Familial acromegaly with pituitary adenoma

Annual incidence of acromegaly is three to four per million people. The mean age at diagnosis is between 40 to 45 years. Apart from rare cases, acromegaly is caused by somatotroph adenoma of the anterior pituitary. Most pituitary tumors are sporadic, although a few occur with familial aggregation.

We report about siblings, a 25 year old woman (patient A) and her 20 year old brother (patient B). Both displayed acral overgrowth and enlarged frontal bones, nose and jaw. At the age of 23 years patient A underwent a transsphenoidal microsurgical extirpation of a pituitary adenoma. Pathology report confirmed the diagnosis of GH-secreting pituitary adenoma. However a big residual tumor remained. In consideration of this result patient B refused surgical therapy and decided to receive pharmacological treatment as primary therapy.

Patient A and patient B showed elevated GH and IGF-1 levels and a failure to suppress GH secretion during oral glucose tolerance test. A pituitary adenoma could be detected in both cases by MRI.

The DNA testing for inherited MEN 1 mutations (exon 2–10 chromosome 11q13) was negative. Also no other endocrinopathy could be detected neither in the two patient nor in their family members. Although symptoms were arising before 30 years of age, there was no indication for an association with the Carney complex.

As incidence of acromegaly in the general population is extremely low, the appearance of similar clinical features in siblings without other manifestations of MEN 1 or the Carney complex strongly suggests an inherited pituitary syndrome distinct from the known syndromes. Isolated familial acromegaly has been reported in approximately 20 families. Most of these of these cases occur early before the age of 30. An underlying genetic transmission outside the 11q13 has to be considered as the molecular basis of familial acromegaly with pituitary adenoma.