Unconjugated, sulpho- and glucurono-conjugated androgen hormone metabolites have been determined in the urine of patients with rheumatoid arthritis. An increase in the excretory rate of unconjugated 5 beta-reduced <em>17</em>-<em>ketosteroids</em> and a decrease in that of <em>17</em>-<em>ketosteroid</em> conjugates, especially in dehydroepiandrosterone sulphate and in the sum of dehydroepiandrosterone, etiocholanolone and androsterone glucuronoside were observed. In contrast to unconjugated metabolites, there was less significant change in the 5 beta-metabolite conjugates in urine. Corticosteroid treatment resulted in an additional decrease of metabolite excretion by patients. Further study is necessary to determine the causative factors in the altered steroid pattern observed in this severe, non-endocrine disease.

The adrenal gland uptake of 131I-6-beta-iodomethyl-19-norcholesterol (NP-59) was calculated using a semioperator-independent computer algorithm in <em>17</em> patients with Cushing's syndrome (CS). Twelve had ACTH-dependent and 5 had ACTH-independent CS. The mean adrenal gland uptake (percentage of administered dose) of NP-59 was 0.74 +/- 0.18% (range, 0.21-2.02%) in CS and was significantly higher than that of normal subjects (0.33 +/- 0.02%). Patients with the ectopic ACTH syndrome and ACTH-independent CS manifested the highest uptakes (mean, 1.18 +/- 0.08%; range, 0.74-2.02%). In the patients with ACTH-dependent CS, a significant correlation was observed between 24-h urinary free cortisol excretion and NP-59 adrenal gland uptake (r = 0.97, P less than 0.001). No relationship was seen between NP-59 uptake and urinary free cortisol in ACTH-independent CS or between NP-59 uptake and urinary <em>17</em>-hydroxycorticosteroids, <em>17</em>-<em>ketosteroids</em>, cortisol secretion rate, plasma cortisol, or ACTH levels in either ACTH-dependent or ACTH-independent CS. We conclude that in addition to localizing the sites(s) of adrenocortical hypersecretion in CS, the level of NP-59 adrenal uptake is a reflection of cortisol excretion in ACTH-dependent disease and may be utilized as another parameter to quantitate adrenal disease activity in CS.

Endocrine disturbances associated with myotonic dystrophy (MD) include testicular atrophy, hyperinsulinemic glucose intolerance, thyroid abnormalities, and low or low normal urinary <em>17</em>-<em>ketosteroid</em> (<em>17</em>-KS) excretion. Since the major circulating precursors of urinary <em>17</em>-KS are dehydroepiandrosterone sulfate (DHAS) and dehydroepiandrosterone (DHA), a decrease in adrenal androgen production has been suggested. This possibility was studied in 19 MD patients and 19 age- and sex-matched normal subjects. Each patient had a 24-h urine collection for <em>17</em>-KS and cortisol determinations, a 4-h iv infusion of 25 micrograms tetracosactrin with serial measurements of serum DHAS, DHA, and cortisol, and an insulin-induced hypoglycemia test. Sixteen patients had 0800 and 2400 h serum collections for cortisol estimations. Serum DHAS [1.0 +/- 0.5 (+/- SD) vs. 3.9 +/- 1.9 mumol/liter; P less than 0.0005] and DHA (5.9 +/- 2.7 vs. 11.0 +/- 7.1 nmol/liter; P less than 0.005) levels were significantly lower in MD patients than in normal subjects; cortisol levels were higher (540 +/- 222 vs. 394 +/- 128 nmol/liter; P less than 0.01), almost certainly a reflection of stress. A normal diurnal cortisol rhythm was found in all 16 subjects. Cortisol responses to insulin-induced hypoglycemia were normal, increasing from 345 +/- 243 nmol/liter to a maximum of 831 +/- 282 nmol/liter. Urinary <em>17</em>-KS excretion was low or low normal, while urinary cortisol levels were normal in 18 and mildly elevated in 1 patient. There was a significant correlation between <em>17</em>-KS and DHAS levels (r = 0.46; P less than 0.05). DHAS, DHA, and cortisol responses to tetracosactrin infusion were similar in patients and normal subjects. It is concluded that 1) in MD patients, serum DHAS and DHA concentrations are significantly lower than those in normal subjects, explaining the frequent reports of low or low normal <em>17</em>-KS excretion; 2) the reduced DHAS and DHA concentrations are most likely due to decreased production rather than increased clearance; and 3) glucocorticoid production is normal.

The Zucker obese (fa/fa) rat is a model of hypertrophic/hyperplastic obesity. These rats develop marked hyperinsulinemia, insulin resistance, and pancreatic beta-cell hyperplasia. In the present study, chronic (22 weeks) administration of the <em>17</em>-<em>ketosteroid</em>, dehydroepiandrosterone (DHEA), to obese Zucker rats significantly decreased body weight, and retroperitoneal and parametrial fat pad weights. In addition, beta-cell hyperplasia was reduced as well as pancreatic insulin content. DHEA treatment of lean Zucker rats also reduced body weight, fat depot weight, pancreatic islet diameter, and pancreatic insulin content. These data indicate that DHEA treatment appears to inhibit insulin synthesis and beta-cell proliferation. Whether this is due to a direct effect on the pancreas or due to improvement of peripheral insulin sensitivity remains to be elucidated.

The purpose of the study was to analyse bone density in patients with noninsulin-dependent diabetes mellitus with respect to such factors as the magnitude of obesity, serum cortisol concentration and <em>17</em>-<em>ketosteroid</em> excretion and insulinemia level. Bone density was measured by ultrasonography, insulin was determined by radioimmunoassay, and steroid level by using the method of Zimmerman. The patients had imminent and overt osteoporosis. The highest serum cortisol concentration was in groups with lower T-score significant negative correlation between cortisol and SOS index. The lowest <em>17</em>-<em>ketosteroid</em> level was detected in the patients with the lowest T-score; a significant correlation was observed between <em>17</em>-<em>ketosteroids</em> and BUA index. The present findings indicate an imbalance between bone protective and resorptive factors. This leads to osteopenia in patients with noninsulin-dependent diabetes mellitus despite a protective effect of obesity.

The dynamic excretion of aldadiene, the principal metabolite of spironolactone with biological activity, was studied in normal subjects and patients with liver cirrhosis following administration of spironolactone. Aldadiene appeared in the three-days urine collection in around 3% of the dose. There was no significant difference in the biological half-life, calculated from the urinary pattern, and in the rate of excretion in patients with hepatopathy and hospitalized controls. Healthy volunteers without hospitalization exhibited the most rapid elimination of the metabolite. An increase of spironolactone dose enhanced the per cent rate of aldadiene excretion, while the biological half-life did not change. Spironolactone decreased the rate of dehydroepiandrosterone and androsterone excretion even after a single dose. Determination of total <em>17</em>-<em>ketosteroids</em> is of no value on evaluation of adrenal function during spironolactone therapy, due to a Zimmermann-positivity of spironolactone metabolites.

We report the case of a patient whose periods of periodic catatonia were abolished by thyroid hormone and reserpine. A ratio of fractions in the urinary <em>17</em>-<em>ketosteroids</em> was a good indicator for the treatments.