In patients with prolactinomas, the magnitude of prolactin elevation is generally proportionate to tumour size. This is an important concept because modest degrees of prolactin excess in patients with large sellar masses demonstrated on MRI scan may not represent prolactinomas, or in some cases a diagnosis other than a pituitary adenoma. Patients with hyperprolactinemia can be either asymptomatic or demonstrate clinical manifestations of prolactin excess (please see Table 1). Hyperprolactinemia often leads to central hypogonadism in patients of both genders, primarily caused by suppression of hypothalamic gonadotropin- releasing hormone (GnRH) pulsations.
Table1. Clinical manifestations of hyperprolactinemia and prolactinomas
In women, hyperprolactinemia is often associated with galactorrhoea, irregular menstrual cycles (oligomenorrhea or secondary amenorrhea) and infertility. Bone loss may occur as a consequence of long- standing hypogonadism. In contrast, hyperprolactinaemic women with regular menses are unlikely to develop osteoporosis because of an elevated prolactin level unless prior amenorrhea had occurred. Women may develop hyperandrogenism (hirsutism, acne) as a consequence of stimulation of adrenal androgen secretion by prolactin excess. In men, hyperprolactinemia may lead to low libido, erectile dysfunction, and infertility. Gynaecomastia may develop in some men; however, galactorrhoea is quite uncommon in men. Anaemia and bone loss may occur in men with long- standing hypogonadism. Children and adolescents of both genders may present with delayed puberty, including primary amenorrhea in girls.
Patients with large sellar masses (including macroprolactinomas) may develop anterior hypopituitarism and require thorough evaluation of anterior pituitary function. However, diabetes insipidus is distinctly rare in patients with pituitary adenomas who did not undergo pituitary surgery.
Additional evidence of mass effect may occur in patients with macroadenomas. Headache may occur as a result of pressure exerted on the dura. Patients with pituitary apoplexy typically pre sent with severe headache of acute onset as a result of haemorrhage within a pituitary adenoma. Patients whose tumours extend into the suprasellar cistern may experience visual field deficits as a con sequence of compression of the optic apparatus. Central scotomas may occur as a result of prechiasmatic optic nerve compression, whereas impingement on the optic chiasm may result in bitemporal vision loss; compression of one of the optic tracts may lead to homonymous hemianopsia.
Pituitary tumours may also extend laterally into the cavernous sinuses where they may impinge upon cranial nerves III, IV, V1, V2, VI. However, the vast majority of patients with cavernous sinus involvement have no clinical evidence of cranial nerve dysfunction, with the exception of patients with pituitary apoplexy or occasional patients with aggressive pituitary adenomas, who may experience ophthalmoplegia, facial pain or numbness. Very infrequently, large pituitary tumours compressing the temporal lobes may cause complex partial seizures. Giant prolactinomas that extend into the third ventricle may lead to obstructive hydro cephalus. Tumours that extend inferiorly may erode the sphenoid and extend into the sphenoid sinus. These patients may rarely experience rhinorrhoea as a result of cerebrospinal fluid (CSF) leak, precipitated by dopamine agonist therapy that causes shrinkage of a macroprolactinoma and unmasks rents in the dura and bone, and require surgical intervention to correct the leak.
A minority of patients have manifestations of associated conditions, including patients with the MEN 1 syndrome, who often have primary hyperparathyroidism (90%) or entero- pancreatic neuroendocrine tumours (30– 40%). These conditions are dis cussed in separate chapters. To identify the possibility of MEN 1 syndrome in the absence of a pertinent family history, it is prudent to measure serum calcium levels in all patients presumed to have prolactinomas.
