62: Pituitary Tumors and Syndromes

Key Points

• Disease summary:

  • Pituitary tumors are typically of monoclonal origin (although not always); they are benign, often slow-growing, adenomas of the sella arising sporadically or rarely in the context of hereditary genetic syndromes accounting for 10% to 15% of all diagnosed intracranial neoplasms. Their true incidence is difficult to determine, as they are often asymptomatic. They can be effectively managed, as they are rarely malignant. Small pituitary tumors go largely undetected and are often only documented during postmortem studies; over 20% of the adult population may have a pituitary adenoma, identified incidentally by imaging studies (called “incidentalomas”). Significant morbidity occurs due to the pituitary tumor’s effect on hormone secretion and compression of regional structures. Other symptoms include those from mass effects.

Pituitary tumors can be classified as follows:

1. Common tumors of the sella turcica

   1. Pituitary adenomas include nonfunctioning adenomas and tumors that hypersecrete hormones: growth hormone (GH)-omas (accounting for 20% of surgically treated lesions), prolactinomas (PRL; 50%), adrenocorticotropic hormone (ACTH)-producing adenomas (15%), and rarely thyroid-stimulating hormone (TSH)-omas, and gonadotropinomas (FSH-LH-omas).

   2. Craniopharyngiomas are epithelial tumors arising from remnants of Rathke pouch and account for 3% of all intracranial tumors.

   3. Supra- and parasellar meningiomas which account for 15% of all intracranial tumors.

   4. Miscellaneous benign cysts: Rathke cleft cysts, intrasellar colloid cysts, arachnoid cysts.

2. Rare tumors of the sella turcica: Optico-hypothalamic gliomas, metastases, chordomas, inflammatory lesions, germinomas, hypothalamic harmartomas, chondromas, epidermoids.

3. Miscellaneous pituitary tumors: Granular cell tumor, paragangliomas, pituitary carcinomas (~0.2% operated pituitary neoplasms), mucocele, chiasmatic cavernoma, hypothalamic lipoma, and sarcoidosis.

• Pathogenesis:

  • Pituitary tumors may be a manifestation of an underlying monogenic syndrome, such as McCune-Albright syndrome (MAS), multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), multiple endocrine neoplasia type 4 (MEN4), and familial isolated pituitary adenomas (FIPA); alternatively, no single gene may be responsible. Some of these genes predispose to sporadic pituitary tumors, such as the aryl hydrocarbon receptor-interacting protein (AIP).

• Twin studies:

  • Pituitary tumors are rarely inherited, however, in the very small number of these patients there is usually a family history of other endocrine (parathyroid or pancreas) tumors.

• Environmental factors:

  • There are no known environmental causes.

• Genome-wide associations:

  • A suggestive linkage on chromosome 19q13.41 has been identified as a possible modifier for the severity of acromegalic features in patients with isolated familial somatotropinoma.

• Pharmacogenomics:

  • There are very few pharmacogenetic studies that assess the role of certain polymorphisms in the responsiveness to medications used in pituitary adenomas (eg, dopamine agonists and somatostatin analogues). NcoI T + genotype (homozygotes or heterozygotes for T allele), a D2 dopamine receptor (DRD2) polymorphism, has been associated with unresponsiveness to cabergoline treatment in patients affected with PRL-oma.

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria for Pituitary Tumors

The investigation of a patient presenting with evidence of a pituitary tumor has three main objectives:

1. Investigation of any hormonal ...