SUN-191 Congenital Hypopituitarism Due to a Novel LHX3 Mutation in a Neonate: A Near Missed Surgical Intervention

Abstract Disclosure: M.V. Reddy: None. R.R. Paramahamsa: None. D.A. Kaju: None. D. Lasyaswi: None. Background: Congenital hypopituitarism (CH) may present as isolated or combined pituitary hormone deficiencies, with most cases being sporadic. However, familial cases are known, often linked to mutations in transcription factors crucial for pituitary gland development, such as the LHX3 gene. Mutation in this gene can result in CH along with extra-pituitary manifestations like spine abnormalities and sensorineural hearing loss (SNHL). To date, only 40-50 cases of LHX3 mutation have been reported. We describe an intriguing case of CH due to LHX3 mutation in a neonate from India. Clinical Case: An 8-day-old female newborn, the product of a consanguineous marriage, was born by LSCS at full term with a birth weight of 2.7 kg, presented with feeding difficulties (on OG feeds) and shortness of breath from birth. Initially admitted to another hospital on the first day of birth, she was intubated for poor respiratory effort and extubated on the fourth day after improvement. During this period, she experienced multiple episodes of hypoglycaemia, with the lowest recorded blood glucose level being 37 mg/dl. Persistent feeding refusal, regurgitation, and vomiting led to a diagnosis of GERD, and fundoplication was advised but declined by her parents, who sought a second opinion at our hospital. On examination, the baby was lethargic with poor tone and activity, depressed nasal bridge, wide anterior fontanelle, low set ears, and facial dysmorphism. Vitals at admission included PR of 156/min, RR of 52/min, BP of 66/35 mm Hg. Initial workup at our centre revealed random blood glucose of 47 mg/dl, low freeT3 (1.6pmol/L, Normal- 3.5-7.8), low freeT4 (3.12pmol/L, N-9-25), low TSH (0.01 Miu/ml, N-1.7-9.1), indicating central hypothyroidism. Suspecting panhypopituitarism, serum cortisol (3.89 mcg/dl, N-6.7-22.6) and ACTH (2.5 pg/ml,N- 10-90) levels were assessed and found to be low. MRI Sella showed an absent pituitary gland, suggesting empty sella syndrome. Hydrocortisone and levothyroxine therapy was initiated which improved the patient's symptoms, feeding (accepting oral feeds), and activity. Clinical Exome Sequencing confirmed a homozygous deletion of size ∼7.69 Kb, on chromosome 9, comprising of the LHX3 gene, a copy number variant was detected, confirming the diagnosis of CH. The patient was stable at discharge and came for follow-up after a month and was investigated for other anterior pituitary hormones, which were also low- LH (0.21mU/ml. N-0.25-6.79), FSH (0.15 mU/ml, N-0.2-15.73), Prolactin (0.52ng/ml, N-3.97-70.99). She was planned for initiating GH therapy, assessment of hearing and spine abnormality on further follow up. Conclusion: This case highlights the importance of genetic analysis in CH, especially in consanguineous marriages, and underscores the need for early recognition and treatment of associated endocrine deficiencies to prevent morbidity and unnecessary surgery. Presentation: Sunday, July 13, 2025