ASSOCIATION OF PERIPHERAL 5-HYDROXYINDOLE-3-ACETIC ACID, A SEROTONIN DERIVATIVE, WITH METABOLIC SYNDROME AND LOW-GRADE INFLAMMATION.

OBJECTIVE: The constellation of metabolic abnormalities seen in metabolic syndrome (MetS) has been linked to atherosclerosis and adverse cardiovascular outcomes due to heightened inflammation. Accumulating evidence suggests that peripheral 5-hydroxyindole-3-acetic acid (5-HIAA), the derivative end-product of serotonin (5-HT), might be involved in the pathogenesis of obesity, and abnormal lipid and glucose metabolism. We examined the association between serum 5-HIAA concentrations and MetS and also highly sensitive C-reactive protein (hsCRP). METHODS: We assessed 180 healthy adults (110 males and 70 females) in a cross-sectional setting. Anthropometric indices and blood pressure were measured, as were laboratory parameters including fasting 5-HIAA concentrations. The associations between 5-HIAA and individual components of MetS, as well as MetS as a single entity, were investigated with bivariate correlation and logistic regression analyses. RESULTS: Eighty-nine individuals (49.4%) were diagnosed with MetS. Significant correlations were found between 5-HIAA concentrations and age (r = 0.184), waist circumference (r = 0.415), high-density lipoprotein (HDL) cholesterol (r = -0.148), systolic blood pressure (r = 0.374), diastolic blood pressure (r = 0.355), homeostasis model assessment of insulin resistance (r = 0.201), and hsCRP (r = 0.453) were found (P<.05 in all tests). In logistic regression, 5-HIAA was significantly associated with 4 MetS components including central obesity, raised triglycerides, raised blood pressure, and raised fasting plasma glucose (FPG) (P<.05). Moreover, 5-HIAA was a predictor of MetS as a single entity, and the relationship persisted after adjusting for hsCRP (odds ratio [OR] = 4.41, 95% confidence interval [CI]: 2.58-7.67, P<.001). CONCLUSION: Elevated concentrations of 5-HIAA are seen in individuals with MetS. Increased 5-HIAA is also associated with hsCRP, a marker of chronic low-grade inflammation underlying MetS.

Severe hypercalcemia due to metastatic pancreatic neuroendocrine tumor: a case report.

BACKGROUND: Hypercalcemia of malignancy, as a paraneoplastic syndrome, is the most common metabolic disorder that accounts for 30% of malignancies and usually has a poor prognosis. Neuroendocrine tumors are uncommon and arise from neuroendocrine cells throughout the body. Actually, paraneoplastic hypercalcemia in neuroendocrine tumors is unusual and mostly associated with parathyroid hormone-related protein (PTHrP) secretion. CASE PRESENTATION: We report a 51-year-old Iranian man who presented with nausea, vomiting, and significant weight loss for 1 month. Laboratory data revealed calcium of 26 mg/dl, accompanied by low level of PTH. Octreotide scan revealed a large donut-shaped octreotide avid lesion in the epigastric region at the right side of the mid-abdomen, with multiple varying size foci of abnormally increased radiotracer uptake in the epigastric region and both lobes of the liver. Endoscopic ultrasonography demonstrated a large heterogeneous mass lesion with irregular outline and good demarcation in the body of the pancreas with diffuse foci of calcification. Percutaneous biopsy of the liver mass demonstrated a well-differentiated neuroendocrine tumor (low grade) confirmed by immunohistochemistry with strongly positive chromogranin and synaptophysin stain. Hypercalcemia was treated with hydration, few sessions of hemodialysis, calcitonin, and denosumab injection. However, the patient developed symptomatic hypocalcemia. Oncology consultation led to prescription of long-acting octreotide 30 mg monthly and everolimus daily. CONCLUSION: Pancreatic neuroendocrine tumor could lead to malignant hypercalcemia; secretion of PTHrP is the most common cause, and signs and symptoms are usually milder than paraneoplastic syndrome due to hematologic and solid tumor. Generally, survival is better; however, its treatment is challenging, and primary debulking surgery is often required. A team approach to management is important at all points.

Systemic Kikuchi-Fujimoto disease bordering lupus lymphadenitis: A fresh look?

A 31-year old woman with persistent fever for 6 weeks and unresponsive to antibiotic therapy came for rheumatologic investigation. After computed tomography (CT) studies of her neck, thorax and abdomen revealed bilateral cervical, axillary and retroperitoneal lymph node enlargements, histopathologic evaluation of the resected nodes showed features of histiocytic necrotizing lymphadenopathy suggestive of Kikuchi-Fujimoto's lymphadenopathy. Kikuchi-Fujimoto Disease (KFD) involving the retroperitoneal nodes is extremely unusual and even more challenging to diagnose when there are no early signs of extranodal involvement or abdominopelvic pain. We present a case of systemic KFD involving the cervical, axillary and retroperitoneal lymph nodes and emphasize the clinical interest to properly differentiate between the benign condition of KFD that requires no more than minimal to low dosage steroid therapy and the potentially life-threatening lupus lymphadenitis that mandates intensive immunosuppressive treatment.

Evaluation of plasma MMP-8, MMP-9 and TIMP-1 identifies candidate cardiometabolic risk marker in metabolic syndrome: results from double-blinded nested case-control study.

AIMS: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are dysregulated in metabolic syndrome (MetS) and associated with atherosclerosis and cardiovascular disease (CVD). Previous studies on the association between MMPs/TIMPs and MetS are controversial. We aimed to evaluate circulating MMP-8, MMP-9 and TIMP-1 in a group of MetS individuals and healthy controls to find the potential marker associated with MetS and its components. METHODS: 243 MetS individuals participated in a nested case-control design, of whom 63 were excluded (study subjects for analysis n=180; 87 MetS cases, 93 controls). We employed the International Diabetes Federation criteria using national waist circumference cutoffs for case definition. Anthropometric and biochemical measurements were done using standard methods. RESULTS: Plasma MMP-8, TIMP-1, tumor necrosis factor-alpha (TNF-α), highly sensitive C-reactive protein (hs-CRP) and MMP-8/TIMP-1 ratio were significantly higher in MetS cases (P for all < 0.05). Each component of MetS except raised fasting plasma glucose positively correlated with MMP-8 and numbers of MetS components increased with higher MMP-8. In all regression models, MMP-8 was a significant predictor of MetS and in the final model the relationship persisted even after adjusting for pro-inflammatory cytokines hs-CRP and TNF-α (odds ratio=6.008, 95% confidence interval: 1.612-22.389, P=0.008). CONCLUSION: Strong associations of MMP-8 with components of MetS in univariate, bivariate and multivariate models suggest plasma MMP-8 as a potential cardiometabolic risk marker for MetS. Higher MMP-8 in MetS is possibly mediated through mechanisms both dependent and independent of chronic low grade inflammation.

Hypoadrenal syndrome in a patient with amyloidosis secondary to familial Mediterranean fever.

Amyloidosis is a common complication of poorly controlled familial Mediterranean fever (FMF). A variety of organs including kidneys, heart, liver, thyroid and adrenal glands may be clinically affected. However, involvement of adrenal glands leading to significant inefficiency is rarely seen in FMF patients with amyloidosis. The impairment of neuroendocrine immune system in FMF together with proteinuria in renal amyloidosis is a challenge while interpreting adrenal function tests. Here we present a case report of a 42-year-old man with FMF and renal failure due to amyloidosis whose disease course was complicated by adrenal insufficiency.