Beyond Kallmann: Fibroblast growth factor receptor 1 mutation presenting as multiple pituitary hormone deficiency: A case report

Abstract Fibroblast growth factor receptor 1 ( FGFR1 ) mutation is a well-known cause of Kallmann syndrome (congenital hypogonadotropic hypogonadism). Although rare, recent studies have highlighted that heterozygous loss-of-function mutations in FGFR1 can also lead to multiple pituitary hormone deficiency (MPHD). We present a case of a 30-year-old male who presented with the absence of secondary sexual characteristics since adolescence and infertility for 2 years. He also had a history of short stature. He had bilateral small testes (2 mL) and a micropenis with a stretched penile length of 5 cm. Biochemical evaluation revealed deficiencies of thyroid, adrenal, growth hormone, and gonadal axis, consistent with MPHD. Contrast-enhanced magnetic resonance imaging of the brain demonstrated a partially empty sella with a markedly hypoplastic pituitary gland and thin infundibulum. Whole-exome sequencing identified a heterozygous missense variation in the FGFR1 gene. The patient was initiated on hydrocortisone and levothyroxine replacement, followed by testosterone therapy. This case highlights FGFR1 mutation as a rare cause of MPHD associated with pituitary hypoplasia and partially empty sella, emphasizing the importance of genetic testing in unexplained hypopituitarism for appropriate diagnosis, counseling, and management.