The clinical and autopsy findings in a case of adrenocorticotropic hormone unresponsiveness associated with hypertrophic cardiomyopathy are reported. A four-month-old female with feeding difficulties and skin hyperpigmentation from two months of age was admitted with convulsions. She was hypoglycemic with normal serum electrolytes and the presence of hypertrophic cardiomyopathy was indicated by electrocardiogram and echocardiogram. Cardiac arrest occurred on the second hospital day. Low serum cortisol, high plasma adrenocorticotropic hormone, low urinary <em>17</em>-<em>ketosteroids</em>, and normal urinary aldosterone excretion were documented after her death. Hypoplasia of the adrenal cortex with a persistent fetal zone and concentric hypertrophy of the heart were found at autopsy. We propose that the pathogenesis of this disease lies in impaired remodelling of the fetal adrenal cortex into the permanent cortex, and postulate an effect of adrenocorticotropic hormone on the myocardium as the cause of hypertrophic cardiomyopathy.

We attempted to determine compounds in human urine which, differing from <em>17</em>-OHCS, show high values in healthy individuals, decrease with failing health, clearly decline with advancing disease and finally reach very low values in severe disease. We have initially established that <em>17</em>-<em>ketosteroid</em> sulfates (<em>17</em>-KS-S) are the compound we were searching for. Hans Selye regarded stress as the rate of wear and tear and <em>17</em>-OHCS as its indicator, but we considered that, differing from inanimate objects, living organisms consume energy to cope with stress and "repair" "wear and tear" of the tissue "and recover" its function. This concept led us to determine the organism's requirements for two mechanisms: "Wear and tear" which could be represented by the secretion of <em>17</em>-OHCS (Selye), and "repair and recovery", which could be determined by the amounts of <em>17</em>-KS-S (Nishikaze) derived from dehydroepiandrosterone sulfate (DHEA-S), a product of the adrenal cortex, which enhances neuronal survival, long-term memory, maintains the function of peripheral tissues (skin, bone-muscle, gastro-intestinal and vascular system etc.), increases lipid metabolism, protein anabolism (antiobesity, antiatherosclerosis etc.) and stimulates the immune system. We hold that the stress response is a series of biological processes, beginning with CRH.ACTH and Catecholamines, Cortisol (<em>17</em>-OHCS), followed by Insulin, acting as an anabolic agent and finally DHEA-S (<em>17</em>-KS-S) induces tissue repair utilizing the energy produced. Low levels of urinary <em>17</em>-KS-S are observed not only in cases of low cortisol or catecholamines secretion, but also when these are elevated. Normalization of these levels is followed by an increase in <em>17</em>-KS-S excretion. Balanced changes of hormones, such as <em>17</em>-KS-S, <em>17</em>-OHCS, Cortisol, Catecholamines and Insulin are seen in a normal organism under healthy lifestyles and disruption of the balance induces an apparent reduction in <em>17</em>-KS-S. From this perspective, we hope to research the interrelations between biologically antagonistic <em>17</em>-KS-S and <em>17</em>-OHCS as well as other agents, focusing particularly on <em>17</em>-KS-S, which represents a contact point for mind and body, which is kept in healthy balance by appropriate sleeping and exercise programs along with adequate food intake.

Steroid profiles of women suffering from idiopathic hirsutism show in more than 50% of the cases of 10--100 fold increase in the excretion of dehydroepiandrosterone (DHEA) compared with normal values. The excretion of DHEA was reduced much more than that of other <em>17</em>-<em>ketosteroids</em> if the adrenals (NNR) were suppressed by dexamethasone (DXM). Within one week they reached values at the compound noise level of the gas chromatograms. If the ovaries were stimulated with human chorionic gonadotropin during continued suppression of the NNR with DXM no increase of DHEA could be detected.

E2 deficiency in elderly people has directly an effect on the skeleton and can lead to osteoporosis. As <em>17</em>β-hydroxysteroid dehydrogenase type 2 (<em>17</em>β-HSD2) catalyses the conversion between active <em>17</em>β-hydroxysteroid estradiol (E2) and testosterone (T) into their less active <em>17</em>-<em>ketosteroid</em> and has been found in bones, <em>17</em>β-HSD2 inhibitor may provide a new approach in the onset of osteoporosis. Bicyclic substituted hydroxyphenylmethanone derivatives were synthesised as steroidomimetics of the substrate E2 and were evaluated for their <em>17</em>β-HSD2 inhibition and their selectivity toward <em>17</em>β-HSD1, catalysing the reverse reaction the conversion of estrone (E1) into E2. Highly selective compounds (11, 12, 14, 21 and 22) have been identified, the most promising one (12) showing an IC(50) value in the low nanomolar range (101 nM) and a selectivity factor of 13 toward <em>17</em>β-HSD1. These results make compound 12 an interesting candidate for further biological evaluation.

A two-month-old female with clinical manifestations of Cushing's syndrome including mild virilization exhibited an unusual steroid pattern illustrating difficulties in diagnosis of this disorder in infancy. Unequivocal abnormalities were limited to serial elevations of serum cortisol concentration, hyperresponsiveness to ACTH, resistance of serum cortisol to dexamethasone suppression, and elevation of testosterone and dehydroepiandrosterone sulfate concentration. On the other hand, twenty-four hour urinary <em>17</em>-hydroxysteroid, <em>17</em>-<em>ketosteroid</em>, free cortisol, and 6B-hydroxycortisol excretion were normal for the age. At laparotomy the adrenals were only minimally enlarged, and their architecture was normal by light microscopy. Following total adrenalectomy, adrenal slices were transplanted into the rectus abdominis muscles. Progressive hypertension developed three weeks later, suggesting adrenal regeneration. The infant then developed acute Salmonella enteritis and expired. At autopsy, the adrenal transplant showed outer cortical preservation, inner zone degeneration, and some growth into the surrounding tissue. The unfavorable outcome notwithstanding, this study adds to existing data in the adult that adrenal autotransplantation may have significant therapeutic value in Cushing's syndrome treated by bilateral adrenalectomy.

The authors report a case of Steinert's disease in a woman and discuss the endocrine profile of this disease after giving an account of the criteria of diagnosis. Disorders of gonad function are mild in women, primary testicular atrophy is very frequent in man with reduction in <em>17</em>-<em>ketosteroids</em> and testosterone. Thyroid function was normal but, in a few cases, a low fixation curve was found (our case) corrected by TSH stimulation. The frequency of cataract emphasizes the interest of this sign for detection. Diabetes, associated with hyperinsulinism, seemed more frequent than in a population without Steinert's disease. The pathogenesis of these endocrine disorders appears secondary and is ill explained if one considers it as a single disease. Better knowledge, no doubt linked to progress in biochemistry of normal and myopathic muscle, will help to explain the pathogenesis.