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)
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)
BACKGROUND: Androgen secreting adrenocortical tumours are rare in children and the determination of their malignant potential can be difficult. OBJECTIVES: To assess the presentation, histology, and clinical behaviour of these tumours. SETTING: Two tertiary referral centres. STUDY DESIGN: Retrospective analysis of children diagnosed with an androgen secreting adrenocortical tumour between 1976 and 1996. PATIENTS: Twenty three girls and seven boys aged 0-14 years. RESULTS: Pubic hair was observed in all children, clitoromegaly or growth of the phallus in 23 children, acceleration of linear growth in 22 children, and advanced bone age (> 1.5 years) in 18 children. Hypersecretion of androgens was detected by assessment of serum androgen concentrations alone in four patients and by 24 hour urine steroid excretion profiles in 22 patients. All 16 tumours measuring < 5 cm in diameter were benign. Of the tumours measuring 5-9 cm, three were malignant and seven were benign, whereas all four tumours > 10 cm were malignant. Histological slides were available for reassessment in 25 children. Although mitoses and necrosis were more characteristic of tumours with malignant behaviour, no exclusive histological features of malignancy were seen. CONCLUSION: Histological criteria for malignancy are not reliable, whereas tumour size is important in assessing malignant potential. (+info)
The histopathology and ultrastructural features of an adrenocortical oncocytoma are reported. The tumour was discovered incidentally during investigation for hypertension in a 72 year old female. Oncocytic tumours of the adrenal cortex are rare, with only 20 examples described in English language reports. Most have been non-functioning and benign, like the present example. Molecular studies may help assess the significance of oncocytic change in the pathogenesis and behaviour of oncocytic neoplasms. (+info)
Cloning of a novel kinase (SIK) of the SNF1/AMPK family from high salt diet-treated rat adrenal.
PCR-coupled cDNA subtraction hybridization was adapted to identify the genes expressed in the adrenocortical tissues from high salt diet-treated rat. A novel cDNA clone, termed salt-inducible kinase (SIK), encoding a polypeptide (776 amino acids) with significant similarity to protein serine/ threonine kinases in the SNF1/AMPK family was isolated. An in vitro kinase assay demonstrated that SIK protein had autophosphorylation activity. Northern blot revealed that SIK mRNA levels were markedly augmented by ACTH treatment both in rat adrenal glands and in Y1 cells. SIK may play an important role in the regulation of adrenocortical functions in response to high plasma salt and ACTH stimulation. (+info)
Autocrine role of IGF-II in proliferation of human adrenocortical carcinoma NCI H295R cell line.
In adrenocortical tumors, the malignant phenotype is associated with rearrangements (paternal isodisomy) at the 11p15 locus and IGF-II gene overexpression, strongly suggesting that the IGF system is a major determinant of adrenocortical tumor progression. The aim of this study was to validate an in vitro model for investigating the involvement of the IGF system in adrenocortical tumorigenesis. We analyzed the production of IGF mRNA and proteins, IGF-binding proteins (IGFBPs) and IGF receptors by the NCI H295R cell line, which is derived from a human adult adrenocortical carcinoma. H295R cells were shown to proliferate for a long period (26 days) in the absence of serum or any added growth factor. Northern blot analyses showed high IGF-II mRNA contents in H295R cells. The cells secreted large amounts of IGF-II protein (14 ng/10(6) cells per 48 h) although no IGF-I protein was detected. Western ligand blot analyses of conditioned media detected the presence of large amounts of a 34 kDa protein, which was identified as IGFBP-2 by immunoblotting. The presence of high-affinity binding sites for IGF-I and IGF-II on H295R cells was shown by binding experiments using radiolabeled IGFs and confirmed by reverse transcription PCR analyses showing type 1 and type 2 IGF receptors. Proliferation of H295R cells was inhibited by anti-IGF-II antibody (45%) and by anti-type 1 IGF receptor antibody (53%) indicating that IGF-II is an autocrine growth factor for these cells and that its effects are, at least in part, mediated by the type 1 IGF receptor. These findings confirm the involvement of the IGF system in adrenocortical tumors and suggest that the H295R cell line is a suitable in vitro model for studying the molecular mechanisms of adrenocortical tumor proliferation. (+info)
Evidence for a potential role for HDL as an important source of cholesterol in human adrenocortical tumors via the CLA-1 pathway.
CLA-1, a human homologue of rodent scavenger receptor class B1 (SR-B1), has been identified as a receptor for high density lipoprotein (HDL) and is highly expressed in the adrenal gland. Several studies have indicated that HDL might be a source of cholesterol for steroidogenesis in the adrenal gland. In this study, we show that ACTH and its second messenger cAMP stimulated CLA-1 protein expression in a human adrenocortical cell line. We also determined whether CLA-1 plays an important role in steroidogenesis by investigating CLA-1 expression levels in various adrenal tumors including the adenomas of Cushing's and Conn's syndrome. Western blot analysis showed that CLA-1 expression was much higher in the tumors of Cushing's syndrome than in non-tumor lesions of Conn's syndrome and pheochromocytoma. We were able to detect a strong CLA-1 signal in tumors of Conn's syndrome, too. On the other hand, much less CLA-1 expression was detected in Cushing's adenoma adjacent adrenal glands. The immunohistochemical analysis showed that CLA-1 was expressed in the outer region of the adrenal cortex mainly in plasma membranes of the cortical cells but not in the medulla. These findings demonstrated for the first time that ACTH increased CLA-1 protein in cultured human adrenocortical cells, and that cortisol- and aldosterone-secreting adenomas had high CLA-1 proteins in their cell surfaces. (+info)
A patient with preclinical Cushing's syndrome and excessive DHEA-S secretion having unilateral adrenal carcinoma and contralateral adenoma.
We report a case of preclinical Cushing's syndrome in a 54-year-old male associated with bilateral adrenocortical tumours. Physical findings and general laboratory data were unremarkable except for mild hypertension (158/90 mmHg) and impaired glucose tolerance. Endocrinological evaluation revealed the presence of autonomous cortisol secretion including unsuppressible serum cortisol by 8 mg dexamethasone test (11 microg/dl), high serum DHEA-S (3580 ng/ml, normal: 400-3500) and increased urinary 17-KS excretion (31.0-35.8 mg/day, normal: 5.8-21.3). CT scan demonstrated the presence of tumours in both adrenals and bilateral adrenalectomy was subsequently performed. Histological examination of the resected specimens revealed an adrenocortical carcinoma on the right side and an adenoma on the left side with noticeable cortical atrophy in non-neoplastic adrenals. Immunohistochemical study of steroidogenic enzymes demonstrated that all the steroidogenic enzymes involved in cortisol biosynthesis were expressed in both right and left adrenal tumours. Enzymatic activities of 21, 17alpha, 18, 11beta-hydroxylases were detected in both right and left adrenals except for the absence of 11beta-hydroxylase activity in the left adrenal adenoma. Results of in vitro tissue steroidogenesis examined in short-term tissue culture of the specimens revealed no significant differences between carcinoma and adenoma in cortisol production, but the production of adrenal androgens in carcinoma was significantly higher than that in adenoma, which may indicate the importance of evaluating adrenal androgen levels in patients with adrenocortical neoplasms. (+info)