J. Alaghband-Zadeh

Investigation of Hirsutism: Testosterone is Not Enough:

SUMMARY In a consecutive series of 41 hirsute women clinically classified as benign androgen excess, only 34% were found to have elevated plasma ‘total’ testosterone (T), 22% having subnormal sex hormone binding globulin (SHBG). When expressed as the ratio T/SHBG (‘free androgen index’), 85% of the patients had values above the normal range. It is concluded that this index is more reliable than total testosterone in assessing androgen status in female patients.

Evidence for a raised concentration of a circulating sodium transport inhibitor in essential hypertension.

A cytochemical technique that measures the ability of plasma to stimulate guinea-pig renal glucose-6-phosphate dehydrogenase (G6PD) activity in vitro, which is a marker of its ability to inhibit Na+-K+-adenosine-triphosphatase (Na+-K+-ATPase), was used in 19 patients with essential hypertension and 23 normotensive, healthy subjects. The ability of plasma to stimulate G6PD was significantly greater in the hypertensive patients when they were taking their normal sodium diet than in the normotensive subjects, and was significantly correlated with blood pressure. The ability of plasma to stimulate G6PD was inversely correlated with plasma renin activity in the hypertensive patients and increased with age and sodium intake in the normotensive subjects. These results support the hypothesis that essential hypertension, and also perhaps the increase in blood pressure with age in communities that consume large quantities of salt, is in part due to an increase in a circulating concentration of an inhibitor of Na+-N+-ATPase.

EFFECT OF SODIUM INTAKE ON ABILITY OF HUMAN PLASMA TO INHIBIT RENAL Na+-K+-ADENOSINE TRIPHOSPHATASE IN VITRO

Abstract An inhibitor of renal sodium-potassium-dependent ATPase was demonstrated in human plasma by a cytochemical technique. Circulating levels of this activity were 25 times greater in plasma taken when five healthy subjects were on a high-salt diet than in plasma obtained when they were on a low-salt diet. These results are consistent with the proposal that urinary sodium excretion is in part controlled by a circulating natriuretic substance.

STUDIES ON THYROID STIMULATING HORMONE AND THE LONG-ACTING THYROID STIMULATING HORMONE

The basis of cytochemical bioassays is that the selected hormone will markedly alter some chemical activity of its target cells. In the case of thyroid stimulating hormone, it is well known that the hormone induces endocytosis of colloid by the thyroid follicle cells, and the endocytotic vesicles (containing the colloid) fuse with lysosomes (Wollman, 1969 ; Dumont, 1971). There is also some evidence that the stability of lysosomal membranes is diminished when changes occur at the cell membrane (Bitensky, 1963); from studies on the lysosomes of macrophages it is generally believed that the secondary lysosomes, namely the complex formed when primary lysosomes fuse with endocytotic vesicles, have less stable membranes than do the uninfluenced primary lysosomes. It follows, therefore, that one effect of thyroid stimulating hormone (TSH) and of the long acting thyroid stimulating hormone (LATS) could well be reflected in a change in the stability of the lysosomal membranes in the cells of the follicles. Recently a number of studies have been made in which the stability of lysosomes in particular cells has been measured (e.g. Bitensky el al., 1973); these depend on the rate at which a chromogenic substrate, leucine 2-naphthylamide, penetrates the lysosomal membranes, the colour being measured by microdensitornetry. It therefore seemed reasonable to see whether this quantitative cytochemical procedure for measuring Iysosomal stability could be used to monitor the effect of TSH and of LATS acting on thyroid tissue maintained in vitro.

Double-blind trial of oral 1,25-dihydroxy vitamin D3 versus placebo in asymptomatic hyperparathyroidism in patients receiving maintenance haemodialysis.

Fifty-seven patients who had been receiving maintenance haemodialysis for a mean of 4.6 years were given 0.25-0.5 microgram oral 1,25-dihydroxy (1,25-(OH)2) vitamin D3 or a placebo in a double-blind manner for one to two years. In patients with normal radiographs (mean plasma parathyroid hormone concentration 205 microliterEq/ml) 1,25-(OH)2 vitamin D3 prevented the development of the radiological appearances of hyperparathyroidism. In patients with abnormal radiographs (mean plasma parathyroid concentration 709 microliterEq/ml) 1,25-(OH)2 vitamin D3 arrested or reversed the radiological changes of hyperparathyroidism. Nevertheless, the response was slow and the concentration of the hormone remained considerably raised (mean 445 microliterEq/ml). It is concluded from these results that giving 1,25-(OH)2 vitamin D3 to patients receiving maintenance haemodialysis who have normal hand radiographs or minimal erosions is beneficial. In patients with more advanced hyperparathyroidism parathyroidectomy should be considered unless there is a rapid response.

Significance of an index of insulin resistance on admission in non-diabetic patients with acute coronary syndromes

BACKGROUND Insulin resistance is associated with ischaemic heart disease and has been proposed as a risk factor for subsequent myocardial infarction. AIM To investigate the potential use of a recently proposed insulin resistance index in identifying insulin resistance in patients admitted with an acute coronary syndrome. METHODS Single centre study of 441 non-diabetic patients admitted with chest pain to a coronary care unit and followed prospectively for a median of three years for outcome. Admission glucose and insulin concentrations were measured and from these values an admission index of insulin resistance (AIRI) calculated. Its association with other known factors in the insulin resistance syndrome, and subsequent outcome, was examined. RESULTS The AIRI was greater in patients with myocardial infarction than in a control group without myocardial infarction (p < 0.0001). A Cox regression model for subsequent cardiac death identified previous myocardial infarction (p < 0.0001), infarct size (p < 0.0001), and AIRI (p = 0.0033) as positive risk predictors. Patients of Indian subcontinent ethnic origin had greater AIRI values than white patients: mean (SD) 7.5 (1.3) v 4.6 (0.2), p < 0.001. CONCLUSIONS A simple index of insulin resistance measured on patients admitted with myocardial infarction provides an important predictive measure of poor outcome and is superior to admission glucose measurement. It may be useful in identifying patients admitted with myocardial infarction who could benefit from alternative early management strategies.

Antenatal corticosteroid therapy and risk of osteoporosis.

Objective To assess the risk of maternal osteoporosis associated with antenatal corticosterioid administration for neonatal respiratory distress syndrome prophylaxis.

Comparison of paired short Synacthen and insulin tolerance tests soon after pituitary surgery.

The cortisol responses to hypoglycaemia (insulin tolerance test, ITT) and tetracosactrin (short Synacthen test, SST) were compared after hypophysectomy to evaluate the SST for the assessment of hypothalamo-pituitary-adrenocortical (HPA) axis function in the immediate post-operative period. In 12 patients who were tested a mean of 21 months postoperatively (range 1–96) peak plasma cortisol in the SST correlated with that in the ITT (r = 0·90). Correlation was also seen in 12 patients tested a mean of 9 days (range 4–18) after hypophysectomy (r = 0·73). Basal-peak cortisol increments did not correlate. The peak plasma cortisol response in each test was classified by comparison with a reference value of 550 nmol/L. On this basis there was a notable discrepancy between the ITT and SST results in only one patient who was tested 4 days after hypophysectomy. The close correlation between ITT and SST responses after pituitary surgery extends into the immediate post operative period and indicates that the latter test can be used to screen HPA axis function at this time.

A longitudinal study of biochemical markers of bone turnover during normal pregnancy and pregnancies complicated by pre-eclampsia

Objectives To test the hypothesis that the increased bone turnover observed in established pre‐eclampsia is present earlier in pregnancy prior to the diagnosis of pre‐eclampsia.

Hypothalamic and plasma total nitrate/nitrite concentrations in spontaneously hypertensive rats

Stable end‐products of nitric oxide (NO) metabolism, nitrates and nitrites, were measured in hypothalamic extracts and plasma samples of Okamoto spontaneously hypertensive (SH) rats. The mean total nitrate/nitrite concentration was significantly lower in the hypothalami of SH rats compared with the normotensive Wistar Kyoto (WKY) control animals (P < 0.01). In contrast, their plasma concentrations were significantly higher (P < 0.05). These results indicate that the hypertensive state in SH rats is associated with a diminished production of hypothalamic NO, while the raised plasma nitrate/nitrite levels could reflect an increased compensatory endothelial NO synthase activity in these animals compared with the WKY controls.