(UroToday.com) The 2021 American Urological Association (AUA) Summer School series included a session on the Evaluation and Management of Adrenal Masses moderated by Dr. Neal E. Rowe, and a presentation from Dr. Rowe discussing the management of functional adrenal tumors, specifically hypercortisolism. Hypercortisolism is Cushing’s Syndrome, which is defined as the prolonged and inappropriate exposure to excessive glucocorticoids. Excess cortisol can be due to increased ACTH secretion (ACTH-dependent, 85% of cases), independent adrenal overproduction (ACTH-independent, 10% of cases), or exogenous corticosteroids. Production of cortisol is intimately associated with the hypothalamic-pituitary-adrenal axis:
Dr. Rowe notes that when diagnosing and managing patients with functional adrenal masses, there are five key aspects that he uses as a guide:
- Identify patients for screening
- Screening
- Endocrinology (confirmatory tests)
- Localization (to assess ACTH dependency)
- Treatment
Indications for hypercortisolism are when a patient has clinical (Cushing’s Syndrome) plus radiological indications (adrenal incidentaloma). There are many clinical features of Cushing’s Syndrome, including:
- Most common: central obesity, moon facies, facial plethora, decreased libido, purple striae, and menstrual disturbances
- Common: erectile dysfunction, hirsutism, hypertension, muscle weakness, buffalo hump, and glucose intolerance
- Less common: osteopenia, depression, recurrent infection, acne, alopecia, and headache
There are several ways to screen for hypercortisolism, including (i) an overnight 1mg dexamethasone test (most commonly performed), (ii) late-night salivary cortisol (but with false positives in depression, altered sleep, and chronic illness), and (iii) 24-hour urinary free cortisol (but lacks sensitivity for adrenal incidentalomas and mild Cushing’s syndrome). As follows is an algorithm for assessing patients with suspected Cushing’s syndrome:
To assess the localization of hypercortisolism, ACTH is evaluated: if ACTH is low, the hypercortisolism is localized to the adrenal gland, whereas if ACTH is high, the hypercortisolism is localized to the pituitary gland or is ectopic. Dr. Rowe highlighted that a clinical pearl for working up hypercortisolism is that ACTH-independent hypercortisolism is more likely to be from unilateral adrenal disease rather than bilateral disease.
Dr. Rowe then presented several cases of hypercortisolism. The first patient was a 50-year-old woman with central obesity, moon facies, and hypertension. Given her Cushing’s features, she was deemed appropriate for screening and subsequently underwent a 24-hour urinary free cortisol study, which showed hypercortisolism. A confirmatory dexamethasone suppression test was also positive and an ACTH dependency test revealed high levels of ACTH localized to the pituitary gland. A pituitary MRI confirmed a pituitary macroadenoma, which was treated with trans-sphenoidal resection by neurosurgery. However, over 14 years of follow-up, the patient had a gradual return of symptoms, and repeat testing confirmed increased urinary free cortisol, a positive dexamethasone suppression test, and increased ACTH, however, repeat pituitary MRI could not identify a lesion to target. She was subsequently diagnosed with ACTH-dependent Cushing’s Syndrome (Cushing’s disease) with failed pituitary management. Treatment options for this patient include cabergoline (only successful in ~25% of Cushing’s disease) or bilateral adrenalectomy. She opted for surgery and had staged bilateral laparoscopic adrenalectomies, with marked improvement in her symptoms, and is now on lifelong glucocorticoid and mineralocorticoid replacement.
The second case involved a 24-year old woman referred from her family physician with a growing left adrenal incidentaloma (4.0 cm). A previous functional investigation six years ago was negative and she had no clinical manifestations of Cushing’s Syndrome, pheochromocytoma, or Conn’s syndrome. As follows is the patient’s CT imaging and the left adrenal incidentaloma:
Given the patient’s growing adrenal adenoma, she is an appropriate patient for screening and thus underwent a 24-urinary free cortisol study, which showed hypercortisolism. A confirmatory dexamethasone test was positive and she was diagnosed with subclinical Cushing’s Syndrome. Dr. Rowe notes that although this was labeled as subclinical, this disease was associated with morbidity secondary to the patient’s hypertension, impaired fasting glucose, and increased visceral fat deposition. An ACTH dependency test confirmed low ACTH and the hypercortisolism was deemed an adrenal source. The patient then underwent laparoscopic left adrenalectomy; minimally invasive adrenalectomy reduces the morbidity associated with long-term exposure to elevated levels of cortisol.
Dr. Rowe concluded this portion of his presentation on hypercortisolism with the following patient scenarios that are common for urologists:
- A patient with an adrenal adenoma and ACTH-independent hypercortisolism
- A patient with ACTH-secreting pituitary adenoma that fails pituitary treatment (trans-sphenoidal surgical resection or radiotherapy)
- A patient with ACTH-independent hypercortisolism secondary to bilateral disease (macronodular hyperplasia and primary pigmented nodular adrenocortical disease), which is rare
Presented by: Neal E. Rowe, MD, University of Ottawa, Ottawa, Ontario, Canada
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the AUA2021 May Kick-off Weekend May 21-23.