Search

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is an exceptionally rare autosomal dominant condition caused by a germline heterozygous mutation of the fumarate hydratase gene. It manifests as multiple piloleiomyomas, associated with numerous, early-onset uterine leiomyomas in female patients, as well as a highly increased risk of renal cell carcinoma (RCC), most often type 2 papillary RCC. HLRCC has been described in association with adrenal cortical hyperplasia, pheochromocytoma, adrenal cortical carcinoma, and other solid tumors, but the exact relationship between these disorders has not yet been clarified. We present a case of HLRCC associated with bilateral adrenal cortical hyperplasia and discuss the pathogenesis, clinical and paraclinical features of HLRCC, as well as the adequate management of these patients.

Objectives Currently, laparoscopic adrenalectomy is the gold standard technique for suitable patients with adrenal masses. In this study, we aimed to assess the postoperative results of patients who underwent laparoscopic adrenalectomy. Methods Between January 2014 and October 2019, 76 cases were operated and retrospectively evaluated. Laparoscopic transabdominal adrenalectomy was applied to the patients. Demographic profiles, preoperative indications, intraoperative and postoperative complications, mortality and length of hospital stay were evaluated. Results Seventy-six patients (30 male, 46 female) with a mean age of 47.2±11.7 (range 22-71) years underwent laparoscopic adrenalectomy. Thirty-nine of the patients had right; 33 of the patients had left adrenal masses. Three patients had bilateral adrenal cortical hyperplasia. One patient was operated for paraganglioma. Conversion to open adrenalectomy was observed in four patients (5.26%). Nine patients (11.8%) experienced intraoperative and postoperative complications. Intraoperative and postoperative complications were bleeding from spleen (2 cases) and upper pole of kidney (1 case), renal artery injury (1 case), bleeding from liver parenchyma (2 cases), ischemia of spleen and pancreas (1 case), small intestinal injury (1 case) and incisional hernia (1 case). The complication rate is acceptable and comparable with other studies in the literature. Conclusion Laparoscopic adrenalectomy can be safely applied in suitable patients with acceptable complications and low conversion rates.

Primary aldosteronism (PA) is a major cause of endocrine hypertension 1. There are two major subtypes. One is unilateral PA, mainly due to aldosterone‐producing adenoma (APA) and the other is bilateral PA, mainly due to idiopathic hyperaldosteronism (IHA). It is important to determine the PA subtype because the recommended treatment for APA is an adrenalectomy and that for IHA is pharmacological therapy with a mineralocorticoid receptor antagonist 2. Adrenal venous sampling (AVS) is recommended for determining the PA subtype 3. Regardless of its diagnostic efficacy, AVS is a difficult procedure. The catheterization of the right adrenal vein is particularly difficult because of its small diameter 4. By contrast, the left adrenal vein is catheterized in almost all patients because it enters the left renal vein, which can be used as a guide to the left adrenal vein. However, in the rare case of an anomalous left adrenal vein, it is difficult to cannulate the left adrenal vein 5. In this report, we describe the successful left adrenal vein cannulation under contrast‐enhanced computed tomography (CT) guidance in a patient with PA and left inferior vena cava (IVC) whose left adrenal vein drained directly into the IVC.

Adrenal hyperplasia is non-malignant enlargement of the adrenal glands, which is often bilateral. It can be incidental or related to indolent disease process and may be related to benign or malignant etiologies causing biochemical alterations in the hypothalamic-pituitary-adrenal axis which controls steroidogenesis and in particular cortisol production. Clinical significance of the adrenal hyperplasia is variable ranging from asymptomatic finding to serious manifestations of Cushing syndrome. This is often associated with anatomical changes in the adrenal glands, which typically manifests as diffuse and sometimes nodular enlargement of the adrenal glands radiologically. Approaching adrenal hyperplasia requires careful clinical and biochemical evaluation in correlation with imaging review to differentiate ACTH-dependent and ACTH-independent etiologies. CT is the primary modality of choice for adult adrenal imaging owing to reproducibility, temporal and spatial resolution and broader access, while MRI often serves a complimentary role. Ultrasound and MRI are most commonly used in pediatric cases to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation and imaging features of different types and mimics of adrenal cortical hyperplasia.

Primary aldosteronism is the most common cause of secondary hypertension, incurring significant cardiovascular morbidity and mortality. Our understanding of this disease has evolved substantially during the past decade. Recently, the molecular basis of primary aldosteronism has begun to be unraveled, with the discovery of mutations in potassium channel (KCNJ5), ATPases (ATP1A1, ATP2B3), and calcium channel (CACNA1D), and aberrant Wnt/β-catenin signaling. The most recent data suggest that 95% of cases are sporadic, whereas 5% of cases are hereditary. Pathologic correlates of primary aldosteronism include adrenal cortical hyperplasia, adenoma, and carcinoma. Although the most common clinical presentation is bilateral adrenal cortical hyperplasia, this entity is usually treated medically. Therefore, in the setting of primary aldosteronism, surgical pathologists are most commonly exposed to adrenocortical adenomas and the odd occasional carcinoma. This review provides an update on the current knowledge of primary aldosteronism and discusses the clinicopathologic correlations of this important disease.

Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth, or enlargement, of the adrenal glands, specifically the cortex, although the cortex cannot be definitively identified by conventional imaging. Controlled by the pituitary gland, the adrenal cortex drives critical processes, such as the production of cortisol, mineralocorticoid and sex hormones. Any disruption in the multiple enzymes and hormones involved in these pathways may cause serious or life-threatening symptoms, often associated with anatomical changes in the adrenal glands. Diagnosis and treatment of adrenal cortical hyperplasia requires a thorough clinical evaluation. As imaging has become more robust so has its role in the diagnosis and treatment of adrenal conditions. CT has been the primary modality for adrenal imaging owing to reproducibility, temporal and spatial resolution and broad access. MRI serves a complimentary role in adrenal imaging and can be used to further evaluate indeterminate CT findings or serve as an adjunct tool without the use of ionizing radiation. Ultrasound and fluoroscopy (genitography) are most commonly used in children and foetuses to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation, laboratory workup and imaging features of adrenal cortical hyperplasia, both congenital and acquired.

Cystic degeneration of the adrenal cortex is a common age-related finding in the Sprague-Dawley (SD) rat strain occurring more frequently in females. Compression of the adjacent cortex, a common hallmark of benign adrenal cortical tumors, often accompanies foci of cystic degeneration, creating a diagnostic challenge. Accurately differentiating these relatively common degenerative changes from proliferative lesions is critical in safety assessment studies. Cystic degeneration typically arises in the zona fasciculata of the adrenal cortex and often causes compression along the margin of the lesion. The degenerating cells are large, with abundant eosinophilic cytoplasm, or contain clear cytoplasmic vacuoles. Mitotic figures are generally uncommon. In many cases, cystic degeneration appears to arise in areas of hypertrophy in the zona fasciculata. In contrast, adrenal cortical hyperplasia and adrenal cortical adenoma are frequently comprised of smaller cells that cause compression of adjacent cortex, and in some cases mitotic figures are observed. Cytological detail and growth patterns should be considered more useful criteria than compression alone for separating degenerative cystic lesions from proliferative lesions in the adrenal cortex of SD rats.

An extra-adrenal retroperitoneal paraganglioma was observed in a 10.5-year-old male Boxer dog. Additionally, the dog had an aortic base tumor, multiple thyroid adenomas, multiple testicular interstitial cell tumors, bilateral nodular adrenal cortical hyperplasia, and parathyroid gland hyperplasia. The hypothesis that the retroperitoneal mass represents a primary extra-adrenal paraganglioma rather than metastatic mass from the aortic body tumor is considered. Either primary or metastatic extra-adrenal retroperitoneal paragangliomas are rarely reported in dogs.

Adrenal masses include lesions derived from the adrenal cortex and medulla as well as metastatic tumors to the adrenal glands. The principal cortical masses include adrenal cortical hyperplasia, adenomas, and carcinomas. The principal adrenal medullary masses include pheochromocytomas and neuroblastic tumors. The pathological distinction of benign from malignant adrenocortical tumors can usually be done with the Weiss criteria, but there are some exceptional tumors that are difficult to classify. Distinguishing between benign and malignant pheochromocytomas is often difficult and relies mainly on the presence of metastatic disease. Neuroblastomas show a spectrum ranging from highly malignant undifferentiated neuroblastomas to benign ganglioneuromas. Immunohistochemical analyses can be very helpful in the differential diagnosis of adrenocortical tumors and pheochromocytomas and in separating these lesions from metastatic tumors. Recent molecular studies have provided new insights into regulatory molecules in both adrenocortical and medullary tumors.

McCune-Albright syndrome (polyostotic fibrous dysplasia, café-au-lait skin spots, and precocious puberty) is a genetically mosaic disorder with populations of mutant and normal cells in affected organs. Cushing syndrome, a rare feature of the condition, usually affects infants and is the result of corticotropin-independent primary bilateral adrenal disease, usually interpreted as nodular adrenocortical hyperplasia. In this study of 9 patients with Cushing syndrome and McCune-Albright syndrome, light microscopy revealed a characteristic bimorphic pattern of diffuse and nodular hyperplasia and a distinctive form of cortical atrophy with apparent zona glomerulosa hyperplasia in 8 patients, all very young. The pattern could be explained by the presence of a mosaic distribution of mutant and normal cells in the adrenal glands. The findings are different from those in inherited or other forms of genetically caused Cushing syndrome. The ninth patient, aged 17 years, had an adrenal adenoma and diffuse cortical hyperplasia in each adrenal gland.

Two patients had a long history of hypertension and one of them also had a nephrotic-range proteinuria secondary to focal segmental scleronephrosis which had been diagnosed by kidney biopsy. They presented with uncontrolled hypertension. Laboratory examination suggested hypersecretion of catecholamines by the left adrenal glands in both patients and primary aldosteronism in one of them. A computed tomography scan revealed small nodules on left adrenal gland in both patients. Patients underwent laparoscopic left adrenalectomy. After surgery, blood pressure was normalized and proteinuria was resolved. Most interestingly, prominent adipocytes infiltrated were detected in the adrenal cortex and were associated with the presence of lymphocytes, which suggested that adipocytes might have a role in the pathogenesis of these diseases in our patients.

17α-Hydroxylase/17-20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia. Genetic defects causing combined 17OHD lead to the impaired production of cortisol and sex steroids, accumulation of mineralocorticoids, and compensatory overproduction of pituitary adrenocorticotropic hormone. Consequently, individuals with this enzymatic defect present with both adrenal cortical hyperplasia and variable degrees of hypertension, hypokalemia, and sexual immaturity. The patient was aged 15 years and 3 months and she was diagnosed with 17OHD while she was being evaluated for complaints of delayed puberty. In the present case, p.Y27*(c.81C>A) mutation was revealed in the sequence analysis of the CYP17A1 gene. The same mutation was reported in a 20-year-old Turkish girl in Germany, who was investigated for delayed puberty in 2005. The previous case was reported to be normotensive and normokalemic. The presence and differences in the severity of hypertension in cases with the same mutation and total enzymatic deficiency may indicate that genes predisposed to hypertension, obesity due to genetic and environmental factors, and some other factors may play a role in the clinical presentation of hypertension.

The adrenal glands are small endocrine organs located on the bottom pole of each kidney. Anatomically they are composed of cortical and medullar parts. Due to dysfunctional processes they can transform into the pathological lesions (in both cortex and medulla). The incidentally detected adrenal lesions have become an arising clinical problem nowadays. The crucial issue for an accurate treatment strategy is relevant diagnosis. Distinguishing between benign and malignant lesions is often difficult during the standard histological examination. Hence the alternative methods of differentiation are investigated. One of them is Fourier transform infrared spectroscopy which allows the analysis of the biomolecular composition of the studied tissue. In this paper we present the very preliminary FTIR studies for defining the biomolecular pattern of three types of adrenal lesions: adenoma (AA) and adrenal cortical hyperplasia (ACH) – both derived from adrenal cortex as well as pheochromocytoma (PCC) – from the medullar part of the gland. All studied cases were classified as benign lesions. The general observations show that cortically derived tissues are rich in lipids and they are rather protein depleted while for medullar pheochromocytoma there is the opposite relationship. Furthermore, the unequivocal differences were noticed within the “fingerprinting” range. In addition subtle shifts in absorption band positions were observed between studied cases.

We report a case of an adenomatoid tumor (AT) of an adrenal gland with micronodular adrenal cortical hyperplasia (ACH). A 51-year-old man was found to have newly developed hypertension with clinical evidence of primary aldosteronism. A computerized tomogram of the abdomen revealed a solitary mass in the right adrenal gland. He underwent a right adrenalectomy for a presumptive clinical diagnosis of a solitary aldosterone-producing adrenal cortical adenoma. On histopathologic examination, the adrenal gland demonstrated an AT, diagnosed by the characteristic histological features, immunohistochemical stain results, and electron microscopic findings. The surrounding adrenal cortex showed multiple small hyperplastic cortical nodules. After the adrenalectomy, the patient's blood pressure normalized. Primary AT of the adrenal gland coexisting with micronodular ACH associated with hypertension has not been previously reported.

Laparoscopic adrenalectomy (LA) is a preferred method for the removal of small adrenal masses. However, the role of LA for surgical treatment of large adrenal masses is less established. We evaluated the outcomes of LA for large (>/=5 cm) adrenal masses. We retrospectively reviewed 24 consecutive patients who underwent LA for large adrenal masses at a tertiary care university hospital. The average age of the 24 patients was 49 years, and each underwent laparoscopic resection of a large adrenal mass. All LAs were performed via a lateral transperitoneal approach. The average (+/- standard deviation) size of the masses was 6.8 +/- 1.5 cm (range, 5-11). Pathologic diagnoses included adrenal cortical adenoma (10 cases), pheochromocytoma ( 7), cyst/pseudocyst ( 3), myolipoma ( 2), and adrenal cortical hyperplasia ( 2). Statistical analysis was performed with a two-sample t test. The average operating time was 178 +/- 55 minutes (range, 120-300), and average blood loss was 87 +/- 69 mL (range, 20-300); the averages were nonsignificantly greater in the right LA group than in the left LA group (203 vs. 166 minutes, P = 0.89; 124 vs. 77 mL, P = 0.14). The average duration of nothing-by-mouth (NPO) status was 0.7 days (range, 0-4), and the average time until return to a regular diet was 1.74 +/- 0.9 days (range, 1-5). The average length of stay was 2.5 +/- 1.9 days (range, 1-10). One patient had a transient episode of pseudomembranous colitis. There were no conversions to open adrenalectomy and no major morbidities or mortalities. LA is safe and effective for surgical treatment of large adrenal masses. Both right and left large adrenal masses can be approached laparoscopically with equal success. The role of minimally invasive approaches to adrenal malignancies necessitates further investigation.

Advanced imaging often reveals adrenal tumors and tumor-like conditions in both symptomatic and asymptomatic patients. When adrenal disease is clinically suspected, cross-sectional imaging can be helpful in evaluating the etiology of the patient's symptoms. When adrenal disease is incidentally identified, what the clinician and patient really want to know is whether the findings are benign or malignant, as this ultimately will affect their next step in management. Using radiologic-pathologic correlation, we broadly classify common, uncommon, and rare tumors and tumor-like conditions that can occur in the adrenal as benign or malignant. This classification follows predominant trends in observed biologic behavior while acknowledging those tumors that may behave in the minority in an unpredictable manner. We review the clinical background and presentation of functional adrenal tumors including Conn syndrome, Cushing syndrome, and catecholamine-secreting tumors, as well as their relationship with adrenal anatomy. We discuss a variety of benign tumors, including adrenal cortical adenoma (including oncocytoma) and pheochromocytoma, as well as uncommonly and rarely encountered tumors such as myelolipoma, hemangioma, lymphangioma, schwannoma, ganglioneuroma, and adenomatoid tumor. A variety of tumefactive but nonneoplastic lesions are addressed, including adrenal cortical hyperplasia, adrenal hemorrhage, adrenal cysts, and infections. Malignant tumors discussed include adrenal cortical carcinoma, the rare malignant pheochromocytoma, lymphoma, metastases, and sarcomas. For each tumor and tumor-like lesion, the clinical presentation, epidemiology, key imaging findings, diagnostic differential considerations, and management options are briefly addressed. Finally, an approach to the workup of suspected or incidentally discovered tumors is presented based on a selected literature survey and our clinical experience. Radiologists play an important role in identification and diagnosis of adrenal tumors and tumor-like conditions in both symptomatic and asymptomatic patients.

Background/objectives Obesity is a major risk factor for the development of type 2 diabetes and other debilitating diseases. Obesity and diabetes are intimately linked with altered levels of adrenal steroids. Elevated levels of these hormones induce insulin resistance and cause cardiovascular diseases. The mechanisms underlying obesity-related alterations in adrenal steroids are still not well understood. Here, we investigated how diet-induced obesity affects the morphology and function of the mouse adrenal cortex. Methods We fed animals either a high-fat diet (HFD) or a normal diet (60% kcal from fat or 10% kcal from fat, respectively) for 18 weeks. We then assessed various aspects of adrenal gland morphology and function, as well as basal plasma concentrations of steroid hormones and ACTH. Results We show that adrenal glands of mice fed a HFD release more corticosterone and aldosterone, resulting in higher plasma levels. This increase is driven by adrenal cortical hyperplasia, and by increased expression of multiple genes involved in steroidogenesis. We demonstrate that diet-induced obesity elevates Sonic hedgehog signaling in Gli1-positive progenitors, which populate the adrenal capsule and give rise to the steroidogenic cells of the adrenal cortex. Feeding animals with a HFD depletes Gli1-positive progenitors, as the adrenal cortex expands. Conclusions This work provides insight into how diet-induced obesity changes the biology of the adrenal gland. The association of these changes with increased Shh signaling suggests possible therapeutic strategies for obesity-related steroid hormone dysfunction.

Adrenal cortical hyperplasia is characterized by an increase in cortical cells, which usually occurs bilaterally. Adrenal cortical hyperplasia generally affects both adrenal glands and may be diffuse or nodular or show features of both patterns. Adrenal glands may show hyperplasia primarily and secondarily. Primary adrenocorticotropic hormone (ACTH)-independent cortical hyperplasia is seen sporadically or in Carney complex. ACTH-dependent cortical hyperplasia occurs in congenital adrenal hyperplasia (adrenogenital syndrome), an autosomal recessive defect in an enzymatic step of steroid synthesis (most commonly 21-hydroxylase). The adrenal glands are enlarged as the result of continuous stimulation of the adrenal cortex by ACTH. Congenital adrenal hyperplasia is the most common cause of primary adrenal insufficiency in children. Secondary adrenal cortical hyperplasia is caused by pituitary ACTH adenoma, often a microadenoma, or ectopic ACTH production. The adrenal glands show a diffuse and/or micronodular pattern. These specimens, however, rarely are removed and evaluated by pathologists, because removal of the pituitary tumor is the mainstay of treatment. Other ectopic sites of ACTH production may occur and may be associated with hypercortisolism.

Inhibin normally is produced by ovarian granulosa cells and testicular Sertoli cells. Extragonadal inhibin expression also has been detected in the placenta, pituitary gland, and liver. It may be difficult to make a distinction between adrenal cortical tumors, pheochromocytoma, and metastatic carcinomas including renal cell and hepatocellular carcinoma. Immunohistochemical expression of inhibin alpha-subunit was evaluated to determine whether any usefulness of immunostaining could be found for inhibin alpha-subunit in the differential diagnosis of adrenal glandular lesions. The authors performed immunostaining against inhibin alpha-subunit on 5 cases of normal adrenal gland, 1 case of adrenal cortical hyperplasia, 25 cases of adrenal cortical adenoma, 6 cases of adrenal cortical carcinoma, 21 cases of pheochromocytoma, 8 cases of metastatic carcinoma, and 10 cases of primary renal cell carcinoma. Normal adrenal gland showed a strong immunoreactivity against inhibin alpha-subunit, especially in the inner layer of the adrenal cortex, representing the zona reticularis, but adrenal medulla was negative for inhibin alpha-subunit. Adrenal cortical hyperplasia associated with Cushing's syndrome showed a strong, diffuse immunoreactivity for inhibin alpha-subunit. Immunoreactivity against the inhibin alpha-subunit was identified in all cases of adrenal cortical adenoma and carcinoma, especially in the adrenal cortical neoplasm with Cushing's syndrome, which showed a strong reactivity. However, immunoreactivity was absent in two metastatic carcinomas from the liver and colon and most of the pheochromocytomas, except three cases with weak focal positivity for inhibin alpha-subunit. Four cases of metastatic renal cell carcinoma and 10 cases of primary renal cell carcinoma revealed no immunoreactivity. Metastatic adenocarcinoma from the prostate showed a weak immunoreactivity for inhibin alpha-subunit. Metastatic hepatoblastoma was negative against inhibin alpha-subunit with endogenous biotin blocking. Immunoexpression for inhibin alpha-subunit is useful for making distinction between adrenal cortical tumors, pheochromocytoma, and metastatic carcinoma. Inhibin alpha-subunit may be valuable as part of a diagnostic immunohistochemical panel in adrenal glandular lesions.

Distinction between benign adrenal cortical proliferative lesions and adrenal cortical carcinoma has been approached by a combination of histological, immunohistochemical, and macroscopical parameters. Modern imaging studies allow detection of small adrenal cortical lesions that may be incorrectly diagnosed. Differentiation between benign and malignant tumors of the adrenal cortex was attempted by microdissection of nine cases of adrenal cortical hyperplasia, 10 cortical adenomas, and 18 adrenal cortical carcinomas with subsequent polymerase chain reaction (PCR) amplification for loss of heterozygosity (LOH) of five microsatellites of putative tumor suppressor gene loci: p53 gene (17p), the neuroblastoma candidate gene (1p), the p16 gene (9p), the von Hippel Lindau gene (3p), and the retinoblastoma gene (13q). None of the hyperplastic lesions or cortical adenomas showed LOH of any of the gene markers used. Conversely, genetic changes were observed in 61% (11 of 18) of the cases of carcinoma. Forty-four percent of the lesions showed LOH for p53 (7 of 16). LOH of 1p, 3p, and 9p were seen in 22%, 22%, and 26%, respectively. LOH of the retinoblastoma gene was seen in 80% or four of five of the informative cases studied. We conclude that LOH studies may be used to distinguish malignant from nonmalignant adrenal cortical proliferations. Relative infrequency of LOH in 3p may furthermore help to differentiate adrenal lesions from clear cell carcinomas of the kidney.

OBJECTIVE: To determine the specific cytomorphologic criteria for diagnosing benign adrenal cortical nodule (BACN) by fine needle aspiration (FNA). STUDY DESIGN: The smears from 162 adrenal FNA biopsies were reviewed. A diagnosis of BACN was rendered in 50 cases (31%). The cytologic features of BACN were compared to those of primary and metastatic malignant tumors of the adrenal gland, and the size of BACN as measured by computed tomography was recorded. RESULTS: Bubbly, vacuolated, lipid background; large, cohesive tissue fragments with a syncytial nesting arrangement admixed with sinusoidal endothelial cells; and abundant oval, round, bare nuclei are the three cytomorphologic features most often seen in BACN. The combination of these three features was observed in 40 cases (89%) of BACN and was seen in 4 cases of metastatic carcinoma (6%) in which there was also coexisting adrenal cortical hyperplasia None of the other primary or metastatic malignancies showed this combination of cytomorphologic features. The mean size of BACN was 2.5 cm, with a standard deviation of 1 cm and a range of 1-5 cm. The sizes of the four metastatic carcinomas with coexisting adrenal cortical hyperplasia were 6.5, 6, 5 and 1.5 cm, respectively (mean, 4.8). CONCLUSION: Our data suggest that combined cytologic features of bare nuclei; bubbly, vacuolated background; and large, cohesive tissue fragments with sinusoidal endothelial cells in a small adrenal nodule (

Mice lacking the imprinted Cdk inhibitor p57(KIP2) have altered cell proliferation and differentiation, leading to abdominal muscle defects; cleft palate; endochondral bone ossification defects with incomplete differentiation of hypertrophic chondrocytes; renal medullary dysplasia; adrenal cortical hyperplasia and cytomegaly; and lens cell hyperproliferation and apoptosis. Many of these phenotypes are also seen in patients with Beckwith-Wiedemann syndrome, a pleiotropic hereditary disorder characterized by overgrowth and predisposition to cancer, suggesting that loss of p57(KIP2) expression may play a role in the condition.

Widespread use of cross-sectional imaging has resulted in an increased incidence of detection of adrenal lesions. Congenital and acquired nonneoplastic disorders of the adrenal gland include congenital adrenal hyperplasia, adrenal cyst, adrenal cortical hyperplasia, adrenal hemorrhage, adrenal tuberculosis, adrenal histoplasmosis, adrenohepatic fusion, and adrenal trauma. In this chapter, the imaging features of congenital and acquired nonneoplastic diseases of the adrenal gland are described.

In cortical adrenal gland tumours there are discrepancies between morphological criteria for malignancy and biological behaviour. This makes it difficult to select the appropriate treatment. We have studied morphometric and DNA densitometric features of 24 adrenal proliferative lesions (hyperplasia, adenoma, and carcinoma) by means of slide cytometry. All variables have been correlated with pathological diagnosis. The samples were selected from paraffin-embedded tissue, and representative lesions were Feulgen stained. Densitometric study showed aneuploid cell lines in every carcinoma, 5 of 8 adenomas, and 5 of 10 hyperplastic lesions. Both DNA nuclear content (mean ploidy of 2.11 c, 2.41 c, and 3.05 c) mean nuclear area (average of 31.26 microns 2, 35.92 microns 2, and 42.39 microns 2) showed progressive increase from hyperplasia to adenoma, and carcinoma. Mean shape factors were lowest in adenomas (1.69) and highest in carcinomas (1.82). Those karyometric variables which showed statistically significant differences (p < 0.05) among diagnostic groups were included in a stepwise three-way discriminant analysis. Only three parameters, shape factor (p = 0.0008), mean ploidy (p = 0.0012), and adrenal weight (p = 0.0055) persisted as independent predictive factors. Using the three variables selected by discriminant analysis on our cases, 100% of the adenomas were correctly classified, 83% of the carcinomas, and 80% of the hyperplasias. Tumour weight and nuclear shape factor differentiated adrenal cortex adenoma from carcinoma, while mean ploidy distinguished adrenal cortical hyperplasia from carcinoma. Nuclear pleomorphism (shape factor) and DNA-ploidy are the most important nuclear features in predicting the biological course of proliferative adrenal cortex lesions, although by themselves they are not bona-fide discriminators.

Primary hyperaldosteronism is a potential cause of hypertension. Unilateral adrenal adenoma and bilateral adrenal cortical hyperplasia are the most common causes of primary hyperaldosteronism. Adrenal venous sampling is employed as the gold standard test to differentiate between these two different causes when the results of other studies in the work-up protocol are non-diagnostic or ambiguous. Adrenal venous sampling can be a challenging procedure, especially in the presence of anomalous venous drainage patterns. Knowledge of normal adrenal venous anatomy, as well as possible variants, is therefore important to ensure a successful procedure. The authors describe an unusual variant of left adrenal venous drainage directly into the IVC.

CLINICAL pictures which accompany functioning tumors of the adrenal cortex are neither specific nor diagnostic. Other pathologic conditions produce similar or even identical symptoms. Only one of these other conditions need be mentioned here; namely, adrenal cortical hyperplasia.* For therapeutic reasons it is very important to distinguish cases of adrenal cortical tumor from adrenal cortical hyperplasia and from the other clinical and pathologic entities which simulate both of them. The discussion that follows centers around the chemical and biologic methods that can be employed to help make these distinctions. Urine of patients who have functioning adrenal cortical tumors usually contains excessive amounts of both androgens and 17-ketosteroids. The former can be determined only by biologic methods, whereas the latter, which include not only androgenic steroids but others which seem to be biologically inert, can be determined by chemical methods. Kenyon, Gallagher, Peterson, Dorfman and Koch (1937) (27) ...

Hypothalamic CRH is the primary positive regulatory factor of the pituitary-adrenal axis. The purpose of our study was to analyze the chronic effects of CRH on the production and secretion of POMC peptides from both the anterior lobe (AL) and neurointermediate lobe (NIL) of the pituitary by mimicking the syndrome of ectopic CRH secretion from neuroendocrine tumors. We first generated stably transfected W2 medullary thyroid carcinoma cell lines with a rat CRH expression vector under the transcriptional control of a cytomegalovirus gene promoter. These cell lines constitutively expressed the foreign gene, accurately processed the encoded prepro-CRH, and secreted biologically active CRH with an estimated potency equivalent to that of synthetic CRH-(1-41)NH2. The cell line designated W2CRH-7 was implanted sc in the syngeneic rat strain WAG/Rij and produced tumors that abundantly secreted CRH into the peripheral circulation. Four weeks postimplantation, W2CRH-7, but not wild-type W2, cells caused significant increases in the AL content of beta-endorphin-like immunoreactivity comparable to that caused by adrenalectomy (ADX). Plasma ACTH and serum beta-endorphin-like immunoreactivity were increased to a greater extent by ADX than by W2CRH-7 cell implantation. The NIL of both male and female rats showed either no change or a tendency to decreased beta-endorphin concentrations with no change in the acetylation or carboxy-shortening profiles judged by cation exchange chromatography in response to the ectopic CRH treatment. Rats of both sexes maintained a profound activation of the pituitary adrenal axis up to 16 weeks postimplantation, with normalized adrenal gland weights 5 times that of controls. The chronic secretion of CRH by W2CRH-7 cells resulted in a complete cessation of body growth in all rats up to the maximum time tested of 16 weeks. The lack of growth was partly ameliorated by concomitant ADX, suggesting an important role for adrenal glucocorticoids in these effects. We conclude that 1) the transplantable W2CRH-7 cell line provides a highly effective and reproducible means of sustained CRH treatment that mimics the syndrome of ectopic CRH expression by neuroendocrine tumors; 2) AL corticotrophs respond to chronic CRH by a sustained production and secretion of POMC peptides, leading to a marked adrenal cortical hyperplasia, with no evidence of biologically significant desensitization; 3) chronic CRH tends to decrease the NIL content of beta-endorphin,with remarkably little effect on posttranslational processing; and 4) the syndrome of chronic ectopic CRH in WAG/Rij rats includes a cessation of body growth at least partly due to products of the adrenal glands.

The frequency of documented endocrine diseases in rodents and other small mammals varies considerably among the species maintained as pets, biomedical research animals, or display animals in zoos. The clinical diagnosis of endocrine diseases almost never occurs in free-ranging animals in their native habitat. Feral animals that have clinical endocrine disease, such as neoplasia, adrenal cortical hyperplasia, or diabetes, would exhibit clinical signs of altered behavior that would result in their removal by predators. The diagnosis of endocrine disease thus takes place in the relatively protective environment of captivity. This observation should forewarn pet owners and clinicians caring for these animals that the environment contributes to the development of endocrine diseases in these animals.

We report a case of unilateral primary adrenal cortical hyperplasia associated with hyperaldosteromsm in a 39-yr-old Chinese man. The patient presented with hypertension hy pokalemia, primary hyperaldosteronism(1) suppressed renin activity, and was complicated with aortic dissection. The aortic dissection required emergency realignment while unilateral laparoscopic adrenalectomy was performed subsequently Pathologic examination of the adrenal lesion revealed multiple cortical nodules (up to 1 4 cm in diameter). No telomerase activity was detected in the adrenal lesion. A review of the literature showed that unilateral adrenal cortical hyperplasia has a predilection for the left side occurring more often in males. We conclude that unilateral adrenal cortical hyperplasia is a rare but unique entity and that unilateral adrenalectomy is the treatment of choice.

The cheetah ( Acinonyx jubatus) is an endangered species with low fecundity and premature death in captivity. A previous survey determined that renal failure as a result of glomerulosclerosis was a major cause of death in captive populations. This study characterizes the morphologic, histochemical, and epidemiologic properties of glomerulosclerosis in this population. Kidneys from 87 cheetahs were examined by light microscopy; kidneys from six of those cheetahs were examined by electron and fluorescent microscopy using special stains specific for collagen, glycoproteins, reticulin, and fibrin. Immunohistochemistry for the advanced glycosylation end products (AGEs), pyrraline and pentosidine, also was performed on these cases. Glomerulosclerosis was present to some degree in 82% of the population, and in 30% of cheetahs the sclerosis was moderate to severe. Affected cheetah kidneys had thickened glomerular and tubular basement membranes, culminating in glomerulosclerosis. Thickened basement membranes were positive for collagen, glycoproteins, reticulin, and AGEs. Ultrastructurally, membrane material was homogeneous and fibrillar without electron-dense deposits. This glomerular lesion in cheetahs resembles diabetic glomerulopathy in humans and chronic progressive nephropathy in rats. No cheetahs had lesions of diabetes. However, adrenal cortical hyperplasia was prevalent and highly correlated with glomerulosclerosis in this population. If cheetahs with glomerulosclerosis had hypercorticoidism, then hyperglycemia and glomerular hypertension could lead to progressive AGE and plasma protein accumulations in membrane lesions. As in rats, daily feeding of high-protein diets and lack of genetic variation in the population may further contribute to the high prevalence of glomerulosclerosis in captive cheetahs.

A new syndrome, characterized by hypertrophy and hyperplasia of the juxtaglomerular apparatus of the kidneys, aldosteronism resulting from adrenal cortical hyperplasia, and persistently normal blood pressure is described in two patients. Overproduction of aldosterone could not be prevented by sodium loading or by administration of albumin intravenously; it was associated with hypokalemic alkalosis and Pitressin-resistant impairment of urinary concentrating ability. In both subjects, increased amounts of circulating angiotensin were demonstrated; infusion of angiotensin II produced rises of blood pressure in both subjects considerably less than the rises induced by comparable doses in normal subjects. The sequence of events, (1) primary resistance to the pressor action of angiotensin, (2) compensatory overproduction of renin and thus of angiotensin, and (3) stimulation of adrenal cortex by angiotensin is consistent with all the information available about the syndrome.

Single or multiple semispherical to bilobulated fluid-filled cystic structures of variable size were observed on the dorsal aspects of the urinary bladder of four male and two female ferrets ( Mustela putorius furo). All ferrets had been neutered. On physical examination, the cysts were palpated as caudal abdominal masses. Three of the six ferrets presented with dysuria, and two ferrets had signs compatible with endocrine dysfunction. Adrenal cortical hyperplasia or neoplasia were observed in all of the five ferrets examined. Sex hormones assayed in one of the six ferrets revealed elevated levels of serum estrodiol. The posterior aspect of the cysts was located on and/or attached to the trigone or neck of the bladder, with variable intraluminal communication with the bladder and/or the urethra. The anterior aspect of the cysts projected dorsally or dorsocranially into the caudal abdomen. The cysts were thin walled and contained urinelike fluid ( n = 5) or viscous yellow fluid ( n = 1). Histologically, the cyst walls were composed of three layers, epithelium, muscle, and serosa, with fibrovascular stroma between layers. The epithelium consisted of simple to stratified transitional, columnar, or squamous epithelial cells. The muscular layer consisted of intermittent bundles and/or single to double layers of continuous to discontinuous smooth muscle. The serosal layer consisted of loose fibrous stroma covered by flattened mesothelial cells. The cystic anomalies in these ferrets were most likely derived from the urogenital glands/ducts or other remnants.

Vascular tumours are very uncommon in the kidney and most of these have been described in single case reports. Some of these can be diagnosed radiologically so the histological features of many of these tumours are not well recognised. We report a case of a haemangioma arising from within the renal vein in a patient with chronic renal failure and bilateral adrenal cortical hyperplasia. The tumour has an unusual sinusoidal architecture and focal extrame-dullary haematopoiesis reminiscent of the spleen. As expected, the endothelial cells stain positively for CD31 and CD34 but negative for CD8. We will also briefly discuss the clinical and histological features of this unusual tumour based on literature reviews.

The ultrastructural features of 30 adrenal cortical carcinomas have been reviewed and compared with those seen in adrenal cortical adenomas, adrenal cortical hyperplasia, and the normal cortex. A broad range of ultrastructural appearances was found among the carcinomas, but the differences were mainly in the amount of cytoplasmic lipid, number of lysosomes, and quantity and architecture of the mitochondria and endoplasmic reticulum. Structural variants among the carcinomas included lipid-rich, oncocytic, and glycogen-rich cells. Electron microscopy can be extremely useful in differential diagnoses that include adrenal cortical carcinoma.

多発性内分泌腺腫症1型の1例を報告する.症例は56才女性,大腿骨頚部内側骨折で発病し,副甲状腺ホルモン,甲状腺ホルモン,コルチゾール,ガストリン,グルカゴン様免疫活性の高値を認めた.副甲状腺腫瘍摘出術時,単発性の腺腫を確認した.術後高力ルシウム血症は改善したが,割甲状腺ホルモン以外のホルモンの高値は持続した.腎不全により死亡,剖検所見では甲状腺はび漫性に腫大し,組織学的には過形成の像を呈し,両側副腎にも皮質の過形成,膵島微小腺腫を確認した.家族性は認められなかった.過形成および腺腫により5ホルモンの過剰分泌を呈した興味ある1例と考えられた.

1. Radioimmunoassay has been used to detect and estimate the urinary excretion of deoxycorticosterone (DOC) in normal, hypertensive and hypokalaemic subjects. The range of excretions in ten healthy normal subjects was 41–232 pmol (13.7–76.7 ng) daily, with a mean of 124 pmol (41 ng). 2. In fourteen subjects with essential hypertension without metabolic disturbance the range found was 29–144 pmol (9.7–47.7 ng) daily, with a mean of 87 pmol (28.8 ng), which is not significantly different from that in normal subjects. 3. In twelve patients with Cushing's syndrome due to adrenal cortical hyperplasia the range found was 26–542 pmol (8.7–179 ng). Ten of these twelve patients had values within normal limits. 4. Of nine subjects showing hypokalaemia, eight had elevated excretion of deoxycorticosterone with values from 263 to 5515 pmol (87–1820 ng) daily. Seven of these were hypertensive and two were normotensive. The elevated excretion of deoxycorticosterone found in hypokalaemic subjects is thus not confined to those with hypertension. 5. No correlation has been found between excretion rates for aldosterone and deoxycorticosterone. Raised excretion of the latter provides an indicator of disturbed adrenal cortical metabolism.

A 47-year old woman is presented who had a left adrenal pheochromocytoma with manifestations also indicative of ectopic ACTH syndrome. The excised adrenal gland showed both an adrenal medullary tumor and adrenal cortical hyperplasia. Immunostaining also showed the presence in the tumor of ACTH and beta endorphins. The immediate post-adrenalectomy decline of catecholamines, ACTH, cortisol and beta endorphins indicate that the adrenal itself was the source of these hormones. This patient, the thirteenth now reported in the literature, represents one form of ectopic ACTH syndrome in which the lesion is benign, and in which a successful outcome can be anticipated.

Summary Pregnant rats were treated with pharmacologically equivalent doses of cortisone, corticosterone and dexamethasone between the 12th und 22nd day of pregnancy. As there was no interference with parturition, the litters could be divided. The developement of the weigths of body, adrenals and pituitary was examined on the day of birth, the 7th and 14th day of life. Pituitary and body weight show an exuberant increase (rebound effect) as compared with the controls with a peak around the 8th day, the adrenal weight showed a corresponding peak around the 12th day of life. The exuberant increase of weight of the adrenals is correlated with an increased mitotic activity within the zona glomerulosa. Nuclear counts/constant area reveal an increase in the size of the cells of the zona glomerulosa together with the exuberant weight increase on the 7th and 14th day and of the zona fasciculata (only on the 14th day, this increase is apparently delayed) as compared with the controls. This phenomenon suggests an alteration of the functional state with an increase in cytoplasmic structures (mitochondria, deposits, endoplasmic reticulum).

Summary Extensive involvement of the urinary tract and related structures by malakoplakia presented difficult diagnostic problems in two elderly individuals. At post-mortem examination there was bilateral adrenal cortical hyperplasia in both patients and, in one, there was also a pancreatic glucagonoma and diffuse hyperplasia of the pancreatic islet tissues. There is now an increasing body of evidence that malakoplakia is associated with hypercorticosteroidism possibly due to an effect on macrophage exocytotic mechanisms. The coexistence of malakoplakia and glucagonoma has not been previously described.

The immunosuppressive action of adrenal glucocorticosteroids is well-known, and depressed cell-mediated immunity and adrenal cortical hyperplasia have been described in tumor-bearing animals. This study was designed to evaluate the effect of removing the source of lympholytic steroids by adrenalectomy upon tumor growth rate, thymus weight, and thymocyte incorporation of iodine 125 (125I) deoxyuridine into DNA. Newly derived methylcholanthrene-induced immunogenic fibrosarcomas were used in male syngeneic mice. Log dosages of 10(4), 10(5), and 10(6) viable tumor cells as single cell suspension were injected subcutaneously into the popliteal space of adrenalectomized and control mice. Tumor size was followed serially with caliper measurements, and the animals were killed 4 weeks after inoculation. Adrenalectomized mice inoculated with 10(4) cells had smaller tumors (P less than 0.02), heavier thymi (P less than 0.01), and more thymic DNA synthesis (P less than 0.05) than their tumor-bearing controls. No differences were seen between populations receiving 10(5) or 10(6) tumor cell inoculations. A second experiment was carried out in which intact controls, adrenalectomized animals, and sham adrenalectomy animals were inoculated with 10(4) tumor cells and killed 28 days later. Tumor growth rate and volume were significantly decreased for the adrenalectomized mice, which had higher thymus weights and DNA synthesis. These findings suggest that pretreatment adrenalectomy slows the growth of antigenic tumor cells and prevents thymic involution after tumor growth in a syngeneic murine system.

SummaryVarying daily doses of a steroidal inhibitor of 3β-hydroxysteroid dehydrogenase (2α-cyano-4,4,17α-trimethylandrost-5-en-17β-ol-3-one), were administered to pregnant rats on the 15 th to 20th days of gestation to determine whether this inhibitor could produce the biological manifestations of the human disease associated with deficient activity of this enzyme. A single dose of the inhibitor was also administered to pregnant rats on various days to determine the critical periods for production of these manifestations. Infants with this disorder have hyperplastic adrenal cortices deficient in activity of the 3β-enzyme, incomplete masculine development in males resulting in hypospadias with shortening of the anogenital distance, and clitoral hypertrophy without urethral orificial displacement in females. The experimental fetuses had adrenal cortical hyperplasia (average of 5.9 ± 1.32 mg against 2.2 ± 0.26 mg controls), deficient histochemical activity of the 3β-enzyme in the adrenals and testes, increas...

ONE OF THE striking characteristics of functioning tumors of the adrenal cortex is the variety and variability of the clinical pictures which they produce. Even a cursory review of the reported cases and a glance at the photographs which usually accompany the case reports are sufficient to satisfy anyone who is skeptical regarding the truth of this statement. Such a review shows not only that the often described classical clinical pictures are different among boys, girls, men and women, but that grossly similar tumors produce widely different clinical effects even among members of the same sex and age groups. In some instances only one or two striking endocrine abnormalities will be present, to the relative or absolute exclusion of others. Some patients will be extremely weak; others unnaturally vigorous. Some will have striae, or hypertension, or diabetes or polycythemia, or all of these; others will not. Some cases present in all details the syndrome described by Cushing; in others the appearance of the...

The urinary concentration of gonadotrophin (ICSH)-inhibiting substance was found to be markedly reduced to absent in 5 patients with Stein-Leventhal syndrome, while it was present in amounts usually found in normal subjects in one patient with mild adrenal cortical hyperplasia. It is possible that the Stein-Leventhal syndrome may result from the unregulated action of ICSH on the ovary, associated with a reduction in the postulated secretion of “inhibitor.”

The fact that the adrenal cortex contributes to the metabolic pool of androgens in the body and the 17-ketosteroids in the urine is well known. Hirschmann (1941) was able to isolate androsterone and etiocholanol-3(α)-one-17 from the urine of ovariectomized women in concentrations almost equivalent to that isolated from the urine of normal women. In Addison’s disease the urinary titer of androgens and 17-ketosteroids is significantly reduced. In patients with adrenal cortical hyperplasia or tumors, the concentration of androgens and 17-ketosteroids is increased. Although the evidence indicates that some of the androgens found in normal urine were derived from the adrenal cortical steroids, little is known of the mechanism of the conversion of these steroids to major androgen metabolites, such as androsterone and etiocholanol-3(α)- one-17. Of the three C-19 compounds which have been isolated from adrenal tissue, one, Δ4-androstenedione-3, 17, has been shown to yield androsterone and etiocholanol-3(α)-one-17...

SummaryVarying daily doses of a steroidal inhibitor of 3β-hydroxysteroid dehydrogenase (2α-cyano-4,4,17α-trimethylandrost-5-en-17β-ol-3-one), were administered to pregnant rats on the 15 th to 20th days of gestation to determine whether this inhibitor could produce the biological manifestations of the human disease associated with deficient activity of this enzyme. A single dose of the inhibitor was also administered to pregnant rats on various days to determine the critical periods for production of these manifestations. Infants with this disorder have hyperplastic adrenal cortices deficient in activity of the 3β-enzyme, incomplete masculine development in males resulting in hypospadias with shortening of the anogenital distance, and clitoral hypertrophy without urethral orificial displacement in females. The experimental fetuses had adrenal cortical hyperplasia (average of 5.9 ± 1.32 mg against 2.2 ± 0.26 mg controls), deficient histochemical activity of the 3β-enzyme in the adrenals and testes, increas...

Several steroids in the urine and adrenal tissue of a boy with Cushing's syndrome and a basophilic adenoma of the pituitary gland have been studied. The outstanding observation was that large quantities of free cortisol were excreted; a considerable amount of this hormone was also found in the adrenal tissue. There appeared to be deficiencies in the mechanisms for conjugation with glucuronic acid, for the reduction of the Δ4-3-keto grouping and for the dehydrogenation of 11β-hydroxysteroids. In this paper we also report the identification and isolation of 6β,17α,21-triol-4-pregnene-3,11,20-trione (6β-hydroxycortisone).