transduction; Thyroid Gland; Thyroidectomy; Triiodothyronine; Vasopressins

Vascular reactivity to vasoconstrictors in relation to altered thyroid function was studied in two preparations: aortic strips and the isolated perfused kidney. To assess whether the possible alterations in vascular reactivity were restricted to a specific agonist or whether they involved the contractile system, receptor-mediated and nonspecific smooth muscle stimulants were used. Male Wistar rats were divided into three groups: control, hyperthyroid and hypothyroid rats. Aortic strips from hypothyroid rats were less sensitive to phenylephrine and KCl when the data were expressed in absolute values or as percentages of the maximum responses. Sensitivity and reactivity in strips from hyperthyroid rats were similar to those observed in control strips. Renal vasculature obtained from hypothyroid rats also showed a markedly reduced sensitivity to phenylephrine, with normal maximal responses. The response to vasopressin at 3-10(-11) mol/l was also decreased, as was the reactivity to barium chloride. In contrast, renal vasculature of hyperthyroid rats showed markedly enhanced reactivity to all agonists: the concentration-response curves were characterized by a similar threshold and a greater maximal response. These results demonstrate that hypothyroidism is accompanied by a marked decrease in sensitivity to vasoconstrictors in large arteries as well as in resistance vessels. This decrease may be secondary to a generalized alteration in the contractile system of vascular smooth muscle cells and may play a role in the decreased blood pressure in these animals. In contrast, isolated perfused kidneys of hyperthyroid rats showed increased vascular reactivity to vasoconstrictors, which may play a role in the maintenance of elevated blood pressure in these animals.

Topics: Animals; Aorta, Thoracic; Barium Compounds; Blood Pressure; Chlorides; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Kidney; Male; Methimazole; Muscle Contraction; Muscle, Smooth, Vascular; Perfusion; Phenylephrine; Potassium Chloride; Rats; Rats, Wistar; Thyroxine; Vascular Resistance; Vasoconstrictor Agents; Vasopressins

In the hyperthyroid state, delta psi m, delta pHm and therefore delta p are increased in rat liver. An enhanced delta p accords with a higher energy output. The subcellular distribution of adenine nucleotides in different thyroid states does not reflect the driving force for mitochondrial adenine-nucleotide translocase (that is delta psi m). Therefore, a change in delta psi m cannot be solely responsible for the postulated stimulation of adenine-nucleotide transport by THs. This is also the case for the changes in delta pHm, and in the subcellular distribution of malate, 2-oxoglutarate and glutamate, that are observed under the influence of THs. T3 induces calcium influx into the liver cell within minutes. It increases respiration and gluconeogenesis with the same kinetics. Therefore, it is suggested that, as with glucagon and vasopressin, calcium is the mediator of these changes. The delta p is increased with T3 and glucagon treatment but not with vasopressin. The changes in delta psi m and delta pHm appear to be the result of the individual actions of these hormones on ATP-consuming and ATP-producing reactions. The delta psi p is only increased with T3 treatment. This is related to the different mechanisms of enhancing intracellular calcium that are used by vasopressin, glucagon and T3.

Topics: Animals; Glucagon; Hydrogen-Ion Concentration; Hyperthyroidism; Hypothyroidism; Liver; Male; Mitochondria, Liver; Rats; Rats, Wistar; Thyroid Hormones; Triiodothyronine; Vasopressins

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

1. Regulatory interactions between the hypothalamoneurohypophyseal vasopressin (VP) axis and the endocrine systems of the anterior pituitary have been investigated in the rat by observing changes in VP mRNA expression following endocrine manipulations. 2. An increase in the level, but not size, of VP mRNA was found in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus and in the neurointermediate lobe (NIL) of the pituitary following hypothyroidism (induced by drinking 6-n-propyl-2-thiouracil; PTU) and adrenalectomy. Hypothyroidism induced by alternative procedures (surgical thyroidectomy or PTU injections) did not exert similar effects. 3. Treatment with the dopamine agonist bromocriptine to reduce prolactin secretion raised levels of VP mRNA in the NIL only. Castration did not up-regulate VP mRNA levels. 4. Since the observed effects on VP mRNA levels occur in the absence of changes in plasma osmolality, these results provide evidence of nonosmotic regulation of VP gene expression, an effect which is observed most clearly in the NIL pool of VP mRNA. Furthermore, the effects are distinct from changes in VP mRNA levels associated with raised plasma osmolality since the VP mRNA size was not increased.

Topics: Adrenalectomy; Animals; Bromocriptine; Gene Expression Regulation; Hypothalamo-Hypophyseal System; Hypothyroidism; Male; Orchiectomy; Osmolar Concentration; Propylthiouracil; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyroidectomy; Vasopressins

Using in situ hybridization histochemistry, we have investigated the effect of thyroid hormone on the expression of several peptide mRNAs in the hypothalamic paraventricular nucleus (PVN) of adult male rats. Hypothyroidism was induced by surgical ablation of the thyroid gland. The animals (control sham-operated, thyroidectomized, thyroidectomized+T4 replaced rats) were studied 28 and 50 days after surgery. Sections of the PVN were hybridized using synthetic oligonucleotide probes complementary to mRNA for thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), galanin (GAL), enkephalin (ENK), neurotensin (NT), vasoactive intestinal polypeptide (VIP) and vasopressin (VP). GAL mRNA was also analyzed in the anterior paraventricular, arcuate, and dorsomedial nuclei of the hypothalamus. At the PVN level, a feedback effect of thyroid hormone on TRH synthesis was demonstrated by the TRH mRNA increase in hypothyroidism and by its decrease in hyperthyroidism. Hypothyroidism caused a dramatic decrease in GAL mRNA in parvo- and magnocellular PVN neurons both 28 and 50 days after thyroid ablation, whereas no effect was seen in VP mRNA, the main peptide hormone coexisting with GAL. The T4 replacement prevented the GAL mRNA impairment. Hypothyroidism did not influence GAL mRNA in the anterior PVN, perifornical area or in the arcuate nucleus, whereas a decrease in GAL mRNA was observed in the dorsomedial nucleus. VIP mRNA, which is undetectable in the PVN of normal animals, was present in several PVN neurons after thyroidectomy. CRH mRNA was decreased after thyroidectomy, whereas the T4 restitution caused an upregulation. The levels of ENK or NT mRNA were not significantly affected by the thyroid status. The present results show that, in addition to TRH mRNA, other hypothalamic peptide mRNAs are affected by thyroid hormone levels.

Topics: Animals; Corticotropin-Releasing Hormone; Enkephalins; Galanin; Hypothalamic Hormones; Hypothalamus; Hypothyroidism; In Situ Hybridization; Male; Neurotensin; Paraventricular Hypothalamic Nucleus; Peptides; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyroidectomy; Thyrotropin-Releasing Hormone; Thyroxine; Vasoactive Intestinal Peptide; Vasopressins

In this paper we describe the modification of the galanin (GAL)-like immunostaining in the hypothalamus of rats, which were made hypothyroid at 52 days after birth. On 21st day after the surgical ablation of the thyroid gland, the staining of the GAL-immunoreactive fibers in the median eminence decreased and on the 84th day disappeared almost totally. The GAL-immunoreactive distribution in other areas of the hypothalamus, e.g. the anterior hypothalamus and the dorsomedial nucleus, is only slightly affected by the absence of thyroid hormones, whereas the GAL-staining of medulla oblongata (vagal complex) is equal in both control and hypothyroid rats. In hypothyroid colchicine-treated rats, we were unable to stain GAL-immunoreactive neurons in the paraventricular nucleus (PVN). Oxytocin- and vasopressin-like material was present in the magnocellular neurons and the staining pattern in hypothyroid rats was the same as that of control animals. Our data show a marked reduction in the expression of the GAL-like immunoreactivity of the PVN and median eminence of adult hypothyroid rats. The possible role of this deficit in the pathogenesis of the GH secretion impairment that is observed in hypothyroid rats is discussed.

Topics: Animals; Fluorescent Antibody Technique; Galanin; Hypothalamus; Hypothyroidism; Male; Median Eminence; Oxytocin; Paraventricular Hypothalamic Nucleus; Peptides; Rats; Rats, Inbred Strains; Vasopressins

The effects of calmodulin antagonists on the capacity of hydrogen-translocating shuttles were studied in the perfused rat liver. The capacity was estimated by measuring the changes in the rate of production of glucose from sorbitol during the oxidation of ethanol [T. Sugano, T. Ohta, A. Tarui, and Y. Miyamae. Am. J. Physiol. 251 (Endocrinol. Metab. 14): E385-E392, 1986]. Thyroxine given to intact rats increased the activity of alpha-glycerophosphate dehydrogenase (alpha-GPD). Glucocorticoid replacement in adrenalectomized rats decreased the activity of the alpha-GPD to values obtained after treatment with PTU. In either thyroxine-treated or steroid-replaced rats, the capacity of hydrogen-translocating shuttles increased markedly. However, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), trifluoperazine, and chlorpromazine inhibited the increased capacity in steroid-replaced rats and had no effect on the increased capacity in thyroxine-treated rats. W-7 inhibited the stimulatory effects of norepinephrine on the capacity of the malate-aspartate shuttle without inhibition of efflux of intracellular Ca2+. The stimulatory effects of vasopressin on the malate-aspartate shuttle were also inhibited by W-7, trifluoperazine, and chlorpromazine. The results suggest that the malate-aspartate shuttle may be regulated by Ca(2+)-calmodulin.

Topics: Adrenalectomy; Alanine; Aminooxyacetic Acid; Animals; Asparagine; Calcium; Calmodulin; Chlorpromazine; Glycerolphosphate Dehydrogenase; Hyperthyroidism; Hypothyroidism; Liver; Male; Mitochondria, Liver; NAD; Oxidation-Reduction; Perfusion; Propylthiouracil; Rats; Rats, Inbred Strains; Reference Values; Sorbitol; Sulfonamides; Thyroxine; Trifluoperazine; Triiodothyronine; Vasopressins

Topics: Adult; Arginine Vasopressin; Cortisone; Diagnosis, Differential; Histiocytosis, Langerhans-Cell; Humans; Hypothyroidism; Male; Mouth Diseases; Periodontal Diseases; Vasopressins

We studied osmoregulation of plasma vasopressin (AVP) in eight patients with untreated myxedema due to primary hypothyroidism. All patients had severe thyroid hormone deficiency due to chronic thyroiditis and had been receiving no medication at the time of this study. AVP release was defined by 5% hypertonic saline infusion test in all patients, and urinary diluting capacity was estimated by the iv water-loading tests in five patients. Plasma AVP was measured by sensitive and specific RIA. The mean basal plasma AVP level in the patients (0.5 +/- 0.1 pmol/L) was significantly lower (P less than 0.01) than that in normal adults (2.5 +/- 0.5 pmol/L). During hypertonic saline infusion, the rise in plasma AVP was normal or subnormal in all patients. In two patients who showed mild to moderate hyponatremia in the basal state and mild urinary diluting defect during water loading, plasma AVP was appropriately suppressed in each case. These results indicate that inappropriate elevation of plasma AVP is not common in myxedema, and that impaired water excretion is due mainly to AVP-independent mechanisms.

Topics: Adult; Aged; Female; Humans; Hypothyroidism; Middle Aged; Myxedema; Osmolar Concentration; Radioimmunoassay; Thyroid Hormones; Thyrotropin; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Both dose-response curves and time-courses of plasma glucose levels after single maximal doses showed that in vivo glycogenolytic responsiveness to glucagon and epinephrine was significantly higher in developing hypothyroid rats, whereas it remained unchanged after vasopressin and angiotensin II injections. In contrast with the decreased basal activity of phosphorylase(a), the glucagon-stimulated activity increased in hypothyroid rats, whereas it was only slightly modified under vasopressin stimulation. Daily thyroxine treatment abolished these abnormalities. Thus, there is a close correlation between glucose output and enzyme activation. The maximal binding capacity of [3H]vasopressin and [125I]glucagon was significantly decreased in hypothyroid rats, without changes in the apparent dissociation constant of hormone from its specific receptor. Daily thyroxine treatment also abolished this deficit, which moreover appeared to be independent of possible changes in plasma hormone levels. With respect to glucagon action, neither basal nor Gpp(NH)p-stimulated adenylate cyclase activities were affected in hypothyroid rats. Glucagon-sensitive adenylate cyclase activity and the apparent activation constant appeared to be unaffected. The apparent discrepancy between the results obtained from in vivo and in vitro experiments is discussed on the basis of different membrane transducing phenomena and related intracellular mechanisms underlying the biological response to hormonal stimulation.

Topics: Adenylyl Cyclases; Angiotensin II; Animals; Blood Glucose; Epinephrine; Female; Glucagon; Hypothyroidism; Kinetics; Liver; Liver Glycogen; Phosphorylase a; Phosphorylases; Rats; Rats, Inbred Strains; Vasopressins

In hepatocytes obtained from hypothyroid rats, phorbol myristate acetate (PMA) and vasopressin diminished the accumulation of cyclic AMP and the stimulation of ureagenesis induced by isoprenaline or glucagon without altering significantly the accumulation of cyclic AMP induced by forskolin. Pretreatment with PMA markedly reduced the stimulation of ureagenesis and the accumulation of cyclic AMP induced by isoprenaline or glucagon. In membranes from cells pretreated with PMA, the stimulation of adenylate cyclase induced by isoprenaline + GTP, glucagon + GTP or by Gpp[NH]p were clearly diminished as compared to the control, whereas forskolin-stimulated activity was not affected. The data indicate heterologous desensitization of adenylate cyclase. It was also observed that the homologous (García-Sáinz J.A. and Michel, B. (1987) Biochem. J. 246, 331-336) and this heterologous beta-adrenergic desensitizations were additive. Pertussis toxin treatment markedly reduced the heterologous desensitization of adenylate cyclase but not the homologous beta-adrenergic desensitization. It is concluded that the homologous and heterologous desensitizations involve different mechanisms. The homologous desensitization seems to occur at the receptor level, whereas the heterologous probably involves the guanine nucleotide-binding regulatory protein, Ns.

Topics: Adenylate Cyclase Toxin; Adenylyl Cyclases; Animals; Colforsin; Cyclic AMP; Drug Interactions; Enzyme Activation; Female; Glucagon; Guanosine Triphosphate; Guanylyl Imidodiphosphate; Hypothyroidism; Isoproterenol; Liver; Pertussis Toxin; Propranolol; Protein Kinase C; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta; Tetradecanoylphorbol Acetate; Urea; Vasopressins; Virulence Factors, Bordetella

The effects of congenital hypothyroidism on both the structure and function of the renal medulla were studied by comparing, in 1-month old rats, the structural features of collecting tubules with the capacity of vasopressin to bind membrane preparations and the related adenylate cyclase activation. With the exception of a reduced caliber, hypothyroidism had no effect on the density, total number, distribution of tubules according to epithelial thickness, or on the number of epithelial cells, or their area. The binding capacity of vasopressin and the related adenylate cyclase activation were equally reduced by about 50%, without changes in (i) the basal or guanylyl-imidodiphosphate (Gpp(NH)p)-stimulated adenylate cyclase activities, (ii) the apparent dissociation constant (KD) of labelled vasopressin from its specific receptor or (iii) the apparent activation constant (Kact) of vasopressin for adenylate cyclase. Taken together, these results clearly demonstrate that congenital hypothyroidism exerts a direct influence on the developing responsiveness of the renal medulla, mainly by reducing the density of active hormone receptors per cell, instead of reducing cell number or cell membrane area.

Topics: Adenylyl Cyclases; Animals; Congenital Hypothyroidism; Female; Guanylyl Imidodiphosphate; Hypothyroidism; Kidney Medulla; Kidney Tubules; Kidney Tubules, Collecting; Kinetics; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Receptors, Vasopressin; Vasopressins

Topics: Aged; Humans; Hyponatremia; Hypothyroidism; Male; Vasopressins

The effects of propylthiouracil (PTU) treatment on renal vasopressin sensitive adenylate cyclase in young and adult rats were studied by measuring the binding of tritiated vasopressin and adenylate cyclase activation by vasopressin in kidney medulla plasma membranes. Thyroxine therapy completely corrected the effects of PTU treatment on the vasopressin-adenylate cyclase system. Thus, the abnormalities observed after a such treatment are directly related to thyroid deficiency and not to toxic effects of PTU. The inability of the kidney to normally concentrate urine in developing and adult animals with induced hypothyroidism was mainly related to the reduction of the number of binding sites without significant changes in the basal and guanylyl-imidodiphosphate (Gpp(NH)p)-stimulated adenylate cyclase activities, the apparent dissociation constant (Kbind) of labeled vasopressin from its specific receptor and the apparent activation constant (Kact) of vasopressin for adenylate cyclase. These results also show that thyroid deficiency has more effect on the ontogenesis of receptors than on their turnover, and demonstrate that a normal antidiuretic response occurs at very low receptor occupancy. Since, on the one hand, the hypothyroidism-induced abnormalities in renal medulla responsiveness to vasopressin were reversible and, on the other, only a permanent therapy consisting of two daily physiological doses of thyroxine from birth to the age of sacrifice fully restored them, the responsiveness of developing kidney to thyroid hormones appears to be fundamentally different from that of the CNS.

Topics: Adenylyl Cyclases; Animals; Enzyme Activation; Guanylyl Imidodiphosphate; Hypothyroidism; Kidney; Osmolar Concentration; Propylthiouracil; Rats; Receptors, Angiotensin; Receptors, Vasopressin; Thyroxine; Urine; Vasopressins

The effects of propylthiouracil (PTU) treatment on the plasma vasopressin level, on the number of hepatic (V1) or renal (V2) vasopressin receptors and on the hormone-sensitive adenylate cyclase activity in the kidney of developing rats were studied in parallel. In addition, we investigated the corrective effects of thyroxine therapy on the plasma vasopressin level and parameters related to the liver, and the effects of vasopressin therapy on the parameters related to the kidney. As already reported in the case of the number of V2 receptors and adenylate cyclase activity in the kidney, the deficient plasma vasopressin level in hypothyroid rats was completely corrected by two daily physiological doses of thyroxine given from birth to the age of sacrifice (1 month). Unlike the V1 receptors, the V2 receptors are known to be highly dependent on their specific circulating ligand. Since, first of all, the deficit was similar in the numbers of V1 and V2 receptors in hypothyroid rats, and, secondly, the treatment of hypothyroid rats by two daily physiological doses of long lasting vasopressin was found ineffective to recover the deficit in the number of V2 receptors, it can be concluded that thyroid deficiency directly alters vasopressin receptor biosynthesis in both liver and kidney, instead of acting via the depressed plasma vasopressin level.

Topics: Animals; Congenital Hypothyroidism; Hypothyroidism; Kidney; Liver; Propylthiouracil; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Receptors, Vasopressin; Thyroxine; Vasopressins

1 The effects of congenital hypothyroidism on the postnatally developing hypothalamus and, particularly on the developing magnocellular nuclei and their vasopressinergic neurons, were studied by means of complementary approaches, such as histology, biochemistry and immunocytochemistry. 2 In normal rat, all the results show a precocious development of hypothalamus, and particularly of its magnocellular nuclei. 3 In hypothyroid rat, in showing that the nucleic acid and protein content of hypothalamus is diminished by the same magnitude than its wet weight, the results display a normal average cellularity and cell size. In the magnocellular nuclei of 10, 20 and 30 day-old rats, the neuronal density and cell size appear to be unaffected, except for the NSO at 35 days of age in which the two parameters are increased and decreased, respectively. With respect to vasopressinergic neurons in 35 day-old rats, their density and percentage in total cell population, as well as the axonal density are somewhat increased, the greater differences always significant being shown only in the NPV. Whatever the nuclei considered, the density of axonal varicosities does not differ from normal value. Finally, the vasopressin concentration of hypothalamus is significantly increased. Thus, it may be concluded that the mainly prenatal development of these vasopressinergic hypothalamic nuclei seems to be relatively spared from neo- and postnatal thyroid deficiency.

Topics: Animals; Cell Count; Congenital Hypothyroidism; DNA; Hypothalamus; Hypothyroidism; Immunohistochemistry; Neurons; Neurophysins; Proteins; Rats; Vasopressins

Hyponatremia is usual during myxedema coma. Hereafter we report two cases with increased plasma arginine vasopressin (AVP). Patients were admitted because of hypothyroid coma. In each case, there was an hyponatremia with normal urine sodium and low serum osmolality. Renal function was normal. On hormonal results, primary hypothyroidism was evident. Plasma AVP was increased. The plasma cortisol of one patient was high. Immediate therapy associated: water restriction, hypertonic saline infusion, furosemide, oral thyroid hormones with low doses. On the fourth day, conscience improved obviously. Natremia and plasma AVP went back to normal state before returning to euthyroid state. Patients went on improving along with normalizing thyroid status. Hyponatremia can be a serious sign of hypothyroidism. In case of myxedema coma with hyponatremia, clinical improvement seems to be related to fast correction of water and electrolyte disturbances and we prefer to give low doses of thyroid hormones at first. The hyponatremia and increased plasma AVP mechanisms are complex. However, in each of these cases, plasma AVP come back to normal before returning to euthyroid state. In one case, high plasma cortisol level rules out adrenal insufficiency as causal mechanism of electrolyte disorders.

Topics: Aged; Coma; Female; Humans; Hyponatremia; Hypothyroidism; Male; Myxedema; Vasopressins

The mean resting concentration of cytosolic free Ca2+ [( Ca2+]i) in parenchymal liver cells, as determined with the intracellular Ca2+ indicator quin2, was lowered by about 30% in hypothyroidism (0.17 microM vs. 0.27 microM in normal cells). The [Ca2+]i level in hypothyroid cells at 10 s following stimulation by noradrenaline (1 microM) was about 64% lower than in normal cells (0.33 microM vs. 1.0 microM). The response to noradrenaline in hypothyroid cells was slower in onset (significant at 5 s vs. 3 s in euthyroid cells), and the maximum of the initial [Ca2+]i increase was reached later (14 s vs. 8 s in normal cells). In hypothyroid hepatocytes the initial increase was followed by a slow but prolonged secondary increase in [Ca2+]i. With vasopressin similar results were found. Chelation of extracellular Ca2+ with EGTA immediately prior to stimulation had no effect on the initial [Ca2+]i increase. Treatment with T3 in vivo (0.5 micrograms/100 g body weight daily during 3 days) completely restored the basal and stimulated [Ca2+]i in hypothyroid cells. The half-maximally effective dose of noradrenaline was the same in euthyroid and hypothyroid liver cells (1.8 X 10(-7) M). Hypothyroidism had no significant effect on the number of alpha 1-receptors determined by [3H]prazosin labeling in crude homogenate fractions, while the Kd for [3H]prazosin was 21% lower than in the euthyroid group. These results show that thyroid hormone has a general stimulating effect on intracellular Ca2+ mobilization by Ca2+-mobilizing hormones, probably at a site distal to the binding of the agonist to its receptor. The results also support our idea that thyroid hormone may control metabolism during rest and activation, at least partially, by altering Ca2+ homeostasis.

Topics: Animals; Calcium; Cytosol; Hypothyroidism; Liver; Male; Norepinephrine; Oxygen Consumption; Prazosin; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Triiodothyronine; Vasopressins

Postnatal development of glycogen phosphorylase activation by the cAMP-independent pathway was examined in isolated rat hepatocytes from control and propylthiouracil-treated congenital hypothyroid rat pups. At 5 days postnatum there was complete phosphorylase activation by beta-adrenergic stimulation, glucagon, and the calcium ionophore A23187, but no activation by alpha-adrenergic stimulation. Activation of phosphorylase by angiotensin or vasopressin was less than in hepatocytes from adult rats (P less than 0.01). At 28 days postnatum activation by all of these hormones was complete. In the propylthiouracil-treated group hormone responsiveness was similar to the control at 5 days postnatum. However, alpha-adrenergic (P less than 0.025), angiotensin, and vasopressin (P less than 0.05) activation was decreased at 28 days postnatum, and beta-adrenergic, glucagon, and A23187 activation was complete. The attenuated responses were restored by thyroxine replacement from 15 days postnatum. [32P]Pi incorporation into phosphatidylinositol by epinephrine and vasopressin in 28-day propylthiouracil-treated rats was lower than the control (P less than 0.01). We speculate that the diminished phosphorylase response of hepatocytes to alpha-adrenergic, vasopressin, or angiotensin stimuli in the early neonatal period could be related to low receptor numbers and the weaker phosphoinositide response during this period. Also, the depressed phosphorylase response to alpha-adrenergic, vasopressin, and angiotensin stimulation in congenital hypothyroidism at 28 days postnatum could be related to a decrease in number of plasma membrane receptors for these agonists.

Topics: Angiotensin II; Animals; Animals, Newborn; Calcimycin; Cyclic AMP; Dose-Response Relationship, Drug; Epinephrine; Female; Glucagon; Hypothyroidism; Liver; Phentolamine; Phosphorylase a; Phosphorylases; Pregnancy; Rats; Rats, Inbred Strains; Time Factors; Vasopressins

The relation between Ca2+ efflux, Ca2+ mobilization from mitochondria and glycogenolysis was studied in perfused euthyroid and hypothyroid rat livers stimulated by Ca2+-mobilizing hormones. Ca2+ efflux, induced by noradrenaline (1 microM) in the absence or presence of DL-propranolol (10 microM) from livers perfused with medium containing a low concentration of Ca2+ (approx. 24 microM), was decreased by more than 50% in hypothyroidism. This correlated with an equal decrease of the fractional mobilization of mitochondrial Ca2+, which could account for 65% of the difference between the net amounts of Ca2+ expelled from the euthyroid and hypothyroid livers. With vasopressin (10 nM) similar results were found, suggesting that hypothyroidism has a general effect on mobilization of internal Ca2+. In normal Ca2+ medium (1300 microM), however, the effect of vasopressin on net Ca2+ fluxes and phosphorylase activation was not impaired in hypothyroidism, indicating that Ca2+ mobilization from the mitochondria in this case plays a minor role in phosphorylase activation. The alpha 1-adrenergic responses of Ca2+ efflux, phosphorylase activation and glucose output, glucose-6-phosphatase activity and oxygen consumption in hypothyroid rat liver were completely restored by in vivo T3 injections (0.5 micrograms per 100 g body weight, daily during 3 days). Perfusion with T3 (100 pM) during 19 min did not influence hypothyroid rat liver oxygen consumption and alpha 1-receptor-mediated Ca2+ efflux. However, this in vitro T3 treatment showed a completely recovered alpha 1-adrenergic response of phosphorylase and a partly restored glucose-6-phosphatase activity and glucose output. The results indicate that thyroid hormones may control alpha 1-adrenergic stimulation of glycogenolysis by at least two mechanisms, i.e., a long-term action on Ca2+ mobilization, and a short-term action on separate stages of the glycogenolytic process.

Topics: Animals; Calcium; Calcium Chloride; Glucose; Glucose-6-Phosphatase; Glycogen; Hypothyroidism; Liver; Male; Mitochondria, Liver; Norepinephrine; Propranolol; Rats; Rats, Inbred Strains; Thyroid Hormones; Thyroidectomy; Triiodothyronine; Vasopressins

The actions of hormones which are associated to cAMP-dependent and calcium-dependent mechanisms of signal transduction were studied in hepatocytes obtained from rats with different thyroid states. In cells from euthyroid and hyperthyroid rats, the metabolic actions of epinephrine were mediated mainly through alpha 1-adrenoceptors; beta-adrenoceptors seem to be functionally unimportant. In contrast, both alpha 1- and beta-adrenoceptors mediate the actions of epinephrine in hepatocytes from hypothyroid animals. Phosphatidylinositol labeling was strongly stimulated by epinephrine, vasopressin and angiotensin II in cells from eu-, hyper- or hypothyroid rats. However, metabolic responsiveness to vasopressin and angiotensin II was markedly impaired in the hypothyroid state. The glycogenolytic response to the calcium ionophore A-23187 was also impaired, suggesting that hepatocytes from hypothyroid rats are less sensitive to calcium signalling. The persistence of alpha 1-adrenergic responsiveness in the hypothyroid state suggests that the mechanism of signal transduction for alpha 1-adrenergic amines is not identical to that of the vasopressor peptides. alpha 1-Adrenergic stimulation of cyclic AMP accumulation was not detected in cells from hypothyroid rats. These data suggest that factors besides calcium and besides cAMP are probably involved in alpha 1-adrenergic actions. Metabolic responses to glucagon and to the cAMP analogue dibutyryl cAMP were not markedly changed during hypothyroidism, although cAMP accumulation produced by glucagon and beta-adrenergic agonists was enhanced. In hyperthyroidism, cell responsiveness to epinephrine, vasopressin, angiotensin II and glucagon was decreased, but sensitivity to cAMP was not markedly altered. The factors involved in this hyposensitivity to hormones during hyperthyroidism are unclear.

Topics: Angiotensin II; Animals; Calcium; Cyclic AMP; Gluconeogenesis; Glycogen; Hyperthyroidism; Hypothyroidism; Liver; Liver Glycogen; Phosphatidylinositols; Rats; Receptors, Adrenergic, alpha; Urea; Vasopressins

Topics: Adrenal Cortex; Aged; Humans; Hyponatremia; Hypothyroidism; Male; Vasopressins

To explore a possible downward setting of the hypothalamic osmoreceptors in the hyponatremia of hypothyroidism, 4 adolescent patients with hypothyroidism were studied. Plasma and urine osmolality were measured on random paired simultaneous samples, and following a water load. The osmotic threshold was determined by the isovolemic infusion of hypertonic NaCl, and compared to the osmotic threshold of 6 healthy subjects. Random paired urine and plasma osmolality revealed inappropriately high urine osmolality for the given plasma osmolality. A water load produced a normal dilution of urine. Osmotic threshold was found at plasma osmolality of 286-287 mosm/kg, compared to 286.7 +/- 1.0 in 6 normal individuals. It is concluded that none of the known types of the syndrome of inappropriate ADH secretion could account for the hyponatremia in the hypothyroid patients, and that patients with hypothyroidism have normal osmoreceptors as measured by the osmotic threshold test.

Topics: Adolescent; Blood; Child; Female; Humans; Hyponatremia; Hypothyroidism; Male; Osmolar Concentration; Urine; Vasopressins; Water-Electrolyte Balance

The effects of hypothyroidism on the hepatic alpha 1-receptor system were studied in isolated rat liver cells. Phenylephrine and vasopressin caused concentration-dependent activation of glycogen phosphorylase and release of 45Ca from 45Ca-loaded cells in either normal or thyroidectomized rats. However, the magnitude of both responses to phenylephrine was markedly suppressed after thyroidectomy and could be restored to near normal levels by in vivo treatment with 1-triiodothyronine (0.25 mg/kg/day) for 4 days. The potency of vasopressin to induce phosphorylase activation and 45Ca release was only slightly reduced by thyroidectomy. Binding of [3H]prazosin to putative alpha 1-receptors in purified liver plasma membranes revealed that the above changes were accompanied by a decrease in the density of binding sites from 567 +/- 51 fmol/mg of protein in controls to 326 +/- 51 fmol/mg in thyroidectomized rats and a return to 498 +/- 23 fmol/mg in thyroidectomized rats treated with 1-triiodothyronine. The affinity of binding sites for [3H]prazosin or for alpha-receptor agonists was the same in the three groups of rats and affinity for epinephrine was unaffected by the presence of guanyl-5'-yl imidodiphosphate (30-100 microM). From these findings, it appears that a reduction in the number of hepatic alpha 1-receptors is responsible for the selective decrease in alpha-adrenergic responses in the hypothyroid rat liver. These changes are opposite to those previously reported for hepatic beta-receptors.

Topics: Animals; Binding, Competitive; Calcium; Enzyme Activation; Epinephrine; Hypothyroidism; In Vitro Techniques; Kinetics; Liver; Male; Phenylephrine; Phosphorylases; Prazosin; Rats; Rats, Inbred Strains; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Thyroidectomy; Vasopressins

Short term (48 h) administration in vivo of either T4 or T4, but not the biologically inactive D-isomer of T3, was associated with a decrease in basal glycogen phosphorylase alpha activity and an increase in phosphorylase alpha phosphatase activity of rat hepatocytes. This influence of thyroid hormones on hepatic phosphorylase alpha and phosphorylase phosphatase activities was shown to be dose dependent. As little as 0.0025 mg T3/kg BW administered in vivo at 48, 24, and 3 h before liver excision increased the phosphatase activity by 20%. The administration of 0.25 mg T3/kg BW on the same schedule increased the phosphatase activity by nearly 100%.

Topics: Angiotensin II; Animals; Epinephrine; Female; Glucagon; Hypothyroidism; Isoproterenol; Liver; Phosphoprotein Phosphatases; Phosphorylase a; Phosphorylase Phosphatase; Phosphorylases; Rats; Rats, Inbred Strains; Thyroxine; Triiodothyronine; Vasopressins

A 45-year-old woman with myxedema coma due to primary hypothyroidism manifested hyponatremia, impaired water excretion, and elevated urine osmolarity as well as natriuresis suggestive of a syndrome of inappropriate antidiuretic hormone secretion. However, plasma vasopressin was undetectable or very low and plasma aldosterone levels were suppressed in the presence of hyponatremia. Subsequent replacement therapy with levothyroxine caused a rapid decline in sodium clearance which was independent of the change in glomerular filtration rate, and corrected the impaired water excretion and hyponatremia. Plasma vasopressin levels returned to the normal range after the correction of hyponatremia. Thus, the results indicate that neither vasopressin nor aldosterone plays a dominant role in the pathogenesis of the hyponatremia in this patient. It appears that thyroid hormone deficiency itself caused the derangement of tubular cell function, which resulted in the development of the impaired water excretion and hyponatremia.

Topics: Coma; Female; Glomerular Filtration Rate; Humans; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Middle Aged; Myxedema; Osmolar Concentration; Sodium; Thyroxine; Vasopressins

Deficiencies of corticotrophin (ACTH), growth hormone, and prolactin were documented in a woman with diabetes mellitus and Sheehan's syndrome. The patient's ACTH deficit appeared to be secondary to a hypothalamic abnormality since on two occasions the patient had a marked plasma ACTH response to vasopressin but not to insulin induced hypoglycaemia. It is postulated that the deficits of these three adenohypophysial hormones were instrumental in causing a severely impaired aldosterone secretory capacity in response to sodium restriction and an angiotensin infusion. In addition, the patient had an unusual form of thyroid dysfunction that was in part reversed with hydrocortisone replacement. The patient's unfortunate death during a hypoglycaemic crisis allowed correlation between her extensive antemortum endocrine testing and her pathologic anatomy.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Adult; Aldosterone; Angiotensin II; Diabetes Complications; Female; Growth Hormone; Humans; Hypopituitarism; Hypothyroidism; Insulin; Pituitary Gland, Anterior; Prolactin; Vasopressins

Topics: Demeclocycline; Female; Humans; Hyponatremia; Hypothyroidism; Inappropriate ADH Syndrome; Middle Aged; Vasopressins; Water-Electrolyte Imbalance

A patient with diabetes insipidus and hypothyroidism developed anovular menstrual cycles. Ovulation, which was followed by pregnancy, was induced by the administration of clomiphene. In the later stages of pregnancy, an increase in the dosage of vasopressin was necessary to achieve a satisfactory control of the symptoms of diabetes insipidus. Labour was induced before the estimated date of confinement by the intravenous administration of oxytocin and an intra-partum haemorrhage necessitated delivery by the lower-segment caesarean section. The post-partum period was uneventful. Lactation was suppressed on request from the patient.

Topics: Adult; Anovulation; Clomiphene; Diabetes Insipidus; Female; Humans; Hypothyroidism; Infertility, Female; Labor, Induced; Ovulation; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Vasopressins

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

A hypothyroid, 72-year-old woman with idiopathic hypopituitarism manifested severe hyponatremia, plasma hypoosmolality, and inappropriately elevated urine osmolality suggestive of a syndrome of inappropriate antidiuretic hormone secretions. The hyponatremia did not respond to demeclocycline hydrochloride, and antidiuretic hormone (ADH) levels measured by a specific radioimmunoassay were appropriately suppressed. Subsequent replacement therapy with levothyroxine sodium resulted in correction of the hyponatremia. Thus, both direct assay as well as hormone blockade failed to show an action of ADH in mediating the water retention.

Topics: Aged; Demeclocycline; Female; Humans; Hyponatremia; Hypopituitarism; Hypothyroidism; Sodium; Thyroxine; Vasopressins

Twenty-four h urinary vasopressin excretion was measured by bioassay in 15 patients with untreated hypothyroidism and compared with plasma sodium concentration. Four patients had raised excretion of an antidiuretic substance and in 3 of these patients excretion was reduced after thyroid replacement therapy. The criteria applied supported the view that the antidiuretic substance was arginine vasopressin. Plasma sodium concentration was normal in all these 4 patients. A further 4 patients had hyponatraemia without raised arginine vasopressin excretion. The results suggest that: (1) excess arginine vasopressin secretion is not the cause of the hyponatraemia of hypothyroidism and (2) an increased secretion of arginine vasopressin does occur in some cases of normonatraemic hypothyroidism, the cause requiring further elucidation.

Topics: Adult; Aged; Arginine Vasopressin; Female; Humans; Hyponatremia; Hypothyroidism; Male; Middle Aged; Osmolar Concentration; Sodium; Vasopressins

Topics: Diseases in Twins; Humans; Hyponatremia; Hypothyroidism; Infant; Kidney; Male; Sodium; Syndrome; Vasopressins; Water-Electrolyte Imbalance

The plasma vasopressin response to acute water ingestion was evaluated in 20 patients with myxedema prior to definitive treatment and in eight of these same patients following therapy of their hypothyroidism. Vasopressin levels were elevated and failed to completely suppress following water ingestion in 15 subjects (75 per cent). Two hypothyroid patients with elevated plasma vasopressin levels (10 per cent) had a normal renal response to the water challenge suggesting partial end organ hormonal unresponsiveness. In three (15 per cent) of the five patients with suppressible vasopressin, water excretion was impaired indicating a nonvasopressin-mediated renal defect. In eight patients restudied after achievement of a euthyroid state, vasopressin inhibition and urinary excretion were normal following the oral water load. Although intrinsic renal changes in the hypothyroid state may contribute to the observed defect in water diuresis, the present study suggests a role of endogenous vasopressin in this disorder.

Topics: Adult; Aged; Arginine Vasopressin; Body Water; Humans; Hypothyroidism; Male; Middle Aged; Myxedema; Vasopressins; Water

Topics: Adult; Aged; Female; Humans; Hyponatremia; Hypothyroidism; Male; Middle Aged; Vasopressins

A case report is presented in which myxedema coma and inappropriate antidiuretic hormone secretion developed as a result of radiation therapy and surgery to the neck area in a patient with recurrent metastatic squamous cell carcinoma of the floor of the mouth. Laboratory findings of low thyroxine level and the findings of persistent hyponatremia and hypoosmolality of serum in spite of persistent sodium loss in the urine were helpful in diagnosing the problem. Treatment included thyroid hormone replacement and fluid restriction resulting in complete reversal of her condition. We believe that patients with head and neck cancer who have undergone a course of radiation to the neck, and particularly when thyroid function might have been altered by previous subtotal thyroidectomy as part of a curative resection, should be carefully followed with periodic thyroid function assays and serum electrolytes with particular attention to serum sodium values.

Topics: Carcinoma, Squamous Cell; Coma; Female; Head and Neck Neoplasms; Humans; Hyponatremia; Hypothyroidism; Middle Aged; Myxedema; Neoplasm Metastasis; Radiation Injuries; Vasopressins

The authors report a case of coma due to peripheral myxoedema with severe hyponatremia (111 mq) and low urinary sodium. The clinical and metabolic disorders regressed within ten days under treatment with thyroid. The frequency of hyponatremia during myxoedema coma is recalled and the pathogenic mechanism discussed. Although the adrenal origin seems excluded, there is possibly some hypervasopresinism, but it seems finally that the thyroxin-dependent hyponatremia is of renal origin.

Topics: Coma; Female; Humans; Hydrocortisone; Hyponatremia; Hypothyroidism; Kidney; Male; Mineralocorticoids; Myxedema; Vasopressins

Topics: Diabetes Insipidus; Goiter; Graves Disease; Humans; Hyperpituitarism; Hyperthyroidism; Hypothyroidism; Lithium; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms; Vasopressins

To test the effect of thyrotropin-releasing hormone (TRH) on serum arginine vasopressin (AVP) in euthyroid and hypothyroid individuals, 500 mug of TRH was administered to four euthyroid subjects and three patients with primary hypothyroidism. Serum AVP was significantly depressed below basal levels from 30 to 60 min in the euthyroid and hypothyroid subjects after administering the releasing agent. The basal serum AVP in the hypothyroid subjects (3.1 +/- 1.1 muU/ml) was not significantly greater than the basal serum AVP in the euthyroid subjects (2.8 +/- 1.2 muU/ml). The maximal incremental depression in serum AVP after TRH in the hypothyroid subjects (1.4 +/- 0.7 muU/ml) was similar to the depression observed in the euthyroid subjects (1.8 +/- 0.9 muU/ml). These data suggest that TRH may have a physiologic role in modulation of AVP release in man.

Topics: Arginine Vasopressin; Humans; Hypothyroidism; Male; Osmolar Concentration; Prolactin; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Vasopressins

Patients underlying the permanent endocrine substitution need a particular control and a competent conduction on account of their endangering by intercurrent events. Highly specialised knowledge of the physician and intensive collaboration of the patient from this reciprocity lead to essential aspects of the prophylaxis of the crisis-like exacerbations exhibited in detail. The optimum substitution is supplemented by issuing information and emergency cards. When the patient possesses such cards they will become of decisive importance in an urgent therapy necessary outside the controlling facility.

Topics: Arginine Vasopressin; Brain Edema; Diabetes Insipidus; Dihydrotachysterol; Humans; Hydrocortisone; Hypoparathyroidism; Hypothyroidism; Muscle Cramp; Pituitary Diseases; Thyroid Hormones; Vasopressins

Topics: Adult; Affective Symptoms; Aged; Behavior; Brain Diseases; Depression; Hormones, Ectopic; Humans; Hydrocephalus, Normal Pressure; Hypothyroidism; Male; Neurocognitive Disorders; Nutrition Disorders; Psychotherapy; Psychotropic Drugs; Risk; Suicide Prevention; Thinking; Vasopressins

Twenty-six patients with the syndrome of inappropriate secretion of antidiuretic hormone were reviewed. The underlying diseases were bronchogenic carcinoma (12 cases); myxoedema (five cases); diseases of the nervous system (five cases); bronchopneumonia, carcinoma of the oesophagus, acute intermittent porphria and chlorpropamide therapy (each one case). Serum sodium levels ranged between 104 and 125 mEq per litre. Eighteen patients presented neurological manifestations, which in 14 were considered to be due to hyponatraemia. Neurological signs included disorders of consciousness (stage I and II coma), extrapyramidal signs, asterixis and epileptic seizures. An hyponatraemic coma was the first manifestation of the syndrome in five cases. In all cases where the EEG was recorded it showed non-specific signs of metabolic coma. The fundi never showed signs of intracranial hypertension. Blood urea and creatinine levels were invariably low in the euthyroid patients; these values were normal or elevated in patients with myxoedema and hyponatraemia. Hypokalaemia was frequent, and hypocalcaemia constant. In eleven cases an excess of water intake revealed the clinical syndrome: six patients were excessive beer drinkers and five had received extensive intravenous infusions. In one case the deleterious effect of diuretics was evident, and in another, the syndrome became evident during radiotherapy of an oesophageal tumour. Treatment of the syndrome was successful in all cases. A review of the literature concerning the various pathogenic mechanisms corresponding to the different underlying diseases is presented. The concept of aberrant hormonal production by a tumour is illustrated by an electron microscopic study.

Topics: Adult; Aged; Carcinoma, Bronchogenic; Cerebrovascular Disorders; Esophageal Neoplasms; Female; Hormones, Ectopic; Humans; Hyponatremia; Hypothyroidism; Lung Neoplasms; Male; Middle Aged; Myxedema; Neurologic Manifestations; Vasopressins; Water Intoxication

Topics: Animals; Diabetes Mellitus, Experimental; Dogs; Hypothyroidism; Insulin; Kidney; Natriuresis; Norepinephrine; Potassium; Sodium; Urea; Vasopressins

Topics: Aged; Bronchopneumonia; Female; Humans; Hyponatremia; Hypothyroidism; Secretory Rate; Vasopressins

Free water clearance (CH2O) was measured during hypotonic saline infusion in Sprague-Dawley and in Brattleboro (DI) rats with 131I-induced hypothyroidism and their age-matched controls. At peak urine flow, which was similar in hypothyroid DI (HDI) and control DI (CDI) rats, inulin clearance (CIn/kg) and CH2O/kg were 23 and 20% (P less than 0.02) lower in HDI. Fractional urine flow and fractional sodium excretion were 30 and 40% (P less than 0.001) higher in HDI. Utilization of distal delivery of filtrate for CH2O, formation was 16% less in HDI (P less than 0.01). Papillary osmolality was not higher in HDI rats. Data in Sprague-Dawley rats were similar to those of the DI rats, indicating that endogenous ADH was effectively suppressed. It is concluded: 1) delivery of filtrate out of the proximal tubule was not diminished in hypothyroid rats in spite of a decrease in CIn; 2) despite a similar delivery of filtrate to the distal diluting site, CH2O formation was less in hypothyroid rats than in controls; 3) these data suggest that a defect in the diluting segment could be unmasked at high rates of filtrate delivered to the distal nephron; 4) this defect could be either due to impaired sodium chloride reabsorption or due to increased backdiffusion of water in the distal nephron.

Topics: Animals; Diabetes Insipidus; Female; Glomerular Filtration Rate; Hypothyroidism; Inulin; Kidney; Kidney Concentrating Ability; Kidney Tubules; Kidney Tubules, Distal; Male; Organ Size; Rats; Thyroxine; Vasopressins

Topics: Animals; Hypothyroidism; Male; Rats; Thyroid Gland; Thyroid Hormones; Vasopressins

Six children with human growth hormone (hGH) deficiency became hypothyroid during the course of their therapy with hGH. This was accompanied by a decreasing growth rate, clinical symptoms of hypothyroidism and decreased serum T4 concentrations. Three of the 6 patients returned to the euthyroid state, both clinically and biochemically, with cessation of hGH therapy, and reinstitution of hGH precipitated hypothyroidism again in 2 of the three. The patients who remained hypothyroid have evidence of multiple pituitary trophic hormone deficiencies while those who reverted to euthyroidism appear to have isolated hGH deficiency. Evaluation of thyroid function while on hGH showed low T4, free T4 and T3 concentrations. The serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was absent or markedly blunted in 4 of 6 patients while receiving long-term hGH therapy but was normal or exaggerated in all patients when tested before or after only 5 days of hGH therapy. These data indicate that exogenous hGH results in an inhibition of the TSH response to TRH. The mechanism of this inhibition is unclear, but we postulate that it may be mediated by somatostatin secretion in response to pulse doses of hGH.

Topics: Age Determination by Skeleton; Body Height; Craniopharyngioma; Diabetes Insipidus; Dwarfism, Pituitary; Female; Growth; Growth Hormone; Humans; Hypopituitarism; Hypothyroidism; Male; Thyroid Gland; Thyroxine; Vasopressins

Topics: Adenylyl Cyclase Inhibitors; Adult; Cyclic AMP; Diabetes Insipidus; Digestive System; Humans; Hypothyroidism; Lithium; Male; Muscle, Smooth; Vasopressins

Topics: Adrenocorticotropic Hormone; Arginine; Diethylstilbestrol; Dihydroxyphenylalanine; Endotoxins; Female; Glucagon; Glucocorticoids; Glucose; Gonadal Steroid Hormones; Growth Hormone; Humans; Hypoglycemia; Hypothyroidism; Insulin; Male; Obesity; Physical Exertion; Pituitary Function Tests; Pseudomonas; Puberty; Sleep; 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: Adolescent; Adult; Brain Diseases; Child; Female; Goiter, Endemic; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Hypothyroidism; Male; Pituitary Function Tests; Pituitary Hormone-Releasing Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Vasopressins

Topics: Acromegaly; Edema; Endocrine System Diseases; Humans; Hyperaldosteronism; Hyperthyroidism; Hyponatremia; Hypothyroidism; Syndrome; Vasopressins

Topics: Adult; Aged; Alkalosis; Bendroflumethiazide; Biological Assay; Blood Urea Nitrogen; Bromine; Carbon Dioxide; Chlorides; Chlorpropamide; Chlorthalidone; Creatinine; Diagnosis, Differential; Diuretics; Female; Furosemide; Humans; Hydrochlorothiazide; Hypokalemia; Hyponatremia; Hypopituitarism; Hypothyroidism; Male; Methyclothiazide; Middle Aged; Natriuresis; Osmolar Concentration; Polythiazide; Potassium Isotopes; Radioisotope Dilution Technique; Radioisotopes; Sodium Isotopes; Tritium; Vasopressins; Vomiting; Water-Electrolyte Balance

Topics: Adolescent; Adult; Aged; Animals; Carcinoma, Bronchogenic; Central Nervous System Diseases; Child; Diuretics; Dogs; Electroencephalography; Female; Glomerular Filtration Rate; Humans; Hyponatremia; Hypothyroidism; Iatrogenic Disease; Kidney; Kidney Concentrating Ability; Lung Neoplasms; Male; Middle Aged; Neurologic Manifestations; Polyradiculopathy; Rats; Vasopressins

Topics: Animals; Hypothyroidism; Intraocular Pressure; Rabbits; Vasopressins

Topics: Blood Urea Nitrogen; Blood Volume; Craniocerebral Trauma; Hematocrit; Hodgkin Disease; Humans; Hypernatremia; Hyperpituitarism; Hyponatremia; Hypothyroidism; Male; Middle Aged; Renin; Sodium; Suicide; Vasopressins; Water-Electrolyte Balance

Topics: Adult; Antithyroid Agents; Female; Glucagon; Goiter; Humans; Hypothyroidism; Imidazoles; Iodides; Male; Methimazole; Pituitary Gland; Radioimmunoassay; Stimulation, Chemical; Thyroid Function Tests; Thyrotropin; Time Factors; Vasopressins

Topics: Aged; Brain Damage, Chronic; Bronchial Neoplasms; Humans; Hypothyroidism; Male; Vasopressins; Water-Electrolyte Balance

Topics: Humans; Hypertension; Hypogonadism; Hypothyroidism; Myxedema; Thyroid Function Tests; Vasopressins

Topics: Arginine; Child; Deficiency Diseases; Endocrine System Diseases; Fasting; Growth; Growth Disorders; Growth Hormone; Humans; Hypoglycemia; Hypothyroidism; Insulin; Radioimmunoassay; Stimulation, Chemical; Turner Syndrome; Vasopressins

Topics: Aged; Female; Humans; Hyponatremia; Hypothyroidism; Myxedema; Sodium; Thyroid Hormones; Vasopressins; Water-Electrolyte Balance

Topics: Child; Dehydration; Drug Therapy; Humans; Hypernatremia; Hypothalamus; Hypothyroidism; Metabolism; Neoplasms; Neurosurgery; Pinealoma; Pituitary-Adrenal Function Tests; Prednisone; Thirst; Triiodothyronine; Vasopressins; Water-Electrolyte Balance

Topics: Aged; Female; Humans; Hypothyroidism; Vasopressins

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

Topics: Adrenocorticotropic Hormone; Cushing Syndrome; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetic Nephropathies; Endocrine Glands; Endocrine System Diseases; Hormones; Humans; Hypercalcemia; Hypothyroidism; Liver Diseases; Lung Neoplasms; Neoplasms; Nephrosis; Polycythemia; Pseudopseudohypoparathyroidism; Vasopressins

Topics: Abdomen; Anemia; Angiotensins; Antihypertensive Agents; Blood Circulation; Bradykinin; Coronary Vessels; Ganglionic Blockers; Heart Diseases; Hypertension; Hyperthyroidism; Hypothyroidism; Liver Circulation; Niacin; Pharmacology; Polycythemia; Serotonin; Shock; Vasopressins; Xanthines

Topics: Deamino Arginine Vasopressin; Hyperthyroidism; Hypopituitarism; Hypothyroidism; Iodine Isotopes; Iodine Radioisotopes; Oxytocin; Pharmacology; Physiology; Pituitary Gland; Thyroid Function Tests; Vasopressins

Topics: Arginine Vasopressin; Hypothyroidism; Kidney; Polyuria; Vasopressins; Water

Topics: Animals; Arginine Vasopressin; Electrolytes; Hypothyroidism; Ions; Oxytocin; Potassium; Rats; Sodium; Sodium, Dietary; Vasopressins