Hypothalamic-pituitary-testicular function in 70 patients with myotonic dystrophy

Hypothalamic-pituitary-testicular function was studied in 70 patients with myotonic dystrophy (MD). The diagnosis was confirmed by electromyography. The mean age of the patients was 36.2 +/- 13.2 yr and the duration of the disease was 11.17 +/- 8.01 yr. Testicular atrophy (testes less than or equal to 12 ml on a Prader orchidometer) was present in 65.5% of patients. Fertility among married patients was 66.6%. Mean testosterone plasma levels were 438 +/- 298 ng/dl vs 520 +/- 185 ng/dl in the control group (P = NS). Basal plasma FSH and LH levels, and their response after the administration of 100 mcg of LH-RH were significantly increased although a wide dispersion was observed. Sperm count was carried out in 27 cases, showing a normal count in 7, oligospermia in 12, and azoospermia in 8 patients. Testicular biopsy was performed in 45 patients being normal in 2, showing mild testicular damage in 8, moderate in 14, and severe in 18; it was nule in 3 of them. A significant relationship between testicular atrophy and the sperm count (p less than 0.01), testicular damage and testicular atrophy (p less than 0.025), and sperm count and testicular damage (p = 0.017) was found. Basal plasma FSH and LH level were significantly related to the degree of damage in the testicular biopsy. All these findings indicate a primary testicular pathology, prevailing tubular over interstitial damage. We have not found any association between the duration of the disease and gonadal dysfunction.     

Hypothalamic-pituitary-testicular function in end-stage non-alcoholic liver disease before and after liver transplantation

OBJECTIVE Gonadal dysfunction is common in chronic liver disease, but most of the previous studies have been restricted to men with alcohol-Induced liver disease. We have evaluated hypothalamic-pituitary-testicular function In patients with end-stage non-alcoholic liver disease before and at 6 and 12 months after hepatic transplantation. DESIGN A prospective study of hypothalamic-pituitary-testicular endocrine function before and after cadaveric hepatic transplantation. PATIENTS Fifty four consecutive patients with end-stage, non-alcohollic liver disease were evaluated before and after liver transplanatation. MEASUREMENTS Hypothalamic-pitultary-testicular(HPT) axis function was evalutated under basal conditions by single morning measurements of plasma total and free testosterone, sex hormone-binding globulin and by plasma LH and FSH responses to 100 μg i.v. GnRH. RESULTS Men with chronic non-alcoholic liver disease had reduced levels of total and free teststerone and increased levels of SHBG compared with controls with normal liver function. Total and free testosterone were positively correlated with basal and stimulated LH (but not FSH) concentrations. Gonadotrophin responses to GnRH were preserved but delayed compared with healthy controls consistent with a predominantly hypothalamic defect in regulation of pitultary-testicular function. Increasing severity of underlying liver disease was associated with declining total and free testosterone as well as peak GnRH-stimulated LH concentrations. Splronolactone treatment was associated with decreased circulating testosterone levels only in men with liver disease of lntermedlate severity (Child-Pugh class B). Following hepatic transplantatlon, total and free testosterone and SHBG concentrations returned progressively towards eugonadal control levels over the first 12 months but total and free testosterone levels remained subnormal. CONCLUSIONS Hypothalamic-pitultary regulation of testicular function Is Impaired in end-stage non-alcoholic liver disease In proportion to the severlty of underlying liver disease. Splronolactone reduces circulating testosterone but only among men with Chlld-Pugh B liver cirrhosis. Gonadal function Improves, but is not normalized, over the first year following successful liver transplantation.     

Hypothalamic-pituitary-testicular axis and seminal parameters in hyperthyroid males.

Information on the effect of abnormal thyroid function on male reproduction is less available than that for the female. To assess the effects of hyperthyroidism on hypothalamic-pituitary-testicular axis and on spermogram parameters, 25 male patients (19-47 years old) suffering from active Graves' disease were studied. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL) were measured before and after administration of 100 microg GnRH plus 200 microg thyrotropin-releasing hormone (TRH). Testosterone (T), estradiol (E2), and 17-hydroxyprogesterone (17-OHP) were determined before and after 5000 IU human chorionic gonadotropin (HCG) administration. Serum sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), androstenedione and bioavailable testosterone (bioT), and bioavailable estradiol (bioE2) were also measured. Spermograms according to World Health Organization (WHO) criteria were determined in 21 patients. Hormonal and seminal studies were repeated in six patients after 7 to 19 months of euthyroidism achieved after treatment for hyperthyroidism. As a control group, 10 normal men were evaluated. Impaired sexual function, gynecomastia, and low testicular volume were found in 12, 6, and 3 hyperthyroid patients. Mean basal LH was significantly higher than the control group (7.8 +/- 4.7 vs. 5.0 +/- 1.9 mIU/mL, respectively, p < 0.02), with hyperresponse to GnRH. The response of PRL to TRH was lower in patients versus control group (30 minutes: 3.9 +/- 3.4 and 12.0 +/- 2.8 ng/mL, p < 0.01). Basal levels of steroids and SHBG were significantly higher in patients than in normal men (T: 9.3 +/- 3.3 vs. 5.4 +/- 1.6 ng/mL, p < 0.005; E2: 62.2 +/- 25.2 vs. 32.1 +/- 11.0 pg/mL, p < 0.005; 17-OHP: 2.4 +/- 0.9 vs. 1.1 +/- 0.5 ng/mL, p < 0.001; SHBG: 102.3 +/- 37.3 vs. 19.0 +/- 5.0 nmol/L, p < 0.01). The maximal increment of T and 17-OHP after HCG was lower in hyperthyroid patients than in normal men (p < 0.019 and p < 0.001, respectively). Basal bioT was lower in patients than controls (1.7 +/- 0.8 and 3.1 +/- 1.9 ng/mL, p < 0.02). The following incidence of abnormal semen parameters was found: asthenospermia 85.7%, hypospermia 61.9%, oligospermia 42.9%, necrospermia 42.9% and teratospermia 19.0%. In euthyroidism, a normalization of 85% of seminal alterations was observed in the limited number of patients evaluated. Our results confirm that hyperthyroidism causes marked alterations of the gonadotropic and PRL axis and dramatically affects spermatic function. BioT measurement was useful to identify hypoandrogenism in these patients in spite of the high concentration of total testosterone. The restoration of most semen parameters when euthyroidism was achieved suggests that the alterations were induced by the Graves' disease.     

Adrenocortical function tests in dogs with hyperfunctioning adrenocortical tumours.

The response has been studied in nine dogs with hyperadrenocorticism due to adrenocortical tumours to the administration of dexamethasone, insulin, lysine-vasopressin and tetracosactide by measuring the changes in plasma cortisol concentration. Administration of dexamethasone did not produce a decrease in the plasma concentration of cortisol in any of these dogs. Administration of insulin caused slight increases in the plasma concentration of cortisol in four out of eight dogs. Lysine-vasopressin increased the plasma concentration of cortisol in eight out of nine dogs, three responded supranomally. Eight out of the nine dogs responded to tetracosactide administration, three responded supranormally, It is concluded that in the dog, in contrast to man, the lysine-vasopressin test cannot be used to differentiate between pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to an adenocortical tumour. Apparently pituitary ACTH is not completely depleted in dogs with hyperfunctioning adrenocortical tumours.     

Effect of prolactin on adrenocortical and gonadal function in normal men.

Dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (A), testosterone (T), estrone (E1), estradiol (E2) and gonadotropins were measured in 3 normal adult men before and after administration of 50 mg ovine prolactin for 5 days. No significant change as a result of ovine prolactin administration was observed in any of the parameters examined.     

Changes in adrenocortical function in male and female guinea-pigs during maturation.

Adrenal cortisol secretion is greater in female than male guinea-pigs and declines with maturation in animals of both sexes. In an attempt to determine the intra-adrenal mechanisms responsible for age and sex influences on corticosteroid output, adrenocortical enzyme activities were compared in sexually immature (3 weeks) and mature (17 weeks) animals. Adrenal mitochondrial protein concentration decreased with maturation in male and female guinea-pigs. 11beta-Hydroxylase activity in adrenal mitochondria was also lower in mature than immature guinea-pigs but greater in males than females. Neither mitochondrial cytochrome P-450 concentration nor cholesterol side-chain cleavage activity varied with age or sex. Adrenal microsomal protein concentration and 21-hydroxylase activity were similar in male and female guinea-pigs of the same age but far greater in mature than immature animals. Microsomal cytochrome P-450 concentration was unaffected by age or sex. Adrenal delta4-steroid (cortisol) hydrogenase activity increased with maturation in both male and female guinea-pigs and was higher in males than females. These observations indicate that cortisol secretion, as modified by age and sex, correlates closely with adrenal steroid reductive but not oxidative metabolism, suggesting that changes in delta4-hydrogenase activity are responsible, at least in part, for the decline in adrenal secretion during maturation in guinea-pigs.     

Control of renal and adrenocortical function by the renin-angiotensin system in two euryhaline teleost fishes

Plasma ions and cortisol levels were measured sequentially during the adaptation of European eels (Anguilla anguilla) from fresh water (FW) to sea water (SW). The importance of the renin-angiotensin system in the regulation of this adaptation was assessed using captopril (SQ14225, an inhibitor of angiotensin I-converting enzyme). The effects of captopril on renal function in FW- and SW-adapted trout were also examined. During the first 5 hr in sea water, plasma levels of cortisol in eels increased threefold, plasma sodium rose steadily from 137 to 156 mmol/l and plasma potassium fell from 2.1 to 1.6 mmol/l. In contrast, captopril-treated eels when adapted to sea water had plasma cortisol levels twice those of controls. Captopril treatment did not affect the electrolyte responses to seawater adaptation. Captopril injected into eels which were fully adapted to and wholly maintained in sea water had no effect on plasma levels of cortisol, sodium, and potassium. Plasma cortisol was 30% lower in freshwater eels 2 hr after an injection of captopril but plasma sodium and potassium levels were unchanged. In both FW- and SW-adapted trout, captopril infusions doubled the glomerular filtration and urine production rates and the tubular transport maxima for glucose without changes in plasma composition.     

Size at birth and adrenocortical function in childhood

OBJECTIVE The mechanisms underlying the association between reduced size at birth and cardiovascular disease and non-insulin-dependent diabetes mellitus in adult life are not known. One possibility is that the intra-uterine environment has permanent effects on the function or activity of the hypothalamo-pituitary-adrenal axis. We tested this by relating size at birth to the urinary excretion of adrenal androgen and glucocorticoid metabolites in a population sample of 9-year-old children. SUBJECTS AND METHODS One hundred and ninety children (89 boys and 101 girls) of known present height, weight and size at birth collected a 24-hour urine sample. The urinary breakdown products of dehydroepiandrosterone sulphate and of cortisol and cortisone were measured by gas chromatography and their respective breakdown products summed (‘adrenal androgen metabolites’ and ‘glucocorticoid metabolites’). Excretion was expressed in μg/day. RESULTS Urinary adrenal androgen metabolite excretion was higher in children who had been light at birth. A 1-kg decrease in birthweight was associated with a 40% (95% CI 9–79%) increase in metabolite excretion. Excretion was positively associated with current weight and age, but the relation with birth weight was independent of weight, age or sex. Urinary glucocorticoid metabolite excretion was positively associated with current weight, but not independently with age. The urinary excretion of total glucocorticoid metabolites was higher in children who had been light at birth, but the relation was best described as U-shaped, with the highest average urinary glucocorticoid metabolite excretion being found in children who had been either light or heavy at birth. The U-shaped (quadratic) relation persisted after adjustment for sex and current weight (P for quadratic term 0.006). CONCLUSION These findings suggests that the intra-uterine environment, as measured by fetal size at birth, has long-lasting effects on the function of the hypothalamo-pituitary-adrenal axis.     

Residual adrenocortical function after bilateral adrenalectomy for pituitary-dependent Cushing's syndrome.

The incidence of residual, functioning adrenal tissue in patients treated by total bilateral adrenalectomy for Cushing's disease is not known. Between 1962 and May 1988 50 patients with Cushing's disease were treated by bilateral adrenalectomy. Of these patients, 29 underwent surgery between 1962 and 1980, when bilateral adrenalectomy was the treatment of first choice in our hospital in patients with pituitary-dependent Cushing's syndrome. In 37 patients the presence or absence of cortisol-producing tissue could be evaluated (follow-up period, median and range, 8.3 and 0.1-18.9 yr). Evidence of functioning cortisol-producing tissue (plasma cortisol level > 50 nmol/L after stopping glucocorticoid and mineralocorticoid substitution therapy for 24 h) was found in 9 patients (24%). Plasma cortisol levels in these 9 patients varied between 60 and 330 nmol/L (mean +/- SD, 180 +/- 100 nmol/L). Signs and symptoms of recurrent Cushing's syndrome were present in only 1 patient. There was no difference in plasma ACTH levels and duration of follow-up between the patients with and without evidence of functioning cortisol-producing tissue. In all 9 patients detectable aldosterone levels indicated endogenous mineralocorticoid production, whereas in only 1 patient adrenaline was detectable in the circulation. In 8 of the 9 patients suspected of functioning cortisol-producing tissue we performed a stimulation test with synthetic ACTH (1-24). In 2 patients plasma cortisol levels rose, in 6 they remained virtually unchanged. Although we found clinically relevant signs and symptoms of Cushing's syndrome in only 1 of the 50 patients, the relatively high incidence of residual, functioning adrenal tissue after "total" adrenalectomy for pituitary-dependent Cushing's syndrome necessitates continuous surveillance for recurrent Cushing's syndrome. There is no place for routine administration of full replacement doses of glucocorticoids after total adrenalectomy.