MON-043 Multiple Pituitary Hormone Deficiency in an Adult With Likely PROP1 Mutation

Abstract Disclosure: V.K. Babu: None. S. Phatak: None. Introduction: Pituitary development involves the interaction of transcription factors in the oral and neuroectoderm. Abnormalities in this process can lead to congenital hypopituitarism, which can affect one cell line (isolated hormone deficiency) or multiple cell lines (combined pituitary hormone deficiency (CPHD)). The incidence of CPHD is 1 in 4000 live births. Defects during early development may affect the eye, olfactory bulbs, midline structures, and forebrain leading to syndromic hypopituitarism (septo-optic dysplasia, holoprosencephaly); whereas later events lead to non-syndromic (NS) hypopituitarism. We present the case of a young female with NS CPHD. Case presentation: A 22-year-old African American female presented to our clinic with desire for fertility and no other complaints. She had primary amenorrhea and had not developed secondary sexual characteristics. She was followed by pediatric endocrinology from the ages of 4 to 19 for central hypothyroidism, GH deficiency, and central hypogonadism. She had history of medication non-adherence due to significant social stressors from parental incarceration and unstable housing. She was prescribed levothyroxine, conjugated estrogen, and somatropin injections which she received inconsistently only through her school. At our initial visit, she was off her medications for at least 3 years. No significant family history was noted. Physical exam revealed a pre-pubertal female with tanner stage 1 genitalia, stage 3 breasts, intact hearing, and no phenotypic abnormalities. She was 57 inches (in) tall compared to a mid-parental height of 62 in. Labs at 4:30pm showed TSH 2.19mIU/mL, Free T4 0.23ng/dL, ACTH 21 ng/L, Cortisol 9.2 ug/dL, Estradiol <5 pg/mL, FSH 0.2 mIU/mL, LH <0.2 mIU/mL, Prolactin 1.6 ng/mL, IGF-1 Z-score -9.4, and sodium 139. Her bone age was 13 years 6 months compared to a chronological age of 22 years 10 months. Her pelvic US showed an atrophic uterus with a small right ovary and no outlet obstruction on speculum exam by OBGYN. Pituitary MRI showed diminutive pituitary gland and stalk. Discussion: Transcription factors control the formation of the anterior pituitary. Non-syndromic causes include POU1F1 and PROP1 mutations. The expression of POU1F1 is triggered by PROP1 and causes the differentiation and proliferation of thyrotroph, lactotroph, and somatotroph cells. About 65% of POU1F1 cases are autosomal recessive and 35% are autosomal dominant. PROP1 causes 11% of all CPHD, of which 7% are sporadic. Although milder than POU1F1 defects, it is associated with hypogonadism and adrenal insufficiency (AI). Imaging demonstrates a normal or hypoplastic anterior pituitary with normal posterior pituitary structures. We believe our patient has a sporadic PROP1 mutation despite not having AI. She has restarted hormonal replacements and is pending genetic testing. Presentation: Monday, July 14, 2025