Rathi Prasad1, Adeline K Nicholas2, Nadia Schoenmakers2, John Barton3. 1. Department of Paediatric Endocrinology, Royal London Hospital, Barts Health NHS Trust, London, United Kingdom, Rathi.Prasad@nhs.net. 2. University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom. 3. Department of Paediatric Endocrinology, Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom.
Abstract
INTRODUCTION: Heterozygous mutations or haploinsufficiency of NKX2-1 are associated with the brain-lung-thyroid syndrome incorporating primary hypothyroidism, respiratory distress, and neurological disturbances. CASE PRESENTATION: We report a patient presenting in the neonatal period with multiple pituitary hormone deficiency including central hypothyroidism and hypoadrenalism, growth hormone deficiency, undetectable gonadotrophins, and a small anterior pituitary on MRI. CGH microarray revealed haploinsufficiency for NKX2.1 and during subsequent follow-up, she has exhibited the classic triad of brain-lung-thyroid syndrome with undetectable tissue on thyroid ultrasonography. Whilst the role of NKX2-1 is well described in murine pituitary development, this report constitutes the first description of multiple pituitary dysfunction in humans associated with the syndrome and haploinsufficiency NKX2-1. CONCLUSION: The report highlights a potential need for pituitary screening in patients with established brain-lung-thyroid syndrome and implicates NKX2.1 in human pituitary disease.
INTRODUCTION: Heterozygous mutations or haploinsufficiency of NKX2-1 are associated with the brain-lung-thyroid syndrome incorporating primary hypothyroidism, respiratory distress, and neurological disturbances. CASE PRESENTATION: We report a patient presenting in the neonatal period with multiple pituitary hormone deficiency including central hypothyroidism and hypoadrenalism, growth hormone deficiency, undetectable gonadotrophins, and a small anterior pituitary on MRI. CGH microarray revealed haploinsufficiency for NKX2.1 and during subsequent follow-up, she has exhibited the classic triad of brain-lung-thyroid syndrome with undetectable tissue on thyroid ultrasonography. Whilst the role of NKX2-1 is well described in murine pituitary development, this report constitutes the first description of multiple pituitary dysfunction in humans associated with the syndrome and haploinsufficiencyNKX2-1. CONCLUSION: The report highlights a potential need for pituitary screening in patients with established brain-lung-thyroid syndrome and implicates NKX2.1 in humanpituitary disease.
Authors: Sebastian Alexis Vishnopolska; Maria Florencia Mercogliano; Maria Andrea Camilletti; Amanda Helen Mortensen; Debora Braslavsky; Ana Keselman; Ignacio Bergadá; Federico Olivieri; Lucas Miranda; Roxana Marino; Pablo Ramírez; Natalia Pérez Garrido; Helen Patiño Mejia; Marta Ciaccio; Maria Isabel Di Palma; Alicia Belgorosky; Marcelo Adrian Martí; Jacob Otto Kitzman; Sally Ann Camper; Maria Ines Pérez-Millán Journal: J Clin Endocrinol Metab Date: 2021-06-16 Impact factor: 6.134