An international survey on hypoglycemia among insulin-treated type I and type II diabetes patients: Turkey cohort of the non-interventional IO HAT study.

BACKGROUND: Limited real-world data are currently available on hypoglycemia in diabetes patients. The International Operations Hypoglycemia Assessment Tool (IO HAT) study was designed to estimate hypoglycemia in insulin-treated type I (T1DM) and type II (T2DM) diabetes mellitus patients from 9 countries. The data from Turkey cohort are presented here. METHODS: A non-interventional study to determine the hypoglycemia incidence, retrospectively and prospectively, in Turkish T1DM and T2DM patients using a 2-part self-assessment questionnaire. RESULTS: Overall, 2348 patients were enrolled in the Turkey cohort (T1DM = 306 patients, T2DM = 2042 patients). In T1DM patients, 96.8% patients reported hypoglycemic events (Incidence rate [IR]: 68.6 events per patient-year [ppy]), prospectively, while 74.0% patients reported hypoglycemic events (IR: 51.7 events ppy), retrospectively. In T2DM patients, 95.9% patients (IR: 28.3 events ppy) reported hypoglycemic events, prospectively, while 53.6% patients (IR: 23.0 events ppy) reported hypoglycemic events, retrospectively. Nearly all patients reported hypoglycemia during the prospective period. CONCLUSIONS: This is a first patient-reported dataset on hypoglycemia in Turkish, insulin-treated diabetes patients. A high incidence of patient-reported hypoglycemia confirms that hypoglycemia remains under-estimated. Hypoglycemia increased healthcare utilization impacting patients' quality of life. Hypoglycemia remains a common side effect with insulin-treatment and strategies to optimize therapy and reduce hypoglycemia occurrence in diabetes patients are required. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02306681 (Date of registration: 12 Nov 2014; retrospectively registered).

The relationship between glucose metabolism disorders and malignant thyroid disease.

BACKGROUND: Previous studies have shown a positive relationship between insulin resistance and several common adult cancers. The present retrospective study aimed to investigate the association between glucose metabolism disorders (GMDs) and the prevalence of thyroid cancer. METHODS: We investigated the data of 4272 patients who had undergone fine-needle aspiration biopsy (FNAB) of thyroid nodules. The biopsy results were evaluated as diagnostic or non-diagnostic and the diagnostic results were classified as benign, malignant, and indeterminate. In this study, we included 2234 of the above patients who had undergone FNAB at our hospital and whose biopsy results were evaluated as diagnostic and were classified as either benign or malignant. We obtained the cytologic data and the glucose metabolism status of these patients retrospectively. RESULTS: Of the 2234 patients, 629 (28.1 %) had GMD (impaired fasting glucose, impaired glucose tolerance). Malignant cytology was determined in 106 (4.7 %) patients overall. Of the 629 patients with GMD, 582 (92.5 %) patients had benign cytology and 47 (7.5 %) patients had malignant cytology. Fifty-nine (3.7 %) of the 1605 normoglycemic patients had malignant cytology. Malignant cytology was determined more frequently in the patients who had GMDs (p < 0.001). CONCLUSION: The results demonstrated that thyroid cancer prevalence was higher in patients with GMD. According to our results, GMD should be considered as a risk factor for malignancy in the evaluation of thyroid nodules.

A Case Report of Concurrent Graves' Disease and Subacute Thyroiditis Following SARS-CoV-2 Vaccination: An Autoimmune/Inflammatory Syndrome (ASIA).

BACKGROUND: The response against adjuvants in vaccines is presented as autoimmune/inflammatory syndrome (ASIA). In this case report, we presented both SAT and Graves' disease in a patient as ASIA following the BNT162b2 mRNA COVID-19 vaccination. CASE PRESENTATION: A 31-year-old woman was admitted to the endocrinology outpatient clinic with the complaint of neck pain following the second dose of the BNT162B2 SARS-CoV-2 (Pfizer/BioNTech) vaccine. On physical examination, her thyroid gland was tender on palpation. Her thyroid function tests were compatible with hyperthyroidism, and inflammatory markers were high. In the thyroid ultrasonography (US) examination, we observed bilateral diffuse hypoechoic areas in the thyroid gland and increased vascularity in some parts of the thyroid. Anti-thyroid stimulating hormone receptor antibodies (TRAB) were positive. Overall, we considered concurrent subacute thyroiditis (SAT) and Graves' disease. CONCLUSION: The present study may be the first report to evaluate SAT and Graves' disease as ASIA following mRNA COVID-19 vaccination. Clinicians should be aware of possible vaccine-related complications.

A Case Report of Conversion from Hashimoto's Thyroiditis to Graves' Disease in Type 1 Diabetic Patient Following the COVID-19 Vaccination.

BACKGROUND: A considerable number of COVID-19 vaccines became available following the outbreak. Yet, various inflammatory and autoimmune complications have been reported following vaccination. We aimed to report the case of a type 1 diabetic patient converting from Hashimoto's thyroiditis to Graves' disease after the fourth dose of COVID-19 vaccine, thought to trigger an autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). CASE PRESENTATION: A thirty-one-year-old female patient with type 1 diabetes and Hashimoto's thyroiditis applied to our clinic with complaints of palpitations, anxiety, and weight loss one month after the fourth dose of COVID-19 vaccine (2 doses of CoronaVac + 2 doses of Pfizer/BioNTech). She was receiving levothyroxine 50 mcg/day. When her thyroid function tests showed thyrotoxicosis, we initially considered thyroxine-related exogenous thyrotoxicosis. However, we considered Graves' disease upon persisting thyrotoxicosis despite thyroxine withdrawal, positive serum TSH receptor antibody titers, and other imaging findings. Therefore, various autoimmune and inflammatory events have been reported after the COVID-19 vaccination. Adjuvants in vaccines can trigger autoimmune events, which lead to ASIA syndrome. COVID-19 vaccines may cause increased TSH receptor antibody levels or change the balance in the activity of blocking and stimulating antibodies, which may cause a conversion from Hashimoto's to Graves' disease. CONCLUSION: This was the first case report where the patient experienced a conversion from Hashimoto's to Graves' disease after COVID-19 vaccination, which may ultimately be related to ASIA syndrome. Yet, more data is needed to elucidate such a relationship, and patients should closely be checked regularly after four doses of vaccination.

The Experience of our Center in Patients Undergoing Insulin Degludec/ Insulin Aspart Co-formulation Therapy.

AIM: A co-formulation containing insulin degludec and insulin aspart (IDegAsp) is available for the treatment of diabetes in Turkey. We aimed to evaluate the clinical results of switching to IDegAsp treatment for Type 2 diabetes. METHODS: A total of 217 patients with type 2 diabetes treated with IDegAsp and having follow-up data were included. The patients were divided into 3 groups. Group 1 switched from basal insulin to IDegAsp, group 2 switched from twice-daily premixed insulin regimen to IDegAsp, and group 3 switched from intensive and thrice-daily premixed insulin regimen to IDegAsp. Groups were evaluated in terms of changes in insulin dose, the number of injections, and changes in HbA1c. RESULTS: The mean follow-up period was 7.5 ± 4.4 months. The mean age was 62.8 ± 12.9 years. The mean duration of diabetes was 15.3 ± 8 years. There was a significant decrease in HbA1c and glucose (p < 0.0001 and p < 0.0001, respectively). HbA1c was significantly reduced in group 1 (p < 0.0001) while insulin dose and the number of injections increased (p < 0.0001 and p < 0.0001, respectively). HbA1c, insulin dose, and the number of injections in group 2 and group 3 (p = 0.001, p = 0.002, p < 0.0001, respectively, and p < 0.0001, p = 0.043, p < 0.0001, respectively) were significantly reduced. CONCLUSION: This study includes real-life experiences involving a remarkable number of patients in the literature. IDegAsp treatment provided effective blood glucose regulation and caused a significant decrease in the insulin dose and the number of injections, resulting in increased quality of life among those who had to receive twice or more insulin injections.

Acoustic Radiation Force Impulse Elastography and Ultrasonographic Findings of Achilles Tendon in Patients With and Without Diabetic Peripheral Neuropathy: A Cross-Sectional Study.

AIMS: We aimed to evaluate the elastographic features of Achilles tendon with Acoustic Radiation Force Impulse in patients with and without diabetic neuropathy. METHODS: According to the presence of peripheral neuropathy, 45 patients with type 2 diabetes were divided into 2 subgroups. Those with peripheral neuropathy were defined as group I (22 patients) and those without peripheral neuropathy were defined as group II (23 patients). A total of thirty age-, gender-, and body mass index-matched healthy individuals were selected as controls. All participants underwent both ultrasonographic and Acoustic Radiation Force Impulse elastographic examination in order to evaluate Achilles Tendon thickness and stiffness. RESULTS: Achilles tendon thicknesses were similar between groups (p=0.991). Achilles tendon thicknesses of both patient groups were significantly higher than the control group (group I vs control p=0.01; group II vs control p=0.006). Stiffness values of Achilles tendons were similar between the control group and group II (p=0.993). Shear Wave Velocity was significantly lower in group I than group IIand control group (p<0.001). CONCLUSION: Diabetic patients with neuropathy have thicker and softer Achilles tendon while the elasticity of Achilles tendon in diabetic patients without neuropathy is similar to the healthy controls. Softening of the Achilles tendon may be an early sign of diabetic foot and reveal the patients with a risk of diabetic foot.

Uncoupling protein gene UCP1-3826A/G, UCP2 Ins/Del and UCP3-55C/T polymorphisms in obese Turkish children.

BACKGROUND: Mitochondrial uncoupling proteins (UCP) 1, 2 and 3 are members of the anion carrier protein family located in the inner mitochondrial membrane. There are various controversial reports on UCP genotypes and obesity in adults and children. This study aims to investigate the link between mostly studied UCP polymorphisms (UCP1-3826A/G, UCP2 Insertion/Deletion (Ins/Del) polymorphism of exon 8, and UCP3-55C/T Polymorphisms) and obesity in Turkish children. Furthermore, the relationships of UCP polymorphisms are also analyzed within the scope of metabolic parameters of obese children. METHODS: Molecular screening of the UCP1, UCP2, and UCP3 gene polymorphisms was carried out in 189 children aged 6 to 18 years, 102 of who had exogenous obesity (54 girls) and 87 of whom were healthy controls (48 girls). In the obese group, fasting lipids, glucose and insulin levels were measured. In 60 obese children, an oral glucose tolerance test (OGTT) was performed with 0, 30, 60, 90 and 120 minutes of sampling for plasma glucose and insulin levels. RESULTS: The frequency of UCP polymorphisms was similar in obese and non-obese children. In obese children, fasting lipids, glucose and insulin levels were not different among the UCP 1, 2 and 3 genotypes. While no relationship was found between the UCP 1 and 3 genotypes and glucose/insulin levels during OGTT, carriers of the Insertion allele with UCP2 Ins/Del polymorphism had significantly higher 30-minute insulin levels (p=0.018). CONCLUSIONS: Polymorphisms of the UCP1-3826A/G, UCP2 Ins/Del, and UCP3-55C/T are not associated with obesity and related pathologies in Turkish children. However, the presence of the Ins allele of the UCP2 gene has been found to have an unfavorable influence on early insulin excursion after glucose loading.

Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism.

BACKGROUND: Mitochondria are the main production site of free oxygen radicals, which can cause organ dysfunction by oxidation of cellular macromolecules such as carbohydrates, lipids and proteins. Oxidative stress may result from either overproduction of these species or from failure of the antioxidant defence systems. Thyroid hormones have well-known effects on mitochondrial oxygen consumption, but data about how hypothyroidism affects oxidative stress are controversial, and little is known about oxidative stress in subclinical hypothyroidism. Total antioxidant status (TAS) gives information about all of the antioxidants in the organism, while malondialdehyde (MDA) is a lipid peroxidation marker used to assess lipid peroxidation due to increased oxidative stress. We aimed to determine how hypothyroidism and subclinical hypothyroidism affect serum MDA and TAS. SUBJECTS AND METHODS: Serum TAS, MDA, C-reactive protein levels and lipid compositions were studied in 20 hypothyroid, 40 subclinical hypothyroid and 40 healthy subjects. RESULTS: MDA was elevated in both hypothyroid and subclinical hypothyroid patients compared with controls, while TAS levels show no significant differences between groups. Low-density lipoprotein (LDL) cholesterol levels were significantly high in both hypothyroid and subclinical hypothyroid patients. Triglyceride levels were high only in hypothyroid patients when compared with the controls. MDA showed a correlation with LDL cholesterol, total cholesterol and triglyceride. CONCLUSIONS: These results suggest an increased oxidative stress in both hypothyroid and subclinical hypothyroidism states, which can be explained by both the insufficient increase in the antioxidant status and the altered lipid metabolism in these cases.

49,XXXXY syndrome with autoimmune diabetes and ocular manifestations.

OBJECTIVE: We report a rare case of 49,XXXXY syndrome with autoimmune diabetes (requiring insulin therapy), bilateral cataracts and unilateral glaucoma. CLINICAL PRESENTATION AND INTERVENTION: A 25-year-old man with mental retardation presented with multiple skeletal abnormalities, polyuria and polydipsia. He had high glucose concentrations, without ketonuria, and hypergonadotropic hypogonadism. Ophthalmic examination revealed a polar cataract in both eyes and increased intraocular pressure in the left eye. The anti-islet cell antibody test was positive, and anti-glutamic acid decarboxylase autoantibody levels were elevated. Karyotype analysis revealed 49,XXXXY. Intensive insulin therapy and testosterone replacements were started. CONCLUSION: The autoimmune nature of diabetes that we observed in our patient seems to be predisposed by hypogonadism. Cataract and glaucoma in this case seem to be the result of diabetes, and an association of these ocular manifestations with the syndrome 49,XXXXY seems unlikely.

Clinicopathological characteristics of thyroid cancer in patients on dialysis for end-stage renal disease.

BACKGROUND: The prevalence rate of thyroid cancers in patients with renal failure is variable in different studies. Our aim was to determine the prevalence and clinicopathological characteristics of thyroid cancers in the dialysis population and to evaluate the potential risk factors. METHODS: We performed a retrospective analysis on end-stage renal disease (ESRD) patients on dialysis and thyroidectomized patients without ESRD (2000-2006). Then we compared the data of thyroid cancer patients on dialysis (n = 9) with the data of patients who had histopathologically verified benign thyroid disease on dialysis (n = 23) and with the histopathological data of thyroid cancer patients without ESRD. RESULTS: Papillary thyroid cancer (PTC) was the only histotype that was found in 9 of 420 (2.1%) ESRD patients on dialysis. Multifocal PTC was found in eight of nine patients; of them, four had follicular variant of PTC (FVPTC). Two patients had lymphatic metastasis at diagnosis. Eight PTCs were classified as tumor-node-metastasis (TNM) stage I and one as stage II. Among the analyzed factors, age (r = 0.374, p = 0.01) and duration of dialysis (r = 0.436, p = 0.007) showed a significant positive correlation with the occurrence of thyroid cancer. CONCLUSIONS: We conclude that the prevalence of thyroid cancer in patients undergoing dialysis was not higher than that in the background population. Age and duration of dialysis showed a significant positive correlation with the occurrence of thyroid cancer in patients on dialysis. Among the histotypes, there may be higher percentage of PTC, FVPTC, and multifocality in dialysis patients. The effect of these characteristics on prognosis of thyroid cancer in dialysis patients is needed to be further evaluated.

Radioactive iodine in the treatment of type-2 amiodarone-induced thyrotoxicosis.

OBJECTIVE: Amiodarone-induced thyrotoxicosis (AIT) is usually classified into two types: type 1, in which a high iodine content triggers the autonomous production of thyroid hormone; and type 2, in which destructive thyroiditis causes the release of preformed thyroid hormone. AIT is a difficult management problem that sometimes requires ablative thyroid therapy. The use of radioactive iodine (RAI) therapy in patients with type-1 AIT who had a 24-hour radioactive iodine uptake (RAIU) value of >10% has been previously reported. Despite its documented efficacy at usual doses (10-30 mCi) in patients with type-1 AIT, the efficacy of RAI in those with type-2 AIT has never been questioned, because type-2 patients usually have low RAIU. We thought that high adjusted-dose RAI might be an attractive alternative to thyroid gland ablation in patients with type-2 AIT. PATIENTS AND METHODS: Four patients with type-2 AIT who required thyroid ablation were included in the study. These individuals were either poor candidates for surgery or had refused surgery. The size of the thyroid gland in all subjects was within normal limits, and each thyroid was characterized by a homogenous echotexture on ultrasonography, the absence of vascularity on Doppler sonography, a low (<4%) 24-hour RAIU value and the absence of thyroid autoantibodies-all of which are characteristic of type-2 AIT. RESULTS: The patients were initially treated with thionamides and glucocorticoids. All patients except one achieved euthyroidism before RAI therapy. All four patients received one dose of RAI (range 29-80 mCi) and followed up for 12 months. No exacerbation of thyrotoxicosis was noted after RAI therapy. Hypothyroidism (in three patients) or euthyroidism (in one patient) was achieved in first six months. CONCLUSIONS: In patients with type-2 AIT, RAI treatment may be the therapy of choice for thyroid gland ablation.

Evaluation of brain natriuretic peptide levels in hyperthyroidism and hypothyroidism.

BACKGROUND: Brain natriuretic peptide (BNP) is secreted from the ventricular myocardium in response to volume expansion and pressure overload. Serum BNP levels are also affected by thyroid function status, which was mostly related to a direct stimulatory effect of thyroid hormones on the secretion of BNP. Although the diagnostic value of BNP in heart failure is undisputed, its value in the presence of the thyroid dysfunction has been recently questioned. The aim of this study was to evaluate the influence of thyroid dysfunction on BNP levels. METHODS: Evaluation of 18 overt and 47 subclinical hyperthyroid patients together with 39 subclinical and 13 overt hypothyroid patients was carried out in a cross-sectional study. Thirty-three age-, sex- and body mass index (BMI)-matched control subjects were also included. RESULTS: BNP levels were more than five times higher in hyperthyroid than euthyroid control subjects (P < 0.001). BNP levels were also higher in subclinical hyperthyroidism than euthyroid control subjects (P = 0.09). Correlation analysis revealed that free T4 and free T3 concentrations were associated with high serum BNP levels. The BNP level in patients with subclinical or overt hypothyroidism was similar to that of the controls. CONCLUSION: The current study provides additional insight into the diagnostic value of BNP in the presence of coexistent thyroid dysfunction and demonstrates important independent effects of thyroid hormones upon BNP plasma concentrations.

Needle-free delivery of lidocaine for reducing the pain associated with the fine-needle aspiration biopsy of thyroid nodules: time-saving and efficacious procedure.

OBJECTIVE: Fine-needle aspiration biopsy (FNAB) is a mandatory procedure in evaluation of thyroid nodules. However, it is sometimes perceived as a painful procedure by the patients. Efficacy of the needle-free injection of local anesthesia for reducing the pain associated with other cutaneous procedures that involve needle insertion was previously reported. In this double-blind, placebo-controlled clinical trial, we evaluated the effectiveness of a needle-free injection of lidocaine in achieving satisfactory pain control in patients undergoing FNAB of thyroid nodules. DESIGN: Patients were allocated to receive either lidocaine administered by needle-free injection system (n = 55) or placebo (isotonic saline) (n = 52) 2-3 minutes before FNAB. A series of four aspirations of each nodule was performed. The patients rated pain associated with the procedure according to a 100-mm visual analog scale (VAS), an 11-point numeric rating scale (NRS), and a four-category verbal rating scale (VRS). MAIN OUTCOME MEASURE: The two groups studied were similar with respect to age, sex, thyroid volume, nodule size, and nodule site. When the effectiveness of lidocaine was compared with that of placebo, the mean VAS score was 11.4 +/- 13.6 mm versus 38.2 +/- 35.5 mm (p < 0.0001) and the mean NRS score was 1.4 +/- 1.5 points versus 3.9 +/- 2.6 points (p < 0.0001), respectively. The absolute numbers according to VRS score in each group was also significantly different (p < 0.0001). The percentage of patients with "no pain" or "mild pain" in the lidocaine group (90.9%) was significantly higher than that in the placebo group (44.2%) (p < 0.0001). Less than 10% of the patients in lidocaine group experienced moderate pain and none experienced severe pain. No adverse treatment-related effects were observed. CONCLUSIONS: To our knowledge, this is the first study demonstrating that the needle-free delivery of lidocaine is an effective, useful, and noninvasive method of providing local anesthesia for the FNAB of thyroid nodules.

A new perspective in diagnosing polycystic ovary syndrome.

Recently, the term of "possible" polycystic ovary syndrome (PCOS) has been used for defining cases in which biochemical evaluations are incomplete but clinical phenotypes are suggestive of PCOS. The aim of this study was, by using Rotterdam 2003 criteria, to detect possible PCOS cases and compare their characteristics and insulin sensitivity status with confirmed PCOS subjects. One-hundred-eighteen women who admitted with complaints and symptoms suggesting PCOS were included. Insulin sensitivity status of the cases was calculated with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Cases fulfilling Rotterdam 2003 criteria were defined as confirmed PCOS, whereas indeterminate subjects as possible PCOS. Confirmed PCOS was detected in 70 (59.3%) and possible PCOS in 48 (40.7%) cases. Confirmed PCOS was most prevalent among subjects with hirsutism and menstrual dysfunction; 32 (80.0%) vs. 8 (20%), (p=0.000). Body mass index and HOMA-IR values did not differ between groups: confirmed PCOS versus possible PCOS; 25.46+/-5.55 kg/m(2) vs. 26.75+/-7.55 kg/m(2), 3.37+/-4.12 vs. 3.21+/-2.50, (p>0.05). Family history of type-2 diabetes mellifus was similar within both groups (p>0.05). Many PCOS patients seem to be undiagnosed due to inadherence to diagnostic work-up and/or to not fulfill Rotterdam 2003 criteria. These criteria may not be sufficient to cover the entire spectrum of PCOS.

Lanreotide autogel and insulin sensitivity markers: report of 5 acromegalic patients and literature review.

OBJECTIVE: To evaluate the short-term effects of Lanreotide Autogel on insulin sensitivity markers among acromegalic patients with pituitary tumors. DESIGN: Prospective clinical trial with six months of follow-up. SETTING: A tertiary endocrinology clinic. MATERIALS AND METHODS: Naïve patients (patient No. 1 and patient No. 3) and patients who experienced prior somatostatin analogue treatment (patient No. 2, patient No. 4, and patient No. 5) were included. Before and after 6 months of Lanreotide Autogel therapy, insulin sensitivity in each subject was determined using homeostasis model assessment of insulin resistance and beta-cell function formula. Euglycemic hyperinsulinemic clamp test was also performed to evaluate whole insulin sensitivity and was indicated as an 'M' index. RESULTS: All patients experienced reduction in their HOMA-beta. We noted major HOMA-beta decreases accompanied by pronounced increases in M indices for patients Nos. 1, 2 and 3 (1.03 vs. 8.22, 2.98 vs. 4.70, and 5.09 vs. 13.09, respectively). The increases in M indices of these patients were with marked decreases in GH levels (34.20 vs. 15.30 microg/l, 4.25 vs. 0.74 and 5.0 vs. 0.66 ng/mL, respectively). Minor decline in HOMA-beta and worsened M index and almost stable GH were observed in patients Nos. 4 and 5. Except for patient No. 3, all participants showed declining HOMA-IR. CONCLUSIONS: Short-term Lanreotide Autogel treatment has been observed to improve M indices of acromegalic patients whose GH levels exhibited marked reduction. This amelioration seemed to be related to decreases in GH levels rather than to a direct drug effect.

Serum osteoprotegerin concentration with strontium ranelate treatment for postmenopausal osteoporosis: an open, prospective study.

BACKGROUND: Strontium ranelate (SR) is a new antiosteoporotic agent with antiresorptive and bone-forming properties. The exact mechanism by which SR exerts its effects is not clearly understood. Bone resorption requires interaction between osteoblasts and osteoclasts. Osteoblasts produce a ligand for receptor activator of nuclear factor-κB (RANK). They also secrete osteoprotegerin, a decoy protein that blocks the interaction of RANK with its ligand, thereby inhibiting the differentiation and activity of osteoclasts. SR also has been associated with osteoblast proliferation and decreased osteoblast-induced osteoclast differentiation via increased osteoprotegerin messenger RNA expression in human osteoblasts. OBJECTIVE: The aim of this study was to investigate the relationship between SR treatment and serum osteoprotegerin concentration in women with post-menopausal osteoporosis (PMO). METHODS: This open, prospective study was conducted in women admitted to the outpatient endocrinology clinic of Baskent University Faculty of Medicine, Adana Medical Center, Ankara, Turkey, for the evaluation of PMO. Women with PMO who enrolled were administered elemental calcium 1000 mg/d and vitamin D 800 IU/d for 1 month before the study period. After obtaining baseline serum samples for determining osteoprotegerin concentrations, patients were assigned to the treatment or control groups at a 5:2 ratio and SR 2 g/d was administered to the treatment group. The control group continued to receive only calcium and vitamin D. Serum osteoprotegerin concentration was measured again after 3 months of treatment. RESULTS: Thirty-five women (treatment group: n = 25; mean [SD] age, 59.80 [7.38] years; control group: n = 10; mean [SD] age, 56.60 [5.06] years) enrolled in the study. A total of 32 women-24 in the treatment group and 8 in the control group-completed the study. Compared with baseline, mean [SD] serum osteoprotegerin concentration did not change significantly after 3 months in either the treatment group (4.91 [1.24] pmol/L vs 4.71 [1.19] pmol/L) or the control group (5.36 [2.82] pmol/L vs 5.10 [2.19] pmol/L). CONCLUSION: The results of this small study found that serum osteoprotegerin concentrations were not significantly changed by SR treatment for 3 months among women with PMO.

Surgery for hyperthyroidism in Down syndrome: case report.

Thyroid disorders are common in patients with Down syndrome (DS). In these patients, hyperthyroidism occurs much less frequently than hypothyroidism, but it is likely to be underestimated. We report a case of an adult man with DS and hyperthyroidism. After 2 years of antithyroid therapy in a special facility, he was referred to our center with recurrence of hyperthyroidism with leukopenia and elevations of liver enzymes 14 months after remission. The patient underwent subtotal thyroidectomy, with rapid preparation with inorganic iodine and prednisone. After thyroidectomy the patient was found to have hypothyroidism and was given thyroid replacement therapy. We also review the literature on the treatment options for hyperthyroidism with DS. We conclude that the role of surgery in the treatment of hyperthyroid patients with DS has yet to be defined.

Long-term outcome of Graves' disease patients treated in a region with iodine deficiency: relapse rate increases in years with thionamides.

BACKGROUND: Graves' disease (GD) is an autoimmune disease affecting the thyroid gland and eyes and is treated with three therapeutic modalities. This prospective study was designed to find out the outcome of patients with GD treated with thionamides, radioactive iodine (RAI) or surgery in an iodine deficient region. MATERIALS AND METHODS: Fifty-six nonsmoking patients (mean age 38.9 +/- 13.7 years) with GD were enrolled and followed for a mean period of four years. They were analyzed with respect to their treatment options and their outcome. RESULTS: Remission rate by thionamides was 74.4% in the first year but decreased to 65.1% in the following four years (p=0.0001). Remission rate achieved in the second year did not predict long-term remission with thionamides. Long-term remission rates for RAI and surgery were 100% during about seven years of follow-up. These remission rates for RAI and surgery were reached in the first year and did not reveal a statistically significant change in the following years. Thyroidectomy, both subtotal and total, was carried out without any complication. Graves' ophthalmopathy emergence and progression were not found to be correlated with the preferred therapeutic modality of thyrotoxicosis. CONCLUSION: Long-term thionamide therapy offered a relatively low rate of long-term remission in a region with iodine deficiency. Two years of remission achieved by thionamides did not predict long-term remission in patients living in iodine-deficient areas. RAI and thyroidectomy in experienced hands proved to be better therapeutic alternatives that can be carried out safely.

Severe hypertriglyceridemia-induced pancreatitis during pregnancy.

Chylomicronemia syndrome is a rare disorder characterized by the presence of chylomicrons in the fasting state. An acute and potentially life-threatening complication of chyiomicronemia syndrome is severe acute pancreatitis. We report a case of a 24-year-old primigravida with severe hypertriglyceridemia-induced pancreatitis. We reviewed the clinical course and treatment of hypertriglyceridemia-induced pancreatitis. She was admitted in the 37th week of gestation with severe abdominal pain, which was radiating to the back, and having uterine contractions. Cesarean delivery was performed under spinal anesthesia, and a healthy male infant was born. Intraoperative findings included milky peritoneal fluid collection. Elevated pancreatic enzymes with significant hypertriglyceridemia (10,092 mg/dL) suggesting acute pancreatitis were also found on chemical analysis. The diagnosis of acute pancreatitis was confirmed by computed tomography scan. Treatment with continuous intravenous insulin--glucose, cessation of oral intake, and nasogastric decompression--dramatically decreased the triglyceride levels to 608 mg/dL within five days. She was discharged as symptom free with strict dietary intervention after 10 days. Intravenous insulin is a low-cost and effective alternative treatment in hypertriglyceridemia-induced pancreatitis during pregnancy. To our knowledge, such a high triglyceride level has not previously been reported in pregnancy.

Preventive and therapeutic effects of relaxin on bisphosphonate related osteonecrosis of the jaw: an experimental study in rats / Efeitos preventivos e terapêuticos da relaxina na osteonecrose da mandíbula relacionada a bisfosfonatos: um estudo experimental em ratos

Objective: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging complication of chronic bisphosphonate (BP) use. The hormone relaxin is able to induce the multistep differentiation process of human osteoclastogenesis, exhibits antifibrotic and anti-inflammatory actions, and promotes vasodilatation, wound healing, and angiogenesis. The present study aimed to evaluate the effects of relaxin in the prevention and management of BRONJ. Material and Methods: Thirty-six male Sprague Dawley rats were randomly divided into four groups. Rats in group 1 (n = 10) received relaxin and BP simultaneously for 12 weeks. Rats in group 2 (n = 10) received injections of BP for 12 weeks, followed by relaxin for another 12 weeks. Rats in group 3 (n = 10) received only BP injections, and those in group 4 (control, n = 6) received only saline. Necrosis and inflammation in the rats' mandibles were evaluated as indicators of BRONJ. Results: Necrosis and inflammation were not detected in group 1 (BP + relaxin). In group 3 (BP only), incidence rates of necrosis and inflammation were 90% and 60%, respectively. Conclusions: Our findings suggest that relaxin may be potently effective in preventing BRONJ and have some benefit in the treatment of existing BRONJ (AU)

Objetivo: A osteonecrose da mandíbula relacionada ao bisfosfonato (BRONJ) é uma desafiadora complicação do uso crônico de bisfosfonato (BP). O hormônio relaxina é capaz de induzir o processo múltiplo de diferenciação da osteoclastogênese humana, exibe ações anti-fibróticas e anti-inflamatórias e promove vasodilatação, cicatrização de feridas e angiogênese. O presente estudo teve como objetivo avaliar os efeitos da relaxina na prevenção e tratamento do BRONJ. Material e Métodos: Trinta e seis ratos Sprague Dawley machos foram divididos aleatoriamente em quatro grupos. Os ratos do grupo 1 (n = 10) receberam relaxina e BP simultaneamente por 12 semanas. Os ratos do grupo 2 (n = 10) receberam injeções de BP por 12 semanas, seguidos de relaxina por mais 12 semanas. Os ratos do grupo 3 (n = 10) receberam apenas injeções de BP e os do grupo 4 (controle, n = 6) receberam apenas solução salina. Necrose e inflamação nas mandíbulas dos ratos foram avaliadas como indicadores de BRONJ. Resultados: Necrose e inflamação não foram detectadas no grupo 1 (BP + relaxina). No grupo 3 (somente BP), as taxas de incidência de necrose e inflamação foram de 90% e 60%, respectivamente. Conclusões: Nossos resultados sugerem que a relaxina pode ser potentemente eficaz na prevenção do BRONJ e ter algum benefício no tratamento do BRONJ existente.(AU)