(1/137) Primary aldosteronism with aldosterone-producing adrenal adenoma in a pregnant woman.

A 30-year-old pregnant woman complained of muscle weakness at 29 weeks' gestation. She was hypertensive with severe hypokalemia. Lower plasma renin activity and higher aldosterone level than the normal values in pregnancy suggested primary aldosteronism. A cesarean delivery was performed at 31 weeks' gestation because of pulmonary congestion. The neonatal course was uncomplicated. The laparoscopic adrenalectomy for a 2.0-cm right adrenal adenoma resulted in normalizing of her blood pressure and serum potassium level. Although primary aldosteronism is rare, especially during pregnancy, it should be always considered as one of etiologies of hypertension in pregnancy.  (+info)

(2/137) The expression of inhibin/activin subunits in the human adrenal cortex and its tumours.

Inhibins and activins are dimeric proteins of the transforming growth factor-beta superfamily which have been shown to be expressed in the adrenal cortex. Recent studies have suggested a role for these peptides in the pathogenesis and/or function of adrenal tumours. To investigate further their physiological and pathological roles, we have documented immunoreactivity for inhibin alpha, betaA and betaB subunits in normal adult and fetal human adrenals, in hyperplastic adrenals and in adrenal tumours. In the normal and hyperplastic adult gland, diffuse immunopositivity was demonstrated for beta subunits, suggesting that activins (beta beta dimers) can be expressed in all zones. Inhibin alpha was limited to the zona reticularis and the innermost zona fasciculata in the normal gland, extending centripetally into the zona fasciculata in hyperplasia, supporting a role for ACTH in the regulation of expression, and suggesting that expression of inhibins (alpha beta dimers) is restricted. Immunopositivity for all three subunits was seen in both fetal and definitive zones of the fetal cortex, indicating that both inhibins and activins could be expressed in both. Immunopositivity for all three subunits was seen in most adrenocortical tumours. Loss of immunopositivity for inhibin alpha in a subgroup of carcinomas might indicate a role in tumour progression. The greater intensity of staining for inhibin alpha in tumours associated with Cushing's syndrome again suggests a link with cortisol production.  (+info)

(3/137) Analysis of genomic alterations in sporadic adrenocortical lesions. Gain of chromosome 17 is an early event in adrenocortical tumorigenesis.

Genetic changes underlying the tumorigenesis of sporadic adrenocortical tumors are poorly characterized. To search for characteristic genomic imbalances involved in adrenocortical tumors, we examined 41 adrenocortical lesions (12 carcinomas, 23 adenomas, and 6 hyperplasias) by comparative genomic hybridization. Our results show that genetic alterations are more frequent in malignant than in benign lesions and that they rarely occur in hyperplastic lesions. The most frequent DNA copy number changes in adrenocortical carcinomas included losses of 1p21-31, 2q, 3p, 3q, 6q, 9p, and 11q14-qter, as well as gains and amplifications of 5q12, 9q32-qter, 12q, and 20q. The genomic aberrations prevalently occurring in adrenocortical adenomas were gains of 17q, 17p, and 9q32-qter. Gains found in 2 of 6 adrenocortical hyperplastic lesions involved chromosome 17 or 17q only. These data indicate that oncogenes determining the early tumorigenesis of adrenocortical tumors may exist on chromosome 17 and that the number of genomic alterations is closely associated with tumor behavior in adrenocortical tumors.  (+info)

(4/137) Recurrence of adrenal aldosterone-producing adenoma.

Conn's syndrome (adrenal aldosterone-producing adenoma) and bilateral adrenal hyperplasia are the most common causes of primary aldosteronism. The treatment of choice for patients with aldosterone-producing adenoma is unilateral total adrenalectomy. Recurrence after adequate surgery is exceptional. We present a patient with recurrence of an aldosterone-producing adenoma in the right adrenal gland 9 years after adenomectomy of a aldosterone-producing adenoma in the same adrenal gland. We conclude that adenomectomy is not an adequate therapy for patients with adrenal aldosterone-producing adenoma.  (+info)

(5/137) PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11C-metomidate.

The purpose of the study was to evaluate PET with the tracer 11C-metomidate as a method to identify adrenal cortical lesions. METHODS: PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT. All patients subsequently underwent surgery, except 2 who underwent biopsy only. The lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2), and nodular hyperplasia (n = 1). The remaining were noncortical lesions, including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases. RESULTS: All cortical lesions were easily identified because of exceedingly high uptake of 11C-metomidate, whereas the noncortical lesions showed very low uptake. High uptake was also seen in normal adrenal glands and in the stomach. The uptake was intermediate in the liver and low in other abdominal organs. Images obtained immediately after tracer injection displayed high uptake in the renal cortex and spleen. The tracer uptake in the cortical lesions increased throughout the examination. For quantitative evaluation of tracer binding in individual lesions, a model with the splenic radioactivity concentration assigned to represent nonspecific uptake was applied. Values derived with this method, however, did show the same specificity as the simpler standardized uptake value concept, with similar difference observed for cortical versus noncortical lesions. CONCLUSION: PET with 11C-metomidate has the potential to be an attractive method for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from noncortical lesions.  (+info)

(6/137) Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm.

Inhibins are gonadal glycoprotein hormones whose main endocrine function is to inhibit pituitary FSH secretion. In addition to testes and ovaries, other steroid-producing organs are sites of inhibin alpha subunit expression. To study the role of inhibins in human adrenal gland, we screened a panel of 150 adrenals (10 normal adrenals, 25 adrenocortical hyperplasias, 65 adrenocortical adenomas, 30 adrenocortical carcinomas and 20 phaeochromocytomas) for inhibin alpha expression. mRNA levels of inhibin alpha subunit were studied in 57 samples and all tissues were stained immunohistochemically with an inhibin alpha subunit-specific antibody. Inhibin alpha mRNA was detected in all adrenocortical tissues. Virilizing adenomas possessed a 10-fold higher median inhibin alpha mRNA expression than did normal adrenals. Bilaterally and nodularly hyperplastic adrenals and other than virilizing adrenocortical tumours had their median inhibin alpha mRNA levels close to those of normal adrenals. Immunohistochemically, inhibin alpha subunit was detectable in all normal and hyperplastic adrenals, as well as in 73% of the adrenocortical tumours. However, the percentage of inhibin alpha-positive cells varied greatly in different tumour types. The median percentage of positive cells was 10 in non-functional and Conn's adenomas, 30 in Cushing's adenomas and 75 in virilizing adenomas. In malignant adrenocortical tumours the median percentage of inhibin alpha-immunopositive cells was 20 in non-functional carcinomas, 30 in Conn's carcinomas, 65 in Cushing's carcinomas and 75 in virilizing carcinomas. All phaeochromocytomas were negative for inhibin alpha subunit both at the mRNA level and immunohistochemically. Our data show that inhibin alpha subunit is highly expressed in both normal and neoplastic androgen-producing adrenocortical cells, with less expression in cortisol-producing and hardly any in aldosterone-producing cells. This suggests a specific role for inhibins in the regulation of adrenal androgen production. We did not find any significant difference in inhibin alpha expression between benign and malignant adrenocortical tumours. Thus inhibin alpha gene does not seem to have a tumour suppressor role in human adrenal cortex.  (+info)

(7/137) Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors.

OBJECTIVE: To evaluate the roles of the CDKN1C (P57KIP2) gene, which encodes for the cyclin-dependent kinase inhibitor CDNC, and the TP53 tumor suppressor gene in adrenal tumorigenesis, as a means of investigating the molecular basis of sporadic adrenal tumors, which is unknown. DESIGN: Screening for the presence CDKN1C and TP53 mutations and analyzing the expression pattern of CDNC, P53 and its downstream effector CDN1 (P21WAF1/CIP1) in a series of 79 sporadic adrenal tumors. METHODS: Single-strand conformation polymorphism and sequencing were used for mutation analysis of CDKN1C and TP53 in blood and adrenal tissue samples. In a subgroup of 48 tissues, CDKN1C expression was evaluated by RT-PCR and immunohistochemistry. Immunohistochemical analysis of P53 and CDN1 was performed. RESULTS: No somatic mutations of CDKN1C were found in the tumors analyzed, in spite of low/absent CDNC expression in adrenocortical adenomas and carcinomas. Mutations in the TP53 gene were present in 70% of adrenocortical carcinomas, associated with abnormal P53 and CDN1 expression, but not in benign neoplasms. In the normal adrenal cortex, CDNC expression was strictly nuclear and confined to the cortical zone (i.e. zona glomerulosa and reticularis), with no staining in the medulla. CONCLUSIONS: Mutations in the TP53 gene are frequent in adrenocortical carcinomas and might be used as a marker of malignancy. In the normal adrenal cortex, the zone-specific pattern of expression of CDNC suggests a role in adrenal differentiation.  (+info)

(8/137) Localization of the endothelin system in aldosterone-producing adenomas.

Endothelin-1 (ET-1) could play a role in the regulation of aldosterone secretion of the human adrenal gland. The presence of the endothelin-converting enzyme 1 (ECE-1) and ET-1 suggests that there is a local ET system in the adrenal cortex, but the in situ synthesis of ET-1 remains to be confirmed. The cellular distribution of the whole ET system was evaluated in 20 cases of aldosterone-producing adenomas. Polymerase chain reaction studies gave strong signals for ECE-1 mRNA and the mRNAs for endothelin type A (ET(A)) and B (ET(B)) receptors and faint signals for prepro-ET-1 mRNA. In situ hybridization showed ET(A) receptors scattered throughout the adenoma, in both secretory cells and vascular structures (score, +). There were more ET(B) receptors (score, ++), but they were restricted mainly to the endothelium. ECE-1 mRNA and protein were ubiquitous and abundant in secretory cells (score, +++) and vascular structures (score, ++); the enzyme was active on big ET-1. There was no prepro-ET-1 mRNA in the cortex, except in the thickened precapillary arterioles present in only 30% of the aldosterone-producing adenomas studied. ET-1 immunoreactivity was detected in vascular structures (score, +), probably bound to receptors, suggesting that ET-1 has an endocrine action. The low concentrations of ET-1 could also indicate that it acts in a paracrine-autocrine fashion to control adrenal blood flow. The discrepancy between the concentrations of ECE-1 and its substrate suggests that ECE-1 has another role in the adrenal secretory cells. Our data indicate that ET probably is not a primary cause of the development or maintenance of the adenoma.  (+info)