Evaluation of chronic pruritus and associated skin findings in patients with diabetes mellitus.

Background/aim: To explore the dermatological lesions associated with chronic pruritus in patients who were followed up at our clinic for type 1 and type 2 diabetes mellitus (DM). Materials and methods: The study population consisted of 249 patients with DM, who presented to the endocrinology clinic at Ankara University Faculty of Medicine between January 2022, and March 2022, regardless of whether they had reported experiencing pruritus symptoms. The visual analog scale and 5-D itch scale were used to determine the severity of itching in patients. Dermatological examination findings were also evaluated. Results: Of the 249 patients with DM, mean duration since diabetes was diagnosed was 12 ± 9.2 [median 10 (0.3-46)] years, and the mean HbA1c levels were 8.1% ± 2.1%. Pruritus was detected in 77 (30.9%) patients and the mean duration of diabetes diagnosis was 13.4 ± 9.7 years. Examination of the microvascular and macrovascular complications showed that the incidence of retinopathy, nephropathy, neuropathy and peripheral arterial disease was 31.2% (p = 0.003), 31.2% (p = 0.005), 66.2% (p < 0.001) and 10.4% (p = 0.038), respectively, in the group with pruritus. These incidences were significantly higher in the group with pruritus than in those without pruritus. Dermatological examination showed that the most common condition was xerosis (64%), followed by fungal skin infection (16%) and bullous pemphigoid (8%). No skin findings were noted in 7% of patients who complained of itching. Conclusion: Chronic pruritus may be associated with several factors such as poor glycemic control, high BMI and microvascular and macrovascular complications in patients with DM. Especially in patients with severe generalized pruritus who do not respond to standard antipruritic treatments, the use of DPP-4 inhibitors, a class of oral antidiabetic agents, should be questioned and all medications being used by the patient should be reviewed.

Calcitonin levels in washout samples vs. cytology in the detection of malignant lymph node metastasis in recurrent medullary thyroid cancer

Background/aim: Calcitonin level in fine-needle aspirate washout fluid (Ct-FNA) was extensively studied for thyroid nodules and lymph nodes (LN). However, the data was scarce for neck recurrences/metastases of medullary thyroid cancer (MTC). Thus, the diagnostic accuracy of Ct-FNA and cytology in the detection of neck LN metastases of recurrent MTC cases were assessed. Materials and methods: The database of MTC patients between 2010 and 2021 was retrospectively reviewed. A total of 32 patients with recurrent MTC and suspicious LN who underwent FNA and Ct measurement from washout samples were included in this study. Preoperative serum Ct (sCt), Ct-FNA, Ct-FNA/sCt ratio, cytology data were recorded for all participants. Results: Median sCt of 32 patients and Ct-FNA washout fluid levels of operated suspicious 44 LNs were 723 (54­9000) pg/mL and 1800 (151­9500) pg/mL, respectively. The diagnostic accuracy of Ct-FNA washout fluid was greater than cytology (95.4% vs. 86%, respectively). Using a cut-off level of >638.5 pg/mL, the Ct-FNA predicted the diagnosis of LN metastasis of recurrent MTC with a sensitivity of 80% and specificity of 94.9%. Furthermore, using a cut-off level of >1.16, the Ct-FNA/sCt ratio well predicted the diagnosis of LN metastasis of recurrent MTC with a sensitivity of 92.3% and specificity of 100%. Conclusion: As Ct-FNA has greater diagnostic accuracy in our study, it would be complementary to cytology results to localize metastatic LNs in recurrent MTC. Furthermore, for the first time, we demonstrated that the Ct-FNA/sCt ratio was a better predictor of metastatic LNs in recurrent MTC than a particular cut-off for Ct-FNA alone.

Diagnostic accuracy of parathyroid hormone levels in washout samples of suspicious parathyroid adenomas: A single-centre retrospective cohort study.

INTRODUCTION: Minimally invasive surgery is an alternative surgical approach for primary hyperparathyroidism with less surgical trauma and anaesthesia complications. When combined with intraoperative measurement of parathyroid hormone (PTH), cure rates are exceeding 97%. Preoperative intact PTH determination in washout samples is really very useful when parathyroid lesions cannot be easily distinguished from thyroid lesions or sometimes lymph nodes. Herein, we aimed to report our institutional experience about parathyroid fine-needle aspiration (FNA) method and suggest a cut-off ratio for this purpose. METHODS: In our clinic, we performed ultrasonography (USG)-guided parathyroid FNA procedure for 131 patients diagnosed with primary hyperparathyroidism between January 2005 and January 2016. Both cytologic evaluation and intact PTH determination were performed in washout samples. Eighty-seven of the study group also had a parathyroid scintigraphy. Both demographic features and laboratory results were all recorded. RESULTS: Median serum PTH level was 142 (113-197), while mean PTH washout level was 1824 (0-3953). When three of the localization techniques are compared with each other, FNA-PTH washout group had a better diagnostic accuracy (90.8%) when compared to cytology (7.92%) and MIBI (67.8%) groups. Both MIBI and FNA-PTH washout group had 100% positive predictive value (PPV) and 100% specificity. We found values greater than 436.5 pg/mL for FNA-PTH washout with a sensitivity of 90.3% and specificity of 88.9% (P < 0.01 and AUC 94.3 (87.8-100)) and a cut-off for FNA/serum PTH greater than 3.05 with a sensitivity of 91.2% and specificity of 89% (P = 0.02 and AUC 94.5 (88.8-100)) which implicate parathyroid lesions. CONCLUSION: According to the literature, PTH determination in washout samples has a specificity of 75%-100% and sensitivity of 70%-100%. This approach has better results than both cytology and scintigraphy in case of concomitant multinodular thyroid disease in experienced hands. Although there is not a definite cut-off for PTH levels in washout samples, we agree with the need of ratios rather than cut-offs in this issue.

Cancer rates and characteristics of thyroid nodules with macrocalcification.

AIMS: The aim of this study was to determine the malignant potential of thyroid nodules with macrocalcifications and to evaluate the role of other sonographic findings in the diagnosis of malignancy in thyroid nodules besides macrocalcifications. METHODS: The findings of 8250 patients who applied to our outpatient clinic and underwent thyroid ultrasonography(US) between 2008 and 2021 were retrospectively reviewed. We included a total of 296 patients with 296 macrocalcified nodules (macrocalcification group) and an age- and sex matched group of 300 patients (control group) with the cytopathologic and/or histopathologic data of fine-needle aspiration biopsy (FNAB) of thyroid nodules without calcification. Demographic characteristics of these patients, US characteristics of the nodules, and thyroid function tests were recorded. Cytopathological data of FNAB were classified according to BETHESDA. RESULTS: The malignancy rate was 14.2% (42/296) in the macrocalcification group and 5.3% (16/300) in the control group (p < 0.001). There was no significant relationship between interrupted peripheral calcification and malignancy. Hypoechoic or markedly hypoechoic appearance, irregular border, solid structure, presence of accompanying pathological lymphadenopathy on sonographic examination and upper and middle zone localization were other sonographic features that increased the risk of malignancy of a nodule. The presence of autoimmunity was not found to be associated with the risk of malignancy. TSH and calcitonin levels of malignant nodules were higher than benign nodules. There was no significant difference between gender and malignancy. In the univariate analysis, it was found that the presence of macrocalcification increased the risk of malignancy 2.935 times. (OR:2.935, p < 0.001.95% CI for OR 1.611-5.349) In addition, being younger, being in the high TIRADS category, and being in the upper and middle zones were factors that increased the risk of malignancy. Gender, TSH level, nodule volume and structure were not associated with malignancy. However, after multivariate analysis, factors that significantly increased the risk of malignancy were younger age, higher TIRADS category, and nodule localization. CONCLUSION: In our study, the malignancy rate was higher in the macrocalcification group than in the control group. However, no correlation was found after multivariate analysis. In the multivariate analysis, younger age, higher TIRADS category, and nodules located in the upper and middle zone were other factors associated with malignancy. There was no association between peripheral interrupted calcification and malignancy risk.

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.

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.

Determination of insulin-related lipohypertrophy frequency and risk factors in patients with diabetes.

INTRODUCTION: Insulin, which is used in the treatment of diabetes mellitus (DM), may lead to the development of lipohypertrophy (LH) which can negatively affect the management of diabetes mellitus. Two common methods to detect LH are palpation and superficial subcutaneous ultrasonography (SSU). We investigated the frequency of non-palpable LH using SSU, as well as examining risk factors. METHOD: We included in our study patients who had been receiving insulin injections at least twice a day for over one year without palpable LH. The epidermis and the subcutaneous tissue thickness of each region were examined using SSU. The presence of LH and associated risk factors for LH were evaluated. RESULTS: We included 136 patients in our study. The mean age of all patients was 52.87±14.93 years, 59.6% were female and 73.5% had type 2 DM. The duration of DM and insulin usage were 15.76±9.20 and 11.42±8.26 years, respectively. The mean body mass index (BMI) of all patients was 30.59±7.40kg/m2. Non-palpable LH was detected in 87.5% (n=116) of the patients using SSU. In the multivariate logistic regression analyses, total cholesterol level, short-acting insulin dose and coronary artery disease (CAD) were associated with LH presence. CONCLUSION: Non-palpable LH can be seen at high rates in patients who have multiple insulin injections. Palpation is likely not enough to detect LH and we believe it would be appropriate to evaluate the presence of LH using SSU, especially for those who need high-dose insulin to control hyperglycaemia.

Determination of insulin-related lipohypertrophy frequency and risk factors in patients with diabetes.

INTRODUCTION: Insulin, which is used in the treatment of diabetes mellitus (DM), may lead to the development of lipohypertrophy (LH) which can negatively affect the management of diabetes mellitus. Two common methods to detect LH are palpation and superficial subcutaneous ultrasonography (SSU). We investigated the frequency of non-palpable LH using SSU, as well as examining risk factors. METHOD: We included in our study patients who had been receiving insulin injections at least twice a day for over one year without palpable LH. The epidermis and the subcutaneous tissue thickness of each region were examined using SSU. The presence of LH and associated risk factors for LH were evaluated. RESULTS: We included 136 patients in our study. The mean age of all patients was 52.87±14.93 years, 59.6% were female and 73.5% had type 2 DM. The duration of DM and insulin usage were 15.76±9.20 and 11.42±8.26 years, respectively. The mean body mass index (BMI) of all patients was 30.59±7.40kg/m2. Non-palpable LH was detected in 87.5% (n=116) of the patients using SSU. In the multivariate logistic regression analyses, total cholesterol level, short-acting insulin dose and coronary artery disease (CAD) were associated with LH presence. CONCLUSION: Non-palpable LH can be seen at high rates in patients who have multiple insulin injections. Palpation is likely not enough to detect LH and we believe it would be appropriate to evaluate the presence of LH using SSU, especially for those who need high-dose insulin to control hyperglycaemia.

The Association of Histologically Proven Chronic Lymphocytic Thyroiditis with Clinicopathological Features, Lymph Node Metastasis, and Recurrence Rates of Differentiated Thyroid Cancer.

The influence of chronic lymphocytic thyroiditis (CLT) on clinicopathological features and behavior of differentiated thyroid carcinoma (DTC) is still debated. In the present study, we aimed to evaluate the prognosis of DTC on the presence of CLT. A total of 649 total thyroidectomized patients (379 female, 270 male) with DTC, who had follow-up data for at least 36 months were included. Clinical, histopathological data, preoperative thyroid peroxidase antibody (TPO-ab), thyroglobulin antibody (Tg-ab), thyroid-stimulating hormone (TSH) levels, and presence of recurrent/persistent disease (R/PD) were evaluated retrospectively. Presence of CLT was defined by histopathology. Frequency of CLT was 32% (n = 208) among DTC patients. Mean tumor size (maximal diameter) was smaller in CLT group when compared to non-CLTs (p = 0.006). Capsular invasion, vascular invasion, tumor stage, risk groups, and R/PD were negatively associated with CLT (p < 0.01, p = 0.04, p = 0.03, p = 0.02, p < 0.01, respectively). Extrathyroidal extension was more frequent in non-CLT group when compared CLT (p = 0.052). Preoperative TSH level was positively associated with lymph node metastasis (LNM) and higher in patients with lateral LNM when compared to central LNM (p < 0.01). Central LNM, lateral LNM, stage 4 tumor, and intermediate- and high-risk tumor groups increased the risk of R/PH, 2.5-, 2.9-, 12.7-, 2.3-, and 4.2-fold, respectively. Presence of CLT was independently related with favorable outcomes, as the risk of R/PD was decreased by 0.49-fold. In conclusion, coexistence of CLT was negatively associated with tumor size, capsular invasion, vascular invasion, and tumor stage in DTC. Risk of R/PD was decreased by approximately half in patients with CLT.

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.

Effects of telmisartan and losartan treatments on bone turnover markers in patients with newly diagnosed stage I hypertension.

INTRODUCTION: Telmisartan is an angiotensin-II receptor type-1 blocker and a partial agonist for peroxisome proliferator-activated receptor-γ. The aim of this study was to determine the potential effects of telmisartan on bone metabolism and turnover markers. METHODS: Forty-two patients with newly diagnosed stage I hypertension who were prescribed telmisartan 80 mg/day or losartan 100 mg/day were included. Serum levels of calcium, phosphorus, 25-hydroxy vitamin D, bone-specific alkaline phosphatase, osteocalcin, interleukin 6 and 24-hour urinary N-terminal telopeptide were measured at the beginning and after 12 weeks of treatment. RESULTS: When treatment arms were evaluated together, significantly increased 25-hydroxy vitamin D levels (p=0.01), and decreased parathormone (PTH) (p<0.001), bone-specific alkaline phosphatase (p=0.01), osteocalcin (p=0.045), urinary N-terminal telopeptide (p<0.001) and interleukin 6 levels (p=0.006) were observed. After eliminating the 25-hydroxy vitamin D effect, significant changes were not observed at any of the parameters. None of the levels of parameters were different between groups. CONCLUSIONS: Neither telmisartan, despite its partial peroxisome proliferator-activated receptor-γ agonistic effect, nor losartan treatment had significant effects on bone turnover markers in newly diagnosed stage I hypertensive patients.

The Prognostic Roles of the Ki-67 Proliferation Index, P53 Expression, Mitotic Index, and Radiological Tumor Invasion in Pituitary Adenomas.

The fourth edition of the World Health Organization (WHO) classification of pituitary tumors recommended evaluation of tumor proliferation and invasion to identify aggressiveness. We aimed to assess the prognostic roles of the Ki-67 proliferation index, mitotic index, P53 expression, and cavernous sinus invasion in pituitary adenomas (PAs). Among the 601 patients who underwent transnasal/transsphenoidal adenomectomy from 2001 to 2016, 101 patients (16.8%) who had tumors with a high (≥ 3%) Ki-67 index (group A) and a control group consisting of 43 patients with a low (< 3%) Ki 67 index who were matched for age, gender, and tumor type were included. Mitotic index and P53 expressions were evaluated. Patient characteristics, histopathology reports, pre/postoperative magnetic resonance imaging (MRI), and follow-up data were assessed retrospectively. The frequency of macroadenomas and mean tumor size were greater in group A when compared to group B (67.4 vs. 94.1%, p< 0.01 and 25 ± 10.6 vs. 18 ± 11 mm, p< 0.01, respectively). Invasion to cavernous sinus was found in 53 (36.8%) patients and was more frequent in group A (p<0.01). The mean number of surgery was higher in group A than group B (p< 0.05). The mean follow-up period was 46.6 ± 34 months. The postoperative MRIs and follow-up data for at least 24 months were available in 117 patients. Recurrence risk was higher in group A than group B (p = 0.03). Tumors with high Ki-67 proliferation index were grouped as 3-5, 6-10, 11-15, and > 15%. The risk of recurrence was not different between groups of high Ki-67 index. The optimal cutoff point of the Ki-67 proliferation index that predicted recurrence was 2.5% with 84.6% sensitivity and 47.4% specificity. The cavernous sinus invasion on MRI was associated with recurrence (p = 0.03). Tumor size and recurrence risk were not associated with P53 expression. High P53 expression was related with cavernous sinus invasion (p = 0.03). The mitotic index was not associated with recurrence risk and tumor invasion. Recurrence risk was higher in tumors with ≥ 2 histopathological atypia criteria (p = 0.01). High Ki-67 index with a 2.5% cutoff point and cavernous sinus invasion on MRI are reliable markers for predicting recurrence in PAs. Recurrence risk is also higher in tumors with two histopathological aggressiveness criteria. Strict follow-up and more aggressive treatment approaches may be necessary for invasive-proliferative PAs.

Thyrotoxic hypokalaemic periodic paralysis in a Turkish population: three new case reports and analysis of the case series.

OBJECTIVE: Thyrotoxic hypokalaemic periodic paralysis (THPP) is an uncommon condition with intermittent episodes of muscle weakness and occasionally severe paralysis. THPP is a common complication of hyperthyroidism in Asian populations, and has also been reported in other ethnic groups including Caucasians. This study aimed to conduct an analysis of THPP in a Turkish population, and is to our knowledge the first analysis of a homogeneous Caucasian group. SUBJECTS: Forty cases with THPP were identified in the Turkish population. Three out of the 40 were new cases and were assigned as index cases. Two cases were not included in the analysis because of lack of data. RESULTS: THPP was diagnosed in 10 cases during the first attack and was observed to have a significant shorter complete recovery time statistically in this group (P < 0.01). The majority of cases were hypokalaemic, while there were two normokalaemic cases. Classification of the cases according to their potassium (K) levels revealed that the group with K levels < 2.5 mEq/l had a statistically longer amelioration time than the group with K levels > or = 2.5 mEq/l. When the cases were classified according to intravenous or oral application of K, the mean amelioration time was 6.8 +/- 3.6 h for the intravenous group and 13.1 +/- 7.6 for the oral group. Mean complete recovery times of the groups were 29.4 +/- 16.2 h and 52.8 +/- 18.0 h, respectively. The intravenous group had a shorter amelioration time and complete recovery time, and both were statistically significant (P < 0.05 for each). CONCLUSIONS: THPP may be seen among Caucasians. Diagnosing THPP during the first attack might decrease the recovery time. The level of hypokalaemia seems to affect the recovery time and initial low K levels may lead to more deterioration in a patient's health compared with mild or near-normal levels. Intravenous, rather than oral, application of K may be advantageous for shortening both the amelioration and complete recovery times.

Vitamin D receptor gene polymorphism and osteoporosis in the Turkish population.

Osteoporosis is one of the most important medical problems facing the aging population. It is defined as a decrease in the bone mass leading to an unacceptably high risk of fractures. Osteoporosis is a multifactorial disease. It is well established that genetic factors are involved in the pathogenesis of osteoporosis. Polymorphism of the vitamin D receptor (VDR) gene has been reported to play a major role in variations for genetic regulation of bone mass. Its role within various ethnic populations is not clear. The purpose of this project was to determine the frequencies of VDR genotypes in Turkey. Three polymorphisms of the VDR gene were analyzed using the polymerase chain reaction-restriction fragment length polymorphism technique. The sample for our study was comprised of postmenopausal women in Turkey, 100 of whom were diagnosed with osteoporosis. They were compared with 146 healthy controls. BsmI genotype frequencies in Turks resemble Caucasians rather than Asians, and Taq genotype frequencies in Turks neither resemble Caucasians nor Asians. The genotype frequencies of VDR were not statistically different between patients with osteoporosis and the control group. Among VDR haplotypes, bbAATT and bbTtAa are more frequent in the osteoporosis group than the control group.

The efficacy of fluorine-18-choline PET/CT in comparison with 99mTc-MIBI SPECT/CT in the localization of a hyperfunctioning parathyroid gland in primary hyperparathyroidism.

AIM: The aim of this study was to determine the role of fluorine-18-choline (F-FCH) PET/CT in comparison with technetium-99m-methoxyisobutylisonitrile (Tc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism and to investigate whether maximum standardized uptake value (SUVmax) may be indicative of disease severity. PATIENTS AND METHODS: Thirty-five primary hyperparathyroidism patients (24 females, 11 males, mean age: 55.31±12.27, range: 25-72 years) who underwent Tc-MIBI SPECT/CT and F-FCH PET/CT and had inconclusive neck ultrasonography (USG) were studied. The diagnostic power of both modalities and the relationship between SUVmax and biochemical [serum parathormone (PTH), calcium, phosphorus, vitamin D3 levels, urinary calcium excretion/24 h] and clinical (bone mineral densitometry and urinary USG results) parameters were analyzed. RESULTS: In 29 of 35 patients, Tc-MIBI SPECT/CT and F-FCH were concordant (κ=0.64, P=0.001). In five of 35 patients with a negative SPECT/CT, F-FCH PET/CT accurately localized parathyroid adenomas. In one patient, F-FCH was false negative and Tc-MIBI SPECT/CT showed the lesion. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Tc-MIBI SPECT/CT and F-FCH PET/CT were calculated to be 78, 100, 100, 70, 86%, and 96, 100, 100, 93, and 97%, respectively. SUVmax was correlated with lumbal T scores (P=0.026). The mean serum PTH levels were significantly higher (P=0.026) and lumbal and femur T scores were significantly lower (P=0.04 and 0.008) in patients with SUVmax greater than 4.4 (i.e. the mean SUVmax calculated in positive cases). CONCLUSION: F-FCH PET/CT has a high diagnostic power in primary hyperparathyroidism and can be used for further evaluation of patients with inconclusive neck USG and Tc-MIBI SPECT/CT. SUVmax of the hyperfunctioning parathyroid gland seems to be predictive of disease severity in terms of serum PTH and bone mineral densitometry results. Studies with larger patient groups are needed to support these data.

Higher schizotypy predicts better metabolic profile in unaffected siblings of patients with schizophrenia.

RATIONALE: Type 2 diabetes (T2D) is more frequent in schizophrenia (Sz) than in the general population. This association is partly accounted for by shared susceptibility genetic variants. OBJECTIVE: We tested the hypotheses that a genetic predisposition to Sz would be associated with higher likelihood of insulin resistance (IR), and that IR would be predicted by subthreshold psychosis phenotypes. METHODS: Unaffected siblings of Sz patients (n = 101) were compared with a nonclinical sample (n = 305) in terms of IR, schizotypy (SzTy), and a behavioural experiment of "jumping to conclusions". The measures, respectively, were the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Structured Interview for Schizotypy-Revised (SIS-R), and the Beads Task (BT). The likelihood of IR was examined in multiple regression models that included sociodemographic, metabolic, and cognitive parameters alongside group status, SIS-R scores, and BT performance. RESULTS: Insulin resistance was less frequent in siblings (31.7%) compared to controls (43.3%) (p < 0.05), and negatively associated with SzTy, as compared among the tertile groups for the latter (p < 0.001). The regression model that examined all relevant parameters included the tSzTy tertiles, TG and HDL-C levels, and BMI, as significant predictors of IR. Lack of IR was predicted by the highest as compared to the lowest SzTy tertile [OR (95%CI): 0.43 (0.21-0.85), p = 0.015]. CONCLUSION: Higher dopaminergic activity may contribute to both schizotypal features and a favourable metabolic profile in the same individual. This is compatible with dopamine's regulatory role in glucose metabolism via indirect central actions and a direct action on pancreatic insulin secretion. The relationship between dopaminergic activity and metabolic profile in Sz must be examined in longitudinal studies with younger unaffected siblings.

Course of Aggressive Somatotroph, Corticotroph and Mammotroph Tumors under Temozolomide; Report of Three Cases and Review of the Literature.

Treatment of aggressive pituitary tumors may be challenging. Temozolomide (TMZ) is a promising agent when conventional treatment methods fail. We present three patients with aggressive pituitary tumors with atypical morphology, who were resistant to conventional treatments and treated with TMZ. First case had a somatotroph adenoma, second a corticotroph adenoma, and the third a macroprolactinoma. We also reviewed the literature reporting TMZ efficacy in somatotroph, corticotroph and mammotroph tumors of pituitary. TMZ, 150-200 mg/m2 for 5 days in 28 days schedule was given to all patients. Among our patients, even though only the case of macroprolactinoma had a favorable response to TMZ treatment, both radiological and hormonal recurrences occurred 30 months after cessation of TMZ treatment. Then TMZ treatment was applied again. Cases of somatotroph and corticotroph adenomas had progressed under TMZ treatment and patients were lost due to mass effect of the tumor. Review of the literature demonstrated 67.3%, 60% and 26.7% overall response rates to the TMZ treatment in prolactinoma, corticotropinoma and somatostatinoma cases, respectively. There is still need to define response criteria uniformly to TMZ treatment in aggressive pituitary tumors and duration of response should be reported for reliable evaluation of results.

Effects of thyroxine therapy on right ventricular systolic and diastolic function in patients with subclinical hypothyroidism: a study by pulsed wave tissue Doppler imaging.

INTRODUCTION: The effects of l-thyroxine (l-T(4)) replacement for subclinical hypothyroidism (SH) on right ventricle (RV) functions has not been previously studied by means of pulsed wave tissue Doppler imaging (PWTDI). We investigated the effects of l-T(4) therapy on RV function in patients with SH using PWTDI. PATIENTS AND METHODS: Fifty-three patients with newly diagnosed SH and 25 controls were evaluated by standard echocardiography and PWTDI. After euthyroidism was restored by l-T(4), measurements were repeated. Myocardial systolic wave (S(m)) velocity, isovolumic acceleration (IVA), myocardial precontraction time (PCT(m)), and PCT(m) to contraction time (CT(m)) ratio were calculated as systolic indices. Early (E(m)) velocity, late (A(m)) velocity, E(m) to A(m) ratio, and myocardial relaxation time (RT(m)) were determined as diastolic measurements. RESULTS: S(m) was similar in patients and controls, whereas IVA was significantly lower in patients with SH (P < 0.001). SH patients had significantly decreased E(m) velocity, whereas A(m) velocity and E(m) to A(m) ratio did not differ. PCT(m) and RT(m) were significantly longer, and PCT(m) to CT(m) ratio was significantly higher in patients (P = 0.002, P = 0.002, P < 0.001, respectively). S(m) velocities were similar before and after l-T(4) replacement, whereas IVA significantly increased after therapy (P < 0.001). E(m) tended to increase (P = 0.05), whereas A(m) and E(m) to A(m) ratio were not changed. PCT(m), PCT(m) to CT(m) ratio, and RT(m) decreased significantly (P < 0.001 for all). CONCLUSIONS: SH is associated with RV systolic and diastolic dysfunction, and l-T(4) treatment improves these abnormalities. PWTDI, especially IVA, may be a suitable tool for the early detection of RV systolic dysfunction.

Evidence from autoimmune thyroiditis of skewed X-chromosome inactivation in female predisposition to autoimmunity.

The etiologic factors in the development of autoimmune thyroid diseases (AITDs) are not fully understood. We investigated the role of skewed X-chromosome inactivation (XCI) mosaicism in female predisposition to AITDs. One hundred and ten female AITDs patients (81 Hashimoto's thyroiditis (HT), 29 Graves' disease (GD)), and 160 female controls were analyzed for the androgen receptor locus by the HpaII/polymerase chain reaction assay to assess XCI patterns in DNA extracted from peripheral blood cells. In addition, thyroid biopsy, buccal mucosa, and hair follicle specimens were obtained from five patients whose blood revealed an extremely skewed pattern of XCI, and the analysis was repeated. Skewed XCI was observed in DNA from peripheral blood cells in 28 of 83 informative patients (34%) as compared with 10 of 124 informative controls (8%, P<0.0001). Extreme skewing was present in 16 patients (19%), but only in three controls (2.4%, P<0.0001). The buccal mucosa, and although less marked, the thyroid specimens also showed skewing. Analysis of two familial cases showed that only the affected individuals demonstrate skewed XCI patterns. Based on these results, skewed XCI mosaicism may play a significant role in the pathogenesis of AITDs.

Altered tear composition in smokers and patients with graves ophthalmopathy.

OBJECTIVES: To analyze, compare, and contrast tear composition in healthy nonsmokers, smokers who were otherwise healthy, and patients with Graves disease (GD) accompanied by Graves ophthalmopathy (GO) of varying severity. METHODS: Reflex tears were collected using Schirmer strips from 37 healthy nonsmokers, 33 otherwise healthy smokers, 51 patients with GD, and 85 patients with GO. Thyrotropin receptor-stimulating activity and serum thyroid-stimulating antibodies were measured. Pooled tear samples from healthy nonsmokers, healthy smokers, and patients with GO were separated by means of electrophoresis. Proteins expressed in healthy smokers, patients with GO, and healthy nonsmokers were separated by means of electrophoresis and analyzed by mass spectrometry. RESULTS: Based on the 97th percentile of findings from healthy nonsmokers, specific thyrotropin receptor-stimulating activity was detected in 25% of the tear samples from healthy smokers, 32% of those from patients with GD, and 41% of those from patients with GO. Clinical activity scores correlated with serum thyroid-stimulating antibody levels but not tear thyrotropin receptor-stimulating activity. Electrophoresis revealed additional proteins of 30 to 41 kDa in the tear samples from patients with GO and healthy smokers compared with samples from healthy nonsmokers. These proteins were identified as zinc-alpha2-glycoprotein and lactoferrin but have no thyrotropin receptor-stimulating activity. CONCLUSIONS: We demonstrate similar changes in tear composition in patients with GO and healthy smokers compared with healthy nonsmokers. Expression of zinc-alpha2-glycoprotein and lactoferrin is increased and their molecular weights are modified, suggesting degradation and/or changes during glycosylation, which may affect the bioactivities of zinc-alpha2-glycoprotein and lactoferrin. Clinical Relevance Smoking, which is a significant risk factor for the development of GO, modifies tear composition.