Hyperprolactinemia in children and adolescents: clinical characteristics and etiological spectrum

This study aimed to evaluate the etiological, clinical, and biochemical characteristics of pediatric patients diagnosed with hyperprolactinemia, a condition with a diverse range of underlying causes. We analyzed 160 pediatric patients diagnosed with hyperprolactinemia between January 2018 and January 2025. Hyperprolactinemia was defined by prolactin levels exceeding 25 ng/mL in girls and 20 ng/mL in boys on at least two separate occasions, with blood samples collected between 8:00 AM and 9:00 AM. Patients were categorized into two groups based on etiology: Group-1 (Pituitary and Hypothalamic Disorders, n = 38), including prolactinomas (n = 18), non-functioning pituitary adenomas (n = 8), craniopharyngiomas (n = 7), and empty sella (n = 5); and Group-2 (Non-Pituitary and Hypothalamic Disorders, n = 122), including polycystic ovary syndrome (PCOS) (n = 40), drug-induced hyperprolactinemia (n = 33), macroprolactinemia (n = 20), and idiopathic hyperprolactinemia (n = 29). Clinical presentations, biochemical findings, and treatment responses were assessed. The median age at diagnosis was 15.2 years (range: 2-17.9 years), with a female predominance of 73.1%. The median prolactin level was 45.8 ng/mL (range: 38.3-14,350), with significantly higher levels in Group-1 (213 ng/mL) compared to Group-2 (43.6 ng/mL, p < 0.05). No significant differences between groups were found for age, weight, height, or BMI SDS. The most common presenting symptoms were menstrual irregularities, galactorrhea, headache, and pubertal delay. Overweight/obesity were present in 48.8% of the cohort, with the highest prevalence in patients with PCOS (70%). A significant positive correlation between BMI-SDS and prolactin levels was found in patients with PCOS (r = 0.406, p = 0.009). Cabergoline achieved a 100% success rate in prolactinoma patients, with a significant decrease in BMI SDS observed after one year of treatment (p < 0.05). In patients with drug-induced hyperprolactinemia, most cases (82%) were associated with risperidone, and prolactin levels normalized after discontinuation or switching medications.

Our study emphasizes the complex nature of pediatric hyperprolactinemia, with various underlying causes and diverse clinical presentations. Effective management requires careful attention to both endocrine and metabolic factors. A multidisciplinary approach involving pediatric endocrinologists, neurologists, and psychiatrists is crucial for diagnosis and treatment. Further research, particularly on genetic factors and the relationship between hyperprolactinemia and conditions like PCOS, is needed to improve understanding and treatment strategies for pediatric hyperprolactinemia.

• Hyperprolactinemia in children and adolescents is a rare condition with diverse etiologies, including pituitary tumors, polycystic ovary syndrome (PCOS), medication use, and macroprolactinemia. • Prolactinomas are considered the most common pathological cause of hyperprolactinemia, often requiring dopamine agonist therapy.

• Unlike previous reports, PCOS was the most common etiology of hyperprolactinemia in this study, and a significant correlation was observed between prolactin levels and BMI-SDS in patients with PCOS. • Cabergoline treatment was highly effective in prolactinoma patients and also contributed to a significant reduction in BMI-SDS.