What follow-up is recommended for a patient with an incidentally discovered adrenal adenoma on computed tomography, low morning cortisol on dexamethasone suppression test, normal estradiol, low free and bioavailable testosterone, and normal metanephrine, normetanephrine, aldosterone, renin, and aldosterone‑to‑plasma renin ratio?

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Follow-Up for Incidental Adrenal Adenoma with Mild Autonomous Cortisol Secretion

This patient has mild autonomous cortisol secretion (MACS) based on the low morning cortisol after dexamethasone suppression, and requires annual clinical screening for new or worsening metabolic comorbidities, but no further imaging or hormonal testing is needed if the adenoma is <4 cm and radiologically benign (<10 HU). 1

Understanding the Clinical Picture

Your patient's biochemical profile reveals:

  • Low AM cortisol post-dexamethasone = Mild autonomous cortisol secretion (MACS)
  • Normal metanephrines/normetanephrines = Pheochromocytoma excluded
  • Normal aldosterone/renin/ARR = Primary aldosteronism excluded
  • Low testosterone levels = Potentially attributable to cortisol excess
  • Normal estradiol = No evidence of feminization/adrenocortical carcinoma

The low testosterone (both free and bioavailable) in the setting of MACS is clinically significant, as autonomous cortisol secretion can suppress the hypothalamic-pituitary-gonadal axis and contribute to hypogonadism.

Specific Follow-Up Algorithm

If the adenoma is <4 cm and radiologically benign (<10 HU on non-contrast CT):

No further imaging or hormonal testing is required. 1 Instead:

  1. Annual clinical assessment focusing on:

    • Blood pressure monitoring (hypertension development/worsening)
    • Fasting glucose and HbA1c (diabetes development/worsening)
    • Lipid panel (hyperlipidemia development/worsening)
    • Bone density assessment if risk factors present (osteoporosis from cortisol excess)
    • Weight and body composition changes (central obesity, metabolic syndrome)
    • Cardiovascular risk stratification 1, 2

  2. Address the low testosterone: The hypogonadism may be secondary to MACS and could improve with adrenalectomy if surgery is pursued, or may require testosterone replacement if managed conservatively.

If the adenoma is ≥4 cm (even if radiologically benign):

Repeat imaging in 6-12 months 1, 3

  • If growth is <3 mm/year: No further imaging needed 1
  • If growth is >5 mm/year: Consider adrenalectomy after repeating functional work-up 1

Surgical Consideration

Younger patients with MACS who have progressive metabolic comorbidities attributable to cortisol excess can be considered for adrenalectomy after shared decision-making. 1

Key factors favoring surgery:

  • Patient age (younger patients benefit more from intervention)
  • Presence of difficult-to-control hypertension
  • New-onset or worsening diabetes
  • Symptomatic hypogonadism (low testosterone) potentially reversible with surgery
  • Progressive metabolic syndrome features
  • Osteoporosis or fragility fractures

The 2023 CUA/AUA guidelines 1 and 2023 European Society of Endocrinology guidelines 2 both emphasize that MACS carries increased morbidity and mortality risk, making surveillance and treatment of associated comorbidities paramount.

Critical Pitfalls to Avoid

  1. Don't assume "subclinical" means "clinically insignificant": MACS is associated with increased cardiovascular events, metabolic complications, and mortality even without overt Cushing's syndrome 2

  2. Don't repeat hormonal screening unnecessarily: If initial comprehensive screening is normal except for MACS, repeated hormonal testing adds minimal value 4. The exception is if the mass grows >5 mm/year 1

  3. Don't ignore the testosterone deficiency: This may be cortisol-related and could improve with adrenalectomy if surgery is pursued

  4. Don't order routine pheochromocytoma screening on follow-up: With normal initial metanephrines and a benign-appearing adenoma, repeat screening is not indicated 1, 2

Multidisciplinary Discussion

Consider endocrinology referral or multidisciplinary team discussion if 1:

  • The patient develops worsening metabolic comorbidities
  • Surgery is being considered
  • The mass demonstrates growth on follow-up imaging
  • Clinical uncertainty exists regarding management

The evidence strongly supports that small (<4 cm), lipid-rich adenomas with MACS rarely progress to clinically significant disease 5, but the metabolic consequences of even mild cortisol excess warrant ongoing clinical vigilance rather than biochemical or radiological surveillance.

References

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