Biomedical subjects
Publications and source records attributed to C G Semple.
Over a 20 year period 4 of 40 (10%) female patients with Cushing' syndrome also had a solitary thyroid nodule. In 3 cases this was an autonomous 'hot' nodule. In the same population only one case of presumed Graves' disease was seen. It is postulated that the association of autonomous thyroid nodule and Cushing's syndrome may represent a variant of multiple endocrine neoplasia.
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We have examined the hormone status of ten healthy adult males who completed the Glasgow marathon. Serum thyroxine, free thyroxine, triiodothyronine and thyroid stimulating hormone were unaffected by the exertion. Serum cortisol as well as other steroid hormones, androstenedione, dehydroepiandrosterone sulphate and oestradiol showed distinct rises (p less than 0.01) but serum testosterone fell significantly (p less than 0.01). There was no change in sex hormone binding globulin capacity but a significant fall in LH levels (p less than 0.05) accompanied the fall in serum testosterone. The mechanism of the fall in serum testosterone in this situation requires clarification but it is unlikely to have adverse consequences.
Seven male patients with cyanotic congenital heart disease were studied. Serum testosterone, androstenedione, dehydroepiandrosterone, thyroxine and triiodothyronine levels did not differ significantly from control values. Thyroid stimulating hormone and prolactin responses to injected thyrotrophin releasing hormone were normal. Impaired gonadotrophin responses to injected gonadotrophin releasing hormone were noted in two patients. The hypothalmic-pituitary-testicular axis appears to be better preserved in cyanotic congenital heart disease than in chronic obstructive airways disease and restrictive lung disease for a similar degree of hypoxia. Possible explanations are discussed.
Each of 62 females were studied for a period of between two and 72 months (mean 36 months) following the removal of a prolactinoma by transsphenoidal pituitary surgery. Our aims were to define the relationships between pre- and post-operative features, the operative findings and the functional outcome. Pre-operative serum prolactin (PRL) concentrations correlated with tumour diameter (r = 0.55, p less than 0.001). Following surgery two groups of patients were identified: Group 1, 46 spontaneously and regularly menstruating patients and Group 2, 16 patients with persistent amenorrhoea. The patients in Group 1 had significantly lower pre-operative and post-operative serum (PRL) concentrations (p less than 0.02 and p less than 0.001 respectively) and significantly greater PRL responses to thyrotrophin releasing hormone (TRH) and metoclopramide stimulation after surgery (p less than 0.001). There was not a significant difference in tumour size between the groups. Forty-four (96 per cent) of the patients in Group 1 had normal post-operative serum PRL concentrations within one week of surgery. By comparison (p less than 0.001) only 42 and 20 per cent respectively of Group 1 patients who were tested had normal TRH and metoclopramide evoked PRL secretion following surgery. Return of regular menstruation was associated with cessation of galactorrhoea in 44 patients (96 per cent) and ovulation occurred in 37 of 38 menstruating patients for whom data are available. All patients with normal TRH and metoclopramide stimulation tests menstruated spontaneously. Nevertheless most patients who menstruated did so in spite of retaining suppressed PRL responses. Of 46 patients followed to date whose serum PRL was normal one week after surgery, seven later were found to have an elevation of serum PRL outside the normal range but in only two has this been persistent. We suggest that a single measurement of serum PRL one week following transsphenoidal pituitary surgery for prolactinoma provides a good basis for deciding about the future management of patients who desire menstruation and pregnancy.
Calcium ions seem to be essential for the release of many hormones. The calcium antagonist verapamil which is used as an anti-arrhythmic and anti-anginal agent has an inhibitory effect on the release of follicle stimulating hormone (FSH), luteinising hormone (LH), and thyrotrophin stimulating hormone (TSH) when given as an intravenous infusion to normal volunteers. As verapamil is usually given orally we studied pituitary-testicular and pituitary-thyroid function before and after completing a 4-week course of oral verapamil. The oral preparation did not have any significant effect on the endocrine parameters studied.
Anabolic steroids have widespread metabolic effects but, to date, their proven clinical indications have been limited. Recently the 17 alpha-alkylated steroid, stanozolol, has been shown to be of value in a variety of commonly occurring vascular diseases. Its endocrine effects have received little attention and we have investigated the effect of administering a 14 d course of stanozolol (10 mg orally per day) on a variety of important hormonal pathways in nine healthy male subjects. Significant changes occurred as follows: a 55% reduction in serum testosterone levels was noted and was accompanied by reductions in 'derived' free testosterone, sex hormone binding globulin and LH levels; total T4 and T3 levels fell in association with a decrease in thyroxine binding globulin, but no alteration was detected in TSH or free T4 levels. Changes in vitamin D status, with falls in 25-hydroxycholecalciferol and vitamin D binding globulin were also observed. These effects were reversible on stopping treatment. Stanozolol therapy therefore leads to a number of hormonal changes, probably by an action at both pituitary and hepatic levels.
Nineteen patients thought to have Cushing's disease were treated by transsphenoidal microsurgery; the type of operation performed depended upon the findings in the individual patient. Seventeen patients remitted. Failures occurred in a patient with an invasive macroadenoma and in a patient who was subsequently found to have a thymic carcinoid tumour secreting ACTH. One patient who remitted suffered a recurrence during pregnancy, 30 months after operation. The ten patients (Group I) who had a selective removal of a microadenoma or a limited resection of the gland were often GH deficient, but seven regained cortisol reserve and all ten regained normal pituitary-thyroid and pituitary-gonadal responses. By contrast abnormalities of pituitary function were common in nine patients who had a radical or total hypophysectomy. We conclude that transsphenoidal microsurgery is the best treatment for Cushing's disease and that, when feasible, a selective microadenomectomy is the most appropriate operation.
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Verapamil, a calcium antagonist used to treat angina pectoris, inhibits insulin release in vitro and, when administered intravenously to humans, decreases glucose tolerance. Oral verapamil, 120 mg/day for 1 week increasing thereafter to 240 mg/day in divided doses, was given to nine non-diabetic patients with angina pectoris for 4 weeks. The glucose and insulin responses to a standard glucose load showed no significant difference before and after verapamil. Oral verapamil in the doses used in this study had no significant effect on glucose tolerance in non-diabetics.
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Trilostane has been used to treat 6 patients with Cushing's syndrome, 4 with an adrenal adenoma and 2 with pituitary driven disease. Three patients responded clinically and biochemically to trilostane. Although effective in some cases of Cushing's syndrome, the variability of the effect of trilostane may limit its usefulness as a therapeutic agent.
Trilostane, a competitive inhibitor of the 3 beta-hydroxysteroid dehydrogenase enzyme system, has adrenal blocking activity and has been used to treat Cushing's syndrome and other disease. To investigate is effect on the normal human hypothalamic-pituitary-testicular axis, trilostane (initially 240 mg/day) was given to ten healthy adult males, the dose increasing at weekly intervals by 240 mg/day up to 960 mg/day. When chromatography was used to remove trilostane and metabolites from the assay system, serum testosterone was found to fall on trilostane therapy (P less than 0.01) and this was accompanied by a rise in LH (P less than 0.01). The responses of FSH and LH to LHRH were unaffected by treatment. It is concluded that trilostane inhibits human testicular 3 beta-hydroxysteroid dehydrogenase and male patients on trilostane should be monitored for sexual dysfunction and impairment of testicular steroidogenesis.
Trilostane has been used to treat Cushing's syndrome and other adrenocortical disorders. To investigate its effect on the normal adrenal gland, trilostane (initially 240 mg/day) was given to ten healthy men, the dose increasing at weekly intervals by 240 mg/day up to a final dose of 960 mg/day. The drug was well tolerated although one subject withdrew after the first week because of gastrointestinal side effects. Trilostane had no significant effect on aldosterone levels or blood pressure. The mean 24-h urinary free cortisol excretion rose from 14.2 to 22.0 mumol/mol creatinine (P less than 0.01) before and after trilostane 240 mg/day but did not rise thereafter. Early morning serum cortisol and plasma ACTH levels did not change on trilostane. The mean increment in serum cortisol after the i.v. injection of 0.25 mg of ACTH was reduced from 398 nmol/l before trilostane to 287 nmol/l on 240 mg/day and to 291 nmol/l on 960 mg/day (P less than 0.01). Insulin-induced hypoglycaemia while on 960 mg/day produced a maximum increment in serum cortisol of 361 +/- 118 nmol/l (mean +/- SD) although one subject had a subnormal increment of 180 nmol/l (normal greater than 200 nmol/l). Plasma ACTH rose with hypoglycaemia in all cases. We conclude that trilostane has only a minor effect on the normal hypothalamic-pituitary-adrenocortical axis.
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Thyroid function was evaluated in 16 patients with end-stage renal failure, 8 treated by maintenance haemodialysis (HD) and 8 by continuous ambulatory peritoneal dialysis (CAPD), and compared with 8 healthy subjects. Serum total thyroxine (T4) and triiodothyronine (T3) concentrations were low in both groups (p less than 0.01) with T3 significantly lower in the CAPD than the HD group (p less than 0.01). Serum-free thyroxine (FT4) concentrations were low in CAPD patients with respect to normal (p less than 0.01). Basal thyroid-stimulating hormone (TSH) concentrations did not differ significantly from normal but the TSH responses to thyrotrophin-releasing hormone were depressed in both groups. While CAPD may improve control of some biochemical and haematological parameters as compared with HD, it does not have a beneficial effect on thyroid function.