Introduction: Chromosome Xq26.3 microduplications have recently been identified, and explained this 11-year-old girls marked tall stature. Her severe phenotype illustrates X-linked acrogigantism (X-LAG) and demonstrates therapeutic benefit from growth hormone receptor blockade.
Case: A 5.6-year-old girl presented with growth acceleration from 3 years and appearance of secondary dentition, greasy skin and blackheads from age 4. Past medical and family histories were unremarkable. Examination revealed height SDS +4.25 and mild coarsening of facial features. IGF1 was elevated (79 nmol/l (420)) with normal prolactin, TFTs and gonadotrophins. GH was elevated at baseline (38 μg/l) and failed to suppress on OGTT (nadir 16 μg/l). Serial contrast-enhanced MRIs over 6 years showed mild pituitary hyperplasia although no tumour. Genetic screening for MEN1, AIP, and leucocyte GNAS mutations was negative.
Treatment with somatostatin analogue, lanreotide (Somatuline Autogel), 20082012 achieved partial IGF1 reduction, although not normalisation with no reduction in height velocity. Concomitant cabergoline achieved no further IGF1 reduction. Aged 9 years, medication was stopped due to side effects and insufficient therapeutic benefit. Aged 11, there was increased height velocity (10.8 cm/year), predicted final height 6 ft 4 inch and increased IGF1 (106.4 nmol/l (9.857.2)). An alternative somatostatin analogue, octreotide (Sandostatin Lar), was trialled. After initial IGF1 reduction (61.1 nmol/l), IGF1 elevation continued as did increased growth.
Pegvisomant, a GH receptor antagonist, was trialled May 2015. In 2 months, there was IGF1 normalisation (24.3 nmol/l), ring size reduction, improved general well-being and no height gain.
Testing for chromosome Xq26.3 microduplication confirmed a genetic diagnosis of X-LAG and testing of her parents indicated a de novo mutation.
Summary: The case illustrates how discoveries in pituitary genetics have given a recent diagnosis to a child with severe growth hormone excess and pituitary hyperplasia. The initial response to pegvisomant therapy is encouraging and supports consideration of its use in similar somatostatin analogue resistant cases.
25 - 27 Nov 2015
British Society for Paediatric Endocrinology and Diabetes