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    Is vitamin D supplementation a new hope for the therapy of the septic shock?
    (2013) Yilmaz, Hakki; Şahiner, Enes Seyda; Darçın, Tahir; Çelik, Hüseyin Tuğrul; Bilgiç, Mukadder Ayşe; Akçay, Ali T.
    Vitamin D is mainly known for its traditional role in the bone mineralization and calcium homeostasis. Recent studies have shown that vitamin D receptors (VDR) are present in almost all the tissues and cells in the human body. In addition, several studies have revealed that vitamin D is important in immunomodulation, regulation of inflammation and cytokines, cell proliferation, cell differentiation, apoptosis, angiogenesis, muscle strength, and muscle contraction. Patients with sepsis have high mortality rate and high deficiency in vitamin D. In addition, septic patients have decreased vitamin D binding-protein (DBP) levels which further exacerbate the vitamin D deficiency. The role of vitamin D treatment in sepsis syndrome has been evaluated in animal model of sepsis where 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] administration was associated with improved blood coagulation parameters in sepsis associated with a disseminated intravascular coagulation. Vitamin D treatment in vitro has also been demonstrated to modulate levels of the systemic inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-?) and interleukin 6 (IL-6), as well as inhibit the lipopolysaccharide (LPS)-induced activation and vasodilation of vascular endothelium. Vitamin D may enhance the induction of the antimicrobial peptides, cathelicidin and b-defensin, which have been described on mucosal and epithelial surfaces acting as the body's first line of defense against viral and bacterial pathogens. Vitamin D supplementation may divert attention from relatively simple, natural, and low-costmethods of preventing severe sepsis and septic shock. Further prospective, randomized and controlled clinical trials of adjunctive vitamin D therapy in patients who are vitamin D deficient are needed in the management of human sepsis syndrome. © 2014 Elsevier B.V., All rights reserved.; MEDLINE® is the source for the MeSH terms of this document.
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    Subclinical hypothyroidism in combination with vitamin D deficiency increases the risk of impaired left ventricular diastolic function
    (Institute of Experimental Endocrinology peter.golla@degruyter.com, 2015) Yilmaz, Hakki; Çakmak, Muzaffer; Darçın, Tahir; Inan, Osman; Gürel, Özgül Malçok; Bilgiç, Mukadder Ayşe; Bavbek, Nüket
    Objective. Subclinical hypothyroidism and vitamin D deficiency are common. The diastolic function of patients with both subclinical hypothyroidism and vitamin D deficiency remains unknown. This study aimed to investigate diastolic dysfunction in patients with both subclinical hypothyroidism and vitamin D deficiency. Subjects and Methods. This study included 254 patients. All patients underwent standard Doppler echocardiography. Patients who had risk factors for diastolic dysfunction or had used L-thyroxine and vitamin D within the previous 3 months were excluded. Vitamin D deficiency was defined as a 25-OH-vitamin D level lower than 20 ng/ml, and vitamin D sufficiency was defined as a 25-OHvitamin D level ?30 ng/ml. Subclinical hypothyroidism was defined as a TSH level of 4.5-10 mU/l when the free T4 concentration was normal. Results. The patients were divided into 4 groups. Group 1 (n=71) included patients with subclinical hypothyroidism and vitamin D deficiency; Group 2 (n=66) included patients with subclinical hypothyroidism and vitamin D sufficiency; Group 3 (n=65) included euthyroid patients with vitamin D deficiency; and Group 4 (n=52) included euthyroid patients with vitamin D sufficiency. LAVI (31.3±3.2, 28.7±3.0, 28.4±3.4, and 27.9±3.9; p<0.001) and E/E’ values (11.2±2.7, 8.9±2.7, 9.1±2.9, 8.8±2.5; p<0.001) were significantly higher in Group 1 than in Groups 2, 3 and 4. E’ values were significantly lower in Group 1 than in Groups 2, 3 and 4. Conclusion. The coexistence of subclinical hypothyroidism with vitamin D deficiency can lead to further deterioration in the LV diastolic function via the regulation of intracellular calcium and induction of inflammatory activity. Therefore, close follow-up of the diastolic functions of these patients could be beneficial. © 2018 Elsevier B.V., All rights reserved.
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    The coexistence of renal cell carcinoma and diffuse large B-cell lymphoma with hypercalcemic crisis as the initial presentation
    (Institute of Experimental Endocrinology ueenregu@kramare.savba.sk, 2014) Yilmaz, Hakki; Namuslu, Mehmet; Bilgiç, Mukadder Ayşe; Bavbek, Nüket; Akçay, Ali T.
    Introduction. Severe hypercalcemia can be life threatening. The causes of hypercalcemia can be divided into seven categories: hyperparathyroidism, vitamin D-related causes, malignancy, medications, other endocrine disorders, genetic disorders, and miscellaneous causes. Evaluation of a patient with hypercalcemia should include a careful history and physical examination focusing on clinical manifestations of hypercalcemia, risk factors for malignancy, causative medications, and a family history of hypercalcemia-associated conditions (e.g. kidney stones). Hypercalcemia was clasified as serum levels of calcium: 1) mild hypercalcemia (calcium < 12 mg/dl), 2) moderate hypercalcemia (calcium between 12 and 14 mg/dl), and 3) severe hypercalcemia (calcium > 14 mg/dl). We should keep in mind that severe hypercalcemia was originated from two or more causes. This is the first report in the literature; renal cell carcinoma (RCC) and diffuse large B-cell lymphoma (DLBCL) presented severe paraneoplastic hypercalcemia. Case presentation. We report a case of a 63-year-old Turkish man with RCC and DLBCL who showed severe hypercalcemia (calcium=15.01 mg/dl) accompanied by elevation of serum parathyroid hormone-related protein (PTH-rP) as the initial presentation. While hypercalcemia is one of the complications of various types of cancerous diseases, it has not been reported still as the first presentation of the coexistence of RCC and DLBCL. After radical nephrectomy, the patient underwent six courses of chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and achieved a complete remission that lasts 2 years. Conlusion. This case report describes a patient with two different malignancies (RCC and DLBCL) with the unusual presentation of hypercalcemia. We review the differential diagnosis and treatment of malignant hypercalcemia. We suggest that coexistence of DLBCL with RCC, although rare, should be considered as a possible causative in hypercalcemia of unknown underlying disease. © 2015 Elsevier B.V., All rights reserved.