Treatment of pituitary adenomas

Most pituitary adenomas are managed through one of two doors: switching off a hormone that the tumour secretes, or decompressing the structures it presses on. For most adenomas the surgical door comes first, because removing the tumour is the only chance of cure, and transsphenoidal surgery reaches the sella through the sphenoid sinus without opening the skull. The prolactinoma is the exception, treated with drugs rather than surgery, and a non-functioning adenoma that causes no mass effect may need no treatment at all.

Prolactinoma

Prolactinomas are treated medically first because the signal that normally restrains the lactotroph can be supplied as a drug. Dopamine agonists — cabergoline is preferred to bromocriptine — bind the dopamine D2 receptor on the lactotroph and suppress both prolactin secretion and tumour growth. They normalise prolactin and shrink the tumour in about 80-90% of patients, so transsphenoidal surgery is reserved for the minority who cannot tolerate the drug, do not respond to it, or need urgent decompression. When prolactin has been normal and the tumour is no longer visible on MRI after at least 2 years of treatment, the drug can be slowly withdrawn under continued follow-up. A microprolactinoma that causes no symptoms needs no treatment at all.

Growth hormone adenoma

Acromegaly and gigantism, the syndromes of growth hormone excess, are treated by transsphenoidal surgery first, because complete removal offers the only chance of cure; roughly 20% of microadenomas and 40% of macroadenomas are not cured and need long-term medical treatment. When the tumour persists, the first drug is a somatostatin receptor ligand such as octreotide or lanreotide, which suppresses growth hormone release; how well it works depends on how much of the somatostatin receptor subtype 2 the tumour expresses. If control is still not achieved, pegvisomant, which blocks the growth hormone receptor instead of secretion, or cabergoline can be used, and radiotherapy is reserved for residual tumour that drugs cannot control.

Cushing’s disease

An ACTH-secreting adenoma produces Cushing’s disease, the form of cortisol excess that comes from the pituitary, and the first-line treatment is selective removal of the tumour by transsphenoidal surgery, which achieves remission in most patients in experienced centres. When surgery is not curative or not possible, the options include repeat surgery, radiotherapy (whose effect takes months to years to appear), drugs that lower cortisol such as the steroidogenesis inhibitor ketoconazole or the somatostatin receptor ligand pasireotide, and bilateral adrenalectomy. Adrenalectomy removes the source of cortisol almost completely but leaves permanent adrenal insufficiency, so it commits the patient to lifelong replacement.

Thyrotroph adenoma

A TSH-secreting adenoma causes hyperthyroidism with an inappropriately normal or high TSH. Transsphenoidal surgery is first-line; when it does not achieve remission, somatostatin analogues (octreotide or lanreotide) control hormone secretion and reduce tumour size, and radiotherapy is a further option.

Non-functioning and gonadotrope adenomas

Adenomas that produce no clinically active hormone do not respond to the drugs used for the secreting tumours, so the decision is between surgery and surveillance. Transsphenoidal surgery is first-line when the tumour compresses the optic chiasm or causes another mass effect. An incidental, non-functioning macroadenoma without mass effect does not need immediate surgery; it is followed with regular hormonal, imaging and visual-field checks. Nothing shrinks these tumours medically.

Comparing the options

Side by side, the choice of first-line treatment follows the tumour type:

These options assume a sporadic tumour of a single type. Some adenomas instead arise within inherited syndromes, and the non-functioning tumours raise a diagnostic problem of their own: distinguishing them from a prolactinoma, because the treatment differs.