Clinical Course of Adrenal Myelolipoma

A Long-Term Longitudinal Follow-up Study

Oksana Hamidi; Ram Raman; Natalia Lazik; Nicole Iniguez-Ariza; Travis J. McKenzie; Melanie L. Lyden; Geoffrey B. Thompson; Benzon M. Dy; William F. Young Jr; Irina Bancos

Disclosures

Clin Endocrinol. 2020;93(1):11-18. 

In This Article

Discussion

In this longitudinal follow-up study, we characterized demographics, clinical presentation and management of 305 consecutive patients with adrenal myelolipoma followed for a median of 4.5 years. We found that most myelolipomas were small (median tumour size of 2.3 cm), asymptomatic, and remained stable in size on follow-up imaging. Similar to our findings, another large retrospective study of 150 patients with myelolipoma discovered on imaging showed that mean tumour size was 2.1 cm and only 8% of myelolipomas measured ≥6 cm.[16] In contrast, a recent review of previously reported cases and case series (420 patients) summarized that myelolipomas are usually large tumours averaging at 10.2 cm, with 36% of tumours measuring <10 cm.[12,17] The discrepancy between our findings and previously reported case series suggests a potential publication bias of primarily describing symptomatic myelolipoma cases.

Overall, myelolipomas remain stable in size or grow slowly. We found that median tumour size minimally increased from 2.3 to 2.6 cm and only 16% of myelolipomas grew by more than 1 cm over 4.5 years of median follow-up. In our longitudinal follow-up study, the annual growth rate ranged from −6 to 14 mm/y. Similarly, others reported >5 mm tumour growth in 16% of myelolipomas.[16] In a small study of 12 patients followed for 2.3 years, tumour size increased by a mean of 2 mm/y.[18] Similarly, tumour growth was shown in 11/69 (16%) patients with myelolipoma in another study, ranging from 0.8 to 7.1 mm/y (median, 1.6 mm/y) over 3.9 years of follow-up.[16] Although one study found that tumour growth was more likely in younger patients and longer duration of follow-up,[16] we found that significant tumour growth was associated with larger initial tumour size and presence of haemorrhagic changes, but not with age, sex or mode of discovery. Based on our findings, small myelolipomas without haemorrhagic changes do not require imaging follow-up, whereas large myelolipomas or those with haemorrhagic changes on initial imaging should undergo additional follow-up or undergo resection.

Most adrenal myelolipomas do not require surgical intervention or monitoring. In our cohort, 12% of patients underwent resection of myelolipoma. Surgical resection was more common in younger patients, in those with symptoms of mass effect, in patients with larger tumours, or tumours that had radiographic haemorrhagic changes or increased in size. In accordance with other studies, laparoscopic adrenalectomy appears safe and effective.[19–21] One study recommended surgical resection for all lipomatous tumours ≥3.5 cm, in addition to tumours leading to mass effect symptoms and those with uncertain diagnosis based imaging characteristics.[17] However, our findings support that conservative management is preferred for most patients with myelolipomas due to their benign and indolent nature. Surgery may be indicated for large symptomatic myelolipomas, those with diagnostic uncertainty, or those with significant tumour growth.

Spontaneous rupture and retroperitoneal haemorrhage of myelolipoma are exceedingly rare and more commonly described in large tumours measuring more than 6–7 cm.[13] While radiographic haemorrhagic changes were seen in 9 (3%) patients in the present study, acute haemorrhage/tumour rupture requiring surgical intervention was reported in only 3 (0.9%) patients, all with myelolipomas ≥6 cm. Another study of incidentally discovered myelolipomas identified no cases of myelolipoma with retroperitoneal haemorrhage.[16] In contrast, several studies reported up to 4.5% of cases with tumour rupture, most in large myelolipomas greater than 10 cm.[12,22,23] Higher prevalence of tumour rupture in previous reports raises a concern for publication bias.

Current guidelines for the management of adrenal incidentaloma do not propose hormonal evaluation for obvious myelolipoma.[14,15] Although adrenal myelolipomas do not contain any adrenal cortical or medullary components and are not hormonally active, coexisting hormone hypersecretion and adrenocortical adenomas are reported in 7.5% and 5.7% of myelolipoma cases, respectively.[12] Hormonal hyperfunction in patients with myelolipoma is likely due to adrenal collision tumours coexisting with myelolipomas or coexisting ipsilateral or contralateral adrenal cortical adenomas or hyperplasia.[13] In our study, hormonal hypersecretion due to coexisting adrenal adenoma or hyperplasia was observed in 9.5% of cases. There were no cases of pheochromocytoma or adrenocortical carcinoma in the present study. Therefore, hormonal workup should be considered in patients with suspected coexisting adrenal adenoma and those with overt features of hormone excess (such as primary aldosteronism and overt Cushing syndrome), rather than all patients with myelolipoma.

Our study has several limitations including its retrospective design, limited length of follow-up, differences in follow-up and management strategies of patients over time, and partial workup and management done outside of our institution. First, prevalence of myelolipoma may be misrepresented in our study as we only evaluated patients who underwent abdominal imaging and the true rate and longitudinal history in those individuals without imaging follow-up could not be ascertained. Thus, all point estimates are based on available data and the possibility of initial imaging detection bias cannot be excluded. Many adrenal myelolipomas were diagnosed based on imaging characteristics and did not undergo histopathological confirmation of the diagnosis. Therefore, some of the tumours could have been misdiagnosed as myelolipoma based on the presence of macroscopic fat. Yet, the majority of myelolipomas rely on radiographic characteristics and cannot be histopathologically confirmed in clinical practice. Of importance, only those patients that had at least 6 months of serial imaging were included in the longitudinal analysis, which could potentially represent a repeat imaging bias and reflect underlying clinical concern and/or other high-risk features. Additionally, indications for surgery varied based on an individual circumstance; therefore, symptomatic and/or large myelolipomas with concerning radiographic characteristics such as haemorrhage were more likely to be removed, contributing to selection bias. Another important limitation of our study is limited evaluation for CAH, with only 4% of our cohort undergoing evaluation for coexisting CAH. In our opinion, screening for CAH should be considered in all patients with bilateral myelolipomas, cortical adenomas or hyperplasia even in the absence of overt clinical findings. Strengths of the study include a large sample size and consecutive cohort of patients, as well as availability of detailed medical records.

In conclusion, most myelolipomas are small, asymptomatic, remain stable in size over time, and do not require surgical intervention or follow-up. In contrast, myelolipomas ≥6 are more likely to cause mass effect symptoms and have radiographic haemorrhagic changes. Hormonal excess is rare and is attributed to concomitant adrenocortical adenomas or hyperplasia. Adverse events such as tumour rupture and acute retroperitoneal haemorrhage are exceedingly rare. Tumour growth is associated with larger myelolipomas and presence of radiographic haemorrhagic changes. Surgical resection should be considered in symptomatic patients with large tumours, evidence of haemorrhage or tumour growth.

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