A Novel TSH Receptor Gene Variant Associated with Non-Autoimmune Hyperthyrotropinemia: A Case Report

Area of Science:

• Endocrinology
• Genetics
• Molecular Biology

Background:

• Thyroid-Stimulating Hormone (TSH) resistance is characterized by reduced sensitivity to TSH, necessitating elevated TSH levels for normal thyroid hormone production.
• Hyperthyrotropinemia, a condition of elevated TSH, can be caused by various factors, including genetic mutations affecting the TSH receptor.

Observation:

• A 15-year-old female with hyperthyrotropinemia presented with tachycardia after levothyroxine dose increase.
• Thyroid ultrasound and antibody tests were normal; however, subclinical hypothyroidism was noted.
• Genetic testing revealed a novel TSHR gene variant (p.C598R) in the patient and her father, suggesting an inherited condition.

Findings:

• A novel loss-of-function mutation in the TSH receptor (TSHR) gene, p.C598R, was identified.
• In-silico analysis confirmed a loss-of-function phenotype for this TSHR variant.
• The mutation was associated with a TSH resistance phenotype in the affected individuals.

Implications:

• This discovery expands the known genetic causes of TSH resistance.
• Understanding this novel mutation aids in diagnosing and managing patients with unexplained hyperthyrotropinemia.
• Further research into TSHR variants can improve diagnostic accuracy and therapeutic strategies for thyroid disorders.