[Cortisol substitution in adrenal cortex insufficiency].
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Biomedical subjects
Publications and source records attributed to H K Kley.
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A functional diagnosis of the diencephalohypophyseal system was carried out in patients with Sheehan syndrome, chromophobic adenoma, craniopharyngioma, prolactin-producing pituitary tumours, acromegaly, hypothalamo-pituitary dwarfism and constitutional retardation. A combined insulin hypoglycaemia/LH-RH/TSH test was performed to define frequency and extent of anterior pituitary insufficiency. With these illnesses, almost generally, a somatotropic insufficiency (except in acromegaly) was found. An impairment of gonadotropic function was often present, in general a pathologic LH-RH test correlating with a more or less developed androgen deficiency. An adrenocorticotropic insufficiency was found in most patients with sheehan syndrome, chromophobic adenoma and craniopharyngioma while in acromegaly and hypothalamo-pituitary dwarfism it was present less frequently, necessitating a substitution with corticoids. The TRH test reflects only incompletely a secondary hypothyroidism, and can be normal with organic processes of the diencephalo-hypophyseal region, making a T3 and T4 estimation in the blood decisive for a thyroid hormone substitution. A clear-cut separation of the hypothalamic from the pituitary cause of the insufficiency is neither possible with the LH-RH nor with the TRH test.
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The plasma concentrations of estrogens as well as their relationship to testosterone are determined in male patients suffering from fatty liver, chronic hepatitis and cirrhosis of the liver. By stimulation and suppresion tests the contribution of the adrenal gland and the testes to the elevated estrogens are investigated, demonstrating that enhanced peripheral conversion of androgens to estrone rather than to estradiol appears to be more effective in sustaining plasma levels in hepatic cirrhosis. Futhermore, the effect of testosterone application was studied in male patients with alcohol-induced cirrhosis of the liver in order to realize possible side-effects of an androgenic substitution therapy. It is concluded that clinical signs of hyper-estrogensim and hypoandrogenism in male patients with hepatic cirrhosis may in part be attributed to the increase of estrogens and the decrease of total and free testosterone, as is best shown by the ration of the heterosexual hormones which are grossly shifted in favour of the estrogens.
The effect of the antiserotoninergic agent cyproheptadine (C) on the adrenal system was studied in male rats, the adrenocorticol function of which was assessed by analysis of the urinary excretion of free corticosterone. After a feeding period with 0.5--0.7 mg C/kg body weight/day for several months significant differences in the urinary excretion of free corticosterone were only found when the rats were exposed to systemic stress stimuli as cold (increase from 118.7 +/- 5.3 to 305.5 +/- 5.1 vs. 417.8 +/- 48.6 ng/d in the controls; p less than 0.001) and hunger (no increase of free corticosterone in treated animals as compared to an increase to 446.0 +/- 53.6 ng/d in the controls). In contrast to these findings no effect of C was seen when studying the neurotropic stress stimuli reserpine and ether. The same was true when measuring free corticosterone under basal conditions and after ACTH- or metyrapone stimulation. It is concluded that serotonin plays a major role as hypothalamic neurotransmitter in systemic but not in the studied neurotropic stress stimuli. The site of serotonin action does not comprise adrenal synthesis of steroids and the hypothalamic-pituitary-adrenal feedback system, as is shown by the ACTH- and metyrapone stimulation tests.
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Endocrinological symptoms of, on the one hand, hypothalamic-hypophyseal Cushing's syndrome and, on the other, ectopic ACTH syndrome (usually caused by bronchial carcinoma) can often not be distinguished. Reliable differentiation of these two forms of secondary hypercortisolism is necessary, because in hypothalamic-hypophyseal Cushing's syndrome therapy is more and more frequently directed at the anterior pituitary and hypothalamus rather than attempted by bilateral adrenalectomy. The following method was used for distinguishing between the two in six patients: blood was withdrawn by catheter from the jugular vein and the inferior petrosal sinus and the ACTH concentrations measured. Compared with ACTH concentration in a peripheral vein (e.g. cubital vein) that in the jugular vein was higher in five patients by a factor of 1.47 +/- 0.1 and in the inferior petrosal sinus by 2.39 +/- 0.64. A positive diagnosis of hypothalamic-hypophyseal Cushing's syndrome can thus be made. In one patient the diagnosis of ectopic ACTH syndrome could be made from the gradient of ACTH concentration between the cardiac right ventricle and the bronchial artery (1 : 3.75), before there was radiological demonstration of the bronchial carcinoma.
Both in patients with primary (n = 15) and secondary (n = 10) adrenal insufficiency a conventional substitution with 30 mg cortisol daily (3 single doses of 15, 10 and 5 mg) leads to an unsatisfactory adjustment in most cases. Plasma maximal values after the morning dose were obtained only between 9 and 11 a.m. and were 3.5 times higher than cortisol values of healthy probands (n = 35). The half-life of cortisol in plasma (t1/2 = 0.8-3.2 hrs) varied to such an extent that some patients had subnormal values relatively quickly or that concentrations above normal were found permanently. The same also applies to free cortisol in plasma. The amount of free cortisol in urine cannot be used as a parameter of a physiological substitution of cortisol. The individual adjustment of the treatment plan can thus be only established according to cortisol concentrations in plasma.
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