Bilateral co-secretory lesions presenting with coexisting Cushing syndrome and primary aldosteronism: a case report.

BACKGROUND: There is an increasing number of cases of aldosterone- and cortisol-producing adenomas (A/CPAs) reported in the context of primary aldosteronism (PA). Most of these patients have PA complicated with subclinical Cushing's syndrome; cases of apparent Cushing's syndrome (CS) complicated with aldosteronism are less reported. However, Co-secretory tumors were present in the right adrenal gland, a cortisol-secreting adenoma and an aldosterone-producing nodule (APN) were present in the left adrenal gland, and aldosterone-producing micronodules (APMs) were present in both adrenal glands, which has not been reported. Here, we report such a case, offering profound insight into the diversity of clinical and pathological features of this disease. CASE PRESENTATION: The case was a 45-year-old female from the adrenal disease diagnosis and treatment centre in West China Hospital of Sichuan University. The patient presented with hypertension, moon-shaped face, central obesity, fat accumulation on the back of the neck, disappearance of cortisol circadian rhythm, ACTH < 5 ng/L, failed elevated cortisol inhibition by dexamethasone, orthostatic aldosterone/renin activity > 30 (ng/dL)/(ng/mL/h), and plasma aldosterone concentration > 10 ng/dL after saline infusion testing. Based on the above, she was diagnosed with non-ACTH-dependent CS complicated with PA. Adrenal vein sampling showed no lateralization for cortisol and aldosterone secretion in the bilateral adrenal glands. The left adrenocortical adenoma was removed by robot-assisted laparoscopic resection. However, hypertension, fatigue and weight gain were not alleviated after surgery; additionally, purple striae appeared in the lower abdomen, groin area and inner thigh, accompanied by systemic joint pain. One month later, the right adrenocortical adenoma was also removed. CYP11B1 were expressed in the bilateral adrenocortical adenomas, and CYP11B2 was also expressed in the right adrenocortical adenomas. APN existed in the left adrenal gland and APMs in the adrenal cortex adjacent to bilateral adrenocortical adenomas. After another surgery, her serum cortisol and plasma aldosterone returned to normal ranges, except for slightly higher ACTH. CONCLUSIONS: This case suggests that it is necessary to assess the presence of PA, even in CS with apparent symptoms. As patients with CS and PA may have more complicated adrenal lesions, more data are required for diagnosis.

Vitamin D inhibits bone loss in mice with thyrotoxicosis by activating the OPG/RANKL and Wnt/ß-catenin signaling pathways.

Objective: Vitamin D and thyroid hormones have crucial roles in bone metabolism. This study aims to explore the effects of vitamin D on bone metabolism in mice with thyrotoxicosis and its mechanisms. Methods: 12-week-old mice were randomly divided into 6 groups (6 mice/group), the control (CON) group, vitamin D (VD) group, low-dose LT4 (Low LT4) group, low-dose LT4+VD (Low LT4+VD) group, high-dose LT4 (High LT4) group, high-dose LT4+VD (High LT4+VD) group, LT4 was provided every day and vitamin D3 every other day for 12 weeks. Thyroid function, 25-hydroxy vitamin D, type I collagen carboxy-terminal peptide (CTX), and type I procollagen amino-terminal peptide were determined. In addition, microcomputed tomography, bone histology and histomorphometry, a three-point bending test, and the mRNA expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and ß-catenin in bone were conducted. Results: The BMD of lumbar vertebrae and femur decreased and the bone microstructure was destroyed significantly in thyrotoxicosis mice. Addition of vitamin D improved the BMD and bone microstructure only in the low LT4+VD group. Mice with thyrotoxicosis had a significantly higher level of CTX (P<0.05), which was decreased by treatment with vitamin D (P<0.05). The eroded surface per bone surface (Er. S/BS) of the cancellous bone and elongated surface/endocortical perimeter (Er. S/E Pm) of the cortical bone significantly increased in the Low LT4 and High LT4 groups (P<0.05). Treatment with vitamin D significantly decreased the Er. S/BS and Er. S/E Pm. But, treatment with vitamin D did not significantly improve the toughness and rigidity of bones. The ratio of OPG to RANKL and mRNA expression of ß-catenin in the Low LT4+VD group were higher than that in the Low LT4 group (P<0.05). Conclusion: In mice with thyrotoxicosis, treatment with vitamin D can inhibit bone resorption and improve the BMD and trabecular bone architecture by increasing the ratio of OPG to RANKL and upregulating the expression of Wnt/ß-catenin.

Clinical analysis of the serum muscle enzyme spectrum of patients with newly diagnosed Sheehan's syndrome.

We investigated the factors associated with serum muscle enzyme elevation in patients with Sheehan's syndrome. A total of 48 patients who were newly diagnosed with Sheehan's syndrome were included and divided into 3 groups: Group 1, creatine kinase (CK) ≥ 1000 U/L; Group 2, 140 < CK < 1000 U/L; and Group 3, CK ≤ 140 U/L. Differences in serum muscle enzymes, serum electrolytes, blood glucose and hormones were compared among the 3 groups. A Spearman correlation analysis and multiple linear regression analysis were performed on serum muscle enzymes and the other variables. Four patients in Group 1 underwent electromyography. Fourteen, 26 and 8 patients were divided into Group 1, Group 2, and Group 3, respectively. The levels of plasma osmolality, serum sodium, free triiodothyronine (FT3) and free thyroxine (FT4) in Group 1 were lower than those in Group 3 at admission (P < .05). There were significant differences in CK, CK-MB, aspartate aminotransferase, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase among the three groups (P < .05). CK was correlated with serum sodium (r = -0.642, P < .001), serum potassium (r = -0.29, P = .046), plasma osmolality (r = -0.65, P < .001), FT3 (r = -0.363, P = .012), and FT4 (r = -0.450, P = .002). Moreover, creatine kinase isoenzyme-MB (CK-MB) was correlated with serum sodium (r = -0.464, P = .001) and plasma osmolality (r = -0.483, P < .001). The multiple linear regression showed that serum sodium was independently and negatively correlated with CK (r = -0.352, P = .021). The electromyogram results supported the existence of myogenic injury. Sheehan's syndrome is prone to be complicated by nontraumatic rhabdomyolysis, with both a chronic course and acute exacerbation. Serum muscle enzymes should be routinely measured. For patients with CK levels > 1000 U/L, a CK-MB/CK ratio < 6% can be a simple indicator to differentiate rhabdomyolysis from acute myocardial infarction. Abnormal serum muscle enzymes observed in Sheehan's syndrome may be associated with hypothyroidism and with hyponatremia in particular.

Two cases of aldosterone and cortisol producing adenoma with different histopathological features: A case report.

RATIONALE: Primary aldosteronism (PA), including aldosterone and cortisol producing adenoma (A/CPA), is the most common trigger of secondary hypertension. The prevalence of A/CPA may be higher than what we could recognize previously with similar studies, but only a few relevant immunohistochemical reports have confirmed this information. Collecting more clinical features and immunohistochemistry data may help us to understand A/CPA, which is very important for avoiding misdiagnosis and improving outcomes in patients with A/CPA. PATIENT CONCERNS: Both individuals included in this study had hypertension for >10 years. Computed tomography scans revealed the presence of adrenal nodules 1 year ago in patient A and 10 months ago in patient B (based on the date of the final version of this report). The relevant clinical features support PA accompanied by subclinical Cushing syndrome. DIAGNOSIS: Aldosterone and cortisol producing adenoma. INTERVENTIONS: The adrenal adenoma on the affected side was removed and pathological examination and immunohistochemistry were performed. Both the patients received short-term hydrocortisone treatment. OUTCOMES: The blood pressure of both patients improved after surgery. Cytochrome P450 (CYP)11B1, CYP11B2, parathyroid hormone receptor 1 (PTH1R), calcium-sensing receptor (CaSR), and vitamin D3 receptor (VD3R) were all positively expressed, but the histopathological features of the expression region differed. LESSONS: The occurrence of A/CPA may be related to calcium metabolism disorders. For A/CPA, the diversity in immunohistochemistry suggests many uncertainties regarding the pathogenesis of the disease. A/CPA should be considered in new clinical and pathological classifications of PA to gain more attention from the medical community.

Aldosterone/direct renin concentration ratio as a screening test for primary aldosteronism: a systematic review and meta-analysis.

Background: Primary aldosteronism (PA) refers to a spontaneous increase in adrenal aldosterone secretion, and is considered the main cause of secondary hypertension. The main aldosterone screening methods include plasma aldosterone-to-renin ratio (ARR) and plasma aldosterone/direct renin concentration ratio (ADRR). The ARR method has many limitations such as complex operation, several influencing factors, and difficulty in standardization. Relatively speaking, ADRR has gradually attracted attention due to its simple operation, stable results, and easy standardization. However, different research results have suggested that the diagnostic efficacy of ADRR in the screening of primary aldosteronism varies greatly. Meta-analysis may be a way to provide evidence-based medicine. Therefore, it is necessary to conduct a meta-analysis of the diagnostic efficacy of ADRR in primary aldosteronism to clarify the role of ADRR in the screening of PA. Methods: The words "primary aldosteronism", "primary hyperaldosteronism", "aldosterone", "renin concentration", "hypertension" and "screening test" were used as search terms. Literature searches were conducted in the databases of PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. According to the PICOS principles studies exploring the effectiveness of ADRR in screening for PA were included in the analysis. The research data were independently extracted and analyzed by 2 researchers. Quality assessment of diagnostic accuracy studies (QUADAS-2) was used to analyze the risk bias of the included studies. Results: The results showed that 10 studies met the inclusion criteria, with a total of 2,806 subjects. The meta-analysis found that the overall sensitivity and specificity were 0.87 [95% confidence interval (CI): 0.85-0.89], 0.85 (95% CI: 0.83-0.86), respectively. The area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve was 0.9333. The pooled positive likelihood ratio (PLR), pooled negative likelihood ratio (NLR), and pooled diagnostic odds ratio (DOR) were 5.84 (3.67-9.30), 0.16 (0.12-0.22), and 39.82 (22.84-69.44), respectively. Discussion: This study confirmed that ADRR screening for PA has good sensitivity and specificity. Therefore, ADRR can be used to screen for PA. But the risk and problematic control should be considered.

Interactions between nuclear receptors glucocorticoid receptor α and peroxisome proliferator-activated receptor α form a negative feedback loop.

Both nuclear receptors glucocorticoid receptor α (GRα) and peroxisome proliferator-activated receptor α (PPARα) are involved in energy and lipid metabolism, and possess anti-inflammation effects. Previous studies indicate that a regulatory loop may exist between them. In vivo and in vitro studies showed that glucocorticoids stimulate hepatic PPARα expression via GRα at the transcriptional level. This stimulation of PPARα by GRα has physiological relevance and PPARα is involved in many glucocorticoid-induced pathophysiological processes, including gluconeogenesis and ketogenesis during fasting, insulin resistance, hypertension and anti-inflammatory effects. PPARα also synergizes with GRα to promote erythroid progenitor self-renewal. As the feedback, PPARα inhibits glucocorticoid actions at pre-receptor and receptor levels. PPARα decreases glucocorticoid production through inhibiting the expression and activity of type-1 11ß-hydroxysteroid dehydrogenase, which converts inactive glucocorticoids to active glucocorticoids at local tissues, and also down-regulates hepatic GRα expression, thus forming a complete and negative feedback loop. This negative feedback loop sheds light on prospective multi-drug therapeutic treatments in inflammatory diseases through a combination of glucocorticoids and PPARα agonists. This combination may potentially enhance the anti-inflammatory effects while alleviating side effects on glucose and lipid metabolism due to GRα activation. More investigations are needed to clarify the underlying mechanism and the relevant physiological or pathological significance of this regulatory loop.

[Performance Verification of Plasma Renin and Aldosterone Examination with Chemiluminescence Immunoassay and Its Screening Efficacy for Primary Aldosteronism].

OBJECTIVE: To evaluate the performance of chemiluminescence immunoassay (CLIA) in examining renin and aldosterone and to determine its value for screening for primary aldosteronism (PA). METHODS: According to the relevant documents of Clinical and Laboratory Standards Institute (CLSI), we verified the precision, linear range and carryover rate of examining renin and aldosterone with CLIA. The study included 91 suspected PA patients, using two methods, CLIA and radioimmunoassay (RIA), to examine renin and aldosterone levels in order to compare the correlation between the two methods and their value for PA screening. RESULTS: The precision, linear range and carryover rate of examining renin and aldosterone with CLIA met the requirements. In patients with suspected PA, the correlation coefficients of renin, aldosterone and aldosterone-to-renin ratio (ARR) assessed by CLIA and RIA were 0.901, 0.861 and 0.847 respectively (all P<0.001). When the patients were in the upright position and the ARR was 5.636 (ng/dL)/(ng/L), the CLIA method had 79.1% sensitivity and 93.7% specificity for PA screening; when ARR was 14.084 (ng·dL －1)/(ng·[mL·h] －1), the RIA method had 93.0% sensitivity and 83.3% specificity for PA screening. When the patients were in the supine position, and the ARR was 5.640 (ng/dL)/(ng/L), the CLIA method had 97.7% sensitivity and 81.2% specificity for PA screening; when ARR was 33.494 (ng·dL －1)/(ng·[mL·h] －1), RIA had 95.3% sensitivity and 70.8% specificity for PA screening . CONCLUSION: The performance of the CLIA kit in assessing the concentration of renin and aldosterone meets the clinical requirements. Regarding preliminary PA screening, upright-position ARR had higher specificity, but lower sensitivity compared with supine-position ARR.

Catgut Implantation at Acupoint Reduces Immune Reaction in a Rat Model of Allergic Rhinitis.

Allergic rhinitis (AR), an IgE-mediated response, is characterized by a Th2-type immunological pattern together with mast cells activation. Acupuncture, with the use of implanted catgut, is a traditional therapy that has been widely applied for the treatment of AR. However, the exact mechanism of the immunomodulatory effects of catgut implantation at acupoint (CIAA) remains unclear, in part due to the lack of a suitable laboratory animal model. We developed and optimized a rat model of ovalbumin- (OVA-) induced allergic inflammation, characterized by increased IL-4, sIgE, and SP and reciprocal decrease of IFN-γ. In the present study, we have further used this model to address the immunomodulatory effects of CIAA stimulation at Yingxiang (LI20) and Zusanli (ST36) acupoints and to elucidate the mechanisms involved in the regulation of SP, sIgE, IL-4, IFN-γ, TLR2, and TLR4. After AR model was established via OVA challenge, the rats were randomized as follows: control, model, sham-operated, 1-week CIAA (C1), 2-week CIAA (C2), and Budesonide nasal spray. The C1 and C2 groups were subjected to the bilateral acupoint Yingxiang (LI20) and Zusanli (ST36), respectively. Multiple analyses and quantifications were performed, which revealed that due to the persistent stimulus to acupoints by embedding catgut, the C2 group improved AR symptoms, compared to the C1 group. We conclude that CIAA at the Yingxiang (LI20) and Zusanli (ST36) acupoints effectively reduces allergic symptoms and inflammatory parameters in the rat model of AR. Thus, CIAA treatment is potentially an alternative therapeutic modality in AR.