What is the treatment for acquired adrenal androgenic overactivity?

Treatment of Acquired Adrenal Androgenic Overactivity

Surgical intervention with adrenalectomy is the primary treatment for adrenal androgenic overactivity, particularly when associated with adrenocortical tumors or when there are signs of virilization. 1

Diagnostic Approach

Before initiating treatment, proper diagnosis is essential:

1. Laboratory Testing:

   • Serum testing for excess androgens including DHEAS, testosterone, 17β-estradiol, 17-OH progesterone, androstenedione, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol 1
   • Higher levels of these hormones suggest greater disease burden

2. Imaging:

   • Non-contrast CT as first-line imaging to distinguish benign from suspicious lesions 1
   • If indeterminate on non-contrast CT, proceed to washout CT or chemical-shift MRI 1
   • Adrenal masses with >10 HU on non-contrast CT are more suspicious for functional tumors 1

3. Clinical Assessment:

   • Look for signs of virilization: hirsutism, acne, androgenic alopecia, menstrual irregularities, clitoromegaly 2
   • Assess for metabolic complications: hypertension, diabetes, obesity 1

Treatment Algorithm

1. For Adrenal Tumors with Androgenic Overactivity:

• Surgical Management:

  • Unilateral adrenalectomy of the affected gland is the treatment of choice 1
  • Minimally-invasive surgery (MIS) should be performed when feasible 1
  • For suspected adrenocortical carcinoma (ACC), minimally-invasive adrenalectomy can be offered if the tumor can be safely resected without rupturing the capsule 1
  • For larger ACCs or those with locally advanced features, open adrenalectomy should be considered 1

• Perioperative Considerations:

  • Meticulous perioperative management of hormonal, glucose, electrolytes, and blood pressure abnormalities is critical 1

2. For Non-Surgical Cases or Adjuvant Therapy:

• Medical Management:

  • For adrenocortical carcinoma with androgen excess:
    • Mitotane is recommended for patients with incomplete resection or high-risk features (Ki67>10%) 1
    • For inoperable disease with high tumor burden and rapid progression: combination cytotoxic chemotherapy plus mitotane (EDP-M) 1
    • For less fit patients or those with low tumor burden: mitotane monotherapy 1

• For Non-Classical Congenital Adrenal Hyperplasia (NCCAH):

  • Glucocorticoids to suppress adrenal androgen production 2
  • Alternative therapies include antiandrogens (cyproterone acetate, spironolactone) and estrogen-progestin combinations for women 2

Follow-Up Protocol

• Post-Surgical Monitoring:

  • Regular follow-up every 3 months including abdominal CT (or MRI), thoracic CT, and monitoring of initially elevated steroids 1
  • After 2 years, intervals may be gradually increased 1
  • Follow-up should continue for at least 10 years 1

• For Non-Surgical Cases:

  • Monitoring every 2-4 months during the first year 1
  • Assess for improvement in clinical signs of androgen excess
  • Monitor hormone levels to evaluate treatment efficacy

Special Considerations

• Adrenal Insufficiency Risk:

  • Patients undergoing surgical removal of functioning adrenal tumors may develop adrenal insufficiency postoperatively 3
  • Hydrocortisone replacement may be necessary (typically 15-25 mg/day in divided doses) 3
  • Dose adjustments needed during stress, illness, or surgery 3

• Fertility Concerns:

  • Women with androgenic overactivity may experience infertility due to androgen excess, dysovulation, and progesterone-mediated implantation issues 2
  • Treatment of the underlying cause can improve fertility outcomes

• Pitfalls to Avoid:

  • Do not perform adrenal mass biopsy routinely for work-up of adrenal masses 1
  • Do not misdiagnose as polycystic ovary syndrome, which can delay appropriate management 2
  • Avoid undertreatment of metabolic complications associated with androgen excess 1

The management of adrenal androgenic overactivity requires a systematic approach with appropriate diagnostic testing followed by targeted intervention, with surgical management being the cornerstone of treatment for tumorous causes and medical therapy for non-tumorous etiologies.