Severe sensory-autonomic neuropathy and endocrinopathy in insulin-dependent diabetes

A patient developed insulin-dependent diabetes mellitus at the age of 9 years, complicated by a sensory/autonomic polyneuropathy which presented with a respiratory arrest at the age of 41 years. The neuropathy increased in severity over the subsequent two decades. At the age of 52 years she had hypopituitarism, hypothyroidism and low normal adrenal function. Autopsy at the age of 59 years revealed loss of pituitary tissue with evidence of hypophysitis, a lymphocytic thyroiditis and severe adrenal atrophy with lymphocytic infiltration of the medulla. The pancreas showed reduced numbers and size of the islets of Langerhans with total loss of immunoreactivity for insulin but intact glucagon-producing cells. These features are consistent with a type 2 autoimmune polyendocrine syndrome, in which lymphocytic hypophysitis has not previously been recorded. There was severe loss of myelinated nerve fibres in the sural nerve and rostrally accentuated fibre degeneration in the gracile fasciculi, but only mild cell loss in the dorsal root ganglia. This combination suggests the presence of a central-peripheral distal axonopathy. The cervical sympathetic ganglia were severely atrophic. Minor inflammatory infiltration was observed in the dorsal root and sympathetic ganglia. Significant vascular abnormalities were not present in the peripheral nerves. This, and the pattern of nerve fibre degeneration, suggest that in this case the neuropathy was likely to have been related to metabolic rather than vascular causes. The inflammatory infiltrates in sensory and sympathetic ganglia raise the possibility of an autoimmune inflammatory contribution to the neuropathy.