Low Bone Density and High Sclerostin in Non-Functioning Pituitary Adenoma.

PURPOSE: Sclerostin reduces bone formation by inhibiting the Wnt signaling pathway in bone tissue. This study evaluated the serum sclerostin level in non-functioning pituitary adenoma (NFPA) patients and analyzed its relationship with bone metabolism. METHOD: The data of the patients who applied to the Dicle University Endocrinology, diagnosed with non-functioning pituitary adenoma, and the control group consisting of healthy individuals were included in the study. Serum sclerostin levels and DXA analysis parameters were evaluated and compared with healthy control groups. RESULTS: The study consisted of 39 patients (F / M: 27/12) with NFPA (patient group) and 43 control groups (F / M: 26/17). There was no difference in terms of gender, age, height, weight and serum calcium, phosphorus, creatinine, 25-OH vitamin D, parathyroid hormone levels. Serum sclerostin levels (32.31 ± 1.53 ng / ml) in the patient group was found to be significantly higher than the control group (22.45 ± 8.9 ng / ml) (p < 0.001). BMD (Patients groups vs control group); total lumbar BMD (0.951-1.56 gr / cm2) (p < 0.001), femoral neck BMD (0.752-1.15 g / cm2) (p < 0.001), femoral total BMD (0.995- 1.63 gr / cm2) (p < 0.001), were found to be statistically significantly lower. CONCLUSION: This study provides the first evidence that serum sclerostin levels were increased in non-functioning pituitary adenomas, which showed that bone parameters were negatively affected.

Are There Differences in the Management of Acute Pancreatitis Cases Due to Severe Hypertriglyceridemia in Pregnant Women?

BACKGROUND The aim of this study was to determine the prognosis of severe disease and treatment approaches of both normal and pregnant, especially in patients with severe pancreatitis due to hypertriglyceridemia. MATERIAL AND METHODS We included 30 patients (20 females and 10 males) in this study whose follow-ups and treatments were performed after a diagnosis of hypertriglyceridemia-induced acute pancreatitis between January 2011 and May 2017. Patient personal information, such as age, sex, pre-treatment and post-treatment triglyceride levels, receipt of anti-hyperlipidemic treatments or plasmapheresis, and family history, were collected from hospital records and patient files. Patients with severe pancreatitis history, score, and prognosis were included to increase the value of our study. Mild and moderate cases were excluded. RESULTS The mean age of the patients was 35±6 years. Twenty-four patients (80%) received an anti-hyperlipidemic treatment before their pancreatitis attacks. Plasmapheresis was performed on 8 patients before their pancreatitis attacks. Eighteen patients (60%) had a family history suggesting familial hypertriglyceridemia. Twelve patients (40%) were pregnant. CONCLUSIONS The treatment of hypertriglyceridemia-induced acute pancreatitis was mostly confined to supportive, palliative treatments. However, plasmapheresis is a possible treatment option and should be used in the early stages of this disease. The response to medical treatment and support treatment was better in pregnant patients than in the other patient group, and pregnant patients did not require plasmapheresis.

Association of clinical and laboratory parameters with ambulatory arterial stiffness index in acromegaly patients.

OBJECTIVE: In this study, we determined the relationship between the ambulatory arterial stiffness index (AASI) and clinical and laboratory parameters in patients with acromegaly. METHODS: Sixty-five patients with acromegaly, who visited to Dicle University Medical Faculty Department of Endocrinology (33 females and 32 males), were included in this study. The study control group consisted of 65 subjects. Demographic and clinical data were recorded. Laboratory data (complete blood count, blood urea nitrogen, creatinine, electrolytes, albumin, lipid profile, growth hormone [GH], insulin-like growth factor-1, and the 75-g oral glucose tolerance test) performed over the last year were evaluated. The AASI was obtained from 24-hour ambulatory blood pressure monitoring records of all patients. This study was completed in 15 months from 2013 to 2015. RESULTS: Twelve patients (18.4%) had diabetes and 21 patients (32%) had hypertension. The mean AASI value was 0.41 ± 0.14. The mean AASI value in the control group was 0.25 ± 0.09. Growth hormone (GH) levels were positively correlated with the AASI values. AASI values tended to be higher in hypertensive subjects than that in normotensive individuals. CONCLUSIONS: Our results show that the AASI value increased in patients with acromegaly, independent of the increase in blood pressure. The AASI was strongly dependent on the degree of the GH increase in patients with acromegaly and may have an important role predicting cardiovascular risk in patients with acromegaly.

Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes.

Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of pituitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients.

Myocardial Performance Index for Patients with Overt and Subclinical Hypothyroidism.

BACKGROUND Hypothyroid has several effects on the cardiovascular system. Global myocardial performance index (MPI) is used in assessment of both left ventricular (LV) systolic and diastolic function. We compared MPI in hypothyroidism patients vs. normal control subjects. MATERIAL AND METHODS Eighty-two hypothyroid patients were divided into 2 groups: a subclinical hypothyroid (SH) group (n=50), and an overt hypothyroid (OH) group (n=32). The healthy control group (CG) constituted of 37 patients. TSH, FT3, and FT4, anti-TPO, anti-TG, insulin, lipid values, and fasting glucose levels were studied. All patients underwent an echocardiographic examination. Myocardial performance indexes were assessed and standard echocardiographic examinations were investigated. RESULTS MPI averages in OH, SH, and control groups were 0.53±0.06, 0.51±0.05, and 0.44±0.75 mm, respectively. MPI was increased in the OH and SH groups in comparison to CG (p<0.001, p<0.001, respectively). CONCLUSIONS MPI value was significantly higher in hypothyroid patients in comparison to the control group, showing that regression in global left ventricular functions is an important echocardiographic finding. Future studies are required to determine the effects of this finding on long-term cardiovascular outcomes.

Four decades without diagnosis: Sheehan's syndrome, a retrospective analysis.

AIM: Sheehan's syndrome (SS) remains a frequent cause of hypopituitarism in undeveloped and developing countries, but due to improvements in obstetric care, it is rare in developed countries. We aimed to share the results of a retrospective study analyzing the demographic, clinical, imaging, and hormonal characteristics of a large group of patients with SS, and also increase awareness of this syndrome especially in developed countries. METHODS: The medical records of 124 patients with SS patients who were followed up in the Endocrinology Department of Dicle University between 1995 and 2015 were assessed retrospectively. RESULTS: The mean period of diagnostic delay was 20.37 ± 8.34 years on average. 5.7% of patients with SS were literate; 62% of patients delivered at home. Anemia was identified in 64.5% of SS patients. Mean blood sodium levels were 129.8 ± 11.3 mEq/L. The mean urine densities were 1013 ± 6.5. Osteoporosis and osteopenia were found in 44 (35.4%) and 71 (57.2%) patients, respectively, According to pituitary magnetic resonance imaging (MRI) analyses, 92 (74.2%) patients with SS had completely empty sella, 29 (23.3%) had partially empty sella, and 1 patient had microadenoma, and 2 had normal pituitary MRI results. CONCLUSIONS: Improved obstetric care and effective interventions for postpartum hemorrhage have limited the prevalence of SS in developed countries. However, in developing countries like Turkey, SS due to postpartum bleeding remains common. Thus, physician's awareness of the symptoms of SS is urgently required to avoid the associated morbidity and mortality.

Serum prolidase activity and oxidative status in patients with diabetic neuropathy.

We found no data in the literature related to oxidative stress index (OSI), total oxidative status (TOS) and prolidase activity in patients with diabetic neuropathy (DN). In this study, we aimed to evaluate the oxidative status of DN patients via measurement of TOS and serum total antioxidant status (TAS) and estimation of OSI using new automated methods. Thirty-eight healthy participants, 40 diabetic patients without neuropathy, and 39 patients with DN were included. Electrophysiological and neurological examinations were performed. The activity of prolidase and levels of TOS and TAS were determined in the serum of patients. The level of TAS was lower, while the levels of TOS and OSI, and activity of prolidase were higher in both DN and diabetic control groups compared with the healthy subjects (p < 0.05). Prolidase activity was found to be higher in the DN group than in the diabetic control group (p = 0.001). In conclusion, the presence of high TOS and OSI levels together with low levels of TAS in diabetic patients with or without neuropathy may support a role of oxidative stress in the pathogenesis of diabetes mellitus. In addition, increased serum prolidase activity in DN may be interpreted as evidence of increased collagen turnover.

Insulin resistance in type 2 diabetes mellitus may be related to bone mineral density.

The mechanism of bone mineral density (BMD) changes in type 2 diabetes mellitus is not clear. We aimed to investigate the effect of insulin resistance in type 2 diabetics on BMD. Insulin resistance was determined using the homeostasis model assessment index (HOMA-IR). Nineteen type 2 diabetic patients with a HOMA-IR <2.7 (mean age, 51.5±9.6yr; body mass index [BMI], 27.3±5.1kg/m(2); duration of diabetes, 10.5±7.3yr) were included in Group A, and 30 BMI- and age-matched type 2 diabetic patients with a HOMA-IR ≥2.7 were included in Group B. The BMD was measured with dual-energy X-ray absorptiometry. Independent t-test was used for statistical analysis. The Group A values for mean fasting glucose and insulin levels were 160.1±77.0mg/dL and 4.79±2.89µU/L, respectively, whereas the Group B values were 195.1±58.9mg/dL (p>0.05) and 19.30±16.89µU/L (p=0.0001). Significantly higher total lumbar vertebra T-score (p=0.02) and total lumbar vertebra BMD in Group A were determined than Group B (p=0.033). The lumbar vertebra total Z-score was significantly lower in Group B (p=0.042). Marked insulin resistance may have a negative effect on BMD in type 2 diabetics, while the presence of hyperinsulinemia may be associated with the low BMD.

Assessment of bleeding disorders in Sheehan's syndrome: are bleeding disorders the underlying cause of Sheehan's syndrome?

Sheehan's syndrome (SS) is an adenopituitary insufficiency caused by hypovolemia secondary to excessive blood loss during or after childbirth. However, the mechanism of postpartum hemorrhage and ischemia is not clear. We aimed to evaluate the bleeding disorders among patients with SS, in comparison with healthy controls. In addition, we investigated underlying causes in postpartum hemorrhage that begin the event. The present study was conducted at the Dicle University School of Medicine. Forty-eight patients with SS and 50 age-matched female healthy controls were included. Biochemical and hormonal variables were measured, as was platelet function by means of closure times (PFA-100 testing using collagen plus epinephrine and collagen plus ADP), von Willebrand factor (vWF) level, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and coagulation factors. Although PT and INR were significantly higher in patients with SS (both P<0.01), aPTT and levels of fibrinogen, vWF, and factors II, V, VII, VIII, IX, X, XI, and XII did not differ significantly. Closure times with collagen/epinephrine and collagen/ADP also did not differ significantly between patients with SS and control patients. The nonspecific etiology and presence of excessive postpartum hemorrhage in patients with SS suggest that coagulation disorders may play a role in their predisposition to bleeding. The increased PT and INR noted might implicate bleeding diathesis as the underlying etiology, although no significant decreases were noted in factor levels. Further studies are needed to elucidate this complex mechanism of this disorder.

Analysis of thrombophilic genetic mutations in patients with Sheehan's syndrome: is thrombophilia responsible for the pathogenesis of Sheehan's syndrome?

The gene mutations of Factor V R506Q (FV-Leiden), prothrombin (FII G20210A), methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C and PAI-1 4G/5G are well-established risk factors for thrombosis. We aimed to investigate the prevalence of these gene mutations and their possible impact on the development of pathogenesis in patients with Sheehan's syndrome (SS). 40 female patients with SS compared to a control group of 45 healthy women. The presence of FV-Leiden, FII G20210A, MTHFR C677T, MTHFR A1298C and PAI-1 4G/5G gene mutations were assessed by polymerase chain reaction analysis with a light cycler analyzer. An odds ratio of greater than one is considered to increase the risk of SS disease as found in Factor V Leiden, FII G20210A, MTHFR C677T, MTHFR A1298C and PAI-1 4G/5G polymorphism, as follows respectively: 1.13, 1.85, 6.00, 8.14 and 1.45. MTHFR C677T and MTHFR A1298C polymorphism were found significantly higher in SS patients than the control group (P<0.001), however FV-Leiden, FII G20210A and PAI-1 4G/5G polymorphism showed no significant difference (P>0.05). The level of plasma total homocysteine (tHcy) was significantly higher in patients with SS than in the control group (P<0.001). We suggest that the genetic mutations of FV-Leiden, FII G20210A, MTHFR C677T, MTHFR A1298C and PAI-1 4G/5G increase the risk of SS. Also, high plasma tHcy levels may be a risk factor for the development of SS.

Biochemical characteristics and calcium and PTH levels of patients with high normal and elevated serum 25(OH)D levels in Turkey: DeVIT-TOX survey.

Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and generally not associated with symptoms of hypercalcemia. High doses of cholecalciferol need to be avoided to protect against vitamin D toxicity and related complications. Strict adherence to the clinical guidelines for treating vitamin D deficiency can ensure safe and effective treatment. PURPOSE: We observed a tendency to use high doses of cholecalciferol for vitamin D deficiency treatment or vitamin D supplementation. We aimed to determine the biochemical characteristics of patients with high normal and elevated serum 25(OH)D levels. METHODS: An online invitation was sent to all tertiary endocrinology clinics in Turkey to complete an online retrospective survey (DeVIT-TOX Survey) for patients diagnosed with high serum 25(OH)D levels (> 88 ng/mL) between January 2019 and December 2019. The patients were evaluated according to the presence of signs and symptoms of hypercalcemia and doses of vitamin D intake, evaluated into the following three groups according to their 25(OH)D levels: group 1, > 150 ng/mL; group 2, 149-100 ng/mL; and group 3, 99-88 ng/mL. RESULTS: A total of 253 patients were included in the final analysis (female/male: 215/38; mean age, 51.5 ± 15.6 years). The average serum 25(OH)D level was 119.9 ± 33 (range, 88-455) ng/mL, and the average serum calcium level was 9.8 ± 0.7 (range, 8.1-13.1) mg/dL. Most (n = 201; 75.4%) patients were asymptomatic despite having high serum 25(OH)D and calcium levels. The serum 25(OH)D level was significantly higher in the symptomatic groups than in the asymptomatic groups (138.6 ± 64 ng/mL vs. 117.7 ± 31 ng/mL, p < 0.05). The most common cause (73.5%) associated with high serum 25(OH)D levels was the inappropriate prescription of a high dose of oral vitamin D (600.000-1.500.000 IU) for treating vitamin D deficiency/insufficiency in a short time (1-3 months). The cut-off value of 25 (OH) D level in patients with hypercalcemia was found to be 89 ng/mL [median 116.5 (89-216)]. CONCLUSIONS: High dose of vitamin D intake is associated with a high serum 25 OH D level, without symptoms of hypercalcemia. Inappropriate prescription of vitamin D is the primary cause for elevated 25(OH) D levels and related hypercalcemia. Hypercalcemia may not be observed in every patient at very high 25(OH) D levels. Adherence to the recommendation of guidelines is essential to ensure safe and effective treatment of vitamin D deficiency.

Serum resistin and adiponectin levels in young non-obese women with polycystic ovary syndrome.

INTRODUCTION: Although polycystic ovary syndrome (PCOS) was described more than half a century ago, the underlying cause of PCOS is still unknown. The aim of our study was to evaluate whether serum resistin and adipocytokine levels alter and its changes relate with low grade inflammation in non-obese young women with PCOS. SUBJECTS AND METHODS: Newly diagnosed 31 young non-obese women with PCOS (mean age 21.8 +/- 5.4 years; body mass index (BMI): 23.8 +/- 6.6 kg/m(2)) and 25 BMI- and age-matched, regular-cycling, healthy women (mean age 24.9 +/- 5.7 years; BMI: 23.1 +/- 5.8 kg/m(2)) were included the study Anthropometric measurements were evaluated. Resistin, adiponectin, glucose, insulin, hormone profiles, Lipoprotein (Lp)(a), high sensitive C reactive protein (hs-CRP), and homocysteine levels were measured in the beginning of oral glucose tolerance test. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. RESULTS: Non-obese young women with PCOS had high adiponectin levels (28.01 +/- 6.47 ng/ml in PCOS vs. 23.89 +/- 7.70 ng/ml in control subjects, p = 0.034), whereas serum resistin levels were not significantly different compared with healthy controls (14.14 +/- 6.6 ng/ml in PCOS vs. 13.78 +/- 4.26 ng/ml in control subjects). There were no significant differences between two groups in terms of fasting insulin, Lp(a), homocysteine, and hs-CRP levels. Mean HOMA-IR value of patients with PCOS was similar with control subjects (1.93 +/- 0.73 in PCOS; 1.15 +/- 0.54 in control group). CONCLUSIONS: Resistin levels did not change in non-obese young women with PCOS whereas adiponectin level in non-obese young women with PCOS was significantly higher than control subjects, perhaps, because of no insulin resistance. Circulating resistin levels may not be candidate to play a role in pathogenesis of PCOS without insulin resistance or obesity.

Increased Serum Sclerostin Levels in Patients With Active Acromegaly.

CONTEXT: Bone mineral density is normal in acromegalic patients and the cause of increased fracture risk that characterizes active acromegaly is unknown. OBJECTIVE: This study compared serum sclerostin levels between patients with active acromegaly and healthy individuals. DESIGN, SETTING, AND PARTICIPANTS: The serum sclerostin levels of patients with active acromegaly were compared with those of healthy volunteers in a cross-sectional study. The mean age of the 30 acromegaly patients (male/female: 14/16) was 47.26 ±â€…12.52 years (range, 18-64 years) and that of the healthy volunteers (male/female: 17/13) was 44.56 ±â€…10.74 years (range, 19-62 years). IGF-1 and GH levels were measured using an electrochemiluminescence method, and serum sclerostin levels using an ELISA. The Mann-Whitney U test was used to compare sclerostin levels between the 2 groups. The correlations of sclerostin level with IGF-1 and GH were determined using Spearman's test. RESULTS: The 2 groups did not differ in age or sex (P > 0.05). The median GH and IGF-1 levels in the patient group were 2.49 ng/mL (range, 0.22-70.00 ng/mL) (interquartile range [IQR], 1.3-4.52) and 338.5 ng/mL (range, 147-911 ng/mL) (IQR, 250-426), respectively. The median GH and IGF-1 levels in the control group were 0.95 ng/mL (range, 0.3-2.3) and 144 ng/mL (range, 98-198), respectively. The median sclerostin level was 29.95 ng/mL (range, 7.5-78.1 ng/mL) (IQR, 14.37-37.47) in the acromegaly group and 22.44 ng/mL (range, 8.45-36.44 ng/mL) (IQR, 13.71-27.52) in the control group (P < 0.05). There was a moderate positive correlation between the sclerostin and IGF-1 levels (rho = 0.54; P < 0.01), and between the sclerostin and GH levels (rho = 0.41; P < 0.05). CONCLUSIONS: High sclerostin levels may contribute to the increased fracture risk seen in patients with acromegaly.

Sheehan's syndrome as a rare cause of anaemia secondary to hypopituitarism.

Although its exact mechanism is unclear, anaemia is well recognised as a feature of hypopituitarism; and anaemia is associated with Sheehan's syndrome (SS). We aimed to evaluate the frequency and severity of anaemia and other haematological changes among patients with Sheehan's syndrome, in comparison with healthy controls. Sixty-five SS patients and 55 age-matched female healthy controls were included. Biochemical and hormonal assessments and haematological evaluations were carried out, and groups were compared. The mean number of red blood cells, as well as mean haemoglobin, iron and erythropoietin levels, total iron-binding capacity and transferrin saturation were all significantly lower in SS patients compared to controls. SS patients had significantly higher rates of anaemia (80.0% vs. 25.5%, p = 0.0001), iron deficiency (44.6% vs. 5.4%, p = 0.001), leukopenia (20.0% vs. 5.4%, p = 0.015), thrombocytopenia (9.2% vs. 0.0%, p = 0.028) and bicytopenia (21.5% vs. 1.8%, p = 0.001) compared to controls. Anaemic SS patients had normochromic-normocytic anaemia (55%) or hypochromic-microcytic anaemia (45%). Anaemia is frequently associated with Sheehan's syndrome and responds to appropriate replacement therapy. Hypopituitarism should be considered as a possible cause of anaemia, and a hormone examination should be undertaken promptly, particularly in patients with anaemia resistant to therapy and/or with a history suggestive of Sheehan's syndrome.

Evaluation of insulin sensitivity in hyperprolactinemic subjects by euglycemic hyperinsulinemic clamp technique.

The background and aim of the study is to evaluate insulin sensitivity in hyperprolactinemic subjects via euglycemic hyperinsulinemic clamp technique. Sixteen hyperprolactinemic subjects and 12 healthy subjects were included in the study. HOMA-B and HOMA-IR values of groups were calculated. Euglycemic hyperinsulinemic clamp technique was performed in both groups, and the M value of the groups was defined. Mann-Whitney U and chi-square tests were used in statistical analysis. Basal insulin level of hyperprolactinemic patients were higher than the control group (6.85 +/- 4.68; 3.66 +/- 0.88 microU/ml respectively; P < 0.05). Mean HOMA-IR and HOMA-B values of patients were higher than control group (1.49 +/- 1.30; 0.78 +/- 0.27 respectively; P = 0.02 and 136.28 +/- 72.53; 64.77 +/- 23.31, respectively, P < 0.001). M values of the patients were statistically lower than the control group (5.64 +/- 2.36; 7.05 +/- 1.62 kg/mg/min respectively; P < 0.05). (1) Hyperprolactinemic patients were more insulin resistant than control subjects. (2) Insulin resistance in hyperprolactinemic patients is not associated with obesity or anthropometric parameters such as fat content, waist circumference and BMI.

WITHDRAWN: SERUM NT-PRO TYPE BRAIN NATRIURETIC PEPTIDE LEVELS IN NEWLY DIAGNOSED ACROMEGALIC PATIENTS.

Ahead of Print article withdrawn by publisher.

Sheehan's syndrome and its impact on bone mineral density.

INTRODUCTION: Although there have been few studies investigating osteoporosis in isolated hormone deficiencies or other causes of hypopituitarism, the relationship between Sheehan's syndrome (SS) and osteoporosis has not been investigated. In the present study, we aimed to evaluate bone mineral density (BMD) in patients with SS in comparison with healthy women. METHODS: Sixty-one patients with SS and 62 matched healthy controls were included. Biochemical, hormonal assessments and BMD evaluations were carried out in patients and controls, and a subgroup analysis according to menopausal status was done (premenopausal < 50 years; postmenopausal > 50 years). RESULTS: The mean levels of serum anterior pituitary hormones were significantly lower in pre- and postmenopausal patients with SS compared with respective control groups (p < 0.0001). For both pre- and postmenopausal subjects, compared with respective controls, serum calcium and ALP levels, femur-T score, femur-Z score, spine (L1-L5)-T score, spine (L1-L5)-Z score and BMD values were lower, and phosphorus and parathyroid hormone (PTH) levels were higher in patients with SS. CONCLUSIONS: Patients with SS had low BMD. The possible mechanism responsible for osteoporosis may be hypogonadism, growth hormone deficiency and disorders of parathyroid hormone and calcium metabolism. But the contribution of each anterior pituitary hormone deficiency on bone loss should be clarified in further prospective studies.

Levels of proinflammatory cytokines and hs-CRP in patients with homozygous familial hypercholesterolaemia.

OBJECTIVE: Homozygous familial hypercholesterolemia (FH) is an extremely rare (1/1,000,000) condition characterized by markedly increased LDL cholesterol levels and a significantly increased risk of premature coronary heart disease (CHD). We aimed to evaluate the levels of high-sensitivity C-reactive protein (hs-CRP) and proinflammatory cytokines, which are known to be associated with atherogenesis, in patients with this condition. METHOD AND RESULTS: A total of 10 patients with homozygous FH (5 women and 5 men, mean age 17.0 +/- 6.9 years, body mass index (BMI) (18.8 +/- 1.9 kg/m2) and 16 healthy controls were included. hs-CRP levels, proinflammatory cytokine levels and lipid parameters were measured and compared between patients and control subjects. Homozygous FH patients had significantly higher total cholesterol, LDL-cholesterol and Lp(a) levels and significantly lower triglyceride and HDL cholesterol levels, compared to controls (P = 0.0001, for all). Serum hs-CRP (3.7 +/- 1.3 mg/L vs. 0.6 +/- 0.6 mg/L) and IL-1beta, IL-2R, IL-6, IL-8, IL-10, TNF-alpha levels were all significantly higher in the homozygous FH group, compared to controls (P = 0.0001, for all). CONCLUSIONS: Homozygous FH patients have significantly higher levels of hs-CRP and circulating proinflammatory cytokines, which may explain their increased risk of atherosclerotic disease. hs-CRP is an important biomarker that may be helpful in the identification of asymptomatic CHD in FH patients.

Alternative treatment of resistant hypoparathyroidism by intermittent infusion of teriparatide using an insulin pump: A case report.

Hypoparathyroidism usually responds to oral active vitamin D and calcium, but, although rare, some patients do not respond to this treatment. A 47-year-old Caucasian female presented to our medical unit with classical oral treatment-resistant hypocalcemia after thyroidectomy. Teriparatide was infused through the insulin pump with dosage set to 1 unit which equals to 2.5 µg of teriparatide. In conclusion, intermittent subcutaneous infusion of teriparatide using an insulin pump is a safe and effective treatment modality to ensure normocalcemic conditions in patients with classical treatment-resistant hypoparathyroidism. 39th Turkey Congress of Endocrinology and Metabolic Diseases, May 3-7, 2017, Antalya, Turkey.

Mutations in the amino-terminal region of proopiomelanocortin (POMC) in patients with early-onset obesity impair POMC sorting to the regulated secretory pathway.

CONTEXT: Mutations in the proopiomelanocortin (POMC) gene that impair the synthesis or structure of POMC-derived peptides predispose to human obesity. OBJECTIVE: Our objective was to identify and characterize novel mutations in the POMC gene found in patients with early-onset obesity. DESIGN AND PATIENTS: The POMC gene was screened in 500 patients with severe early-onset obesity. The biosynthesis, processing, sorting, and secretion of wild-type POMC and two newly identified POMC mutants was studied using metabolic labeling, Western blotting, and immunoassay analysis of lysates and conditioned media of transiently transfected beta-TC3 cells. RESULTS: Two novel heterozygous missense mutations in POMC (C28F and L37F) were identified in unrelated probands with early-onset obesity and their overweight or obese family members. Both mutations lie in a region of the N terminus of POMC that has been suggested to be involved in its sorting to the regulated secretory pathway. Metabolic labeling studies indicate that whereas the mutations do not reduce intracellular levels of POMC, both mutations (C28F>L37F) impair the ability of POMC to be processed to generate bioactive products. Studies of the secretion of POMC products suggest, particularly with C28F, that the impaired propeptide processing of these mutations results, at least in part, from a mistargeting of mutant POMC to the constitutive rather than the regulated secretory pathway. CONCLUSION: These mutations in patients with early-onset obesity represent a novel molecular mechanism of human POMC deficiency whereby naturally occurring mutations in its N-terminal sequence impair the ability of POMC to enter the trafficking pathway in which serial propeptide processing normally occurs.