Landscape of congenital adrenal hyperplasia cases in adult endocrinology clinics of Türkiye-a nation-wide multicentre study.

BACKGROUND AND AIMS: Congenital adrenal hyperplasia (CAH) is a group of disorders that affect the production of steroids in the adrenal gland and are inherited in an autosomal recessive pattern. The clinical and biochemical manifestations of the disorder are diverse, ranging from varying degrees of anomalies of the external genitalia to life-threatening adrenal insufficiency. This multicenter study aimed to determine the demographics, biochemical, clinical, and genetic characteristics besides the current status of adult patients with CAH nationwide. METHODS: The medical records of 223 patients with all forms of CAH were evaluated in the study, which included 19 adult endocrinology clinics. A form inquiring about demographical, etiological, and genetic (where available) data of all forms of CAH patients was filled out and returned by the centers. RESULTS: Among 223 cases 181 (81.16%) patients had 21-hydroxylase deficiency (21OHD), 27 (12.10%) had 11-beta-hydroxylase deficiency (110HD), 13 (5.82%) had 17-hydroxylase deficiency (17OHD) and 2 (0.89%) had 3-beta-hydroxysteroid-dehydrogenase deficiency. 21OHD was the most prevalent CAH form in our national series. There were 102 (56.4%) classical and 79 (43.6%) non-classical 210HD cases in our cohort. The age of the patients was 24.9 ± 6.1 (minimum-maximum: 17-44) for classical CAH patients and 30.2 ± 11.2 (minimum-maximum: 17-67). More patients in the nonclassical CAH group were married and had children. Reconstructive genital surgery was performed in 54 (78.3%) of classical CAH females and 42 (77.8%) of them had no children. Thirty-two (50.8%) NCAH cases had homogenous and 31 (49.2%) had heterogeneous CYP21A2 gene mutations. V281L pathological variation was the most prevalent mutation, it was detected in 35 (55.6%) of 21OHD NCAH patients. CONCLUSION: Our findings are compatible with the current literature except for the higher frequency of 110HD and 17OHD, which may be attributed to unidentified genetic causes. A new classification for CAH cases rather than classical and non-classical may be helpful as the disease exhibits a large clinical and biochemical continuum. Affected cases should be informed of the possible complications they may face. The study concludes that a better understanding of the clinical characteristics of patients with CAH can improve the management of the disorder in daily practice.

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.

No association of Gaucher disease with COVID-19-related outcomes: a nationwide cohort study.

BACKGROUND: It is well documented that patients with chronic metabolic diseases, such as diabetes and obesity, are adversely affected by the COVID-19 pandemic. However, when the subject is rare metabolic diseases, there are not enough data in the literature. AIM: To investigate the course of COVID-19 among patients with Gaucher disease (GD), the most common lysosomal storage disease. METHODS: Based on the National Health System data, a retrospective cohort of patients with confirmed (polymerase chain reactionpositive) COVID-19 infection (n = 149 618) was investigated. The adverse outcomes between patients with GD (n = 39) and those without GD (n = 149 579) were compared with crude and propensity score-matched (PSM) groups. The outcomes were hospitalisation, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality. RESULTS: The patients with GD were significantly older and had a higher frequency of hypertension (HT), Type 2 diabetes mellitus (T2DM), dyslipidaemia, asthma or chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, heart failure and cancer. Although hospitalisation rates in Gaucher patients were found to be higher in crude analyses, the PSM models (model 1, age and gender matched; model 2, matched for age, gender, HT, T2DM and cancer) revealed no difference for the outcomes between patients with GD and the general population. According to multivariate regression analyses, having a diagnosis of GD was not a significant predictor for hospitalisation (P = 0.241), ICU admission/mechanical ventilation (P = 0.403) or mortality (P = 0.231). CONCLUSION: According to our national data, SARS-CoV-2 infection in patients with GD does not have a more severe course than the normal population.

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.

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.

The acromegaly registry of ten different centers in Turkey.

OBJECTIVES: To describe biochemical and clinical features, and therapeutic outcomes of acromegaly patients in Turkey. METHODS: Retrospective multicenter epidemiological study of 547 patients followed in 10 centers of the Turkish Acromegaly registry. RESULTS: A total of 547 acromegaly patients (55% female) with a median age of 41 was included in this study. Majority of patients had a macroadenoma (78%). Transsphenoidal surgery was performed as primary treatment in 92% of the patients (n = 503). Surgical remission rate was 39% (197/503) in all operated patients. Overall disease control was achieved in 70% of patients. Remission group were significantly older than non-remission group (p = .002). Patients with microadenomas had significantly higher remission rates than patients with macroadenomas (p < .001). Patients with microadenomas were significantly older at the time of diagnosis when compared to patients with macroadenomas (p < .001). Preoperative growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were significantly lower in the remission group (p < .001). Initial IGF-1 and GH levels were significantly higher in macroadenomas compared to microadenomas (p < .001). Medical treatment was administered as a second-line treatment (97%) in almost all patients without remission. Radiotherapy was preferred in 21% of the patients mostly as a third line treatment. CONCLUSIONS: This is one of the largest real life studies evaluating the epidemiological characteristics and treatment outcomes of patients with acromegaly who were followed in different centers in Turkey. Transsphenoidal surgery in the treatment of acromegaly still remains the most valid method. Medical treatment options may improve long-term disease outcomes in patients who cannot be controlled with surgical treatment (up to 70%).

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.

Could a nonfunctional adrenal incidentaloma be a risk factor for increased carotid intima-media thickness and metabolic syndrome.

BACKGROUND: This study was designed to detect the potential association of a nonfunctional adrenal incidentaloma (NFAI) with insulin resistance and associated metabolic disturbances, with a subsequent increase in cardiovascular risk factors. METHODS: Eighty-three NFAI patients and 56 volunteers (controls) without any adrenal abnormalities on computed tomography (CT) were included. Fasting blood glucose (FBG), fasting insulin, lipid profiles, uric acid, homocysteine, fibrinogen, high sensitivity C-reactive protein (hs-CRP), and adiponectin levels were measured in both groups. Blood pressure (BP), waist circumference, body mass index (BMI), and carotid intima media thickness (CIMT) were evaluated in both the patients and volunteers. RESULTS: There were no significant difference between the NFAI and control groups with respect to age, sex, BMI, waist circumference, systolic and diastolic BP, smoking, concomitant disease, and medications. Fasting insulin and glucose levels and homeostasis model of assessment-insulin resistance (HOMA-IR) scores were significantly higher in the NFAI group as compared with those in the control group (p<0.01). The frequency of metabolic syndrome in the NFAI group was higher than that in the control group (p<0.01). All the lipid fractions, except triglyceride (TG), (p<0.05), homocysteine (p=0.01), and fibrinogen levels (p<0.001), were significantly higher in the NFAI group as compared with the levels in the control group. There were no significant differences between the NFAI and control groups in terms of uric acid, hs-CRP, and adiponectin levels. The CIMT values in the NFAI group were significantly higher than those in the control group (0.74±0.14 vs. 0.53±0.09, p<0.001). The mean CIMT value showed a statistically positive correlation with age (r=0.245, p=0.004); the HOMA-IR score (r=0.490, p<0.001); and FBG (r=0.521, p<0.001), fasting insulin (r=0.432, p<0.001), total cholesterol (TC) (r=0.267, p=0.002), and fibrinogen (r=0.398, p<0.001) levels in the NFAI group. CONCLUSIONS: The results indicated that the NFAI patients had an elevated risk of insulin resistance, with metabolic syndrome and increased CIMT values. Long-term follow-up studies should be designed to evaluate postsurgical alterations in metabolic parameters and cardiovascular risk factors in NFAI patients.

The influence of thyroid nodule size on the diagnostic efficacy and accuracy of ultrasound guided fine-needle aspiration cytology.

BACKGROUND: Diagnostic accuracy of fine-needle aspiration cytology (FNAC) in large and subcentimeter nodules is still debated. We aimed to evaluate the impact of nodule size on efficacy of the ultrasound-guided FNAC. METHODS: B-mode grayscale ultrasound (US), US-guided FNAC according to Bethesda system and histopathological data of 514 nodules from 371 patients, who underwent thyroidectomy were examined retrospectively. Nodules were grouped by maximal diameter; group A nodules were smaller than 10 mm (n = 59), group B nodules were between 10 and 29 mm (n = 218), and group C nodules were 30 mm or greater (n = 130). RESULTS: Sensitivity, specificity, and accuracy of FNAC was 92.0%, 100%, and 95.1% in group A, 80.7%, 99.1%, and %92.9 in group B, 70.0%, 98.9%, and 95.8% in group C nodules, respectively. The prevalence of papillary thyroid cancer (PTC) and incidental PTC were 44.2% (n = 164) and 6.4% (n = 24), respectively. Malignancy rate was more frequent in group A when compared to groups B and C (P < 0.01). Nodule size was positively associated with follicular cancer risk (P = 0.009). The thyroid stimulating hormone level was positively associated with malignancy (P = 0.02) and optimal cut-off value was 0.96 mIU/L. False-negative rate was 8.0%, 19.3%, and 30.0% in groups A, B, and C nodules, respectively. CONCLUSIONS: Although the malignancy rate was low in nodules ≥30 mm, diagnostic surgery for large nodules should be considered because of decreased reliability of FNAC, ineffectiveness of clinical and sonographic criteria. False-negative rate was relatively low and malignancy rate was high in subcentimeter nodules, supporting the accuracy of FNAC.

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.

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.

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.

Management of differentiated thyroid cancer in the presence of resistance to thyroid hormone and TSH-secreting adenomas: a report of four cases and review of the literature.

BACKGROUND: An increased or normal serum TSH concentration, despite elevated thyroid hormone levels, is observed in resistance to thyroid hormone (RTH) and TSH-secreting adenomas (TSHomas). When coexistent with a differentiated thyroid cancer (DTC), maintenance of a suppression of TSH is challenging. OBJECTIVES: The aim of the study was to discuss the pitfalls arising from the failure to suppress TSH secretion in DTC and the strategies for proper treatment of DTC in association with RTH and TSHoma. METHODS: Four unusual cases of DTC associated with TSHoma (2 cases), RTH (1 case), and an elevated TSH of unknown etiology (1 case) are presented, and the literature is reviewed. RESULTS: Although a persistent mild TSH elevation may not be a risk factor for the development of DTC, it represents an important problem during the treatment of DTC. Aggressive treatment options should be applied in the proper order to prevent tumor recurrence and persistence in the absence of ideal TSH suppression. CONCLUSIONS: Although there is no agreed consensus regarding the management of DTC in the presence of persistent hyperthyrotropinemia, complete tumor removal followed by radioablation and attempts to reduce the serum TSH to the lowest tolerable level are recommended. The outcomes in the reported cases have not been unfavorable, despite the persistence of nonsuppressed TSH.

Role of cytological characteristics of benign thyroid nodules on effectiveness of their treatment with levothyroxine.

INTRODUCTION: Levothyroxine (LT4) therapy has been used for the treatment of euthyroid nodular goiter, but there are controversial results about its usefulness. We aimed to evaluate the possible role of benign nodules' cytological characteristics in response to LT4 therapy. MATERIAL AND METHODS: In total, 93 patients with 128 nodules were included in the study; 74 of the nodules were treated with LT4 (group 1), and 54 of them had no medication (group 2). The subgroups consisted of adenomatous nodules, colloid nodules and cystic nodules. RESULTS: In group 1, mean thyroid volume and mean nodule volume were reduced significantly (p = 0.002 and p = 0.022, respectively) with low-normal level thyrotropin (TSH) suppression (between 0.3 mIU/ml and 1.0 mIU/ml), while there were no significant changes in group 2. When we evaluated changes of the initial and last nodule volumes in cytological subgroups, only colloid nodules in group 1 had significant reduction (p = 0.040) and the others had no significant changes. By omitting the colloid nodules, when the other nodules were revaluated, there were no significant changes in either group. CONCLUSIONS: On the basis of these results, obtained from a large sample of Anatolian patients, it is possible that LT4 therapy leads to significant reductions of both thyroid volume and nodule size in colloid nodules, but not in other kinds of benign nodules.

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

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

Epidemiologic survey: reference ranges of serum insulin-like growth factor 1 levels in Caucasian adult population with immunoradiometric assay.

Gender, age adjusted, population based reference ranges are necessary to use insulin-like growth factor 1 (IGF-1) as a diagnostic marker or for therapeutic monitoring in growth hormone (GH) related diseases. The aim of the present study was to describe the serum IGF-1 distribution and to calculate age and gender specific reference values for Caucasian adult population. A representative sample of 1002 male and 1039 female, totally 2041 participants aged above 18 years old was examined. The subjects suffering from diabetes mellitus, renal diseases, liver diseases, cancer, or diseases of pituitary gland were excluded by medical history, physical examination, and laboratory tests. The subjects were not using any drug that could affect IGF-1 levels. Body mass index (BMI)>30 or<18 kg/m2 were excluded. Serum IGF-1 concentrations were determined by immunoradiometric assay (IRMA). Serum IGF-1 concentrations were declined with age in both males and females after the age of 18. Males had significantly higher serum IGF-1 levels than females in the age groups 18-24, 50-69 (P<0.05), but not in others (P>0.05). The present study established age and gender specific reference ranges for serum IGF-1 levels calculated for Caucasian adult population with IRMA that could be used in medical practice.

Acquired ichthyosis associated with type 1 diabetes mellitus.

Acquired ichthyosis is an uncommon disease which is characterized by symmetric scaling of the skin. Acquired ichthyosis has been described in association with a variety of underlying causes, including malignancies, drugs, infections, endocrine, metabolic and autoimmune diseases. Acquired ichthyosis associated with diabetes mellitus has been reported only in one case. We report the case of a new-onset diabetes mellitus with a one-month history of generalized acquired ichthyosis and palmoplantar keratoderma corroborated with skin biopsy, which completely disappeared after regulation of blood glucose levels with insulin therapy.

High prevalence of thyroid dysfunction and autoimmune thyroiditis in adolescents after elimination of iodine deficiency in the Eastern Black Sea Region of Turkey.

In the present study we evaluated the effects of iodine intake on the prevalence of thyroid dysfunction, autoimmunity, and goiter in two regions with different iodine status after two years of iodization in Turkey. In total 1733 adolescent subjects were enrolled into the study (993 from an iodine-sufficient area--the Eastern Black Sea Region (group 1) and 740 from an iodine-deficient area--Middle Anatolia (group 2)). We measured free thyroxine (FT(4)), thyrotropin (TSH), antithyroid peroxidase antibodies (Anti-TPO), antithyroglobulin antibodies (Anti-Tg), and urinary iodine (UI), and examined the thyroid gland by ultrasound. Median urinary iodine excretion was found to be significantly different in group 1 and group 2 (139 micro/l vs 61micro/l, p < 0.001). Hyperthyroidism was more frequent in group 1 (3.6% vs 0.7%; p < 0.001), but the hypothyroidism rate was similar between groups (1.8% vs 1.4 %; p>0.05). The percentage of anti-Tg positive subjects was found to be 17.6% in group 1 and 6.4% in group 2; that of anti-TPO positive subjects was 4.3% in group 1 and 1.5% in group 2. The prevalence of antithyroid antibody (anti-Tg and/or anti-TPO) positivity was significantly higher in group 1 than in group 2 (18.52% vs 6.62%; p < 0.001). Thyroid volumes of the hyperthyroid subjects in both groups were significantly higher than hypo- and euthyroid subjects. In conclusion, iodine supplementation in Turkey has resulted in the elimination of iodine deficiency in the Eastern Black Sea Region, and this has been accompanied by an increase in the prevalence of autoimmune thyroiditis and thyroid dysfunction.