Myron Miller

Recognition of Partial Defects in Antidiuretic Hormone Secretion

Abstract A dehydration procedure has been used to identify patients with partial antidiuretic hormone (ADH) deficiency. The test consists of water deprivation until the osmolality of hourly voided ...

Drug-induced dilutional hyponatremia

IN recent years, several pharmacologic agents have been shown to have water-retaining properties. At first, the antidiuretic actions were used to advantage in the treatment of patients with diabetes insipidus. However, more recently there have been numerous reports of serious water retention and dilutional hyponatremia as a consequence of the water-retaining drugs. This report has been prepared to summarize the drugs and the problems that they have produced and to alert the medical profession to the problems. Pathophysiology of Water Retention The maintenance of water balance in man results from the interaction of factors controlling water intake and water loss. .xa0.xa0.

Clofibrate-Induced Antidiuresis

Normal subjects and patients with antidiuretic hormone (ADH) deficiency were studied to determine the mechanism of the antidiuretic action of clofibrate. Before clofibrate treatment, the patients ability to concentrate urine with a standardized dehydration procedure correlated with the amount of ADH which was excreted. During clofibrate administration all six patients with ADH deficiency developed an antidiuresis which was like that of ADH, since there was no change in sodium, potassium, total solute, or creatinine excretion. There was a correlation between the patients ability to concentrate urine during dehydration and the subsequent response to clofibrate, and the excretion of ADH during dehydration correlated with the excretion of ADH on clofibrate therapy. Clofibrate-induced antidiuresis in these patients was partially overcome by ethanol and by water loading. Clofibrate interfered with the ability of patients and subjects to excrete a water load and prevented the water load from inhibiting ADH excretion in the normal subjects. These studies suggested that clofibrate was acting through endogenous ADH and this thesis was supported by the failure of clofibrate to produce an antidiuresis when injected into rats with total ADH deficiency (Brattleboro strain) although an antidiuresis was produced in water-loaded normal rats. When the drug was injected into Brattleboro rats with exogenous ADH, clofibrate either did not alter or it inhibited the action of the ADH. The data demonstrate that clofibrate has a significant ADH-like action. This action appears to be mediated through the release of endogenous ADH.

Chlorpropamide-Induced Water Retention in Patients with Diabetes Mellitus

Abstract Two patients with diabetes mellitus who were treated with chlorpropamide developed a symptomatic clinical state of hyponatremia and water intoxication. Chemical abnormalities and symptoms ...

Urinary antidiuretic hormone in polyuric disorders and in inappropriate ADH syndrome.

Abstract Urinary antidiuretic hormone (ADH) excretion was measured by radioimmunoassay in patients with polyuric disorders and with the inappropriate ADH syndrome. The hormone was undetectable in p...

Water Intoxication and Thioridazine (Mellaril

Excerpt The occurrence of water intoxication in patients who have the ability to dilute urine normally is very unusual (1). Normal adults can excrete between 10 and 14 ml/min of solute-free water, ...

Dissociated patterns of nocturnal prolactin, cortisol, and growth hormone secretion after stroke.

The secretory activity of the hypothalamic-pituitary axis is influenced by suprahypothalamic regulatory mechanisms. To evaluate the effect of brain lesions on hormonal patterns, we investigated eight patients convalescing from hemispheric stroke and five sex- and age-matched healthy volunteers. Studies were conducted during two consecutive nights with continuous polygraphic recording and sequential blood sampling. Nocturnal plasma hormone measurements showed a normal rhythm of cortisol (a marker of ACTH), elevated prolactin concentrations (p &;t 0.05) and low growth hormone values (p < 0.05). The study suggests that major suprahypothalamic lesions influence hypothalamic function so as to facilitate prolactin secretion and inhibit growth hormone release. They have no effect on the more basic pattern of ACTH-cortisol secretion, however.

Antidiuretic Action of Prolactin in the Rat with Diabetes Insipidus

Rats with hereditary hypothalamic diabetes insipidus, devoid of endogenous ADH, exhibited a prompt antidiuresis when injected subcutaneously or intraarterially with ovine prolactin. The antidiuresis was accompanied by a decrease in free water clearance and an increase in urine osmolality without a change in osmolal clearance or creatinine excretion. Measurement of PAH and insulin clearances indicated that prolactin had no effect on renal plasma flow or glomerular filtration rate. Prolactin injection caused a transient decrease in urinary sodium excretion, but proximal tubular sodium reabsorption, estimated by lissamine green transit time, was unaffected. The antidiuretic effect of prolactin could not be attributed to ADH contamination of the ovine prolactin preparation. Kidney cyclic AMP content was increased significantly 5 min after injection of prolactin. Thus, prolactin has an antidiuretic effect similar to that which occurs as a result of ADH action on the kidney and does not require either the release or the presence of ADH in order to cause the antidiuresis. Further, the impaired water excretion cannot be attributed to an increase in proximal tubular sodium reabsorption or to alteration of renal hemodynamics. It is suggested that prolactin has a direct ADH-like action on the kidney resulting in antidiuresis.

Failure of postictal growth hormone rise in a patient with thalamic lesions

A patient with bilateral thalamic lesions had a spontaneous generalized convulsion during nocturnal polygraphic recording. Postictal measurements of cortisol and prolactin showed the expected rise of plasma values at 30 and 60 minutes after the seizure, but growth hormone did not increase. This observation suggests that suprahypothalamic mechanisms regulating growth hormone release differ from those involved in the neural control of cortisol-ACTH and prolactin secretion. The thalamus may intervene as a regulatory center in the release of growth hormone.

Evidence that Glyburide-Induced Diuresis is not Mediated by Inhibition of ADH

The sulfonylurea, chlorpropamide, has a well defined antidiuretic effect mediated both through increased ADH release and potentiation of ADH action on the kidney. In contrast, the sulfonylureas tolaza