Adrenal Cortical Adenoma

Background

• Adrenal cortical adenomas are benign neoplasms of the adrenal cortex that may or may not secrete hormones.
• Adrenal incidentaloma refers to an adrenal mass, typically ≥ 1 cm in diameter, discovered serendipitously during a radiologic exam performed for reasons other than suspected adrenal disease; adrenal cortical adenoma is the most common cause.
• Most adrenal cortical adenomas are nonsecreting and asymptomatic, and thus are discovered incidentally during routine imaging performed for unrelated reasons.
• Types of adrenal cortical adenomas include:
  • Nonfunctioning adenomas.
  • Functioning adenomas that release:
    • cortisol, resulting in hypercortisolism, either subclinical or overt Cushing syndrome
    • aldosterone, resulting in primary hyperaldosteronism
    • estrogens or androgens, resulting in feminization, virilization, or hirsutism (rare)
• The cause is unknown but abnormalities in the cAMP signaling pathway are linked to most of the genetic and molecular alterations associated with benign adrenal tumors.

Evaluation

• Clinical presentation varies depending on the type of adrenal cortical adenoma.
  • Most patients are asymptomatic if the adenomas are nonfunctioning.
  • Patients with adenomas that secrete:
    • cortisol (hypercortisolism or Cushing syndrome) may present with signs and symptoms associated with hypertension, diabetes mellitus type 2, osteopenia, osteoporosis, opportunistic and fungal infections, or neuropsychiatric disorders
    • aldosterone (hyperaldosteronism or Conn syndrome) may present with manifestations of hypokalemia and hypertension
    • estrogens or androgens (male feminization or female virilization) may present with a history of low libido or oligomenorrhea and symptoms such as gynecomastia, hirsutism, and acne
• All incidental adrenal masses require a comprehensive workup.
• Goals of an initial investigation of an adrenal mass are to distinguish between:
  • benign and malignant causes
  • functioning and nonfunctioning tumors
• Consider computed tomography and/or magnetic resonance imaging to identify an adrenal cortical mass and a likely benign or malignant status.
• Assess the functioning status for:
  • hypercortisolism in all patients with an incidental adrenal mass - initially screen with an overnight low-dose (1 mg) dexamethasone suppression test, followed by additional confirmatory tests
  • hyperaldosteronism in patients with hypertension with an incidental adrenal mass - initially screen for patients with a morning plasma aldosterone concentration:plasma renin ratio > 20, followed by additional confirmatory tests
• Consider fine-needle aspiration biopsy if there is a suspected metastasis or an infection on imaging and after pheochromocytoma has been ruled out.

Management

• Nonfunctioning adenomas < 4 cm without suspicious radiologic features usually do not need surgical resection unless the patient is symptomatic, but they may require an initial radiologic follow-up at 3-6 months with a periodic radiologic follow-up.
• Consider resecting most adrenal masses that are ≥ 4 cm and those with concerning radiologic features (Weak recommendation).
• For cortisol-producing adenoma with symptoms of hypercortisolism (Cushing syndrome):
  • surgical resection of adrenal tumor is the primary treatment of choice
  • consider treatment with exogenous glucocorticoids after surgery until the hypothalamic-pituitary-adrenal axis has recovered (typically 6-18 months) (Weak recommendation)
  • consider medications to manage hypercortisolism in the preoperative and perioperative period
  • long-term follow-up includes the treatment of specific comorbidities associated with Cushing syndrome and lifelong testing for recurrence
• For cortisol-producing adenoma without signs and symptoms of hypercortisolism (subclinical Cushing syndrome), consider:
  • adrenalectomy in patients with worsening hypertension, abnormal glucose tolerance, osteoporosis, dyslipidemia (Weak recommendation)
  • adrenalectomy for patients < 40 years old or with recent onset or worsening of hypertension, diabetes, or hypertension
  • perioperative glucocorticoid therapy and postoperative evaluation of the hypothalamic-pituitary-adrenal axis (Weak recommendation)
  • repeat hormone screening annually for 5 years but there is no widely accepted guideline for follow-up if not surgically treated
• For aldosterone-producing adenoma:
  • consider laparoscopic adrenalectomy as the treatment of choice for unilateral aldosterone-producing adenoma (Weak recommendation)
  • administer mineralocorticoid receptor blockers for unilateral aldosteronomas that are not candidates for surgery, or bilateral idiopathic hyperaldosteronism (Strong Recommendation)
  • follow-up may involve regular monitoring of electrolytes and renal function if the patient is on medical therapy and blood pressure monitoring after adrenalectomy