The circadian (circannual for oxalic acid) variations of 13 urinary variables (volume, creatinine, calcium, oxalic acid, glycolic acid, <em>17</em>-<em>ketosteroids</em>, <em>17</em>-hydroxycorticosteroids, phosphates, urea, uric acid, chloride, sodium, and potassium) have been documented in 7 calcium oxalate renal stone formers and 7 healthy men (control group). Urine was collected every 4 h over a period of 24 h. All subjects had the same synchronization: diurnal activity from 07(00) to 23(00) +/- 1 h and nocturnal rest; meals were given at fixed clock hours (08(00), 12(30) and 20(00) +/- 1 h). A statistically-significant rhythm (p less than 0.05) was validated for all variables except urea and calcium in healthy men. In renal stone formers, 6 variables (calcium, oxalic acid, and glycolic acid in particular) had no detectable circadian rhythm. However, a periodicity of c. 8 h (ultradian rhythm) was demonstrated for calcium and oxalic acid with peaks being located around 02(00), 10(00), and 18(00). No circannual variations in oxalic acid output could be observed. The present study shows an alteration of the periodicity of calcium and oxalic metabolisms, i.e. the loss of a circadian (24-h) rhythm and the occurrence of an ultradian rhythm of 8 h. The risk of calcium-oxalate crystallisation appears thus greater at 02(00), 10(00), and 18(00). Furthermore, any study dealing with oxalic acid excretion should state the season of urine collection when comparing renal stone formers and healthy subjects, as significant differences in oxaluria may appear during the summer months and not during the rest of the year.

During clinical studies on a 34-year-old man with marked hypogonadism secondary to pituitary gonadotrophin insufficiency, an attempt was made to determine whether the testes were capable of androgen production when stimulated by exogenous chorionic gonadotrophin (A.P.L.).Androgen excretion before and after chorionic gonadotrophin administration was studied. Total and fractionated <em>17</em>-<em>ketosteroid</em> patterns suggested a severe Leydig cell deficiency which was confirmed by testicular biopsy.Panhypopituitarism was considered excluded by a normal response to metyrapone ditartrate, by a normal serum PBI and a normal radioactive iodine uptake. Genetic disorders were likewise excluded to the extent possible by determining that the chromosome pattern was normal and by determining that no similar condition existed in another member of the same family. The association of anosmia with gonadotrophin insufficiency in this case suggests a primary disorder in the hypothalamo-mamillary-tuber cinereum area.

S-petasin, a kind of sesquiterpene ester, is the anti-inflammatory ann analgesic component of the butterbur (Petasites hybridus). The clinical benefit of S-petasin is the spasmolytic activity, but its side effects on the reproductive endocrinology are not clear yet. The present study was to explore the effects of S-petasin on the secretion of testosterone in vivo and in vitro. We found that single intravenous injection of S-petasin (1 microg/kg) decreased basal plasma testosterone concentration in adult male rats. The enzymatically dispersed rat testicular interstitial cells were incubated with S-petasin (0-4.3 x 10(-5)M) in the presence or absence of human chorionic gonadotropin (hCG, 0.05 IU/ml), forskolin (adenylyl cyclase activator, 10(-5) M), and androstenedione (testosterone biosynthesis precursor, 10(-9) M) at 34 degrees C for 1 h. The concentrations of testosterone in the incubation medium were measured by radioimmunoassay. S-petasin at 4.3 x 10(-7) M was effective to reduce the basal and hCG-stimulated release of testosterone in rat testicular interstitial cells. The stimulatory effects of testosterone secretion induced by forskolin and androstenedione were significantly reduced by S-petasin at 4.3 x 10(-5) M and 4.3 x 10(-6) M, respectively. These results suggest that S-petasin inhibits the production of testosterone in rat testicular interstitial cells in part through diminishing the activities of adenylyl cyclase and <em>17</em>-<em>ketosteroid</em> reductase.

In this study, we reviewed the diagnostic efficiency of laboratory tests that are performed for assessment of patients with Cushing's syndrome or adrenal insufficiency. Baseline laboratory data from patients subsequently diagnosed with adrenal dysfunction were analyzed for tests performed between 1987 and 1989 at our institution. Results were analyzed for 36 patients diagnosed with pituitary-dependent Cushing's syndrome, 15 with ectopic Cushing's syndrome, 12 with adrenal-dependent Cushing's syndrome, 20 with primary adrenal insufficiency, and 7 with secondary adrenal insufficiency. Tests reviewed were plasma cortisol, plasma corticotropin, urinary free cortisol, urinary <em>17</em>-<em>ketosteroids</em>, urinary ketogenic steroids, low-dose and high-dose dexamethasone suppression, and metyrapone stimulation. Our findings suggest that a substantial proportion of diagnoses could be based on the results of three tests--plasma corticotropin, plasma cortisol, and urinary free cortisol. We present a nomogram that combines the results of plasma corticotropin and plasma cortisol testing to enhance the diagnostic efficiency of these tests.

The child with testicular enlargement in the absence of gonadotrophin stimulation presents a difficult diagnostic dilemma. Leydig cell tumors, Leydig cell hyperplasia, and tumors of adrenal rest tissue are the primary etiologic considerations. Because of considerable overlap in clinical presentation, careful biochemical and histologic evaluations are necessary to make the diagnosis. These should include serum levels of testosterone, dehydroepiandosterone, androstenedione, <em>17</em>-hydroxyprogesterone, and 11-desoxycortisol, as well as urinary levels of <em>17</em>-<em>ketosteroids</em>. If diagnostic changes in the biochemical profile are not present, then testicular biopsy is indicated. Encapsulation, presence or absence of the crystalloids of Reinke, degree of seminiferous tubule maturation, and the site of any abnormal tissue are important observations in the examination of the tissue specimen. Once the diagnosis has been established, then appropriate and specific medical or surgical therapy can be instituted. With appropriate treatment, the long-term prognosis in each condition is good.

A 6 5/12-year-old boy with polyostotic fibrous dysplasia, café-au-lait pigmentation of the skin, and precocious pubertal development was studied for two years. Parathormone, calcium, phosphorus, testosterone, cortisol, and growth hormone levels were within normal limits. Urinary <em>17</em>-<em>ketosteroids</em>, <em>17</em>-ketogenic steroids, and estrogens were at the upper limits of normal. After GnRH stimulation, there was only a very slight increase in LH and no increase in FSH. There was no increase in TSH after TRH, and plasma levels of T4 and T3 were normal. The plasma prolactin level was within normal limits, and increased after TRH stimulation (with a second, delayed upsurge). Abnormal distribution of 131I in the thyroid was evident, without clearcut evidence of hyperfunctioning areas after TSH stimulation and T3 suppression tests followed by conventional scanning and gamma camera scintiphotography. Our findings do not support the claimed, single, hypothalamic origin of the disease that is presumed to result in overproduction of releasing hormones; they are more in keeping with a pleiotropic, scattered peripheral lesion, possibly of embryonal origin.

Twenty-four hirsute female patients were treated with 100 mg of depo-medroxyprogesterone acetate intramuscularly every 15 days. Twenty-three showed definite improvement from their abnormal hair growth. All patients with initially elevated <em>17</em>-<em>ketosteroids</em> in 24-hour urine collections showed a decrease of these metabolites with treatment. In eleven patients the initial plasma testosterone level was elevated and returned to normal values with treatment. The first patient who was submitted to this therapy stopped the treatment for 5 months and started having abnormal hair growth again. With other patients, after initial treatment with depo-medroxyprogesterone acetate intramuscularly, we started using contraception pills containing medroxyprogesterone; this maintained the reduced ectopic hair growth. The most important side effect was amenorrhea.

In a double-blind study, candicidin therapy resulted in over-all clinical improvement of benign prostatic hypertrophy symptoms in 78.1 per cent of treated patients compared with 10 per cent for patients given a placebo. Histologic review of prostates of candicidin-treated patients showed more stroma relative to the epithelium. The epithelium was less active with more cuboidal than columnar cells. There were fewer papillary infoldings, and the epithelium contained more true cysts than did the prostates of patients given a placebo. Urinary testosterone, <em>17</em>-<em>ketosteroids</em>, <em>17</em>-hydroxycorticosteroids, and serum androgen, follicle-stimulating hormones, and corticosteroid levels ramained within normal values with candicidin therapy.

A case of malignant interstitial cell tumor of the testis is reported and the literature is reviewed. Malignant interstitial cell tumors occur exclusively in adults. Gynecomastia was noted in 12% of the cases. Elevated plasma levels or increased urinary excretion of estrogen, <em>17</em>-<em>ketosteroid</em>, or testosterone were demonstrated in 64% of the patients. Vessel invasion, which occurred in 74% of the patients, appears to be the only reliable histologic feature for predicting malignant behavior. There is no proved sensitivity to radiation or chemotherapeutic regimens in patients with disseminated tumor. Once the diagnosis of malignancy is histologically established, inguinal and retroperitoneal lymph node dissections, even in the absence of clinical evidence of metastasis, may be beneficial in providing early staging of the tumor and, perhaps, in preventing subsequent lymphatic spread.

Sympathoadrenal activity, adrenocortical function and androgenic status were studied in five well-trained mountaineers during the different phases of a mountaineering expedition during the ascent of Mt Pabil (7,102 m) in the Ganesh Himal massif. Sympathoadrenal activity was evaluated by measuring urinary excretion of adrenaline, noradrenaline, metanephrines, and vanillinmandelic acid. Adrenocortical function was assessed by measuring urinary excretion of free cortisol, <em>17</em> OHCS (<em>17</em>-hydroxycorticosteroids) and androgenic status by measuring testosterone glucuronide, Adiol (5 alpha-androstane-3 alpha, <em>17</em> beta diol) and <em>17</em>KS (<em>17</em>-<em>ketosteroids</em>). Reference values were obtained at Chamonix at 1,037 m during rest. During trekking noradrenaline increased significantly while Adiol and <em>17</em>-KS decreased. The fall in the urinary androgenic pool persisted during the next phases of the expedition. At base camp (4,800 m) noradrenaline, its metabolites and free cortisol increased mainly during physical activity. Above 6,000 m, adrenaline, noradrenaline, their metabolites, free cortisol and <em>17</em>-OHCS reached a maximum value. During the return to sea level, the urinary level of these parameters was still high. The drop in the urinary androgenic pool observed during trekking and exposure to high altitude confirms results obtained in other studies on prolonged efforts. This hypoandrogenicity may play an important role in the metabolic adaptations as well as in the mental state of the climbers. The increase of sympathoadrenal activity and of adrenocortical function may be considered as a regulatory element in the adaptative response to hypoxia and other stressors proper to high altitude.