Endocrine Abstracts

Introduction: Two childhood cases of somatotroph pituitary adenomas caused by aryl hydrocarbon receptor interacting protein (AIP) mutations highlight the importance of screening for familial isolated pituitary adenoma (FIPA) genes and wider family implications.

Case 1: A 13.5-year-old girl presented with 5 years growth acceleration and size ten feet, with no headache or visual disturbance. Examination: coarse facial features, large hands and feet, height SDS +2.8. Investigations: marked IGF1 elevation (208 nmol/l (23–90)), oral glucose tolerance test (OGTT) showed elevated baseline GH (>40 μg/l) and unsuppressed nadir (19.1 μg/l). An 18 mm pituitary mass with suprasellar extension was surgically resected. Unfortunately post-operative sphenoidal abscess resulted in permanent left temporal upper quadrantanopia. Following surgery, height velocity and IGF1 normalised, other pituitary function is normal and no medical treatment required. A heterozygous frameshift AIP mutation c.376_377del;p.Q126fs was identified, diagnosing FIPA.

Case 2: A 10.3-year-old boy presented with daily headaches and sudden onset blurred vision, with recent growth acceleration and increased shoe size. Examination: height SDS 2.8 with blurred temporal visual fields. A 23 mm pituitary adenoma with suprasellar extension was identified on urgent MRI and resected transsphenoidally. Post-operatively: histologically immunopositive for GH, elevated IGF1 (91.4 nmol/l), elevated baseline GH (41.2 μg/l), and OGTT nadir (17.5 μg/l), pituitary function otherwise normal. Long-acting somatostatin analogue was commenced. Targeted genetic testing of the AIP gene identified a disease-causing missense mutation c.811C>T;p.R271W.

Family testing was important as AIP mutations show autosomal dominant inheritance with 30% penetrance. In both cases the mother proved to be AIP carrier and siblings are under investigation.

Summary: About 50% of identified AIP-kindreds have no known family history. Childhood-onset isolated GH-secreting tumours may be index cases of FIPA and should prompt AIP mutational analysis. This facilitates management focussed on GH excess allowing discontinuation of other endocrine tumour screening and prompts cascade screening of family members to allow early identification of GH excess in family members.