Short stature-delayed bone age due to thyroid hormone metabolism deficiency

Short stature-delayed bone age due to thyroid hormone metabolism deficiency is a rare endocrine disorder caused by defects in the intracellular metabolism of thyroid hormones, leading to a form of congenital hypothyroidism. This condition is primarily associated with mutations in the SBP2 (SECISBP2) gene, which encodes a selenocysteine insertion sequence-binding protein essential for the synthesis of selenoproteins, including the deiodinase enzymes responsible for converting the prohormone thyroxine (T4) into the biologically active triiodothyronine (T3). Impaired deiodinase activity results in abnormal thyroid hormone levels, typically characterized by elevated T4 and reverse T3 (rT3) with low T3 levels, and mildly elevated TSH. The condition primarily affects the skeletal and endocrine systems. Key clinical features include proportionate short stature, significantly delayed bone age, and growth retardation during childhood. Patients may also exhibit features of mild hypothyroidism at the tissue level despite apparently normal or elevated circulating T4 levels, which can make initial diagnosis challenging. Additional features may include transient hearing impairment, mild intellectual delay, and increased sensitivity to oxidative stress due to broader selenoprotein deficiency. The thyroid hormone profile is distinctive and helps guide diagnosis. Treatment options are limited and primarily supportive. Selenium supplementation and careful thyroid hormone replacement with T3 (liothyronine) have been explored in some patients, with variable clinical benefit. Growth hormone therapy is generally not indicated unless concurrent growth hormone deficiency is documented. Long-term monitoring of growth, bone maturation, thyroid function, and neurodevelopmental outcomes is recommended. The condition is extremely rare, with only a small number of families reported worldwide.

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