Abstract

Tetrahydrobiopterin (BH4) deficiency causes hyperphenylalaninemia and impaired synthesis of serotonin and dopamine. Individuals with BH4 deficiency require personalized neurotransmitter replacement therapy to optimize treatment outcomes. An effective way to measure the success of this treatment is through serum prolactin levels; hyperprolactinemia indicates inadequate treatment and requires adjustments.Here, we report a 11-year- old girl with a diagnosis of BH4 deficiency who developed growth failure and persistent hyperprolactinemia despite L- dopa supplementation. Laboratory evaluation for growth failure revealed normal biochemical and thyroid hormone profiles, with decreased serumInsulin-like Growth Factor1 (IGF-1) and Insulin-like Growth Factor Binding Protein 3(IGFBP-3), delayed bone age, and markedly elevated prolactin. Accordingly, growth hormone stimulation tests were conducted, revealing suboptimal responses and confirming growth hormone deficiency. In light of growth hormone deficiency and persistent hyperprolactinemia, cerebral magnetic resonance imaging was performed, demonstrating a solid pituitary lesion highly suggestive of prolactinoma. These findings suggest that in patients with BH4 deficiency, hyperprolactinemia resistant to L-dopa therapy may indicate the development of prolactinoma. Therefore, in resistant cases, regular laboratory follow-up and cranial imaging are clinically important.