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This Review Article overviews the literature on diabetes insipidus (DI) associated with pregnancy and labor in Japan published from 1982 to 2019. The total number of patients collected was 361, however, only one-third of these cases had detailed pathophysiologic information enabling us to identify the respective etiology and subtype. Pregnancy-associated DI can be divided into 3 etiologies, central (neurogenic) DI, nephrogenic DI, and excess vasopressinase-associated DI. Neurogenic DI has various causes: for example, DI associated with tumoral lesions in the pituitary and neighboring area, DI associated with Sheehan's syndrome and/or pituitary apoplexy, and DI associated with lymphocytic infundibuloneurohypophysitis (LINH, stalkitis). Nephrogenic DI results from defective response of the kidney to normal levels of vasopressin. However, the most interesting causal factor of pregnancy-associated DI is excess vasopressinase, caused either by excess production of vasopressinase by the placenta or defective clearance of vasopressinase by the liver. Hepatic complications resulting in pregnancy-associated DI include acute fatty liver of pregnancy (AFLP) and HELLP syndrome (syndrome of hemolysis, elevated liver enzymes, low platelets), as well as pre-existing or co-incidental hepatic diseases. A possible role of glucose uptake in putative stress-induced DI and the importance of correct diagnosis and treatment of pregnancy-associated DI, including use of 1-deamino 8-D arginine vasopressin, are also discussed.

A 20-year-old Japanese man with a hypothalamic tumor (most likely germ-cell tumor) which caused secondary hypoadrenalism, hypogonadism and diabetes insipidus developed hypercalcemia and acute renal failure. The serum levels of intact PTH (iPTH), PTH-related protein (PTH-rP), 1,25-dihydroxy vitamin D (1,25- (OH)2 D), ACTH, cortisol, gonadotropins and testosterone were decreased, but his serum levels of triiodothyronine (T3) and thyroxine (T4) were within the normal range at admission, with depressed TSH and slightly increased thyroglobulin. The hypercalcemia was refractory to extensive hydration and calcitonin, but was ameliorated by pamidronate. After irradiation of the hypothalamic tumor, panhypopituitarism gradually developed. The patient has been normocalcemic for the last 2 years and is doing well under replacement therapy with glucocorticoid, L-thyroxine, methyltestosterone and 1-desamino D arginine vasopressin (dDAVP). As to the mechanism of euthyroidism at admission, transient destructive thyroiditis associated with hypopituitarism or delayed development of hypothyroidism following the hypoadrenalism was suggested. This is the first reported case of hypercalcemia in secondary hypoadrenalism due to hypothalamic tumor. Hypercalcemia was most likely induced by increased bone resorption, which was probably elicited by the combined effects of deficient glucocorticoid and sufficient thyroid hormones in addition to hypovolemia and reduced renal calcium excretion. Furthermore, severe dehydration due to diabetes insipidus and disturbance of thirst sensation caused by the hypothalamic tumor aggravated the hypercalcemia, leading to acute renal failure.

We encountered a pregnant woman with transient diabetes insipidus which developed during the third trimester. A hypertonic saline infusion study did not concentrate the osmolality of urine. Her laboratory data showed hypokalemia, hyperreninemia, an increased concentration of plasma aldosterone and an increased urinary excretion rate of prostaglandin E2, which resembled hyperprostaglandin E-syndrome. T1-weighted magnetic resonance imaging of the posterior pituitary gland revealed decreased intensity. Polyuria reached 4-6 L daily, and urine osmolality remained dilute despite a lapse of four days since treatment with intranasal 1-desamino-8-D-arginine vasopressin (dDAVP: 10-25 microg every 12 h). The patient was conservatively managed without medical treatment, then delivered in the 38th week of pregnancy without complication. The osmolality of the patient's urine was higher than that of the plasma when tested 3 days postpartum. The abnormality of magnetic resonance imaging of the posterior pituitary gland disappeared at 6 months after delivery. We consider that subclinical nephrogenic diabetes insipidus in our patient was exacerbated during pregnancy.

A highly sensitive and simple radioimmunoassay for the measurement of 8-arginine vasopressin (AVP) in human plasma has been developed. The dose response curve ranges from 0.025 to 8 pg/tube. This simple extraction technique employing an ODS C18 column recovered 87.1 +/- 10.4 (mean +/- SD)% of AVP in the range of 1-10 pg/ml added to 0.5 ml plasma. Determination of AVP in each fraction of plasma, which was gel-filtrated through a Sephadex G25 (1 X 25 cm), revealed that the fraction of plasma AVP was superimposed on that of authentic AVP, and interference of non-specific substances was completely eliminated by an ODS C18 column. Using the assay, 13 of 16 patients with diabetes insipidus (DI) showed plasma AVP concentrations ranging from 0.03 to 0.21 pg/ml, and the other 3 patients had less than 0.03 pg/ml. The AVP concentrations of DI were clearly distinguished from those obtained in normal subjects (0.30-4.20 pg/ml, n = 65). The within and between assay variability was about 10% each. Plasma AVP concentrations (mean +/- SD) of normal subjects (n = 6) standing, sitting, and supine after an overnight of fluid deprivation were 2.41 +/- 1.15, 1.95 +/- 0.85 and 0.97 +/- 0.48 pg/ml (30 min after) respectively. Plasma AVP concentrations of normal subjects (n = 6) after water load (20 ml/kg wt) were clearly reduced from 1.89 +/- 1.00 (before) to 0.42 +/- 0.21 (standing for 60 min) and also from 0.89 +/- 0.41 to 0.40 +/- 0.22 pg/ml (supine for 60 min).