The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Dec 1990
Androgen response to endogenous insulin secretion during the frequently sampled intravenous glucose tolerance test in normal and hyperandrogenic women.
Women with ovarian hyperandrogenism frequently have insulin resistance, whose underlying mechanism remains to be determined. In the present study we have investigated the relationship between insulin sensitivity and the acute effect of endogenous insulin secretion on circulating androgen levels. Insulin sensitivity, glucose-mediated insulin release, and glucose/insulin-stimulated androgen responses were determined during a frequently sampled iv glucose tolerance test in a group of 19 women with clinical evidence of polycystic ovary syndrome (PCOS) and 9 age- and weight-matched controls. ⋯ Other androgen levels showed a modest nonsignificant decline during the study in PCOS and control groups. These findings confirm the weight-independent insulin resistance of some hyperandrogenic women. The failure of glucose-stimulated endogenous insulin secretion to significantly depress DHEA levels in insulin-resistant women with PCOS may account in part for their androgen excess.
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J. Clin. Endocrinol. Metab. · Jan 1990
Dynamics of 24-hour endogenous cortisol secretion and clearance in primary hypothyroidism assessed before and after partial thyroid hormone replacement.
Although various abnormalities of hypothalamic pituitary adrenal function have been reported in primary hypothyroidism, neither 24-h patterns of pulsatile cortisol release nor estimation of its endogenous secretion and clearance rates have been fully investigated in this clinical setting. We studied pulsatile and circadian patterns of cortisol secretion in six hypothyroid men [mean free T4 index, 0.59 +/- 0.22 (+/- SE); mean TSH, greater than 50 mU/L] by sampling blood at 20-min intervals for 24 h before (unreplaced) and then after 5-7 months of partial replacement treatment with levo-T4. Compared to a normal group, hypothyroid men had significantly elevated 24-h mean serum concentrations of cortisol (419 vs. 254 nmol/L; P less than 0.001), with no change in serum cortisol-binding globulin concentrations. ⋯ Partial replacement therapy with levo-T4 caused significant decreases in 1) mean 24-h serum cortisol concentrations (419 vs. 323 nmol/L; P less than 0.05); 2) mean cortisol peak amplitudes (527 vs. 375 nmol/L; P less than 0.05); 3) mean prepeak nadir concentrations (298 vs. 221 nmol/L; P less than 0.05); and 4) mean half-life of cortisol disappearance (155 vs. 112 min; P less than 0.0019). In summary, the present study of cortisol secretory dynamics in hypothyroid men has shown elevated mean 24-h serum concentrations of cortisol with preserved circadian rhymicity and normal endogenous production rates, but prolonged half-lives of cortisol disappearance. In conjunction with normal serum cortisol-binding globulin concentrations, these largely reversible findings suggest that significant hypercortisolemia in primary hypothyroidism is primarily due to decreased metabolic clearance of cortisol and a presumptive decrease in the negative feedback effect of cortisol on the hypothalamo-pituitary axis.
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J. Clin. Endocrinol. Metab. · Jan 1990
Randomized Controlled Trial Clinical TrialEffects of chronic testosterone administration in normal men: safety and efficacy of high dosage testosterone and parallel dose-dependent suppression of luteinizing hormone, follicle-stimulating hormone, and sperm production.
In normal men, chronic testosterone (T) administration results in negative feedback suppression of gonadotropin and sperm production. However, azoospermia is achieved in only 50-70% of men treated with high dosages of T. Furthermore, the relative sensitivity of LH and FSH secretion to chronic administration of more physiological dosages of T is unclear. ⋯ We conclude that 1) LH and FSH secretion are equally sensitive to the long term negative feedback effects of T administration; 2) sperm production is suppressed in parallel with the LH and FSH reductions induced by chronic T administration; and 3) even at the clearly supraphysiological dosage of 300 mg/week, T enanthate does not reliably induce azoospermia in normal men. However, there was also no evidence of a stimulatory effect of this T dosage on spermatogenesis. Furthermore, we found no evidence of major adverse health effects of T administered chronically even at the highest dosage.
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J. Clin. Endocrinol. Metab. · Oct 1989
The abnormal response of polycystic ovarian disease patients to exogenous pulsatile gonadotropin-releasing hormone: characterization and management.
Pulsatile GnRH administration for induction of ovulation is often ineffective in polycystic ovarian disease (PCOD) patients. To clarify and correct the endocrine mechanisms underlying this deranged response we gave pulsatile GnRH (5 micrograms, iv, every 60 min) to idiopathic hypogonadotropic hypogonadism (IHH) patients with primary amenorrhea for 19 cycles and to PCOD patients for 24 cycles before (pre-A) and for 25 cycles after (post-A) GnRH analog suppression. Compared to IHH, pre-A cycles were characterized by elevated LH, estradiol, and testosterone; reduced luteal phase progesterone; and low ovulatory (38%) and pregnancy rates (8%). ⋯ A worse endocrine pattern and a lower ovulatory rate (50%) were obtained when a second consecutive post-A cycle occurred without repeating GnRH analog suppression. No signs of even mild ovarian hyperstimulation and no multiple pregnancies were recorded in the post-A cycles. We conclude that in PCOD 1) deranged pituitary sensitivity, excessive ovarian androgen secretion, and obesity critically affect folliculogenesis and ovulation; 2) pituitary-gonadal suppression with a GnRH analog markedly improves the endocrine and clinical responses to pulsatile GnRH ovulation induction; 3) optimal results can be achieved only when each pulsatile GnRH cycle is preceded by GnRH analog suppression; and 4) pulsatile GnRH is highly effective and safe for ovulation induction, provided that PCOD subjects are pretreated with a GnRH analog.
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J. Clin. Endocrinol. Metab. · Jul 1989
Biological activity of autoantibodies associated with Graves' dermopathy.
To test the hypothesis that Graves' dermopathy is due to cross-reactivity of thyroid autoantibody(ies) with a cellular target in pretibial skin, we tested the serum and serum immunoglobulin fraction of 20 such patients for their effects on the metabolic activities of cultured thyrocytes (rat FRTL cells), human pretibial skin fibroblasts, and human fibroblasts of other origins. The incorporation of 3H-labeled thymidine, amino acids, and glucosamine into DNA, protein, and glycosaminoglycans, respectively, was measured. TSH and the serum of each of the 20 patients with Graves' dermopathy markedly stimulated the synthesis of DNA, protein, and glycosaminoglycans by FRTL cells, but not by fibroblasts, whereas assays of serum from 38 of 40 patients with Graves' disease without dermopathy did not stimulate these processes in FRTL cells more than normal serum. ⋯ Serum dermopathy-associated antibodies disappeared with the disappearance of the skin lesions. These results suggest that the serum of patients with dermopathy contains antibodies that recognize a component of the TSH receptor different from that recognized by serum of Graves' patients without dermopathy, the former acting in some manner to induce lesions in pretibial skin. The skin target remains unidentified.