Transsphenoidal surgery is a safe and effective treatment for Cushing's disease and our results compare favourably with those from published series, the majority of which comprise relatively small numbers. The presence of an intrasellar lesion and postoperative serum cortisol < 50 nmol/l are good predictors of remission in the long term but historically in our centre this can only be achieved in a significant number of patients at the expense of some degree of hypopituitarism. However, the surgical outcome for Cushing's disease, including a reduced frequency of hypopituitarism, can be improved if patients are operated on by a single pituitary surgeon, using selective adenomectomy as the preferred surgical approach wherever possible.

Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 microg, 3 times daily, increased to 200 micro g three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 microg/liter). Five-point GH profiles were performed at 0, 4, 12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk. The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During sc Oct, serum GH fell to less than 5 mU/liter in 9 patients (38%), and IGF-I fell to normal in 8 patients (33%). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49% (range, 12-73), and for macroadenomas it was 43% (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/liter in 11 of 14 patients (79%), and IGF-I was normal in 8 of 15 patients (53%). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24%. At the end of the study 79% of patients had mean serum GH levels below 5 mU/liter, 53% had normal IGF-I levels, and 73% showed greater than 30% tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 microg/liter).

Gestational diabetes is carbohydrate intolerance, with onset or first recognition of hyperglycaemia during pregnancy. Several studies have suggested that gestational hyperglycaemia is associated with adverse maternal and fetal outcomes, promoting the case for screening. Conversely, others argue that screening for gestational diabetes may colour the clinical judgement, influencing further management, e.g. more 'unjustified' caesarean sections. Additionally, the lack of definitive data either on a clear-cut glycaemic threshold for the development of adverse outcomes or on the impact of intervention is emphasized by opponents of screening. This review attempts to evaluate the available data on screening for gestational diabetes. Oral glucose tolerance test is promoted on the basis that the diabetogenic stress of pregnancy is encountered during late gestation and is best recognized in the fed state. There are different tests, including the 1 h/50-g, 2 h/75-g and 3 h/100-g tests, with practical limitations, including the time and cost involved and the unpleasant supra-physiological glucose load that is unrelated to body weight, and issues of reproducibility and sensitivity/specificity profiles. Despite its convenience, the poor sensitivity of random glucose has precluded its routine use for screening. Fasting glucose appears to be promising but further testing is required to ensure satisfactory sensitivity/specificity in different populations. Despite its limitations, the oral glucose tolerance test has become established as the 'most acceptable' diagnostic test for gestational diabetes. More convenient methods, e.g. fasting or random or post-load glucose, have to be validated therefore against the oral glucose tolerance test to gain acceptance for routine screening.

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OBJECTIVE We previously showed that in patients with diabetes mellitus, glycated hemoglobin (HbA1c) monitoring outside international guidance on testing frequency is widespread. Here we examined the relationship between testing frequency and diabetes control to test the hypothesis that retest interval is linked to change in HbA1c level. RESEARCH DESIGN AND METHODS We examined repeat HbA1c tests (400,497 tests in 79,409 patients, 2008–2011) processed by three U.K. clinical laboratories. We examined the relationship between retest interval and 1) percentage change in HbA1c and 2) proportion of cases showing a significant HbA1c rise. The effect of demographics factors on these findings was also explored. RESULTS Our data showed that the optimal testing frequency required to maximize the downward trajectory in HbA1c was four times per year, particularly in those with an initial HbA1c of ≥7% (≥53 mmol/mol), supporting international guidance. Testing 3-monthly was associated with a 3.8% reduction in HbA1c compared with a 1.5% increase observed with annual testing; testing more frequently provided no additional benefit. Compared with annual monitoring, 3-monthly testing was associated with a halving of the proportion showing a significant rise in HbA1c (7–10 vs. 15–20%). CONCLUSIONS These findings provide, in a large, multicenter data set, objective evidence that testing outside guidance on HbA1c monitoring frequency is associated with a significant detrimental effect on diabetes control. To achieve the optimum downward trajectory in HbA1c, monitoring frequency should be quarterly, particularly in cases with suboptimal HbA1c. While this impact appears small, optimizing monitoring frequency across the diabetes population may have major implications for diabetes control and comorbidity risk.

BACKGROUND:Estimates suggest that approximately 25% of requests for pathology tests are unnecessary. Even in diabetes, for which international guidance provides recommended testing frequency, considerable variability in requesting practice exists. Using the diabetes marker, Hb A 1c , we examined (a) the prevalence of under-and overrequesting, (b) the impact of international guidance on prevalence, and (c) practice-to-practice variability.

Abbreviations 21 DNA

Pheochromocytomas (PCCs) are rare catecholamine producing neuroendocrine tumors. The majority of these tumors (85 %) arise from the adrenal medulla. Those arising from the extra-adrenal neural ganglia are called paragangliomas (PGLs). Paroxysmal hypertension with sweating, headaches and palpitation are the usual presenting features of PCCs/ PGLs. Gene mutations are reported in 32-79 % of cases, making genetic screening mandatory in all the cases. The malignancy rates are 10-15 % for PCCs and 20-50 % for PGLs. Measurement of plasma or 24-hour urinary fractionated metanephrines is the best biochemical diagnostic test. Computed tomography or magnetic resonance imaging has high sensitivity (90-100 %) and reasonable specificity (70-90 %) for the anatomical localization. The functionality is assessed by different radionuclide imaging modalities such as metaiodobenzylguanidine (MIBG) scintigraphy, positron emission tomography or single photon emission computed tomography. The only modality of curative treatment is tumor excision. Proper peri-operative management improves the surgical outcomes. Annual follow up with clinical and biochemical assessment is recommended in all the cases after treatment. Children, pregnant women and older people have higher morbidity and mortality risk. De-bulking surgery, chemotherapy, radiotherapy, molecular agents like sunitinib and everolimus, radionuclide agents and different ablation procedures may be useful in the palliation of inoperable/metastatic disease. An update on the diagnostic evaluation and management of PCCs and PGLs is presented here.