Adrenal Myelolipoma 

Adrenal Myelolipoma – 6 Interesting Facts

1. Adrenal myelolipomas are benign tumors that can be reliably characterized on cross-sectional imaging (CT or MRI); biopsy is not recommended
2. May be associated with concomitant adrenal cortical tumors or adrenal hyperplasia; consider testing patients with myelolipoma for adrenal hormone excess
3. Large tumors (greater than 6 cm) may cause symptoms of mass effect or intratumoral hemorrhage and may be considered for adrenalectomy
4. Patients with adrenal myelolipomas greater than 6 cm that are not removed should undergo interval imaging (6-12 months) to assess for growth or change in characteristics
5. Most adrenal myelolipomas do not grow or cause symptoms; complications are rare but include acute hemorrhage and tumor rupture, which may lead to hemorrhagic shock
6. Refer to multidisciplinary endocrine team if diagnosis is unclear or associated with hormonal excess or if patient requires adrenalectomy owing to mass effect

Alarm Signs and Symptoms

• Although rare, acute hemorrhage with tumor rupture is an emergency and presents with symptoms of abdominal pain, nausea, and vomiting with hemorrhagic shock
• Rapid growth of suspected adrenal myelolipoma should prompt reconsideration of diagnosis and suspicion of malignancy

Basic Information

Terminology

• Adrenal myelolipomas are benign tumors composed of mature fat and hematopoietic tissue
• By definition, they are not hormonally active because they do not contain adrenal cortical tissue

Epidemiology

• Adrenal myelolipomas comprise approximately 3% to 6% of all adrenal masses ¹ and are the second most common type of benign adrenal mass (after adrenocortical adenoma)³
• Prevalence in general population (aged 40 years or older) is 0.32%;³ diagnosed equally in female and male patients at median age of 55 to 65 years¹
• Adrenal myelolipomas are identified due to symptoms of mass effect in 5% of cases¹ but are most often detected on imaging ordered for another reason
  • 95% of patients with adrenal myelolipoma have unilateral tumor with median size of 2 to 4 cm at time of diagnosisv²
  • Patients with adrenal myelolipomas larger than 6 cm (14%) are more likely to present with bilateral disease (3% versus 20%), report symptoms of mass effect (0% versus 32%), and have intratumoral hemorrhagic changes (1% versus 14%)⁵

Etiology and Risk Factors

• Adrenal myelolipomas are typically considered idiopathic; multiple theories exist regarding pathogenesis⁴
  • Metaplastic change¹
    • Theoretical mechanism includes metaplasia of reticuloendothelial cells owing to stress, infection, trauma, or embolism of bone marrow cells
  • Hormonal activation⁴
    • This theory posits that tumor formation is caused by overstimulation of adrenals by ACTH
      • Increased incidence in patients with prolonged increased levels of ACTH (as in the case of congenital adrenal hyperplasia)
        • Nearly one-quarter of patients with genetically confirmed congenital adrenal hyperplasia have adrenal tumors; 36.6% of these tumors are myelolipomas³
        • Patients with genetically confirmed congenital adrenal hyperplasia present with much higher prevalence of adrenal myelolipomas (8.6%) than patients without the condition (0.32%)³

Diagnosis

Approach to Diagnosis

• Myelolipomas are most often detected incidentally on imaging performed for a nonadrenal process (85%-90%) or during cancer staging (5%-10%)¹
• Characteristic radiographic appearance of macroscopic fat components can establish diagnosis without additional radiologic testing; biopsy is not indicated⁴
• After detection and diagnosis on imaging, workup including history, physical examination, and laboratory studies should be directed toward identifying signs and symptoms related to either hormonal excess or mass effect, tumor growth, tumor hemorrhage, or concomitant adrenal hormone excess
• Current guidelines do not recommend further investigation of incidentally discovered adrenal lesions with diameter less than 1 cm, unless clinically indicated⁹

Workup

History

• Direct history- taking toward identifying any symptoms related to:
  • Mass effect (eg, abdominal, back, and flank pain; early satiety; positional shortness of breath)
  • Concomitant adrenal hormonal excess
    • Hypercortisolism: weight gain, easy bruising, hypertension, diabetes, virilization, proximal muscle weakness, fatigue⁹
    • Hyperaldosteronism: hypertension, fluid retention, history of hypokalemia⁴

Physical Examination

• Assess vital signs including pulse and blood pressure⁹
• Evaluate for physical signs of hormonal excess:
  • Skin atrophy, bruising, facial rounding (moon facies), wide-based red or purple striae, centripetal obesity, supraclavicular and dorsocervical (buffalo hump) fullness
• Evaluate for palpable abdominal mass
  • Only very large adrenal myelolipomas may be palpable

Laboratory Tests

• Myelolipomas do not lead to adrenal hormone excess
  • However, they can be associated with adrenocortical adenoma or hyperplasia
  • Perform hormonal workup in patients with suspected concomitant adrenal hormone excess as informed by clinical presentation⁹
  • Screen for:
    • Autonomous cortisol secretion
      • 1-mg overnight dexamethasone suppression test is initial screening test
        • 8 AM cortisol values greater than 1.8 mcg/dL are consistent with mild autonomous cortisol secretion
        • Abnormal results (cortisol levels greater than 1.8 mcg/dL) should be further evaluated with 24-hour urinary free cortisol, baseline serum ACTH, dehydroepiandrosterone sulfate, and high-dose (8 mg) overnight dexamethasone suppression tests⁹
    • Primary aldosteronism
      • Indicated if patient has hypertension or hypokalemia
      • Assess serum potassium, plasma aldosterone, and plasma renin activity levels⁹
    • Congenital adrenal hyperplasia
      • Consider in patients with large or bilateral tumors
      • Measure 17-hydroxyprogesterone level³
    • Pheochromocytoma
      • Coincidental associations with myelolipoma and pheochromocytoma are very rare
      • Measure plasma or 24-hour urine metanephrine and catecholamine levels

Imaging Studies

• Noncontrast CT is most appropriate imaging modality to diagnose adrenal myelolipoma (Figure 1)
  • Adrenal myelolipoma is diagnosed on imaging with its characteristic well-circumscribed, rounded, or elliptical encapsulated pattern of macroscopic fat components with attenuating myeloid components
  • Myelolipomas may have different proportions of fat and myeloid tissue giving them hypodense and heterogeneous radiographic appearance
  • Atypical radiologic features (eg, hemorrhage, calcification) may be observed
• On unenhanced CT results, lipomatous portion appears dark (−100 Hounsfield units); depending on proportions of fat and myeloid tissue, most adrenal myelolipomas are −20 to −50 Hounsfield units
• On MRI results, myelolipomas have high signal intensity on T1-weighted images owing to macroscopic fat content, which is confirmed by demonstrating loss of signal intensity within fatty component on out-of-phase images

Differential Diagnosis

Table

Table 1. Differential Diagnosis: Adrenal myelolipoma.

Condition	Description	Differentiated by
Adrenocortical adenoma	Most common type of incidental adrenal mass detected on imaging	Similar to adrenal myelolipomas on imaging in that they are well-demarcated round or oval lesions but appear more homogeneous than myelolipomas with low attenuation values owing to high-fat content (<10 HU)Do not have characteristic heterogeneous radiographic pattern of macroscopic fat mixed with myeloid componentsMay or may not produce cortisol or aldosterone
Adrenocortical carcinoma	Rare primary malignancy of adrenal gland	Size tends to be >6 cmIrregularly shapedCentral areas of necrosis and hemorrhage, resulting in variable enhancementDifficult to distinguish from adenoma or myelolipoma when detected early at small size when aggressive features may be absentMay or may not be functional (eg, secreting glucocorticoids, mineralocorticoids, or androgens)Usually have high unenhanced CT attenuation (>20 HU); hemorrhagic changes may lead to low attenuationAny concern for malignancy should prompt surgical resection or close imaging follow-up at 3 months
Retroperitoneal liposarcoma	One of most common primary retroperitoneal malignancies Can be confused with extra-adrenal (retroperitoneal) myelolipoma on cross-sectional imaging	Technetium Tc 99m sulfur colloid scan can differentiate extra-adrenal myelolipoma from liposarcoma because myelolipoma uptakes tracer and liposarcoma does notCore needle biopsy may be needed to diagnose liposarcoma
Adrenal metastasis	Metastasis to adrenal gland is most common with primary malignancies of lung, breast, melanoma, kidney, or colon/rectum	Suspect adrenal metastasis in patient with history of cancer or other metastatic lesions visible on imagingAdrenal metastases on contrast imaging have strong enhancement and prolonged washout
Pheochromocytoma	Adrenal medullary tumor	Most pheochromocytomas are functional and can be detected by elevated plasma or 24-hour urine metanephrine or normetanephrine levelsPheochromocytomas are lipid poor; rapid enhancement with delayed washout is often characteristic of pheochromocytoma on contrast-enhanced CTOn MRI, pheochromocytomas are hyperintense on T2-weighted images

Caption: HU, Hounsfield units.

Treatment

Approach to Treatment

• Figure 2. Algorithm for management of suspected adrenal myelolipoma.1,3,5,9,11

• No high-quality evidence on management of adrenal myelolipomas exists, and no trials have been performed; guidance is based on retrospective studies and expert opinion (Figure 2)
• Small myelolipomas (less than 4-6 cm) with pathognomonic features on imaging do not require treatment or follow-up if they are asymptomatic¹
• Indeterminate imaging features (not fully consistent with myelolipomas) or any concern for malignancy should prompt surgical resection or short-term imaging follow-up at 3 months
• Large myelolipomas (greater than 6-10 cm) are more likely to grow
  • Monitor clinically for symptoms of mass effect. Depending on concern, interval imaging should be performed at 6 to 12 months
• Adrenalectomy is undertaken in minority of cases; specific indications include:¹
  • Patients with concomitant adrenal hormone excess (depending on type and site)
  • Myelolipomas with tumor growth of 1 cm or more during interval follow-up⁵
    • Approximately 16% increase in size by more than 1 cm
  • Large adrenal myelolipomas that are causing symptoms of mass effect
  • Adrenal myelolipomas that present with evidence of intratumoral hemorrhage
    • Larger adrenal myelolipomas (greater than 6 cm) may be at higher risk of intratumoral hemorrhage, which can lead to rupture
• Adrenalectomy is definitive treatment of adrenal myelolipoma; no recurrence has been reported

Treatment Procedures

• Laparoscopic adrenalectomy is preferred surgical approach for benign adrenal masses 6 cm or less and should be performed by surgeons experienced in the procedure
• For benign-appearing adrenal tumors greater than 6 cm, laparoscopic adrenalectomy may be performed by experienced adrenal surgeons who are able to resect mass en bloc
• Open adrenalectomy may be required for resection of large adrenal myelolipomas

Admission Criteria

• Workup for asymptomatic adrenal myelolipoma can be performed in outpatient setting
• Indications for admission include radiographic evidence of acute intratumoral hemorrhage or rupture, which may present with abdominal pain, nausea, and vomiting with hemorrhagic shock

Follow-up

Monitoring

• No surgery or ongoing monitoring is required in patients with small asymptomatic adrenal myelolipoma (less than 4-6 cm) with clear radiographic diagnosis¹
• Imaging
  • Large adrenal myelolipomas (greater than 6 cm) may benefit from imaging at 6 to 12 months because they may lead to symptoms of mass effect or acute hemorrhage or demonstrate interval growth
  • If imaging characteristics are not definitive for adrenal myelolipoma: surgical resection or close follow-up imaging at 3 months²
• Laboratory testing
  • Repeat hormonal testing is not recommended if initial findings are unremarkable and no new symptoms of hypersecretion or worsening of comorbidities have occurred¹⁰

Complications

• Rare complications of adrenal myelolipomas include acute hemorrhage and tumor rupture
  • Acute hemorrhage or rupture is rare, occurring in 6.8% of cases, and is associated with large myelolipomas greater than 8 to 10 cm¹
  • Symptoms of acute hemorrhage or rupture include abdominal pain, nausea, and vomiting with hemorrhagic shock

Prognosis

• 85% of adrenal myelolipomas do not grow or cause symptoms⁵
• When indicated, surgical adrenalectomy is definitive treatment; no recurrences have been reported

Referral

• Patients who meet the following criteria should be referred and managed by multidisciplinary endocrine team:¹⁰
  • Evidence of hormone excess
  • Significant tumor growth (greater than 1 cm) during follow-up imaging
  • Symptoms of mass effect
  • Presence of congenital adrenal hyperplasia

References

1.Calissendorff J et al. Adrenal myelolipomas. Lancet Diabetes Endocrinol. 2021;9(11):767-775. DOI 34450092

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2.Song JH et al. The incidental adrenal mass on CT: prevalence of adrenal disease in 1049 consecutive adrenal masses in patients with no known malignancy. AJR Amer J Roentgenol. 2008;190(5):1163-1168.

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3.Nermoen I et al. Prevalence and characteristics of adrenal tumors and myelolipomas in congenital adrenal hyperplasia: a systematic review and meta-analysis. Endoc Pract. 2020;26(11):1351-1365.

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4.Decmann Á et al. Adrenal myelolipoma: a comprehensive review. Endocrine. 2018;59(1):7-15.

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5.Hamidi O et al. Clinical course of adrenal myelolipoma: a long-term longitudinal follow-up study. Clin Endocrinol (Oxf). 2020;93(1):11-18.

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6.Yeomans H et al. Limited value of long-term biochemical follow-up in patients with adrenal incidentalomas–a retrospective cohort study. BMC Endocr Disord. 2015;15:6.

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7.Patrova J et al. Clinical outcomes in adrenal incidentaloma: experience from one center. Endocr Pract. 2015;21(8):870-877.

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8.Shenoy VG et al. Adrenal myelolipoma: controversies in its management. Indian J Urol. 2015;31(2):94-101.

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9.Zeiger MA et al. American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas. Endocr Pract. 2009;15(Suppl 1):1-20.

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10.Fassnacht, M et al. Management of adrenal incidentalomas: European Society of Endocrinology clinical practice guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocr. 2016;175(2):G1-G34.

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11.Marty M et al. Diagnostic accuracy of computed tomography to identify adenomas among adrenal incidentalomas in an endocrinological population. Eur J Endocrinol. 2018;178(5):439-446.

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