Pituitary Macroadenoma

Pituitary macroadenoma is the most common benign suprasella tumour in adults, usually presenting as hormonal imbalances or visual disturbances due to mass effect.

Description

Pituitary macroadenomas are benign, non-secreting or secreting tumours of the pituitary gland, larger than 1 cm in diameter. They represent the most common type of pituitary tumours, accounting for a significant proportion of sellar masses.

Pathogenesis

These tumours arise from the adenohypophyseal cells of the anterior pituitary gland. The exact pathogenesis is unclear, but may involve genetic mutations, hormonal influences, or a combination of both.

Subtypes

• Functioning Macroadenomas: Secrete pituitary hormones, such as prolactin, growth hormone, or ACTH.
  • Most somatotroph adenomas manifest as a macroadenoma
  • Most prolactinomas are microadenomas (in young women) but can appear as macroadenomas in men and children.
• Non-functioning Macroadenomas: Do not secrete hormones but can cause symptoms due to mass effect.

Epidemiology, Risk Factors & Associations

• Incidence peaks in the 30-60 year age group.
• Associated with multiple endocrine neoplasia syndrome type 1 (MEN1)
  • Pituitary tumours are usually diagnosed at an earlier age, have a higher degree of aggressiveness and invasiveness, are more often resistant to treatment, and have higher rates of tumour recurrence than sporadic pituitary adenomas¹
  • Approximately 65% to 85% of pituitary tumours are macroadenomas².

Clinical Features

• Hormonal dysregulation symptoms, depending on tumour type
  • Prolactin-Secreting Macroadenoma (Prolactinoma):
    • Galactorrhoea: Abnormal lactation in non-pregnant individuals.
    • Amenorrhoea: Absence of menstrual periods in women.
    • Gynaecomastia: Breast enlargement in men.
    • Infertility: Due to hormonal imbalance.
    • More commonly associated with cavernous sinus invasion, causing mass effect usually upon the oculumotor and abducens nerves
  • Growth Hormone-Secreting Macroadenoma:
    • Acromegaly in Adults: Enlarged extremities, facial features, and organs.
    • Gigantism in Children: Excessive height and growth due to early onset.
  • ACTH-Secreting Macroadenoma:
    • Cushing’s Disease: Weight gain, especially in the face and abdomen, thin skin, easy bruising, hypertension, and diabetes.
  • TSH-Secreting Macroadenoma:
    • Hyperthyroidism: Weight loss, increased appetite, heat intolerance, anxiety, and palpitations.
  • FSH/LH-Secreting Macroadenoma:
    • Infertility: Altered menstrual cycle in women or low testosterone levels in men.
    • Sexual Dysfunction: Reduced libido, erectile dysfunction in men, or vaginal dryness in women.
• Visual disturbances due to optic chiasm compression.
  • Bitemporal hemianopia (loss of one half of a vertical visual field) – decussating fibres from the nasal half of each retina are responsible for the temporal visual field.
• Headaches and other neurological symptoms.

Complications

• Visual field deficits, typically bitemporal hemianopia.
• Pituitary apoplexy: Sudden haemorrhage or infarction of the tumour, a neurosurgical emergency. Can occur following medical treatment of prolactinoma or irradiation of mass.
• Hypopituitarism: Reduced secretion of one or more pituitary hormones.
• Chronic headaches.

Pathological Features

Histopathology

• Macroscopic: Well-circumscribed intra-sellar mass, may extend into the suprasellar cistern.
• Microscopic: Variable cellular composition, reflecting the cell of origin.

Serology

• Prolactin – There is a correlation between the size of the tumour and the serum prolactin level³
  • Levels of 100–250 ng/mL (4348–10 870 pmol/L) are typical for a microadenoma
  • Levels greater than 250 ng/mL suggest a macroadenoma
  • Levels greater than 10 000 ng/mL (434 780 pmol/L) are common in larger macroadenomas (>3 cm)

Radiological Features

General Features

• Intra-sellar solid mass without a separate identifiable pituitary gland
• May have haemorrhagic, necrotic or cystic components. Calcification is usually rare.
• May extend through diaphragm sellae into suprasella cistern. Bilateral indentation by the diaphragm sellae forms a snowman or figure of eight morphology.
• May cause remodelling of the sella turcica – usually enlarged and thinned.
• May invade cavernous sinus and encase the internal carotid artery without narrowing. Encasement of more than two-thirds is generally considered a sign of cavernous sinus invasion.
• Prolactin-secreting tumours are most commonly associated with cavernous sinus invasion, and it is typical for prolactin concentrations to elevate when these neoplasms extend into sinus

CT

• Non-contrast: May show a hyperdense or isodense mass in the sellar region. Calcification is rare.
• C+ Arterial/Venous: Moderate enhancement patterns.

MRI

• T1: Isointense or hypointense to grey matter.
• T2: Typically isointense to grey matter. Larger lesions may have heterogeneous signal intensity due to cystic degeneration, necrosis or haemorrhage. A hypointense rim is often present.
• DWI/ADC: Usually does not show restricted diffusion.
• T1 Gad+: Usually enhances heterogenously.
• SWI: Susceptibility artefact likely represents haemorrhagic components rather than calcification

NM

• PET FDG: Highly avid

Grading and Staging

No specific grading or staging system; assessment based on size, invasiveness, and hormonal activity.

Diagnosis

• Clinical evaluation for hormonal disturbances
• MRI is the imaging modality of choice for visualisation and characterisation.
• Hormonal assays to identify functioning adenomas.

Differential Diagnosis

See primary tumours of the pituitary gland.

• Pituitary microadenoma (smaller than 1 cm).
• Pituitary Carcinoma: Indistinguishable. Rare.
• Craniopharyngioma: Distinctive calcifications and cystic components. More likely to be T1 hyperintense.
• Meningioma: Separable from pituitary gland. Dural attachment and tail may be apparent. Usually more marked enhancement and hyperdense on non-contrast CT.
• Rathke’s cleft cyst: Non-neoplastic cystic lesion in the sellar region. Intramural nodule is specific but not sensitive.
• Pituitary metastasis: Less defined mass, with bony destruction rather than remodelling.
• Lymphocytic hypophysitis: Lymphocytic infiltration of pituitary stalk. Seen in peripartum patient or females (9:1 ratio with men). Parasellar signal is low on T2, a specific finding.

Management

• Transsphenoidal surgery for most macroadenomas. Resection is complicated by cavernous sinus invasion.
• Medical therapy for prolactinomas and adjunctive treatment for other functioning tumours.
• Radiation therapy for residual or recurrent tumours.
• Regular monitoring of visual fields and hormonal levels.

References

1. Di Ieva, A., Rotondo, F., Syro, L.V., Cusimano, M.D. and Kovacs, K., 2014. Aggressive pituitary adenomas—diagnosis and emerging treatments. Nature Reviews Endocrinology, 10(7), pp.423-435. ↩︎
2. Syro, L.V., Scheithauer, B.W., Kovacs, K., Toledo, R.A., Londono, F.J., Ortiz, L.D., Rotondo, F., Horvath, E. and Uribe, H., 2012. Pituitary tumors in patients with MEN1 syndrome. Clinics, 67, pp.43-48. ↩︎
3. Molitch, M.E., 2017. Diagnosis and treatment of pituitary adenomas: a review. Jama, 317(5), pp.516-524. ↩︎