An unusual steroid-producing ovarian tumour: case report.

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.

Growth hormone and segmental growth in survivors of head and neck embryonal rhabdomyosarcoma.

AIMS: To assess the impact of treatment for embryonal rhabdomyosarcoma on spinal growth and limb length and examine the response of these parameters to growth hormone (GH) treatment. METHODS: We conducted a retrospective case note review of 17 survivors of head and neck rhabdomyosarcoma followed up at a single institution. All children had been treated with chemotherapy and local radiotherapy. Growth velocity, height, sitting height, and subischial limb length SDS scores were analysed. RESULTS: Growth failure secondary to isolated GH deficiency (GHD) developed in 7/17 patients. GHD occurred at a median (range) of 3.4 (1.3-9.9) years after radiotherapy tumour doses of 46 (40-50) Gy. Growth velocity, height, and subischial limb length SDS were significantly reduced in the GHD group and improved with GH therapy. CONCLUSIONS: GH treatment resulted in a significant improvement in sitting height SDS. We discuss the unexpected improvement in spinal growth in survivors with GHD.

Increased response of cortisol and ACTH to corticotrophin releasing hormone in centrally obese men, but not in post-menopausal women.

There is evidence for enhanced hypothalamo-pituitary-adrenal axis (HPAA) activity in centrally obese premenopausal women. This has led to the hypothesis that increased cortisol production rates may be an aetiological factor in the genesis of central obesity. However, the relationship of obesity and body fat distribution to HPAA activity in men and postmenopausal women has not been established. We carried out CRH tests in 13 men and 8 post-menopausal women. We measured 24 h urine cortisol metabolites prior to the CRH test in each subject, as an indication of cortisol production rate. There was a significant direct relationship between central obesity as measured by the ratio of subscapular:triceps skinfold thickness (STR)--and the ACTH/cortisol response to CRH in men, but not in postmenopausal women. There was no relationship between obesity or body fat distribution and 24h urine cortisol metabolites. This study provides evidence for hyperactivity of the HPAA in centrally obese men, but not in postmenopausal women.

Thyroid and sympathetic influences on plasma leptin in hypothyroidism and hyperthyroidism.

OBJECTIVES: To determine the dependence of plasma leptin concentrations upon circulating noradrenaline (NA) and thyroid hormones (TH) in humans. DESIGN: Cross-sectional study in 40 newly diagnosed untreated patients with primary thyroid disease, and 69 lean and obese euthyroid control subjects. MEASUREMENTS: Plasma leptin, NA, free T3 (fT3) and TSH in the fasting state. Anthropometry and % body fat (electrical bioimpedance). RESULTS: Leptin levels were highest in 37 obese euthyroid and 22 hypothyroid (median [interquartiles]31.5 [19.0- 48.0], 19.2 [11.5-31.5] ng ml(-1)), and lowest in 32 lean euthyroid and 18 hyperthyroid subjects (6.6 [3.9-14.4], 8.9 [5.5-11.1]; ANOVA, P< 0.0001). Plasma NA was similar in all groups (P= n.s.). In obese controls, TSH correlated with % body fat and leptin (r= 0.67, r= 0.61; P< 0.001). Treatment of hypothyroidism (n= 10) with T4 reduced leptin from 20.8 [11.8-31.6] to 12.9[4.6-21.2] (P= 0.005) with no change in BMI. CONCLUSIONS: Thyroid status modifies leptin secretion independently of adiposity and NA. The data suggest leptin-thyroid interactions at hypothalamic and adipocyte level.

Central obesity, depression and the hypothalamo-pituitary-adrenal axis in men and postmenopausal women.

OBJECTIVE: We examined the relationship of adiposity to pituitary-adrenal responses to corticotrophin-releasing hormone (CRH) in men and postmenopausal women, controlling for the influence of depression. DESIGN: Studies of CRH responses, cortisol metabolite levels and depression scores in relation to adiposity in men and postmenopausal women. SUBJECTS: Thirteen men: age (median, interquartile range) 62 y (52-63), body mass index (BMI) 29.0 kg/m2 (26.3-33.1), waist circumference (waist) 105 cm (97-111), waist:hip ratio (WHR) 1.03 (0.98-1.07), subscapular to triceps skinfold thickness ratio (STR) 2.0 (1.2-2.4), total body fat (TBF) 25.4 kg (19.8-28.8); and eight women: age 54 y (53-62), BMI 30 kg/m2 (23-41), waist 86 cm (79-117), WHR 0.94 (0.87-1.10), STR 1.0 (0.85-1.07), TBF 35.0 kg (18.7-48.8). MEASUREMENTS: A standard CRH test was conducted with additional basal samples taken for leptin and interleukin 6 (IL-6). Total urine cortisol metabolites (TCM) and the ratio of urinary cortisol:cortisone (Fm/Em) metabolites were measured. Depression scores were measured by the General Health Questionnaire (GHQ-30) and Hospital Anxiety and Depression Scale (HAD) questionnaire. All subjects completed an overnight dexamethasone suppression test. RESULTS: The basal to peak percentage increments (%inc.) in adrenocorticotrophic hormone (ACTH) and cortisol in men correlated directly with STR (ACTH %inc. r=0.70, P<0.01; cortisol %inc. r=0.55, P=0.05); this relationship was independent of depression scores. In women, the ACTH area under incremental curve (AUIC) correlated negatively with STR (r=-0.81, P<0.05). In men, but not in women, there was a significant correlation between GHQ-30 score and ACTH AUIC (r=0.62, P<0.05) and cortisol AUIC (r=0.72, P<0.01). Depression scores were consistently and directly related to indices of obesity and central obesity. There were no significant relationships in either sex between urinary TCM or Fm/Em ratio and BMI, waist, WHR, TBF, STR or CRH responses. The urinary Fm/Em ratio was higher in men than in women (median 0.74 vs 0.66, P<0.05). In men, but not in women, GHQ-30 scores correlated positively with urinary TCM (r=0.57, P=0.05) and HAD-depression scores were inversely related to the urine Fm/Em ratio (r=-0.65, P<0.05). All subjects suppressed normally with dexamethasone. CONCLUSIONS: Cortisol metabolite levels were increased in depression in men, but were not related to adiposity in either sex. We demonstrate that central obesity in men, but not postmenopausal women, is associated with an enhanced pituitary-adrenal response to CRH and that this relationship is independent of depression score. International Journal of Obesity (2000) 24, 246-251

An in vivo study of the cortisol-cortisone shuttle in subcutaneous abdominal adipose tissue.

OBJECTIVE: Previous in vitro studies have demonstrated significant 11-beta hydroxysteroid dehydrogenase (11 beta-HSD) oxo-reductase activity in visceral, but not subcutaneous adipose stromal cells. We have conducted an in vivo study of the cortisol-cortisone shuttle in subcutaneous abdominal adipose tissue. DESIGN: We measured arteriovenous (A-V) differences in serum cortisol and cortisone across subcutaneous abdominal adipose tissue and forearm muscle in a heterogeneous group of subjects. PATIENTS: We studied 34 subjects (male:female = 12:22), age median (interquartile range) 45 (19-65) years, body mass index 32.7 (20.4-77.1) kg m-2, total body fat 34.4 (5.6-119.1) kg. MEASUREMENTS: Serum cortisol and cortisone were measured in serum samples from a radial artery, superficial epigastric vein and deep forearm vein. Abdominal adipose and forearm blood flow rates were measured by 133Xenon washout and plethysmography, respectively. RESULTS: For cortisone, there was significant (P < 0.001) clearance by adipose tissue, with an A-V difference of 4 (1-7) nmol/l. For cortisol there was a trend for arterial concentrations (203 (142-292) nmol/l) to be lower than venous (225 (152-263) nmol/l), but this was not significant. The adipose tissue cortisone clearance rate correlated with total body fat (r = 0.35, P = 0.05). CONCLUSIONS: We have demonstrated 11 beta-HSD oxo-reductase activity in subcutaneous abdominal adipose tissue, which may be increased in obesity.

Assessing a murmur, saving a life: current trends in the management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy, formerly called idiopathic hypertrophic subaortic stenosis (IHSS), is the leading cause of sudden cardiac death in young people. Hypertrophic cardiomyopathy is a non-dilated cardiomyopathy primarily affecting the left ventricle, left atria, intraventricular septum, and mitral valve. It is an autosomal dominant genetic disorder that impairs diastolic and systolic function. Diagnosis is complex due to the heterogeneity of the disease. Symptoms and morphology are not always related and clinical signs may be absent or limited to a soft systolic murmur. The first symptom of hypertrophic cardiomyopathy is frequently sudden cardiac death. Echocardiogram is an accurate diagnostic tool. Asymptomatic patients are generally not treated. Treatment for symptomatic patients begins with beta or calcium channel blockers. Antiarrhythmics may be added to protect against sudden cardiac death. Surgical intervention is done if other treatments fall and involves removal of a portion of the obstructive septum. Operative mortality is 5% with a 60% reduction in symptoms. A promising alternative to surgery is dual-chamber pacemakers. Patient and family teaching is the emphasis of long-term management.

Acromegaly presenting with diabetic ketoacidosis.

Diabetes in acromegaly is usually non-insulin dependent and is secondary to insulin resistance caused by growth hormone excess. Diabetic ketoacidosis is a result of relative 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.

Imipenem/cilastatin therapy for serious bacterial infections.

Imipenem was administered intravenously with cilastatin to patients with suspected or documented significant infections. The mean peak serum level of imipenem 30 min after infusion of a 500 mg dose was 18.4 micrograms/ml, and the mean trough level (30 min before infusion) was 2.4 micrograms/ml. The organisms isolated before therapy included Enterobacteriaceae, Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and anaerobes. The response rate in 25 assessable patients was 96%, with 40% experiencing a complete cure and 56% improvement. Therapy failed in only one instance because an isolate of P. aeruginosa was mistakenly reported to be susceptible on disk testing. Toxicity in the 33 patients treated was generally minimal and included phlebitis, mild liver function abnormalities, eosinophilia, and thrombocytosis. The emergence of resistant organisms during therapy was very uncommon. Imipenem/cilastatin is a promising agent for the treatment of complicated infections.