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Biomedical subjects

A G Smals

Publications and source records attributed to A G Smals.

At least 109 records · Page 6Linked to original sources
PubMed1986

The corticotropin-releasing-hormone test versus the high-dose dexamethasone test in the differential diagnosis of Cushing's syndrome.

The diagnostic accuracy of the corticotropin-releasing-hormone (CRH) test was compared with that of the oral high-dose dexamethasone suppression test in the differential diagnosis of Cushing's syndrome. A false-negative response to CRH was present in 9% (2 of 22) of patients with pituitary-dependent Cushing's disease and to high-dose dexamethasone in 11% (2 of 18). All 3 patients with Cushing's syndrome due to an adrenal adenoma were unresponsive to both CRH and dexamethasone. The only patient with ectopic corticotropin secretion had a false-positive response of corticotropin to dexamethasone and no response of corticotropin to CRH. Simultaneous failure of both tests to indicate the cause of Cushing's syndrome did not occur in this series, except in 1 patient with Cushing's disease and overt macronodular hyperplasia. It is concluded that the diagnostic accuracy of the CRH test in patients with Cushing's syndrome is comparable to that of the high-dose dexamethasone test and that the highest discriminatory score in the differential diagnosis of Cushing's syndrome is achieved by using both a CRH test and a high-dose dexamethasone test.

17-Hydroxycorticosteroids↗
PubMed1986

Human pancreatic growth hormone releasing hormone fails to stimulate human growth hormone both in Cushing's disease and in Cushing's syndrome due to adrenocortical adenoma.

An absent or severely blunted hGH response to an i.v. bolus injection (100 micrograms) of human pancreatic growth hormone releasing hormone (hpGRF 1-44) was found in seven female patients with Cushing's syndrome (five with pituitary dependent Cushing's disease and two due to an adrenal adenoma) and four men with pituitary dependent Cushing's disease. Three of the female and three of the male patients had an adequate hypoglycaemia after insulin administration. All these patients showed an absent or blunted hGH response after insulin induced hypoglycaemia. The GHRH data in these patients are in agreement with those in older literature on hGH responsiveness to stimuli such as L-dopa, arginine and insulin induced hypoglycaemia. It is concluded that hypercortisolism inhibits hGH release to various stimuli at the pituitary level.

Adenoma↗
PubMed1986

Sex difference in human growth hormone (GH) response to intravenous human pancreatic GH-releasing hormone administration in young adults.

Intravenous administration of a 100-micrograms dose of human pancreatic GH-releasing hormone (human pancreatic GHRH1-44, indicated by GHRH) disclosed a sex difference in GH responsiveness. The maximum GH increments [41 +/- 11 (SEM) vs. 15 +/- 4 ng/ml, P* less than 0.05] and the areas under the curves (419 +/- 105 vs. 148 +/- 53 area U, P* less than 0.05) were significantly higher in 12 men than in 10 women. No significant correlation was found in either group between the basal plasma estradiol or testosterone levels and the maximum or integrated GH response to GHRH. Serum PRL levels significantly increased in both groups within 5 min after GHRH injection (men, P less than 0.001 vs. t = 0; women, P less than 0.05 vs. t = 0). The areas under the curves of the PRL responses (355 +/- 184 vs. 189 +/- 73 area U) and the maximum PRL increments (58 +/- 18 vs. 36 +/- 6 mU/l, P* greater than 0.10) were similar. In conclusion, a sex difference in GH responsiveness to GHRH was found between young adult men and women. Recent in vivo and in vitro data reveal a similar sex difference in rodents and an enhancing effect of androgens, but not estrogens, on the GH response to GHRH. These findings support the theory that in humans testosterone also plays a key role in the genesis of this sex difference.

Adult↗
PubMed1986

Responsivity of adrenocorticotropin to corticotropin-releasing hormone and lack of suppressibility by dexamethasone are related phenomena in Cushing's disease.

The ACTH and cortisol responses to 100 micrograms ovine corticotropin-releasing hormone (CRH) in 19 consecutive patients with Cushing's disease were compared with those in 13 normal subjects. In 2 patients with Cushing's disease, plasma ACTH and cortisol did not increase after CRH administration. Compared to the normal subjects, maximal ACTH increments [135 +/- 25 (+/- SEM) vs. 42 +/- 6 pg/ml; P less than 0.001, by Wilcoxon's two-sample test] and maximal cortisol increments (17.7 +/- 1.8 vs. 9.4 +/- 1.1 micrograms/100 ml; P less than 0.01 by Wilcoxon's test) after CRH were significantly higher in the 17 CRH-responsive patients with Cushing's disease. In the normal subjects, there was a significant negative correlation between the basal cortisol level and the maximal ACTH (r = -0.65; P less than 0.05, by Spearman's rank correlation test) and cortisol (r = -0.95; P less than 0.001, by Spearman's test) responses to CRH. In contrast, in the CRH-responsive Cushing patients, there was no significant correlation between the basal cortisol level and the maximal ACTH (r = 0.10; P greater than 0.10, by Spearman's test) and cortisol (r = 0.14; P greater than 0.10, by Spearman's test) increments after CRH treatment. In the normal subjects, there was no significant correlation between the basal ACTH level and the maximal ACTH increments after CRH administration (r = -0.24; P greater than 0.10, by Spearman's test). Again in contrast, in the CRH-responsive Cushing patients, maximal ACTH increments after CRH treatment correlated positively with basal ACTH levels (r = 0.69; P less than 0.005, by Spearman's test). Moreover, in these patients, the maximal ACTH increments after CRH were positively correlated with the ACTH levels after suppression with higher and lower doses of dexamethasone. We conclude that in Cushing's disease, unlike in normal subjects, circulating cortisol is not the major modulator of ACTH and cortisol responses to CRH, and that in these patients, responsivity of ACTH to CRH and lack of suppressibility by dexamethasone are related phenomena.

Adolescent↗
PubMed1985

Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease.

Premature arteriosclerosis and thromboembolic events are well-known complications of homozygous homocystinuria due to cystathionine synthase deficiency. It is unknown whether heterozygosity for homocystinuria predisposes to premature vascular disease. We explored the frequency of excessive homocysteine accumulation after standardized methionine loading in 75 patients presenting with clinical signs of ischemic disease before the age of 50:25 with occlusive peripheral arterial disease, 25 with occlusive cerebrovascular disease, and 25 with myocardial infarction. In seven patients in each of the first two groups but in none of the patients in the third group, heterozygosity for homocystinuria was established on the basis of pathological homocysteinemia after methionine loading and cystathionine synthase deficiency in skin fibroblast cultures. Because the frequency of heterozygosity for homocystinuria in the normal population is 1 in 70 at the most, we conclude that this condition predisposes to the development of premature occlusive arterial disease, causing intermittent claudication, renovascular hypertension, and ischemic cerebrovascular disease.

Adult↗
PubMed1985

Improved identification of heterozygotes for homocystinuria due to cystathionine synthase deficiency by the combination of methionine loading and enzyme determination in cultured fibroblasts.

Previous data on tentative identification of the carrier state for homocystinuria due to cystathionine synthase deficiency using methionine loading or measurement of cystathionine synthase activity in tissue extracts are conflicting. We studied the results of standardized oral methionine loading in 20 obligate heterozygotes and compared them with those of determination of cystathionine synthase activity in cultured fibroblasts. Special attention was devoted to our recently reported observation on the small but striking differences in methionine metabolism between healthy pre- and postmenopausal women and men. Fasting and after load peak levels of methionine in serum did not discriminate the carriers from the control subjects. The mean fasting level of total homocysteine was only significantly higher in the group of premenopausal heterozygotes than in the corresponding control group. Nevertheless, the individual values overlapped with the normal range in 4 of 12 premenopausal heterozygotes. After loading peak levels of total homocysteine in 18 out of the 20 obligate heterozygotes exceeded the upper limit of the ranges in the three control groups. Thus, this parameter discriminated 90% of the obligate carriers. Measurement of cystathionine synthase activity in cultured fibroblasts from a skin biopsy identified the obligate heterozygotes to a similar degree (85%). No significant correlation between the measurements of cystathionine synthase activity and the after load peak levels of total homocysteine in the individual heterozygotes was established. Combination of both methionine loading and determination of cystathionine synthase activity in cultured fibroblasts identified all of these carriers.

Adolescent↗
PubMed1985

Disease-free interval and estrogen receptor activity in tumor tissue of patients with primary breast cancer: analysis after long-term follow-up.

Specific estrogen receptor activity (ER) was found in 115 of 175 (66%) tumors of patients treated for primary breast cancer in the period 1974-1981; 60 patients had ER-negative tumors. All patients were under observation for at least 48 months (median 76 months). The 24 patients who received adjuvant chemotherapy as part of their initial treatment, were excluded from the analysis of the disease-free interval (DFI). Groups of patients with ER-positive or ER-negative tumors did not differ significantly in clinical characteristics. Patients with ER-positive tumors had a significantly longer DFI than those with ER-negative tumors only in the first year after initial treatment. After prolonged observation a significant difference in recurrence rates was no longer found. In premenopausal women, the DFI was not different for those with ER-positive compared to those with ER-negative tumors, not even in the first year of observation. However, in postmenopausal women, those with ER-positive tumors had a significantly longer DFI up to 3 years after initial treatment but not thereafter. There was no difference in DFI between the ER-positive and ER-negative groups when the tumor stage was taken into account. It is concluded that the ER status of the primary tumor affects prognosis only on the short term.

Breast Neoplasms↗
PubMed1985

Effect of aromatase inhibition by delta 1-testolactone on basal and luteinizing hormone-releasing hormone-stimulated pituitary and gonadal hormonal function in oligospermic men.

Aromatase inhibition by delta 1-testolactone (TL), 500 mg twice daily for 4 weeks, in nine patients with idiopathic oligospermia lowered circulating estradiol (E2) levels by about 30%, enhanced the secretion of follicle-stimulating hormone (+ 30%), 17-hydroxyprogesterone (17-OHP) (+ 40%), and testosterone (T) (+ 30%), but did not affect serum luteinizing hormone levels. Despite E2 lowering, there was an accumulation of 17-OHP over T, suggesting 17, 20-lyase inhibition. Unexpectedly, administration of TL almost completely deleted the T response to continuous luteinizing hormone-releasing hormone infusion present before TL therapy, despite similar gonadotropin release. Because the 17-OHP response to the luteinizing hormone-releasing hormone infusion was even higher during therapy, the 17,20-lyase lesion seemed aggravated despite substantial reduction of E2 levels. Although the present data suggest that estrogens play a less dominant role in the origin of the late steroidogenetic lesion than previously assumed, the suggestion also arises that TL per se, in addition to its antiestrogenic action, exerts an inhibiting effect on the 17,20-lyase locus, which may obscure the beneficial effect of reducing E2.

Adult↗
PubMed1985

ACTH and cortisol responses to ovine corticotrophin-releasing factor in patients with primary and secondary adrenal failure.

The ACTH and cortisol responses to an intravenous bolus injection of 100 micrograms ovine CRF were studied in 19 patients with adrenal failure. In all eight patients with primary adrenal failure, plasma ACTH levels increased from a mean basal level of 1494 +/- 431 (SEM) pg/ml to peak value of 2601 +/- 1220 pg/ml at 10 min. In comparison with healthy subjects absolute ACTH increments after ovine CRF were significantly augmented in the patients with Addison's disease (P* less than 0.001), and the absolute ACTH responses after ovine CRF were positively correlated with the basal plasma ACTH levels. The 11 patients with secondary adrenal insufficiency could be subdivided into two groups: (A) those having little or no ACTH and cortisol response to ovine CRF (five patients) and (B) those having prolonged and pronounced ACTH responses with a biphasic pattern and a delayed second peak (six patients), followed in all patients by a marked cortisol increase. These data demonstrate that the CRF-test can discriminate between hypothalamic and pituitary causes of secondary adrenal failure.

Addison Disease↗
PubMed1985

Aromatase inhibition by delta 1-testolactone does not relieve the gonadotropin-induced late steroidogenic block in normal men.

Aromatase inhibition by delta 1-testolactone [(17 oxa-D-homo 1,4 androstanediene-3,17 dione) 500 mg twice daily for 10 days] in nine normal men lowered circulating estradiol (E2) levels by about 25%, enhanced the secretion of FSH, 17-hydroxyprogesterone (17-OHP), and to a lesser degree testosterone (T), but did not affect serum LH levels. Despite E2 lowering there was greater accumulation of 17-OHP than of T after 7 days of treatment, suggesting 17,20-lyase inhibition. Unexpectedly, administration of delta 1-testolactone almost halved the T response to hCG (Pregnyl, 1500 IU), but did not affect the 17-OHP response. Thus, E2 lowering by testolactone aggravated the hCG-induced 17,20-lyase block present before testolactone administration. Although the present data might suggest that estrogens do not play a role in the genesis of the hCG-induced late steroidogenic block, the results suggest that testolactone per se, in addition to its reported antiestrogenic action, inhibits 17,20 lyase.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Disparity of thyrotropin (TSH) and prolactin responses to TSH-releasing hormone in obesity.

The effect of TRH administration on TSH and PRL release was investigated in 11 obese women and 16 normal weight women. There were no differences in basal serum levels of estradiol, T3, T4, TSH, or PRL between the 2 groups. The increment of TSH levels in the obese group [mean maximum change (delta max), 19.3 +/- 3.0 (+/-SEM) mIU/liter] was significantly higher (P less than 0.025) than that in the control group (delta max, 11.3 +/- 1.3 mIU/liter), whereas PRL levels rose significantly less (P less than 0.025) in these obese women than in the control group (delta max, 738 +/- 132 and 1311 +/- 133 mIU/liter, respectively). Since serotonin is known to stimulate PRL and inhibit TSH release, deficiency of serotonin has been hypothesized as the cause of this disparity between TSH and PRL levels in obesity.

Adolescent↗
PubMed1984

The anomalous effect of some ACTH-fragments missing the amino acid sequence 1-10 on the corticosteroidogenesis in purified isolated rat adrenal cells.

The corticosteroidogenicity of ACTH-derived peptides was tested in a purified isolated rat adrenal cell system. The activity was related to the activity of standard ACTH (synthetic hACTH; potency fixed at 100). The peptides ACTH NH2 and ACTH showed steroidogenicity at pharmacological doses (potencies: 0.00067 and 0.00032, respectively). None of the peptides tested inhibited or potentiated the ACTH-induced steroidogenesis at low doses (0.5-50 000 pg). The results suggest the presence of a second center within the ACTH molecule capable of inducing steroidogenesis.

Adrenal Cortex↗