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Biologic and radiologic investigations in the diagnosis of Cushing syndrome are evaluated. A two-step diagnostic procedure is propounded. The combination of absence of overnight suppression of plasma cortisol by dexamethasone and elevation of urinary free cortisol and midnight plasma cortisol levels establishes the diagnosis of Cushing syndrome in most patients. The next step is to determine the precise cause of Cushing syndrome by baseline plasma ACTH assays, the high-dose dexamethasone test and the visualization of the adrenals by iodocholesterol scintigraphy and/or computed tomography.

A study of ACTH response to orally given metyrapone were carried out with 32 normal subjects aged 18 months to 15. Effectiveness of adrenal inhibition was supported by delta F > 5 microgram or cortisol level after metyrapone < 3 microgram/100 ml. The strong positive correlation between delta F and delta ACTH indicates the high sensibility of delta ACTH as an index of the responsiveness. No correlation was found between delta ACTH and weight, height, or age. Mean level (M +/- 2 SEM) are established: plasma ACTH level at 8 before metyrapone = 32,1 +/- 7,5 pg/ml; plasma ACTH level at 8 after metyrapone = 271,8 +/- 57 pg/ml; delta ACTH = 240 +/- 6 pg. Including these considerations, biological ACTH variability, and reproductibility of determinations, an abnormal response seems to be proved by plasma ACTH level at 8 after metyrapone < 100 pg/ml or/and delta ACTH < 70 pg. A normal response is established by delta ACTH > 150 pg.

We have observed a secreting tumor of the testis classified as an intermediate malignant teratoma type A. This hormone secreting tumor was associated to bilateral gynecomasty. Surgery with radiotherapy were followed by disappearance of all symptoms for two years. Hormone levels, that were abnormal, returned to normal. Next to seminomas, testis teratomas are grouped in different types according to their differentiation, from well organized tissues to totally anaplastic cells. Clinical manifestations of these lesions are essentially dependent on their secretory capacity. Gynecomasty secondary to oestrogenic production of chorionic gonadotrophins or pituitary hormones, is the usual symptom; one may encounter hyperthyroidism or hypercortisolism. Generally, resection of the tumor is followed by a return to normal hormone values; recurrence of pathological values is often a sign of metastatic evolution. The treatment is orchidectomy with radiotherapy or eventually with chemotherapy.

The usefulness for the diagnosis of Cushing's syndrome of urinary free cortisol and urinary 17-hydroxycorticosteroid (17-OHCS) determination was compared by measuring these substances in 17 normal and 28 obese subjects and in 19 patients with established Cushing's syndrome. These measurements were repeated in 16 obese subjects and 11 Cushing's syndrome patients after oral administration of dexamethasone (2 mg/day for 2 days, then 8 mg/day for 2 days). As a group, the patients with Cushing's syndrome had higher (p less than 0.001) excretion rate of both free cortisol and 17-OHCS, but the values observed in this group overlapped with those of normal and obese subjects. The overlap was not significantly different for free cortisol and 17-OHCS excretion. In each obese subject, oral dexamethasone decreased the urinary excretion rate of both free cortisol and 17-OHCS. Seven out of the eleven patients with Cushing's syndrome had no decrease of urinary free cortisol or 17-OHCS, whereas both values were slightly lower in one and decreased to levels similar to those obtained in obese subjects in the three remaining patients. It is concluded that there is no advantage in measuring free cortisol excretion instead of 17-OHCS excretion, either before of after a pituitary-adrenal suppression test, for the diagnosis of Cushing's syndrome.

In three young girls with isosexual precocity and fibrous dysplasia of bones, plasma gonadotropins (LH and FSH) response to releasing hormone (LH-RH) has been much under the mean response in true female precocious puberty. These data and those previously reported in the literature suggest that MacCune-Albright's syndrome correlates to an hypothalamo-pituitary dysfunction rather than to a true prematurity.

Electrolytes disturbances during operative period are believed to be related to an hyperaldosteronism produced by anaesthetic management and surgery. Effects of ethrane anaesthesia and surgery on hydroelectrolytic metabolism and endocrin function were investigated in 11 patients submitted to an abdominal surgery. Plasma and urinary levels of aldosterone were increased (x3) significantly (p less than or equal to 0.001) during operation, then decreased gradually in post-operative period, and return to normal values when Na/K ratio is reversed in urines. Relationship between hyperaldosteronism and other changes in endocrine function are established by determination of following hormones: A.C.T.H., cortisol, plasma renin activity (P.R.A.) catecholamines in plasma and urinary levels of 17-ceto, 17-hydroxysteroids and catecholamines. Ethrane anesthesia give a good neurovegetative stability since plasma catecholamines levels are not affected significatively. Plasma aldosterone level is correlated with urinary aldosterone and plasma renin activity. Plasma A.C.T.H. is much more increased at the operative time and decreases rapidly instead of plasma cortisol which decreases more slowly. Relationship of this hyperaldosteronism with anesthetic management, surgical stress intestinal transit disturbances, other endocrine function changes is discussed.

The 24-hour urinary excretion rates of creatinine, vanilmandelic acid (VMA), 17-hydroxycorticosteroids, 17-ketosteroids were analysed in 30 female twin pairs. For each of these variables, a comparative study based on the breakdown of total variance into interpair and intrapair variance was undertaken, first on identical (MZ) and fraternal (DZ) twins and then on twins who live together or separately. The comparison of test results shows a strong likeness in the MZ group and in the living together group with respect to the urinary excretion of 17-OH. The variability of VMA excretion can be explained by genetic factors while the variability of 17-ketosteroids and creatinine can be explained with reference to environmental factors.

The adrenocortical function was studied in 23 patients with hyperthyroidism. The half-life of tritiated cortisol was significantly shortened; metabolic clearance rate was about twice increased, and production rate of cortisol was significantly increased in hyperthyroidism. The mean plasma concentration was unmodified. After return to euthyroid state, all the values were normalized in 7 patients.

The extraction ot total urinary 17-keto and 17-hydroxy steroids has been effected by a rapid procedure involving pre-packed kieselguhr column chromatography. This work successively studies the correlation of this technique with the classical extraction by mechanical agitation (42 and 61 subjects), its reproducibility, repeatability and recovery of added internal standards. The proposed method seems convenient for routine clinical analysis.

The circadian rhythm of plasma cortisol and urinary 17-hydroxy-corticosteroids has been studied in 6 normal volunteers both in basal conditions and after the administration of a single dose of 30 mg of a banthine derivative (the beta methyl-beta-isopropylaminoethyl ester bromide of xantene-9-carbonic acid, "Pervagal") given orally once a day at different hours (midnight, 4 AM, 8 AM, noon, 4 PM, 8 PM). The vagolytic drug inhibits the cortisol secretion only when administered at 4 PM, 8 PM or midnight, whereas it is ineffective when given at different hours. If don't exist circadian variations of the bio-availability of the drug employed, our results suggest that also in human beings as well as in experimental animals, the cholinergic mechanisms are effective, over all if not exclusively, in starting the circadian activation of the hypothalamo-pituitary-adrenal system.

In eight apparently healthy young men a circadian rhythm (P less than 0,05) in urinary 17-hydroxycorticosteroids (17 OHCS) and tetrahydro-11-deoxycortisol (THS) has been demonstrated before (A), during (B) and after (C) a 36 h sustained oral administration of metyrapone (7.50 g in ten doses of 0.75 g every 4 h). Subjects synchronization: light-on 0715; light-off 2300. 17 OHCS have the acrophase phi located at 1430 (2:30 p.m.) in the three circumstances. Only traces of THS are excreted during A. During B and C when THS is excreted, a circadian rhythm is validated (p less than 0.05) with a phi at 1430.

Thirty-four cases of corticosurrenaloma with clinical onset before 15 years of age have been studied. Higher frequency in girls (65 percent of the cases) and in young age (80 percent before 5 years of age, 43 percent before 2 years), association with personal or familial other tumors and malformations, are noticeable features. Virilism is the major manifestation in children (83 percent of the cases), either isolated or associated with hypercortisolism and/or feminization. Hormonal assays are of little value, and the dynamic adrenal tests are of some help only in small tumors or isolated hypercortisolism. Radiological diagnosis by urography with cavography, arteriography, is easy in most cases. Evaluation of prognosis is very difficult. Clinical and biological data are not significant, histological data are often of little help. Only a very large mass, and occurrence of metastases (liver, lungs) evidence malignancy. This series does not allow to assess definitely the best therapeutic regimen. Surgery has to be performed as soon as possible. The effects of radiations have not yet been ascertained. High doses of op'DDD have led to a sustained remission of the tumor or metastases in 2 patients, and perhaps to a longer survival in 4 others.

In this research involving 172 cases of acute primary polyradiculoneuritis, the authors draw attention to the frequency and seriousness of the autonomic disorders, notably circulatory disorders (arterial hypertension, bradycardia), water retention, disorders in glucose metabolism. They have found a close correlation between the development of arterial hypertension and levels of VMA and the cathecholamines and between the appearance of hyperglycaemia and the level of urinary 17 OH. Free water clearance is often negative and becomes positive as the paralytic syndrome improves. The biological picture is identical with that brought about by inappropriate secretion of HAD. From the therapeutic point of view, caution is advised in using certain procedures and in prescribing certain drugs.