Biomedical subjects
Publications and source records attributed to A G Smals.
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In 3 of 6 patients with pituitary-dependent Cushing's disease, a paradoxical increase of plasma cortisol was observed both after LRH (delta max, 13.9 +/- 3.7 microgram/100 ml; 113 +/- 52%) and TRH (delta max, 8.0 +/- 2.9 microgram/100 ml; 53 +/- 18%) administration, the maximum values being achieved 30--60 min after the iv bolus injection. In the remaining 3 patients and in 15 control subjects, plasma cortisol levels did not rise in response to either LRH or TRH administration but rather showed a slight to distinct decrease during the study period. The paradoxical cortisol response in half of the patients with Cushing's disease may be the consequence of loss of specificity of the pituitary receptor or alteration in the hypothalamo-pituitary pathways.
A single im injection of 1500 IU hCG significantly increased plasma testosterone levels for at least 96--120 h in normal men (n = 7), patients with isolated gonadotropin deficiency (n = 6), and boys with delayed puberty (n = 7); the maximum values [1315 +/- 309, 370 +/- 177, and 963 +/- 249 ng/100 ml (mean +/- SD), respectively] were achieved after 72 h in each group. Repeated daily injections of 1500 IU hCG for 3 days increased plasma testosterone levels in the same subjects at 72 h after the start to levels (1342 +/- 412, 407 +/- 199, and 1052 +/- 449 ng/100 ml, respectively) similar to those found in the single dose experiment. The levels achieved at 24 and 48 h also did not differ significantly in the two experiments. The data indicate the lack of additional leydig cell stimulation by repeated hCG injections given within 48 h after a single dose.
Using a sensitive measuring device, 3-day hCG administration (Pregnyl; 1500 IU daily) was shown to temporarily increase ulnar growth velocity from prepubertal (0.40 +/- 0.35 mm/3 weeks to pubertal values (1.1 +/- 0.64 mm/3 weeks) in 10 boys with delayed puberty. This growth-promoting effect of diagnostic hCG administration, which was demonstrable for 3--9 weeks, was associated with an overt rise in plasma testosterone from 129 +/- 126 to 818 +/- 419 ng/100 ml and an approximate doubling of the serum alkaline phosphatase activities from 193 +/- 46 to 376 +/- 115 U/liter, suggesting an initiated growth spurt.
Four weeks high dose spironolactone treatment (Aldactone Searle, 100 mg q. i. d.) significantly enhanced the TSH (delta max. 8.5 +/- 4.1 vs. 4.6 +/- 3.1 microunits/ml, P less than 0.05) and T3 (delta max. 32 +/- 27 vs. 11 +/- 16 ng/100 ml, P less than 0.05) responses to an intravenous TRH/LH-RH bolus injection in 6 eumenorrhoeic euthyroid hypertensive women, without affecting basal serum TSH, T3 or T4 levels or the basal and stimulated LH, FSH and prolactin values (P greater than 0.10). The mean serum testosterone, 17-hydroxyprogesterone and oestradiol levels were also similar before and during therapy. Spironolactone, possibly by virtue of its antiandrogenic action, may exert its enhancing effect on pituitary-thyroid function by modulating the levels of receptors for TRH in the thyrotrophs or by altering the T3 receptor in the pituitary permitting a greater response to TRH.
Pronounced hypoaldosteronism was found in three young women with hypertension and symptoms of mineralocorticoid overproduction--i.e., hyporeninaemia, hypokalaemia, and a fall in blood-pressure after diuretic therapy. Plasma 11-deoxycorticosterone and 18-hydroxy-11-dooxycorticosterone concentrations were normal Treatment with dexamethasone induced a return to normal of blood-pressure and plasma-potassium and an increase in plasma-renin activity and urinary aldosterone excretion. The data suggest that hypertension in these patients is maintained by overproduction of an unknown adrenocorticotropindependent mineralocortocoid.
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1. Pronounced hypoaldosteronism was found in five young women with low-renin hypertension and characteristic features of the mineralocorticoid hypertensive syndrome. 2. There was no overproduction of the mineralocorticoids 11-deoxycorticosterone and 18-OH-11-deoxycorticosterone. 3. Dexamethasone restored blood pressure to normal, decreased body weight, increased plasma potassium, and increased plasma renin activity and aldosterone excretion in all patients. 4. The data suggest overproduction of an unknown adrenocorticotrophic hormone-dependent mineralocorticoid maintaining hypertension in these patients.
In nine patients with Klinefelter's syndrome, mean basal plasma levels of testosterone (302 +/- 145 ng/100 ml) and its major precursor, 17 alpha-hydroxyprogesterone (17-OHP; 86 +/- 46 ng/100 ml), were significantly lower (P less than 0.01 to less 0.05) than in eight eugonadal men (605 +/- 180 and 136 +/- 39 ng/100 ml, respectively). The ratio of 17-OHP to testosterone, however, was comparable in both groups (0.29 +/- 0.09 vs. 0.24 +/- 0.08; P less than 0.10). In the Klinefelter patients, basal plasma testosterone and 17-OHP levels were positively correlated (rs = 0.87). Administration of hCG for 3 days raised plasma testosterone and 17-OHP levels in both groups. In the Klinefelter patients, the plasma 17-OHP rise exceeded the testosterone increment, leading to a statistically significant increase (0.48 +/- 0.19) of the 17-OHP to testosterone ratio, whereas this ratio remained virtually unchanged in the control subjects (0.20 +/- 0.06). Together, these findings indicate that in the basal state testicular steroidogenesis is globally attenuated, whereas short term hCG stimulation shows that the later steps in the biosynthesis of testosterone may be rate limiting in Klinefelter's syndrome.
The functioning of the hypothalamo-pituitary-adrenal axis was assessed in 10 adult women with idiopathic hirsutism treated for 2 weeks with the anti-androgen cyproterone acetate in a dose of 50 mg b. d. daily and in 4 patients treated for at least 3 months. Basal plasma ACTH and cortisol levels and the cortisol response to 8 h ACTH infusion were comparable before and during short-term treatment. The plasma ACTH and cortisol responses to insulin induced hypoglycaemia before and during anti-androgen therapy also were of the same order of magnitude. In the 4 patients treated for at least 3 months also no suppressive effect of the anti-androgen on basal plasma cortisol levels was observed. From these data the conclusion seems warranted that short-term cyproterone acetate treatment in the given dose not significantly influences pituitary-adrenal function in adult women with idiopathic hirsutism.
The functioning of the hypothalamo-pituitary-target organs axis was assessed in 3 patients with 'fertile eunuch' syndrome (FE) and 6 patients with 'classic' hypogonadotrophic hypogonadism (HH) with or without hyposmia. Both groups of patients did not differ from each other with regard to basal serum prolactin levels, pituitary growth hormone and thyrotrophin reserve and the thyroid or adrenal gland function. Both groups differed, however, with respect to the hypothalamo-pituitary-gonadal function: 1. the pituitary LH response to exogenous LH-RH was (low)-normal in FE and blunted in HH; 2. the basal FSH levels were normal in FE and undetectable in HH; 3. the basal LH levels were normal in FE and 3/6 patients with HH and low in the remaining three; 4. the basal and HCG stimulated plasma testosterone concentrations were significantly higher in FE than HH. The data suggest that FE represents a less severe form of LH-RH deficiency, rather than a distinct disorder.
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In a group of 13 healthy male adults in the Netherlands, a seasonal variation in circulating serum thyroxine (T4) and triiodothyronine (T3) levels was found, inversely correlating with the seasonally altering environmental temperature. Lowest serum T4 and T3 levels were found in the summer.
Elevated plasma testosterone levels were found in 8 women with Cushing's disease and oligo-or amenorrhea and/or hirsutism. In 4 men with Cushing's syndrome either due to adrenal hyperplasia or adenoma, plasma testosterone levels were lowered. Three of these 4 men complained of impotence or loss of libodo. Evidence for a major adrenal origin of the elevated testosterone values in the women with Cushing's disease was derived from the parallel suppression of cortisol and testosterone during dexamethasone administration, the testosterone responsiveness to ACTH and its dramatic fall after adrenalectomy. In the men with Cushing's syndrome the lowered plasma testosterone values were further suppressed by high doses of dexamethasone irrespective of concomitant cortisol suppression. Adrenalectomy or adenotomy restored the decreased plasma testosterone levels to normal. In women with Cushing's syndrome adrenal hyperandrogenism may account for the sexual and gonadal disturbances, in men glucocorticoid induced suppression of Leydig cell function may be responsible.
Conventional thyroid function indices (serum T4, T3, TSH and thyroidal RAIU before and after TSH) appeared to be normal in most of 25 clinically euthyroid patients with chromatine positive Klinefelter's syndrome. Administration of TRH, however, revealed a decreased TSH reserve in the Klinefelter patients, both off or on testosterone treatment, in comparison to euthyroidal eugondal male controls. Preliminary data suggest that this blunted TSH respnse to TRH is not a characteristic of Klinefelter's syndrome per se but might be caused by the concurrent hypergonadotrophism. Despite the blunted TSH response, the TRH mediated T3 response in the Klinefelter patients was about equal to that in the male controls.
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