Alia Munir

Management of Diabetes Mellitus in Cushing’s Syndrome

Active Cushing’s syndrome is associated with insulin resistance induced by the high and prolonged circulating level of glucocorticoids. In endogenous Cushing’s syndrome the overall incidence of diabetes mellitus and insulin resistance is very likely to be under-reported as not all patients are actively investigated with glucose tolerance tests. Whilst it is common clinical experience that management of diabetes mellitus is necessary in patients with Cushing’s syndrome there is a dearth of literature-based evidence to support which regimes are the most effective. Therefore, a pragmatic approach is necessary on an individualized patient basis, whereby patients are stratified according to the severity of their impaired glucose homeostasis. The most effective means of control of diabetes mellitus in a patient with active Cushing’s syndrome is to lower the levels of circulating cortisol. This may initially be achieved by using adrenal steroidogenesis blockade with drugs including metyrapone, ketaconazole, or, on occasion, mitotane. The rapid action of metyrapone is particularly suitable in this circumstance. Despite this, diabetes-specific therapy is often necessary and metformin and PPAR-γ agonists may be of use, but in the acute setting insulin therapy is frequently needed. Definitive management directed against source driving Cushing’s syndrome is often highly effective at either reducing the severity of diabetes, or allowing its complete resolution. Patients experiencing diabetes mellitus in the context of exogenously administered glucocorticoids may well require insulin therapy for the period that the high levels of steroids are being administered. Despite resolution of Cushing’s syndrome after definitive treatment patients may continue to exhibit insulin resistance. This and other cardiovascular risk factors require ongoing and long-term attention.

Continuous glucose monitoring in patients with insulinoma

Background  Insulinomas are rare neuroendocrine tumours that are usually small and may take time to localize. They cause recurrent life‐threatening spontaneous hypoglycaemia. Recurrent hypoglycaemia causes loss of hypoglycaemia awareness, putting the patient at further risk, but this has rarely been described in insulinoma. We describe the utility of continuous glucose monitoring (CGM) in patients with insulinoma.

Assessment and Management of Anti-insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome.

Abstract Context Insulin autoimmune syndrome (IAS), spontaneous hyperinsulinemic hypoglycemia due to insulin-binding autoantibodies, may be difficult to distinguish from tumoral or other forms of hyperinsulinemic hypoglycemia, including surreptitious insulin administration. No standardized treatment regimen exists. Objectives To evaluate an analytic approach to IAS and responses to different treatments. Design and Setting Observational study in the UK Severe Insulin Resistance Service. Patients Six patients with hyperinsulinemic hypoglycemia and detectable circulating anti–insulin antibody (IA). Main Outcome Measures Glycemia, plasma insulin, and C-peptide concentrations by immunoassay or mass spectrometry (MS). Immunoreactive insulin was determined in the context of polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC). IA quantification using ELISA and RIA, and IA were further characterized using radioligand binding studies. Results All patients were diagnosed with IAS (five IgG, one IgA) based on a high insulin/C-peptide ratio, low insulin recovery after PEG precipitation, and GFC evidence of antibody-bound insulin. Neither ELISA nor RIA result proved diagnostic for every case. MS provided a more robust quantification of insulin in the context of IA. One patient was managed conservatively, four were treated with diazoxide without sustained benefit, and four were treated with immunosuppression with highly variable responses. IA affinity did not appear to influence presentation or prognosis. Conclusions IAS should be considered in patients with hyperinsulinemic hypoglycemia and a high insulin/C-peptide ratio. Low insulin recovery on PEG precipitation supports the presence of insulin-binding antibodies, with GFC providing definitive confirmation. Immunomodulatory therapy should be customized according to individual needs and clinical response.