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We report a case of Cushing's syndrome following obsessional abuse of a potent topical steroid lotion applied exclusively to the scalp, and which resolved after the lotion was withdrawn. This case exemplifies the danger of prolonged undersupervised use of potent topical steroids and caution is necessary with all long-term prescriptions.

Plasma glucose and insulin concentrations, body weight, and skinfold thickness were measured at 16 and 36 wk of pregnancy and 5–7 days after delivery in 37 women with normal glucose tolerance. Nine thin women [less than 80% ideal body weight (IBW)], 10 normal women (90-110% IBW), and 10 obese women (more than 120% IBW) were allowed to eat according to appetite. Another eight obese women were advised to restrict their carbohydrate intake to between 150 and 180 g while maintaining the calorie content of their diet between 1800 and 2000 cal. The thin, normal, and obese women displayed a net weight increase between 16 wk and 5–7 days after delivery of 6.3, 2.8, and 4.9 kg, respectively. The dieted obese women, however, showed a mean weight loss of 2.3 kg. There was a strong association between the overall pregnancy weight gain and the change in skinfold measurements between 16 wk and delivery in the women studied. A significant decrease in glucose tolerance was observed in all four groups, although this was least in the dieted women and greatest in the thin. The mean basal and glucose-stimulated insulin concentrations of the two obese groups were found to be significantly higher at 16 wk than those of the normal women. In the thin, normal, and obese subjects the mean basal and glucose-stimulated insulin concentrations at 36 wk were double those observed at 16 wk of pregnancy. A much smaller increase in insulin concentrations occurred between 16 and 36 wk in the dieted obese group. It is concluded that obesity preceding pregnancy produces a stress on carbohydrate metabolism, which can be ameliorated if an isocaloric diet with mild carbohydrate restriction is advised. No adverse effect on neonatal outcome was observed.

The metabolism of unlabelled human monocomponent insulin was studied in a group of six patients being treated with combined oestrogen-progestogen oral contraceptives (OC) and compared with a group of ten normal subjects. The parameters of insulin metabolism were determined by a priming dose-continuous infusion technique which enabled measurements of metabolic clearance rate (MCR) of insulin to be made at four separate steady state hormone concentrations spanning the physiological range. In normal subjects MCR was greatest at low insulin concentrations, falling from 24.7 ml/kg/min. at 16 muU/ml to 11.4 ml/kg/min. at a mean concentration of 280 muU/ml. In the OC group, MCR averaged 20.5 ml/kg/min. and did not change with increasing plasma insulin concentration. The plasma half-disappearance time (T 1/2) was longer than normal in the OC group (5.6 vs. 4.4 min., p less than 0.05) despite a higher MCR. The prolonged T 1/2 indicated that the apparent distribution space was increased in those on OC (166.6 vs. 82.7 mg/kg., p less than 0.0025). The results are interpreted as indicating increased capillary permeability to insulin and increased peripheral degradation. The fact that MCR did not fall in the OC group with increasing plasma insulin concentrations whereas it did in normal subjects, suggested that OC leads to the loss of saturable component of insulin degradation that is present in normal subjects. Insulin sensitivity (as judged by induced hypoglycaemia) was reduced in the OC group while growth hormone responses were within the normal range. Plasma cortisol was increased in those taking OC but the response to insulin induced hyperglycaemia was less marked than normal. The results indicate a significant alteration in insulin metabolism in these subjects, which may contribute to the impairment of carbohydrate tolerance seen in some women taking combined OC.

Marked hyperglycaemia and hyperinsulinaemia were observed in two normal women in premature labour treated with an intravenous infusion of a beta-sympathomimetic drug and intramuscular dexamethasone injections. Similar therapy in a chemical diabetic patient caused diabetic ketoacidosis, while treatment of an insulin dependent diabetic with dexamethasone alone resulted in a major increase in her insulin requirements. It is suggested that the diabetogenic effects of beta-sympathomimetic drugs and dexamethasone may be additive and that regular plasma glucose estimations should be made when they are used, especially in patients with impaired glucose tolerance.

Diurnal plasma free fatty acid (FFA) and glucose concentrations were measured in 23 normal women, 13 chemical diabetics, and 11 insulin-dependent diabetics in late pregnancy. The mean diurnal FFA value was lowest in the insulin-requiring diabetics and highest in the chemical diabetics. Although no association was found between percentile birthweight and maternal mean fasting or diurnal FFA, there was a positive correlation between percentile birthweight and both mean maternal fasting plasma glucose and mean diurnal glucose in normal and chemical diabetic women. These observations support the view that glucose is the major substrate used by the fetus, but birthweight may be influenced more by the total substrate crossing the placenta than by maternal levels of either glucose or FFA alone.

The effect of prolonged maternal hyperglycaemia on fetal plasma glucose and insulin concentrations was investigated in eight normal and nine diabetic patients. It was found that under fasting conditions the fetal glucose concentration in gestational diabetic pregnancies tended to be lower than in normal pregnancies. Insulin measurements suggested that this may be due to fetal hyperinsulinism in the diabetic group. During glucose infusion, regardless of the degree of maternal hyperglycaemia, the fetal glucose concentration was limited in 12 out of 13 cases to less than 200 mg/100 ml, with only small differences between normal and diabetic pregnancies. It is proposed that the placenta prevents unlimited transport of glucose to the fetus; yet in diabetic pregnancies a sequence of increased maternal-fetal glucose transport, fetal hyperinsulinism, and fetal hypoglycaemia may contribute to the observed perinatal mortality.

Serial retinal photographs have been taken of a fourteenyear-old girl with long-standing, poorly controlled diabetes mellitus who presented with severe hypercholesterolemia. Selective fluorescence contrast photography revealed masses of dilated hairpin capillary loops in the retina. Over a period of eight months of strict diabetic control the retinal vasculature returned to normal. The findings are discussed with reference to the origin and reversibility of retinal vascular changes in diabetes.

At St. Mary's Hospital Medical School in London, 22 outpatients, 21 women and 1 man, underwent oral glucose tolerance tests. Carbohydrate intake was standardized for 3 days prior to each test. 13 of the women were on oral contraceptive therapy of the combination type. Tests were performed either at 9 AM after a fast from 10 PM the previous night or at 3 PM after only a light dry breakfast. In the total group, glucose tolerance was found to be impaired in the PM, significant differences (p less than .05 or better) from the AM obtained at 60-150 minutes after glucose. Accompanying the general trend of glucose tolerance impairment in the PM was the finding of delayed and impaired insulin secretion in the PM, the AM and PM values reaching statistically significant differences at 30, 60, and 120 minutes (p less than .05). Measurements of growth hormone indicate fluctuations of this parameter are unlikely to be the cause of the diurnal fluctuations of glucose tolerance. No evidence was obtained to show the impaired carbohydrate tolerance of women on oral contraceptives is due to loss of diurnal rhythm, their pattern of AM and PM tests being very similar to the pattern of the total group. In general, then, the mild abnormalities of the AM tests of oral contraceptors are likely to be exaggerated in the PM tests. It is still undetermined whether the degree of chemical diabetes occurring is harmful to the asymptomatic pill user. The hypothesis that obese subjects lose diurnal rhythm, showing similar AM and PM results, was borne out (p less than .01).

SUMMARY Various aspects of thyroid activity of a non-iodine-containing thyroid analogue, 3:5:3′-trichloro-d-thyronine (d-trichlor-thyronine = d-ClT3) have been studied and compared with those of 3:5:3′-triiodo-l-thyronine (l-triiodo-thyronine = l-T3). As judged by the suppression of radio-iodine uptake in normal subjects, d-ClT3 is about six thousand times less active than l-T3 as an inhibitor of TSH production. Acute loading tests in hypothyroid patients showed that, judged by the effect on b.m.r., d-ClT3 is over 1600 times less potent than l-T3. Maintenance studies in hypothyroid patients showed that d-ClT3 at a dosage of 90 mg./day for 1 month achieved only partial restoration of the euthyroid state, and failed to maintain it in patients previously receiving other replacement therapy; this is 1500 times the minimum maintenance dose of l-T3. It was, however, found that the blood cholesterol levels fell to, or remained within, normal limits in all cases, suggesting that, like many other d-isomers, d-ClT3 has a relatively high hypocholesterolaemic potency. There is no evidence that d-trichlor-thyronine possesses greater pituitary-suppressive than calorigenic potency; it is therefore unlikely to be of value in the treatment of Graves' disease.

Twenty-four subjects received three oral glucose tolerance tests, in the morning, afternoon, and evening of separate days. The mean blood sugar levels in the afternoon and evening tests were similar, and they were both significantly higher than those in the morning test. Plasma immunoreactive insulin levels, however, were highest in the morning test. The pattern of insulin levels during the afternoon and evening tests resembled that described as typical of maturity-onset diabetes.

The effects of a maternal intravenous glucose load on the fetal plasma levels of glucose and insulin have been studied in 11 patients before the onset of labour. Within five minutes the fetal plasma glucose concentration rose significantly, indicating a rapid transfer of glucose across the placenta. Following this, the rate of fall in fetal plasma glucose closely reflected that in the mother. Serial fetal insulin estimations carried out in 8 of the 11 subjects following maternal glucose showed an early rise in fetal insulin in four and a delayed rise in one; in the remaining three there was no definite change. It is concluded that the blood glucose level of the fetus is controlled by that of the mother, but that the fetal pancreas at term may respond to hyperglycaemia by the secretion of insulin.

Clinical comparative research was carried out in order to determine the effects on carbohydrate and lipid metabolism of synthetic gonadal steroids administered alone and in various combinations. 496 premenopausal Caucasian women were studied before and during the use of OCs (oral contraceptives), so that each woman was her own control. They were divided into groups according to the OC preparation being taken. None of the observed changes in the metabolic parameters correlated with the duration of OC usage. Estrogen usage exerted significant metabolic effects, but only in the fasting state. The effects of pregnane and nortestosterone derived (estrane and gonane) progestagens given alone were also limited to the fasting state. Estrogens lowered the fasting plasma glucose and elevated the fasting pyruvate and triglyceride levels; pregnane progestagen raised the fasting pyruvate levels; estrane-gonane progestagens lowered fasting pyruvate, triglyceride and cholesterol levels. None of the preparations altered oral glucose tolerance or insulin responses. In combination preparations, estrogenic effects were antagonized by estrane and gonane progestagens, but not by a pregnane progestagen. The ideal OC should contain 30-35 mug estrogen combined with less than 1 mg of an estrane progestagen in order to reduce possible metabolic side effects.

This is a cross-sectional study of the effects on carbohydrate and lipid metabolism in 316 women of oral contraceptives (OCs) given continuously for at least 2 years as compared with 358 women not on the pill. The 2 groups were matched for age, weight, height, and parity. The aim of this study was to ascertain whether any differences could be detected between different ethnic groups living in the same environment, and secondly, to examine the differences between OCs containing different progestogens. The mean duration of OC use was 61.3 months with a range from 32.4-90.2 months. OCs used were combined pills containing 50 mcg ethinyl estradiol. A total of 125 women were on pills containing the progestogen estrane and 170 were on Gonane. The remaining 21 women were taking a 17-OH-progesterone derived progestogen. Metabolic differences between Chinese and Malay women were not significant. For those women not on the pill, differences were minimal. Chinese women on OCs showed lower fasting plasma glucose values and this is a similar pattern in Western women. Malay women showed little change in fasting blood sugar. Judged by incremental glucose values, both Chinese and Malay women responded in exactly the same way to OCs; for plasma triglycerides and cholesterol, the metabolic effects of OCs seem to be greater in Chinese than in Malay women. The 19-nortestosterone and levonorgestrel pills appeared to have similar minimal effects on fasting and glucose values although insulin values after glucose were higher for levonorgestrel than for 19-nortestosterone; this suggests insulin resistance. The major difference between the 2 pills is seen in fasting plasma lipids. The relatively antiestrogenic progestagen levonorgestrel seems to effectively counteract hyperlipidemia seen in women using OCs containing a 19-nortestosterone progestogen. In general, the findings in this study closely parallel those seen in Western women.

In order to study the relation between plasma magnesium and blood glucose concentrations in diabetes, diurnal profiles were obtained in nine diabetic patients and five healthy subjects. A significant inverse relationship between the two variables was found in seven of the nine diabetic patients and in one healthy subject. This could not be attributed solely to changes in plasma albumin, and its mechanism is unclear. Plasma magnesium levels in diabetes are closely dependent on blood glucose concentration.

Experience in the management of 100 cases of acromegaly is described. Three quarters of these had been referred directly to the endocrine clinic at the Middlesex Hospital. The remainder were referred from the Royal Post-graduate Hospital because they were thought unsuitable for yttrium implantation. The patients were studied by clinical assessment of severity, by measurement of basal growth hormone levels on three separate mornings, and by a review of possible complications. Particular attention was paid to diabetes, hypertension, cardiomegaly, respiratory, vascular and skeletal changes as well as visual field defect. Aggressive treatment was recommended in 77 patients. It was not recommended in the remainder on account of age, intercurrent illness or the apparent mildness of the condition. Fifty-nine patients were treated by trans-sphenoidal hypophysectomy. In 46 of the 59 patients the mean basal growth hormone level has been reduced to 5 ng/ml or less. In 39 this followed operation, in five operation and subsequent X-ray therapy and in two operation and the continuing effect of previously implanted yttrium. Of these 46 patients in whom the growth hormone level has been reduced to normal, 26 do not show any deficiency of anterior pituitary trophic hormones, 13 have gonadotrophin defect (in eight of these it was present before the operation) and seven require full replacement therapy. One patient died at home six weeks after the operation from a pulmonary embolus. There was one case of CSF rhinorrhoea which stopped spontaneously and three of acute frontal sinusitis. Trans-sphenoidal hypophysectomy is shown to be an effective means of treating acromegaly. If the basal level of growth hormone is not reduced to normal by six weeks after operation, it is recommended that a course of X-ray therapy should be given. This does not apply if irradiation has been used before operation.

Plasma human placental lactogen (HPL) concentrations have been measured at frequent intervals over 24 hours in 24 normal women, 13 chemical and 13 insulin dependent diabetic patients during the third trimester of pregnancy. Most of the women studied displayed variation in HPL levels during the day, but there was no evidence of a diurnal rhythm, nor significant changes following meals or during the nocturnal fast. The mean plasma HPL concentrations over 24 hours in the chemical and insulin dependent diabetic patients (5-9+/-SD 1-3 and 5-9+/-1-7 microng/ml respectively) were greater than those in normal women (5-1+/-1-2 microng/ml) but this difference was not significant. No significant change in plasma HPL concentrations was observed during a five-hour oral glucose tolerance test in either the normal or chemical diabetic group. It is suggested that in normal pregnant women HPL does not itself contribute to glucose homeostasis but acts as a 'regulator' which alters the actions of certain maternal hormones to achieve a favourable environment for fetal growth.

Summary Two-hourly plasma glucose measurements were made over a 24-hour period in 24 pregnant women with chemical diabetes treated by dietary carbohydrate restriction alone. The values obtained between midnight and 0600 hours displayed the best correlation with the mean of the diurnal values, the strongest individual correlation being at 0200 hours. During the daytime, the mean of the plasma glucose values before breakfast (0600 hours) and lunch (1200 hours) and two hours after supper (2000 hours) provided the strongest correlation with the mean diurnal value and these are recommended as the routine sampling times for assessment of diabetic control in pregnant women with dietary treatment for chemical diabetes.

Experience in the management of 100 cases of acromegaly is described. Three quarters of these had been referred directly to the endocrine clinic at the Middlesex Hospital. The remainder were referred from the Royal Post-graduate Hospital because they were thought unsuitable for yttrium implantation. The patients were studied by clinical assessment of severity, by measurement of basal growth hormone levels on three separate mornings, and by a review of possible complications. Particular attention was paid to diabetes, hypertension, cardiomegaly, respiratory, vascular and skeletal changes as well as visual field defect. Aggressive treatment was recommended in 77 patients. It was not recommended in the remainder on account of age, intercurrent illness or the apparent mildness of the condition. Fifty-nine patients were treated by trans-sphenoidal hypophysectomy. In 46 of the 59 patients the mean basal growth hormone level has been reduced to 5 ng/ml or less. In 39 this followed operation, in five operation and subsequent X-ray therapy and in two operation and the continuing effect of previously implanted yttrium. Of these 46 patients in whom the growth hormone level has been reduced to normal, 26 do not show any deficiency of anterior pituitary trophic hormones, 13 have gonadotrophin defect (in eight of these it was present before the operation) and seven require full replacement therapy. One patient died at home six weeks after the operation from a pulmonary embolus. There was one case of CSF rhinorrhoea which stopped spontaneously and three of acute frontal sinusitis. Trans-sphenoidal hypophysectomy is shown to be an effective means of treating acromegaly. If the basal level of growth hormone is not reduced to normal by six weeks after operation, it is recommended that a course of X-ray therapy should be given. This does not apply if irradiation has been used before operation.

Diurnal plasma glucose profiles and oral glucose tolerance during pregnancy were studied in normal women, chemical diabetics, and insulin-requiring diabetics. In normal women the mean diurnal plasma glucose rose by only 0.22 mmol/1 (4 mg/100 m1) during pregnancy. Mild chemical diabetes resulted in an increase in both the mean diurnal glucose concentration and the fluctuation of plasma glucose levels during the day. Fluctuation in glucose concentration in insulin-dependent diabetics was about three times that found in non-diabetic women of similar gestation, with relative hyperglycaemia during the day and hypoglycaemia at night. In non-diabetic women and those with chemical diabetes the mean dirunal glucose correlated closely with the total area under the three-hour oral glucose tolerance curve and significantly, but less closely, with the two-hour glucose tolerance test value.

SUMMARY Plasma glucose, plasma insulin and blood pyruvate levels were measured during two identical oral glucose tolerance tests carried out a few days apart on fifty-two normal or mildly diabetic subjects. No systematic differences could be detected between the first and second test. Several different functions derived from the tests were examined both for reproducibility and sensitivity in detecting departures from normal: a ‘clinical value index’ as calculated for each of these functions taking both reproducibility and sensitivity into account. This index was higher for the area under the glucose tolerance curve than for the glucose value at any single selected point during the test or for the ‘H’ index. The coefficient of variation for the glucose area was found to increase with increasing impairment of glucose tolerance, and confidence limits for this function were defined, enabling a significance of a single abnormal test to be assessed. Day-to-day variations in glucose tolerance were found not to be the result of fluctuations in the insulin response, nor to be related to the fasting pyruvate level before the test. It seems most likely that these variations result from fluctuations in glucose absorption and distribution.

Estimation of plasma glucose and immunoreactive insulin concentrations in normal subjects after an overnight fast showed that subjects with high basal plasma glucose levels tended to have high plasma insulin concentrations. A similar correlation between glucose and insulin levels was seen in patients with obesity and various endocrine disorders. The suppression of plasma insulin levels associated with hypoglycaemia was used to derive an "amended insulin-glucose ratio," which appeared to be a good discriminant for the diagnosis of insulinomas. In normal subjects the ratio was less than 30 muU insulin/mg glucose, in obese subjects less than 50 muU/mg, and most of the patients with insulinomas had values over 200 muU/mg.