Information
Editors
Pituitary Tumours
Essentials
- About 90% of pituitary tumours are benign adenomas, i.e. glandular tumours.
- The tumours may be hormonally active and become manifest as clinically identifiable syndromes associated with the excessive hormone production.
- Inactive small adenomas do usually not cause symptoms and often are incidental findings.
- Large macroadenomas may cause symptoms not related to the hormone production by local compression (especially visual field defects and/or impairment of vision) or they may block the normal hormone production.
Epidemiology
- Seen as incidental findings (incidentalomas) in about every tenth patient who undergoes cranial MRIs for other reasons, but the prevalence of clinically significant adenomas is 1/1 000.
Symptoms and signs indicating pituitary tumour
- Symptoms of hormone deficiency
- In men, loss of libido and impotence, for example; in women secondary amenorrhea (gonadotropin deficiency)
- Abnormal fatigue (hypocortisolism, hypothyroidism)
- Thirst and increased urinary frequency (deficiency of antidiuretic hormone)
- The possibility of a pituitary tumour should also be borne in mind as a cause of
- hypothyroidism (disproportionately low TSH level)
- hyponatraemia (hypocortisolism).
- Symptoms of excessive hormone secretion
- Even small pituitary adenomas may cause clinically significant symptoms that are due to excessive hormone secretion.
- Symptoms of hyperprolactinaemia such as galactorrhoea and amenorrhoea
- Increase in shoe and ring size, sweating, headache, problems of joints and dental occlusion as symptoms of acromegaly
- Weight gain, facial rounding, susceptibility to bruises, muscular atrophy, bone loss, elevated blood pressure and blood sugar, as well as mood problems as symptoms of Cushing's syndrome
- Compression symptoms in surrounding tissues
- Most commonly visual symptoms (bitemporal visual field defect, impaired vision, paresis of muscles moving the eyeball)
- Headache
- Acute headache and diplopia as symptoms of pituitary bleeding(pituitary apoplexy)
Hypopituitarism
- Hormone deficiencies usually develop in the following order:
- Growth hormone, resulting in children in slowing down of growth
- Gonadotropins, resulting in hypogonadism
- In women menstrual disturbances, amenorrhoea
- In men decreased libido, impotence, decreased beard growth, muscle weakness, decreased energy, decreased haemoglobin concentrations
- TSH, resulting in mild hypothyroidism
- TSH level disproportionately low in relation to low level of free T4 (hypothyroidism). In patients with hypothyroidism even TSH levels that fall within the reference range are disproportionately low, suggesting a central defect.
- ACTH, resulting in hypocortisolism
- Symptoms milder than in Addison's disease
- Hyponatraemia common
Findings indicating hypothalamic disorder
- Deficiency of antidiuretic hormone (ADH), resulting in the development of diabetes insipidus. Symptoms include increased urinary frequency and strong feeling of thirst.
- Hyperprolactinaemia resulting from damage to the pituitary stalk (hyperprolactinaemia often relatively mild, < 600 mU/l
- Prolactinoma is a more common reason for hyperprolactinaemia than pituitary stalk damage, leading to more clearly increased prolactin concentration.
Symptoms of excessive hormone secretion
- Prolactinoma is the most common pituitary tumour
- In microadenoma serum prolactin concentration is usually 1 000-4 000 mU/l, in macroadenoma clearly increased (> 5 000 mU/l)
- In women galactorrhoea and hypogonadotropic hypogonadism resulting in menstrual disturbances, amenorrhoea and infertility
- In men loss of libido, impotence and infertility
- Remember to exclude hypothyroidism as the cause of hyperprolactinaemia.
- Nearly all psychotropic drugs (excluding benzodiazepines) and metoclopramide cause hyperprolactinaemia.
- Hyperprolactinaemia caused by psychotropic drugs is often mild. Prolactin is at the level of 1 000-2 000 mU/l. It is insignificant in an asymptomatic person (no galactorrhoea or menstrual disturbances).
- Symptomless hyperprolactinaemia may be caused by harmless macroprolactinaemia (prolactin as an inactive polymer, can be determined by a blood test).
- Acromegaly
- Thick, oily skin and hyperhidrosis are early symptoms.
- Thickening lips, enlarging nose and tongue
- Enlargement of distal parts of the body (chin, hands, feet)
- Hypertension, diabetes
- Sweating and fatigue, snoring, arthralgia, headache
- Cushing's disease
- Typical habitus (central obesity, supraclavicular fullness, proximal muscle atrophy, thin skin, bruising tendency)
- Hypertension, diabetes based on insulin resistance
- Osteoporosis
- Menstrual disturbances
- Mental sensitivity
- Thyrotropinoma (TSH-producing adenoma, TSHoma)
- Hyperthyroidism, diffuse goiter
- Despite the elevated free T4 and free T3 levels, the TSH level is not low.
Diagnosis
- Hypopituitarism is excluded by determining serum cortisol and free thyroxine (T4) concentrations, as well as, in men, testosterone concentration and, in premenopausal women, oestradiol concentration if the menstrual cycle is irregular or in case of amenorrhoea. If diabetes insipidus is suspected, urine osmolality and plasma sodium concentration are determined.
- In case of suspected excessive hormone production
- Prolactinoma: prolactin
- Acromegaly: growth hormone (GH), insulin-like growth factor-1 (IGF-1); 2-hour glucose challenge test, if necessary, with blood glucose and GH. Evaluation of the results requires special competence, so specialised care should be consulted when the suspicion of acromegaly is raised.
- Cushing's disease: as screening tests 1.0 mg or 1.5 mg dexamethasone test and/or 24-h urinary free cortisol
- In patients taking oestrogen: 24-h urinary free cortisol, as oestrogen will interfere with serum cortisol assay
- Confirmation by further tests in specialized health care
- Imaging
- MRI of the sellar region (in specialized care)
Investigation of pituitary incidentaloma
- Besides an adenoma, a pituitary tumour may be e.g. a craniopharyngioma, meningioma, pituicytoma, seminoma, lymphoma, a metastasis of some other tumour, Rathke's pouch cyst or hypophysitis.
- Investigation of an incidental finding in the pituitary gland, a incidentaloma, should take place in the specialized health care where specialists in neuroradiology and endocrinology evaluate the radiological and hormonal nature of the tumour.
- If the size of a lesion resembling adenoma is over 10 mm, the hyper- and hypoactivity of the pituitary gland, as well as visual pathway symptoms are investigated within specialized care. If the tumour does not secrete hormone and does not put pressure on the optic chiasm, it will be monitored within specialized care at 6-12 month intervals.
- If the size of an incidentaloma is smaller than 10 mm, a prolactinoma should be excluded. Other hormonal investigations are done if the patient has symptoms which fit hypersecretion or hyposecretion of hormones. If the patient is asymptomatic, monitoring by imaging is not required at all if the size of the change is smaller than 4 mm. If the size of the incidentaloma is 5-9 mm, an MRI of the pituitary gland is usually performed twice at a 12-month interval to exclude growth tendency.
Treatment
- Surgical resection of the tumour in a unit that has a multiprofessional team (neurosurgeon, neuroradiologist and endocrinologist) with experience in the diagnostics and treatment of pituitary tumours.
- Pharmacological treatment
- Cabergolineor quinagolide for prolactinoma. Previously used bromocriptine is not available anymore.
- In patients who have been moved to primary care, the drug therapy of hyperprolactinaemia caused by a microadenoma whose size is smaller than 4 mm may be discontinued postmenopausally when the treatment of galactorrhoea and menstrual irregularities is no longer clinically meaningful.
- Octreotide, lanreotide, cabergoline, pegvisomant and pasireotide for acromegaly
- Radiotherapy in selected cases
References
- Raappana A, Koivukangas J, Ebeling T et al. Incidence of pituitary adenomas in Northern Finland in 1992-2007. J Clin Endocrinol Metab 2010;95(9):4268-75. [PubMed]
- Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 2010;72(3):377-82. [PubMed]