Diagnosis and Management of Pituitary Adenomas

Abstract

ImportancePituitary adenomas are neoplasms of the pituitary adenohypophyseal cell lineage and include functioning tumors, characterized by the secretion of pituitary hormones, and nonfunctioning tumors. Clinically evident pituitary adenomas occur in approximately 1 in 1100 persons.ObservationsPituitary adenomas are classified as either macroadenomas (≥10 mm) (48% of tumors) or microadenomas (<10 mm). Macroadenomas may cause mass effect, such as visual field defects, headache, and/or hypopituitarism, which occur in about 18% to 78%, 17% to 75%, and 34% to 89% of patients, respectively. Thirty percent of pituitary adenomas are nonfunctioning adenomas, which do not produce hormones. Functioning tumors are those that produce an excess of normally produced hormones and include prolactinomas, somatotropinomas, corticotropinomas, and thyrotropinomas, which produce prolactin, growth hormone, corticotropin, and thyrotropin, respectively. Approximately 53% of pituitary adenomas are prolactinomas, which can cause hypogonadism, infertility, and/or galactorrhea. Twelve percent are somatotropinomas, which cause acromegaly in adults and gigantism in children, and 4% are corticotropinomas, which secrete corticotropin autonomously, resulting in hypercortisolemia and Cushing disease. All patients with pituitary tumors require endocrine evaluation for hormone hypersecretion. Patients with macroadenomas additionally require evaluation for hypopituitarism, and patients with tumors compressing the optic chiasm should be referred to an ophthalmologist for formal visual field testing. For those requiring treatment, first-line therapy is usually transsphenoidal pituitary surgery, except for prolactinomas, for which medical therapy, either bromocriptine or cabergoline, is usually first line.Conclusions and RelevanceClinically manifest pituitary adenomas affect approximately 1 in 1100 people and can be complicated by syndromes of hormone excess as well as visual field defects and hypopituitarism from mass effect in larger tumors. First-line therapy for prolactinomas consists of bromocriptine or cabergoline, and transsphenoidal pituitary surgery is first-line therapy for other pituitary adenomas requiring treatment.

Cushing Syndrome

“…When surgical therapies have failed or are not feasible, medical therapy has been increasingly used for all types of endogenous Cushing syndrome as symptomatic treatment to control hypercortisolism. Inhibitors of adrenal steroidogenesis are an established treatment for hypercortisolism in patients with all forms of endogenous Cushing syndrome, especially among patients who are not candidates for surgery or who have persistence or recurrence of the underlying tumor . Osilodrostat is approved in the US for Cushing disease and levoketoconazole is approved in the US for Cushing syndrome.…”

“…Ketoconazole, metyrapone, and osilodrostat are approved in Europe and other regions for Cushing syndrome. Mitotane is approved for adrenal cancer . Ketoconazole, metyrapone, and etomidate have been used off-label in the US for all forms of Cushing syndrome …”

“…Mitotane is approved for adrenal cancer . Ketoconazole, metyrapone, and etomidate have been used off-label in the US for all forms of Cushing syndrome …”

“…Due to their efficacy and rapid onset of action, these agents can be used for both long-term and acute treatment of life-threatening hypercortisolism such as in patients with immunosuppression and sepsis (eTable in the Supplement). Within this steroidogenesis inhibitor class of drugs, osilodrostat is the most potent in decreasing cortisol, but symptoms consistent with possible adrenal insufficiency may occur in almost half of the patients . Doses should be increased slowly and close observation is needed .…”

“…The estimated incidence of Cushing syndrome attributable to endogenous production of cortisol ranges from about 2 to 3 per million people to 8 per million people annually . The most common cause of endogenous Cushing syndrome is Cushing disease, in which a benign pituitary adenoma oversecretes corticotropin . Cushing syndrome from excess endogenous cortisol production may be also caused by a benign or malignant adrenal tumor that secretes cortisol or by a benign or malignant nonpituitary corticotropin-secreting tumor (ectopic Cushing syndrome).…”