Clinical Case Seminar. Peculiar prolactinomas in patients with pituitary developmental gene mutations: from an adult endocrinologist perspective.
BACKGROUND
Congenital hypopituitarism is a syndrome which is associated with single or multiple pituitary hormone deficiencies. Mutations in a number of developmental genes have been linked to combined pituitary hormone deficiencies, the most common being mutation in the pituitary homeobox protein prophet of the Pit 1 gene (PROP1). PROP1 exhibits DNA-binding and transcriptional activities. On magnetic resonance imaging, most patients with PROP1 mutation have a hypoplastic pituitary gland. Occasionally, transient pituitary enlargement before definite involution is reported. Kallmann syndrome (KS) is a human developmental genetic disorder which is a clinically (isolated hypogonadotropic hypogonadism-IHH) and genetically heterogeneous disease. Routine neuroimaging in classical IHH is thought to be of limited clinical value and normal anatomy of the hypothalamic-pituitary region is often reported. For neither disorder are there many reports on imaging during adulthood. Nor are there any guidelines concerning long-term imaging follow-up in patients with developmental pituitary disorders.


OBJECTIVE
Our aim was to present unusual endocrine and imaging abnormalities which developed in adulthood in two patients with developmental pituitary disorders.


METHODS
We report a female with combined pituitary hormone deficiencies (GH, TSH, gonadotropin and ACTH), except for prolactin, as a consequence of PROP1 mutation, and a male with KS (anosmia and IHH) due to Kal 2 gene (fibroblast growth factor receptor 1- FGFR1) mutation, both of whom in adulthood presented with prolactinomas.


CONCLUSIONS
Both patients with developmental gene mutations, after long-term correction of their sex steroid status, developed prolactinomas. Although the exact mechanism of pituitary tumorigenesis is not known, we speculate that sex steroids may have facilitated prolactinoma development from the prolactin cell pool which underwent uncontrolled proliferation in the setting of a developmental disorder.
Faculty of Medicine, University of Belgrade, Serbia.
Mirjana
M
Doknic
Sandra
S
Pekic
Milorad
M
Civcic
Vera
V
Popovic
D000328:Adult; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007018:Hypopituitarism / Q000235:genetics / Q000473:pathology; D017436:Kallmann Syndrome / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D010902:Pituitary Gland / Q000254:growth & development* / Q000473:pathology; D010911:Pituitary Neoplasms / Q000235:genetics*; D011388:Prolactin / Q000378:metabolism; D015175:Prolactinoma / Q000235:genetics* / Q000473:pathology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics
D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D011388:Prolactin; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1