A Rare Association of Adrenal Lipoma and Primary Hyperaldosteronism: A Case Report

INTRODUCTION

Adrenal lipomas are a very rare tumors of adrenal gland, with around 24 cases being reported in the literature till now. These are benign tumors, being reported to originate commonly from the right adrenal gland with a female predilection. Most of these tumors are non-functional and asymptomatic, with most of them being diagnosed on autopsy or as an incidentaloma on imaging. Among symptomatic patients, back or loin pain is the common presenting feature, with one case presenting with paroxysmal hypertension.¹ There are no cases being reported of adrenal lipoma associated with hormonal secretion in the literature until now.

Primary hyperaldosteronism is one of the common causes of resistant hypertension which can increase cardiovascular morbidity and mortality. It can be associated with hypokalemia in some people. It is usually caused by an adrenal adenoma, unilateral or bilateral adrenal hyperplasia (BAH), or in rare cases adrenal carcinoma or inherited conditions of familial hyperaldosteronism. It is important to diagnose it appropriately as it can be treated effectively with either medical or surgical modalities.²

We report a rare case, probably the first case, of association of adrenal lipoma with primary hyperaldosteronism, who was treated successfully with surgery.

CASE DESCRIPTION

A 57 years old female, with uncontrolled type 2 diabetes mellitus and hypertension since about 5 years, was admitted with right lower limb cellulitis and lower respiratory tract infection. She was on three antihypertensive medications and yet the blood pressure was high (180/100 mm Hg). Her initial blood investigations during admission showed: hemoglobin–10.6 gm/dL, total leukocyte count-23200 cells/microL, HbA1c–9.5%, serum sodium–132 mmoL/L, potassium–4.1 mmoL/L, serum creatinine–0.8 mg/dL. Computed tomography of the chest, which was done for her lung infection, revealed a lipid rich right adrenal adenoma (incidentaloma), of size 21 × 17 mm (Fig. 1). Clinically, she did not have any specific symptoms or signs of Cushing syndrome, pheochromocytoma or primary hyperaldosteronism, except for resistant hypertension. There was no clinical evidence of adrenal insufficiency either. Baseline 8 am cortisol was found to be normal–22.93 μg/dL. The 2D echocardiogram was normal except for grade I diastolic dysfunction. She was treated for her infection, following which she recovered and discharged.

Hormonal evaluation for right adrenal adenoma was with-held initially and then done later on follow-up after stopping the antihypertensive medications which are known to interfere with the hormonal evaluation. During this period, her blood pressure was managed with prazosin and verapamil. The investigations showed: 8 am cortisol–14.9 μg/dL, potassium–4.1 mmoL/L; post over-night dexamethasone suppression test cortisol–1.7 μg/dL, plasma free metanephrines–89.3 pg/mL (<100), plasma free normetanephrines–472 pg/mL (216), 24 hours urinary normetanephrines–91.26 μg, plasma renin activity (PRA)–0.32 ng/mL/hour, serum aldosterone–12.1 ng/dL. The aldosterone renin ratio (ARR) was 37.81, which was found to be elevated and suggestive of primary hyperaldosteronism. Then she underwent confirmatory test in the form of saline infusion test (SIT). Post-infusion serum aldosterone level was 6.99 ng/dL, which was in the indeterminate range, although some studies have shown the value of >6.8 ng/dL is sensitive and specific to diagnose primary hyperaldosteronism.³ In view of resistant hypertension, right adrenal adenoma and high ARR and post-SIT aldosterone levels, a diagnosis of primary hyperaldosteronism secondary to right adrenal adenoma was considered. Adrenal venous sampling was not done, as it was not feasible in our patient. She was started on spironolactone 25 mg twice a day along with prazosin and verapamil. Following spironolactone treatment, her blood pressure reduced from 160/86 to 110/72 mm Hg within couple of days. However, she developed hyponatremia for which she had to be hospitalized and treated. Spironolactone was discontinued and was advised for surgical treatment for right adrenal adenoma. After adequate glycemic and blood pressure control, she underwent uneventful laparoscopic right adrenalectomy (Fig. 2). The histopathological report of operative specimen (lesion) revealed well-capsulated adipocytic lesion composed of lobules of mature adipocytes and thin septa, suggestive of adrenal lipoma (Fig. 3). There were also foci of adrenocortical hyperplastic nodules of size <0.5 cm composed of large polygonal cells with foamy rich cytoplasm and well-defined cell border and oncocytic cytoplasm (Fig. 4).

Following surgery, her blood pressure normalized and was maintained with telmisartan 40 mg and cilnidipine 5 mg. The dose of oral antidiabetic medications was also reduced over a period. Postoperative PRA was 1.17 ng/mL/hour, serum aldosterone was 9.93 ng/dL and ARR was 8.48, which showed biochemical normalization (Table 1). She is under regular follow-up for 6 months postoperatively and is doing fine.

DISCUSSION

Adrenal lipomas are a very rare, benign adrenal tumors, belonging to a group of adrenal lipomatous tumors, with around 24 documented cases being reported in the English literature. The prevalence of adrenal lipomas is very low.¹ In two of the case series reported till now, the prevalence was found to be 0.7% of all primary adrenal tumors in one study⁴ and 4% of all adrenal lipomatous tumors.⁵ About two third of these adrenal lipomas are reported among the Asian population. These tumors occur commonly in males, in contrast to other adrenal lipomatous lesions which are frequent in females. They commonly occur in the sixth decade, as was in our case as well. Adrenal lipomas are more frequently seen in the right adrenal gland (right-to-left ratio = 2.4–1).¹ Our patient also had the tumor in right adrenal gland.

The adrenal lipomas noted in the literature till now are all non-functional. Hence, most of these tumors are diagnosed as incidental findings either at autopsy or as incidentalomas at radiological examination. Some of these cases are associated with symptoms, mainly because of the mechanical effect of the tumours.¹ The case reported by Lange in 1966 showed paroxysmal hypertension, which was assumed to be due to mechanical irritation of the adrenal medulla by the tumor to produce catecholamines.⁶ Other symptoms associated with adrenal lipoma are abdominal or loin pain.

The dimension of adrenal lipomas published in the literature ranges from 10 to 200 mm and the weight ranges from 7 to 2900 gm. Apart from detected at autopsy, the adrenal lipomas were often detected as incidentalomas on radiological examination. Computed tomography, ultrasonography, magnetic resonance imaging of the abdomen done for a different indication identifies an adrenal incidentaloma.^1,7 In our patient too, computed tomography was done in view of lung infection, which detected a right adrenal incidentaloma.

Nevertheless, the diagnosis of adrenal lipoma can only be made on histological examination. On macroscopic examination, the tumor appears well demarcated and composed of yellow adipose tissue. On cut section, most of the tumors are yellow, homogeneous and soft.¹ One reported case showed patches of hemorrhages in the tumor due to bleeding from the vessels in the lipoma resulting in retroperitoneal bleeding.⁸ On microscopic examination, adrenal lipoma is composed of mature adipose tissue. Calcification, inflammation, and necrosis are also reported in few patients. The absence of myeloid elements differentiates adrenal lipoma from adrenal myelolipoma, which is more common in prevalence. Hence, adequate tissue blocks should be sampled and examined to rule out the presence of myeloid elements. Of the 24 adrenal lipomas in the literature, 6 were detected at autopsy and 18 were detected at examination of surgical resected specimens.¹

Treatment of adrenal lipomas includes surgical resection, either by a laparoscopic or open approach. Among the patients’ follow-up data available, none of them had any signs of local recurrence or malignancy. Prognosis is good unless the tumors are associated with any complication.¹

In our patient, the tumor was detected as an adrenal incidentaloma (lipid-rich adenoma) on computed tomography of the chest which was done for the lung infection. Our patient was having resistant hypertension. Apart from this, our patient neither had any local symptoms nor any features of hormone excess/deficiency. In view of the above, after the lung infection subsided, she underwent the hormonal evaluation, which revealed primary hyperaldosteronism. We suspected the source of aldosterone excess to be the adrenal adenoma and treated her initially with spironolactone and followed by surgical excision of the right adrenal gland. It was only after the histopathological examination of the surgical specimen, that it was confirmed the tumor was adrenal lipoma. However, there were also foci of adrenocortical hyperplastic nodules in the excised adrenal gland.

There is no literature to show any association between adrenal lipoma and primary hyperaldosteronism, as all the case published reports have shown that adrenal lipomas are non-functional.¹ However, our patient had resistant hypertension, which responded immediately to spironolactone and then following right adrenalectomy, her blood pressure was well controlled with a small dose of two antihypertensive agents. There was biochemical normalization of hyperaldosteronism as well, postoperatively. So, our patient had excess aldosterone production.

The adrenal lipomas and myelolipomas belong to same group of adrenal lipomatous tumors, and may share the same origin and pathogenesis. There are some cases of adrenal myelolipomas associated with excess hormone production including aldosterone.⁹

The excess aldosterone production in our patient could either be from the right adrenal lipoma or from adrenocortical hyperplastic nodules noted in rest of the gland, with the latter hypothesis appearing the best explanation. Nevertheless, we cannot rule out the possibility of adrenal lipoma being the source as well. However, it remains to be further validated.

CONCLUSION

Although very rare, adrenal lipomas should always be considered when evaluating adrenal tumors. They are usually non-functional and asymptomatic, but can be associated with symptoms related to local tumor per se and hormone hypersecretion. Hence, it is important to subject all these patients for biochemical evaluation before surgery to avoid untoward complications. Whether these tumors are completely non-functional or are associated with hormone hypersecretion, needs to be evaluated. The pathogenesis of hormone hypersecretion, if at all, by these tumors needs to be looked for.

ORCID

Basavaraju Santosh https://orcid.org/0009-0006-0021-8167

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