Sirazum Choudhury

Gastrointestinal hormones and their role in obesity.

Purpose of reviewPandemic obesity is the most pressing health issue of this century. The most successful treatment so far is bariatric surgery, but for various reasons, surgery cannot be applied to all patients who require treatment. Gastrointestinal hormones are likely to play a key role in the success of bariatric surgery. This article examines in detail three of these gut hormones: peptide YY, oxyntomodulin and pancreatic polypeptide, and reviews how recent developments may offer new targets for therapy. Recent findingsBoth the free fatty acid 2 and the melanocortin 4 receptors have been discovered to regulate peptide YY and glucagon-like peptide-1 secretion, and drugs targeting these may represent new antiobesity therapies. Dual agonism of glucagon-like peptide-1 and glucagon receptors, for example with oxyntomodulin, has synergistic effects in reducing appetite and increasing energy expenditure. Plasma pancreatic polypeptide concentration correlates with visceral adiposity, and may serve as a biomarker for metabolic syndrome. SummaryGut hormones continue to show promise on an individual basis as anti-obesity treatments, but combination therapies are needed to achieve beneficial effects comparable to bariatric surgery. Innovative pathways for stimulating native gut hormone secretion may well provide an alternative method for weight loss without necessitating the administration of gut hormone analogues via injection.

Risk profile of the RET A883F germline mutation: an international collaborative study

Context The A883F germline mutation of the rearranged during transfection (RET) proto-oncogene causes multiple endocrine neoplasia 2B. In the revised American Thyroid Association (ATA) guidelines for the management of medullary thyroid carcinoma (MTC), the A883F mutation has been reclassified from the highest to the high-risk level, although no well-defined risk profile for this mutation exists. Objective To create a risk profile for the A883F mutation for appropriate classification among the ATA risk levels. Design Retrospective analysis. Setting International collaboration. Patients Included were 13 A883F carriers. Intervention The intervention was thyroidectomy. Main Outcome Measures Earliest age of MTC, regional lymph node metastases, distant metastases, age-related penetrance of MTC and pheochromocytoma (PHEO), overall and disease-specific survival, and biochemical cure rate. Results One and three carriers were diagnosed at age 7 to 9 years (median, 7.5 years) with a normal thyroid and C-cell hyperplasia, respectively. Nine carriers were diagnosed with MTC at age 10 to 39 years (median, 19 years). The earliest age of MTC, regional lymph node metastasis, and distant metastasis was 10, 20, and 20 years, respectively. Fifty percent penetrance of MTC and PHEO was achieved by age 19 and 34 years, respectively. Five- and 10-year survival rates (both overall and disease specific) were 88% and 88%, respectively. Biochemical cure for MTC at latest follow-up was achieved in 63% (five of eight carriers) with pertinent data. Conclusions MTC of A883F carriers seems to have a more indolent natural course compared with that of M918T carriers. Our results support the classification of the A883F mutation in the ATA high-risk level.

Prednisolone has the same cardiovascular risk profile as hydrocortisone in glucocorticoid replacement

Introduction Patients who need glucocorticoid replacement in both primary and secondary adrenal insufficiency (AI) have the choice of either once-daily prednisolone or thrice-daily hydrocortisone. A recent European study found no difference between prednisolone and hydrocortisone users in several markers including glucose, weight, body mass index, systolic and diastolic blood pressure and waist circumference, although an increase in cholesterol and low-density lipoprotein (LDL) was suggested in a subgroup of these patients. The aim of this study was to expand the evidence base for the use of these agents as replacement therapy. Methods Data from 82 patients on hydrocortisone and 64 patients on prednisolone for AI at Imperial College Healthcare NHS Trust were analysed. Results There was no significant difference in total cholesterol, LDL levels or any other risk factors between hydrocortisone and prednisolone patients. Prednisolone was subjectively significantly more convenient than hydrocortisone (P = 0.048). Conclusions Prednisolone once daily is more convenient than hydrocortisone thrice daily, and there is no difference in the markers of cardiovascular risk measured. Because prednisolone mimics the circadian rhythm better than other glucocorticoids, it should be considered as an alternative to hydrocortisone for AI.

The scandal of generic drug pricing: drug regulation policies need review

We welcome the news that the Competitions and Market Authority is now taking drug companies such as GlaxoSmithKline, Pfizer, and Flynn Pharma to task for overcharging the NHS for generic drugs.1 In December, the authority announced that it was investigating Actavis for inflating the price of hydrocortisone, a WHO essential medicine used to treat adrenal insufficiency.2 The price of hydrocortisone has risen by …

Clinical roles in clinical biochemistry: a national survey of practice in the UK

Background Using an online survey, we collected data to present a picture of how clinical authorization is performed in the UK. Methods A 21-question survey was uploaded to www.surveymonkey.com, and responses were invited via the mail base of the Association for Clinical Biochemistry and Laboratory Medicine. The questionnaire examined the intensity and function of the duty biochemist role and how different types of authorization are used to handle and release results. Results Of 70 responses received, 60 were suitable for analysis. Responses were received from every region of the UK. A typical duty biochemist shift started on average at 8:50, and finished at 17:25. The mean duration was 8 h 58 min. Clinical scientists are the most abundantly represented group on duty biochemist rotas. Higher banded clinical scientists and chemical pathologists covered out-of-hours shifts. Results were handled differently depending on the level of abnormality and the requesting area. Normal results tended to be released either directly from the analyser or after technical then autoauthorization (90%). A greater preference for clinical authorization was seen for abnormal and critical results originating from outpatients (49% and 69%, respectively) or general practice (51% and 71%) than for inpatients (33% and 53%) or A&E (25% and 37%). Conclusions The handling and authorization of biochemistry results varies greatly between laboratories. The role is clearly heterogeneous in the UK. Guidance from the Association for Clinical Biochemistry and Royal College of Pathologists may help to clarify the essential roles of the duty biochemist.

Glucocorticoid replacement in Addison disease

Marcus Quinkler (Imitating the cortisol profile improves the immune system. Nat. Rev. Endocrinol. 14, 137–139 (2018))1, the authors suggest that optimum glucocorticoid replacement for the treatment of Addison disease is oncedaily modifiedrelease hydrocortisone (MRhydrocortisone), instead of thricedaily standard hydrocortisone. Standard hydrocortisone is administered thricedaily because it has a short halflife. Prednisolone2, however, offers a cheaper oncedaily replacement for the treatment of Addison disease, costing £43 per annum in the United Kingdom compared with £2,900 for MRhydrocortisone. To date, randomized controlled trials comparing outcomes from different glucocorticoid replacement regimens in patients with adrenal failure have only been carried out with MRhydrocortisone. The utility of cheaper drugs like prednisolone is unknown because of a reluctance to conduct expensive randomized controlled trials to test them. For patients with Addison disease, the dose of glucocorticoid and the timing of treatment are crucial for achieving a satisfactory quality of life. If a patient does not receive a high enough dose of glucocorticoid at the right time, they are at increased risk of morbidity and mortality resulting from an Addisonian crisis. In the past, most clinicians have erred on the side of excess replacement to avoid such a crisis3–5 but the association of high doses of glucocorticoid with cardiovascular mortality is concerning. identical to that of MRhydrocortisone. We now need a randomized controlled trial to compare oncedaily prednisolone with oncedaily MRhydrocortisone and thricedaily hydrocortisone to determine which of the three has the best outcomes. We believe that prednisolone, when used at the correct dose, might be the perfect replacement therapy in view of its very low cost, widespread availability and perfect plasma profile when taken once daily7. There is evidence that it is at least not inferior to the currently most widely used therapy, thricedaily hydrocortisone2.

Prednisolone 3 mg once daily should be the glucocorticoid replacement for hypopituitarism

Prednisolone is an alternative glucocorticoid that can be used for steroid replacement therapy1. It is structurally similar to hydrocortisone with the exception of a double bond between C1 and C2 on the first carbocyclic ring (Figure 1). This double bond gives prednisolone a longer half-life than prednisolone, permitting a one dose per day regimen. We herein present a case highlighting that prednisolone 3mg once daily can be used effectively in hypopituitarism.