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Autoantibodies to vasopressin cells in idiopathic diabetes insipidus: evidence for an autoimmune variant.

Autoantibodies to vasopressin-secreting cells of human hypothalamus were detected by means of indirect immunofluorescence (IFL) in 13 patients with diabetes insipidus (DI). 11 of 30 patients (36 . 7%) with "idiopathic" and 2 of 32 (6 . 3%) with symptomatic DI were positive, and 139 control patients were negative. The specificity of the reaction vasopressin cells was demonstrated with a 4-layer double-fluorochrome IFL test in which the second sandwich consisted of rabbit antivasopressin or anti-oxytocin counterstained with rhodaminated anti-rabbit immunoglobulin. 5 patients had also antibodies to oxytocin-producing cells. The antibodies reacted with cytoplasmic components distinct from the hormone; they were of IgG, IgA, or IgM class or a combination of these classes, and half of them fixed complement. Maximum titres were 1:32, and the antibodies could not be absorbed out by incubation with vasopressin, oxytocin, neurophysin I, or neurophysin II. Some sera stained as yet unidentified small cells in the hypothalamus. This report suggests that autoimmunity extends to the hypothalamus. Vasopressin-cell antibodies may prove to be useful markers for the diagnosis of an autoimmune variant of diabetes insipidus.

Adolescent↗

A case of nephrogenic diabetes insipidus caused by obstructive uropathy due to prostate cancer.

Nephrogenic diabetes insipidus (DI) secondary to chronic urinary tract obstruction is a rare disease. The exact cause is unknown but it is likely that increased collecting duct pressures cause damage to the tubular epithelium, resulting in insensitivity to the action of arginine-vasopressin (AVP). A 77-year-old man complaining of polyuria and polydipsia was treated with alpha glucosidase inhibitor under the impression of polyuria due to diabetes mellitus. But his symptoms did not improve. Water deprivation and AVP administration study revealed that the patient had nephrogenic DI. Urinary tract obstruction due to an enlarged prostate was suggested as a principal cause of nephrogenic DI. The patient underwent transurethral resection of the prostate and bilateral subcapsular orchiectomy. After surgery, the urine osmolarity was normalized and the patient became symptom-free. We report a case of nephrogenic DI due to obstructive uropathy which was cured by surgery eliminating obstruction.

Adenocarcinoma↗

Differential clinical courses of pregnancies complicated by diabetes insipidus which does, or does not, pre-date the pregnancy.

We present six cases of diabetes insipidus (DI) complicating pregnancy. In three cases, DI was manifested during pregnancy and required the administration of desmopressin acetate (1-desamino-8-D-arginine vasopressin, DDAVP). All these cases exhibited abnormal laboratory data such as an elevation of liver enzymes or a decrease in serum antithrombin III. The remaining three cases had suffered from DI before pregnancy which was well controlled on DDAVP. The clinical courses of these pregnancies were all uneventful subsequent to therapy. If DI is first recognized during pregnancy, attention should be paid to the possibility of abnormal liver function and eclampsia.

Adult↗

1-Deamino-8-D-arginine vasopressin and urine cyclic adenosine monophosphate excretion in diabetes insipidus.

The response to 1-deamino-8-D-arginine vasopressin (DDAVP), an intranasally administered analogue of vasopressin, was investigated in children and adults with central diabetes insipidus. To assess the action of DDAVP on the distal nephron, cyclic adenosine monophosphate (cAMP) excretion was assayed in urine collected 4 hr before and during four subsequent 4-hr periods after intranasal administration of 5 micrograms DDAVP. Maximal effects on urine volume and concentration were observed between 4 and 12 hr, coinciding with an elevated cAMP excretion in seven subjects. The pretreatment 4-hr cAMP excretion (micrograms/gm creatinine) correlated inversely with age (p less than 0.02) and surface area (p less than 0.001). Subsequent cAMP excretion after DDAVP increased inconsistently with no relationship to duration of antidiuresis, indicating that urinary cAMP is a poor index of antidiuretic hormone action on the distal nephron. We also confirmed that DDAVP intranasally induces antidiuresis in patients with diabetes insipidus over approximately 12 hr.

Adolescent↗

The neuroanatomical and neurovascular organization of normal fetal hypothalamic explants in the third cerebral ventricle of Brattleboro rats with homozygous diabetes insipidus.

This investigation has combined microangiography, immunocytochemistry, coupled with transmission and scanning electron microscopy to discuss the neuroanatomical interactions that occur in the brains of Brattleboro rats with diabetes insipidus, following stereotaxic placement of normal fetal hypothalamic fragments into the third cerebral ventricle. Following surgical placement of 17 day post-coitus hypothalamic fragments, host rats with chronic autosomal homozygous diabetes insipidus were killed and their brains were prepared for analysis. A significant degree of explants (68%) flourished and grew in the lumen of the third cerebral ventricle of recipient hosts. Explants were rapidly invaded by host vessels from two routes. Vessels arose from the underlying mantle plexus of portal capillaries which remained fenestrated in the lower one-third of the explants and developed neurovascular (neurohemal) zones. The second source of vessels arose from bed capillaries of the adjacent paraventricular nucleus and adjacent hypothalamus. In contrast to vessels arising from the contact zone, these latter vessels remained unfenestrated. Small clusters of immunocytochemically positive neurons (neurophysin positive) were seen throughout the explants. Numerous healthy magnocellular neurons harboring numerous dense core vesicles and exhibiting multiple axosomatic and axodendritic synapses were seen throughout the neuropil of explants. Axon profiles were noted to terminate upon the abluminal basal lamina of perivascular spaces surrounding fenestrated capillaries in the lower one third of explants. None of the host animals exhibited physiological return to normal parameters of urine output, drinking behavior, and/or urine osmolarity. However the growth and development of explants in the third cerebral ventricle of DI hosts coupled with the emergence of bonafide neurovascular zones supports a potential anatomical substrate for the central delivery of neuropeptide hormones in this experimental model.

Animals↗

[DDAVP in the treatment of acute neurosurgical diabetes insipidus].

The effects of a synthetic vasopressin analogue, DDAVP (1-deamino-8-d- arginine-vasopressin) were studied in 5 adults and 2 children with acute central diabetes insipidus secondary to neurosurgery. 5 mcg DDAVP was administered intranasally twice a day to the two children, whereas the adults received the drug i.m. (1 mcg twice a day, 3 patients; 1 mcg once a day, 1 patient; 4 mcg twice a day, 1 patient). All subjects displayed an early, prolonged response (12-24 hr). There were no side-effects. The effectiveness of DDAVP, its prolonged action, and virtual freedom from side-effects when given intranasally or parenterally make it the drug of choice in the treatment of acute neurosurgical diabetes insipidus.

Adolescent↗

Diabetes insipidus.

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Diabetes Insipidus↗