Subclinical Cushing's syndrome due to adrenal myelolipoma

Archives of Pathology & Laboratory Medicine, Jul 1997 by Boronat, Mauro, Moreno, Amalia, Cajal, Santiago Ramon y, Pineda, Eva, Et al

In exceptional cases, adrenal myelolipomas have been diagnosed because of their association with different endocrine disorders. Fortuitous finding of these tumors in patients with Cushing's disease, Nelson's syndrome, and congenital adrenal hyperplasia has led some authors to postulate that adrenocorticotropin oversecretion could play a role in the pathogenesis of adrenal myelolipomas.7 To date, causal relationship between excessive adrenocorticotropin levels and myelolipomas has not been definitively demonstrated.

On the other hand, functioning myelolipomas have been found to cause adrenal hypersecretory syndromes themselves. These cases seem to be the result of the presence of intratumoral hyperplastic or adenomatous adrenal cells mixed with elements of the myelolipoma. These combined adrenal and myelolipomatous tumors are typically silent, but they have been reported to induce hyperaldosteronism,8 pheocromocytoma,9 and adrenocorticotropin-independent Cushing's syndrome.1-4 Characteristics of four reported cases of Cushing's syndrome due to primary adrenal myelolipomas are summarized in Table 2. In three of these cases,1-3 the diagnosis was suspected because of clinically evident Cushing's syndrome, but the remaining case was also disclosed by an incidental finding of an adrenal mass during a radiologic abdominal exploration for a problem unrelated to adrenal function.4

In our patient, endocrine assessment demonstrated persistent high urinary cortisol excretion. Surgical removal of the incidentaloma achieved normalization of urinary cortisol levels, and its pathologic examination resembled the picture found in previous reports of Cushing's syndrome due to adrenal myelolipoma.

Apart from hypertension and obesity, however, clinical signs and symptoms of classic Cushing's syndrome were absent in our patient. Concurrent intake of phenytoin prevented exclusion of a subtle alteration in plasma cortisol suppressibility, but it does not explain the increased levels of urinary free cortisol. The rhythm of cortisol secretion and adrenocorticotropin response to stimulation with corticotropin-releasing hormone were normal.

It is now well documented that many adrenal incidentalomas, previously thought to be nonfunctioning, display autonomous glucocorticoid secretion, although they produce adrenocortical hormones in amounts insufficient to cause clinically apparent disease.5,9 In these cases, results of endocrine evaluation are variable. Loss of circadian rhythm and failure of the suppression of plasma cortisol following the administration of dexamethasone typically occur before hypercortisolism is present,6,10 but isolated patients have displayed high urinary free cortisol and low levels of dehydroepiandrosterone sulfate as the only disorders in adrenocortical function,10 such as occurred in our case.

Adrenal incidentalomas causing subclinical Cushing's syndrome are presumed to be cortical adenomas, but most of these tumors are not surgically removed and definitive pathologic diagnosis is therefore not established. We have reported a case of subclinical Cushing's syndrome induced by an adrenal adenomyelolipoma. Taking into account that some of these tumors lack typical radiologic features,11 it is possible that they may be responsible for other cases of preclinical Cushing's syndrome.