Stefan R. Bornstein, MD; Constantine A. Stratakis, MD; George P. Chrousos, MD
Adrenocortical masses are among the most common tumors in humans. However, only a small proportion of these tumors cause endocrine diseases (such as primary hyperaldosteronism, hypercortisolism, hyperandrogenism, or hyperestrogenism), and less than 1% are malignant. In recent years, several of the molecular and cellular mechanisms involved in adrenal tumorigenesis have been unraveled. As a result, alterations in intercellular communication, local production of growth factors and cytokines, and aberrant expression of ectopic receptors on adrenal tumor cells have been implicated in adrenal cell growth, hyperplasia, tumor formation, and autonomous hormone production. Genetic and chromosomal abnormalities, including several chromosomal loci and the genes coding for p53, p57, and insulin-like growth factor II, have been reported in adrenal tumors. In addition, chromosomal markers have been identified in several familial syndromes associated with adrenal tumors; these include menin, which is responsible for multiple endocrine neoplasia type I, and the hybrid gene that causes glucocorticoid-remediable hyperaldosteronism. Algorithms for endocrine testing and imaging procedures are now available to codify screening for, confirmation of, and differentiation of causes of primary hyperaldosteronism and the Cushing syndrome. Improved radiologic, computerized radiologic, and magnetic resonance imaging techniques, as well as selective catheterization studies, are useful in localizing adrenal tumors and in distinguishing between benign and malignant lesions and between functional and nonfunctional nodules. Finally, recent refinements in the field of minimally invasive general surgery have made laparoscopic adrenalectomy the method of choice for removing adrenal tumors; this type of surgery allows shorter hospital stays, lower morbidity rates, and faster recovery.
Intermingling of adrenocortical and chromaffin tissue. Chromaffin cells are immunostained red with antibodies to chromogranin A (Clone Dako A3, Dako, Copenhagen, Denmark; original magnification, ×200). Endothelial cells immunostained with antibodies to CD31 (Dako) ( ) are in direct contact with adrenocortical cells in the zona fasciculata ( ). The reaction was visualized with 3-amino-ethylcarbasole (original magnification, ×800). Electron µgraph of a nerve cell ( ) in apposition with an adrenocortical cell. The latter shows vesicular mitochondria ( ) and extends filopodia ( ) to the nerve cell. Scale, 0.5 µm. Electron µgraph of a macrophage in direct contact with adrenocortical cells. Macrophages show lysosomes ( ), rough endoplasmic reticulum ( ), and pinocytotic vesicles ( ). Adrenocortical cells have ample mitochondria with characteristic vesicular internal membranes, smooth endoplasmic reticulum, and Golgi complex ( ). Scale, 1 µm. NUC = nucleus.
Adrenal nodules ( ) originating within the adrenal medulla ( ). Medullary cells are stained with an antibody to chromogranin A (original magnification, ×60). Lymphocytic infiltration in a cortisol-producing adrenal adenoma causing the Cushing syndrome. Lymphocytes characterized with antibodies to CD45 (Clone 2B 11, Dako, Copenhagen, Denmark) are in direct contact with adrenal tumor cells. No signs of autoimmune disease or inflammation were seen in this patient. The reaction was visualized with 3-amino-ethylcarbasole (original magnification, ×200). C = cortex.
This algorithm suggests tests that are used for screening, confirmation, and localization of aldosterone-producing tumors. To convert aldosterone values to pmol/L, multiply by 27.744; to convert urinary aldosterone excretion to nmol/d, multiply by 2.774; to convert 18-hydroxycorticosterone values to nmol/L, multiply by 0.0276. If there is more than one item, follow the respective numbers throughout the algorithm. CT = computed tomography; MRI = magnetic resonance imaging.
For the diagnosis of primary hypercortisolism, this algorithm suggests tests that are used for screening, confirmation, and localization of a cortisol-producing or corticotropin ( )-producing tumor. To convert serum cortisol values to nmol/L and to convert urine free cortisol values to nmol/d, multiply by 2.759. If there is more than one item, follow the respective numbers throughout the algorithm. BIPSS = bilateral inferior petrosal sinus sampling (measurement of plasma corticotropin concentrations in the inferior petrosal sinuses and a peripheral vein ); CRH = corticotropin-releasing hormone; CT = computed tomography; MRI = magnetic resonance imaging.
Adrenal CT of a 61-year-old woman with primary hyperaldosteronism and bilateral adrenal nodules ( ) did not identify an increased lipid content in either adenoma. In-phase MRI also failed to differentiate between the two sides. A loss of signal content of the functional aldosteronoma was shown by out-of-phase MRI. Venous sampling and surgery confirmed a right aldosteronoma. (Courtesy of J.L. Doppman).
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Bornstein SR, Stratakis CA, Chrousos GP. Adrenocortical Tumors: Recent Advances in Basic Concepts and Clinical Management. Ann Intern Med. 1999;130:759-771. doi: 10.7326/0003-4819-130-9-199905040-00017
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Published: Ann Intern Med. 1999;130(9):759-771.
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