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Longitudinal Hormonal and Pituitary Imaging Changes in Two Females with Combined Pituitary Hormone Deficiency due to Deletion of A301,G302 in the PROP1 Gene¹

Unidade de Endocrinologia do Desenvolvimento, Disciplina de Endocrinologia, Laboratório de Hormônios e Genética Molecular-LIM/42 (B.B.M., M.G.F.O., A.C.L., V.E., I.J.P.A.), and Departamento de Neuroradiologia e Ressonancia Magnética (L.S.S.L.), Hospital das Clinicas, Universidade de Sao Paulo, Sao Paulo, Brazil

Address all correspondence and requests for reprints to: Ivo J. P. Arnhold, M.D., Disciplina de Endocrinologia, Hospital das Clínicas da USP, Caixa Postal 3671, 01060–970 Sao Paulo SP, Brazil. E-mail: iarnhold{at}usp.br

Genomic DNA from 18 patients with combined pituitary hormone deficiency was screened for 2-bp deletion (A301,G302) in PROP1 gene by BcgI restriction endonuclease analysis of PCR-amplified exon 2 gene fragments. Two unrelated female patients were homozygous for this 2-bp deletion. Patient 1 presented at 8.8 yr with severe short stature (-2.9 SD score), slightly enlarged sella turcica at x-rays, and diffusely enlarged pituitary gland (height, 8 mm vs. 4.5 ± 0.6 mm in matched controls) with hyperintense enhanced signal at T1 weighted image at coronal and sagittal views at magnetic resonance imaging (MRI). MRI repeated at age 15 yr revealed a marked reduction of pituitary height (2 mm vs. 5.3 ± 0.8 mm in matched controls). Patient 2 presented at 27 yr with short stature (-5.5 SD score) without pubertal development, normal sella turcica, and a pituitary gland of reduced size (height, 5 mm vs. 6.1 ± 0.3 mm in matched controls) of normal intensity at MRI. Both patients had normal pituitary stalk and normally located neurohypophysis. Hormonal features were characterized by GH, TSH, PRL, LH, and FSH deficiencies. Patient 1 had normal cortisol secretion at 8.8 yr, and at 16.6 yr had developed partial cortisol deficiency, whereas patient 2 maintained normal cortisol secretion at 28.4 yr. We conclude that 1) a large sella turcica and an enlarged pituitary anterior lobe with hyperintense enhanced signal at T1 at MRI can be suggestive of PROP1 deficiency; 2) pituitary morphology can change during follow-up of patients with PROP1 gene mutation; and 3) hormonal deficiencies could include the adrenal axis.

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