Endocrine Abstracts

JOINT2431

Introduction: Pathogenic variants in the TSHB gene are known to cause severe isolated central congenital hypothyroidism (CH). Mutations in this gene are associated with congenital central hypothyroidism, secondary hypothyroidism, and Hashimoto’s thyroiditis. We present the clinical, biochemical, and genetic features of a patient with a central CH phenotype.

Case: A 9-year-old female patient demonstrated delayed developmental milestones, with head control achieved at 9 months and the ability to walk at 2 years of age. She was born with right femoral agenesis and underwent prosthetic surgery at the age of 2. Additionally, she has sensorineural hearing loss and intellectual disability. During the investigation, at the age of 1.5 years, laboratory findings revealed Free T4: <0.4 ng/dl and TSH: 3.25 µU/ml. As a result, L-thyroxine treatment was initiated. The parents are consanguineous (second-degree relatives). The other two siblings are healthy and alive, and there is no similar medical history in the family. Karyotype analysis revealed a normal female karyotype (46, XX). A homozygous pathogenic variant, c.205C>T (p.Gln69*), in the TSHB gene (NM_000549.4) was identified. Sanger sequence analysis revealed that parents were heterozygous. Microarray: arr(1-22)x2,(X)x2, normal Pituitary MRI was normal, and all other pituitary hormones, including prolactin (PRL), were secreted at normal levels. Following the initiation of L-thyroxine therapy, the patient showed positive improvements in neuromotor development.

Conclusion: Isolated TSH deficiency is not detected by routine neonatal TSH-based screening, which represents a significant clinical challenge. In particular, infants presenting with neuromotor retardation in neurology clinics should have thyroid function evaluated, including Free T4 and Free T3 levels. In this case, delayed diagnosis and treatment of profound central hypothyroidism contributed to neurodevelopmental delays.