ESPE Yearbook of Paediatric Endocrinology

Pituitary. 2021;24(2):252-261. doi: 10.1007/s11102-020-01105-4. PMID: 33156432.

Brief Summary: Pituitary gigantism is a rare disease, which can be syndromic, as in McCune-Albright syndrome, Carney complex, MEN1 and MEN4, and the newly described “three P association” (paraganglioma, pheochromocytoma and pituitary adenoma) (1), or non-syndromic caused by mutations in aryl hydrocarbon receptor-interacting protein (AIP) or microduplication of Xq26.3 in X-linked acrogigantism i.e. X-LAG (2). This study reports a cohort of non-syndromic pituitary gigantism.

The authors describe a single center experience of non-syndromic patients. Their cohort comprised 18 patients from Sao Paolo, 4 of whom had pathogenic variants in AIP gene and 2 had X-LAG. The median age at pituitary gigantism diagnosis was 17 [range 15-20] years but the first signs and symptoms were noted 3.5 years earlier (median 14 [range 9-16] years). The X-LAG patients were diagnosed earlier than those with no identified mutations. However, as no growth charts were available, the authors could not verify the previously reported very early onset height acceleration. All patients had elevated levels of GH and IGF1. Pituitary tumors were macroadenomas and positive for GH immunoreactivity.

On top of the clinical description of pituitary gigantism, the paper emphasizes the importance of regular growth measurements and use of growth charts as simple and cheap tools in the detection of this rare disease.

References: 1. Pituitary adenoma with paraganglioma/pheochromocytoma (3PAs) and succinate dehydrogenase defects in humans and mice. Xekouki P, Szarek E, Bullova P, Giubellino A, Quezado M, Mastroyannis SA, Mastorakos P, Wassif CA, Raygada M, Rentia N, Dye L, Cougnoux A, Koziol D, Sierra Mde L, Lyssikatos C, Belyavskaya E, Malchoff C, Moline J, Eng C, Maher LJ 3rd, Pacak K, Lodish M, Stratakis CA. J Clin Endocrinol Metab. 2015 May;100(5):E710–9. 2. Trivellin, G., Daly, A. F., Faucz, F. R., Yuan, B., Rostomyan, L., Larco, D. O., Schernthaner-Reiter, M. H., Szarek, E., Leal, L. F., Caberg, J. H., Castermans, E., Villa, C., Dimopoulos, A., Chittiboina, P., Xekouki, P., Shah, N., Metzger, D., Lysy, P. A., Ferrante, E., Strebkova, N., Mazerkina N., Zatelli M. C., Lodish M., Horvath A., Bertollo de Alexandre R., Manning A. D., Levy I., Keil M. F., de la Luz Sierra M., Palmeira L., Coppieters W., Georges M., Naves L. A., Jamar M., Bours V., Wu T. J., Choong C. S., Bertherat J., Chanson P., Kamenický P., Farrell W. E., Barlier A., Quezado M., Bjelobaba I. Stojilkovic S. S., Wess J., Costanzi S., Liu P., Lupski J. R., Beckers A., Stratakis, C. A. (2014). Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. The New England journal of medicine, 371 (25), 2363–2374.