Carneys complex was first identified as the association of primary adrenal nodular dysplasia, lentigines and cardiac and skin myxomas. Several other endocrine and non-endocrine disorders were subsequently added to the complex, including pituitary tumors and melanotic Schwannomas. We herewith describe a kindred with Carneys complex featuring acromegaly as the common denominator.
Patients & methods: A 42-year-old woman first presented to our attention with acromegaly and died some years later after removal of a melanotic Schwannoma. Her 43-year-old brother was diagnosed with acromegaly and cutaneous angiomyxoma prompting investigation for Carneys complex. Blood samples were collected from affected subjects, their mother and their offspring as well as their apparently healthy siblings for sequencing of the PRKAR1A gene. All subjects were also submitted to OGTT, measurement of IGF-I, prolactin, UFC and ACTH, sonograms and thorough clinical evaluation.
Results: The brother and the two daughters of the index case presented a G>A substitution upstream to exon 4 of the PRKAR1A gene. The mother as well as two siblings presented normal PRKAR1A sequence. Both daughters of the index case (24 and 21 yr) presented abnormal GH responses to OGTT and lentigines in typical sites. The elder daughter also presented increased IGFI levels and a pituitary microadenoma and was started on GH-suppressive therapy. No lesions were detected at cardiac, abdominal and testicular sonogram in family members harbouring the PRKAR1A mutation; adrenal function was normal.
Conclusions: Carneys complex is the association of rare and unusual disorders, initially characterized by adrenal, heart and skin lesions. Acromegaly is known to affect some 10% of patients with the complex but is rarely the premier clinical condition. Our kindred demonstrates that familial acromegaly may be the first sign of Carneys complex and that identification of affected subjects by genetic screening allows early detection and treatment of GH hypersecretion.
01 - 05 Apr 2006
European Society of Endocrinology