Association of serum proprotein convertase Subtilisin/Kexin Type 9 (PCSK9) level with thyroid function disorders.

OBJECTIVE: We aimed at demonstrating the effect of thyroid function status on proprotein convertase subtilisin kexin type 9 (PCSK9) and determining the effect of thyroid hormones on lipid metabolism by comparing the PCSK9 levels of patients with subclinical hypothyroidism, overt hypothyroidism, and hyperthyroidism. PATIENTS AND METHODS: 124 patients with thyroid disorders, aged between 18 and 65 years, were included in this study. The participants were divided into 3 groups. Group 1 comprised 52 patients with subclinical hypothyroidism, Group 2 comprised 40 patients with overt hypothyroidism, and Group 3 comprised 32 patients with hyperthyroidism. In all of these groups, the thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, total cholesterol, fasting serum glucose, antithyroid peroxidase antibody, antithyroglobulin antibody, and PCSK9 levels were measured. RESULTS: No significant difference was found between the 3 groups in terms of age, gender, and body mass indices. Median PCSK9 measurements were 14.55 ng/mL in Group 1, 14.895 ng/mL in Group 2, and 9.775 ng/mL in Group 3. There was a significant difference in the PCSK9 levels between Group 1-Group 3 and Group 2-Group 3 (p <0.0001 and p <0.0001, respectively). A positive correlation between PCSK9 and the TSH levels (r = 0.211, p= 0.019), and a negative correlation (r = -0,239, p = 0.009 and r = -, 0.218, p = 0.015) between the fT3 and fT4 levels were found. CONCLUSIONS: The serum PCSK9 levels were shown to be associated with thyroid dysfunction. However, no relationship was observed between the serum PCSK9 level and thyroid autoantibody positivity, and obesity in this study.

The easy way of evaluating exocrine pancreatic insufficiency in type 2 diabetes : listen to the patients' complaints and look in their eyes!

BACKGROUND AND STUDY AIMS: The objective of this study is to determine the prevalence of exocrine pancreatic insufficiency (EPI) in diabetic patients, and to investigate whether there is a relationship between EPI and diabetes period, gastrointestinal complaints and other diabetic microvascular complications. PATIENTS AND METHODS: A total of 93 participants, consisting of 57 type 2 diabetes patients and 36 healthy volunteers have been included in our cross-sectional study. Participants were questioned for abdominal complaints and weight loss. Fecal elastase-1 (FE-1) was determined in fecal spot samples received from participants. The relationship between EPI and blood glucose, HbA1c, and duration and complications of diabetes were investigated. RESULTS: FE-1 levels were significantly lower in diabetic group compared to control group (p=0.007). The number of patients with FE-1 levels of <200µg/g were significantly higher in diabetic group (p=0.002). A statistically significant negative correlation was determined between FE-1 levels and the duration of diabetes (r= -0.453 p<0.001). FE-1 levels were significantly lower in patients with retinopathy (p= 0.014). In the post-hoc analysis, this difference was due to patients in the proliferative retinopathy group. A significant negative correlation was determined between the presence of retinopathy and FE-1 levels (r=-0.32, p=0.02). Abdominal pain and distension complaints were independent predictive factors that estimate EPI. CONCLUSIONS: An important part of type 2 diabetes patients has EPI and it should be considered in diabetes patients upon abdominal pain and distension. Determination of proliferative retinopathy in the eye examination may also suggest an idea on the possible presence of EPI.

Alternate-day calcium dosing may be an effective treatment option for chronic hypoparathyroidism.

PURPOSE: Conventional treatment of chronic hypoparathyroidism consists of oral calcium supplements and active vitamin D analogs; however, some patients are unable to meet treatment goals despite the high dosage of oral calcium supplementation. We aimed to investigate the effectiveness of alternate-day oral calcium intake in patients with uncontrolled chronic hypoparathyroidism. METHODS: In this retrospective cohort study, we evaluated 66 patients with chronic hypoparathyroidism who were admitted to our hospital between January 2017 and January 2019. Fourteen patients receiving ≥ 2000 mg/day oral elemental calcium and who were admitted to emergency department or our outpatient clinic at least once in the last 3 months for hypocalcemia requiring intravenous calcium replacement were switched to the alternate-day dosing regimen in which patients took calcium orally every other day. We collected and analyzed patients' medical history information, serum and urinary parameters over a 3-month period prior to and following the treatment. RESULTS: Before alternate-day dosing regimen, median oral calcium intake was 3750 mg/day, oral calcitriol intake was 0.88 mcg/day, serum calcium levels were 7.71 mg/dL, serum phosphate levels were 5.35 mg/dL, and 24-h urine calcium levels were 165 mg/day. Following alternate-day dosing regimen, median oral calcium intake was 1500 mg/day, oral calcitriol intake was 0.88 mcg/day, serum calcium levels were 8.25 mg/dL, serum phosphate levels were 5 mg/dL, and 24-h urine calcium levels were 210.5 mg/day. After alternate-day dosing regimen, oral calcium intake decreased and serum calcium levels increased. The number of emergency visits dropped from 21 to 3 after alternate-day dosing regimen. CONCLUSION: Patients with uncontrolled chronic hypoparathyroidism could be controlled more effectively with alternate-day dosing regimen.

The role of insulin - like growth factor - 1 on steatohepatitis.

PURPOSE: Recent studies have revealed that growth hormone and STAT5 were related to hepatosteatosis in mice. Loss of signal transducer and activator of transcription factor-5 leads to hepatosteatosis and impaired liver regeneration. We aimed to investigate the role of IGF-1 in steatosis with normal (SNLFT) and disturbed liver function tests (SDLFT) in humans. METHODS: We included 272 NAFLD patients and 110 age, sex and body mass index (BMI)-matched healty controls. We measured routine blood biochemistry and complete blood count, IGF-1, insulin, c-peptide, ferritin, hsCRP, ESR and HOMA-IR. We subdivided NAFLD patients into SNLFT and SDLFT subgroups. RESULTS: ge, sex and BMI were similar between NAFLD and controls. IGF-1 levels were significantly lower in NAFLD patients (120,6±48,2) than controls (148,9±53,8), (<0,0001). IGF-1 levels were also lower in SDLFT subgroup (93,4±27,8) than SNLFT subgroup (123,1±49,0), (p:0,032). Waist circumference, fasting blood glucose, HbA1c, uric acid, hsCRP, AST, ALT, GGT, WBC, hemoglobin, hematocrit, ferritin, insulin, c-peptid and HOMA-IR measurements were significantly higher in NAFLD patients than controls (for all values: p<0,0001).Cholesterol (p:0,026), triglycerides (p<0,0001), ESR (p:0,006) were significantly higher in NAFLD patients than controls. HDL-chelesterol levels were significantly lower (p:0,002) in NAFLD patients than controls. CONCLUSION: This study supported previous findings of experi-mental studies in that, IGF-1 levels were lower in SNLFT and SDLFT. Growth hormone-IGF-1 system may be involved in the pathogenesis of NAFLD.

Elevated insulin resistance in patients with recurrent aphthous stomatitis.

OBJECTIVES: The role of glucose metabolism disorders in periodontal diseases including recurrent aphthous stomatitis (RAS) is currently attracting attention. The aim of this study is to investigate insulin resistance (IR) in patients with RAS in otherwise healthy individuals. MATERIALS AND METHODS: The study enrolled 81 patients with RAS and 61 healthy control subjects. Blood glucose, insulin, C-peptide, hemoglobin A1c, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and HOMA-IR were measured in each individual. RESULTS: Forty-two of the RAS group were in the active, and 39 of the RAS group were in the passive stage. The levels of c-peptide, insulin, and HOMA-IR were remarkably higher in the RAS group (p = 0.015; p < 0.0001; p < 0.0001, respectively) than the control group. The levels of HbA1c, glucose (p = 0,045), TC (p = 0,008), HDL cholesterol (p = 0,002), and HOMA-IR (p = 0.022) were significantly higher in patients with RAS in the active stage. CONCLUSION: The study revealed an elevated IR in patients with RAS that was not previously shown. IR was more prominent when the patients were in the active stage that elevated inflammatory cytokines may induce IR by interfering with insulin signaling. Further studies, investigating the interplay between RAS, inflammation, and IR are needed. CLINICAL RELEVANCE: Patients who admitted the hospital with RAS might be screened for prediabetes.

Immunoregulatory effects of isotretinoin in patients with acne.

BACKGROUND: In vitro studies have shown that retinoids influence T-cell differentiation. OBJECTIVES: To study the effect of isotretinoin on T-cell differentiation markers in patients with acne. METHODS: A total of 37 patients with acne vulgaris (25 female, 12 male, age 19.6 ± 3.7 years) and 30 age- and sex-matched healthy controls (19 female, 11 male, age 20.5 ± 4.4 years) were included in the study. Screening for biochemical parameters in serum samples were done just before initiation (pretreatment) and after 3 months of isotretinoin treatment (post-treatment) in the acne group. RESULTS: Baseline levels of tumour necrosis factor (TNF)-α (P<0.0001), interleukin (IL)-4 (P<0.0001), IL-17 (P<0.0001) and interferon (IFN)-γ (P=0.002) were significantly higher in the acne group compared with the control group. TNF-α (P<0.0001), IL-4 (P<0.0001), IL-17 (P<0.0001) and IFN-γ (P<0.0001) levels decreased after isotretinoin treatment. TNF-α and IL-4 values after isotretinoin treatment were similar to those of the control group. However, levels of IL-17 (P<0.0001) after isotretinoin treatment were higher than those of the control group, despite a significant decline after treatment. Levels of IFN-γ (P<0.0001) after isotretinoin treatment were lower than those of the control group. CONCLUSIONS: This study shows that isotretinoin treatment significantly decreases TNF, IL-4, IL-17 and IFN-γ levels in patients with acne. We failed to show that isotretinoin redirects naive T helper (Th) differentiation preferentially towards the Th2 cell lineage.

Serum holotranscobalamine, vitamin B12, folic acid and homocysteine levels in patients with vitiligo.

Few studies have investigated the role of vitamin B12 metabolism in vitiligo. We tested the hypothesis that vitamin B12 and folate metabolism might have an influence on the pathogenesis of vitiligo. Full blood count and levels of folic acid, vitamin B12, homocysteine and holotranscobalamine were examined for 69 patients with vitiligo and 52 controls. The vitiligo group had higher levels of homocysteine (P < 0.01) and haemoglobin (P < 0.01) levels, and lower levels of vitamin B12 (P < 0.01) and holotranscobalamine (P < 0.0001) than the control group. Folic acid levels were similar for both groups. In a risk analysis, hyperhomocysteinaemia (≥ 15 µmol/L, P < 0.01) and vitamin B12 deficiency (< 200 pg/mL, P < 0.01) were significant risk factors for vitiligo. Patients with holotranscobalamine levels in the lowest quartile had an increased risk for co-occurrence of vitiligo (P < 0.005). Vitamin B12 deficiency and hyperhomocysteinaemia may share a common genetic background with vitiligo.

Isotretinoin does not induce insulin resistance in patients with acne.

BACKGROUND: Isotretinoin treatment causes hypertriglyceridaemia. Insulin resistance is also associated with hypertriglyceridaemia. It is not known if isotretinoin is related to insulin resistance. AIM: To test this hypothesis, we measured insulin resistance in 48 patients with acne vulgaris (AV) before and after 3 months of isotretinoin treatment. METHODS: In total, 48 patients with AV who attended the dermatology outpatient clinic at Kecioren Research and Training Hospital were included. Screening for biochemical parameters was performed just before the start of treatment (pretreatment) and after 4 months of isotretinoin therapy (post-treatment). The parameters measured were insulin, C peptide, fasting blood glucose, aspartate and alanine aminotransferases (AST, ALT), total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and very low-density lipoprotein cholesterol. Insulin resistance was measured using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) method. RESULTS: Compared with initial values, AST, ALT, TC, LDL-C and triglyceride levels were significantly increased (P < 0.01, < 0.05, < 0.01, < 0.05 and < 0.01, respectively), but there was no significant change in fasting blood glucose, insulin, C-peptide levels or HOMA-IR. CONCLUSIONS: Three months of isotretinoin treatment did not change insulin sensitivity in patients with AV. Further studies with insulin resistance models may even reveal an improvement in insulin resistance, as experimental animal studies have previously shown.

Short-term isotretinoin treatment decreases insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels: does isotretinoin affect growth hormone physiology?

BACKGROUND: Isotretinoin is an effective treatment for acne vulgaris. However, it has numerous side-effects. It was previously reported that serum growth hormone (GH) levels decreased with isotretinoin treatment. OBJECTIVES: To analyse whether isotretinoin has any effects on insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP3) and GH levels. METHODS: Forty-seven patients aged 21.5 +/- 5.1 years (mean +/- SD) with acne vulgaris were included in this study. Isotretinoin therapy was initiated at a dose of 0.5-0.75 mg kg(-1) daily and then adjusted to 0.88 mg kg(-1) daily as maintenance dosage after 1 month. Screening for biochemical and hormonal parameters was performed just before initiation and after 3 months of isotretinoin treatment. RESULTS: IGF-1 and IGFBP3 levels decreased significantly after treatment (P < 0.01), while GH levels did not change. Post-treatment, significant increases were seen in aspartate aminotransferase, total cholesterol, low-density lipoprotein cholesterol, triglycerides and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (P < 0.0001) while high-density lipoprotein cholesterol levels were significantly decreased (P < 0.0001). CONCLUSIONS: Isotretinoin therapy may have an effect on GH physiology, and further studies are needed to understand this association.

HHV-8 is not a cofactor in the pathogenesis of environmentally induced malignant pleural mesothelioma.

After the recognition of human herpes virus 8 (HHV-8) in Kaposi's sarcoma lesions, this new virus has been shown to be associated with various types of malignancy. One of them, body cavity-based lymphoma, is a high grade B-cell lymphoma arising from the body cavities. Similarly, mesothelioma is a tumour that originates from the serosal linings of the pleural, pericardial and peritoneal cavities. One of the striking characteristics of mesothelioma cells is the secretion of interleukin-6 (IL-6). Also, it is known that HHV-8 upregulates the levels of IL-6, and this virally originated IL-6 is a well-established growth factor for HHV-8-associated lesions. Therefore, it was hypothesized that HHV-8 may have a role in the pathogenesis of malignant mesothelioma. Twenty-nine pleural biopsy specimens from environmentally induced malignant mesothelioma patients were investigated for the presence of HHV-8 deoxyribonucleic acid (DNA) using the polymerase chain reaction (PCR). Control pleural samples were collected from 15 biopsy specimens from patients with tuberculosis. From all samples, a segment of the beta-globulin gene was amplified in order to make sure that the DNA was extracted properly and did not contain any inhibitors. The specificity of the PCR amplification was confirmed by means of restriction enzyme analysis using Providencia stuartii I. PCR did not reveal HHV-8 DNA in any of the mesothelioma patients or in the control group. It was possible to amplify a segment of the human beta-globulin gene from all the samples of the patient and control groups. HHV-8 DNA was amplified in the control sample, which was a tissue biopsy specimen from a Kaposi's sarcoma lesion, and it was confirmed that the amplified DNA belonged to HHV-8 by restriction enzyme analysis. Malignant mesothelioma continues to be a public health problem in rural parts of Anatolia, Turkey. The major causal factor of the disease is exposure to asbestos and fibrous zeolite (erionite). It seems that there must be some aetiological factors other than exposure to these minerals as not all patients exposed to asbestos develop the disease and the disease is not always associated with any known exposure. From the present study, it was concluded that human herpes virus 8 does not seem to be associated with environmentally induced malignant mesothelioma in Turkey. Other possible causal factors of malignant mesothelioma should be sought.