Concomitant myasthenia gravis and macroprolactinoma: the immunomodulatory role of prolactin and its potential therapeutic use.

Considerable evidence attests to the role of the hypothalamic-pituitary endocrine axis (HPA) in the maintenance of normal immunocompetence. The immune and neuroendocrine systems are integrally linked and coordinated with bidirectional communication maintaining immune balance. Any disturbance of the normal function of the HPA may significantly alter native immunocompetence and therefore be associated with the development of disorders which have a clearly established autoimmune basis. Molecular and functional evidence shows prolactin, produced by the anterior pituitary, to be a cytokine, exerting its effect via both paracrine and endocrine mechanisms [1]. Its involvement in the activation of multiple immune responses may adversely upregulate certain autoimmune diseases. Myasthenia gravis (MG) has long been recognized as an autoimmune disorder. In this mini review, we present the coterminous presentation of MG and prolactin-secreting macroadenoma. We review published cases in the world literature, discuss pathological mechanism, and consider future targeted therapies.

The novel use of commonly captured data to assess a district's diabetes service that encompasses both primary and secondary care.

AIM: To identify commonly captured data in the UK to look at the performance of a district's diabetes care that encompasses both primary and secondary care. METHODS: Primary care quality outcomes framework (QOF) measures for diabetes, referral rates for first appointment for specialist secondary care and emergency admission rates for diabetes (Dr Foster/HES) were used to produce a performance index scoring system. Illustrative measures from QOF were total diabetes points, DM23 attainment of HbA1c <7% (53 mmol/mol) and its exemption rate (number of patients excluded from analysis). The performance index was used to study the effectiveness of the Medway district diabetes service and this was compared to another district (Guildford) within the same Strategic Health Authority and nationally. RESULTS: Medway has the highest prevalence of Diabetes (6.1%) of the 8 Primary Care Trusts examined, the lowest achievement of diabetes QOF points (96.1%) and the lowest achievement of an HbA1c level <7% (53 mmol/mol) (54.3%). Exemption reporting was the 3rd highest. SAR for first diabetes out-patient appointment to the hospital was low at 281 (predicted 576) 48% of expected. The emergency admission rate was high at 225 (predicted 168) 133% of expected. Thus primary care diabetes needs to raise performance and implement a lower threshold for OPD referral to prevent emergency admissions. CONCLUSION: It is possible to produce an assessment of diabetes care that transcends primary/secondary care that gives a true reflection of a district's performance which will be useful to plan future health service provision.

The effect of starvation on leucine, alanine and glucose metabolism in obese subjects.

The relationship between changes in ketone concentrations and leucine metabolism (seven obese subjects), glucose and alanine metabolism (seven obese subjects) was investigated using radioisotopic techniques after 12 h, 60 h and 2 weeks starvation. Leucine metabolism was also measured in five lean subjects after 12 h and 60 h starvation. In the obese subjects leucine concentration increased after 60 h starvation and leucine metabolic clearance rate, glucose and alanine concentration decreased (P < 0.05). Glucose and alanine production rate (Ra) decreased after 2 weeks (P < 0.05) but there was no change in leucine Ra after 60 h or 2 weeks. In the lean subjects leucine concentration, production rate and oxidation rate were increased after 60 h (P < 0.005, P < 0.05, P < 0.05). Ketone concentration was inversely related to alanine Ra (r = -0.51, P < 0.02) but was not related to measurements of protein metabolism in the obese subjects. This study demonstrates that the effect of short-term starvation on protein metabolism differs in lean and obese subjects. The decrease in glucose Ra during long-term starvation may be in part due to a decreased supply of alanine for gluconeogenesis.

Leucine metabolism in patients with Cushing's syndrome before and after successful treatment.

OBJECTIVE: Results from studies on the effect of glucocorticosteroids on protein turnover in both rat and man have been conflicting. The aim of this study was to investigate the primary cause of muscle wasting in patients with Cushing's syndrome. DESIGN: Studies of whole body 1(-14)C-leucine turnover in patients with Cushing's syndrome before and after successful treatment, and in control subjects. PATIENTS: Eleven patients with Cushing's syndrome before and after (n = 5) treatment and 11 control subjects. MEASUREMENTS: Whole body 1(-14)C-leucine turnover to determine leucine metabolic clearance rate, leucine production rate, leucine oxidation rate and leucine incorporation into protein. RESULTS: Plasma leucine concentration (mean +/- SEM 100 +/- 6 mumol/l), leucine metabolic clearance rate (9.97 +/- 0.11 mumol/min/kg), leucine turnover (0.98 +/- 0.11 mumol/min/kg) and leucine incorporation into protein (0.71 +/- 0.09 mumol/min/kg) were all significantly reduced in patients with Cushing's syndrome compared with control subjects (122 +/- 6 mumol/l, P < 0.05; 13.61 +/- 1.27 mumol/min/kg, P < 0.05; 1.65 +/- 0.12 mumol/min/kg, P < 0.05; 1.46 +/- 0.10 mumol/min/kg, P < 0.001, respectively). Leucine oxidation rate was similar in the patients with Cushing's syndrome and control subjects. When leucine metabolism was expressed in terms of lean body mass (LBM) in five patients with Cushing's syndrome and 11 control subjects, leucine MCR, leucine turnover and leucine oxidation were not significantly different in the two groups. However, leucine incorporation into protein was significantly reduced (P < 0.001) in the patients with Cushing's syndrome (1.07 +/- 0.20 mumol/min/kg LBM) compared with control subjects (1.95 +/- 0.11 mumol/min/kg LBM). CONCLUSION: We conclude from these studies that the muscle wasting associated with Cushing's syndrome is primarily due to a reduction in protein synthesis.

Glucose metabolism in patients with Cushing's syndrome.

Glucose intolerance, sometimes severe enough to cause frank diabetes mellitus, is a frequent feature of Cushing's syndrome. The primary cause of the hyperglycaemia, whether due to glucose over-production or under-utilization, remains unresolved. We therefore measured glucose turnover using an intravenous bolus of 3-3H glucose in 14 normoglycaemic patients with Cushing's syndrome and 14 control subjects. Seven of the patients with Cushing's syndrome were also restudied post-operatively. Plasma glucose concentrations were similar in all three groups whereas glucose metabolic clearance rate (MCR) (1.80 +/- 0.06 ml/min/kg) and glucose turnover rate (9.09 +/- 0.36 mumol/min/kg) were significantly reduced in patients with Cushing's syndrome compared to normal subjects (2.21 +/- 0.1; P less than 0.001; 10.90 +/- 0.50; P less than 0.01) and rose post-operatively to normal values (2.35 +/- 0.14 ml/min/kg; 11.07 +/- 0.48 mumol/min/kg). We conclude from these results that the hyperglycaemia sometimes found in Cushing's syndrome may be primarily due to decreased utilization rather than increased glucose production.

Diurnal variation in glucose and leucine metabolism in non-insulin-dependent diabetes.

Glucose and leucine metabolism were investigated in 5 poorly controlled non-insulin-dependent diabetics (NIDDM) following an i.v. injection of 3-[3H]glucose and 1-[14C]leucine in the morning and evening. In the morning glucose concentration (11.2 +/- 0.8 mmol/l) (mean +/- SEM) and production rate (14.2 +/- 1.3 mumol/min/kg) were significantly greater (P less than 0.001, P less than 0.05) and glucose metabolic clearance rate (MCR) (1.3 +/- 0.2 ml/min/kg) significantly lower (P less than 0.05) than in a group of control subjects. Glucose concentration was lower in the evening (P less than 0.05) as a result of a decrease in glucose production rate (P less than 0.05). Leucine concentration and production rate were not significantly different from normal but leucine oxidation rate was increased (P less than 0.05). There was no diurnal variation in leucine metabolism. Since leucine production is a measure of protein breakdown, the higher morning glucose production rate was not due to an increased supply of gluconeogenic precursors from protein catabolism.

The effect of a high protein diet on leucine and alanine turnover in acid maltase deficiency.

Leucine and alanine production rate was measured in 5 patients with acid maltase deficiency in the postabsorptive state, following 6 months on a normal diet with placebo and 6 months on an isocaloric high protein diet (16-22% protein). Whole body leucine production rate, a measure of protein degradation, expressed in terms of lean body mass was significantly greater than in five control subjects. Following the high protein diet, leucine production rate was decreased in four of the five patients but this was not statistically significant. Alanine production rate expressed in terms of lean body mass was significantly greater than in control subjects. After the high protein diet, alanine production rate and concentration were significantly decreased (p less than 0.05). There were no significant improvements in any of the clinically relevant variables measured in these patients. It is possible that a larger increase in protein intake over a longer time period may have a clinical effect.

Use of memory meters to measure reliability of self blood glucose monitoring.

Glucose reflectance meters equipped with memories were used in 21 insulin-dependent diabetic patients to assess reliability of self blood glucose monitoring records. Results reported in logbooks showed widespread discrepancies when compared with corresponding meter-held records. Discrepancy rates of at least one in five were observed in 11 patients. Unreliable reporting was usually recognized by clinical staff, and associated with high glycosylated haemoglobin levels and poor technique in measuring blood glucose at home.

Intracerebral metastases from ocular melanoma.

A blind painful eye may harbour an unsuspected malignant melanoma. We report a case of ocular melanoma that presented with confusion owing to direct extension via the optic nerve into the anterior cranial fossa.

Protein turnover in acid maltase deficiency before and after treatment with a high protein diet.

A patient with acid maltase deficiency was treated with a high protein diet for 7 months. Protein turnover expressed in terms of lean body mass was shown to be increased in this patient before the diet but was markedly reduced following the diet. The patient improved clinically whilst on the diet both subjectively and in terms of mobility, breathing and reduced peripheral cyanosis at rest.

Supersensitivity to both tyramine and noradrenaline in diabetic autonomic neuropathy.

Cardiovascular responses to intravenously infused tyramine and noradrenaline were measured in five normal subjects, five insulin-dependent diabetics and five insulin-dependent diabetics with autonomic neuropathy. Tyramine infusion produced a statistically significant increase in systolic blood pressure (BP) in the autonomic neuropaths only (p less than 0.001). No change occurred in diastolic BP. Noradrenaline infusion produced a statistically significant increase in systolic BP in the normal subjects (p less than 0.01) and in the autonomic neuropaths (p less than 0.001). The increase in systolic BP in the neuropaths was significantly greater (p less than 0.001) than in normal subjects. Diastolic BP rose significantly only in the normal subjects (p less than 0.05). There was no change in heart rate in response to either agent. Thus super-sensitivity to noradrenaline occurred in patients with diabetic autonomic neuropathy indicating post-denervation hypersensitivity. Tyramine hypersensitivity also occurred indicating that denervation is not complete and suggesting dysfunction at a pre-synaptic level.

A comparative study of the effects of ranitidine and cimetidine on carbohydrate tolerance, growth hormone secretion and the hypothalamic-pituitary-gonadal axis in man.

The effect of chronic oral administration of cimetidine (1 g per day) and ranitidine (300 mg per day) on plasma levels of prolactin (PRL), testosterone, dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG) and human growth hormone was compared in 2 groups of male patients who presented with dyspeptic symptoms. Eight were treated with ranitidine and 9 with cimetidine for 4 weeks. The glucose and insulin response to a 100 g oral glucose load was also assessed. Cimetidine treatment resulted in a significant increase in plasma testosterone levels which was not found in the ranitidine group. No significant change occurred in PRL, LH, FSH, SHBG, DHT and growth hormone. There was no evidence of a significant alteration in carbohydrate metabolism.

Extending the range of blood glucose measurements with Dextrostix and a reflectance meter.

The useful range of blood glucose measurements with Dextrostix can be extended by varying the incubation time and making appropriate corrections to the observed values.