What is the management approach for a patient with a nodule in the adrenal cortex, presenting with sexual dysfunction and mood disorders?

Management of Adrenal Cortex Nodule with Sexual Dysfunction and Mood Disorders

All patients with an adrenal nodule require comprehensive hormonal evaluation to exclude functional tumors, and referral to endocrinology is appropriate given the patient's symptoms that may be related to hormonal excess or deficiency. 1

Initial Hormonal Evaluation Required

The following hormonal assessments must be performed for any adrenal nodule:

Mandatory Screening Tests

• 1 mg overnight dexamethasone suppression test to exclude autonomous cortisol secretion (cortisol should suppress to ≤50 nmol/L or 1.8 µg/dL) 1, 2
• Plasma-free or urinary-fractionated metanephrines to rule out pheochromocytoma, which can cause life-threatening crises and requires specific pre-intervention management 1
• Aldosterone-to-renin ratio if the patient has hypertension or unexplained hypokalemia 1

Additional Testing for Sexual Dysfunction Context

• Sex hormone and steroid precursor levels (DHEA-S, testosterone, androstenedione, 17-hydroxyprogesterone) should be measured given the patient's sexual dysfunction and mood symptoms, as these may indicate virilization or androgen excess from an adrenocortical tumor 1
• Morning total testosterone if male, as levels <300 ng/dL indicate hypogonadism that may contribute to sexual dysfunction 1

Imaging Characterization

• Unenhanced CT is first-line to determine if the nodule is benign (≤10 Hounsfield units suggests lipid-rich adenoma) or requires further evaluation 1
• Washout CT or chemical-shift MRI if the nodule remains indeterminate on unenhanced imaging 1
• Nodules >4 cm have higher malignancy risk and warrant closer scrutiny 1, 2

Connection Between Adrenal Pathology and Patient Symptoms

Autonomous Cortisol Secretion

• Cortisol levels post-dexamethasone >138 nmol/L (>5 µg/dL) define "autonomous cortisol secretion" (formerly called subclinical Cushing's syndrome), which is associated with metabolic abnormalities, hypertension, and mood disorders 2
• This condition can directly cause depression, anxiety, and sexual dysfunction through multiple mechanisms including metabolic derangements and direct CNS effects 2, 3

Androgen-Secreting Tumors

• Adrenocortical tumors may secrete excess androgens or their precursors, paradoxically causing sexual dysfunction in both sexes through disruption of normal hormonal feedback mechanisms 1, 4
• In males, excess adrenal androgens can suppress gonadotropins and testicular function 4

Pheochromocytoma Considerations

• Can present with anxiety, mood disturbances, and sexual dysfunction due to catecholamine excess 1
• Must be excluded before any surgical intervention to prevent hypertensive crisis 1

Management Algorithm Based on Hormonal Results

If Autonomous Cortisol Secretion Detected

• Screen for and aggressively treat hypertension and type 2 diabetes 2
• Consider surgical resection if the patient has comorbidities potentially related to cortisol excess (including mood disorders and metabolic dysfunction), particularly in younger patients 2, 3
• Minimally invasive adrenalectomy is preferred when feasible 1

If Pheochromocytoma Confirmed

• Mandatory surgical resection with preoperative alpha-blockade (phenoxybenzamine) followed by beta-blockade 1
• Minimally invasive surgery when technically feasible 1

If Primary Aldosteronism Confirmed

• Adrenal vein sampling required before offering surgery to confirm lateralization 1
• Unilateral adrenalectomy for confirmed unilateral disease 1

If Nonfunctional Benign-Appearing Nodule

• No surgery indicated if <4 cm and clearly benign imaging features (≤10 HU) 1, 2
• Repeat imaging at 6-12 months if ≥4 cm despite benign features 1
• Sexual dysfunction and mood disorders likely unrelated to adrenal pathology; pursue alternative etiologies 1

Critical Pitfalls to Avoid

• Never biopsy an adrenal mass before excluding pheochromocytoma, as this can precipitate fatal hypertensive crisis 1
• Do not assume sexual dysfunction is unrelated to adrenal pathology without completing full hormonal evaluation, as subtle hormonal excess can manifest primarily as neuropsychiatric and sexual symptoms 1, 2
• Autonomous cortisol secretion is frequently missed because patients lack obvious Cushingoid features but still suffer significant morbidity from mild cortisol excess 2, 3
• Annual hormonal re-evaluation is recommended for nonfunctional nodules ≥4 cm for at least 4 years, as functional transformation can occur 1

Multidisciplinary Discussion Recommended

A multidisciplinary team meeting involving endocrinology, surgery, and radiology should occur when imaging is indeterminate, hormone hypersecretion is detected, the tumor grows significantly on follow-up, or surgery is being considered 1

1, 2, 3, 4