Endocrine Abstracts

Germline AIP mutations (AIP^mut) predispose to young onset somatotroph pituitary adenomas (GHPA) and gigantism. AIP^mut GHPA are often aggressive and resistant to pharmacological treatment, which may be especially challenging in the paediatric setting. We report our experience with two young Italian AIP^mut male patients with incipient gigantism due to childhood pituitary macroadenomas, who both experienced recurrent GH/IGF1 hypersecretion followed by tumour regrowth during puberty.

Case 1: Patient A developed incipient gigantism due to a familial R304X AIP^mut. He was successfully operated on at the age of 9 years. for an intrasellar macroadenoma (12 mm). Two years later, spontaneous puberty occurred and IGF1 increased progressively. Final diagnosis of disease recurrence was made at the age of 14.5 years and pharmacological treatment with cabergoline (CAB) and somatostatin analogues (SSA) was started with a partial response.

Case 2: Patient B complained of visual defects at the age of 11.5 years. in a sporadic setting of accelerated growth. MRI showed a pituitary macroadenoma with suprasellar extension (27 mm), which was successfully operated on. Plasma GH/IGF1/PRL and growth velocity normalized. A germline A277P AIP^mut was found. Soon afterwards spontaneous puberty occurred and IGF1 increased progressively. Two years later he was started on CAB due to modest biochemical/clinical worsening and initial tumour regrowth. Thereafter, an increasingly aggressive tumour recurrence developed, requiring multiple treatment modalities with SSA, CAB and/or pegvisomant. He was re-operated at the ages of 14 and 18 years. and then underwent radiotherapy. Medical therapy was progressively withdrawn, with no need for hormone replacement therapy currently.

Comments: Both patients completed puberty, with heights stabilising at 191 and 190 cm, respectively. Early diagnosis of disease recurrence is of special importance in patients with incipient gigantism, but this may be very challenging during puberty in the absence of radiological evidence of tumour regrowth.