Secondary osteoporosis resulting from specific clinical disorders may be potentially reversible, and thus continuous efforts to find and adequately treat the secondary causes of skeletal fragility are critical to ameliorate fracture risk and to avoid unnecessary treatment with anti-osteoporotic drugs. Among the hyperfunctional adrenal masses, Cushing's syndrome, pheochromocytoma, and primary aldosteronism are receiving particularly great attention due to their high morbidity and mortality mainly by increasing cardiovascular risk. Interestingly, there is accumulating experimental and clinical evidence that adrenal hormones may have direct detrimental effects on bone metabolism as well. Thus, the present review discusses the possibility of adrenal disorders, especially focusing on pheochromocytoma and primary aldosteronism, as secondary causes of osteoporosis.
Cushing Syndrome ; Hyperaldosteronism ; Metabolism ; Mortality ; Osteoporosis ; Pheochromocytoma

OBJECTIVETo compare the incidence of metabolic disorders (MS) in patients with primary aldosteronism (PA) and essential hypertension (EH).

METHODSMS prevalence was observed in 200 EH patients (male 104) and 220 PA patients (male 117) hospitalized to our hospital from August 2005 to March 2007.

RESULTS(1) The prevalence of MS in PA group was significantly higher than that of EH group (47.3% vs. 31.5%, P = 0.009). (2) Blood pressure was significantly higher in PA group than that of EH [SBP: (150.67 +/- 15.45) mm Hg vs. (145.69 +/- 17.13) mm Hg, P = 0.042; DBP: (93.03 +/- 10.51) mm Hg vs. (85.83 +/- 14.44) mm Hg, P = 0.037]. (3) Incidences of abdominal obesity (86.8% vs. 78.5%, P = 0.024) and insulin resistance (insulin sensitivity index: 42.42 +/- 16.11 vs. 49.58 +/- 22.43, P = 0.008) were significantly higher in PA group than in EH group.

CONCLUSIONThe prevalence of MS in hospitalized PA patients was significantly higher than that of EH patients characterized by prevalent abdominal obesity, insulin resistant and severe hypertension.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Hyperaldosteronism ; epidemiology ; metabolism ; Hypertension ; epidemiology ; metabolism ; Incidence ; Male ; Metabolic Syndrome ; epidemiology ; Middle Aged

BACKGROUND: Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA. METHODS: Forty-two patients (mean age 48.8±10.9 years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins. RESULTS: The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was 8.9±0.3 mg/dL (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ρ=−0.424, P=0.031). Moreover, multivariable regression analysis showed that the corrected calcium level was marginally associated with the LVEDD and corrected QT (QTc) interval (β=−0.366, P=0.068 and β=−0.252, P=0.070, respectively). CONCLUSION: Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively.
Adenoma ; Aldosterone ; Calcium* ; Heart Diseases ; Homeostasis ; Humans ; Hyperaldosteronism* ; Hypercalciuria ; Hyperplasia ; Hypocalcemia ; Metabolism* ; Parathyroid Hormone ; Plasma ; Prevalence ; Renin ; Veins

OBJECTIVETo compare plasma concentrations of biomarkers of endothelial dysfunction between patients with primary aldosteronism (PA) and essential hypertension (EH), and to determine whether elevated levels of these biomarkers could predict development of early organ damage.

METHODSThirty-six PA patients and 39 EH patients matched for age, sex, blood pressure and duration of hypertension were included in this study. Plasma levels of biomarkers reflecting endothelial dysfunction (von Willebrand factor, vWF; soluble intercellular adhesion molecule 1, sICAM-1; and oxidized low density lipoprotein, ox-LDL) were detected and compared between PA and EH patients. Left ventricular mass index (LVMI) determined by echocardiography, 24-hour urinary protein quantitative determination and urinary albumin excretion rate (UAER) were analyzed to evaluate early organ damage. Left ventricular hypertrophy was defined as LVMI > 125 g/m(2) in men and > 120 g/m(2) in women, and UAER between 20 µg/min and 200 µg/min was defined as microalbuminuria.

RESULTSvWF [(122.3 ± 53.8)% vs. (113.1 ± 68.3)%], sICAM-1 [(401.0 ± 74.1) µg/L vs. (300.9 ± 87.0) µg/L], ox-LDL [(13.6 ± 10.0) U/L vs. (8.1 ± 5.9) U/L], LVMI [(124.7 ± 33.6) g/m(2) vs. (109.1 ± 25.7) g/m(2)], 24-hour urinary protein quantitation [24 h UPQ, (0.17 ± 0.10) g vs. (0.09 ± 0.04) g] and UAER [(25.9 ± 7.7) µg/min vs. (9.7 ± 5.9) µg/min] were significantly higher in PA group than in EH group (all P < 0.05). Elevated plasma vWF, sICAM-1 levels and plasma aldosterone concentration independently predicted microalbuminuria. Whereas, elevated plasma vWF and ox-LDL levels, plasma aldosterone concentration and systolic blood pressure independently predicted left ventricular hypertrophy.

CONCLUSIONPatients with PA have severer endothelial dysfunction reflected by multiple biomarkers and earlier organ damage than patients with EH, and plasma aldosterone concentration and multiple endothelial dysfunction biomarkers could independently predict early organ damage.

Albuminuria ; Biomarkers ; metabolism ; Female ; Humans ; Hyperaldosteronism ; metabolism ; pathology ; physiopathology ; Hypertension ; metabolism ; pathology ; physiopathology ; Lipoproteins, LDL ; blood ; Male ; Middle Aged ; von Willebrand Factor ; metabolism

No abstract available.
Adrenal Cortex Neoplasms/diagnosis/*metabolism/surgery ; Adrenalectomy ; Adrenocortical Adenoma/diagnosis/*metabolism/surgery ; Adult ; Aldosterone/*biosynthesis ; Cushing Syndrome/diagnosis ; Female ; Humans ; Hydrocortisone/*biosynthesis ; Hyperaldosteronism/metabolism

BACKGROUNDHypertension often persists after adrenalectomy for primary aldosteronism (PA). Many studies have analyzed the outcomes of adrenalectomy for aldosterone-producing adenomas (APA) to identify predictive factors for persistent hypertension. However, differentially expressed genes in persistent postoperative hypertension remain unknown. Our aim was to describe gene expression profile of persistent postoperative hypertension patients with APA.

METHODSIn this study, we described and compared gene expression profiles in persistent postoperative hypertension and postoperative normotension in Chinese patients with APA using microarray analysis. Confirmation was performed with quantitative real time-polymerase chain reaction analysis. Bioinformatic analysis (gene ontology analysis, pathway analysis and network analysis) was used for further research.

RESULTSMicroarray analysis identified a total of 99 differentially expressed genes, including 18 up-regulated and 81 down-regulated genes. Among the dysregulated genes were fat atypical cadherin 1 as well as fatty acid binding protein 4 and other genes that have not been previously studied in persistent postoperative hypertension with APA. Bioinformatics analysis indicated that differentially expressed genes were associated with lipid metabolic process, metal ion binding, and cell differentiation. Pathway analysis determined that five pathways corresponded to the dysregulated transcripts. The mRNAs-ncRNAs co-expression network was composed of 49 network nodes and 72 connections between 18 coding genes and 31 noncoding genes.

CONCLUSIONSThis study revealed differentially expressed genes in persistent postoperative hypertension with APA and provided a resource of candidate genes for exploration of possible drug targets and prognostic markers.

Adenoma ; metabolism ; physiopathology ; surgery ; Adrenalectomy ; Aldosterone ; metabolism ; Blood Pressure ; physiology ; Gene Expression Profiling ; methods ; Humans ; Hyperaldosteronism ; metabolism ; physiopathology ; surgery ; Postoperative Complications ; Retrospective Studies

OBJECTIVETo investigate the effect of potassium deficiency on glucose and insulin metabolism in primary hyperaldosteronism, including aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA).

METHODSTotally 178 patients who were diagnosed as primary hyperaldosteronism (103 patients with APA and 75 with IHA) were divided into hypokalemia group and normal potassium group according to their serum potassium levels. All patients received 3 hours of oral glucose tolerance test and aldosterone test to observe the relationship among glucose, insulin and serum potassium.

RESULTSArea under curve of serum potassium, area under curve of plasma insulin, and fasting serum insulin were significantly lower in the hypokalemia group than in the normal potassium group (P <0. 05, P <0. 01); area under curve of glucose and aldosterone level were significantly higher in the hypokalemia group than in the normal potassium group ( P < 0. 05 ) . The prevalence of metabolic syndrome was significantly higher in IHA than in APA (57. 3% vs 38. 8% ; P < 0. 05).

CONCLUSIONHypokalemia may play an important role in inhibiting insulin secretion in primary hyperaldosteronism.

Adult ; Blood Glucose ; metabolism ; Female ; Glucose Tolerance Test ; Humans ; Hyperaldosteronism ; complications ; metabolism ; Hypokalemia ; complications ; Insulin ; metabolism ; Male ; Metabolic Syndrome ; etiology ; Middle Aged

The coexistence of myelolipoma within adrenal cortical adenoma is extremely rare, for both tumors present usually as separate entities. There are only 16 such cases reported worldwide. To the best of our knowledge, the case we reported here is the first one of myxoid adrenal cortical adenoma associated with myelolipoma reported. A 32-year-old Chinese woman with 4-year history of hypertension was presented in our study. Computed tomography (CT) of the abdomen showed a large heterogeneously-enhancing mass (4.5 cm in diameter) in the left suprarenal region. Clinical history and laboratory results suggest a metabolic disorder as Conn's syndrome. The patient underwent a left adrenalectomy, and a histopathological study confirmed the mass to be a myxoid adrenal cortical adenoma containing myelolipoma. The patient was postoperatively well and discharged uneventfully. In the present case report, we also discuss the etiology of simultaneous myelolipoma and adrenal adenoma associated with Conn's syndrome, and the methods of the diagnosis and differential diagnosis.
Adrenal Cortex Neoplasms ; complications ; diagnosis ; pathology ; Adrenocortical Adenoma ; complications ; diagnosis ; pathology ; Adult ; Biomarkers, Tumor ; metabolism ; Female ; Humans ; Hyperaldosteronism ; complications ; Inhibins ; metabolism ; Myelolipoma ; complications ; diagnosis ; pathology ; Neoplasms, Multiple Primary ; complications ; diagnosis ; pathology ; Synaptophysin ; metabolism ; Tomography, X-Ray Computed ; Vimentin ; metabolism

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant inheritable form of hyperaldosteronism with early onset hypertension. GRA is caused by unequal crossing-over of the steroid 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. As a result of chimeric gene duplication, aldosterone is ectopically synthesized in the adrenal zona fasciculata under the control of adrenocorticotropin. Here, we describe three cases of GRA in a Korean family. The proband-a 21-yr-old female-was incidentally found to have high blood pressure (170/108 mmHg). Her 46-yr-old father had been treated twice for cerebral hemorrhage at the ages of 29 and 39 yr. Her 15-yr-old brother had a 2-yr history of hypertension; however, he was never treated. Their laboratory test results showed normokalemia, hyporeninemia, hyperaldosteronism, and a high plasma aldosterone concentration-to-plasma renin activity ratio. Normal saline loading failed to suppress aldosterone secretion. However, dexamethasone administration effectively suppressed their plasma aldosterone concentrations. Following genetic analyses with PCR and direct sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located between intron 2 of CYP11B1 and exon 3 of CYP11B2.
Adolescent ; Aldosterone/blood ; Aldosterone Synthase/*genetics ; Asian Continental Ancestry Group/*genetics ; Dexamethasone/therapeutic use ; Family ; Female ; Glucocorticoids/*therapeutic use ; Humans ; Hyperaldosteronism/diagnosis/drug therapy/*genetics ; Hypertension/etiology ; Magnetic Resonance Angiography ; Male ; Middle Aged ; Renin/blood/metabolism ; Republic of Korea ; Sequence Analysis, DNA ; Steroid 11-beta-Hydroxylase/*genetics ; Young Adult

Multiple endocrine neoplasia type 1 (MEN1) syndrome includes varying combinations of endocrine and non-endocrine tumors. There are also a considerable number of atypical MEN1 syndrome. In this case, a 68-yr-old woman was referred to the Department of Endocrinology for hypercalcemia. Five years ago, she had diagnosed as primary hyperaldosteronism and now newly diagnosed as parathyroid hyperplasia with laboratory and pathologic findings. Hurthle-cell thyroid cancer was also resected during the parathyroid exploration and small meningioma was found on brain MRI. Her general condition has markedly improved and her adrenal mass and meningioma are being closely observed now. We could find the loss of heterozygosity of the MEN1 locus in parathyroid glands, suggesting a MEN1-related tumor, but not a germline mutation. Considering a variety of phenotypic expression and a limitation of current molecular analysis, periodic follow up will be needed in patients with a MEN1-like phenotype.
Aged ; Base Sequence ; Brain/radionuclide imaging ; Female ; Humans ; Hyperaldosteronism/complications/*diagnosis ; Hyperparathyroidism, Primary/*diagnosis/etiology/pathology ; Loss of Heterozygosity ; Magnetic Resonance Imaging ; Meningeal Neoplasms/complications/*diagnosis/radionuclide imaging ; Meningioma/complications/*diagnosis/radionuclide imaging ; Mutation ; Parathyroid Glands/pathology ; Proto-Oncogene Proteins/genetics/metabolism ; Sequence Analysis, DNA ; Thyroid Neoplasms/complications/*diagnosis/pathology ; Tomography, X-Ray Computed