MELAS syndrome, diabetes and thyroid disease: the role of mitochondrial oxidative stress.

The mitochondrial DNA mutation MTTL1 A3243G causes MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes). The A3243G mutation is also associated with variable endocrinopathies. We describe 2 case histories of patients with the A3243G mutation. The first patient presented with diabetes and uncontrolled Graves’ thyrotoxicosis in association with a strokelike episode, seizures and cortical blindness. The second patient presented initially with primary hypothyroidism and vitiligo, and later with glucose intolerance and hypoadrenalism. She went on to develop the classical features of MELAS syndrome. These cases illustrate the range of endocrine abnormalities associated with this mitochondrial DNA mutation. MELAS syndrome should be considered in patients presenting with disparate endocrine conditions in association with neurological problems such as stroke-like episodes, myoclonic epilepsy, sensorineural deafness and cortical blindness. The development of thyrotoxicosis or the introduction of thyroid hormone replacement may precipitate a ‘bioenergetic crisis’ by imposing cellular oxidative stress.