The impact of vitamin D deficiency on clinical, biochemical and metabolic parameters in primary hyperparathyroidism.

BACKGROUND: It has been suggested that vitamin D deficiency is associated with worse clinical outcomes in primary hyperparathyroidism (PHPT). We aimed to evaluate the relationship between vitamin D deficiency and clinical, biochemical and metabolic parameters in PHPT patients. METHODS: A total of 128 patients with biochemically confirmed PHPT were included. Patients were categorized as vitamin D deficient if 25-OH vitamin D was <50nmol/L, or normal if vitamin D was ≥50nmol/L. Biochemical parameters, bone mineral densitometry (BMD), and urinary tract and neck ultrasonography were assessed. RESULTS: In the study group, 66 (51.6%) patients had vitamin D deficiency and 60 (48.4%) had normal vitamin D levels. Nephrolithiasis and osteoporosis were found in 26.6% and 30.5% of subjects, respectively. The prevalence of metabolic syndrome (MetS), obesity (BMI≥30kg/m2) and hypertension (HTN) were higher in the vitamin D deficient group when compared to the normal group (p=0.04, p=0.01 and p=0.03, respectively). There was no difference regarding the presence of nephrolithiasis and osteoporosis between the groups. The mean adenoma size was similar in both groups. CONCLUSIONS: Vitamin D deficiency was not associated with osteoporosis, nephrolithiasis, adenoma size or biochemical parameters in PHPT. However, vitamin D deficiency may be a risk factor for developing HTN and MetS in PHPT.

Salivary and serum oxidative stress biomarkers and advanced glycation end products in periodontitis patients with or without diabetes: A cross-sectional study.

BACKGROUND: Non-invasive methods for periodontitis diagnosis would be a clinically important tool. This cross-sectional study aimed to investigate the association between oxidative stress, glycation, and inflammation markers and periodontal clinical parameters in periodontitis and periodontally healthy patients with type 2 diabetes and corresponding systemically healthy controls. METHODS: Sixty-seven periodontally healthy (DM-H, n = 32) and periodontitis (DM-P, n = 35) patients with type 2 diabetes, and 54 systemically healthy periodontitis (H-P, n = 26) and periodontally healthy (H-H, n = 28) controls were included. Clinical periodontal parameters, body mass index, fasting glucose, hemoglobin A1c (HbA1c), along with saliva and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), advanced glycation end products (AGE), AGE receptor (RAGE) and high sensitivity C-reactive protein (hsCRP) levels were recorded and analyzed. RESULTS: Salivary 8-OHdG levels were significantly higher in periodontitis compared to periodontally healthy patients, regardless of systemic status (P < 0.001). Salivary MDA levels were significantly higher in all disease groups compared to H-H group (P ≤ 0.004). Serum AGE levels were significantly higher in diabetic groups than systemically healthy groups (P < 0.001) and in H-P compared to H-H (P < 0.001). Bleeding on probing (BOP) and clinical attachment level (CAL) strongly correlated with salivary 8-OHdG and serum hsCRP (P < 0.001). In systemically healthy patients, salivary 8-OHdG was the most accurate marker to differentiate periodontitis from controls (AUC = 0.84). In diabetics salivary 4-HNE and RAGE were the most accurate (AUC = 0.85 for both). CONCLUSION: Salivary 8-OHdG alone or in combination with 4-HNE, AGE and RAGE for diabetics, and salivary 8-OHdG alone or in combination with MDA and hsCRP for systemically healthy persons, could potentially serve as non-invasive screening marker(s) of periodontitis.

Thyroid dysfunctions in adult patients after allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Thyroid dysfunction (TD) is one of the major endocrinopathies shown after allogeneic hematopoietic stem cell transplantation over the long term. The incidence and the risk factors for TD have varied widely. PATIENTS AND METHODS: Two hundred and fifty-nine patients with pre-transplant normal thyroid function tests who survived at least 1 year after allo-HSCT between 2006-2016 were included in the study. RESULTS: Sixty-four patients (25%) developed TD at median of 34 months (range, 1-112 months). Hypothyroidism was detected in 32 patients (12%): 5 patients had primary hypothyroidism, and subclinical hypothyroidism occurred in 27 patients. 18 patients (7%) were diagnosed with hyperthyroidism: 2 patients (0.07%) were treated for primary hyperthyroidism, and 16 patients (6%) were followed for subclinical hyperthyroidism. Euthyroid sick syndrome occurred in 14 cases. None of the patients with thyroid dysfunction developed secondary thyroid malignancy. Receiving high-dose TBI (P = .001) was found to be significant risk for hypothyroidism; older age than median (P = .01) and pre-transplant active disease (P < .0001) were related to hyperthyroidism. CONCLUSIONS: Thyroid dysfunction, mostly hypothyroidism, is a long-term complication after allo-HSCT in 25% of patients. Older age, pre-transplant active disease, and receiving TBI are among the risk factors. Sustained long-term monitoring of thyroid function test should be considered post allo-HSCT.

Frequency of thyroid nodules and thyroid cancer in thyroidectomized patients with Graves' disease.

INTRODUCTION: Incidental thyroid cancers are frequently detected in patients operated on for Graves' disease (GD). There are no clear data about the incidence and risk factors of incidental thyroid cancer in operated GD patients. The aim of this study is to evaluate the risk of thyroid carcinoma in surgically treated GD patients. MATERIAL AND METHODS: The data of 121 GD patients who underwent total thyroidectomy in a single center between 2005 and 2015 were retrospectively evaluated. The diagnosis of thyroid cancer was based on pathological examination. RESULTS: Thyroid cancer was demonstrated in postoperative pathology specimens of 34 patients who were surgically treated for GD (28.1%). Preoperative thyroid ultrasonography (USG) revealed a nodular goiter in 62 (51.2%) patients. Nodules were not detected in the other 59 (48.8%) patients with GD. The frequency of thyroid cancer was significantly higher in patients with nodules (38% vs. 16%; p = 0.009). Thirty-two of the 34 cancer cases had papillary thyroid cancer (PTC), and the remaining 2 had follicular thyroid cancer (FTC). Of the 32 PTC patients, 28 were classical type, 2 patients had the follicular variant, 1 was the oncocytic variant, and 1 was a tall cell variant. CONCLUSIONS: The incidence of thyroid cancer was higher in patients who underwent surgery for GD. In addition to a careful physical examination in the follow-up of the patients with GD, ultrasonographic evaluation should be performed. Surgical treatment should not be delayed in patients with GD when indicated.

Clinical Impact of p27Kip1 and CaSR Expression on Primary Hyperparathyroidism.

We aimed to investigate the expressions of p27 kinase inhibitory protein 1 (p27Kip1) and calcium sensing receptor (CaSR) in adenomas and normal parathyroid tissue and to evaluate the relationship of these molecules with clinical and biochemical parameters in primary hyperparathyroidism (PHPT). Fifty-one patients with histopathologically confirmed parathyroid adenomas and 20 patients with normal parathyroid glands (which were removed incidentally during thyroid resection) were included. Immunohistochemical stainings of CaSR and p27Kip1 were performed in surgical specimens. Clinical features, biochemical parameters, and BMD measurements of patients with PHPT were evaluated retrospectively. Expressions of p27Kip1 and CaSR were decreased in parathyroid adenomas, compared to normal glands (p < 0.05). High intensity of CaSR staining (3+) was more frequent in normal parathyroid tissue (75%) than adenomas (12%) (p < 0.01). Hypertension was not observed in patients with high staining intensity of CaSR (p = 0.032). There was a negative association between CaSR expression and body mass index (BMI) (p = 0.027, r = - 0.313). There was no significant relationship between p27Kip1 and CaSR expressions, serum calcium, plasma parathormone, 25-hydroxy vitamin D levels, and bone density (p > 0.05). The expressions of p27Kip1 and CaSR were decreased in PHPT patients. This reduction may play an important role in the pathogenesis of PHPT. However, neither p27Kip1 nor CaSR expression was found to be useful in predicting prognosis or severity of disease.

Risk Factors and Frequency of Ingrown Nails in Adult Diabetic Patients.

The present study evaluated the properties of nails, frequency of ingrown nails in patients with type 2 diabetes mellitus (DM), risk factors for developing ingrown nails, and effect of diabetic polyneuropathy and vasculopathy on the development and outcome of ingrown nails. Our 6-month epidemiologic prospective study included 300 patients with type 2 DM attending a DM outpatient clinic for routine examinations. The general characteristics and foot changes of the study population were investigated. Diabetic polyneuropathy and vasculopathy were evaluated using a biothesiometer, monofilament tests, and arterial Doppler ultrasonography. The frequency of ingrown nails was 13.6%. Multivariate analysis with logistic regression showed that body mass index (odds ratio [OR] 1.077, 95% confidence interval [CI] 1.007 to 1.15; p = .03), previous trauma (OR 2.828, 95% CI 1.017 to 7,867, p = .042), a weak dorsalis pedis pulse (OR 2.72, 95% CI 1.17 to 6.30, p = .02), trimming type (OR 2.3, 95 CI 1.06 to 4.98), p = .35), onychogryphosis (OR 9.036, 95% CI 2.34 to 34.87, p = .001), and subungual hyperkeratosis (OR 4.3, 95% CI 1.99 to 9.3, p = .001) were predictive variables for ingrown nails in our population. The incidence of onychomycosis was significantly greater in patients with ingrown nails (p = .032) than in patients without ingrown nails. The nail curvature ratio was greater in the patients with ingrown nails than in the group with normal nails. Arterial Doppler ultrasound examinations showed peripheral arterial disease in 19 patients (46.9%) with ingrown nails. The prevalence of ingrown nails was greater in the patients with DM than in the healthy population. Our results indicate that nail type, nail morphology, and diabetic vasculopathy affect the formation and evolution of ingrown nails.

Annexin V expression and anti-annexin V antibodies in type 1 diabetes.

BACKGROUND: Annexin V (AnxV) has potent anticoagulant properties and regulatory functions for apoptosis and inflammation. Antibodies against annexin V (anti-AnxVs) may inhibit AnxV functions, leading to thrombosis during autoimmune diseases. Type 1 diabetes is an autoimmune disease and related with an ongoing autoimmune inflammation and thrombotic complications. There is no study evaluating anti-AnxVs/AnxV in a disease setting. OBJECTIVE: The aim of this study was to evaluate the status of AnxV and anti-AnxVs in patients with type 1 diabetes. METHODS: One hundred twenty-one patients with type 1 diabetes and 92 healthy controls were included in this study. Serum levels of AnxV and anti-AnxVs and expression of the AnxV gene and its common polymorphism in Kozak sequence (-1C>T) were studied. As a functional assay, the binding capacity of AnxV to platelets was evaluated. RESULTS: As compared with controls, type 1 diabetic patients had significantly low serum AnxV levels and AnxV gene expression. The number of anti-AnxV positivity and their serum levels were significantly higher in type 1 diabetic patients than controls. AnxV binding to platelets were significantly decreased in the type 1 diabetic patients. The frequencies of the -1C>T polymorphism of AnxV gene did not differ between groups. CONCLUSIONS: This study demonstrated the significant changes in AnxV levels and its function in type 1 diabetic patients. These results support the hypothesis that the defective AnxV system may have a role in ongoing autoimmune activity and the development of thrombotic complications in type 1 diabetes. Further studies are necessary to elucidate the clinical impact of anti-AnxVs and dysregulated AnxV function in type 1 diabetes.

Circulating glucagon to ghrelin ratio as a determinant of insulin resistance in hyperthyroidism.

Due to stimulated overall metabolism, a state of nutritional inadequacy often ensues, during thyrotoxicosis. We aimed to investigate circulating levels of some major components of the system that regulates energy stores, glucose, and fat metabolism, during thyrotoxicosis compared to euthyroidism. Fasting serum ghrelin, leptin, adiponectin, insulin, glucagon, glucose, as well as body fat composition were analyzed during thyrotoxicosis in 40 hyperthyroid patients (50.5 ± 15.2 years old, 22 females, 31 with Graves disease, and 9 with toxic nodular goiter). The same measurements were repeated an average 3 months later, when all patients achieved euthyroidism. Compared to euthyroidism, in thyrotoxicosis, patients had lower ghrelin and fat mass; had comparable insulin, HOMA-IR, glucagon, and leptin levels; higher levels of circulating adiponectin. Fasting serum glucose tended to be higher during thyrotoxicosis. The unique correlation of HOMA-IR was with the-glucagon to ghrelin ratio-(r = 0.801, p < 0.001) in hyperthyrodism, and with glucagon itself in euthyroidism (r = -0.844, p < 0.001). Circulating levels of ghrelin are decreased; leptin, insulin, glucagon are unchanged; adiponectin are increased during hyperthyroidism. The fasting HOMA-IR tends to be higher, despite the decreased adiposity in hyperthyroidism. The-glucagon to ghrelin ratio-strongly correlates with fasting HOMA-IR in hyperthyroidism.

Improvement in remission rates of the first operation in acromegalic patients.

AIM: The aim of the study was to determine the remission rates of the first operation with respect to the number of surgeons and the parameters important for the prediction of the success. MATERIAL AND METHODS: The study cohort consisted of 180 acromegalic patients who presented over a 29 year. All the patients had undergone transnasal transsphenoidal adenomectomy and then octreotide treatment and/or radiotherapy were applied to the patients who were not cured. Remission criteria was accepted as nadir GH < 1 µg/L with oral glucose tolerance test (OGTT) and normal IGF-1 with respect to age and gender. RESULTS: The postoperative median follow up period was 84 months (range 6-372 months). The remission rate of the first operation before 2003 was 20%, but this rate increased to 51% after 2003 (p=0.018). The most impressive improvement was due to the single experienced surgeon (49% vs. 5.3%) (p < 0.001). The success of the first operation was determined by the tumor size, microadenomas were more successfully treated than macroadenomas (p=0.014). The prevalence of discordance between GH and IGF-1 was 24% in patients cured after first surgery. CONCLUSION: The clinical recognition of acromegaly and outcomes of single experienced surgeons in specialized centers have significantly improved over the last years.

Ultrasound elastography is not superior to grayscale ultrasound in predicting malignancy in thyroid nodules.

BACKGROUND: Several studies have evaluated the ability of ultrasound elastography (USE) to diagnose malignant nodules. However, these studies had important limiting factors, selection bias and small sample size. The aims of the present study were to prospectively assess, in a large group of patients, the diagnostic power of USE for detecting malignancy in thyroid nodules, and to compare this technique with B-mode grayscale ultrasonography (BUS) and power Doppler ultrasonography (PD). METHOD: There were 194 patients with 237 thyroid nodules who were examined using BUS, PD, and USE. USE scores were classified according to the elasticity: score 1 as high, score 2 as intermediate, and score 3 as low (i.e., a high degree of stiffness). Fine-needle aspiration cytology (FNAC) was performed in all nodules at least two different times. Nodules having two benign FNAC readings that did not change the diameter during a 6-month follow-up period were classified as benign. Patients having thyroid nodules with indeterminate, suspicious, or malignant cytology had total or hemithyroidectomy to remove the nodule and treat the malignancy. RESULTS: Fifty eight (25%) nodules in 45 (23%) patients were found to be malignant. USE had a limited sensitivity and a positive predictive value in detecting malignant thyroid nodules and was not superior to BUS. USE had almost the same specificity and a negative predictive value as BUS. A power Doppler type-3 pattern was not of sufficient sensitivity to detect malignancies in thyroid nodules. CONCLUSIONS: In contrast to earlier reports, this current study noted a lower sensitivity and specificity of USE for the diagnosis of malignancy in thyroid nodules than previously reported.

The role of ultrasound elastography in preoperative localization of parathyroid lesions: a new assisting method to preoperative parathyroid ultrasonography.

BACKGROUND: After the definition of minimally invasive procedures, preoperative localization of parathyroid lesions is now crucial. False-positive results up to 30% were reported by B-mode grayscale ultrasonography (US) in localization of parathyroid lesions. Parathyroid adenomas are relatively stiff lesions. Ultrasound elastography (USE) can accurately evaluate tissue stiffness and might detect the stiff parathyroid lesions. OBJECTIVE: The aim of this study is to demonstrate whether USE can detect the level of the stiffness and help the preoperative localization of parathyroid lesions during parathyroid ultrasonography examination. PATIENTS: The patients who were candidates for parathyroidectomy were prospectively enrolled to this study and were evaluated by USE. RESULTS: Seventy-two patients with 93 parathyroid lesions underwent parathyroidectomy. Sixty-three patients including three multiple endocrine neoplasia type-1 patients had primary hyperparathyroidism, three patients with chronic renal disease (CRD) had tertiary hyperparathyroidism, three patients with CRD and two renal transplanted patients had persistent secondary hyperparathyroidism. One patient was excluded. While all parathyroid adenomas exhibited high levels of stiffness (score 3 and 4), 17 (63%) out of 27 parathyroid hyperplasia lesions were shown to have significantly higher elasticity. The evaluation of median strain ratios of parathyroid lesions revealed that parathyroid adenomas demonstrated significantly higher levels of stiffness than hyperplasias (P ≤ 0·001). CONCLUSIONS: This is the first study that evaluates the ultrasound elastographic features of parathyroid lesions. Parathyroid adenomas were shown to appear as stiff lesions, and half of the hyperplasias showed high elasticity. Parathyroid elastography is a novel technique to evaluate parathyroid lesions and might be a guide for surgeons to determine the type of operation to apply.

Hypokalemic paralysis is not just a hypokalemic paralysis.

OBJECTIVE: Although the commonest form of hypokalemic paralysis is the hereditary variety, some patients during course of thyrotoxicosis or with chronic potassium depletion, may exhibit episodic weakness. Approach to the patient with hypokalemic paralysis should be a careful search for the etiology and potassium replacement therapy. METHODS: In this report, two hypokalemic paralysis cases are described. RESULTS: Case 1 is a 29-year-old Caucasian male who developed thyrotoxic periodic paralysis. Case 2 is a 50-year-old female who experienced hypokalemic paralysis due to primary aldosteronism. CONCLUSION: Hypokalemic paralysis usually carries an underlying secret problem. Emergency department workers should give importance to etiological differentiation.

Effect of simvastatin use on bone mineral density in women with type 2 diabetes.

OBJECTIVE: To attempt to clarify the effect of simvastatin, a widely used statin, on the bone mineral density in women with type 2 diabetes. METHODS: We performed a cross-sectional, controlled study of 37 women with type 2 diabetes who were taking simvastatin. Each woman was matched with 2 control subjects who were closest in age, years since menopause (if applicable), and duration of diabetes on the date on which the examination was performed. We measured bone mineral density at the spine and the hip with a dual-energy xray absorptiometry scanner and compared bone density in the 2 study groups. RESULTS: The mean bone mineral density values of patients in the simvastatin group were found to be slightly increased in comparison with those of the control group, both in the lumbar vertebrae and in the femoral neck, but these differences were not statistically significant (P>0.05). CONCLUSION: In this cross-sectional study, we could not demonstrate a positive effect of long-term simvastatin treatment on bone mineral density in women with type 2 diabetes and hypercholesterolemia.

Color flow Doppler sonography for the etiologic diagnosis of hyperthyroidism.

Color flow Doppler sonography (CFDS) is gaining importance for the functional evaluation of the thyroid disorders. We aimed to determine the value of CFDS for the etiological diagnosis of hyperthyroidism. Fifty-five patients with hyperthyroidism (29 Graves' disease [GD] and 26 toxic adenoma [TA]), 24 patients with Hashimoto's thyroiditis (HT), and 39 euthyroid controls were included. Etiological diagnoses were carried out using standard methods. Conventional gray scale sonography was performed, followed by CFDS. Doppler patterns of the glands were scored and peak systolic velocity (PSV) measurements were obtained from intrathyroidal, perithyroidal, and perinodular vasculature. Vascular patterns were significantly more prominent, and the mean PSV values were significantly higher in the GD patients compared to the HT patients ( p < 0.001) and controls ( p < 0.001). Perinodular and intranodular signals and the mean perinodular PSV values were significantly higher in TAs compared to controls. CFDS could differentiate the untreated GD from the HT, which had similar gray scale findings. Hot nodules could also be differentiated from cold nodules with more prominent vascular patterns and significantly higher PSV values. As an inexpensive, fast, and noninvasive imaging procedure, CFDS could be helpful in the initial clinical evaluation and may avoid scintigraphy in a substantial number of thyrotoxic patients.

Effect of sibutramine on blood pressure in patients with obesity and well-controlled hypertension or normotension.

OBJECTIVE: To assess the short-term effects of sibu-tramine on blood pressure (BP) and heart rate (HR) in normotensive and controlled hypertensive obese patients by using ambulatory blood pressure monitoring (ABPM). METHODS: Before and 5 to 7 days after the initiation of sibutramine treatment (10 mg or 15 mg daily), when steady-state concentrations of sibutramine had been reached, ABPM was performed in 81 obese patients. Of this overall study group, 47 patients (26 with normoten-sion and 21 with controlled hypertension) received sibu-tramine in a dosage of 10 mg/day, and 34 patients (18 with normotension and 16 with controlled hypertension) received sibutramine in a dosage of 15 mg/day. RESULTS: Office-measured systolic and diastolic BPs in normotensive and controlled hypertensive groups of patients with obesity were not significantly different before and after treatment with both doses of sibutramine. ABPM results for normotensive obese groups showed that mean systolic and diastolic BPs were not significantly different after treatment with either 10-mg or 15-mg daily doses of sibutramine, in comparison with baseline. Similarly, in the controlled hypertensive obese groups, the ABPM results were not significantly different before and after sibutramine treatment. Moreover, the mean HR did not change significantly after versus before sibutramine treatment in both dosage groups. CONCLUSION: Sibutramine did not induce or exacerbate hypertension and had no effect on HR in normotensive and controlled hypertensive obese patients when used in either of two suggested daily doses (10 mg or 15 mg).

A stepwise approach to the treatment of amiodarone-induced thyrotoxicosis.

Amiodarone-induced thyrotoxicosis (AIT) is a complex therapeutic challenge. Two major forms have been described: type I and type II. Methimazole (MMI) and potassium perchlorate (KCLO(4)) is the treatment of choice for the former, whereas corticosteroids are used for the latter. However, mixed forms appear frequently and it is not easy to prescribe corticosteroids because of side effects. The present study investigated the validity of a stepwise therapeutic approach to AIT. Twenty patients with AIT were given 30-50 mg/d of MMI and 1000 mg/d of KCLO(4) initially for a month. Euthyroidism or a significant decrease in serum thyroid hormone levels could be achieved in 12 of the patients (7 with type I, 5 type II). Prednisolone, 40-48 mg/d was added for the 8 nonresponding patients (7 type I, 1 type II) and euthyroidism was achieved in all. The prednisolone dose was decreased when free thyroxine (T(4)) levels normalized, and MMI was titrated, maintaining euthyroidism until urinary iodine excretion normalized. Mixed forms of AIT may prevail in iodine-deficient areas. Initial classification of the patients may cause unnecessary corticosteroid use in a substantial number of patients with AIT. A stepwise approach is feasible; however, when the patient is gravely ill, MMI, KCLO(4), and prednisolone could be prescribed simultaneously.