Excessive secretion of insulin precursors characterizes and predicts gestational diabetes.

Using assays that specifically measure insulin, intact proinsulin, and 32,33 split proinsulin, we examined the beta-cell secretory response to an oral glucose tolerance test (OGTT) in 64 women with gestational diabetes mellitus (GDM) and 154 pregnant normoglycemic control subjects of comparable age and body mass index. Women with GDM were characterized by a lower 30-min insulin increment (40.8 [34.9-47.6] vs. 58.6 [53.6-64] pmol insulin/mmol glucose, P < 0.001; geometric mean [95% confidence interval]) and a higher plasma insulin level at 120 min (702 [610-808] vs. 444 [400-492] pmol/l, P < 0.001). 32,33 split proinsulin levels were elevated in GDM patients in both fasting (9.1 [7.3-11.4] vs. 6.7 [6.0-7.5] pmol/l, P < 0.02) and 120-min (75.2 [62.9-90.0] vs. 52.2 [46.7-58.3] pmol/l, P < 0.001) samples, respectively. Intact proinsulin levels were significantly elevated at 120 min in the women with GDM (21.3 [18.1-25.1] vs. 14.8 [13.4-16.3] pmol/l, P < 0.001). Thus, the qualitative abnormalities of insulin secretion in GDM patients (low 30-min insulin increment, high 120-min plasma insulin, and elevated 32,33 split proinsulin) are similar to those seen in nonpregnant subjects with impaired glucose tolerance. To determine whether measures of proinsulin-like molecules (PLMs) might assist in the prediction of GDM, women who had a 1-h glucose level of > 7.7 mmol/l after a 50-g glucose challenge at 28-32 weeks' gestation had insulin and PLMs measured in the 1-h sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Post-traumatic hypopituitarism. Six cases and a review of the literature.

The typical patient with post-traumatic hypopituitarism is a young adult male presenting months to years after an automobile accident, following which he was unconscious for several days. He will probably have sustained a fracture of the base of the skull and on recovery is likely to have permanent visual or other neurological sequelae. Temporary or permanent diabetes insipidus may have occurred. The features of panhypopituitarism such as weight loss, fatigue, faintness, loss of libido, and impotence may have been ascribed to depression or the "postconcussion syndrome" and often inappropriate treatment and rehabilitation advised. The striking feature on review of the literature is that the pathological consequences of head injury to the pituitary and hypothalamus have been well described, while only 47 cases of traumatic hypopituitarism have been reported. The most likely reason for this disparity is that head injury of sufficient severity to cause hypothalamic and pituitary damage commonly led to death. More patients now survive, owing to the availability of intensive care; accordingly, most cases have been reported in the last 15 years. However, several patients are described in whom the initiating head injury was not associated with a skull fracture or followed by coma. We recommend that patients with major head injury (defined by post-traumatic amnesia greater than 24 hours), and in particular those with fractures of the base of the skull or diabetes insipidus should be closely monitored for symptoms and signs of endocrine dysfunction and appropriate dynamic pituitary-function tests performed.

The efficacy and safety of lanreotide Autogel in patients with acromegaly previously treated with octreotide LAR.

OBJECTIVE: Lanreotide Autogel is a sustained-release aqueous gel formulation supplied in a prefilled syringe, with injection volume <0.5 ml. The aim of this study was to establish the efficacy and safety of Autogel in patients with acromegaly previously treated with octreotide LAR. DESIGN: A 28-week, open, multicentre study. PATIENTS: Twelve patients with acromegaly, treated with 20 mg octreotide LAR for >4 months, with serum GH levels <10.0 mU/l. METHODS: Autogel (90 mg) was given every 28 days during weeks 0-12. At week 16 the dose was titrated based on GH levels at weeks 8 and 12. If GH levels were <2.0, 2.0-5.0, or >5.0 mU/l, Autogel was reduced to 60 mg, maintained at 90 mg, or increased to 120 mg respectively, for the next three injections. GH and IGF-I levels were reassessed at weeks 24 and 28. RESULTS: Ten patients completed the study. Five remained on 90 mg Autogel throughout the study; in two patients the dose was reduced to 60 mg from week 16; in three patients it was increased to 120 mg. Mean GH levels were: baseline, 3.0+/-1.7 mU/l; week 12, 3.5+/-1.8 mU/l; week 28, 3.3+/-1.6 mU/l (NS). Mean IGF-I levels were: baseline, 212+/-70 microg/l; week 12, 185+/-91 microg/l; week 28: 154+/-61 microg/l (P=0.027). Six patients at baseline and eight at week 28 had normalised GH and IGF-I levels. Three patients reported adverse events: musculoskeletal pain (n=2) and injection-site symptoms (n=1). CONCLUSIONS: Lanreotide Autogel is effective and well tolerated in patients with acromegaly. This study in a small group of patients with well-controlled acromegaly suggests that the majority of patients switched from 20 mg LAR to 90 mg Autogel will have equivalent or better disease control.

Thyroid stimulating hormone measurement by an ultrasensitive assay during thyroxine replacement: comparison with other tests of thyroid function.

Serum thyroid stimulating hormone (TSH) was measured using a highly sensitive enzyme-amplified immunoassay in 37 clinically euthyroid patients receiving thyroxine replacement therapy and compared with other biochemical tests of thyroid function. A highly significant correlation (P less than 0.001) was found between the basal serum TSH and the increase in serum TSH concentration 20 min after the administration of thyrotropin releasing hormone (TRH). The basal serum TSH was negatively correlated with the serum total thyroxine (P = 0.05). When patients results were classified as abnormal or normal many discrepancies were noted between the various thyroid tests. A suppressed serum TSH was found in 65% of patients with a normal serum total thyroxine. However, in patients on thyroxine replacement therapy a basal TSH measured by enzyme-amplified immunoassay provides the same information as a TRH test.

The management of thyroid disease in pregnancy.

The management of hyperthyroidism and hypothyroidism in pregnancy is discussed and illustrated with appropriate cases. The dangers of the usage of high doses of antithyroid drugs and of propranolol are described.

Postural fluid retention in patients with idiopathic oedema: lack of relationship to the phase of the menstrual cycle.

1. Water and electrolyte excretion was measured in the follicular and luteal phases of the menstrual cycle in seven patients with idiopathic oedema and in four post-menopausal patients with this condition. 2. In contrast to previous findings in healthy women, the reduction in urinary flow and sodium excretion on being tilted to the upright position was not significantly different in the follicular and luteal phases in pre-menopausal patients and there were no significant differences between pre- and post-menopausal patients. 3. The percentage increase in packed cell volume on standing was significantly greater in patients with idiopathic oedema than in normal subjects in the luteal phase of the menstrual cylcle. 4. It is postulated that the enhanced retention of electrolytes and water in response to tilting in patients with idiopathic oedema is a compensatory mechanism for the decreased effective blood volume at that time.

Idiopathic oedema: a study of the effects of bromocriptine.

We have studied the effect of bromocriptine in seven patients with idiopathic oedema. Two patients were unable to tolerate the drug; the remaining five were maintained on doses of between 5 and 7.5 mg a day. Symptomatic improvement was noted in two patients and in both of these and one other there was a significant improvement in mean diurnal weight gain. The fall in free water and sodium clearance on standing was reduced by bromocriptine, but there was no significant change in the excessive fall in plasma volume.

Idiopathic oedema of women. A clinical and investigative study.

A clinical and investigative study is reported of 19 patients with 'idiopathic oedema of women'. The resons for defining this as a specific syndrome unrelated to the menstrual cycle are given, and the clinical features reviewed. During a forced water diuresis the flow and composition of the urine and the plasma volume were studied on tilting from the supine to the upright position seven premenopausal and four postmenopausal patients with this disorder. No differences were found in the results obtained in the follicular and luteal phases of the menstrual cycle or in the pre- and post-menopausal patients. The reductions in urinary volume and electrolyte excretion on upright tilting were greater than those observed under similar circumstances during the luteal phase of the menstrual cycle in normal female controls, and attributed to increased proximal renal tubular reabsorption. The rate of loss of isotopically labelled albumin from the intravascular compartment was greater in patients with idiopathic oedema than in control subjects. A reduction in blood volume on tilting occurred in control subjects and patients with idiopathic oedema, but was greater in the latter; and the larger the fall, the greater were the reductions in urinary flow and electrolyte excretion. The effect of administering 9-alpha-fluorohydrocortisone was studied in nine patients with idiopathic oedema. One patient failed to 'escape' from the sodium-retaining action of this mineralocorticoid and developed pulmonary oedema; the others 'escaped' normally. The pathophysiological disturbance in this condition is related to increased loss of fluid from the vascular compartment but the precise aetiological mechanism remains unknown.

Insulin oedema and its clinical significance: metabolic studies in three cases.

Three patients with insulin-dependent diabetes mellitus are described in whom generalized oedema and weight gain followed the administration of excessive monocomponent insulins, in two cases associated with symptomatic hypoglycaemia. Serial measurements of plasma volume and transcapillary escape rate of albumin (TERA) using 125I-labelled albumin, serum colloid osmotic pressure (COP) using a membrane colloid osmometer, packed cell volume (PCV), and serum proteins, showed that oedema was associated with an increased plasma volume and TERA, while serum albumin and total protein concentration and serum COP were reduced. A reduction in daily insulin dose abolished hypoglycaemia and resulted in weight loss, natriuresis, diuresis, a reduction in plasma volume and TERA, and an increase in serum albumin, total protein, and COP. Strict metabolic control in previously poorly controlled patients may cause insulin-induced increments in plasma volume and albumin escape rate.

Mild hypothyroidism and oedema: evidence for increased capillary permeability to protein.

Nine female patients with normal serum total thyroxine (T4) and triiodothyronine (T3) but elevated thyroid stimulating hormone (TSH) levels were studied. Six patients had generalised oedema associated with maximal diurnal weight gains in excess of 1.4 kg. Under conditions of forced water diuresis, before and during physiological replacement of 1-thyroxine, the supine transcapillary escape rate of albumin (TERA) was measured, while the venous colloid osmotic pressure (COP), packed cell volume (PCV) and urinary excretion of water and electrolytes were studied in both the supine and upright positions. The TERA, diurnal weight gain and orthostatic increase in COP fell significantly with treatment. In the six patients with oedema and excessive diurnal weight gains, the retention of salt and water on tilting was reduced with thyroxine treatment. In female patients we consider generalised oedema associated with excessive diurnal weight gain, to be a common and early symptom of hypothyroidism, meriting thyroxine replacement therapy.

Autoimmune thyroid disease and the polymyalgia rheumatica-giant cell arteritis syndrome.

In a study of 250 patients with autoimmune thyroid disease, seven (2.8%) were found to have polymyalgia rheumatica or giant cell arteritis. All cases occurred in female patients over the age of 60 years, a prevalence in this group of 9.3%. No cases of either disorder were seen in a control population of 150 female patients over the age of 50 years attending a cardiac clinic at the same hospital. Awareness of this association may allow earlier diagnosis and treatment of this syndrome in elderly patients with thyroid disease.

Hypothalamic hypogonadism following major head injury.

Endocrine studies, using the four hypothalamic releasing hormones, gonadotrophin releasing hormone, thyrotrophin releasing hormone, corticotrophin releasing hormone and growth hormone releasing hormone, were performed in 33 males after admission with a major head injury. The test was repeated 7 days later in all 33 patients and after 3-6 months in 21 patients. All patients had a period of unconsciousness followed by post-traumatic amnesia of greater than 24 h. The results obtained from investigating the gonadal axis are reported in this paper. The levels of total and free testosterone, basal FSH and basal LH fell significantly during the first 3 days after injury, when the LH and FSH responses to GnRH achieved their highest peak levels. This hormone pattern has not previously been reported in the gonadal axis and may be a consequence of hypothalamic dysfunction. The severity of the injury was negatively correlated to the testosterone concentration on admission and to the basal and peak FSH concentrations 1 week later. Persistent hypogonadism was found in five of the 21 patients retested after 3-6 months, with low testosterone concentrations and three continued to have an exaggerated LH response to GnRH. Thus major head injury frequently results in hypogonadism shortly after injury, with an increased gonadotrophin response to GnRH. In addition, a substantial minority of patients continue to be hypogonadal after 3-6 months. In view of these findings we strongly suggest that all patients should be endocrinologically assessed at intervals following severe head injury.

Toxic shock: clinical presentation and management. II.

The management of toxic shock syndrome poses a challenge to clinicians because the syndrome has only been recently recognized and new complications are still being described. This report describes the major complications which arose in our case and highlights a severe bleeding disorder which was the cause of the patient's death. The bleeding disorder was characterized by normal in vitro coagulation screens, normal platelet aggregation tests, but prolonged skin bleeding time. It was not improved by haemodialysis, platelet transfusion or steroid therapy. We conclude that in cases with severe toxaemia, despite early recognition and appropriate treatment, there is still no effective method of preventing complications. Current avenues for investigation include plasmapheresis, the administration of fresh frozen plasma, and the development of a specific anti-toxin.