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Hyperprolactinaemia in Children – A Common Diagnostic Dilemma

European Endocrinology, 2006(2):81-83; DOI: http://doi.org/10.17925/EE.2006.00.02.81

Prolactin (PRL) is a peptide hormone secreted by lactotroph cells of the anterior pituitary. PRL is predominantly under inhibitory influence of hypothalamic dopamine, whereas thyrotropin-releasing hormone (TRH), among other endogenous substances, is the main PRL-releasing factor. In physiological conditions, PRL secretion is also affected by numerous exogenous influences, such as stress, physical effort, hypoglycaemia, lactation and sleep.
The main activity of PRL is its influence on the mammary gland (the so-called mammotrophic and lactotrophic effect) and the gonads, inhibiting the pulsatile excretion of gonadotropin-releasing hormone (GnRH) and the secretion of follicle-stimulating hormone (FSH) and luteinising hormone (LH).
Since human PRL was purified in 1972, the clinical syndrome of hyperprolactinaemia has been characterised extensively, the predominant symptoms being galactorrhoea, oligomenorrhoea or secondary amenorrhoea, infertility in women and reduced libido, impotence and gynaecomastia in men. In children and adolescents, major clinical signs of hyperprolactinaemic syndrome are delayed puberty, gynaecomastia, galactorrhoea and primary amenorrhoea.
Hyperprolactinaemia represents a common diagnostic dilemma due to the fact that it is often encountered in clinical practice even in the absence of significant pathology. An elevated PRL value, also in asymptomatic patients, creates the need to rule out diverse organic and functional aetiologies of hyperprolactinaemia (see Table 1). Therefore, differential diagnosis of hyperprolactinaemia may be difficult and undiscounted – especially in children and adolescents, in whom the stress of venipuncture even causes mild PRL increase.
Prolactinomas
Prolactinomas, the most common functioning pituitary tumours, are the most frequent cause of hyperprolactinaemia in patients aged two to 80 years; however, these tumours are less frequent in children. Also, hyperprolactinaemia may derive from a pituitary tumour that contains bipotential cells secreting PRL and another pituitary hormone, e.g. growth hormone (GH), or from two distinct adenomas producing various hormones. From this point of view, these hyperprolactinaemic syndromes may overlap other endocrine conditions with affected pituitary function.
For pituitary prolactinoma, the clinical syndrome traditionally described in children is caused by functional alterations resulting from hyperprolactinaemia (i.e. galactorrhoea, gynaecomastia, amenorrhoea and delayed puberty) and/or by the mass effect of the tumour (i.e. headaches, visual field abnormalities, etc.). Interestingly, there is a predominance of macroprolactinoma over microprolactinoma in most paediatric studies; at the time of diagnosis, males present mainly with neurophthalmologic abnormalities secondary to tumoural growth, whereas in females, endocrine-gynaecological symptoms are predominant.