Summary
Pituitary adenomas are benign tumors that often arise sporadically from the anterior pituitary gland. They are classified based on their size as microadenomas or macroadenomas, and whether they produce hormones as secretory (functional) and nonsecretory (nonfunctioning) adenomas. Secretory adenomas produce the pituitary hormone of the corresponding cell type, which results in a state of hyperpituitarism. Nonsecretory macroadenomas, however, destroy the surrounding normal pituitary tissue and result in hypopituitarism. Additionally, large macroadenomas compress the optic chiasm and can thus present with signs of mass effect such as bitemporal hemianopsia. The investigation of choice is a contrast-enhanced cranial MRI, which reveals an intrasellar mass. Assays of pituitary hormones are used to evaluate the patient for endocrine abnormalities, and perimetry is required to document visual field defects. Transsphenoidal surgical resection is the first-line therapy for most pituitary adenomas; however, nonsecretory microadenomas generally only require follow-up, and prolactin-producing pituitary adenomas (prolactinomas) are best treated with dopamine agonists (e.g., cabergoline, bromocriptine). Pituitary irradiation is indicated only if the pituitary adenomas recur and/or if surgical therapy is contraindicated.
Epidemiology
-
Prevalence [1]
- ∼ 80 Cases per 100,000 individuals
- Pituitary adenomas account for about 15% of primary intracranial tumors. [1]
- Peak incidence: 35–60 years [2]
Epidemiological data refers to the US, unless otherwise specified.
Etiology
- Most cases occur sporadically.
- Some cases (∼ 5%) have a genetic/familial association: [3]
- Multiple endocrine neoplasia type 1
-
Carney complex
- The result of a mutation in the PRKAR1A gene which results in loss of function in a negative regulatory subunit (R1α) of protein kinase A resulting in an increased activity of cAMP
- Patients present with cardiac myxoma, spotty skin pigmentation, adrenal gland, testicular, and pituitary adenomas.
-
Familial isolated pituitary adenoma syndrome [4]
- Mutations in the AIP gene
- Patients present with pituitary adenomas without other associated abnormalities.
- Most common familial cause of acromegaly/gigantism
Pathophysiology
- Pituitary adenomas are well circumscribed, intrasellar tumors with monomorphic, polygonal cells arranged in sheets or cords without any connective tissue and/or reticulin.
- Type of tumor according to size
- Pituitary microadenoma: ≤ 10 mm
- Pituitary macroadenoma: > 10 mm
- Type of tumor according to hormone secretion
- Non-secretory pituitary adenomas [5]
-
Secretory pituitary adenomas: hormone secretion → hyperpituitarism
- Most secrete one pituitary hormone, with hyperplasia of only one type of endocrine cell.
- The presence of multiple pituitary hormones should also raise the suspicion of atypical pituitary adenomas or pituitary carcinomas.
| Secretory pituitary adenomas | ||
|---|---|---|
| Origin | Relative frequency (as a percentage of all pituitary adenomas) | Pathophysiology |
| Lactotroph adenoma (prolactinoma) [6] |
|
|
| Somatroph adenoma |
|
|
| Corticotroph adenoma (Cushing disease) |
| |
| Thyrotroph adenoma |
|
|
| Gonadotroph adenoma |
| |
Prolactinomas are the most common pituitary adenomas.
Clinical features
| Type | Secretory adenomas | Non-secretory adenomas [5] |
|---|---|---|
| Microadenomas |
|
|
| Macroadenomas |
|
The symptoms associated with pituitary adenomas depend on the size of the tumor and whether the tumor produces hormones.
Diagnostics
-
Cranial contrast MRI [7]
- Single best imaging
- Reveals an intrasellar mass
- In patients with moderate to severe renal failure, gadolinium-based imaging should be avoided.
-
CT scan [7]
- May be considered when MRI is not accessible or is contraindicated
- Detecting calcification in craniopharyngioma, meningioma or lactotroph adenomas
- Better visualization of the sphenoid septal anatomy
-
Hormone assays [8]
- Basal prolactin levels (See “Diagnostics” in “Hyperprolactinemia.”)
- Insulin-like growth factor-1 (IGF-1) (See “Diagnostics” in “Acromegaly.”)
- 24-hour urine cortisol (See “Diagnostics” in “Cushing syndrome.”)
- Thyroid function tests (See “Diagnostics” in “Hyperthyroidism.”)
- Perimetry: to assess visual field defects [9]
Treatment
-
Prolactinomas [6]
- Asymptomatic microprolactinoma: no treatment
- Symptomatic microprolactinoma or macroprolactinoma: dopamine agonists (e.g., cabergoline, bromocriptine); , which cause the pituitary adenoma to shrink
- Transsphenoidal surgery (± radiotherapy) is generally reserved for very large tumors or prolactinomas that increase in size despite pharmacological therapy. [10]
- Non-secretory pituitary microadenomas (incidentalomas): no treatment (only follow-up)
-
Other pituitary adenomas
- First-line: transsphenoidal hypophysectomy [10]
- Second-line: pituitary irradiation [11]
Following transsphenoidal resection and/or pituitary irradiation, patients may develop hypopituitarism and potentially require lifelong hormone replacement therapy.
Differential diagnoses
-
Intracranial neoplasms
- Craniopharyngioma (suprasellar mass): most commonly in children
- Meningioma (parasellar mass)
- Neurofibroma
- Ectopic germinoma
- Granulomatous disorders invading sellar region or the hypothalamus
- Carotid artery aneurysm
- Lymphocytic hypophysitis
The differential diagnoses listed here are not exhaustive.