Pituitary adenomas arise within the sella turcica. They are classified according to the pituitary hormone which they secrete: most tumours secrete prolactin, growth hormone, or corticotropin. The remainder are often called chromophobe adenomas, and many of them also have some secretory product. They generally grow slowly and may remain clinically silent for many years. Malignant transformation is rare.

Pituitary adenomas gradually enlarge the sella turcica and expand into the suprasellar cisterns. Invasion of the cavernous sinus and sphenoid sinus can also occur. Growth of the tumour impairs pituitary function, inducing hypothyroidism, hypoadrenalism, and hypogonadism. Suprasellar enlargement can compress the optic chiasm, causing bitemporal hemianopia and loss of visual acuity. Patients are generally unaware of this phenomenon until the tumour becomes large and visual acuity begins to fail. Further growth may result in serious cognitive and emotional problems, and may cause hydrocephalus.

Although some adenomas may reduce pituitary function, secretory adenomas can have profound systemic effects. These adenomas are classified by the secretory granules within the tumour cell, which can be identified by endocrine testing or immunocytochemistry of surgical specimens.

The presence of a pituitary adenoma can be ascertained by both radiological and endocrine evaluation. Most pituitary adenomas are identified by MRI scanning (Fig. 1) 2284. Contrast enhancement with gadolinium generally shows a hyperintense lesion enlarging the sella turcica, often compressing or invading the cavernous sinuses and rising to the suprasellar cisterns to compress the optic chiasm. Very small tumours (microadenomas) are often not seen by MRI scanning, although they may appear as hypointense areas following the administration of gadolinium.

Many tumours can be identified by measuring both resting and dynamic levels of the specific hormonal product. All tumours may cause hypopituitarism and patients may demonstrate hypothyroidism, loss of libido, loss of potency, infertility, hypoadrenalism, or diabetes insipidus. Secretory tumours produce specific clinical and endocrine problems.

Prolactin-secreting tumours are usually found in younger women and cause loss of libido, infertility, amenorrhoea, and galactorrhoea. Long-term hyperprolactinaemia may also cause osteoporosis, due to oestrogen deficiency. Prolactinomas can be identified by high levels of prolactin in the serum, ranging from 30 to 5000 ng/ml (normal, 5–15 ng/ml). When the diagnosis is in doubt, assessment following TRH stimulation may help: the normal pituitary gland secretes high levels of prolactin following the administration of TRH. Prolactinomas generally fail to secrete more prolactin in this situation and serum levels remain unchanged, although this test produces many false-positive results. Prolactin levels may also be raised by compression of the pituitary stalk, and other pituitary tumours may therefore cause prolactin levels to rise to 20 to 200 ng/ml. The hypothalamus produces prolactin-inhibiting factor which under ordinary circumstances suppresses prolactin levels to below 15 ng/ml.

Compression of the pituitary stalk by a non-secreting pituitary adenoma, for example, may interrupt the flow of this factor, thus causing a rise of prolactin from the now uninhibited pituitary gland.

Corticotropin-producing tumours cause Cushing's disease, a constellation of symptoms due to cortisol excess. The most prominent of these symptoms are moon face, abdominal striae, buffalo hump, hypertension, and diabetes mellitus. The diagnosis is first suspected by the demonstration of cortisol excess in the serum or in a 24-h urine sample. Cortisol levels may also be raised by other factors such as stress, depression, and some psychotropic drugs; however, this can be totally suppressed by the administration of low doses of dexamethasone. Failure of dexamethasone to suppress cortisol secretion suggests the presence of an adenoma. ACTH, synthesized within the sella turcica, finds its way into the cavernous sinus and then flows into the inferior petrosal vein, where it can be measured by retrograde venous femoral catheterization. If the level of ACTH is greater than that in the systemic venous circulation, a diagnosis of pituitary adenoma is almost certain.

Acromegaly is due to tumours that produce growth hormone. The disease is disfiguring, causing prognathism and overgrowth of joints, especially in the hands and feet. It has significant systemic effects, such as hypertension, cardiomyopathy, and diabetes mellitus. Patients also suffer from excessive sweating, arthralgias, and lassitude. This syndrome is almost exclusively due to a pituitary tumour. The diagnosis of acromegaly depends upon the demonstration of raised serum growth hormone levels, which may range from 5 to 1000 ng/ml or more. Levels of growth hormone may be raised under normal circumstances; however, the administration of glucose suppresses this hormone to below 2 to 3 ng/ml in normal subjects. In acromegaly, however, growth hormone levels fail to be suppressed. If the blood level of somatomedin C is raised, the diagnosis of acromegaly is almost certain. Since acromegaly is almost always the result of a pituitary adenoma, confirmation by endocrine assays is enough to justify exploration of the pituitary gland to cure this disease, whether or not imaging studies demonstrate a tumour.

Tumours that synthesize other pituitary hormones are less common. Tumours producing thyrotropin, luteotropin, and follicle stimulating hormone have been identified, but are very rare. Many tumours, previously called chromophobe adenomas, secrete subunits of glycoprotein hormones. These tumours rarely cause systemic effects, except those due to panhypopituitarism.

Other lesions that may enlarge or obscure the pituitary area include craniopharyngiomas, meningiomas, metastatic tumours, and lesions such as arachnoid cysts and Rathke's cleft cysts. All these lesions may cause hypopituitarism and visual loss and the diagnosis is usually confirmed only at operation.

Most tumours can be successfully managed by the trans-sphenoidal approach, in which the surgeon approaches the sella turcica by a submucosal incision through the nose along the nasal septum approaching the pituitary fossa via the sphenoid sinus (Fig. 2) 2285. Large tumours can often be almost totally removed. Microadenomas causing systemic disease such as Cushing's disease or acromegaly may be totally excised, leaving behind the normal gland. The remission rate following removal of microadenomas varies from 80 to 95 per cent. Recurrence may occur in 5 to 15 per cent of patients who show an initial ‘chemical cure’.

Larger tumours may recur at a variable rate. Although radiotherapy is generally not the principal mode of therapy, it is useful to treat partially removed or recurrent tumours. Medical management is possible for some tumours, especially prolactinomas, which may be controlled by the administration of bromocriptine, a dopamine agonist which inhibits prolactin secretion and reduces tumour size. Most patients with this tumour, usually younger women, are managed in this way; the success rate with therapy ranges from 80 to 90 per cent. Almost all of the patients show shrinkage of the tumour but must be maintained on the drug for life since when bromocriptine is withdrawn most tumours recur. Even giant tumours producing prolactin can be successfully managed by bromocriptine alone. Patients who are unable to tolerate bromocriptine because of gastrointestinal or emotional side-effects may require surgery.

Acromegaly may be partially controlled by bromocriptine or somatostatin analogues, which tend to reduce growth hormone secretion more effectively. However, the latter must be given parenterally and have side-effects, including cholelithiasis.

Very ill patients with Cushing's disease who are not candidates for surgery may be treated with agents that suppress cortisol synthesis, such as ketaconazole. These drugs are not always well tolerated and are not the first line of therapy for the ordinary patient with Cushing's disease.

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Martin JB, Reichlin S. Clinical Neuroendocrinology. Philadelphia: FA. Davis Co., 1987.