Adrenal Myelolipomas in Patients with Congenital Adrenal Hyperplasia: Review of the Literature and A Case Report

ObjectiveTo review the association between congenital adrenal hyperplasia (CAH) and adrenal myelolipomas and report a case of bilateral, giant adrenal myelolipomas in a patient with untreated CAH due to 21-hydroxylase deficiency.MethodsWe describe the patient’s clinical presentation, imaging findings, and laboratory test results and review the relevant English-language literature concerning patients with both CAH and myelolipomas.ResultsA 45-year-old man with untreated CAH due to 21-hydroxylase deficiency presented with increasing abdominal girth and abdominal pain. Computed tomography of the abdomen demonstrated very low-density adrenal masses (22 × 11 cm on the left side and 6 × 5.5-cm on the right side) consistent with adrenal myelolipomas. The left adrenal myelolipoma was resected (24.4 × 19.0 × 9.5 cm; 2557 g). The mass was composed of mature adipose tissue with areas of hematopoietic cells of myeloid, erythroid, and megakaryocytic cell lines. Islands of adrenal cortical cells were scattered between the adipose and hematopoietic tissue. Including the present case, we identified 31 patients with both CAH and myelolipomas who have been described in the English-language literature. The details of these cases were reviewed.ConclusionsPersons with CAH may be at increased risk of developing adrenal myelolipomas, particularly if their CAH is poorly controlled. How and whether chronic exposure of the adrenal glands to high corticotropin levels increases the risk of developing myelolipomas remains a matter of speculation. (Endocr Pract. 2011;17:441-447)     

Asymptomatic Bilateral Giant Adrenal Myelolipomas: Case Report and Review of Literature

ObjectiveTo describe an unusual case of bilateral giant adrenal masses caused by a primary adrenal myelolipoma.MethodsWe present the clinical, laboratory, and pathologic findings in a 32-year-old man with bilateral adrenal masses. The previous reports of bilateral myelolipomas also were reviewed.ResultsDuring a routine examination, a 32-year-old Thai man was found to have an asymptomatic abdominal mass. A computed tomographic scan of the abdomen disclosed bilateral adrenal masses; the one on the left was approximately 27 by 24 by 12 cm, and the one on the right side was 9 by 5 by 5 cm. The computed tomographic scan characteristics showed that both masses consisted mainly of low-density tissues (-30 to -90 Hounsfield units), suggestive of fatty component. An endocrinologic evaluation revealed no evidence of adrenal cortical or medullary functional abnormalities. Bilateral adrenalectomy was performed because of the large size of the lesions and the inability to rule out malignant involvement.ConclusionMyelolipoma is a relatively rare benign tumor of the adrenal glands composed of adipose cells and mature hematopoietic elements. Most such lesions are small, asymptomatic, and unilateral; giant or bilateral myelolipomas are quite rare. To our knowledge, our current case may represent the largest bilateral lesions in the literature. (Endocr Pract. 2007;13:667-671)     

Fine Needle Aspiration of Adrenal Myelolipoma: A Case Report

A case of an adrenal myelolipoma in a 50-year-old woman with endometrial carcinoma is described. The diagnosis was established by computed tomography-guided fine needle aspiration, which is particularly useful for the pre-operative evaluation of adrenal tumours in asymptomatic, high-risk or cancer patients. The criteria used to distinguish extra-adrenal myelolipomas from mass-forming extramedullary haematopoiesis are discussed.     

Computed tomography-guided fine needle aspiration biopsy of adrenal myelolipoma. Case report and review of the literature

A case of adrenal myelolipoma diagnosed by fine needle aspiration (FNA) biopsy is reported. The FNA smears contained the diagnostic picture of mature adipose tissue intermixed with hematopoietic elements, including megakarycytes. The FNA diagnosis was histologically confirmed by study of the resected tumor. This case appears to be the first "giant" adrenal myelolipoma diagnosed by computed tomography-guided FNA biopsy. The literature on adrenal myelolipomas sampled by FNA using imaging guidance is briefly reviewed.     

Prevalence and Characteristics of Adrenal Tumors and Myelolipomas in Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis

Objective: The prevalence of adrenal tumors in congenital adrenal hyperplasia (CAH) is uncertain. Our objective was to estimate the prevalence and characteristics of adrenal tumors and myelolipoma in CAH, and investigate clinical features of this population.Methods: We carried out systematic searches in Medline Ovid and Embase for articles published until January, 2020. Studies with confirmed CAH, biochemically and/or genetically, were included. The two authors independently extracted data from each study.Results: Six cohort studies were included in the prevalence calculation. In addition, 32 case reports on adrenal myelolipomas and CAH were included. The prevalence of adrenal tumors in CAH was 29.3%. When only studies with genetically verified cytochrome P450, Family 21, subfamily A, polypeptide 2 gene (CYP21A2) mutations were included the prevalence was 23.6%. The prevalence of myelolipoma in CAH was 7.4% (verified CYP21A2 mutations 8.6%). The proportion of myelolipoma in the adrenal tumors was 25.4% (genetically verified 36.6%). The median (range) age at tumor diagnosis was 36.0 (12 to 60) years and there were more tumors in males than in females (37.9% versus 22.1%; P<.05). In patients with myelolipomas, 93.5% had an undiagnosed or poorly managed CAH.Conclusion: Patients with CAH had a high prevalence of adrenal tumors, particularly myelolipomas. Those with myelolipomas had a high frequency of late-diagnosed or poorly controlled CAH. Adrenal imaging may be considered in patients with CAH, especially if abdominal pain is present.     

Complete sequencing and mRNA expression analysis of the MEN-I gene in adrenal myelolipoma.

The molecular pathogenesis of adrenal myelolipoma is unclear. Endocrine activity of these tumors and association with other endocrine tumors have stimulated the hypothesis that it may belong to the group of sporadic tumors caused by defects of the gene responsible for multiple endocrine neoplasia type I (MEN-I). DNA of blood and tumoral sections from two patients with adrenal myelolipoma were analyzed by examination of variable number of tandem repeats (VNTR) loci PYGM, D11S987, D11S480, and D11S449 on chromosome 11q13 and by complete direct DNA sequencing of all coding exons and splice junctions of the MEN-I gene. Menin expression was examined by RT-PCR. RT-PCR did not detect menin expression in one adrenal myelolipoma. No loss of heterozygozity on chromosome 11q13 was identified. Intragenic heterozygozity was retained in codon 418 of the menin gene in both patients. No mutation was identified in the coding exons of the menin gene. Complete DNA sequencing yielded no hint that defects of the MEN-I gene are responsible for the formation of adrenal myelolipomas. Adrenal myelolipomas do not share the loss of heterozygozity on chromosome 11q13 observed in some benign adenomatous and many malignant adrenocortical tumors.     

Fine needle aspiration diagnosis of extraadrenal myelolipoma presenting as a pleural mass. A case report

BACKGROUND: Myelolipoma is a benign tumor composed of mature adipose tissue and hematopoietic cells. Although they are commonly found in adrenal glands, extraadrenal myelolipomas (EMLs) are rare but well documented. They have been found in various sites, including mediastinum, liver, stomach, lungs, pelvis, spleen, retroperitoneum, presacral region and mesentery. EMLs must be distinguished from extramedullary hematopoieses, which are also composed of hematopoietic elements but may lack adipose tissue and are associated with anemia and marked bone marrow hyperplasia. CASE: We describe a case of a pleura-based, extraadrenal myelolipoma in a 53-year-old female with unremarkable bone marrow findings that were initially encountered on fluoroscopy-guided fine needle aspiration (FNA). One year later the mass was removed via open thoracotomy. It showed typical EML features histologically. CONCLUSION: EML manifests on aspiration cytology as a cellular specimen with numerous trilineage hematopoietic cells and a variable proportion of mature adipose cells. To our knowledge, FNA cytology of EML has not been found in this location before. Aspiration biopsy offers a simple and reliable method for the diagnosis of EML in the presence of appropriate clinical settings.     

Adrenal pheochromocytoma with contralateral cortisol-producing adrenal adenoma: diagnostic and therapeutic management.

There is evidence for a close interrelation between the adrenomedullary and adrenocortical tissues, and there are well-characterized models of their paracrine interaction. To contribute to the studies of systemic interactions between these tissues, we studied a 52-year-old female patient with a pheochromocytoma and a contralateral cortisol-producing adenoma. Due to a misunderstanding, she presented to her family doctor to have an inherited kidney disease ruled out. An adrenal mass was discovered incidentally by ultrasound. A computerized tomography of the abdomen revealed bilateral adrenal masses. Due to excess catecholamine secretion, bilateral pheochromocytomas based on multiple endocrine neoplasia syndrome were suspected. Laboratory work-up, selective adrenal venous sampling and magnetic resonance imaging studies established the diagnosis of a pheochromocytoma in the right-hand adrenal gland and a cortisol-producing adenoma on the left. Simultaneous bilateral laparoscopic subtotal adrenalectomy was performed. Immunohistochemistry showed positive staining against chromogranin A in a histological specimen obtained from the right-hand adrenal gland, while the left was negative; the left-hand adrenal gland stained positive against the ACTH receptor (MC2R) while the right was negative. Genetically, the patient was negative for MEN2, von Hippel-Lindau disease, and mutations in subunits B, C, and D of the succinate dehydrogenase gene. Although presence of bilateral adrenal adenomas or bilateral adrenal pheochromocytomas in certain inherited disorders are possible, this rare case of an adrenal pheochromocytoma combined with a contralateral cortisol-producing adrenal adenoma may further underline the wide range of complex interactions between the two endocrine systems.     

Cushing's syndrome due to bilateral adrenal macronodular hyperplasia with undetectable ACTH: cell culture of adenoma cells on extracellular matrix

A 59-year-old man developed Cushing's syndrome with massive bilateral adrenal macronodular hyperplasia. Plasma ACTH levels were undetectable both peripherally and in the inferior petrosal sinus. Computed tomography scans of his pituitary were normal. Hypercortisolism was not suppressed by high doses of dexamethasone. His adrenal cells were successfully isolated and grown on bovine corneal extracellular matrix. The cultured cells displayed strikingly rapid growth and hypersecretion of cortisol during incubation with control serum. Addition of the patient's serum to cultured fetal adrenal cells did not accelerate their growth. This was the first experience with our in vitro system in this rare clinical condition. The techniques described here may be used for future in vitro adrenal studies. These in vivo and in vitro data indicate that this patient's bilateral adrenal hyperfunction and growth were independent of ACTH.     

Hyperplasie surrénalienne par bloc en 21 hydroxylase: une cause rare d’hypofertilité masculine et de tumeur du testicule

The authors report the case of a 29-year-old man with bilateral testicular adrenal-like tumors in a context of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Inadequate suppression of ACTH secretion is a dominant etiological factor in the development of testicular masses in CAH. Destruction of the testicular tubules by the adrenal rests and longstanding suppression of the pituitary-gonadal axis can lead to infertility. The presence of testicular adrenal rests must be investigated in any man with CAH due to 21-hydroxylase deficiency and infertility. Similarly, it is important to investigate possible 21-hydroxylase deficiency in patients with bilateral testicular tumors.     

Disseminated histoplasmosis diagnosed by fine needle aspiration biopsy of the adrenal gland. A case report

A case of disseminated histoplasmosis diagnosed by fine needle aspiration (FNA) biopsy of the adrenal gland is reported for a 60-year-old man who presented with a 40-pound weight loss and abdominal computed tomography showing bilateral adrenal enlargement. FNA biopsy of the adrenal gland revealed clusters of macrophages with abundant cytoplasm containing the yeast forms of Histoplasma capsulatum. This case emphasizes that FNA is effective in diagnosing infectious as well as neoplastic conditions of the adrenal glands.     

NK/T-cell lymphoma of bilateral adrenal glands in a patient with pyothorax

ABSTRACT: Primary lymphoma of adrenal glands is rare, and non-B-cell lymphoma associated with pyothorax is also very rare. Here we report the first autopsy case of non-B-cell lymphoma in bilateral adrenal glands of a 79-year-old woman with pyothorax who had an aggressive clinical course. Immunohistochemically, tumor cells showed CD3+, CD45RO+, CD5-, CD7-, CD4-, CD8-, CD10-, CD20-, CD30-, CD79a-, CD138-, CD56-, granzyme B-, TIA-1+ and ALK-. In addition, tumor cells were strongly EBER1-positive by in situ hybridization. In genomic DNA of tumor cells, T-cell receptor rearrangements were not detected by southern blotting. We finally diagnosed this case as extranodal NK/T-cell lymphoma (nasal type).Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8050621197741854.     

Steroidogenesis in human aldosterone-secreting adenomas and adrenal hyperplasias: effects of hypoxia in vitro

The synthesis of adrenal steroids requires molecular oxygen. Because arterial hypoxemia is a common clinical condition, the purpose of the present study was to examine steroidogenesis in vitro under physiological changes in O(2) tension (Po(2)) in cells from human adrenal glands with aldosterone-secreting adenomas (ASA; n=3) or with bilateral adrenal hyperplasia causing Cushing's syndrome (n=4). A decrease in Po(2) from 150 mmHg (mild hyperoxia) to 80 mmHg had minimal effect on steroid production. A reduction to 40 mmHg (still well within the physiological range) significantly inhibited cAMP- and ACTH-stimulated aldosterone, cortisol, and dehydroepiandrosterone (DHEA) production from ASA. Furthermore, cortisol and DHEA production in cells from histologically normal tissue, adjacent to ASA and from bilateral adrenal hyperplasias, was also inhibited under a Po(2) of 40 mmHg. We conclude that physiological decreases in Po(2) to levels typical for adrenal venous Po(2) under mild hypoxia inhibit steroidogenesis. These studies may have implications for oxygen therapy in critically ill patients with functional adrenal insufficiency, as well as for therapeutic options in patients with adrenal neoplasms.     

Adrenal aldosterone-producing adenoma: use of colonic potential in diagnosis and subtraction scanning technique for localisation.

Primary hyperaldosteronism is a potentially curable cause of hypertension, and much interest has been shown in methods of diagnosing the associated hypokalaemic hypertension and localising the adrenal adenoma. In two patients the diagnosis of primary aldosteronism was confirmed by colonic potential measurement and the adenoma localised by a new subtraction technique for early adrenal imaging applied to the use of 131I-19-iodocholesterol. Both patients underwent adrenalectomy and in each case an adenoma was removed. Blood pressure and electrolyte levels returned to normal after operation. In one patient bilateral adrenal phlebography had failed to show the tumour, and sampling of aldosterone concentrations in the adrenal veins had been unsatisfactory.     

Multiple Unilateral adrenal Adenomas in a Patient with Primary Hyperaldosteronism

ObjectiveTo report a rare case of multiple unilateral adrenal adenomas in which immunohistochemistry results confirmed primary hyperaldosteronism in each of 3 adenomas.MethodsWe present the clinical, laboratory, radiographic, and pathologic findings of a case of multiple unilateral adrenal adenomas.ResultsAlthough multiple nodules in both adrenal glands are fairly common in patients with bilateral hyperplasia, multiple unilateral nodules are extremely rare. A 45-year-old woman with a long-standing history of severe hypertension was found to have biochemical parameters consistent with primary hyperaldosteronism, multiple unilateral adrenal adenomas, and immunohistochemical test results confirming primary hyperaldosteronism arising from each of 3 adrenal nodules (measuring 2.2 × 2.2 cm, 1.7 × 0.7 cm, and 0.5 × 0.5 cm).ConclusionThis case illustrates the rare presentation of primary hyperaldosteronism as multiple unilateral adrenal adenomas in which immunohistochemistry results can confirm the suspected preoperative diagnosis as suggested by biochemical and radiographic evidence. (Endocr Pract. 2008;14:76-79)     

Laparoscope resection of ectopic corticosteroid-secreting adrenal adenoma

Tumors originating from ectopic adrenal tissue are relatively rare. In this article, we describe a case with Cushing's syndrome caused by an ectopic adrenal adenoma. A 38 year-old male patient presenting with cushingoid appearance for 2 years was diagnosed to have ACTH-independent Cushing's syndrome based on endocrinological evaluation. Mutiple radiological examinations detected bilateral adrenal atrophy. When the images were investigated in a more expanded scope, a 3.0×3.5×5.3?cm mass was detected in the anterior of left renal hilum and left renal vein. The mass was successfully resected with intraoperative endoscopy and pathological evaluation revealed an ectopic adrenal tumor. It is suggested that when the endocrinlogically confirmed adrenal neoplasm could not be well and definitely localized, the possibility of ectopic adrenal should be presumed and further radiography examinations should extend to the field where ectopic adrenal usually presents.     

Effect of vagotomy on the morphological and functional state of the rat adrenal medulla

After bilateral subphrenic vagotomy in male rats (in 7 and 45 days) there was revealed a sharp dilatation of the venous sinusoids, diminution of the chromaffin tissues area, and a more intensive chromaffin reaction in the adrenal medulla. Vagotomy resulted in a marked alteration of the ultrastructural organization of the secretory cells and the endothelium. Glucose administration to vagotomized animals caused only insignificant variations in adrenaline content in the chromaffin cells. Thus, vagotomy resulted in reduction of the functional activity of the adrenal medulla secretory cells.     

A case report of spontaneous staphylococcal meningitis in a cynomolgus monkey

This report describes a suppurative meningitis in a young cynomolgus. The animal had neutrophil aggregation in the subarachnoid space and hemorrhage in bilateral adrenal glands. Staphylococcus was identified by FISH in brain. To our knowledge, this is the first case of staphylococcal meningitis with Waterhouse‐Friderichsen syndrome in a cynomolgus monkey.