An ambulatory program improves metabolic control and knowledge in adolescents with poorly controlled type 1 diabetes; however, it is effective only while the intervention is maintained.

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We present a case of an obese 22-year-old man with activating GCK variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. We investigated him for asymptomatic hypoglycemia with a family history of hypoglycemia. Genetic testing yielded a novel GCK missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant. Glucokinase enables phosphorylation of glucose, the rate-limiting step of glycolysis in the liver and pancreatic β cells. It plays a crucial role in the regulation of insulin secretion. Inactivating variants in GCK cause hyperglycemia and activating variants cause hypoglycemia. Spleen-preserving distal pancreatectomy revealed diffuse hyperplastic islets, nuclear pleomorphism and periductular islets. Glucose stimulated insulin secretion revealed increased insulin secretion in response to glucose. Cytoplasmic calcium, which triggers exocytosis of insulin-containing granules, revealed normal basal but increased glucose-stimulated level. Unbiased gene expression analysis using 10X single cell sequencing revealed upregulated INS and CKB genes and downregulated DLK1 and NPY genes in β-cells. Further studies are required to see if alteration in expression of these genes plays a role in the metabolic and histological phenotype associated with glucokinase pathogenic variant. There were more large islets in the patient’s pancreas than in control subjects but there was no difference in the proportion of β cells in the islets. His hypoglycemia was persistent after pancreatectomy, was refractory to diazoxide and improved with pasireotide. This case highlights the variable phenotype of GCK mutations. In-depth molecular analyses in the islets have revealed possible mechanisms for hyperplastic islets and insulin hypersecretion.

The corresponding author is not a recipient of a research scholarship.The paper is not based on a previous communication to a society or meeting.

Background Anabolic steroid misuse is very common and has been linked to the development of a severe cardiomyopathy, arrhythmias and sudden death. Case Summary A forty-six year old miner presented to hospital with subacute dyspnoea and palpitations. Investigations revealed atrial fibrillation and a severe dilated cardiomyopathy with left ventricular ejection fraction of 12%. The patient had a history of longstanding exogenous testosterone administration. Haematological investigations demonstrated a marked polycythaemia, with haematocrit of 0.60 L/L (normal 0.40-0.54 L/L). Hormonal investigations revealed an elevated testosterone level of 46.4 nmol/L (normal 8.0–30.0 nmol/L) and suppressed luteinizing and follicle-stimulating hormones, consistent with excess testosterone use. The patient was referred to the endocrinology specialty team for support with ceasing excess testosterone use, while commencing guideline-directed heart failure therapy. At six months’ follow-up, the patient’s left ventricular ejection fraction had normalised and he was asymptomatic. Biochemical indicators of testosterone excess had also normalised. Discussion Anabolic steroids are widely misused, particularly amongst young and middle-aged males. Cardiovascular complications include a potentially reversible severe cardiomyopathy, accelerated coronary disease, dyslipidaemia, arrhythmias and sudden death. It is important to identify a history of anabolic steroid misuse when investigating cardiomyopathy and be alert for indicators such as polycythaemia. Cessation of anabolic steroid missuse may lead to complete reversal of cardiomyopathy but should be undertaken in close partnership with the patient and endocrinologists.