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The activity of nicotinamide N-methyltransferase (NNMT) is tightly linked to the maintenance of the nicotinamide adenine dinucleotide (NAD+) level. This enzyme catalyzes methylation of nicotinamide (NAM) into methyl nicotinamide (MNAM), which is either excreted or further metabolized to N1-methyl-2-pyridone-5-carboxamide (2-PY) and H2O2. Enzymatic activity of NNMT is important for the prevention of NAM-mediated inhibition of NAD+-consuming enzymes poly–adenosine -diphosphate (ADP), ribose polymerases (PARPs), and sirtuins (SIRTs). Inappropriately high expression and activity of NNMT, commonly present in various types of cancer, has the potential to disrupt NAD+ homeostasis and cellular methylation potential. Largely overlooked, in the context of cancer, is the inhibitory effect of 2-PY on PARP-1 activity, which abrogates NNMT’s positive effect on cellular NAD+ flux by stalling liberation of NAM and reducing NAD+ synthesis in the salvage pathway. This review describes, and discusses, the mechanisms by which NNMT promotes NAD+ depletion and epigenetic reprogramming, leading to the development of metabolic plasticity, evasion of a major tumor suppressive process of cellular senescence, and acquisition of stem cell properties. All these phenomena are related to therapy resistance and worse clinical outcomes.

Background: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA. Methods: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration. Results: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0–127.4) in non-NENs and 13.8% (0.0–43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%. Conclusions: AOST is a promising tool to increase the diagnostic accuracy of serum CgA.

A 28-year-old male presented with arterial hypertension and type 2 diabetes mellitus, gradually developing over the last 18 months. Both hypertension and diabetes were inadequately controlled with maximal daily doses of perindopril, amlodipine, metformin, and dapagliflozin. His previous photograph taken 5 years ago showed a lean male with marfanoid features and bumpy lips. Current physical examination disclosed increased blood pressure (148/92 mmHg), a body mass index of 28.2 kg/m2, facial plethora, and a “buffalo hump” (Figure B). Endocrinological evaluation was carried out in order to make the diagnosis of secondary hypertension and secondary diabetes mellitus. Increased 24-hour urinary metanephrine (16, 880 nmol/24 hours, normal < 1300) and normetanephrine (10, 273 nmol/24 hours, normal < 2800) were found, which were highly suggestive of pheochromocytoma. Moreover, the diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing’s disease was made: ACTH 10.1 pmol/L (normal 2.2-13.3), serum cortisol following 1 mg dexamethasone suppression test of 701 nmol/L, and 24-hour urinary-free cortisol of 4754 nmol/24 hours (normal 72-325). Due to previously evident marfanoid features and suspicion of pheochromocytoma, multiple endocrine neoplasia type 2B (MEN 2B) syndrome was suspected. Increased serum calcitonin (1649 ng/L, normal

BACKGROUND The purpose of this study was to detect parameters that could serve as predictors of radioactive iodine (I-131) ablation failure in patients with low-risk and intermediate-risk differentiated thyroid carcinoma (DTC). METHODS Our cohort study included 740 patients with DTC who received postoperative I-131 remnant ablation. Anthropometric, biochemical, and pathohistological parameters were analyzed and correlated with ablation outcome using multivariable logistic regression models. RESULTS Treatment failure rates were higher in patients 2.4 ng/mL predicted treatment failure with 93.8% sensitivity and 52.5% specificity, and in patients with N1b disease, Tg > 14.9 ng/mL with 77.8% sensitivity and 92.9% specificity. I-131 activity was not associated with treatment outcome. CONCLUSION Patients

The aim of this study was to evaluate the efficacy of different radioactive iodine (I- 131) activities used for re-ablation, to compare various combinations of treatment activities, and to identify predictors of re- ablation failure in low- and intermediate-risk differentiated thyroid carcinoma (DTC) patients. The study included 128 consecutive low- and intermediate-risk patients with DTC with ablation failure after total thyroidectomy. Patient characteristics, T status, tumor size, lymph node involvement, postoperative remnant size on whole-body scintigraphy, serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), anti-Tg antibody (TgAb), and Tg/TSH ratio were analyzed as potential predictors of the re-ablation success. Re-ablation was successful in 113 out of 128 patients (88.3 %). Mean first I-131 activity was 2868 ± 914 MBq (77.5 ± 24.7 mCi) and mean second I-131 activity 3004 ± 699 MBq (81.2 ± 18.9 mCi). There was no association between the first, second, and cumulative activity with re-ablation treatment outcome. Treatment failure was associated with higher Tg levels prior to re-ablation (Tg2) (OR 1.16, 95 % CI 1.05–1.29, P = 0.003) and N1a status (OR 3.89, 95 % CI 1.13–13.41, P = 0.032). After excluding patients with positive-to-negative TgAb conversion, Tg2 level of 3.7 ng/mL predicted treatment failure with a sensitivity of 75.0 %, specificity of 80.5 %, and a negative predictive value of 97.1 %. Patients with positive-to-negative TgAb conversion had higher failure rates (OR 2.96, 95 % CI 0.94– 9.29). Re-ablation success was high in all subgroups of patients and I-131 activity did not influence treatment outcome. Tg may serve as a good predictor of re-ablation failure. Patients with positive-to-negative TgAb conversion represent a specific group, in whom Tg level should not be used as a predictive marker of treatment outcome.

Melanoma is considered to be the most immunogenic malignant tumour. This fact is recognized for many years, and certain forms of immunotherapy have been used in melanoma therapy for a considerable time. Treatment options for patients with metastatic melanoma have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents (immunotherapies and targeted therapies). During this period, melanoma immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic Tlymphocyteassociated antigen4 (CTLA4) and, recently, the programmed cell-death protein 1 (PD1) immune checkpoints. These changes in the treatment options have dramatically improved patient outcomes, with the median overall survival of patients with metastatic melanoma increasing from approximately 9 months before 2011 to at least 2 years, and probably longer. Various types of immunotherapy, like pembrolizumab, nivolumab, ipilimumab, combined therapy with nivolumab and ipilimumab, and T-VEC, have been established in recent years as the standard-of-care treatment for metastatic melanoma patients., Melanomi se smatraju najimunogenijim zloćudnim tumorima. Ova je činjenica prepoznata već niz godina, te se neki oblici imunoterapije već dugo primjenjuju u liječenju melanoma. Terapijske opcije za liječenje bolesnika s metastatskim melanomom dramatično su se promijenile u zadnjih pet godina, te je Američka agencija za lijekove (FDA) odobrila osam novih lijekova (imunoterapije i ciljane terapije). Tijekom ovog razdoblja, imunoterapija melanoma promijenila se iz terapije bazirane na citokinima u protutijelima posredovanu blokadu citotoksičnog T-limfocitnog antigena 4 (CTLA-4), a u zadnje vrijeme u protutijelima posredovanu inhibiciju imunoloških kontrolnih točaka, prvenstveno proteina programirane stanične smrti 1 (PD-1). Ove su promjene terapijskih opcija dramatično poboljšale ishod liječenja bolesnika, te se medijan ukupnog preživljenja kod bolesnika s metastatskim melanomom povisio s približno 9 mjeseci prije 2011. godine, na najmanje 2 godine, a vjerojatno i dulje. Različiti oblici imunoterapije, poput pembrolizumaba, nivolumaba, ipilimumaba, kombinirane terapije nivolumabom i ipilimumabom, te T-VEC, postali su zadnjih godina standardni oblici liječenja bolesnika s metastatskim melanomom.

Objectives Randomized trials involving aromatase inhibitors (AIs) in the adjuvant treatment of breast cancer patients have reported increased osteoporosis risk. Bone loss can be reduced with appropriate life style, vitamin D and calcium supplements, and with bisphosphonate therapy. The aim of this analysis was to investigate adherence to vitamin D and calcium in postmenopausal breast cancer patients receiving adjuvant non-steroidal AIs, and oncologists' adherence to the bone health guidelines. Material and methods This prospective study included 438 newly diagnosed patients and those who have already been receiving non-steroidal AIs for up to 3.5 years. Median endocrine therapy duration before recruitment in the study was 10.5 months (interquartile 4.8–26.6). Results Densitometry was performed on 142 patients (32.4%) before initiation of endocrine therapy, and on additional 38 (8.6%) patients at second study visit. Densitometry was not performed on 258 (59%) patients. Vitamin D and calcium were prescribed to 329/438 (75.1%) patients at some point during the study. Patients who took more than 80% of the prescribed dose were considered adherent. Self-reported adherence was 88.4%. Osteoporosis was diagnosed in 24 patients (5.5%) of the total study population, bearing in mind that 258/438 (59%) patients did not have densitometry. Bisphosphonates were prescribed to 54/438 (12.3%) patients, whilst only 19 (35.2%) of those had osteoporosis. Conclusion In this analysis, lack of oncologists' adherence to the bone health guidelines was observed. In addition, a significant proportion of the patients did not adhere to the vitamin D and calcium.

The aim of this analysis was to evaluate adherence of Croatian oncologists to follow‐up criteria as suggested by the current national and international guidelines for women with breast cancer receiving adjuvant endocrine therapy. The use of clinical and diagnostic methods was documented in this prospective, non‐ interventional, multicenter study. A total of 438 post‐menopausal patients receiving adjuvant endocrine treatment with non‐steroidal aromatase inhibitors were included. Average annual frequency for each clinical and diagnostic method was calculated. Median adjuvant endocrine treatment duration before study recruitment was 10.5 months (interquartile 4.7–26.6). Patients were followed up for an average 23.5 ± 4.9 months. Average number of oncological visits was 5.3. Mammograms were performed at mean annual frequency of 0.7, chest radiographs at 0.5, abdominal ultrasounds at 0.9, breast ultrasounds at 1.2, complete blood counts and chemistry panels at 1.7, carcinoembryonic antigen at 0.8, cancer antigen 15‐3 at 1.6, gynaecological examination at 0.3, and densitometry at mean annual frequency of 0.3. In conclusion, among post‐menopausal women with breast cancer receiving adjuvant endocrine therapy in this study, more unnecessary and unproven follow‐up procedures were done compared to the guidelines' recommendations.

Objective were to assess efficiency of various I-131 activities on thyroid remnant ablation in thyroid cancer patients. The significance of patients' characteristics, pathologic features and levels of Tg were analyzed. This study included 259 consecutive differentiated thyroid cancer patients, with disease confined to the thyroid, treated with I-131 after total thyroidectomy. Patients were divided into the three groups: 80 patients receiving low [1110-1850 MBq (30-50 mCi)], 121 intermediate [2775 MBq (75 mCi)] and 58 high [3700 MBq (100 mCi)] postoperative I-131 activities. Six to eight months after the application of radioiodine, measurements of TSH, Tg, anti-Tg antibodies (in hypothyroid state) together with ultrasound exam and whole-body scintigraphy were performed. The ablation was significantly more effective (after the first application) in patients receiving 100 mCi of I-131-89.7 % than in patients receiving lower activities (P = 0.016). There was no significant difference in ablation rate between the 30-50 mCi (77.5 %) and 75 mCi (70.2 %) groups. In the group receiving 30-50 mCi, patients with solitary tumors had significantly higher ablation rate (P = 0.038). In patients receiving 75 mCi ablation rates were higher among older patients (P = 0.005), with infiltration of the single lobe (P = 0.005), and with solitary tumor (P = 0.012). The rates of successful ablation after the second application of I-131 (after 12-16 months) amounted to 96, 97 and 96 % in the 30-50, 75 and 100 mCi groups, respectively. The activity of I-131 and age were independent factors for thyroid ablation failure after the first application of I-131 (model of binary logistic regression). The results of remnant ablation were satisfactory with all activities applied. Although after the first application of I-131 the activity of 100 mCi is significantly more effective in thyroid ablation than the administration of 30-50 mCi and 75 mCi, the ablation rates between all the three groups are similar (almost equal) after the second application. Thus, the activity to be administered may depend on patients' characteristics and a detailed consideration of the merits and demerits of each I-131 activity.

This study was performed in 2002, 6 yr after the introduction of a new regulation on salt iodination with 25 mg KI/kg of salt. The aim of the study was to evaluate whether further significant positive results of improved iodine intake could be observed among schoolchildren in Croatia. A total of 927 schoolchildren of both sexes, aged 6-12 yr, were included in the study. In Croatia, with a population of 4, 437, 460 the research was implemented in four major geographical regions: the Northwestern, Slavonia, Northern Adriatic and Dalmatian regions. Investigations included randomly selected pupils from regional centers and neighboring smaller towns or villages. The results have revealed that thyroid volumes were within the normal range according to the provisional WHO/ICCIDD reference values for sonographic thyroid volume in iodine-replete school-age children, updated in 2001. A significant improvement in medians of urinary iodine excretion was detected in 2002: from 9 microg/dl in 1991 to 14.6 microg/dl in Zagreb, from 4.3 microg/dl in 1995 to 13.1 microg/dl in Split, from 9.4 microg/dl in 1997 to 14.2 microg/dl in Rijeka and from 13.4 microg/dl in 1997 to 14.7 microg/dl in Osijek. An overall median of 14.0 microg/dl of urinary iodine excretion was detected in Croatian schoolchildren. The control of salt at different levels, from production to consumption, including salt produced in all three Croatian salt plants and imported salt, revealed that Croatian salt is adequately iodized. From severe iodine deficiency before the 1950s, through mild-to-moderate iodine deficiency in the 1990s, Croatia has now reached iodine sufficiency.

People of all ages can be affected by iodine deficiency, however, pregnant women and children are especially at a high risk. Because of changes that occur in maternal thyroid hormone economy during pregnancy and the potential unfavorable effects of iodine deficiency on the offspring, an adequate dietary iodine intake throughout the pregnancy is highly important. Therefore, the World Health Organization, United Nations Children's Fund and International Council for the Control of Iodine Deficiency Disorders have proposed that dietary intake of iodine during pregnancy should be 200-300 microg/day to compensate for the augmented T4 requirements in pregnant women. It has been shown that in countries with a longstanding and well-established universal salt iodination program where iodine sufficiency has been reached, there is a fraction of pregnant women that still have low median urinary iodine concentration, which indicates insufficient dietary iodine. Studies performed in such countries emphasize that pregnant women should use multivitamin and/ or mineral tablets specifically prepared for the needs of pregnancy and containing iodine supplements. Only the United States of America and Canada have official recommendations concerning iodine supplementation. In other countries, no such firm decisions have yet been made by medical community and public health authorities. In Croatia, an iodine sufficient country, the situation is the same. There is a need to collect adequate data on iodine supplementation and urinary iodine during pregnancy, along with the universal salt iodination program, so that definitive conclusions can be made.

Thyroid dysfunction is common in the population, especially in women, and thyroid diagnostic tests are among the most often used diagnostic procedures nowadays. Many thyroid societies developed guidelines for the detection of thyroid dysfunction. An interdisciplinary team of experts from the Croatian Thyroid Society studied guidelines of other thyroid societies and international publications, and according to our tradition and clinical practice developed guidelines for rational detection of thyroid dysfunction; hypothyroidism and hyperthyroidism. The aim of these guidelines is to recommend evidence-based and rational approach to the detection of thyroid dysfunction.

Our aim was to assess malignancy risk in adenomatoid nodules and suspicious follicular lesions of the thyroid obtained by fine needle aspiration (FNA) cytology. Retrospective research was performed of 276 patients who underwent thyroid surgery after preoperative ultrasound-guided FNA diagnosis of either adenomatoid nodule, cellular follicular lesion, "suspicious for follicular neoplasm" or follicular neoplasm. Out of 276 patients, FNA reports showed 15 diagnoses (5%) of adenomatoid nodules, 73 (26%) cellular follicular lesions, 76 (28%) "suspicious for follicular neoplasm", and 112 diagnoses (41%) of follicular neoplasm. FNA reports were compared with pathohistological findings. In FNA reports of adenomatoid nodule (N = 15), there were seven (47%) pathohistological diagnoses (PHDs) of nodular goiter, and eight (53%) PHDs of follicular adenoma. In FNA reports of cellular follicular lesion (N = 73), there were 2 (3%) PHDs of thyroiditis, 32 (44%) PHDs of nodular goiter, 38 (52%) PHDs of follicular adenoma, and one (1%) PHD of papillary carcinoma. In FNA reports of "suspicious for follicular neoplasm" (N = 76), there was one (1%) PHD of thyroiditis, 24 (32%) PHDs of nodular goiter, 47 (62%) PHDs of follicular adenoma and four (5%) diagnoses of papillary carcinoma. In FNA reports of follicular neoplasm (N = 112), there were 25 (22%) PHDs of nodular goiter, 72 (64%) PHDs of follicular adenoma, and 15 (14%) PHDs of thyroid carcinoma. We found significant difference (p0.01) between investigated FNA report groups according to malignancy risk. Stratification of cytologic diagnoses of follicular thyroid lesions into different subcategories with various probabilities of malignancy allows more accurate estimation of malignancy risk and individualized patient treatment, when deciding between immediate operation and close follow-ups with repeat FNA.

The aim of the study was to determine the incidence of coexistence of papillary carcinoma and Hashimoto's thyroiditis in cytologic material. Cytologic findings were collected from 10508 patients that underwent ultrasound-guided fine needle aspiration cytology (FNAC) of the thyroid. Hashimoto's thyroiditis was found in 2156 (20.5%) and papillary carcinoma in 269 (2.6%) of 10508 patients with FNAC, whereas both Hashimoto's thyroiditis and papillary carcinoma were present in 42 (0.4%) patients. Among patients with FNAC diagnosis of Hashimoto's thyroiditis, the prevalence of papillary carcinoma was 1.9%. Among patients with FNAC diagnosis of papillary carcinoma, the prevalence of Hashimoto's thyroiditis was 15.6%. There was no statistically significant association between the presence of papillary carcinoma and Hashimoto's thyroiditis in patients undergoing FNAC (p=0.0522). In conclusion, in a large series of patients, the incidence of Hashimoto's thyroiditis and papillary carcinoma coexistence in cytologic material was 0.4%. There was no statistically significant relationship between Hashimoto's thyroiditis and papillary carcinoma in cytologic material.

People of all ages can be affected by iodine deficiency; however, pregnant women and children are especially at a high risk. Because of changes that occur in maternal thyroid hormone economy during pregnancy and the potential unfavorable effects of iodine deficiency on the offspring, an adequate dietary iodine intake throughout the pregnancy is highly important. Therefore, the World Health Organization, United Nations Children's Fund and International Council for the Control of Iodine Deficiency Disorders have proposed that dietary intake of iodine during pregnancy should be 200-300 µg/day to compensate for the augmented T4 requirements in pregnant women. It has been shown that in countries with a longstanding and well-established universal salt iodination program where iodine sufficiency has been reached, there is a fraction of pregnant women that still have low median urinary iodine concentration, which indicates insufficient dietary iodine. Studies performed in such countries emphasize that pregnant women should use multivitamin and/ or mineral tablets specifically prepared for the needs of pregnancy and containing iodine supplements. Only the United States of America and Canada have official recommendations concerning iodine supplementation. In other countries, no such firm decisions have yet been made by medical community and public health authorities. In Croatia, an iodine sufficient country, the situation is the same. There is a need to collect adequate data on iodine supplementation and urinary iodine during pregnancy, along with the universal salt iodination program, so that definitive conclusions can be made., Nedostatak joda može zahvatiti bilo koju dobnu skupinu, ali je ta opasnost osobito visoka kod trudnica i djece. Dostatan unos joda u prehrani kroz cijelo razdoblje trudnoće je veoma važan zbog promjena koje nastaju u kretanju majčinih hormona štitnjače tijekom trudnoće i mogućih negativnih učinaka nedostatka joda na dijete. Stoga su Svjetska zdravstvena organizacija, Fundacija za djecu Ujedinjenih naroda i Međunarodni savjet za kontrolu bolesti uzrokovanih nedostatkom joda predložili unos joda prehranom tijekom trudnoće od 200-300 µg/dan kako bi se nadoknadile povećane potrebe za T4 kod trudnica. Pokazalo se da u zemljama s dugotrajnim i dobro uspostavljenim sveopćim program om za jodiranje soli u kojima je postignut dostatan unos joda uvijek postoji skupina trudnica koje ipak imaju nizak medijan koncentracije joda u mokraći, što pak ukazuje na nedostatak joda u prehrani. U istraživanjima provedenim u takvim zemljama naglašava se kako bi trudnice trebale uzimati tablete multivitamina ili minerala koje sadrže dodatak joda i namijenjene su upravo za primjenu u trudnoći. Sjedinjene Američke Države i Kanada su jedine zemlje koje imaju službene preporuke za dodavanje joda, dok u drugim zemljama takve čvrste odluke medicinske struke i javnozdravstvenih vlasti još nisu donešene. Takva je situacija i u Hrvatskoj, zemlji s dostatnim unosom joda. Uz programe općeg jodiranja soli potrebno je prikupiti dovoljno podataka o dodavanju joda i koncentraciji joda u mokraći za vrijeme trudnoće kako bi se mogli donijeti valjani zaključci.

The aim of the study was to determine the incidence of coexistence of papillary carcinoma and Hashimoto's thyroiditis in cytologic material. Cytologic findings were collected from 10508 patients that underwent ultrasound-guided fine needle aspiration cytology (FNAC) of the thyroid. Hashimoto's thyroiditis was found in 2156 (20.5%) and papillary carcinoma in 269 (2.6%) of 10508 patients with FNAC, whereas both Hashimoto's thyroiditis and papillary carcinoma were present in 42 (0.4%) patients. Among patients with FNAC diagnosis of Hashimoto's thyroiditis, the prevalence of papillary carcinoma was 1.9%. Among patients with FNAC diagnosis of papillary carcinoma, the prevalence of Hashimoto's thyroiditis was 15.6%. There was no statistically significant association between the presence of papillary carcinoma and Hashimoto's thyroiditis in patients undergoing FNAC (p=0.0522). In conclusion, in a large series of patients, the incidence of Hashimoto's thyroiditis and papillary carcinoma coexistence in cytologic material was 0.4%. There was no statistically significant relationship between Hashimoto's thyroiditis and papillary carcinoma in cytologic material., Cilj ove studije bio je utvrditi incidenciju istodobne prisutnosti papilarnog karcinoma i Hashimotova tireoiditisa u citološkim uzorcima. Prikupljeni su citološki nalazi za 10.508 bolesnika podvrgnutih ultrazvučnoj citološkoj punkciji štitnjače tankom iglom (FNAC). Hashimotov tiroiditis je utvrđen kod 2156 (20,5%), a papilarni karcinom kod 269 (2,6%) od tih 10.508 bolesnika, dok je 42 (0,4%) bolesnika imalo i papilarni karcinom i Hashimotov tiroiditis. U bolesnika s Hashimotovim tireoiditisom učestalost papilarnog karcinoma bila je 1,9%, a među bolesnicima s papilarnim karcinomom učestalost Hashimotova tireoiditsa bila je 15,6%. Kod bolesnika podvrgnutih FNAC nije bilo statistički značajne povezanosti između prisutnosti papilarnog karcinoma i Hashimotova tireoiditisa (p=0,0522). Dakle, u citološkom materijalu velikog niza bolesnika utvrđena je incidencija istodobne prisutnosti papilarnog karcinoma i Hashimotova tiroiditisa od 0,4%. U citološkim uzorcima nije utvrđena statistički značajna povezanost između Hashimotova tireoiditisa i papilarnog karcinoma.

The village of Rude is situated near Zagreb, the capital of Croatia in the last Alpine valley on Balkan. In the past, the village was well-known area of severe iodine deficiency disorders (IDD). In 1952', distinguished Croatian endocrinologist Professor Josip Matovinovic carried out detailed village survey. Goiter prevalence in school-age children was 85.0% (with 2.3% of cretins in the village). In 1953, the first regulation on compulsory salt iodination with 10 mg of KI/kg of salt was established in former Yugoslavia. Ten years later a dramatic decrease in goiter prevalence was recorded in all endangered areas of the country and no new cretins appeared. However, at the beginning of 1990' mild to moderate iodine deficiency still persisted in Croatia. In 1991, the village of Rude survey demonstrated goiter prevalence in school-age children of 35.0% and median of urinary iodine excretion (UIE) of 7.4 microg/dL. In 1996, the new obligatory regulation with 25 mg of KI/kg of salt was established in Croatia. The study aim was to monitor IDD status in the village after the new law on compulsory salt iodination. Measurements of UIE and thyroid volumes (Tvol) by ultrasound were performed in 7-11-y-old schoolchildren living in the village of Rude. Medians of UIE and body surface area (BSA)-adjusted Tvol in boys and girls were calculated. The study included 84 children in 1997, 132 in 2000, 72 in 2002, 85 in 2003 and 46 in 2004 for UIE measurement. Thyroid volumes were measured in 1999 (43 boys and 26 girls) and in 2005 (22 boys and 26 girls). Data were compared with the new WHO/ICCIDD reference values. Medians of UIE in schoolchildren from the village of Rude demonstrated rising values in microg/dL: 11.4 in 1997, 14.3 in 2000, 17.3 in 2002, 15.4 in 2003 and 19.0 in 2004. Significant decrease in BSA-adjusted Tvol was recorded from 1999-2005 in boys and girls from the village of Rude and in 2005 Tvol were within the normal range according to the new international reference values for Tvol in iodine-sufficient schoolchildren. As a result of increased iodine prophylaxis, IDD no longer exist in Croatia. Monitoring of IDD status in the village of Rude after new law on compulsory salt iodination in Croatia demonstrated rising medians of UIE together with significant reduction of Tvol. In 2005, Tvol in schoolchildren from the village of Rude were within the normal range according to the new international reference values for Tvol in iodine-sufficient schoolchildren.

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Purpose of the study was to evaluate the role of ultrasonography (US) and US-guided fine needle biopsy (FNAB) in patients with thyroid nodules.

To determine diagnostic relevance of cytologic subclassification of follicular lesions of the thyroid and its role in the therapeutic approach.We performed a retrospective analysis of the data of patients who underwent thyroid surgery at the Sisters of Mercy University Hospital, Zagreb, between March 1995 and February 2001, and had a report of preoperative fine needle aspiration (FNA) biopsy of thyroid follicular lesion, which comprises cellular follicular lesion, suspicious for follicular neoplasm, or follicular neoplasm.Out of 110 patients with preoperative FNA biopsy diagnosis of follicular lesion, 86 (78%) had a lesion corresponding histologically to a neoplasm. However, a malignant tumor was found in only 6% of the patients. In the diagnostic categories of cellular follicular lesion and lesion suspicious for follicular neoplasm, the rate of malignancy was even lower, 3% and 4%, respectively. We found significant difference between FNA and histologic findings in distinguishing non-neoplastic from neoplastic thyroid lesions in the category of cellular follicular lesion and follicular neoplasm.Due to the low malignancy rate in patients with FNA biopsy diagnoses of cellular follicular lesion or lesion suspicious for follicular neoplasm of the thyroid, we suggest close clinical follow-up of such patients, rather than immediate surgical intervention.

Fine needle aspiration (FNA) of the thyroid has been utilized as a diagnostic method for 40 years. The main purpose of thyroid FNA is to differentiate nodules that require surgery from those that do not. The sensitivity of thyroid FNA ranges from 65% to 99%, and its specificity from 72% to 100%. Ultrasound-guided FNA of the thyroid is recommended, especially for sampling of a small, deep nodule. One to four aspirations suffice in single nodular lesions measuring less than 3 cm in diameter. Although the criteria used to establish specimen adequacy are somewhat controversial, most institutions require the presence of follicular cells. FNA diagnosis of thyroid disease is a clinicocytologic diagnosis, and correlation with clinical findings is mandatory for success. At our institution, diagnostic FNA lesions are subdivided into the following general diagnostic categories: benign, indeterminate, and malignant. Benign lesions include lesions with the diagnosis of benign thyroid nodule, nodular goiter, and thyroiditis. Indeterminate lesions include cellular follicular lesion, follicular neoplasm and Hürthle cell neoplasm. Malignant neoplasms include papillary carcinoma, high-grade follicular carcinoma, medullary carcinoma, anaplastic carcinoma, large cell lymphoma, and metastatic carcinoma. No clinical or laboratory test is sensitive and specific enough to distinguish reliably whether a follicular neoplasm identified on FNA is benign or malignant. This position may be changed with the development of molecular approaches to the diagnosis. CD44v6 and galectin-3 seem to be most promising tumor markers for thyroid malignancies of follicular epithelial cell origin., Aspiracijska citologija štitnjače tankom iglom rabi se kao dijagnostička metoda već 40 godina. Glavni cilj aspiracijske citologije štitnjače je razlučiti čvorove štitnjače koji zahtijevaju kirurško liječenje od onih čvorova kod kojih to nije potrebno.Osjetljivost aspiracijske citologije štitnjače varira između 65% i 99%, a specifičnost između 72% i 100%. Preporuča se provoditi ju uz nadzor ultrazvuka, poglavito kod malih, dublje smještenih čvorova. Kod čvorova promjera manjeg od 3 cm dovoljno je izvršiti jednu do četiri aspiracije. Premda se kriteriji za prikladnost uzorka razlikuju od ustanove do ustanove, većina ih zahtijeva prisutnost folikularnih stanica. Citološka dijagnoza bolesti štitnjače zapravo je kliničko-citološka dijagnoza, jer se temelji na korelaciji citomorfološke slike i dostupnih kliničkih podataka. U našoj ustanovi dijagnostičke citološke promjene štitnjače dijelimo u tri glavne kategorije: benigne, neodređenog značaja i maligne. Benigne promjene uključuju dijagnoze kao što su benigni čvor štitnjače, nodularna struma i tireoiditis. Promjene neodređenog značaja uključuju celularnu folikularnu promjenu, folikularni tumor i tumor Hürthleovih stanica. Maligne promjene uključuju papilarni karcinom, slabo diferencirani folikularni karcinom, medularni karcinom, anaplastični karcinom, limfom velikih stanica i metastatski karcinom. Niti jedan klinički ni laboratorijski test nije dovoljno osjetljiv ni specifičan da bi pouzdano razlučio maligne od benignih citološki dijagnosticiranih folikularnih tumora štitnjače. Ovakvo stanje moglo bi se izmijeniti primjenom molekularne dijagnostike tumora pri čem se CD44v6 i galektin-3 nameću kao obećavajući biljezi malignih stanica podrijetla folikularnih epitelnih stanica.