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Conditions

Pituitary adenoma

Pituitary adenomas are benign tumours that occur in the pituitary gland and can affect a patient in a number of ways – for example, by causing hormone deficit or excess. They are sometimes inherited.

Overview

Pituitary adenomas are generally benign growths of the pituitary gland that can result in neurovascular compromise and hormone deficit or excess. They can be familial.

Clinical features

Neurological features of pituitary ademona include:

  • headache – chronic or acute (pituitary apoplexy); and
  • visual disturbance.

Hormonal features of pituitary adenoma include:

  • growth hormone excess:
    • tall stature;
    • diaphoresis;
    • arthralgia;
    • facial changes and prognathism; and
    • increase in the size of the hands and/or feet;
  • hyperprolactinaemia:
    • galactorrhoea; and
    • amenorrhoea;
  • adrenocorticotropic hormone excess:
    • Cushingoid features;
  • thyroid-stimulating hormone excess:
    • features of hyperthyroidism; and
  • hypopituitarism.

Genetics

Pituitary adenomas may develop in the setting of heterozygous constitutional (germline) variants or mosaicism. They are classically described as occurring in syndromic disease (MEN1, CDKN1B, GNAS, SDHx and GPR101) or isolated pituitary disease (AIP and GPR101) as outlined below.

AIP

Heterozygous pathogenic constitutional (germline) variants in the AIP gene can result in familial isolated pituitary adenoma (FIPA). FIPA is defined by the presence of pituitary adenoma in two or more family members, with no other tumours associated with a genetic endocrine syndrome. FIPA accounts for approximately 2% of pituitary adenomas and pathogenic AIP variants account for approximately 10% of FIPA. The condition is typically young onset (under 30 years of age).

MEN1 and CDKN1B

Heterozygous pathogenic constitutional (germline) variants in MEN1 and CDKN1B may result in syndromic pituitary disease and are discussed in the following resources:

Please note that syndromic causes of pituitary adenomas could present first with pituitary adenoma (this is the case in 15% of multiple endocrine neoplasia type 1 (MEN1) patients).

GPR101

Duplication of the GPR101 gene is a recognised cause of pituitary adenoma and pituitary hyperplasia resulting in X-linked acrogigantism (X-LAG). GPR101 duplication usually occurs as part of Xq26.3 microduplication (though smaller duplications have also been seen), occurring as de novo constitutional (germline) or mosaic cases. Rarely, familial disease (FIPA) has been described.

GNAS (mosaicism)

McCune-Albright syndrome is a clinical diagnosis of pathogenic variants in this gene, but genomic testing could be indicated in some cases following multidisciplinary team discussion (the appropriate panel would be R327 Mosaic skin disorders – diseased tissue required). Pituitary manifestations of McCune-Albright syndrome include hyperprolactinaemia or high growth hormone levels secondary to pituitary adenoma or pituitary hyperplasia (often no pituitary adenoma is visible on imaging).

SDHx and MAX

Pathogenic variants in the five SDHx genes and the MAX gene have rarely been reported with pituitary adenoma, and are not included in the R217.1 panel.

More recently, patients with Lynch syndrome (pathogenic variants in MSH2 and PMS2) have been reported as having pituitary adenomas.

For information about testing, see Presentation: Patient with familial pituitary adenoma and Presentation: Patient with young onset pituitary adenoma.

Inheritance and genomic counselling

AIP-associated FIPA is an autosomal dominant condition with incomplete penetrance. Approximately one in five carriers of a pathogenic variant will be affected. The reasons for the incomplete penetrance are unknown. If by the age of 30 a carrier of a pathogenic variant remains unaffected (normal hormones, normal pituitary MRI), they are unlikely to develop disease later on. Due to the variable penetrance of the disease, patients may not have a known family history of pituitary adenoma.

MEN1 and CDKN1B are discussed in Multiple endocrine neoplasia type 1 and Multiple endocrine neoplasia type 4.

The clinical phenotype of X-LAG includes infant-onset (usually under two years of age) growth hormone excess – usually, but not always, with prolactin excess. The majority of cases are found in females with de novo constitutional (germline) variants. Males have somatic mosaicism or develop disease due to constitutional (germline) microduplications inherited from the mother.

McCune-Albright syndrome occurs due to a pathogenic GNAS variant occurring during embryonic development as a post-zygotic change, with the pituitary gland affected in about 25% of cases. It is not an inherited condition.

Management

Management of children with AIP, GPR101 and MEN-related pituitary adenoma is complex and should be delivered via a multidisciplinary team. Advice and multidisciplinary discussion is accessible through the national hypothalamic pituitary axis tumours group.

Management of adults with AIP-related pituitary adenoma should follow published guidelines, with aims to control or minimise tumour volume, normalise hormonal hypersecretion and replace hormone deficits. Care should also be delivered via a multidisciplinary team. AIP-related pituitary adenomas may be more aggressive and refractory to standard therapies (somatostatin receptor ligands) than sporadic pituitary adenomas.

Like AIP, pituitary adenomas and hyperplasia in the setting of X-LAG may respond poorly to somatostatin receptor ligands. Treatment goals are the same as in AIP-related pituitary disease.

Resources

For clinicians

References:

For patients

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  • Last reviewed: 30/05/2023
  • Next review due: 30/05/2025
  • Authors: Dr Ben Loughrey
  • Reviewers: Dr Danielle Bogue, Dr Emile Hendriks, Dr Louise Izatt, Dr Márta Korbonits