ESPE2024 Rapid Free Communications Pituitary, Neuroendocrinology and Puberty 2 (6 abstracts)
1Department of Health Sciences, University of Florence, Florence, Italy. 2Diabetology and Endocrinology Unit, Meyer Children's Hospital IRCCS, Florence, Italy. 3Metabolic and Neuromuscular Unit, Meyer Children Hospital, University of Florence, Florence, Italy
Inherited disorders of biogenic amine metabolism are rare neurometabolic disorders caused by defects in neurotransmitters (dopamine, serotonin, norepinephrine, epinephrine). Dopamine deficiency leads to hyperprolactinemia. Prolactin blood level is used as peripheral indirect biomarker of central dopamine deficiency and can help in adjusting the therapy dosage, which primarily consists of using L-dopa. However, patients may become refractory to L-dopa and they could present hyperprolactinemia; prolactinoma has also been described. Elevated prolactin levels can interfere with the normal pulsatile release of gonadotropins. Even if gonadotropins basal values may not be suppressed, patients could present hypogonadism with amenorrhea, delayed puberty, stunted growth, osteoporosis. In cases of L-Dopa-resistant hyperprolactinemia, lactotroph cells seems to retain the ability to decrease prolactin secretion in response to activation of D2 receptors by dopamine agonists (DA), such as cabergoline. We present three cases followed at Meyer Children’s Hospital IRCCS in Florence, affected by two distinct disorders of biogenic amine metabolism, two with tyrosine hydroxylase (TH) deficiency and one with dihydropteridine reductase (DHPR) deficiency; both conditions are associated with hyperprolactinemia. Patients received the diagnosis in infancy (median 5 months) and were treated with L-Dopa, whose dosage has been adjusted based on prolactin blood levels. All three patients exhibited hyperprolactinaemia despite therapy (macroprolactinaemia has been excluded) and symptoms of hypogonadism such as delayed puberty with stunted growth (one), primary amenorrhea (one), and low bone mineral density (in two cases). The baseline gonadotropin levels were suppressed in two patients and normal in one. Pituitary gland MRI showed in two cases normal findings; one - with TH deficiency - developed a microadenoma, of stable size over time, yet concurrent worsening of hyperprolactinemia and onset of hypogonadism. Patients affected by TH deficiency have been treated with cabergoline, presenting a decrease in serum prolactin concentrations (medium PRL pre therapy 500 ng/mL, post therapy 24 ng/mL), an improvement of symptoms related to hypogonadism (onset of menarche after four months) and a normalization of sex hormones’ levels. No adverse events related to cabergoline have been reported. The patient with DHPR deficiency was treated with gonadotropins with a good response in terms of progression of pubertal stages. In conclusion, alongside monitoring prolactin levels, it is important to evaluate pubertal progression to identify early signs/symptoms of hypogonadism. Long-term outcome studies in children and adolescents are necessary to understand the effects of DA on treating and preventing hyperprolactinemia and its consequences on the pubertal development and growth.