Cutaneous findings in patients with acromegaly and its relationship with concomitant endocrinopathies.

OBJECTIVES: Skin changes in acromegaly are often the first sign of the disease. The aim of this study was to describe the cutaneous findings in patients with acromegaly. In addition, a secondary aim was to investigate the possible association of these findings with remission status and concomitant endocrinopathies. DESIGN, PATIENTS, AND MEASUREMENTS: In this prospective multicenter study, 278 patients over the age of 18 years with acromegaly who were followed up in 14 different tertiary healthcare institutions were included. These patients, who were followed up by the Endocrinology Department, were then referred to a dermatologist for dermatological examination. The frequency of skin lesions was investigated by detailed dermatologic examination. Dermatological diagnosis is reached by clinical, dermatological and/or dermoscopic examination, and rarely skin punch biopsy examinations in suspicious cases. The possible association of the skin findings between remitted and nonremitted patients and with concomitant endocrinopathies were evaluated. RESULTS: The most common skin findings in patients with acromegaly in our study were skin tags (52.5%), cherry angiomas (47.4%), seborrhoea (37%), varicose veins (33%), acneiform lesions (28.8%), hyperhidrosis (26.9%) and hypertrichosis (18.3%). Hypertrichosis was significantly more prevalent in patients nonremitted (p: .001), while xerosis cutis was significantly more prevalent in patients remitted (p: .001). The frequency of diabetes mellitus and hypothyroidism was significantly higher in patients with varicose veins and seborrhoeic keratosis than those without. Additionally, the coexistence of hypothyroidism, hyperthyroidism and galactorrhea was significantly higher in patients with Cherry angioma than in those without Cherry angioma (p-values: .024, .034 and .027, respectively). The frequency of hypogonadism in those with xerosis cutis was significantly higher than in those without (p: .035). CONCLUSIONS: Cutaneous androgenization findings such as skin tag, seborrhoea, acne and acanthosis nigricans are common in patients with acromegaly. Clinicians should be aware that skin findings associated with insulin resistance may develop in these patients. It can be said that the remission state in acromegaly has no curative effect on cutaneous findings. Only patients in remission were less likely to have hypertrichosis. This may allow earlier review of the follow-up and treatment of acromegaly patients presenting with complaints of hypertrichosis. Additionally, it can be said that patients with skin findings such as cherry angioma may be predisposed to a second endocrinopathy, especially hypothyroidism. Including dermatology in a multidisciplinary perspective in acromegaly patient management would be beneficial to detect cutaneous findings earlier.

The Effect of Diabetic Retinopathy and Blood Glucose Regulation on Corneal Biomechanical Parameters.

PURPOSE: The aim of this study was to evaluate the effects of different stages of diabetic retinopathy (DR) and metabolic control of blood glucose levels on corneal biomechanical parameters. METHODS: Diabetic patients were categorized into three groups: no DR group, nonproliferative DR (NPDR) group, and proliferative DR (PDR) group. Of the 141 eyes examined, 40 belonged to the control group, 34 to no DR group, 34 to NPDR group, and 33 to PDR group. Using an Ocular Response Analyzer to measure corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated IOP (IOPcc). IOP was assessed using a Tono-Pen, while central corneal thickness (CCT) was determined using an ultrasonic pachymeter. HbA1c levels were also recorded. We conducted comparisons among these groups across biomechanical parameters and IOP (tonopen), and CCT, while also investigating the impact of HbA1c levels on these parameters. RESULTS: Among any groups show a statistically significant difference in CCT, IOP (tonopen), CH, CRF, IOPg, and IOPcc. In diabetic patients, CRF, CTT, and IOPg values were significantly higher in those with HbA1c levels ≥ 7 mg/dl than in those with HbA1c levels < 7 mg/dl (p = 0.009, p = 0.013, p = 0.038), respectively, while there was no statistically significant difference in IOPcc, CH, and IOP (tonopen). Linear regression analysis showed that CH was positively associated with CCT (p < 0.001) and negatively associated with IOPcc (p < 0.001), while CRF was positively associated with CCT (p < 0.001), HbA1c (p < 0.05), and negatively associated with diagnosis of DR (p < 0.05). CONCLUSION: This study underscores the influence of metabolic control, as reflected by HbA1c levels, on corneal biomechanical parameters in diabetic patients, emphasizing the importance of monitoring and managing glycemic control in this population.

An evaluation of both serum Klotho/FGF-23 and apelin-13 for detection of diabetic nephropathy.

PURPOSE: The aim of our study is to evaluate whether serum Klotho/FGF-23 and apelin-13 can be used as new biomarkers for detection of development of nephropathy. METHODS: In this cross-sectional study, 88 type 2 diabetes mellitus (T2DM) patients and 38 healthy controls were included. The mean duration of T2DM was 11.4 ± 9.7 years. T2DM individuals were categorized into two groups as group 1 with e-GFR < 60 mL/min/1.73 m2 and group 2 with e-GFR > 60 mL/min/1.73 m2. They were also divided into two groups according to their 24 h urine albumin levels, classifying them as follows: normoalbuminuria if less than 30 mg/day and albuminuria if more than 30 mg/day. RESULTS: Mean serum Klotho levels in the T2DM group were observed to be significantly higher than in the control group. Serum apelin-13 levels were observed to be significantly lower in the T2DM group compared to the control group (p < 0.001). In the diabetic group, apelin-13 levels were positively correlated with age, waist circumference, and albuminuria while they were negatively correlated with e-GFR. Apelin-13 levels were seen to be significantly higher in group 1 (p < 0.001). CONCLUSION: Apelin-13 levels were found to be significantly higher in individuals with diabetic nephropathy than in those without diabetic nephropathy. In the diabetic group, a significant relationship was detected between apelin-13 levels and albumin excretion. Based on these findings, we consider that serum Klotho and apelin-13 levels may have a protective effect on diabetic nephropathy and can additionally be used as a biomarker to predict diabetic nephropathy.

Assesment of attainment of recommended TSH levels and levothyroxine compliance in differentiated thyroid cancer patients.

OBJECTIVE: Thyroid-stimulating hormone (TSH) suppression treatment can induce signs and symptoms of hyperthyroidism and hypothyroidism due to inappropriate treatment or poor compliance to the treatment. The current study aimed to investigate TSH levels, frequency of being on target TSH, adherence to levothyroxine (LT4) suppression treatment in differentiated thyroid cancer (DTC) patients after surgery in a multicentric setting. DESIGN AND PATIENTS: This multicentric cross-sectional study was conducted at 21 medical centres from 12 cities in Turkey. DTC patients followed at least one year in the same center included in the study. Clinical data, serum TSH, free thyroxine (FT4), thyroglobulin (Tg) and anti-Tg levels were recorded during the most recent visit. Body mass index, systolic and diastolic blood pressures, pulse rate were measured. LT4 doses were recorded and doses per kilogram of bodyweight were calculated. Pill ingestion habits recorded and adherence to the therapy were evaluated using the Morisky Medication Adherence Scale and categorized as good, moderate or poor compliant based on their scores. Risk stratification forpredicting the disease persistance and/or reccurence was assessed using the American Joint Committee on Cancer-7th edition thyroid cancer staging calculator. TSH serum concentrations were classified as severe suppression (TSH < 0.01 mU/L), moderate suppression (TSH: 0.01-0.1 mU/L), mild suppression (TSHL 0.1-0.5 mU/L), euthyroid (TSH: 0.5-4 mU/L) and hypothyroid (TSH > 4 mU/L). TSH levels can also be classified as on being on target, under the target, or beyond over the target, according to the American Thyroid Association recommendations. RESULTS: A group of 1125 patients (F/M: 941/184, 50.7 ± 11.7 years) were included in the study. The mean LT4 daily dosage was 132.4 ± 39.6 mcg/day. TSH levels showed severe suppression in 99 (%8.8) patients, moderate suppression in 277 (%24.6) patients and mild suppression in 315 (%28) patients and euthyroid range in 332 (%29.5) patients and hypothyroid range in 97 (8.6%). TSH levels were in target in 29.2% of the patients 20.4% of the patients were undertreated, 50.4% overtreated. The daily LT4 dose and LT4 dose/kg were significantly higher in the severe suppression group (p < .001, p < .001). According to the Morisky scale, 564 patients (50.1%) were good compliant, 368 patients (32.7%) were moderate compliant, and 193 patients (17.1%) were noncompliant. Patients with poor compliance need a higher dose of LT4 compared to the good compliance group (p < .001). TSH levels of patients with good compliance were 0.67 ± 1.96 mU/L and TSH with poor compliance was 2.74 ± 7.47 mU/L (p < .001). TSH levels were similar in patients on fixed and alternating dosages. CONCLUSION: In 29.2% of the DTC patients, serum TSH levels were at target levels. Remaining of the study group have TSH levels under or over treatment range, exposing the patient to medication side effects. Majorty of the study group 82.8% have good or moderate adherence to LT4 therapy. Reaching TSH targets requires simplified and applicable guidelines and following the guideline recommendations.

The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation.

Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

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.

Clinical and demographic aspects of Paget disease of bone: A multicentric study from Turkey.

OBJECTIVE: Paget disease of bone (PDB) is a metabolic bone disease that has been rarely reported in the Eastern countries. This study aimed to evaluate the clinical and demographic characteristics of patients with PDB followed up at endocrinology clinics in Turkey. METHODS: An invitation was sent to tertiary endocrinology clinics to complete a survey on the demographic, clinical, radiological, and laboratory parameters, as well as treatment modalities of patients with PDB. This study enrolled clinically and radiologically proven 185 patients with PDB from 18 endocrinology centers based in 10 cities of Turkey. RESULTS: This cohort of PDB had female preponderance (women/men: 105/80) with a mean age, during diagnosis, of 57±10 years. Most of the patients (59.6%) were symptomatic at diagnosis. Bone pain and headache were the predominant clinical symptoms. Polyostotic disease was observed in 67.5% (n=125) of patients. Frequently affected bones were skull (41.6%), pelvis (53.5%), spine (41%), and femur (25.4%). Moreover, 17 patients with skull involvement had hearing loss. Mean serum alkaline phosphatase (ALP) level (552±652 IU/L; range: 280-5762 IU/L) was over the normal reference cutoff with normal serum calcium levels. Intravenous bisphosphonates (zoledronic acid, 5 mg; pamidronate, 60-90 mg) were the most used drugs (75%) for the treatment of PDB. Most of the patients (87.1%) treated with intravenous bisphosphonates responded well, with a decrease in serum ALP level (117±114 IU/L) in the 12th month of therapy. Furthermore, 16 patients relapsed after the second year of therapy; 3 patients did not respond to the initial intravenous bisphosphonate treatment. CONCLUSION: The patients with PDB followed up by endocrinology clinics of Turkey exhibited polyostotic disease with classical clinical, radiological, and biochemical features and women's predominance with good response to intravenous bisphosphonate therapy.

Dopamine Agonist-Induced Impulse Control Disorders in Patients With Prolactinoma: A Cross-Sectional Multicenter Study.

CONTEXT: Dopamine agonist (DA)-induced impulse control disorder (ICD) in patients with prolactinomas is not sufficiently known. OBJECTIVE: To evaluate the prevalence of DA-induced ICDs and possible risk factors related to these disorders in patients with prolactinoma. DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional multicenter study involving 308 patients with prolactinoma followed up in tertiary referral centers who received at least three months of DA therapy. DA-induced ICDs (pathological gambling, hypersexuality, compulsive shopping, and compulsive eating) and impulsivity were assessed using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease and the Barratt Impulsiveness Scale-11, respectively. Patients were evaluated in terms of parameters related to ICD development. RESULTS: Any ICD prevalence was 17% (n = 51). Hypersexuality was most common (6.5%). Although any ICD and hypersexuality were more common in male patients (P = 0.009, P < 0.001, respectively), compulsive eating was more common in female patients (P = 0.046). Current smoking, alcohol use, and gambling history were more frequent (P = 0.033, P = 0.002, P = 0.008, respectively) in patients with any ICD. In Barratt Impulsiveness Scale-11 total, attentional, motor, and nonplanning scores were higher in patients with any ICD (P < 0.001). Current smoking and alcohol use were more frequent (P = 0.007, P = 0.003, respectively) and percentage increase of testosterone levels at last visit was higher (P = 0.021) in male patients with prolactinomas with hypersexuality. CONCLUSION: Any ICD may be seen in one of six patients with prolactinoma who are receiving DA therapy. Endocrinology specialists should be aware of this side effect, particularly in male patients with a history of gambling, smoking, or alcohol use.

A subset of patients with acquired partial lipodystrophy developing severe metabolic abnormalities.

Purpose/Aim of the study: Acquired partial lipodystrophy (APL) is a rare disease characterized by selective loss of adipose tissue. In this study, we aimed to present a subset of patients with APL, who developed severe metabolic abnormalities, from our national lipodystrophy registry. MATERIALS AND METHODS: Severe metabolic abnormalities were defined as: poorly controlled diabetes (HbA1c above 7% despite treatment with insulin more than 1 unit/kg/day combined with oral antidiabetics), severe hypertriglyceridemia (triglycerides above 500 mg/dL despite treatment with lipid-lowering drugs), episodes of acute pancreatitis, or severe hepatic involvement (biopsy-proven non-alcoholic steatohepatitis (NASH)). RESULTS: Among 140 patients with all forms of lipodystrophy (28 with APL), we identified 6 APL patients with severe metabolic abnormalities. The geometric mean for age was 37 years (range: 27-50 years; 4 females and 2 males). Five patients had poorly controlled diabetes despite treatment with high-dose insulin combined with oral antidiabetics. Severe hypertriglyceridemia developed in five patients, of those three experienced episodes of acute pancreatitis. Although all six patients had hepatic steatosis at various levels on imaging studies, NASH was proven in two patients on liver biopsy. Our data suggested that APL patients with severe metabolic abnormalities had a more advanced fat loss and longer disease duration. CONCLUSIONS: We suggest that these patients represent a potential subgroup of APL who may benefit from metreleptin or investigational therapies as standard treatment strategies fail to achieve a good metabolic control.

Evaluation of visual pathways using visual evoked potentials in the patients with impaired fasting glucose and impaired glucose tolerance.

PURPOSE: There are many studies on degeneration of the ganglion cells using visual evoked potential (VEP) in Diabetes mellitus (DM). The present study intended to investigate whether the retinopathy findings would be helpful for detecting the degeneration to develop or not in retinal ganglion cells with the VEP test before being detectable in ophthalmoscopic examination on prediabetic patients. MATERIALS AND METHODS: The present study was conducted prospectively after obtaining approval from the Ethics Committee. In our study, the subjects were divided into three groups as impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and normal patients. They also underwent physical, ophthalmological and VEP examination. Three main components of VEP obtained from these groups were N75, P100, and N145 latency and N75-P100 amplitude. RESULTS: The study participants consisted of the IFG group (n: 30, female/male ratio: 21/9; mean age: 49.17 ± 10.52 years), the IGT group (n: 30, female/male ratio: 23/7; mean age: 47.00 ± 11.09 years), and the Control Group (n: 40, female/male ratio: 30/10; mean age: 48.03 ± 10.96 years). Difference in sex and age between the study groups (p > 0.05). P100 latency was found to increase significantly in comparison between the IGT and Control Group for both eyes (p right: 0.003, p left: 0.001) whereas it did not increase significantly in the comparison between the IFG and the Control Group (p right: 0.065, p left: 0.116). CONCLUSION: It was observed that VEP may be a parameter of predictive value that might be used in evaluating prediabetic cases in terms of retinopathies similar to DM.

Out-of-Reference Range Thyroid-Stimulating Hormone Levels in Levothyroxine-Treated Primary Hypothyroid Patients: A Multicenter Observational Study.

OBJECTIVE: Although levothyroxine (LT4) replacement therapy for hypothyroidism has been established as safe, inexpensive and effective, many studies from different countries reported out-of-reference range thyroid-stimulating hormone (TSH) values for the hypothyroid patients under LT4 treatment. The aim of this study was to determine TSH levels of primary hypothyroid patients under LT4 treatment and to assess self-reported compliance with daily LT4 intake in tertiary care centers in Turkey. DESIGN: In this cross-sectional, observational study, adult patients with primary hypothyroidism, receiving LT4 treatment for at least 6 months, were included. The patients were from 12 tertiary care centers in 9 cities of Turkey. TSH and free T4 levels were recorded from patient files and self-reported compliance with daily LT4 intake was assessed by interviewing the subjects at the last visit. RESULTS: A total of 1,755 subjects (46 ± 13 years; F/M: 89.9/10.1%) with primary hypothyroidism were enrolled. Of the hypothyroid subjects, 44.8% had out-of-reference range serum TSH levels. TSH values were over the reference range (TSH > 4 mIU/L) in 26.2% and were under the reference range (TSH < 0.5 mIU/L) in 18.6% of the patients. Total duration of LT4 treatment was 5.9 ± 4.7 years and mean dose was 1.2 ± 0.6 µg/kg/day. Non-compliant patients (31.1%) had higher TSH levels (6.9 ± 16 vs 3.8 ± 0.9 mIU/L, P = 0.01) compared to compliant patients. CONCLUSION: The results of this study revealed that nearly half of the hypothyroid patients had out-of-reference range serum TSH values, despite under LT4 treatment. Compliance with LT4 treatment seems to be one of the major determinants to reach the target TSH levels in hypothyroid patients.

Impact of telephonic interviews on persistence and daily adherence to insulin treatment in insulin-naïve type 2 diabetes patients: dropout study.

OBJECTIVE: The objective of this study is to evaluate the impact of sequential telephonic interviews on treatment persistence and daily adherence to insulin injections among insulin-naïve type 2 diabetes patients initiated on different insulin regimens in a 3-month period. METHODS: A total of 1,456 insulin-naïve patients with type 2 diabetes (mean [standard deviation, SD] age: 56.0 [12.0] years, 49.1% were females) initiated on insulin therapy and consecutively randomized to sequential (n=733) and single (n=723) telephonic interview groups were included. Data on insulin treatment and self-reported blood glucose values were obtained via telephone interview. Logistic regression analysis was performed for factors predicting increased likelihood of persistence and skipping an injection. RESULTS: Overall, 76.8% patients (83.2% in sequential vs 70.3% in single interview group, (P<0.001) remained on insulin treatment at the third month. Significantly higher rate for skipping doses was noted in basal bolus than in other regimens (27.0% vs 15.0% for premixed and 15.8% basal insulin, respectively, P<0.0001). Logistic regression analysis revealed sequential telephonic interview (odds ratio [OR], 1.531; 95% confidence interval [CI], 1.093-2.143; P=0.013), higher hemoglobin A1c levels (OR, 1.090; 95% CI, 0.999-1.189; P=0.049), and less negative appraisal of insulin therapy as significant predictors of higher persistence. Basal bolus regimen (OR, 1.583; 95% CI, 1.011-2.479; P=0.045) and higher hemoglobin A1c levels (OR, 1.114; 95% CI, 1.028-1.207; P=0.008) were the significant predictors of increased likelihood of skipping an injection. CONCLUSION: Our findings revealed positive influence of sequential telephonic interview, although including no intervention in treatment, on achieving better treatment persistence in type 2 diabetes patients initiating insulin.

A case of familial partial lipodystrophy caused by a novel lamin A/C (LMNA) mutation in exon 1 (D47N).

BACKGROUND: Familial partial lipodystrophy (FPL) is a rare genetic disorder characterized by selective lack of subcutaneous fat which is associated with insulin resistant diabetes. The Dunnigan variety (FPL2) is caused by several missense mutations in the lamin A/C (LMNA) gene, most of which are typically located in exon 8 at the codon position 482. CASE REPORT: Here, we report on a Turkish family with FPL2 which is caused by a novel heterozygous missense LMNA mutation in exon 1 (D47N, c.139G>A), in the rod domain of lamins A/C. Fat distribution and metabolic features of LMNA D47N mutation were similar to typical codon 482 mutation. Metabolic abnormalities were observed as a form of insulin resistant diabetes, hypertriglyceridemia, low HDL cholesterol and hepatic steatosis. There was no evidence for neuromuscular and cardiac involvement. CONCLUSION: Although it is previously known that alterations in the rod domain of type A lamins are involved in cardiac and neuromuscular diseases, our current observation shows that exon 1 LMNA mutations may be associated with partial lipodystrophy without any cardiac and neurological abnormalities, at least at the time of the presentation.

Vitamin D status among adults in the Aegean region of Turkey.

BACKGROUND: Vitamin D is a lipid-soluble hormone found in certain foods and synthesized from precursors in the skin when exposed to ultraviolet light. Vitamin D plays a critical role in bone metabolism and many cellular and immunological processes and low levels have been associated with several chronic and infectious diseases. Vitamin D status is assessed by measuring the concentration of serum 25-hydroxyvitamin D [25(OH)D]. Vitamin D deficiency is reported to be common worldwide, but little has been reported about the vitamin D status of adults in Turkey. In this cross-sectional study, we determined the prevalence of 25(OH)D deficiency in adults residing in a city in the Aegean region of Turkey. METHODS: A survey was conducted on a representative sample of adults over 20 years old in a non-coastal city at the end of the winter season. Of the 209 households selected by random sampling, 8.6% (n = 18) were unoccupied and 21.5% (n = 45) refused to participate. Blood samples were taken and questions about medical history, vitamin supplementation, sunlight exposure, and dietary calcium and vitamin D intake were asked in face-to-face interviews of 391 adults living in the remaining households. RESULTS: The mean serum 25(OH)D concentration was 16.9 ± 13.09 ng/mL, with 74.9% of the subjects having 25(OH)D deficiency (<20 ng/mL), 13.8% having insufficiency (20-29.99 ng/mL), and 11.3% of the subjects having sufficient 25(OH)D (≥ 30 ng/mL) levels. 25(OH)D deficiency was more common among females (78.7%) than males (66.4%, p < 0.05). CONCLUSION: Adults living in an urban, non-coastal setting in Turkey have a high prevalence of vitamin D deficiency.

The prevalence of hyperprolactinaemia in overt and subclinical hypothyroidism.

The aims of this study were to: 1) determine the prevalence of hyperprolactinaemia in patients with newly diagnosed subclinical and overt hypothyroidism, and 2) investigate the change in PRL levels with treatment. In this observational study, patients with a new diagnosis of hypothyroidism in our endocrinology clinic were approached for participation, as were healthy controls. Patients with medical reasons for having elevated PRL levels, lactating and pregnant women were excluded from the study. No patient had kidney or liver disease. After examination to determine if clinical causes of PRL elevation were present, serum levels of thyrotropin (TSH), free thyroxine, free triiodothyronine and PRL were measured and correlation of PRL levels with the severity of hypothyroidism (overt or subclinical) was performed. Fifty-three patients (45 women, 8 men, mean age 45.3 ± 12.2 years) had overt hypothyroidism. One hundred forty-seven patients (131 women, 16 men, mean age 42.9 ± 12.6 years) had subclinical hypothyroidism. One hundred healthy persons (85 women, 15 men, mean age 43.9 ± 11.4 years) participated as controls. The same blood tests were repeated in patients after normalization of TSH levels with L-thyroxine treatment. PRL elevation was found in 36% of patients with overt hypothyroidism, and in 22% of patients with subclinical hypothyroidism. PRL levels decreased to normal in all patients after thyroid functions normalized with L-thyroxine treatment. In the hypothyroid patients (overt and subclinical) a positive correlation was found between TSH and PRL levels (r=0.208, p=0.003). PRL regulation is altered in overt and subclinical hypothyroidism, and PRL levels normalize with appropriate L-thyroxine treatment.

Psychometric properties and responsiveness of the Turkish version of the Diabetes Treatment Satisfaction Questionnaire (s) on a sample of diabetics of three consecutive monitoring periods.

The aim of this study is to test the psychometric properties and the responsiveness of the original (status) version of Turkish DTSQ. The study sample included 88 patients with diabetes mellitus who were evaluated in three consecutive time points. The first data collection time point was during their initial contact to the clinic, and the two following (3rd month and 6th month) were during the monitoring visits to the Celal Bayar University Endocrinology Department in 2007. After the adaptation of the DTSQ to Turkish language by following standard procedures, this instrument was applied to the patients along with WBQ-12 and World Health Organization Quality of Life Measure (WHOQOL-Bref). The reliability of the DTSQ was evaluated by running internal consistency analysis (Cronbach Alpha) and item analysis. Construct validity of the instrument was evaluated by various tests such as Principal Components analysis, Confirmatory Factor Analysis, Concurrent validity and "Known Groups" comparisons. Finally the sensitivity (responsiveness to change) of the DTSQ scores to the changes of the metabolic conditions were assessed. 50.0% of the participants were male with a mean age of 51.1 ± 11.4 (min 22, max 78). Majority of them had type 2 diabetes (86.4%) and 72.7% of these patients had at least one co-morbid chronic conditions. While 53.4% of the patients had been treated by insulin the remaining 46.6% had been taking oral anti-diabetic agents. The results revealed satisfactory alpha values for DTSQ (α > 0.70). All of the three metabolic measures (i.e., FBG, PBG, and HbA1c) had significant correlations with the DTSQ scores. The criterion and construct validity of the scale were found to be very satisfactory. The Turkish version of the DTSQ showed acceptable fit indices (RMSEA = 0.03, CFI > 0.90) with the original (hypothetic) construct. Almost all of the sub-dimensions of the WBQ and WHOQOL were correlated with the DTSQ as expected, indicating a good concurrent validity. DTSQ status version was found to be a reliable and valid instrument for the assessment of treatment satisfaction in Turkish diabetes mellitus patients.

Down-regulation of the auto-aggressive processes in patients with hypothyroid Hashimoto's thyroiditis following substitutive treatment with L-thyroxine.

BACKGROUND: Hashimoto's thyroiditis is a chronic, organ-specific autoimmune disease. It is the most common cause of primary hypothyroidism during the adolescent period, via autoimmune thyroid tissue destruction, affecting 2% of the population. The pathogenesis of Hashimoto's thyroiditis involves a complex interaction between predisposing genetic and environmental factors. OBJECTIVE: In this study, we wanted to investigate the role of cytokines such as IL-2, IL-4, IL-12 and IFN-gamma in the pathogenesis of the disease, and the changes to cytokine levels brought about by treatment with L-thyroxine. METHODS: Sixty five female patients, aged 18-73 years with Hashimoto's thyroiditis, referred to the Celal Bayar University Medical Faculty Endocrinology out-patients clinic, were included in this study. After a 10-12 week period of L-thyroxine treatment, all patients were restored to the euthyroid state. At the beginning and end of the treatment period, serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), autoantibodies against thyroid peroxidase (anti-TPO), autoantibodies against thyroglobulin (anti-Tg) levels were measured using a chemiluminecent, immunometric method, and cytokine levels were measured using ELISA. RESULTS: There was a statistically significant decrease in the serum levels of TSH (p < 0.0001) and a concomitant increase in FT4 serum levels (p < 0.0001). Also, during the post-treatment period, serum levels of anti-Tg (p < 0.01) and anti-TPO (p < 0.001) were significantly lower than during the pre-treatment period. A statistically significant decrease was shown for interleukin (IL)-12 serum levels during the post-treatment period (p < 0.001). However, the decrease in interferon (IFN)-gamma serum levels was not statistically significant (p = 0.276). On the other hand, no change was demonstrated in serum IL-2 and IL-4 levels (p = 0.953 and p = 0.313, respectively) after treatment with L-thyroxine. CONCLUSION: Considering that our study involved a 10-12 week period of treatment, the statistically significant decrease in serum IL-12 levels, and the statistically non-significant decrease in IFN-gamma levels, might indicate that a T helper type 1 inflammatory process had been halted or slowed down.

Evaluation of markers of inflammation, insulin resistance and endothelial dysfunction in children at risk for overweight.

OBJECTIVE: Childhood obesity is associated with impaired endothelial function, insulin resistance and inflammation. Being at risk for overweight has been defined as having a body mass index (BMI) between the 85th and 94th percentile for age and sex. In this study, we looked for features linked to cardiovascular risk in children who are at risk for overweight. DESIGN: Twenty-one children who were at risk for overweight (study group) and 20 children with a BMI between the 25th-74th percentiles (controls) were studied. Fasting blood levels of glucose, insulin, total cholesterol, HDL cholesterol, triglycerides, uric acid, fibrinogen and high sensitive C-reactive protein (CRP) were assessed in both groups. LDL-cholesterol, HOMA-IR and QUICKI indices were calculated. Flow-mediated Vasodilatation (FMD) was determined for the evaluation of endothelial function. RESULTS: Increased HOMA-IR was observed in children who were at risk for overweight. Waist circumference was the main predictor of insulin resistance in these children. Higher levels of CRP were found in the study group compared to controls, while plasma fibrinogen did not differ in the two groups. The children who were at risk for overweight had lower FMD values and slightly elevated lipids compared to controls; however, these differences were not statistically significant. CONCLUSION: Insulin resistance and inflammation indices were higher in children who were at risk for overweight as has been shown for obese children. The data suggest that appropriate treatment strategies for weight control are essential not only for obese children but also for those at risk for overweight.

Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNF-alpha, TGF-beta1 and bone turnover markers in the treatment of postmenopausal osteoporosis.

BACKGROUND: Osteoporosis that is encountered frequently in postmenopausal women, may cause an increased incidence of vertebral and iliac fractures that are associated with excess morbidity. Raloxifene hydrochloride, a selective oestrogen receptor modulator, has been shown to increase bone mineral density and decrease biochemical markers of bone turnover in postmenopausal women, without stimulatory effects on breast or uterus. Levels of proinflammatory cytokines, including IL-6, and TNF-alpha and TGF-beta1 which are important cytokines involved in remodeling, have been evaluated previously in in vitro studies of osteoporosis. However, there seems to be a paucity of in vivo research concerned with changes in these cytokines in osteoporosis. OBJECTIVE: In this study, we evaluated the effects of raloxifene (Evista); Lilly Pharmaceutical Co. USA, 60 mg/day) on biochemical bone turnover markers, serum parathyroid hormone, and 25-OH vitamin D, as well as the serum levels of IL-6, TNF-alpha and TGF-beta1, in 22 postmenopausal, osteoporotic women before and after 12 weeks of raloxifene treatment. METHODS: Well-matched, postmenopausal, non-osteoporotic control subjects were also enrolled in the study. Serum levels of all the parameters were measured in postmenopausal, osteoporotic women at baseline and end of the study. RESULTS: It was found that serum osteocalcin and parathyroid hormone, and urine deoxypyridinoline levels decreased to normal levels with treatment. Serum 25-OH vitamin D levels after treatment in the patient group were higher than those in the control group. Serum IL-6, TNF-alpha and TGF-beta1 levels did not change significantly with treatment. However, serum levels of IL-6 and TGF-beta1 in the patient group after treatment, decreased to levels lower than those found in the control group. Serum TNF-alpha levels in the patient group before and after treatment, were lower than those in the control group. CONCLUSION: Raloxifene treatment reduces bone turnover biochemical markers, parathyroid hormone and induces 25-OH vitamin D in postmenopausal women. Moreover, it also affects some serum cytokine levels in the postmenopausal period.