Severe bradycardia at acute medical take - Think about myxoedema coma.

We report two cases of myxoedema coma that presented to the acute medical take with severe bradycardia. These patients were initially misdiagnosed as bradyarrhythmia of primary cardiac origin. They were then diverted to the cardiology service at another district general hospital (DGH) for admissions. Both cases were subsequently diagnosed with myxoedema coma having screened thyroid function tests on arrival at the cardiology unit. Despite being treated for myxoedema coma, both patients unfortunately succumbed to the disease and later died in the hospital. These cases highlight that clinical suspicion and recognition of myxoedema coma remain significant challenges in a developed world despite readily available and highly sensitive thyroid hormone assays.

Lixisenatide in type 1 diabetes: A randomised control trial of the effect of lixisenatide on post-meal glucose excursions and glucagon in type 1 diabetes patients.

AIMS: The GLP1 agonist lixisenatide is glucagonostatic and reduces post-prandial blood glucose (PPBG) in type 2 diabetes. This study investigates its impact in type 1 diabetes (T1D). METHODS: In a blinded, crossover trial, 25 patients with T1D were randomised to 4 weeks adjunctive treatment with lixisenatide (L) or placebo (P), with a 4-week washout period. The primary outcome was percentage of 3 hours PPBG in target (4-10 mmol/L) assessed by CGM before and after treatment. Participants also underwent post-treatment standardised mixed meal test (MMT, n = 25) and hyperinsulinaemic hypoglycaemic clamp (n = 15). RESULTS: PPBG CGM readings in target were similar between L vs P (Mean % ± SE, breakfast 45.4 ± 6.0 vs 44.3 ± 6.0, P = .48, lunch 45.5 ± 5.8 vs 50.6 ± 5.3, P = .27 and dinner 43.0 ± 6.7 vs 47.7 ± 5.6, P = .30). HbA1C was similar between L vs P (64.7 ± 1.6 vs 64.1 ± 1.6 mmol/mol, P = .30). Prandial insulin fell after lixisenatide (dose change -0.7 ± 0.6 vs +2.4 ± 0.7 units/d, P = .004), but basal insulin dose was similar between groups. The post-MMT glucose area under the curve (AUC) was lower with L than P (392.0 ± 167.7 vs 628.1 ± 132.5 mmol/L × min, P < .001), as was the corresponding glucagon AUC (140.0 ± 110.0 vs 304.2 ± 148.2 nmol/L × min, P < .001). Glucagon and counter-regulatory hormone values at a blood glucose of 2.4 mmol/L during the hypoglycaemic clamp were similar between L and P. CONCLUSION: In T1D, PPBG values were not altered by adjunctive lixisenatide although prandial insulin dose fell. Glucose and glucagon level during an MMT were significantly lower after lixisenatide, without affecting counter-regulatory response during hypoglycaemia.

Does Islet Size Really Influence Graft Function After Clinical Islet Transplantation?

BACKGROUND: It has been proposed that islet transplants comprised primarily of small rather than large islets may provide better graft function, due to their lower susceptibility to hypoxic damage. Our aim was to determine whether islet size correlated with in vivo graft function in islet transplant recipients with C peptide-negative type 1 diabetes when islets have undergone pretransplant islet culture. METHODS: Human pancreatic islets were isolated, cultured for 24 hours and infused by standardized protocols. Ninety-minute stimulated C-peptide concentrations were determined during a standard meal tolerance test 3 months posttransplant. The islet isolation index (IEq/islet number) was determined immediately after isolation and again before transplantation (after tissue culture). This was correlated with patient insulin requirement or stimulated C-peptide. RESULTS: Changes in insulin requirement did not significantly correlate with islet isolation index. Stimulated C-peptide correlated weakly with IEq at isolation (P = 0.40) and significantly with IEq at transplantation (P = 0.018). Stimulated C-peptide correlated with islet number at isolation (P = 0.013) and more strongly with the islet number at transplantation (P = 0.001). In contrast, the correlation of stimulated C-peptide and islet isolation index was weaker (P = 0.018), and this was poorer at transplantation (P = 0.034). Using linear regression, the strongest association with graft function was islet number (r = 0.722, P = 0.001). Islet size was not related to graft function after adjusting for islet volume or number. CONCLUSIONS: These data show no clear correlation between islet isolation index and graft function; both small and large islets are suitable for transplantation, provided the islets have survived a short culture period postisolation.

Safety and efficacy of sitagliptin-metformin in fixed combination for the treatment of type 2 diabetes mellitus.

The biguanide, metformin, is considered first-line treatment for type 2 diabetes. Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor acts through the incretin pathway and has a glucose dependent mode of action. The complementary hypoglycemic properties of these drugs make fixed dose combination treatment an attractive prospect. Evidence from recent clinical trials suggests a beneficial effect of the combination on efficacy, demonstrated by significant improvement of hemoglobin A1c (HbA1c), fasting and postprandial glucose levels. The fixed dose combination is likely to have greater patient tolerability compared with monotherapy with either agent because of low rates of hypoglycemia, weight neutrality, and lower rates of side effects. High acquisition cost and paucity of long-term safety data are, however, potential barriers to their wider use. An overview of the pharmacology and clinical outcomes from recent trials of the metformin-sitagliptin combination and how the combination could fit into the type 2 diabetes treatment algorithm is presented in this review.

Mini-review: pheochromocytomas causing the ectopic ACTH syndrome.

Cushing's syndrome (CS) is a condition associated with high cortisol levels and affects around 0.7-2.4 cases per million population per year [1-3]. Approximately 80 % of cases of CS are secondary to excess adrenocorticotrophin (ACTH) secretion, while in around 20 % the primary abnormality lies in the adrenal, most often an adrenal adenoma or carcinoma. Of the ACTH-dependent causes, some 80-90 % are due to a pituitary adenoma-Cushing's disease-but in a significant proportion the cause is ectopic secretion from a non-pituitary source, the ectopic ACTH syndrome (EAS) [4]. The commonest source of ACTH secretion in these patients is a bronchial carcinoid. However, many other tumors are capable of secreting ACTH, and in most series a small but significant number are secondary to an ACTH-secreting pheochromocytoma. Amalgamating the data from 6 large series of patients with ectopic ACTH, pheochromocytoma was the source of ACTH secretion in 19 out of 363 patients (5.2 %) [5-11]. In this mini-review, we present a patient presenting to our department with a pheochromocytoma as well as Cushing's syndrome due to ectopic ACTH secretion by the pheochromocytoma, and we discuss published cases in the world literature to assess its significance. We emphasize the problems in the simultaneous management of these two serious endocrine conditions.