Revised: June 2014
Patients with tumours of the pituitary gland require multi-disciplinary assessment and follow up. Evaluation should include consultation with an endocrinologist, neurosurgeon and neuro-ophthalmologist
Pituitary tumours can present through mass effects, hormone dysfunction or as an incidental finding on a CT or MRI scan. The mass effect can result in compression of the optic chiasm with visual field compromise. The tumour may produce an excess of hormones and result in acromegaly, Cushing's syndrome or hyperprolactinemia. The tumour may compromise pituitary function and result in panhypopituitarism and/or diabetes insipidus
Patients with acute headaches, nausea, vomiting, visual field deterioration or extra ocular muscle palsies require urgent surgical referral and assessment for pituitary apoplexy.
Growth Hormone Secreting Tumour: Somatotropinoma
These tumours produce gigantism in children and acromegaly in adults. The diagnosis is confirmed by endocrine tests in a patient with typical clinical features of acromegaly. The endocrine tests include measurement of growth hormone and insulin-like growth factor-1 (IGF-1). This is a protein produced by the liver in response to growth hormone stimulation. Elevated growth hormone concentration results in elevation of the IGF-1 concentration. IGF-1 has a much longer half-life than growth hormone and therefore provides an assessment of growth hormone secretion over time. Growth hormone has a very short half-life. It is measured in minutes. There is no place for random growth measurement in the diagnosis of acromegaly. To confirm the diagnosis of acromegaly a glucose tolerance test is done. IGF-1 is measured in the baseline sample and growth hormone is measured after glucose ingestion. IGF-1 must be elevated and the growth hormone does not suppress after glucose. In normal subjects the growth hormone should decrease to <1 ug/l.
The primary treatment of acromegaly is surgical removal of the tumour. This is usually successful in patients with a microadenoma (tumour <10mm) but the results in macroadenomas are disappointing with at least a 50% failure rate. After surgery it is important to reassess growth hormone and IGF-1 concentration to determine if surgical cure was achieved. If the patient has not been cured it is important to initiate the second line of treatment. Acromegaly increases the risk of colonic tumours, hypertension, diabetes, arthritis and cardiac disease and, as a result there is an increased death rate. Therefore, it is important to reduce growth hormone levels. The second line of treatment is octreotide (sandostatin). This is variant of somatostatin, a naturally occurring inhibitor of growth hormone release. Octreotide can be given by subcutaneous injection three times per day. However, now it is more common to use sandostatin LAR, a long-acting form, given by an intramuscular injection once per month. The goal of therapy is to normalize IGF-1 levels. The IGF-1 levels must be monitored throughout therapy. A new drug called Pegvisomant is also used to treat acromegaly, but is not yet available in Canada
Radiation therapy is the third line of treatment for persisting acromegaly. It is considered when sandostatin is not successful or results in side effects. It takes many years for radiation to lower growth hormone levels. Radiation may result in hypopituitarism; therefore, pituitary function should be monitored in the post-treatment interval at least on a yearly basis.
Prolactin Secreting Tumour: Prolactinoma
This is the most common hormonally active tumour. The presentation in women includes menstrual dysfunction, amenorrhea, galactorrhea, and infertility. In men hyperprolactinemia produces impaired libido, low testosterone and erectile dysfunction. In patients with prolactinomas the prolactin is usually >100 ug/L. A prolactin >300 ug/L almost invariably confirms the tumour is a macroadenoma. Non-functioning tumours of the pituitary may result in slightly elevated prolactin usually less than 100 ug/L. This is caused by impairment of hypothalamic transmission of dopamine to the pituitary. This is referred to as the stalk effect.
The primary treatment of prolactinomas is with a dopamine agonist. This results in a dramatic reduction of prolactin and tumour shrinkage in the majority of patients. If a patient presents with visual field impairment, a dopamine agonist may still be used as the primary therapy, but visual assessment is required on a weekly basis to document improvement. If visual fields do not improve in 2 weeks, surgical decompression should be considered.
Two dopamine agonist drugs are approved and available for the treatment of prolactinomas. The first, Bromocriptine, is given one to three times per day and has been used routinely since the early 1970. It is safe to use when fertility is desired and even through pregnancy when necessary. The newer dopamine agonist, carbergoline is long-acting and can be given once or twice per week. In some cases it is also more effective.
Bromocriptine often causes nausea, vertigo, and nasal stuffiness. If the medication cannot be tolerated orally it can be used as a vaginal suppository to reduce side effects. Another option is to switch ot carbergoline as it causes fewer side effects. The only disadvantage of carbergoline is the expense. Carbergoline appears to be safe in pregnancy, but because there is less data, Bromocriptine is still the drug of choice in pregnancy. A microadenoma can be cured surgically in the majority of patients and therefore this should be considered if bromocriptine and carbergoline cannot be tolerated. Patients must be advised not to stop the bromocriptine or carbergoline because the tumour can increase in size within days of stopping the medication. When pregnancy is contemplated, the patient should be assessed by an endocrinologist.
A repeat CT scan should be done 6-12 months after the start of bromocriptine to ensure that tumour size has decreased. Occasionally there is a discrepancy between prolactin response and tumour growth. A decrease prolactin does not guarantee tumour shrinkage.
ACTH Secreting Tumour: Corticotropinoma
ACTH producing pituitary tumours cause Cushing's syndrome. When this diagnosis is suspected referral to an endocrinologist is essential. Confirmation of the diagnosis requires extensive endocrine testing with suppression and stimulation tests and often petrosal sinus sampling for ACTH measurement.
Confirmation of pituitary dependent Cushing's syndrome is followed by transphenoidal exploration. Corticotropinomas are often small and may not be visualized on MRI imaging. The cure rate is 60-80% with trans-sphenoidal surgery.
If surgery fails the two options left are bilateral adrenalectomy and pituitary radiation. Patients who have had a bilateral adrenalectomy must be followed by an endocrinologist to replace the adrenal hormones and for the possible development of Nelson's syndrome. This is the development of a pituitary tumour after adrenalectomy. It is a serious complication as the tumour can be locally invasive and may result in distant metastases. The ACTH level rises dramatically and patients often pigment. The tumour must be treated aggressively with surgery and radiation.
Clinically Non-Functioning Adenoma
These tumours are hormonally silent. They can result in mild hyperprolactinemia from the stalk phenomena. They may result in panhypopituitarism from tumour compression of the normal pituitary gland. These tumours are often large at the time of diagnosis. The lack of hormone production delays diagnosis. Diagnosis is suspected by development of mass effects or as an incidental finding on a CT or MRI scan. Surgery is the primary form of therapy and often radiotherapy is required post-operatively to prevent recurrence. If there is considerable tumour bulk after surgery or serial CT scanning shows an increase in the size of the residual tumour mass referral for radiotherapy is required. After surgery pituitary function should be reviewed by an endocrinologist to exclude hypopituitarism.
Many of these tumours secrete gonadotropins (LH, FSH, alpha-subunit). There is no specific clinical syndrome associated with gonadotropin producing tumours. Pituitary tumours that produce no hormones have been called null cell adenomas. Gonadotropin secreting adenomas and null cell adnomas are clinically indistinguishable, are treated the same and therefore are grouped together.
TSH Secreting Pituitary Tumours
TSH secreting tumours are very rare but should be suspected when a patient develops hyperthyroidism, but the TSH level is not markedly suppressed. The TSH level may be elevated, but is often in the normal range. This is, however, inappropriate because other forms of hyperthyroidism are characterized by marked TSH suppression. These tumours are often large at presentation and surgery is necessary. Radiation and/or sandostatin may be also required.