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A case of adrenogenital syndrome due to 11beta-hydroxylase deficiency is described in a mother, 25 years of age, who had experienced a successful pregnancy 5 years previously. At that time no abnormality had been suspected and pregnancy was achieved without therapy. Subsequently the patient was examined because of secondary sterility. The menstrual cycles were anovulatory. Only slight virilization was observed and blood pressure was normal. Diagnosis was based on the observation of highly increased urinary excretion of 17-ketosteroids and 17-ketogenic steroids, with especially high excretion of tetrahydro-11-deoxycortisol. Following suppression with dexamethasone and adequate maintenance treatment, the patient conceived and had an uneventful pregnancy. This is apparently the first report of pregnancy in adrenogenital syndrome due to 11beta-hydroxylase deficiency.

Sexual development was evaluated in 9 female and 2 male subjects with Prader-Willi syndrome. The process of sexual development and degree of genital development attained were found to be variable but abnormal in all subjects. Hypothalamic-pituitary-gonadal functions were evaluated by measurement of serum Luteinizing Hormone and plasma testosterone responses to stimulation by clomiphene citrate and plasma testosterone responses to stimulation by human chorionic gonadotrophin. The degree of vaginal estrogenization was variable. The testicular biopsies showed abnormalities mainly in the germinal epithelium. In agreement with previous studies, it was concluded that the abnormalities of sexual development in this syndrome are mainly due to a defect in the hypothalamic pituitary axis. Adrenal function was not found to be grossly abnormal. The 17 ketosteroid excretion values were low, probably explaining the rather sparse pubic and axillary hair observed in these patients. The urinary 17-hydroxycorticosteroid creatinine ratios were found to be elevated, probably due to decreased creatinine excretion, reflecting the muscular abnormalities of these subjects.

On the basis of own investigations of the testosteron metabolism in hepatopathy must be assumed that the hypogonadism appearing in liver diseases is to be regarded as peripheral form, i.e. it is not centrally evoked by gonadotropin insufficiency. An own pathogenetic concept is discussed.

To evaluate the usefulness of blood testosterone (T) in monitoring the effects of therapy in congenital virilizing adrenal hyperplasia due to 21- or 11- hydroxylation defect (CVAH), T levels were measured on 45 occasions in 13 patients with CVAH; 32 urinary 17-ketosteroid levels and 31 preganetriol values were available for comparison. Bone age levels, growth data, and medication are listed to help assess the clinical state of the patient at the time of each T determination. Blood T values were above normal for age and sex in untreated patients with CVAH and declined with glucocorticoid suppression. A blood T value of 20 ng/100 ml appeared to distinguish between well-controlled cases and those with inadequate steroid suppression. Serial measurement of blood T in girls and in prepubertal boys with CVAH provides assistance in evaluating chemical control of the disease, particularly when accurate 24-h urine collections cannot be obtained for 17-ketosteroid and pregnanetriol assessments.

Impairment of cortisol metabolism, evidence of endogenous hypercortism and sensitivity to oral corticosteroids are known to occur in patients with chronic liver disease. Measurements were made of plasma 11-OHCS and urinary cortisol levels and other parameters of adrenal function in a group of such patients. The mean plasma total 11-OHCS was lower in patients than in control subjects, although this difference was not statistically significant and the normal circadian rhythm was maintained. However, in patients with chronic liver disease a greater proportion of the 11-OHCS was in the non-protein bound state resulting in an elevation of this fraction. This elevation of non-protein bound 11-OHCS must represent a resetting of the pituitary-adrenal feedback mechanism in these patients. Corticosteroid binding globulin was lower in patients than in control subjects, although the difference was not statistically significant. Urinary cortisol excretion was significantly reduced as was excretion of 17-ketosteroids. Cortisol secretion rate was found to be normal. It is suggested that elevation of plasma non-protein bound 11-OHCS, resulting from impaired metabolism and reduced protein binding of cortisol in patients with hepatic disease, may explain the features of endogenous hypercorticism seen in such patients. Moreover, in the presence of impaired steroid metabolism and reduced protein binding, these patients may exhibit an increased sensitivity to corticosteroid therapy, and therefore administration of a reduced dosage may be advisable.

The mean basal plasma testosterone level in 28 patients with chromatin positive Klinefelter's syndrome was significantly lower than in 58 healthy male controls. In 12 of the patients the hormone levels were in the normal range. In both the eugonadal males and the Klinefelter patients the plasma testosterone levels spontaneously decreased throughout the day, the relative decrease in both groups being of the same order of magnitude. Short term ACTH infusion and the administration of dexamethasone did not significantly influence the plasma testosterone concentration in the Klinefelter patients. These findings do not support the view that the adrenal cortex plays a major role in contributing to the circulating plasma testosterone levels in this syndrome.

Interactions between gonadal hormones and adrenocortical function have been studied in the male rat. After injection (im) of testosterone, the accessory reproductive organs are more stimulated in the castrated rats than in the castrated adrenalectomized rats. Gonadectomy increases lipids, cholesterol and corticosterone in adrenal glands and plasma corticosterone levels. Testosterone reverses these effects.

Five new patients with postmenarchial onset of adrenal virilism related to 21-hydroxylase deficiency are presented. Diagnostic criteria are reviewed. Four pregnancies resulting in 3 term infants occurred after instigation of therapy. Eleven patients similar in clinical presentation are reviewed for comparison. Findings of value in distinguishing these two groups of patients are discussed.

Sixteen students were given flight training according to a highly standardized and rigidly controlled 35-h syllabus. Eight of the group (TG) recieved 10 h of their training in a Link GAT-1 ground trainer and 25 h in a Cherokee 140B. the other eight (AG) recieved all of their training in the airplane. The resting heart rate (HR) of group TG was significantly lower when the ground trainer was to be used than was the resting HR of group AG on equivalent lessons. The difference disappeared when group TG was to fly the airpland. In flight, group AG'S HR was significantly higher than group TG's in the ground trainer. Again the difference disappeared when group TG flew the airpland. Physcial work, as indicated by O2 consumption, was greater in the airplane than in the ground trainer. Urine chemistry indicated only a few and inconsistent points of significant differece between the groups. However, pre- and post-flight differences showed highly significant differences for both TG and AG. Objective flight tests administered four times during the syllabus indicated insignigicant differences between TG and AG, likewise, a check pilot who did not know to which group a student belonged could not differentiate between groups TG and AG. It was concluded that 10 h training in the GAT-1 did not compromise the flying skill as judged by the check pilot.

An efficacy of the method of hormonal therapy--endolumbar hydrocortisone injection in patients with advanced breast cancer has been studied. A remission was gained in 28 of 41 patients. The method proved to be mostly effective in metastases in bones. Changes in the level of estrogens, 17-KS and 17-OCS excretion with the urine during the treatment indicate an endocrinous mechanism of this therapeutic effect. An efficacy of the method in extensive dissemination of the process, its relative simplicity and availability along with the absence of serious complications enabled the authors to hope that the suggested method may be widely used in practice.

1. Urinary 17-oxosteroid conjugates were measured by gas-liquid chromatography in five patients with hereditary coproporphyria. 2. Three patients were in an acute attack and showed significantly increased excretion of sulphate or glucuronide conjugates of aetiocholanolone. There was increased excretion of several other related steroids but no consistent pattern was apparent. 3. In the two patients in remission, excretion of urinary 17-oxosteroids was not increased. 4. The ratio of total urinary aetiocholanolone to androsterone (5beta:5alpha) was found to be significantly elevated for the three patients in an acute attack. Serial measurements were made in two of these patients and showed a highly significant linear correaltion between this ratio and the urinary content of delta-aminolaevulic acid and porphobilinogen. 5. These observations suggest the involvement of the 17-oxosteroids, espically aetiocholanolone, in the pathogenesis of hereditary coproporphyria.

Excretion of 17-KS and 17-OCS was studied in the urine of 86 patients with various cytogenetic variants of gonad dysgenesis of a female phenotype under basic conditions and after ACTH stimulation; in 10 patients endogenous hypophyseal ACTH reserve after block of the adrenal cortex by metopyrone was investigated as well. A conclusion was drawn on the presence in these patients of differnet types of deviations of the adrenal gland function. In some of the cases there is a primary "global" or dissociated injury of the adrenal cortex, apparently directly associated with gonosome anomaly; in other cases--with disturbed regulation of ACTH secretion.

Significantly decreased levels of serum testosterone from the pre-anaesthesia level were found during and up to 7 days following major surgery under general anaesthesia (nitrous oxide, oxygen and halothane following induction with thiopental and succinylcholine chloride) in 18 male patients. On the other hand in the same patients, the serum lutenizing hormone (LH) increased significantly from the pre-anaesthesia level 30 min and 1 h after the beginning of anaesthesia. A slight increase in LH level was also noted on the 7th post-operative day. The determinations of serum testosterone and LH in fiberoptic bronchoscopy under the same general anaesthesia as that used in surgery or local anaesthesia in 26 male patients, revealed that the change in the serum LH during and following surgery seemed to be mainly induced by the general anaesthesia and that the rate of decrease in the serum testosterone may be related to the severity of surgical stress including the anaesthesia. The rate of increase in serum testosterone following the injection of gonadotrophin in 20 males on the 6th post-operative day was similar to that in 10 pre-operative males. The effects of pulmonary lobectomy on serum testosterone and urinary steroids were also studied in 6 males under adrenal suppression with dexamethasone. On the 6th post-operative day, the urinary aetiocholanolone plus androsterone and serum testosterone were found to be half the level of those on the pre-operative day, while the urinary 5beta-pregnane-3alpha, 17alpha, 20alpha-triol remained unchanged. These observations in human are not inconsistent with the report of Tcholakian and Eik-Nes (1971) in dogs namely that a shift in androgen biosynthetic pathway is present in the testis under surgical stress.

Measurement of the excretion of total 17-ketosteroids, androsterone, etiocholanolone, and dehydroepiandrosterone demonstrate in contrast to the well known age dependency of normal women in cases of both mastopathia and breast cancer the following results: 1. the age dependence of the 17-ketosteriod excretion is not marked; 2. the total 17-ketosteroid excretion is lower than that of normal controls, 3. the values of the etiocholanolone excretions and that of the dehydroepiandrosterone excretions are similarly lower.

Dehydroepiandrosterone, androstenedione, testosterone, pregnenolone and progesterone concentration was determined by our sensitive gas-liquid chromatographic method in ovarian tissues obtained from surgery of patients without hirsutism and with Stein-Leventhal syndrome. The steroids, except testosterone, were detectable in all ovaries studied. Dehydroepiandrosterone and androstenedione, regarded as preandrogens, were present in an increased amount in almost all patients with polycycstic ovaries. Gas chromatographic evidence was obtained for the presence of testosterone in two of the cases. The delta4/3betaOH ratio reflecting 3beta-hydroxysteroid dehydrogenase activity was decreased only in same patients with the Stein-Leventhal syndrome suggesting that the impaired function of this enzyme is not an obligatory feature of polycystic ovaries. Concentration of pregnenolone and progesterone measured in a part of cases varied in a great range although the determination was caried out before luteal phase. Simultaneous determination of hormones in both ovarian tissues revealed an active and an inactive period of the gland in the given time, since a great difference of hormone concentration in bilateral ovarian tissues were observed. A comparison of hormone content in ovaries and the urinary excretion of metabolites showed poor correlation between the two parameters of hormone production.

Intermittent hyperthyreosis occurs under various forms of stress, especially heat stress. The clinician may diagnose such cases as masked or apathetic hyperthyroidism or "forme fruste" hyperthyreosis or thyroid autonomy. As most routine and standard tests may here yield inconsistent results, it is the patients' anamnesis which may provide the clue. Our Bioclimatology Unit has now seen over 100 cases in which thyroid hypersensitivity towards heat was the most prominent syndrome: 10-15% of weather-sensitive patients are affected. The patients complain before or during heat spells of such contradictory symptoms as insomnia, irritability, tension, tachycardia, palpitations, precordial pain, dyspnoe, flushes with sweating or chills, tremor, abdominal pain or diarrhea, polyuria or pollakisuria, weight loss in spite of ravenous appetite, fatigue, exhaustion, depression, adynamia, lack of concentration and confusion. Determination of urinary neurohormones allows a differential diagnosis, intermittent hyperthyreosis being characterized by three cardinal symptoms: 1. tachycardia -- every case with more than 80 pulse beats being suspect (not specific); 2. urinary histamine -- every case excreting more than 90 mug/day being suspect. Again the drawback of this test is its lack of specificity, as histamine may also be increased in cases of allergy and spondylitis; 3. urinary thyroxine -- every case excreting more than 20 mug/day T-4 being suspect. This is the only specific test. Therapy should make use of lithium carbonate and beta-blockers. Propyl thiouracil is rarely required.

Beclomethasone dipropionate is a topically active corticosteroid used as an adjuvant in the control of chronic asthma when given by inhalation as an aerosol. It is not intended for treatment of acute attacks. It appears that the main difference between beclomethasone dipropionate and other corticosteroids previously used by inhalation is its high topical activity together with a lower systemic activity due to metabolic inactivation of the swallowed portion of the dose. Clinical experience has shown that at doses of 200 to 600mug daily, beclomethasone dipropionate inhaler is preferable to oral corticosteroids, because of lack of side-effects, when adult patients and children who are inadequately controlled by full doses of sodium cromoglycate and bronchodilators, are first considered to need maintenance corticosteroids. Inhaled beclomethasone dipropionate can allow a worthwhile reduction in maintenance doses of systemic corticosteroids in many patients already receiving these drugs and can replace systemic steroids entirely in some patients, particularly when their initial dose of steroids is less than 10mg daily of prednisone or its equivalent. Substitution should be attempted when the patient's asthma is well controlled on their usual doses of systemic steroids and full doses of other adjuvant therapy. Withdrawal of systemic corticosteroids should be performed slowly and carefully. Because recovery from impaired adrenocortical function caused by prolonged systemic steroid therapy is usually slow, special care is necessary for 9 to 12 months after transfer to beclomethasone dipropionate aerosol until the hypothalamo-pituitary-adrenal axis has sufficiently recovered to cope with emergencies such as trauma, surgery, severe infections or an acute attack of asthma. It is essential that additional therapy including high doses of systemic corticosteroids be used immediately to control any acute exacerbation of asthma which occurs during maintenance therapy with beclomethasone dipropionate aerosol. Tests of adrenal function suggest that beclomethasone dipropionate at dosages of 400 to 800 mug daily has little or no adverse effect. The most common side-effect associated with the continuous use of beclomethasone dipropionate inhaler has been oropharyngeal candidiasis, which appears to be dose-related and more common in women than in men. Systemic steroid withdrawal effects, like being generally unwell, and exacerbation of underlying allergic diseases such as allergic rhinitis, have been reported after substitution of beclomethasone dipropionate inhaler for systemic steroids. However, systemic withdrawal effects seldom occur if systemic steroids are withdrawn slowly.

Urinary 17-ketosteroids were estimated in 29 lepromatous leprosy cases. Correlation between 17-ketosteroid values, histopathologic findings, and serum G.G.P.T. values is discussed. Low values of 17-ketosteroids were associated with definite leproma to liver indicating the value of liver damage to 17-ketosteroids. This was more marked in males than in females.

The effect of Danazol, a synthetic 2,3 isoxazol derivative of 17 alpha-ethinyl testosterone, was assessed in three girls and two boys with sexual precocity. Progression of sexual development ceased during administration of Danazol; the effect upon growth rate and skeletal maturation was equivocal. Serum estrogen and progesterone concentrations in the girls were lower during treatment; serum testosterone and dehydroepiandrosterone levels in the boys were also lower. Serum and urinary luteinizing hormone concentrations were inconsistently suppressed. No effect upon follicle-stimulating hormone levels could be demonstrated. Although Danazol appears to inhibit sexual development, this study indicates that the pituitary-gonadal axis is not completely suppressed. Growth rate is not reverted to normal, and virilization may occur among girls. Because undesirable side effects may outweight desirable results, careful consideration is recommended before Danazol is prescribed in the management of sexual precocity.

A semi-automated determination of 17-oxosteroids in urinary extracts is described using a modified Zimmerman reaction in aqueous phase according to Epstein. In order to eliminate the interfering chromogens a double manifold and a double-beam colorimeter are used in continuous flow. The spectra and the chromogenecity of seven different 17-oxosteroids are presented. The specificity and the reproducibility of this technique are good and the comparison with gas-liquid chromatography and manual Zimmerman reaction shows a good correlation.

The authors determined the amounts of free and total 17-hydroxycorticosteroids (17-OHCS) and 17-ketosteroids (17-KS) in the urine of 11 women in whom epileptic seizures occurred most frequently on the 2nd and 1st day before menstruation and in 7 women with seizures showing no such correlation with the menstrual cycle. A statistically significant decrease of 17-KS was demonstrated in women with premenstrual seizures. In both groups of women the amounts of free 17-OHCS were near the lower normal range, while the amounts of total 17-OHCS were reduced and the obtained results compared with the accepted normal values showed statistically significant differences (p less than 0.01). The obtained results are, however, insufficient for assuming that these hormones play an important role in the mechanism of seizure release in premenstrual period. The authors think, on the other hand, that the statistically significant fall in 17-KS in women with premenstrual seizures may play some role among other factors in the mechanism of seizure release.

The urinary excretion of 14 neutral steroids was measured by gas-liquid chromatography in women with early and advanced breast cancer, in women with early uterine cancer, and in healthy women from urban and rural districts. The premenopausal patients with early breast cancer excreted subnormal amounts of five steroids (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, pregnanetriol, and tetrahydrocorticosterone) and increased amounts of tetrahydrocortisol as compared with the normal subjects of corresponding ages. From our findings, a new parameter was proposed by which a premenopausal breast-cancer patient was separated from the control. Postmenopausal breast-cancer patients excreted greater amounts of five steroids (one steroid from 17-ketosteroids and four from 17-hydroxycorticoids) than the corresponding controls. The discrepancy between premenopausal and postmenopausal breast cancer was tentatively related to ovarian-adrenal dysfunction in the course of aging. Oophorectomy induced a long-lasting tumor regression only in patients with a high value for the ratio of 11-deoxy-17-ketosteroid to 17-hydroxycorticosteroid in urine taken before surgery; the ratio in the responsive patients decreased remarkably after surgery. A constitutional change in 17-ketosteroids, as observed in a postmenopausal breast-cancer patient and a premenopausal healthy woman of urban origin, favored the geographic importance in the genesis of breast malignancy. The steroid abnormalities in uterine cancer were distinguishable from those of breast cancer in both premenopausal and postmenopausal women.

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, 17-ketosteroids, 17-hydroxycorticosteroids, and serum androgen, follicle-stimulating hormones, and corticosteroid levels ramained within normal values with candicidin therapy.