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A DNA sequence polymorphism, revealed by digestion of human DNA with the restriction endonuclease Sst-1 and hybridization with an apolipoprotein A-I complementary DNA clone, has been shown to be located in or close to the 3' noncoding region of the apolipoprotein C-III gene. This polymorphism is found in significantly increased prevalence (P < 0.001) in Caucasian hypertriglyceridemic subjects compared with race-matched controls, and its distribution in normal individuals of differing racial origins is reported. Furthermore, no alteration of high density lipoprotein or apolipoprotein A-I and apolipoprotein C-III phenotypes was observed in individuals with or without the polymorphism.

The rapid onset of virilization in a post-menopausal woman is usually the result of androgen secretion from a tumour of adrenal or ovarian origin. Androgen secreting neoplasms of the ovary are rare and usually show autonomous secretion. Rarely, these may be driven by the high levels of gonadotrophins seen in the post-menopausal state. We describe the case of a 67-year-old woman with high serum testosterone and estradiol in association with the high gonadotrophin levels usually associated with the post-menopausal state. All hormonal parameters showed a significant suppression over 12 h with administration of the GnRH antagonist, cetrorelix. This observation implies that excess hormone synthesis was of ovarian origin and was gonadotrophin driven. Localization of the tumour was not possible by conventional ultrasound or computerized tomography scanning, but was achieved by venous sampling. Complete cure was achieved by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with restoration of the endocrine profile to that expected for a post-menopausal woman. Rapidly acting GnRH antagonists, such as cetrorelix, offer a safe and useful diagnostic and therapeutic option in the management of ovarian steroid-secreting tumours, which show gonadotrophin dependency.

SummaryDiabetes in acromegaly is usually noninsulin dependent and is secondary to insulin resistance caused by growth hormone excess. Diabetic ketoacidosis is a result ofrelative insulin deficiency and is a rare feature of acromegaly. We describe a case of acromegaly presenting with diabetic ketoacidosis. We demonstrate that growth hormone excess can cause diabetic ketoacidosis in the presence of relative, but not absolute insulin deficiency.Keywords: acromegaly, diabetic ketoacidosis, insulin resistance A 40-year-old man was admitted as an emergency with a one-month history of thirst, polyuria and weight loss of 7 kg. On direct questioning, the patient admitted to an increase in the size of his head, hands and feet over the last year. Friends had recently failed to recognise him. On examination, he was clearly acromegalic, severely dehydrated and exhibiting Kussmaul's respiration. Investigations revealed 3+ ketonuria on urinalysis. Blood glucose was 29.1 mmol/l, plasma bicarbonate 7 mmol/l, sodium 132 mmol/l, potassium 3.7 mmol/l, glycosylated haemoglobin (HbAl) 15.0%. Arterial blood gases pH 7.10, pCO2 1.0 kPa, base excess 27 mmolIl.Following the diagnosis of diabetic ketoacidosis, he was treated with an intravenous insulin infusion and fluids containing potassium supplements. Satisfactory diabetic control was achieved with 52 units of Human Mixtard insulin 30 ge daily, given subcutaneously in divided doses. The diagnosis of acromegaly was confirmed by the finding of a raised basal growth hormone level of 37.1 mU/ 1, increasing after a 75-g oral glucose load to >120 mU/l at 30 minutes and 66.2 mU/l at 120 minutes. The corresponding glucose and insulin measurements are shown in the figure and show significant levels of insulin but a flat response to the glucose load.There was evidence of hypogonadotrophic hypogonadism (luteinising hormone <1.0 IU/1, follicle-stimulating hormone 2.7 IU/1, testosterone 1.7 nmol/l), but levels of thyroidstimulating hormone (0.9 mU/l), prolactin (125

A genetic marker identifying the two parental insulin genes has been studied in 51 Caucasian acromegalics by Southern blot hybridization techniques using a cloned insulin gene probe. Two main DNA insertion classes were detected corresponding to the class 1 and class 3 alleles and thus the following genotypes were found: 1/1, 1/3 and 3/3. The acromegalics were subdivided depending on whether they had a normal (n = 30) or abnormal (n = 21) response to a 50 gm oral glucose tolerance test before treatment. The phenotype frequencies in the former group were 1/1, 43%; 1/3, 53%; and 3/3, 4%; and in the latter group the corresponding figures were 76%, 24% and 0%. The relative incidence of concordance of the phenotype 1/1 with abnormal glucose tolerance in acromegaly was 4.2. This phenotype is also associated with insulin dependent (Type 1) diabetes mellitus.