Hypodense Nodularity on Computed Tomography: Novel Imaging and Pathology of Micronodular Adrenocortical Hyperplasia Associated with Myelolipomatous Changes

Nickolas A. Courcoutsakis, Nickolas J. Patronas, David Cassarino, Kurt Griffin, Meg Keil, Judith L. Ross, J. Aidan Carney and Constantine A. Stratakis

Department of Diagnostic Radiology (N.A.C., N.J.P.), Warren Grant Magnuson Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland 20892; Section on Endocrinology and Genetics (N.A.C., K.G., M.K., C.A.S.), Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892; Laboratory of Pathology (D.C.), National Cancer Institute, NIH, Bethesda, Maryland 20892; Pediatric Endocrinology (J.L.R.), Thomas Jefferson University, Philadelphia, Pennsylvania 19107; and Department of Laboratory Medicine and Pathology (J.A.C., emeritus member), Mayo Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Constantine A. Stratakis, M.D., D.Sc., Section on Endocrinology and Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10N262, 10 Center Drive, MSC 1862, Bethesda, Maryland 20892-1862. E-mail: stratakc{at}cc1.nichd.nih.gov.

An 8.5-yr-old white girl with a history of weight gain, mood changes, and early menarche presented for the evaluation of possible Cushing syndrome. Clinical examination revealed mild hypertension, facial plethora, palpable supraclavicular fat pads, and a dorsal fat pad. There were no skin pigmentation changes suggestive of ACTH excess or pigmented spots that would indicate Carney complex (CNC) (1). Family history was essentially noncontributory.

Urinary free cortisol and 17-OH-steroid levels were elevated at baseline and responded paradoxically to dexamethasone administration during Liddle’s test (2). Computed tomography (CT) examination of the adrenal glands demonstrated bilateral adrenal enlargement, the left gland being larger than the right (Fig. 1Go). After contrast enhancement, many small, hypodense, nonenhancing nodules were seen in both glands; the largest (12 mm in diameter) was on the left side (Fig. 2Go, A and B). Three well-delineated, round or ovoid (4, 5, and 12 mm in diameter) lesions with density similar to fat were also demonstrated in the right adrenal (not shown). These features have not been seen before in the imaging of adrenocortical hyperplasia (3, 4).



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FIG. 1. Precontrast CT imaging shows bilateral adrenocortical hyperplasia (arrows), with the left adrenal gland being larger than the right.

 


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FIG. 2. A, CT imaging after injection of a contrast agent and with a slice thickness of 3 mm revealed an enlarged left adrenal gland with a well-delineated multinodular contour. Several hypodense nodules, from 2 to 9 mm in diameter, were also seen (arrows). Histological examination showed that all hypodense nodules corresponded to cortical areas with myeloid metaplasia. B, In the left limb of the left adrenal, a well-delineated ovoid lesion with a greatest diameter of 12 mm and a density similar to fat is seen.

 
The patient underwent bilateral laparoscopic adrenalectomy. Macroscopically, the adrenals were nodular, corresponding to the CT-identified lesions. The left adrenal was larger than the right. Microscopically, there was micronodular hyperplasia (Fig. 3Go, A and B), a common feature of primary pigmented nodular adrenocortical disease (PPNAD) (5). However, the nodules contained little pigment and much fat (myeloid metaplasia). The extranodular atrophic cortex was very uniform.



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FIG. 3. A, Hematoxylin and eosin-stained sections of the right adrenal showed micronodular hyperplasia with myeloid metaplasia and without pigmentation (magnification, x20). B, Cortical nodular cells stained positive for synaptophysin (magnification, x100).

 
The patient did not have skin pigmentation, myxomas, or any of the other major tumor associated with CNC. Molecular analysis for the PRKAR1A gene was negative (data not shown); PRKAR1A mutations are responsible for PPNAD and/or CNC in approximately 50–80% of the reported patients (6, 7).

We conclude that myelolipomatous changes in the nodules of micronodular adrenocortical hyperplasia can make the CT diagnosis of this disorder difficult. The characteristic images are shown in Figs. 1Go and 2Go.

It is unclear at this point, given the negative genetic testing, whether the presented patient indeed had PPNAD or an unrecognized form of micronodular adrenocortical hyperplasia associated with corticotropin-independent Cushing syndrome.


    Footnotes
 
Abbreviations: CNC, Carney complex; CT, computed tomography; PPNAD, primary pigmented nodular adrenocortical disease.

Received January 13, 2004.

Accepted April 27, 2004.


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