The Latest Developments of Functional Molecular Imaging in the Diagnosis of Primary Aldosteronism.

Differentiation of unilateral from bilateral aldosterone hypersecretion is the essential step in the clinical practice of primary aldosteronism (PA). Although adrenal venous sampling (AVS) has been established as the most standard test recommended by the guideline, its invasive and technically difficult nature has facilitated the approach to develop non-invasive functioning imaging as an alternative test. Compared to the conventional adrenocortical scintigraphy with cholesterol derivatives as tracer, the first-generation imaging, both of 11C-MTO/PET and 123I-IMTO/SPECT/CT, the second-generation imaging, bind with high specificity and affinity to CYP11B enzymes and have advantages in shortening the time for obtaining specific images, reducing the radiation exposure to the patient, and resolution of the images. Because of very short half-life of 11C-MTO, 123I-IMTO has a potential for a wider application than 11C-MTO. Sensitivity of identifying an adenoma smaller than 1 cm in diameter is still a common limitation of these new functional imaging methods. The new functional imaging could be supplementary to AVS in lateralization of PA when the results of AVS are not conclusive. To be a substitute for AVS, however, it should fulfill various conditions including high selectivity and binding affinity to CYP11B2, high sensitivity in detecting small adenoma, high resolution image, reduction of radiation exposure, and general versatility. Considering the potential number of patients, cost-effectiveness of the subtype testing in the clinical practice of PA could be one of the issues of the medical expenses. Thus, development of a new non-invasive functional imaging will have a significant impact on the clinical practice of PA and hypertension.

Activation of AMP-activated protein kinase protects against homocysteine-induced apoptosis of osteocytic MLO-Y4 cells by regulating the expressions of NADPH oxidase 1 (Nox1) and Nox2.

BACKGROUND: Elevated plasma homocysteine (Hcy) level is associated with the risk of osteoporotic fracture. While Hcy increases oxidative stress, AMP-activated protein kinase (AMPK) activation ameliorates it. This study aimed to investigate whether Hcy induces apoptosis of osteocytic MLO-Y4 cells through regulating expressions of oxidant and anti-oxidant enzymes and determine the effects of AMPK activation by 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) and metformin on the Hcy-induced apoptosis of the cells. RESULTS: DNA fragment ELISA and TUNEL staining assays showed that Hcy treatments (0.1-5.0 mM) induced apoptosis of MLO-Y4 cells in a dose-dependent manner. The detrimental effect of Hcy was partly but significantly reversed by an antioxidant (N-acetylcysteine) and NADPH oxidase (Nox) inhibitors (apocynin and diphenyleneiodonium). In addition, treatment with AICAR (0.05-0.1 mM) and metformin (10-100 µM) ameliorated Hcy-induced apoptosis of the cells. The favorable effect of metformin on Hcy-induced apoptosis was completely canceled by an AMPK inhibitor Ara-A. Hcy increased the expression levels of Nox1 and Nox2, while it had no effects on the expressions of Nox4 or the anti-oxidant enzymes, superoxide dismutase 1 and 2. Hcy-induced increases in the expressions of Nox1 and Nox2 decreased significantly by treatments with AICAR. CONCLUSION: These findings suggest that Hcy induces apoptosis of osteocytes by increasing the expressions of Nox1 and Nox2, and AMPK activation by AICAR and metformin effectively prevents the detrimental reactions. Thus, AMPK activation may be a potent therapeutic candidate for preventing Hcy-induced osteocyte apoptosis and the resulting bone fragility.

Hypercalcemic crisis due to primary hyperparathyroidism occurring concomitantly with Graves' disease.

We herein describe a case of hypercalcemic crisis in a 52-year-old Japanese woman. She suffered from thirst and fatigue for one month. Her serum calcium (a) levels were 19.0 mg/dL, and she was diagnosed with hypercalcemic crisis. Circulating levels of parathyroid and thyroid hormones were elevated. She was diagnosed with primary hyperparathyroidism accompanied by Graves' disease. Thyroparathyroidectomy was performed after circulating levels of Ca and thyroid hormones were normalized. Both of primary hyperparathyroidism and Graves' disease can contribute and accelerate hypercalcemia, resulting in a state of crisis. The possibility of their coexistence should therefore be taken into consideration in cases of hypercalcemia.