Endocrine Abstracts

Introduction: Maternally inherited diabetes and deafness (MIDD), is a rare entity. Most commonly, it is related to a point mutation in the mitochondrial DNA (mtDNA) at position 3243 (m.3243A>G) encoding the gene for tRNA. A high index of suspicion is required for the diagnosis due to a wide heterogeneity in its clinical presentation which reflects different levels of mutated mtDNA among mitochondria in a given tissue (heteroplasmy). Thyroid cancer risk has never been specifically assessed in this population.

Case-report: We report a 39-year-old male diagnosed with type 2 diabetes mellitus (T2DM) at the age of 29 when he presented with polyuria. His body mass index at diagnosis was 22.6 kg/m² and pancreatic autoimmunity was negative. After the presumed T2DM diagnosis he was started on oral hypoglycemic agents. He was added on insulin after 4 years of diagnosis because of poor glycemic control. He had never experienced any episodes of diabetic ketoacidosis (DKA). He had a subcapsular cataract of the left eye but there was no evidence of retinopathy, neuropathy, kidney disease, muscular weakness or cardiac disease at the time of presentation. His past medical history included a sensorineural hearing loss at 25 years of age. His family history revealed a bilateral hearing loss at the age of 50 in his mother who had also been diagnosed with T2DM and multinodular goiter in the last year. His sister was diagnosed with type 1 diabetes mellitus when she was 15 years of age and on physical examination she also had a multinodular goiter. The patient, his mother and sister underwent genetic testing which confirmed the m.3243A>G mutation with a level of heteroplasmy of 90%, 61% and 5% respectively. During the follow up the patient showed a thyroid papillary microcarcinoma with BRAF-V600E-K mutation. He was referred for thyroidectomy.

Conclusions: This family exemplifies the clinical heterogeneity of MIDD linked to the degree of heteroplasmy in the mitochondria of affected tissues. Probands commonly show high levels of heteroplasmy, they prompt the diagnosis as they are usually the most affected members of their families. Careful phenotyping and systematic evaluation of relatives after the diagnosis of the index case is mandatory due to unique management, prognostic and genetic counseling issues. The distribution of thyroid disease and thyroid cancer risk in this population is elusive. To our current knowledge this is the first reported case of MIDD and concurrent differentiated thyroid carcinoma.