Tumours of the pituitary gland are almost always benign and are usually curable.¹

Pituitary tumours can cause problems by:

• Excessive hormone production
• Local effects of the tumour
• Inadequate hormone production by the remaining pituitary gland

Types of tumour

Pituitary tumours include (in decreasing order of frequency):

• Non-functioning adenomas
• Prolactinomas
• Growth hormone (GH)-secreting
• Adrenocorticotrophic hormone (ACTH)-secreting
• Thyroid-stimulating hormone-secreting
• Leutinising hormone/follicle-stimulating hormone (LH/FSH)-secreting tumours

Hormone production

• The tumours that are often hormonally active are the eosinophilic growth hormone (GH)-secreting adenomas, basophilic adrenocorticotrophic hormone-secreting adenomas and prolactin-secreting adenomas. These tumours may protrude outside of the pituitary fossa (sella turcica):
  • Adrenocorticotrophic hormone-producing tumours:
    Basophilic adenoma, presents with Cushing's syndrome. Enlargement of the tumour is usually slowly progressive. Initially confined to the sella turcica, but may enlarge and become invasive after bilateral adrenalectomy (Nelson's syndrome).
  • Prolactin-producing adenomas:
    Usually intrasellar; are often small (less than 10 mm) but may become large enough to enlarge the sella turcica.
  • GH-producing tumours:
    Eosinophilic - results in gigantism in children and acromegaly in adults. Suprasellar extension is not uncommon. Enlargement of the tumour is usually slowly progressive.
• Non-functioning tumours:
  They cause symptoms by extension beyond the sella, resulting in pressure on surrounding structures. In the absence of endocrine symptoms, visual loss is the usual initial manifestation.

Epidemiology

• The annual incidence of clinically functioning pituitary tumours is estimated to be approximately 1 to 2 per 100,000 of the population.¹
• This is probably an underestimate because they tend to be underdiagnosed.

Presentation

Depends on the hormone secreted by the tumour as well as the pattern of growth of the tumour within the sella turcica.

• Local effects resulting from an expanding pituitary mass:
  • An expanding mass within the pituitary fossa may give rise to headache, neuro-ophthalmological defects or facial pain according to the size and direction of expansion.
    • Headaches: are classically retro-orbital or bitemporal. They tend to be worse on waking. Sudden catastrophic headaches may result from pituitary apoplexy. Very large pituitary tumours may cause obstruction of CSF, resulting in hydrocephalus and expansion of the lateral ventricles.
    • Visual field defects: common but they are often asymptomatic. Bitemporal hemianopia is the classic abnormality but any unilateral or bilateral visual field defect may occur.
    • Ocular nerve palsies cause a squint.
    • Extensive extension into the hypothalamus may result in disorders of appetite, thirst, temperature regulation and consciousness.
• Anterior pituitary hormonal deficiency:
  • Panhypopituitarism or varying degrees of loss of any of the six hormones may occur.
  • Hypopituitarism tends to occur in the following order of leutinising hormone (LH), growth hormone (GH), thyroid-stimulating hormone (TSH), and lastly adrenocorticotrophic hormone (ACTH) and follicle-stimulating hormone (FSH).
  • Therefore the presentation in adults tends to be infertility, oligo/amenorrhoea, decreased libido and erectile dysfunction. Deficiency of LH and GH may result in decreased muscle bulk, decreased body hair, central obesity and small, soft testes.
  • In children, hypopituitarism commonly presents with delayed puberty or impairment of growth.
  • Diabetes insipidus is rarely a presenting feature but may occur following surgery for a pituitary adenoma.
• Hypersecretion of the involved pituitary hormone, e.g. acromegaly, hyperprolactinaemia, Cushing's disease, thyrotoxicosis.

Investigations

• Endocrine studies for hormone hyposecretion and hypersecretion.
• Lateral skull X-ray: may incidentally show enlargement of the fossa but is not a definitive investigation.
• Visual fields: common defects are upper-temporal quadrantanopia and bitemporal hemianopia.
• MRI scan is the preferred imaging investigation and is superior to CT scanning. However, small lesions within the pituitary fossa on MRI that are consistent with small pituitary microadenomas occur in as many as 10% of normal individuals ('pituitary incidentalomas').²

Differential diagnosis

• Other neoplasms of the sellar region include craniopharyngiomas, Rathke's cleft cysts, and, less commonly, meningiomas, germinomas, and hamartomas.³
• Craniopharyngiomas are benign, cystic tumours found above the sella turcica. They present with headaches, visual field defects and hypopituitarism (including growth failure, as often present in childhood and adolescence).
• Other causes of headache, visual field defects, visual disturbance and endocrine dysfunction.

Management

Treatment depends on the type of pituitary tumour and whether it extends into the brain around the pituitary.
Hormone-secreting tumours can be treated by surgery, radiation therapy or by drugs such as bromocriptine (prolactin-secreting adenomas) or somatostatin analogues (growth hormone (GH)-secreting adenomas).

Surgery

Trans-sphenoidal surgery is the usual treatment of choice for lesions confined within the sella turcica and adrenocorticotrophic hormone (ACTH)-secreting adenomas. Frontal craniotomy is rarely required. Lesions extending beyond the confines of the pituitary are most frequently non-functioning chromophobe adenomas and require additional radiation therapy. Rapid deterioration of vision is an immediate indication for surgery.

Radiotherapy

Radiotherapy is reserved for patients whose tumour has been incompletely resected or who remain hypersecretory after surgery.⁴

Somatostatin analogues

These analogues, e.g. Sandostatin®, are now the main medical treatment for GH-secreting tumours and are also used for the rare thyroid-stimulating hormone (TSH)-secreting pituitary tumours.⁴ Octreotide and lanreotide will control GH secretion in the majority of patients with acromegaly and in a minority cause some tumour shrinkage.⁵

Bromocriptine

Drug therapy with bromocriptine has been used with success in patients with prolactin-secreting tumours. The dopamine agonist quinagolide has been used successfully with minimal side-effects in relapsing or refractory cases after bromocriptine failure.⁶While waiting for the effects of radiotherapy, inhibitors of adrenal steroid production, e.g. mitotane, ketoconazole, may be indicated.⁷

Recurrent pituitary tumours

• Patients who develop recurrence following surgical resection can be treated with radiation therapy.¹
• Re-irradiation of recurrent pituitary adenomas in selected patients is reported to have achieved long-term local control with improvement or stabilisation of visual symptoms.¹

Complications

Pituitary apoplexy - sudden onset hypopituitarism caused by an acute infarction of a pituitary adenoma. See separate article Acute Pituitary Failure.

Prognosis

Remission can be obtained in up to 90% of patients with microadenomas and in about 50% to 60% of those with macroadenomas.¹

Document references

1. National Cancer Institute (US); Pituitary Tumors
2. Mavrakis AN, Tritos NA; Diagnostic and therapeutic approach to pituitary incidentalomas. Endocr Pract. 2004 Sep-Oct;10(5):438-44. [abstract]
3. Jagannathan J, Kanter AS, Sheehan JP, et al; Benign brain tumors: sellar/parasellar tumors. Neurol Clin. 2007 Nov;25(4):1231-49. [abstract]
4. Leavens ME, McCutcheon IF, Samaan NA; Management of pituitary adenomas. Oncology (Williston Park). 1992 Jun;6(6):69-79; discussion 79-80. [abstract]
5. Davis JRE, Trainer PJ; Pituitary tumour therapy: using the biology. British Society for Neuroendocrinology; June 2005.
6. Schultz PN, Ginsberg L, McCutcheon IE, et al; Quinagolide in the management of prolactinoma. Pituitary. 2000 Dec;3(4):239-49. [abstract]
7. Chanson P, Salenave S; Diagnosis and treatment of pituitary adenomas. Minerva Endocrinol. 2004 Dec;29(4):241-75. [abstract]

Internet and further reading

• The Pituitary Foundation; GP Fact File
• Macmillan Cancer Suppport (Cancerbackup); Pituitary gland tumours.
• Price DE, Redfern RM; "Did you see it? Where did it go?". BMJ. 2007 Dec 22;335(7633):1284.
• Bevan JS; Management of pituitary tumours. BMJ. 1999 May 8;318(7193):1226-7.

Acknowledgements