What is the pathophysiology of pituitary macroadenomas?

Updated: Apr 20, 2020
  • Author: James R Mulinda, MD, FACP; Chief Editor: George T Griffing, MD  more...
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Pituitary macroadenomas are benign epithelial neoplasms composed of adenohypophysial cells. Primary malignant tumors of the pituitary are extremely rare. Evidence suggests that pituitary adenoma development occurs in several steps, including an irreversible initiation phase followed by tumor promotion.

Pituitary tumor development is a monoclonal process with several contributing factors. Causal contributors include heredity and hormonal influence and genetic mutations. The monoclonal nature of most pituitary tumors suggests that they arise from a mutated pituitary cell. However, the exact pathophysiologic/molecular mechanisms leading to the development of pituitary adenomas remain unknown.

The role of genetic mutations was highlighted in a report suggesting that patients with pituitary tumors from 4 Irish families share a common mutation with a patient from the 18th century who had pituitary tumor–mediated gigantism. [2]

Some pituitary tumors may occur as part of a clinical syndrome. In multiple endocrine neoplasia type 1 (MEN 1), an autosomal dominant genetic disorder, pituitary adenomas (most often prolactinomas) occur in association with tumors of the parathyroid and pancreatic islet cells.

In McCune-Albright syndrome, skin lesions and polyostotic fibrous dysplasia occur with hyperfunctioning endocrinopathies. This syndrome results from an activating mutation (somatic mutation) of the alpha subunit of the Gs protein and involves tissues whose response to hormonal signals is mediated by adenylate cyclase. The most common pituitary tumor in McCune-Albright syndrome is somatotropinoma, resulting in acromegaly. Interestingly, a significant proportion of somatotropinomas in sporadic cases of acromegaly harbor the same mutations.

Carney complex is an autosomal dominant disorder characterized by primary pigmented nodular adrenal disease, cutaneous pigmented lesions (lentigines, blue nevi), Sertoli cell tumors of the testes, acromegaly, melanocytic schwannomas, and cardiac myxomas.

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