Diagnosis, Perioperative Care, and Remission in Cushing Disease

Abstract

Cushing disease (CD) is hypercortisolemia caused by a pituitary tumor. The culprit sellar neoplasm is often too small to detect on neuroimaging, yet its size belies its immense potential morbidity. Modern care of these complex patients demands a dedicated team composed of neurosurgeons, otolaryngologists, and endocrinologists to navigate patients toward a cure. Diagnosis alone is a challenge as CD shares a similar phenotype of cortisol excess with several other disorders that can cause Cushing syndrome. Operative techniques and nuances aside, we summarize the pertinent endocrinologic foundation a neurosurgeon should possess to manage CD. PREOPERATIVECushing syndrome (CS) is the clinical sequelae of glucocorticoid excess. When the most common cause, exogenous glucocorticoid intake, is excluded, one is left with a group of disorders in which tumor (or rarely hyperplastic tissue) either produces excess cortisol or stimulates excess cortisol production indirectly through overproduction of either adrenocorticotropic hormone (ACTH) or corticotrophin-releasing hormone (CRH) (Fig. 1). 1-4 Although essential to mammalian life, cortisol at supraphysiologic doses over a period time engenders a hypercatabolic state manifested by multiple symptoms and signs: decreased libido (100%), weight gain (90%), moon facies (88%), hypertension (85%), glucose intolerance, plethoric facies (80%), reddish striae (65%), hirsutism (65%), menstrual dysfunction, muscle weakness, easy bruising, thinning of the skin, and neuropsychologic disturbances such as depression. 5 Growth retardation is frequently seen in children. On routine screening, CS is found in 2% to 5% of patients with poorly controlled diabetes mellitus type II. 6 Cushing disease (CD) predominates in young women (8:1 compared with men) from age 20 to 40 whereas ectopic ACTH-producing tumors are seen in older males between the ages of 40 and 60 years. 7,8 A brisker temporal onslaught of hypercortisolemic symptomatology is often witnessed in the setting of ectopic ACTH-producing neoplasms such as small cell lung carcinoma. Confirming Hypercortisolism (CS)CD is arguably the most challenging diagnosis to make among the endocrinologic disorders. Several illnesses mimic the phenotype of CD and no single test clinches the diagnosis. Before reaching the operating room for sellar exploration, a patient with presumed CD should have been carefully evaluated with a series of screening and confirmatory tests by a board-certified endocrinologist. The order of testing is crucial as premature confirmatory testing can lead to false positives and false negatives. Individual test results are often equivocal, and it remains the onus of the endocrinologist to weigh the supporting clinical, radiologic, and biochemical evidence before triggering the neurosurgical referral.Cortisol secretion is under the control of ACTH, which is released from the anterior pituitary gland in a pulsatile fashion. Consequently, the serum cortisol level fluctuates throughout the day and manifests a diurnal rhythm, making a...