Diagnostic Challenges in Adrenocortical Carcinoma: Recommendations for Surveillance after Surgical Resection of Selected Adrenal Nodules

ObjectiveTo discuss challenges in the diagnosis of adrenocortical carcinoma and to suggest surveillance measures after removal of selected adrenal nodules.MethodsWe present the case of a 65-year-old man with worsening hypertension and new-onset hypokalemia attributed to primary hyperaldosteronism due to a 3-cm right adrenal nodule.ResultsA laparoscopic right adrenalectomy was performed, and the histologic diagnosis was a benign adenoma. The patient’s hypertension and hypokalemia improved postoperatively but recurred 8 months later, and florid Cushing’s syndrome developed. Magnetic resonance imaging showed an 8-cm mass in the right adrenal bed and multiple hepatic metastatic lesions. Fine-needle biopsy confirmed the presence of adrenocortical carcinoma.ConclusionDespite a comprehensive biochemical, radiologic, and histologic assessment, the diagnosis of adrenocortical carcinoma can be missed. Particularly, we caution against undue reliance on the initial tumor size. We recommend that abdominal imaging be performed every 3 months for the first year and every 6 months for the second year after surgical removal of selected adrenal nodules. (Endocr Pract. 2007;13:636-641)     

Invalidation of TASK1 potassium channels disrupts adrenal gland zonation and mineralocorticoid homeostasis

TASK1 (KCNK3) and TASK3 (KCNK9) are two-pore domain potassium channels highly expressed in adrenal glands. TASK1/TASK3 heterodimers are believed to contribute to the background conductance whose inhibition by angiotensin II stimulates aldosterone secretion. We used task1-/- mice to analyze the role of this channel in adrenal gland function. Task1-/- exhibited severe hyperaldosteronism independent of salt intake, hypokalemia, and arterial 'low-renin' hypertension. The hyperaldosteronism was fully remediable by glucocorticoids. The aldosterone phenotype was caused by an adrenocortical zonation defect. Aldosterone synthase was absent in the outer cortex normally corresponding to the zona glomerulosa, but abundant in the reticulo-fasciculata zone. The impaired mineralocorticoid homeostasis and zonation were independent of the sex in young mice, but were restricted to females in adults. Patch-clamp experiments on adrenal cells suggest that task3 and other K+ channels compensate for the task1 absence. Adrenal zonation appears as a dynamic process that even can take place in adulthood. The striking changes in the adrenocortical architecture in task1-/- mice are the first demonstration of the causative role of a potassium channel in development/differentiation.     

Co-secretion of aldosterone and cortisol by an adrenocortical carcinoma

We report a rare case of adrenocortical carcinoma. A 26-year-old woman presented with hypokalemia and hypertension due to hyperaldosteronism. She had no signs of Cushing's syndrome. Endocrinological data showed excess of aldosterone production and nonsupressible cortisol production on 2 mg of dexamethasone. Magnetic resonance imaging showed left adrenal tumor. Transabdominal left adrenalectomy was performed and histopathological diagnosis was adrenocortical carcinoma. Her blood pressure and hypokalemia returned to normal after adrenalectomy. There is no recurrence after 36 months. We want to emphasis the importance of adrenal tests before the operation even if there are no signs of excess cortisol production.     

Plasma concentration of neuropeptide Y in patients with adrenal hypertension.

The mechanisms of hypertension during primary hyperaldosteronism and Cushing's syndrome are not completely understood. An enhanced vascular sensitivity to noradrenaline has been described in both situations. Neuropeptide Y (NPY) induces direct vasoconstriction and potentiates the action of noradrenaline. Sodium retention and dexamethasone have been shown to increase circulating NPY levels in animals and the expression of NPY in neuroendocrine cells. In order to determine if NPY could be involved in the enhanced vascular sensitivity to noradrenaline associated with adrenocortical hyperactivity, we measured plasma NPY in patients with Cushing's syndrome (n = 26) and primary hyperaldosteronism (n = 15) and compared it with that of hypertensive patients with pheochromocytomas (n = 13) or essential hypertension (n = 51) and with normotensive controls (n = 47). The concentration of NPY-Like immunoreactivity (NPY-Li) (mean +/- S.E.) in controls was 39.6 +/- 3.0 pg/ml. Elevated concentrations were found in 77% of the samples collected from pheochromocytoma patients (1180.4 +/- 394.0 pg/ml). NPY-Li levels in patients with essential hypertension (35.0 +/- 2.6 pg/ml), primary hyperaldosteronism (31.3 +/- 3.9 pg/ml) and Cushing's syndrome (33.1 +/- 4.8 pg/ml) were not different from that of controls. NPY-Li levels in hypertensive and normotensive patients with Cushing's syndrome were similar (38.5 +/- 7.5 vs 24.2 +/- 3.7 pg/ml). No correlation was found between the NPY-Li level and the mean blood pressure at the time of sampling. Our results suggest that NPY is unlikely to be involved in the pathogenesis of hypertension associated with primary hyperaldosteronism and Cushing's syndrome.     

A case of glucocorticoid-suppressible hyperaldosteronism with aldosterone producing adenoma

A 34-yr-old woman with hypertension (142/102 mmHg), hypokalemia, high plasma and urinary aldosterone and low plasma renin activity was studied. A left adrenal tumor and enlarged right adrenal gland were demonstrated by adrenal venography. During administration of dexamethasone (2 mg daily, for 3 weeks), urinary aldosterone excretion decreased abruptly from 22.5 to 9-11 micrograms/day, serum potassium increased and blood pressure fell to 120-130/80-90 mmHg. After left adrenalectomy, all manifestations improved with no medication. The resected adrenal gland revealed clear cell adenoma and micronodular adrenocortical hyperplasia. The patient was considered to be a rare case of glucocorticoid-suppressible hyperaldosteronism with an aldosterone-producing adenoma.     

Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: Adiponectin regulates steroidogenesis

Obesity is frequently associated with malfunctions of the hypothalamus-pituitary-adrenal (HPA) axis and hyperaldosteronism, but the mechanism underlying this association remains unclear. Since the adrenal glands are embedded in adipose tissue, direct cross-talk between adipose tissue and the adrenal gland has been proposed. A previous study found that adiponectin receptor mRNA was expressed in human adrenal glands and aldosterone-producing adenoma (APA). However, the expression of adiponectin receptors in adrenal glands has not been confirmed at the protein level or in other species. Furthermore, it is unclear whether adiponectin receptors expressed in adrenal cells are functional. We found, for the first time, that adiponectin receptor (AdipoR1 and AdipoR2) mRNA and protein were expressed in mouse adrenal and adrenocortical Y-1 cells. However, adiponectin itself was not expressed in mouse adrenal or Y-1 cells. Furthermore, adiponectin acutely reduced basal levels of corticosterone and aldosterone secretion. ACTH-induced steroid secretion was also inhibited by adiponectin, and this was accompanied by a parallel change in the expression of the key genes involved in steroidogenesis. These findings indicate that adiponectin may take part in the modulation of steroidogenesis. Thus, adiponectin is likely to have physiological and/or pathophysiological significance as an endocrine regulator of adrenocortical function.     

Fecal and salivary electrolytes in the diagnosis of primary aldosteronism

Fecal and salivary sodium and potassium concentrations were measured in 22 hypertensive patients with hypokalemia who were undergoing investigation for primary aldosteronism due to an adrenocortical adenoma (Conn''s syndrome). Of eight patients with a high aldosterone secretion rate, five had clearly low fecal Na/K ratios, (including all four patients with Conn''s syndrome), in three the ratios were equivocal. Of 14 patients with hypertension and a normal aldosterone secretion rate, none had a sufficiently low fecal Na/K ratio strongly to suggest hyperaldosteronism, although two were borderline. Salivary electrolyte concentrations were not as consistent an indicator of mineralocorticoid hormone excess. Estimation of fecal sodium and potassium concentrations may be useful in the diagnosis of mineralocorticoid hormone excess and in assessing the results of therapy.     

Case report: schwannoma arising from the unilateral adrenal area with bilateral hyperaldosteronism

Background

We report a rare case of a juxta-adrenal schwannoma that could not be discriminated from an adrenal tumor before surgical resection and was complicated by bilateral hyperaldosteronism. To the best of our knowledge, this is first case in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed.

Case presentation

A 69-year-old male treated for hypertension was found to have a left supra-renal mass (5.8?×?5.2 cm) by abdominal computed tomography. His laboratory data showed that his plasma aldosterone concentration (PAC) was within the normal range, but his plasma renin activity (PRA) was reduced, resulting in an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide in the standing position demonstrated autonomous aldosterone secretion and renin suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected because of the possibility of malignancy and was found to be a benign schwannoma arising from the juxta-adrenal region together with an adrenal gland. The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase). Multiple CYP11B2-positive adrenocortical micronodules were detected in the adrenal gland, indicating micronodular hyperplasia. Although bilateral aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR values were within their respective reference ranges after resection of the unilateral tumor, suggesting that the slight increase in hormone secretion from the remaining right-sided lesion could not be detected after resection.

Conclusion

A clinical and morphologic diagnosis of juxta-adrenal schwannoma is difficult, particularly in a case of hyperaldosteronism, as shown in this case. These data suggest the complexity and difficulty diagnosing adrenal incidentaloma.

     

Evaluation of peritoneal tissue by means of differential scanning calorimetry (DSC)

Abdominal surgeries alter the integrity of the peritoneal layer and cause imbalances among immunological, inflammatory and angiogenic mechanisms within the tissue. During laparoscopic procedures a protective function of the peritoneal layer can be disturbed by the gas used to create a pneumoperitoneum. The aim of this study was to characterize peritoneal tissue by means of differential scanning calorimetry (DSC) as a reference for future investigations on the influence of surgical procedures on the physicochemical state of the peritoneum. Thirty-seven patients participated in the study. Patients were divided into three groups according to the type of surgery: group H - patients who underwent hernia repair; group Ch - patients who underwent laparoscopic cholecystectomy; and group C - patients operated due to rectal cancer. It was observed that onset temperature (T(o)), denaturation temperature (T(m)) and change of enthalpy (ΔH) during thermal denaturation of peritoneal collagen in were significantly different for these three groups of patients. The mean values of onset temperature (T(o)) and denaturation temperature (T(m)) in group H were significantly lower, while DH in this group was significantly higher than in the two other groups (Ch and C). This preliminary study does not answer whether the differences in collagen denaturation found in peritoneal tissue from different groups of patients resulted from a different inherent state of the tissue, or from surgical procedures. However, the results suggest that DSC is an appropriate method to study subtle changes in the physicochemical condition of the peritoneum using small samples obtained during surgical procedures.     

Role of 5-HT in the regulation of the brain-pituitary-adrenal axis: effects of 5-HT on adrenocortical cells

Serotonin (5-HT) plays a pivotal role in the regulation of the brain-pituitary-adrenal axis. In particular, 5-HT has been shown to control the activity of hypothalamic CRF neurons and pituitary corticotrope cells through activation of 5-HT1A and (or) 5-HT(2A/2C) receptor subtypes. 5-HT, acting through 5-HT2 receptors, can also trigger the renin-angiotensin system by stimulating renin secretion and consequently can enhance aldosterone production. At the adrenal level, 5-HT produced locally stimulates the secretory activity of adrenocortical cells through a paracrine mode of communication. The presence of 5-HT in the adrenal gland has been demonstrated immunohistochemically and biochemically in various species. In the frog, rat, and pig adrenal gland, 5-HT is synthesized by chromaffin cells, while in the mouse adrenal cortex, 5-HT is contained in nerve fibers. In man, 5-HT is present in perivascular mast cells. In vivo and in vitro studies have shown that 5-HT stimulates corticosteroid secretion in various species (including human). The type of receptor involved in the mechanism of action of 5-HT differs between the various species. In frogs and humans, the stimulatory effect of 5-HT on adrenocortical cells is mediated through a 5-HT4 receptor subtype positively coupled to adenylyl cyclase and calcium influx. In the rat, the effect of 5-HT on aldosterone secretion is mediated via activation of 5-HT7 receptors. Clinical studies indicate that 5-HT4 receptor agonists stimulate aldosterone secretion in healthy volunteers and in patients with corticotropic insufficiency and primary hyperaldosteronism. Local serotonergic control of corticosteroid production may be involved in the physiological control of the activity of the adrenal cortex as well as in the pathophysiology of cortisol and aldosterone disorders.     

Suppression of ACTH-induced steroidogenesis by supernatants from LPS-treated peritoneal exudate macrophages

The results from a number of clinical and experimental studies have suggested that during endotoxemia, suppression of adrenocortical steroidogenesis may occur. We have examined the possibility that macrophages are the source of a factor that suppresses adrenocortical steroidogenesis. Resident and peptone-elicited peritoneal exudate macrophages (PEM) from C3HeB/FeJ mice were incubated for 4 hr at 37 degrees C in the presence or absence of T cell hybridoma-derived lymphokine (LK) that contained high concentrations of MAF activity (assessed by induction of nonspecific tumoricidal activity in PEM). The LK was removed by rinsing, and fresh medium was added, followed by Salmonella minnesota R595 LPS (final concentration 10 micrograms/ml). After 18 hr at 37 degrees C the PEM supernatants and control medium from flasks without cells were harvested and stored at -20 degrees C. Explanted rabbit adrenocortical cells in 96-well plates were exposed to 30 microliters of PEM supernatant or control medium and ACTH (10 or 100 mU/ml) in a final volume of 120 microliters for 3 consecutive days. The adrenocortical cell supernatants were harvested each day, followed by replenishment of medium, PEM supernatant, and ACTH. Fluorogenic steroid production in wells that received control medium or supernatants from PEM not treated with LPS was normal (0.22 microgram +/- 0.010 (SD) per 5 X 10(4) cells). However, as much as 75 to 95% suppression of steroidogenesis was observed in wells that received supernatants from PEM treated with LK and LPS, compared to 40% suppression in wells that received supernatant from PEM treated with LPS alone. Continued exposure (over 3 days) of adrenocortical cells to supernatants from LPS-treated PEM resulted in progressively decreasing response to ACTH. Comparable suppressive activity was observed in supernatants from LPS-treated bone marrow-derived macrophages. In further experiments, suppression was observed in wells that were pretreated (22 hr) with the appropriate PEM supernatant, and evidence was obtained that the suppressive activity was not due to carry-over LPS. Finally, results from control experiments demonstrated that suppressive PEM supernatants neither inactivate ACTH nor interfere with the assay of fluorogenic steroids. Thus, these results suggest that during endotoxemia, products from LPS-stimulated macrophages may suppress adrenocortical function.     

Carcinoma of Lung with Adrenal Hyperfunction and Hypercalcemia Treated by Parathyroidectomy

A case of severe hypercalcemia secondary to carcinoma of the lung is described in which hypokalemic alkalosis, renal failure and pancreatitis were also present. The relative importance of the few bone metastases found at autopsy is considered, and a probable endocrine-like effect of the tumour in the development of the hypercalcemia is postulated. Treatment of the hypercalcemia included administration of corticosteroids and disodium EDTA, peritoneal dialysis and subtotal parathyroidectomy; the most effective of these was peritoneal dialysis. Subtotal parathyroidectomy failed to produce a further decrease in serum calcium values. The occurrence of hypokalemic alkalosis in the presence of increased adrenocortical function and its relationship to the carcinoma of the lung are discussed. The possibility that this neoplasm produced two factors which caused systemic effects ordinarily associated with the function of endocrine glands must be considered.     

脑室镜和腹腔镜辅助脑室腹腔分流术治疗老年脑积水的疗效

目的:探讨脑室镜和腹腔镜辅助脑室腹腔分流术治疗老年脑积水的疗效。方法:选择我院90例老年脑积水患者,按随机数字表法平均分为A、B、C 3组各30例,A组患者给予传统脑室腹腔分流术治疗,B组患者给予腹腔镜辅助下脑室腹腔分流术治疗,C组患者给予脑室镜和腹腔镜综合辅助下脑室腹腔分流术治疗,比较3组患者治疗有效率及术后并发症发生率。结果:C组患者治疗有效率为90.0%,明显高于A组63.3%及B组76.7%,比较差异具有统计学意义(均P0.05);C组患者术后感染及分流管堵塞并发症发生率明显低于A组和B组,比较差异均有统计学意义(均P0.05);B组和C组脑实质内出血发生率均低于A组,与A组比较差异具有统计学意义(P0.05)。结论:脑室镜和腹腔镜综合辅助下脑室腹腔分流术治疗老年脑积水的疗效显著,术后并发症少,值得推广。     

Adrenal cortical carcinoma: an unusual cause of hyperaldosteronism.

Although secondary hyperaldosteronism due to renal vein thrombosis may occur as a result of renal cell carcinoma or adrenal cortical carcinoma, primary hyperaldosteronism is rarely associated with the latter. This paper describes a patient with adrenal cortical carcinoma who presented with the clinical features of primary hyperaldosteronism 1 year after hypertension had been diagnosed; intravenous pyelography had not been done then. Drug therapy was ineffective, and the patient died 10 weeks after presentation.     

A new variant of 17 alpha-hydroxylase deficiency with hyperaldosteronism in two Japanese sisters

We present a report on two sisters who have 17 alpha-hydroxylase deficiency with hyperaldosteronism. They have hypertension and hypergonadotropic hypogonadism. The steroid profiles suggest that they have 17 alpha-hydroxylase deficiency. In contrast to the classical biochemical findings in 17 alpha-hydroxylase deficiency, both of these patients have hyperaldosteronism. Thus this report describes a new variant of 17 alpha-hydroxylase deficiency with hyperaldosteronism. Dexamethasone suppressed the mineralocorticoid excess, including aldosterone, and improved their hypertension. In the untreated state, ACTH, instead of the renin-angiotensin system, regulated plasma aldosterone levels, but during dexamethasone treatment the renin-angiotensin system regulated these levels.     

Cytologic and immunologic prognosis of infertility. II Prognostic value of studies of immunoglobulins A,M, and G in peritoneal fluid and blood of infertile patients

Immunoglobulins of A, M, and G classes were studied in the blood and peritoneal fluid of 80 women during laparoscopic operation by nefelometry. An increased concentration of these immunoglobulins A, M, G was revealed in the patients with unfavourable prognosis. The immunological changes were seen to depend on the patient's age and the stage of lesion.     

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)     

Falsely High Plasma Potassium Values in Patients with Hyperaldosteronism

The common practice of encouraging forearm exercise as an aid to venepuncture is a potent source of erroneously high plasma potassium levels. This may be sufficient to obscure a suspicion of hyperaldosteronism, with possible serious repercussions in hypertensive patients, in whom the diagnosis of hyperaldosteronism has important therapeutic implications. Plasma is preferable to serum for potassium estimations, and forearm exercise should be avoided before venepuncture for potassium measurements.     

Value of localizing examinations used in the diagnosis of primary hyperaldosteronism

Localizing examinations were performed in 115 patients with the clinical and biochemical signs of the primary hyperaldosteronism between 1975 and 1978. Adenoma of the adrenal cortex was diagnosed in 52 examined patients out of whom 42 underwent surgery, and 12 were classified for the operation. The remaining patients, in whom a cause of hyperaldosteronism was not found, are treated conservatively and followed-up. It was shown that CT-scanning and scintigraphy of the suprarenal cortex are the most convenient techniques in the localization of tumours in patients with the primary hyperaldosteronism. Ultrasound is less valuable diagnostically but may help in tumour localization in about 50% of patients.     

Genetics of Primary Aldosteronism

Objective: The American Association of Clinical Endocrinologists Adrenal Scientific Committee has developed a series of articles to update members on the genetics of adrenal diseases.Methods: Case presentation, discussion of literature, table, and bullet point conclusions.Results: Primary aldosteronism (PA) is the most common form of secondary hypertension. Early detection, surveillance, and treatment of PA may mitigate future cardiovascular risk. The genetics of PA are rapidly evolving, and the consideration for genetic causes of PA are growing. Three inheritable forms of PA are now recognized: familial hyperaldosteronism type I (glucocorticoidremediable aldosteronism), familial hyperaldosteronism type II, and familial hyperaldosteronism type III. The recent discovery of familial hyperaldosteornism type III spurred a flurry of international and collaborative research that is identifying more genetic and molecular causes of PA that relate to mutations in membrane electrolyte transport channels of zona glomerulosa cells.Conclusion: This article reviews the various genetic forms of PA, including a focus on the molecular mechanisms involved, diagnosis, and treatment.Abbreviations: ACTH = adrenocorticotropic hormone ARR = aldosterone to renin ratio FH-I = familial hyperaldosteronism type I FH-II = familial hyperaldosteronism type II FH-III = familial hyperaldosteronism type III GRA = glucocorticoidremediable aldosteronism PA = primary aldosteronism PRA = plasma renin activity