Endocrine Abstracts

Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are responsible for 30% of pituitary gigantism cases. However, pathological accelerated growth and/or tall stature can be unrelated to the growth hormone (GH) axis, and may occur in isolation or as part of a syndrome, such as in Klinefelter, Marfan or Sotos syndromes. We report a five-generation kindred with two brothers with pituitary gigantism due to AIP mutation-positive GH-secreting pituitary adenomas and their first-cousin coincidently also having gigantism due to Marfan syndrome. The proband, presented with accelerated growth (at the age of 10, height SDS+2.1) and was diagnosed with pituitary gigantism due to a pituitary adenoma co-expressing GH and prolactin. Following surgery, octreotide LAR was ineffective and he was started on pegvisomant. His brother presented few years later at the age of 16 with accelerated growth (height=201 cm, SDS+3.9), and was operated on two occasions for somatolactotropinoma. Genetic testing identified a truncating R304* mutation in the AIP gene in these two affected brothers, as well as in eight unaffected family members, who are currently under surveillance. A deceased uncle had acromegaly based on photographs. In the same kindred we identified a tall first-cousin (height 208 cm) due to Marfan syndrome. Clinical and biochemical exclusion of GH-related pituitary gigantism is usually straightforward; however, some conditions may present with acromegaloid features, or tall stature. In this family, the diagnosis of the two brothers with pituitary gigantism may have been hindered by the presence of extreme tall stature in the family (due to Marfan syndrome). Overlapping features between GH excess and other conditions could present challenging issues for patients and their families as well as for their general practitioners.