The clinical features of prolactinoma are attributable to three main factors: hyperprolactinemia, space occupation by the tumor, and varying degrees of hypopituitarism (Table 1). The individual clinical picture will be determined by the gender and age of the patient and the tumor size. In brief, hyperprolactinemia stimulates milk production, particularly from the estrogen-primed breast, and inhibits hypothalamic gonadotropin-releasing hormone (GnRH) release, which leads to hypogonadotropic hypogonadism.
Premenopausal women, most of whom have microprolactinomas, usually have oligomenorrhea or amenorrhea (90%) and/or galactorrhea (up to 80%). Anovulatory infertility is common. Excluding pregnancy, hyperprolactinemia accounts for 10-20% of cases of secondary amenorrhea. In passing, it is worth remembering that most women with galactorrhea do not have menstrual disturbance, hyperprolactinemia, or a pituitary tumor.
Postmenopausal women are, by definition, already hypogonadal and markedly hypoestrogenemic. Hyperprolactinemia in this age group does not, therefore, present with classic symptoms and may be recognized only when a large pituitary adenoma produces headache and/or visual disturbance.
The men with hyperprolactinemia experience reduced libido, impotence (75%), and infertility associated with a reduced sperm count. Such symptoms
Clinical Features of Prolactinoma
A. Caused by prolactin excess
• Reduced libido
B. Caused by tumor size (usually in men)
• Visual failure, classically bitemporal hemianopia
• Cranial nerve palsies
C. Caused by other pituitary hormone deficiency
• Microprolactinoma—other pituitary function usually normal
• Macroprolactinoma—varying degrees of hypopituitarism may be present aLess common features.
are often concealed or ignored, particularly by older men, so men tend to present later with larger tumors causing pressure symptoms (Table 1). Galactorrhea is uncommon in men but does occur occasionally. Weight gain is noted frequently by men with hyperprolactinemia. Prolactinoma is an unusual cause of delayed puberty in both sexes, and some advocate the routine measurement of serum PRL in this situation.
Reduced bone mineral density (BMD) is a well-recognized long-term effect of untreated hyperprolactinemia. Studies of women with hyperprolactinemia and amenorrheia women have shown reductions in trabecular BMD of approx 20% (range 10%-26%) and cortical BMD of 6% (range 2.5%-11%) (3). Reduced estrogen levels, as well as the direct effect of hyperprolactinemia, play a role in osteopenia. A longitudinal follow-up study of untreated women with amenorrheia suggested that BMD loss is progressive in some but not all cases, patients who are overweight and those with higher androgen levels being afforded some protection (4). Restoration of menses after therapy results in an increase in bone density, although it may not return to normal (4,5). Men with hypogonadism secondary to hyperprolactinemia also have significant BMD reductions. In one study of 20 men, 16 had osteopenia at the spine and 6 at the hip (6). Adolescents had lower bone densities at the time of diagnosis, and less improvement was observed after two yr of dopamine agonist therapy, compared with adults with prolactinomas (7).
Table 2 Causes of Hyperprolactinemia
• Anti-emetics (e.g., metoclopramide, domperidone, prochlorperazine)
• Phenothiazines (e.g., chlorpromazine, thioridazine)
• Primary hypothyroidism
• Pituitary tumors
• GH secreting (30% of people with acromegaly)
• Nonfunctioning (stalk pressure or disconnection hyperprolactinemia)
• Hypothalamic lesions (rare)
• Langerhan's cell histiocytosis
• Hypothalamic tumors
• Chest wall stimulation
• Repeated breast self-examination
• Post-herpes zoster
• Liver or renal failure
GH, growth hormone.
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