Newborn Pseudohypoparathyroidism: A Case Report

Background: Pseudohypoparathyroidism(PHP) represents a group of disorders whose main feature consists in a resistance to Parathormone(PTH) action. The most common subtype of PHP is Ia, caused by a mutation in the GNAS1 gene. It is inherited as an autosomal dominant trait but, because of paternal gene imprinting, different phenotypes occur depending on the origin of the mutated gene. When paternally inherited, subjects only manifest the physical syndrome – Albright’s Hereditary Osteodystrophy (obesity, rounded face, brachydactyly, subcutaneous ossifications…). When maternally inherited, in addition to those physical characteristics, multiple hormone resistance (PTH, Thyroid-stimulating Hormone(TSH), gonadotropin…) occurs – PHP-Ia.

Objectives: Case report of a newborn with PHP-1a presenting with hypothyroidism – the importance of family history, a high suspicion level and thorough laboratory workups.

Methods: Reviews of the subject’s and his family’s clinical records.

Results: A 27-year-old female gravida (37 weeks gestation), with genetically proven AHO (paternally inherited GNAS1 mutation), gave birth to a 2360g male that presented with early signs of respiratory distress, for which he was admitted in the NICU. Respiratory symptoms resolved gradually. Because of the family history, at day 6, thyroid hormone testing was requested, showing a free-T4 level of 0.67mg/dL and a TSH concentration of 13.02 IU/mL. Hypothyroidism/TSH insensitivity was diagnosed – levothyroxine therapy was initiated, and thyroid function levels normalized in the following days – discharge on the 18th day of life. Genetic testing revealed the newborn carried the same mutation as the mother, confirming the diagnosis of PHP-1A. An ultra-sound showed a normal but relatively small thyroid gland. Phosphocalcium metabolism and thyroid function (under levothyroxine) remain normal at 3-month follow-up.

Conclusion: While PTH resistance is the main feature of PHP-Ia, TSH resistance may become apparent before hypocalcemia develops, and may be indistinguishable from primary hypothyroidism. Early treatment and continuous monitoring of these patients’ hypothyroidism is paramount in preventing future complications.