Assessing safety and efficacy of TNFi treatment in late onset ankylosing spondylitis: a TURKBIO registry study.

Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate efficacy, safety, and treatment adherence associated with the initial use of TNFi therapy in biologic naive patients diagnosed with LoAS. Patients whose age of onset was ≥ 45 years and < 45 years were classified as having LoAS and YoAS, respectively, based on the age of symptom onset. There were 2573 patients with YoAS and 281 LoAS. Baseline disease activity measures were similar between the groups. No significant differences were seen between the two groups in response to treatment and in remaining on the first TNFi at 6, 12 and 24 months. In the LoAS group, the analysis showed that TNFi discontinuation was linked to VAS pain score (HR 1.04; 95% CI 1.01-1.06). Patient groups had similar rates of adverse events (YoAS: 8.7% vs. LoAS: 11.7%). In both biologic naive LoAS and YoAS patients, the study showed that the initial TNFi therapy was equally effective and safe.

Biological treatment in elderly and young patients with ankylosing spondylitis: TURKBIO real-life data results.

Objectives: This study aims to investigate the effect of age on disease activity and biological treatment in patients with ankylosing spondylitis (AS). Patients and methods: A total of 811 AS patients registered in the TURKBIO registry database between 2011 and 2019 were categorized according to their age at the time of entry into the registry and assigned to one of two groups: young patients, defined as <60 years of age (n=610), and those aged ≥60 years (n=201) were recorded as elderly patients. Demographic, clinical, and laboratory characteristics, along with disease activity markers and other follow-up parameters, as well as current and prior treatments, were electronically recorded during each visit using open-source software. Results: The mean age of the elderly patients was 67±5.8 years, while the mean age of the younger patients was 49.2±10.9 years. Male predominance was lower in the older AS group compared to the younger AS group (p=0.002). During follow-up period, 397 patients (comprising 318 young and 79 elderly individuals) had a history of using at least one biological disease-modifying agent (bDMARD). There was no significant difference between the groups in terms of DMARD and bDMARD-use distributions. First tumor necrosis factor inhibitor (TNFi) retention rates were found to be similar in both groups over 10 years of follow-up. Adverse events were found to be similar in young (19.9%) and elderly (26.8%) AS patients. Conclusion: Research in the TURKBIO cohort reveals that both older and younger patients with AS exhibited similar disease activity levels with comparable treatment approaches. Moreover, the results of TNFi treatments in elderly patients were the same as those observed in younger patients, with no notable increase in safety concerns.

A Case of Isolated Central Nervous System Rosai-Dorfman Disease.

Rosai-Dorfman disease (RDD) is a benign histiocytosis with unknown etiology. It generally occurs in cervical lymph nodes. Isolated central nervous system (CNS) RDD is very rare in the literature. We reported a case of no systemic involvement Rosai-Dorfmann which is rarely seen and shows CNS involvement by mimicking meningioma. A 32-year-old man presented with diplopia and a headache he has been experiencing for the past two years. His neurological examination showed left facial paresthesia, consistent with trigeminal nerve trace. Tendon reflexes were increased at the right side and the right plantar reflex was extensor. Brain magnetic resonance imaging demonstrated irregularly shaped, tumor-like lesions in the bilateral cerebellopontin area that were compressing pons. Rosai-Dorfman disease can be differentiated from IgG4 related disease (IgG4-RD) by its characteristic features such as plasma cell density and emperipolesis seen in its histopathology. Rosai-Dorfman disease can be confused with other diseases radiologically and histopathologically, especially the IgG4-RD, so be careful about differential diagnosis.

Treatment of systemic sclerosis-associated digital ulcers: recommendations of the Turkish Society for Rheumatology.

OBJECTIVES: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc. METHODS: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]. RESULTS: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles. CONCLUSIONS: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

A national, multicenter, retrospective study evaluating retention rate and efficacy of tocilizumab treatment in patients with active rheumatoid arthritis who had an inadequate response to csDMARDs and/or TNF inhibitors.

BACKGROUND: To describe the disease activity and retention rate in rheumatoid arthritis (RA) patients with inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or tumor necrosis factor inhibitors (TNFis) who were prescribed tocilizumab (TCZ) as first-line or second-line biologic treatment in real-world setting. METHODS: Data gathered from patients' files was used in a multicenter and retrospective context. Retention rates and the Disease Activity Score in 28 joints with CRP (DAS28-CRP) were evaluated at time points. The relationship of drug efficacy with factors such as smoking, obesity, and previous use of TNFis was also examined. RESULTS: One hundred and twenty-four patients with a median (IQR) RA duration of 3.7 (7.4) years were included. Mean (SD) age was52.9 (12.9) and 75% of the patients were female. TCZ retention rates in the 6th and 12th months were 94.1% and 86.6%, respectively. In all patients, DAS28-CRP level decreased significantly from baseline to Months 3 and 6. There was an increase in patients with remission and/or low disease activity and a decrease in patients with high disease activity at Month 3 and Month 6 (p < 0.001 for both). Disease activity was similar between subgroups based on body mass index, smoking status, and previous use of TNFis at any time point. Regression analysis showed that absence of concomitant corticosteroid treatment independently was associated with remission/LDA achievement at Month 6 [OR = 0.31, 95% CI (0.14- 0.72), p = 0.006], and Month 12 [OR = 0.35, 95% CI (0.13-0.94), p = 0.037]. Overall, 25 mild adverse events were reported. DISCUSSION: TCZ was found to be effective and safe in RA patients with IR to csDMARDs and/or TNFis. The drug retention rate was considered satisfactory with more than half of the patients continuing TCZ treatment at Month 12.

A real-life analysis of patients with rheumatologic diseases on biological treatments: Data from TURKBIO Registry.

OBJECTIVE: TURKBIO registry, established in 2011, is the first nationwide biological database in Turkey. This study aimed to provide an overview of TURKBIO data collected by June 2018. METHODS: The registry included adult patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr-AxSpA), and psoriatic arthritis (PsA). Demographic and clinical features, disease activity markers, and other follow-up parameters, current and previous treat- ments, and adverse events were registered electronically at each visit using open-source software. The registration of patient-reported outcome measures was carried out electronically by the patients using touch screens. RESULTS: TURKBIO registry included a total of 41,145 treatment series with biologicals. There were 2,588 patients with axSpA (2,459 AS and 129 nr-axSpA), 2,036 with RA, and 428 with PsA. The total number of patients, including those with other diagnoses, was 5,718. In the follow-up period, the number of patients and also visits steadily increased by years. The yearly mean number of visits per patient was found to be 2.3. Significant improvements in disease activity and health assessment parameters were observed following the biological treatments. Biologics were often given in combination with a con- ventional synthetic disease-modifying antirheumatic drug in patients with RA. Infections were the most commonly seen adverse events, followed by allergic reactions. Tuberculosis was observed in 12 patients, malignancy in 18, and treatment-related mortality in 31. CONCLUSION: TURKBIO provided a valuable real-life experience with the use of biologics in rheumatic diseases in Turkey.

Type 2 renal tubular acidosis presenting with joint pain: A case report and literature review.

Fanconi syndrome (FS) can present with hypophosphatemia, renal glycosuria, hypouricemia and aminoaciduria. Phosphate depletion is the most critical clinical aspect of FS as it leads to osteomalacia. Some patients present with symptoms and signs related to hypophosphatemic osteomalacia (HO). Thus, these patients present with these symptoms and are misdiagnosed. From an investigation of the published literature, HO symptoms are found to be non-specific and were thus misdiagnosed in various centers. The present study describes the case of a a 46-year-old male with FS who suffered from joint pain and was first misdiagnosed. After he was referred to the authors' hospital, his case was evaluated and following a consideration of the results of this evaluation, he was diagnosed with idiopathic FS with multiple osteoporotic fractures. Furthermore, the present study performs a brief literature review other cases of patients that were misdiagnosed and whose symptoms were later found to be due to HO are also discussed. It is hoped that the present study may increase the awareness of HO among physicians and may help to draw attention to such cases of patients presenting with non-specific symptoms.

Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration.

BACKGROUND: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. METHODS: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. RESULTS: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. CONCLUSION: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.

Parotid abscess secondary to brucellosis in a patient with primary Sjögren's syndrome.

Swelling in the salivary glands, particularly parotid glands, is observed in approximately one third of Sjögren's syndrome patients. However, such patients should be assessed in terms of causes such as malignancies, infections, amyloidosis, sarcoidosis, and other autoimmune diseases when parotid gland swelling is noted. It should be considered that the incidence of lymphoma increases in Sjögren's syndrome. Unilateral parotid swelling, especially if accompanied by severe pain and redness, should be monitored for suppurative bacterial infections. Brucellosis is a systemic disease that may involve one or multiple organs. It can appear with different clinical manifestations and nonspecific symptoms. Although local abscess formations secondary to brucellosis in different organs have been reported, no evidence for parotid involvement has yet been reported. In this study, a case with primary Sjögren's syndrome and parotid abscess secondary to brucellosis is presented.

ENHO gene expression and serum adropin level in rheumatoid arthritis and systemic lupus erythematosus.

BACKGROUND: Adropin, a secreted protein, is encoded by the energy homeostasis-associated gene (ENHO). It is expressed by a variety of tissues and cells. It has been implicated in several physiological and pathological processes, such as angiogenesis and apoptosis. OBJECTIVES: The aim of the present study was to investigate the ENHO gene expression and serum adropin levels in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). MATERIAL AND METHODS: The study included 36 patients with RA, 22 patients with SLE and 20 healthy controls (HC). Patients with a disease activity score-28-erythrocyte sedimentation rate (DAS28-ESR) >2.6 in the RA group and an SLE disease activity index (SLEDAI) >6 in the SLE group were accepted as active. Serum adropin levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) method. The ENHO gene and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expressions in peripheral blood mononuclear cells were analyzed by real-time polymerase chain reaction (PCR). RESULTS: The ENHO gene mRNA expression was significantly higher in the RA group than in the HC group (p = 0.024), although it was similar between the SLE and HC groups (p = 0.920). On the other hand, there were no significant differences among the study groups in terms of serum adropin levels (p > 0.05 for all). Moreover, there was no significant difference in terms of the ENHO expression and serum adropin levels between active and inactive RA and SLE patients. CONCLUSIONS: Although the ENHO gene expression is increased, serum adropin level is not altered in RA. Similarly, adropin seems not to be associated with SLE. However, the potential link between adropin and inflammatory diseases need to be tested by further studies.

Octreotide ameliorates dermal fibrosis in bleomycin-induced scleroderma

Background/aim: Insulin-like growth factor (IGF)-I is a differentiation and growth factor. Antifibrotic action of octreotide has been reported in pulmonary fibrosis. The present study aimed to research the prophylactic and therapeutic potential of octreotide on a bleomycin (BLM)-induced experimental scleroderma model. Materials and methods: Sixty Balb/c female mice were divided into 6 groups. Daily subcutaneous BLM (100 µg) was injected for 3 weeks in groups II and III and for 6 weeks in groups V and VI. Octreotide (100 µg/kg per day) was injected subcutaneously for the first 3 weeks in group III (prophylactic) and the second 3 weeks in group VI (therapeutic). Mice in groups I, II, and III were sacrificed at the end of the third week, while mice in groups IV, V, and VI were sacrificed at the end of the sixth week. Results: Repeated BLM applications increased dermal inflammatory cell counts and dermal thickness, and led to dermal fibrosis at both the third and sixth weeks. Moreover, mRNA expressions of TGF-ß1 and IGF binding protein (IGFBP)-3 and -5 were higher in the BLM- injected sham groups. On the other hand, IGFBP-3 and -5 mRNA expressions were significantly decreased in both the prophylactic and therapeutic octreotide groups. Similarly, octreotide decreased dermal inflammatory infiltrations and dermal thickness. Conclusion: Octreotide has antifibrotic actions on experimentally induced dermal fibrosis. It can be suggested that IGF-I plays pathogenic roles, and octreotide is a candidate for research in the treatment of scleroderma.

Serum osteopontin and vitronectin levels in systemic sclerosis.

BACKGROUND: Osteopontin a matricellular protein has pro-fibrotic effects and binds integrin such as αvß1 and αvß3. Vitronectin is one of the integrin αvß3 ligands and is a multifunctional glycoprotein. OBJECTIVES: The aim of the present study was to evaluate serum osteopontin and vitronectin levels in a cohort of patients with systemic sclerosis (SSc). MATERIAL AND METHODS: Eighty-six patients with SSc, 46 patients with systemic lupus erythematosus (SLE), and 38 healthy controls (HC) were enrolled in the study. Serum osteopontin, vitronectin, IL-6, and TGF-ß levels were analyzed. RESULTS: Serum osteopontin levels were higher in the SSc and SLE groups compared to the HC group (p < 0.01 and p < 0.001, respectively). However, it was not correlated with disease activity and severity scores in the SSc group. On the other hand, serum vitronectin levels were lower in the SSc group than in the SLE and HC groups (p < 0.001 for both). CONCLUSIONS: These results may suggest that osteopontin levels may be increased due to the inflammatory process and osteopontin has not a specific role on fibrosis in SSc. On the other hand, serum vitronectin levels decrease in SSc in contrast to SLE. It may be concluded that the one cause of decreased serum vitronectin levels in SSc may be its accumulation in fibrotic area.

Coexistence of Ankylosing Spondylitis and Neurofibromatosis Type 1.

Ankylosing spondylitis (AS) is a systemic disease primarily characterized by the inflammation of sacroiliac joints and axial skeleton. Neurofibromatosis type 1 (NF1) is a multisystem genetic disease which is characterized by cutaneous findings, most importantly café-au-lait spots and axillary freckling, by skeletal dysplasia, and by the growth of both benign and malignant nervous system neoplasms, most notably benign neurofibromas. In this case report, we present a 43-year-old male with AS and NF1.

Sleep Quality Is Related to Disease Activity in Patients With Ankylosing Spondylitis: A Polysomnographic Study.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease that is associated with poor sleep quality. OBJECTIVES: The present study aimed to investigate the relationship between disease activity and sleep quality in patients with AS and to evaluate the potential effect of anti-tumor necrosis factor (TNF) treatment on sleep quality and pattern. METHODS: Fifty-nine patients with AS were consecutively included in the study. Twenty-eight patients (47.5%) were receiving anti-TNF, and 31 (52.5%) patients were receiving only nonsteroidal anti-inflammatory drugs (NSAIDs). Demographic and treatment characteristics, spinal mobility measurements, disease activity measurements, and sleep questionnaire results of each patient were recorded. Each patient underwent a polysomnography examination for the evaluation of sleep patterns. RESULTS: When compared with the patients on NSAID treatment, patients receiving anti-TNF treatment had significantly greater total sleep time and sleep efficiency (P = 0.003 and P < 0.001, respectively). They had a significantly lower (better) Pittsburgh Sleep Quality Index, sleep onset latency, number of awakenings, and arousal index (P < 0.001, for all). Moreover, they had a significantly shorter superficial sleep period (stage 1) and a significantly longer rapid eye movement sleep period (P < 0.001 and P = 0.02, respectively). Higher indexes of disease activity (Bath AS Disease Activity Index, Bath AS Functional Index, and visual analog scale) were reflecting poorer sleep quality. CONCLUSIONS: Sleep quality and pattern was markedly better in patients with AS on anti-TNF compared with the patients on NSAID treatments. Increased disease activity can impair the quality of sleep in AS. Improved sleep quality and pattern in patients on anti-TNF treatment may be related to improved disease activity.

Serum adropin level and ENHO gene expression in systemic sclerosis.

Adropin, a secreted protein, is encoded by the energy homeostasis associated (ENHO) gene. It has been implicated in the several physiological and pathological processes such as angiogenesis and apoptosis. Therefore, the aim of present study was to investigate serum adropin levels and ENHO gene expressions in systemic sclerosis (SSc) characterized by vasculopathy, inflammation, and progressive fibrosis of the skin and internal organs. The study includes 27 patients with SSc, 39 patients with Behçet's disease (BD), and 20 healthy controls (HC). Serum adropin levels and ENHO gene expressions by peripheral blood mononuclear cells were analyzed by ELISA method and by real-time PCR, respectively. The serum adropin levels were higher in the SSc and BD groups than in the HC group (p = 0.023 and p < 0.001, respectively). However, there were no significant differences among the groups in terms of ENHO gene expressions (p ANOVA = 0.149). There was no significant difference between the limited and diffuse cutaneous subtypes of SSc in terms of serum adropin level and ENHO gene expression. Moreover, serum adropin level and ENHO gene expression were not associated with the disease activity and severity indexes. ENHO gene expression was correlated with the triglyceride levels in the BD group (r = -0.426, p = 0.027). The augmented serum adropin levels may be expected in the chronic inflammatory disease and seem not to be characteristic of only SSc. However, further studies are needed to explain the precise role of adropin in SSc.

QT dispersion and P wave dispersion in patients with fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is a chronic disease characterized by widespread pain. Somatic complaints associated with the cardiovascular system, such as chest pain and palpitations, are frequently seen in FM patients. P and QT dispersions are simple and inexpensive measurements reflecting the regional heterogeneity of atrial and ventricular repolarization, respectively. QT dispersion can cause serious ventricular arrhythmias. The aim of the present study was to evaluate QT dispersion and P wave dispersion in patients with FM. MATERIAL AND METHODS: The study involved 48 FM patients who fulfilled the established criteria and 32 healthy controls (HC). A standard 12-lead electrocardiogram was performed on all participants. QT dispersion was defined as the difference between the longest and the shortest QT intervals. Similarly, the differences between the shortest and longest P waves were defined as P wave dispersion. RESULTS: The QT dispersion and corrected QT dispersion were shorter in the FM group compared with the HC group (p<0.001 for both). In terms of the P wave dispersion value, there was no significant difference between the FM and HC groups (p=0.088). CONCLUSION: Longer QT and P wave dispersions are not problems in patients with FM. Therefore, it may be concluded that fibromyalgia does not include an increased risk of atrial and/or ventricular arrhythmias.

Serum galectin-3 level in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology characterized by progressive fibrosis. Activated fibroblasts are mainly responsible for fibrosis in SSc. Galectin-3, a ß-galactoside-binding lectin, plays many important regulatory roles in both physiological and pathological processes including proliferation, apoptosis, inflammation, and fibrosis. The purpose of this study was to assess the serum galectin-3 levels in patients with SSc. Thirty-seven SSc patients, 23 systemic lupus erythematosus (SLE) patients (serving as patient control group), and 28 healthy volunteers were enrolled in this study. Disease activity and severity scores were detected with Valentini disease activity index and Medsger disease severity scale in the SSc group and SLE disease activity index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index in the SLE group. The serum levels of galectin-3, vascular endothelial growth factor, transforming growth factor-ß, and interleukin-6 were determined. Compared to the control group, the galectin-3 levels were higher in the SSc and SLE groups. The galectin-3 levels were not correlated with the disease activity and severity indexes in both patient groups. But, the serum galectin-3 levels were higher in the active SSc and SLE subgroups than in the inactive SSc (4.6 ± 5.8 vs. 1.3 ± 1.1 ng/ml, p = 0.015) and SLE (17.4 ± 11.3 vs. 6.5 ± 8.9 ng/ml, p = 0.019) subgroups. These results suggest that galectin-3, which is associated with fibrosis and inflammation by previous studies, may be a prominent biomarker of disease activity in SSc.

The rs3768777-G allele of ITGAV gene is associated with rheumatoid arthritis.

Integrin αvß3 (vitronectin receptor) plays a prominent role in angiogenesis, a key pathogenic feature of rheumatoid arthritis (RA). Moreover, integrin αV (ITGAV) subunit gene has been associated with a susceptibility to RA. The aim of the present study was to detect the potential association between ITGAV gene polymorphisms and a susceptibility to RA in a Turkish cohort. DNA samples were harvested from 160 patients with RA and 144 healthy controls (HC). Three single-nucleotide polymorphisms of ITGAV gene (rs3738919, rs3768777, and rs10174098) were genotyped using real-time PCR. Serum vitronectin levels were analyzed in 30 RA patients, 28 Behçet's disease (BD) patients, and 30 HC subjects. There was no significant difference between the RA and HC groups in terms of the genotypic and allelic distributions of rs3738919 and rs10174098 polymorphisms. However, the prevalence of rs3768777-G allele was higher in the RA group than in the HC group (OR 2.3, 95 % CI 1.6-3.2, p < 0.0001). Moreover, there was a significant association between RA and the genotypic distribution of rs3768777 (GG + AG vs. AA: OR 2.1, 95 % CI 1.3-3.4; GG vs. AG + AA: OR 4.1, 95 % CI 2.1-7.8). Serum vitronectin levels were lower in the RA and BD groups than in the HC group (p ANOVA = 0.002). The rs3738919 and rs10174098 polymorphisms of the ITGAV gene seem not to be associated with susceptibility to RA in Turkish patients. However, rs3768777 increases the risk of RA in this group. These results suggest that the ITGAV gene may be a candidate gene for the etiopathogenesis of RA.

Does smoking affect thyroid gland enlargement and nodule formation in iodine-sufficient regions?

OBJECTIVES: The present study aimed to investigate the effect of smoking on thyroid nodule formation and goiter development in healthy subjects living in Istanbul, an iodine-sufficient region. This study was designed as a prospective, randomized, and observational study. METHODS: Included in the study were voluntary hospital staff and relatives of patients between the ages of 28 and 71 who had no known disease or drug use, who have been living in Istanbul and had been smoking more than 10 cigarettes per day for at least 10years. Nonsmoker volunteers (45) shared similar demographic characteristics and were matched for age to the (46) smokers. By means of thyroid ultrasounds performed in all participants, volumes of the right and left lobes of the thyroid gland, and number, diameter and characteristics of nodules were evaluated. RESULTS: Comparing the smokers and nonsmokers, no statistically significant difference was determined in terms of presence of nodules and volumes of the left and right thyroid lobes (P=0.68, P=0.09, and P=0.63, respectively). Making enhanced diffuse enlargement of the thyroid gland, but not to a statistically significant degree. Smoking was observed to have no effect on non-toxic nodules, or the levels of thyroid-stimulating hormone, free thyroxin, free triiodothyronine, anti-thyroid peroxidase, or anti-thyroglobulin antibodies. CONCLUSIONS: Smoking does not effect, to a statistically significant degree goiter development thyroid nodule formation in iodine-sufficient regions like Istanbul.