Maternally inherited diabetes and deafness with a variable presentation across three generations within a pedigree, South Africa.

Introduction: Maternally inherited diabetes and deafness (MIDD) is caused by the m.3243A>G pathogenic variant in maternally inherited mitochondrial DNA. Diabetes is prevalent in our setting; however, MIDD is rarely diagnosed. This study, undertaken in Pretoria, South Africa, highlights the variable presentation of MIDD in different patients within the same family. Case presentation: A 45-year-old man (proband) with hearing impairment was referred to the endocrine unit in July 2015 due to poor glycaemic control (HbA1c = 13%). His clinical and biochemical features were in keeping with MIDD. A genetic study of accessible maternal relatives was pursued. His mother had difficulty hearing and reportedly died from an unspecified cardiovascular cause. Two sisters with diabetes and deafness died of cardiac-related conditions. One nephew had diabetes (HbA1c = 7.7%), hearing loss and tested positive for m.3243A>G. A third sister tested positive for m3243A>G, but aside from bilateral mild hearing loss in higher frequencies, showed no other signs of target organ damage. Her daughter developed end-stage kidney failure necessitating a transplant, while her son had no biochemical abnormalities and was negative for m.3243A>G. Management and outcome: A multidisciplinary team managed and screened for complications of the patient and his maternal relatives. Proband died prior to genetic testing. Conclusion: Most MIDD patients initially present with symptoms of diabetes only, and it is probable that many cases remain undiagnosed. A high index of suspicion is necessary when encountering a family history of both diabetes and impaired hearing, and screening should be offered to the patient's maternal relatives. What the study adds: This study demonstrates the importance of proper assessment when evaluating a patient with diabetes and a family history of hearing loss.

Implementation research: a protocol for two three-arm pragmatic randomised controlled trials on continuous glucose monitoring devices in people with type 1 diabetes in South Africa and Kenya.

BACKGROUND: Self-monitoring of glucose is an essential component of type 1 diabetes (T1D) management. In recent years, continuous glucose monitoring (CGM) has provided an alternative to daily fingerstick testing for the optimisation of insulin dosing and general glucose management in people with T1D. While studies have been conducted to evaluate the impact of CGM on clinical outcomes in the US, Europe and Australia, there are limited data available for low- and middle-income countries (LMICs) and further empirical evidence is needed to inform policy decision around their use in these countries. METHODS: This trial was designed as a pragmatic, parallel-group, open-label, multicentre, three-arm, randomised (1:1:1) controlled trial of continuous or periodic CGM device use versus standard of care in people with T1D in South Africa and Kenya. The primary objective of this trial will be to assess the impact of continuous or periodic CGM device use on glycaemic control as measured by change from baseline glycosylated haemoglobin (HbA1c). Additional assessments will include clinical outcomes (glucose variation, time in/below/above range), safety (adverse events, hospitalisations), quality of life (EQ-5D, T1D distress score, Glucose Monitoring Satisfaction Survey for T1D), and health economic measures (incremental cost-effectiveness ratios, quality adjusted life years). DISCUSSION: This trial aims to address the substantial evidence gap on the impact of CGM device use on clinical outcomes in LMICs, specifically South Africa and Kenya. The trial results will provide evidence to inform policy and treatment decisions in these countries. TRIAL REGISTRATION: NCT05944731 (Kenya), July 6, 2023; NCT05944718 (South Africa), July 13, 2023.

Hyperthyroidism in molar pregnancy: ß-HCG levels do not always reflect severity.

BACKGROUND: Molar pregnancy is a complication characterised by abnormal benign or malignant proliferation of trophoblastic cells resulting in markedly elevated ß-hCG (human chorionic gonadotrophin) levels, an established marker for the presence of the disease. Owing to the structural homology between ß-hCG and TSH, the raised ß-hCG can result in secondary hyperthyroidism. METHODS: Two patients aged 20 (Case 1) and 31 years (Case 2) presented to the emergency department within a few days of each other complaining of vaginal bleeding associated with abdominal pain. Ultrasound evaluation, ß-hCG and thyroid function tests were performed on both patients. RESULTS: Both had elevated ß-hCG levels and ultrasound evidence of molar pregnancy and were diagnosed with gestational trophoblastic disease (GTD) associated with hyperthyroidism based on thyroid function test results. Case 1 had lower ß-hCG levels and free T4 levels compared with Case 2 but clinical assessment of the former revealed severe illness and more complicated course with the development of a thyroid storm. Case 2 had ß-hCG levels almost double those of Case 1, yet was stable and her levels decreased much faster, reaching and maintaining undetectable levels. CONCLUSIONS: These cases demonstrate that the ß-hCG levels do not always correlate with disease severity and prognosis in patients with GTD.