Waxing and waning of a pituitary mass in a young woman with combined pituitary hormone deficiency (CPHD) due to a PROP-1 mutation

Abstract

We describe a 23-yr old woman with congenital combined pituitary hormone deficiency (CPHD) diagnosed at 10 years of age and a large sellar mass discovered at the age of 19 years, when her first pituitary MRI was performed. The mass (height: 13 mm) extended to the suprasellar region, close to the optic chiasm, showed signal hyperintensity in T1- and hypointensity in T2-weighted images, with no enhancement after gadolinium injection. Although these MRI features were suggestive of Rathke's cleft cyst, cystic craniopharyngioma or previous hemorrhage, no visual symptoms, diabetes insipidus and/or hyperprolactinemia were present. In addition, similar MRI findings had been previously described in a few cases of CPHD due to PROP-1 mutations, which prompted us to carry out a molecular study before any therapeutic decision was made. A 301302delAG PROP-1 mutation was found in her DNA and the patient was closely followed through ophthalmologic evaluation and pituitary MRI scans. During a 3.6-year follow-up, we were able to document a marked initial growth followed by shrinkage and recurrent growth of the PROP-1 sellar mass. The patient remains free of compressive neuro-ophthalmological signs, suggesting that surgical intervention is unnecessary in these cases. However, they must be followed closely with sellar MRIs and campimetry until the mass completely regresses.

Mutations and Pituitary Morphology in a Series of 82 Patients with <i>PROP1</i> Gene Defects

“…They speculated that pituitary enlargement may originate from the intermediate lobe, although histopathological data were missing in the reported cases. Additional observations in further individual cases with PROP1 mutations suggested a more complex (possibly biphasic) development of pituitary size from hypoplasia in early childhood to enlargement at about pubertal age [13,18,26], and the present results would support this finding.…”

“…The true nature, prevalence, and natural development of pituitary masses due to PROP1 mutations have so far been studied only in limited cohorts of patients [3,4,5,13,14,15,16,17,18,19]; therefore, we aimed to establish a representative group of affected patients allowing more detailed analysis over the lifespan.…”

Molecular analysis of PROP1, PIT1, HESX1, LHX3, and LHX4 shows high frequency of PROP1 mutations in patients with familial forms of combined pituitary hormone deficiency

“…Two of them have been reported before (28,39). This mutation is so common that it is considered by several authors as a mutational hotspot (19,25).…”

Evaluation of pituitary imaging in patients with PROP-1 gene mutation

“…Kartojant vaizdinius tyrimus po kiek laiko, kartais būna hipofizės regresija (6,11,12,16). Kelių tyrimų autoriai užfik-savo per atskirus laiko tarpus besikeičiantį hipofizės dydį ("dvibangė hipofizės hiperplazija") (17,18). Manoma, jog PROP-1 geno mutacijos paplitimas įvairiose šalyse labai skiriasi.…”