Audit of multiple insulin injection regimens in a large outpatient diabetic population.

One hundred out-patients treated by multiple insulin injection regimens underwent clinical audit by retrospective analysis of their case-notes. Patients had been on multiple insulin injection therapy (MIIT) for 1.0-4.5 years (median, 3.6 years) and had had diabetes for 2 months-33 years (median, 8.7 years) at the time of starting pen therapy. Median daily insulin dose per patient did not differ significantly following stabilisation on MIIT or at latest follow-up. The median glycated haemoglobin did not change during each of the 4 years of follow-up. During the year prior to commencing MIIT the patients showed no significant alteration in body weight. Patients' weights rose significantly during each subsequent year. Median weight gains were 0.9 kg (P less than 0.005) during the first year, 1.4 kg (P less than 0.005) during the second year, 0.9 kg (P less than 0.05) during the third year and 1.4 kg (P less than 0.05) during year 4. No such weight gain was recorded in a control group of 30 patients matched for age and duration of diabetes and treated by twice daily insulin injections. Multiple insulin injection regimens used over prolonged periods in a routine clinic setting do not alter metabolic control. However, continuing weight gain appears to occur despite similar daily insulin doses.

Inhibition of glucose-induced insulin secretion by calcium channel blocking drugs in-vitro but not in-vivo in the rat.

The organic calcium channel blocking drugs darodipine, nicardipine, diltiazem and verapamil inhibited glucose-induced (8.3 mmol L-1) insulin secretion by rat isolated islets in a concentration-dependent manner. The IC50 values (mumol L-1) for nicardipine, diltiazem and verapamil were 0.0025, 1.94 and 3.6, respectively. There were no significant differences between the potencies of any one drug when compared at two different glucose concentrations (27.8 and 8.3 mmol L-1). Isolated islets were also responsive to the calcium channel activating drugs BAY K 8644 and CGP 28392, which enhanced glucose-induced insulin secretion and prevented the inhibitory effect of verapamil. BAY K 8644 was more potent than CGP 28392. In the anaesthetized rat, neither verapamil (1 mg kg-1 i.v. 10 min before glucose) nor nicardipine (0.2 mg kg-1 i.v.) modified the glucose or insulin response to intravenous glucose whilst producing marked cardiovascular effects. The plasma concentrations of nicardipine (3.9 X 10(-8) M at 10 min post injection) were similar to those producing effects in-vitro whereas the plasma concentrations of verapamil (5 X 10(-7) M) were lower. It thus appears that the islet B cell calcium channel is less sensitive to calcium channel blocking drugs in-vivo than in-vitro. Moreover, in-vivo, the cardiovascular system is more sensitive to these drugs than are the islet B cells, although the potencies of the calcium channel blocking drug in isolated islets are similar to those reported for cardiac muscle and vascular smooth muscle in-vitro.

Tampon-associated toxic shock syndrome--a case report.

We report a case of tampon-associated toxic shock syndrome occurring in a 16-year-old girl. While this condition has been reported almost exclusively from the USA it is likely that TSS will be recognised elsewhere with increasing frequency as physicians become more aware of its existence. We consider that TSS must be considered in any hypotensive female in the reproductive age group with diarrhoeal illness.

Successful treatment of Graves disease in pregnancy with Lugol's iodine.

We report a case of Grave's disease in pregnancy complicated by intolerance of standard antithyroid drug therapy. We describe the success of prolonged use of organic iodine as a primary treatment prior to surgical intervention.

Addison's disease without pigmentation.

Four cases of Addison's disease are described in whom the diagnosis was unexpected or dangerously delayed because of the absence of pigmentation.

Endocrine studies in cyanotic congenital heart disease.

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.

Cushing's syndrome and autonomous thyroid nodules, a variant of multiple endocrine neoplasia?

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.

Transsphenoidal microsurgery for Cushing's disease.

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.

Do different frequencies of self-monitoring of blood glucose influence control in type 1 diabetic patients?

The effect of altering the frequency of self-monitoring of blood glucose upon blood glucose control was assessed in 25 Type 1 diabetic patients. Patients entered a balanced, crossover study in which they were randomly allocated to three 12-week periods. During each period the frequency at which patients self-monitored their blood glucose was: (1) four-point profiles on 2 days per week; (2) four-point profiles on 1 day per week; (3) two-point profiles on every day of the week. There were no significant differences in mean blood glucose concentration, fructosamine or glycosylated haemoglobin concentrations during the three periods. There was no correlation between the frequency at which patients altered insulin doses and measures of metabolic control. Altering the frequency of blood glucose self-monitoring had a variable and uncertain influence upon the frequency at which patients altered insulin doses. Some patients felt unsafe monitoring blood glucose only four times per week. There was however no patient consensus on the best-liked regimen.

Male hypogonadism--a non-specific consequence of illness.

Depressed thyroid hormone levels are commonly found in sick patients. Low serum testosterone concentrations have also been described in men suffering from a number of illnesses. To investigate whether this might be a non-specific marker of illness, various endocrine parameters were measured in 30 male patients in a general medical ward. Patients were suffering from a wide spectrum of medical disorders and were not receiving drugs known to affect endocrine function. Results were compared with a healthy age-matched control group. Serum testosterone concentrations (mean +/- SE) were low in the patient group (8.9 +/- 1.1 vs. 18.2 +/- 1.4 nmol/l, p less than 0.001), correlated significantly with serum T3 levels but were not related to prognosis. Half the patients had testosterone levels below the normal control range. Changes in testosterone concentrations could not be explained on the basis of binding protein changes, hyperprolactinaemia or depressed pituitary secretion of gonadotrophins. Depression of serum testosterone concentrations is a non-specific marker of illness.

Androgen levels in men with diabetes mellitus.

Patients in varying degrees of diabetic ketoacidosis had low serum testosterone levels which rose following recovery (5.4 +/- 1.3----13.7 +/- 1.7 nmol/l, p less than 0.02, mean +/- SE). Blood glucose control of 30 non-ketotic diabetic men (15 insulin-dependent and 15 non-insulin-dependent) did not correlate significantly with serum testosterone concentrations. Although previous authors had suggested that the adrenal androgen status of diabetic patients might be abnormal, adrenal androgens androstenedione and dehydroepiandrosterone sulphate (DHEAS) were similar in our 30 men to age-matched healthy men.

Endocrine responses to marathon running.

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.

Adrenal androgens and illness.

We have studied the adrenal androgen status of medically ill patients, patients before and after cholecystectomy and during recovery from burns injury. In patients ill for less than 2 weeks, serum androstenedione concentrations (mean +/- SEM) were raised (7.94 +/- 0.98 nmol/l) as compared with a control group (4.83 +/- 0.38 nmol/l, P less than 0.005) or with patients ill for more than 2 weeks (5.21 +/- 0.46 nmol/l, P less than 0.02); serum dehydroepiandrosterone sulphate (DHAS) levels were lower in patients ill for more than 2 weeks (1.21 +/- 0.42 mumol/l) than in either the acutely ill group (5.98 +/- 1.06 mumol/l, P less than 0.001) or the control ill group (5.56 +/- 0.59 mumol/l, P less than 0.001). In post-operative patients serum DHAS levels fell to below pre-operative levels reaching a nadir at day 8 (0.54 +/- 0.19 vs 1.66 +/- 0.56 mumol/l, P less than 0.02). In burned patients serum cortisol levels were increased on admission (661 +/- 91 vs 359 +/- 30 nmol/l, P less than 0.005) and remained high over the study period. Serum androstenedione concentrations were also high on admission (7.5 +/- 1.0 vs 3.9 +/- 0.3 nmol/l, P less than 0.02). Serum DHAS concentrations were similar to control values on admission (6.8 +/- 1.2 vs 5.2 +/- 0.7 mumol/l), fell to low levels thereafter reaching a nadir during week 3 (1.6 +/- 0.6 mumol/l, P less than 0.001). Steroid synthesis in times of chronic illness may be diverted from adrenal androgen to corticosteroid pathways ensuring maintained secretion of cortisol, which is essential to the health of ill patients.

Alteration of hormone levels in normal males given the anabolic steroid stanozolol.

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.

Trilostane and the normal hypothalamic-pituitary-adrenocortical axis.

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.

Effect of oral verapamil on glibenclamide stimulated insulin secretion.

In order to study the effect of the calcium antagonist, verapamil, on glibenclamide stimulated insulin release, nine healthy fasted male volunteers were given 5 mg oral glibenclamide with either 120 mg oral verapamil or placebo in a double-blind crossover manner 1 week apart. Blood was withdrawn at intervals for drug, hormonal and glucose estimations. Concomitant administration of verapamil resulted in higher levels of glibenclamide at each time point (P less than 0.01) suggesting that verapamil interferes with glibenclamide metabolism. However, levels of plasma glucose, C-peptide, insulin and glucagon did not differ between the verapamil and placebo studies.

A study of hypothalamic-pituitary-adrenal suppression following curative surgery for Cushing's syndrome due to adrenal adenoma.

The hypothalamic-pituitary-adrenal axis was investigated in all six patients requiring glucocorticoid replacement 2.5-11 years after unilateral adrenalectomy for adrenal adenomas causing Cushing's syndrome. The hypothalamic-pituitary-adrenal axis was assessed by insulin induced hypoglycaemia and CRF testing in each patient. Two patients showed normal cortisol and ACTH responses to hypoglycaemia. Two patients showed subnormal cortisol responses to hypoglycaemia in the presence of high or normal basal ACTH concentrations. ACTH concentrations increased with both hypoglycaemia and CRF. Two patients showed subnormal cortisol responses to hypoglycaemia and CRF. One of these patients showed an ACTH rise following hypoglycaemia but not CRF. Defects at either hypothalamic-pituitary or adrenal levels were demonstrated and recovery of the axis appears to commence at the hypothalamic-pituitary level.

Endocrine effects of examination stress.

1. We have studied endocrine function in nine healthy young men 16 weeks before and immediately after Final degree examinations. Factors other than psychological stress which might have affected hormone levels were excluded. 2. The presence of psychological stress at the time of examinations was confirmed by finding increased values for two self-rating anxiety scales. 3. Urine metadrenaline excretion was increased in all subjects at the time of examination. Serum and early morning urine cortisol as well as pituitary-testicular and pituitary-thyroid function and prolactin levels were unaffected by examination stress. 4. This study questions the popular belief that psychological stress stimulates prolactin secretion and suppresses pituitary-testicular function.