SIMULTANEOUS METASTASES OF PAPILLARY THYROID CARCINOMA AND NEUROENDOCRINE TUMOR OF THE CECUM TO CERVICAL LYMPH NODES: A CASE REPORT.

We present a case of a patient with simultaneous cervical lymph node metastasis of papillary thyroid cancer (PTC) and cecum neuroendocrine tumor (NET). A 45-year-old male patient with the diagnosis of metastatic NET of the cecum underwent fine needle aspiration (FNA) of a positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET) positive nodule in the left thyroid lobe. Due to FNA finding suspect of PTC, the patient underwent total thyroidectomy with central neck dissection. Histopathologic finding revealed PTC of the left thyroid lobe and small solitary lymph node PTC metastasis in the central neck region. Postoperative evaluation with neck ultrasound (US) revealed two enlarged suspected lymph nodes in cervical regions III and IV on the left side of the neck and the patient underwent FNA with measurement of thyroglobulin (Tg) in the aspirates. The FNA finding of the cervical lymph node in the region III revealed PTC metastasis with high Tg value in the aspirate, while FNA finding of the cervical lymph node in the region IV revealed NET metastasis with low Tg value in the aspirate. Postoperative serum Tg value was 17.75 µg/L and the patient underwent 5550 MBq iodine-131 (I-131) therapy. A year after I-131 therapy, follow-up neck US demonstrated complete cure of PTC cervical lymph node metastasis in the region III and stable in size NET cervical lymph node metastasis in the region IV. To our knowledge, this is the first report of simultaneous occurrence of cervical lymph node metastases of PTC and NET of the cecum.

THE CONCENTRATION OF INTERLEUKIN 6 AND TUMOR NECROSIS FACTOR ALPHA IN SALIVA AND BLOOD OF PATIENTS WITH INACTIVE MULTIPLE SCLEROSIS AND COEXISTING HASHIMOTO'S THYROIDITIS.

The concentration of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the blood is higher in patients with active multiple sclerosis (MS) compared to those with inactive disease. The concentration of IL-6 and TNF-α in the blood is higher in patients with Hashimoto's thyroiditis (HT) compared to those with a healthy thyroid. The aim of the study was to assess whether serum IL-6 and TNF-α levels correlated with saliva in patients with inactive MS and whether there was a difference in these groups of patients depending of thyroid status. We also examined the correlation of thyroid stimulating hormone (TSH) levels with thyroid status. The study included 54 patients in the inactive phase of MS. The level of cytokines in the blood was determined by chemiluminescence, and in saliva by ELISA. Blood and saliva IL-6 levels showed positive correlation, while blood and saliva TNF-α levels were not correlated. There was a significantly higher TSH level in patients with inactive MS with positive thyroid antibodies, without therapy, compared with those with negative antibodies.

THE PREVALENCE OF SUBCLINICAL HYPOTHYROIDISM IN THE POPULATION OF ELDERLY NURSING HOME RESIDENTS IN ZAGREB.

The aim of the study was to investigate the prevalence of thyroid dysfunction, positive thyroid peroxidase antibodies (TPOAb) and hypercholesterolemia in elderly and younger subjects, and the association of subclinical hypothyroidism with hypercholesterolemia. The study included 204 elderly (136 females and 68 males, age median 71, range 60-92 years), and 83 younger control subjects (63 females and 20 males, age median 45, range 19-55 years). Subjects with prior thyroid dysfunction were excluded. Serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), TPOAb, total cholesterol, height and weight were measured. Mann-Whitney, χ2-test and Student's t-test were used on statistical analysis. The prevalence of subclinical hypothyroidism (TSH >5 mU/L) in elderly was 7.4% vs. 3.6% in younger subjects, with the highest prevalence of 8.8% in elderly women vs. 4.8% in younger women, and 4.4% in elderly men. The prevalence of hypothyroidism and subclinical hyperthyroidism in elderly subjects was 0.5% and 1.5%, respectively. In women with subclinical hypothyroidism, the prevalence of TPOAb was 77% in elderly women and 67% in younger women (overall 19.9% in elderly and 14.3% in younger women). The mean FT3 level was lower in elderly women as compared with elderly men (p<0.01) and younger women (p<0.05). The mean cholesterol level was higher in elderly subjects in comparison with younger ones (p<0.01), and in elderly women vs. elderly men (p<0.01), but without difference between subclinical hypothyroidism and euthyroid subjects (6.0 mmol/L). In conclusion, subclinical hypothyroidism is the most prevalent thyroid dysfunction in elderly, with the highest prevalence in elderly women, and autoimmune thyroiditis is the most common etiology. Hypercholesterolemia was more related to older age, especially elderly females, but not influenced by subclinical hypothyroidism.

Long-Term Outcome of Differentiated Thyroid Cancer Patients-Fifty Years of Croatian Thyroid Disease Referral Centre Experience.

Background: Indolent nature but a high incidence of differentiated thyroid cancer (DTC) remains a challenge for optimizing patient care. Therefore, prognostic factors present valuable information for determining an adequate clinical approach. Methods: This study assessed prognostic features of 1167 papillary (PTC) and 215 follicular (FTC) thyroid cancer patients that had undergone surgery between 1962 and 2012, and were followed-up up to 50 years in a single institution, till April 2020. Age, gender, tumor size, presence of local and distant metastases at presentation, extrathyroidal extension, disease recurrence, and cancer-specific survival were evaluated. Results: In multivariate analysis, factors affecting the worse outcome were age (p = 0.005), tumor size (p = 0.006), and distant metastases (p = 0.001) in PTC, while extrathyroidal extension (p < 0.001), neck recurrence (p = 0.002), and distant metastases (p < 0.001) in FTC patients. Loco-regional recurrence rate was 6% for PTC and 4.7% for FTC patients, while distant metastases were detected in 4.2% PTC and 14.4% of FTC patients. The 10-year cancer-specific survival rates for PTC and FTC were 98.6% and 89.8%, respectively (p < 0.001). Conclusions: Negative prognostic factors, besides distant metastases, were older age and greater tumor size in PTC, and extrathyroidal extension and neck recurrence in FTC patients. The recurrence and mortality rates were very low.

99mTc-MIBI SPECT/CT SCINTIGRAPHY AND ULTRASOUND OF THE ANTERIOR NECK REGION IN DIAGNOSING PARATHYROID GLAND PATHOLOGY IN PATIENTS WITH THYROID NODULES.

Parathyroid scintigraphy with 99mTc-MIBI is an imaging technique used in nuclear medicine and performed in patients with suspected hyperparathyroidism (HPT). The objective of this study was to evaluate the role of this technique in patients who, along with suspected HPT, also have thyroid nodules. Retrospective analysis included a period of 8 years (2006-2013). The study included 91 patients with clinical or laboratory suspected HPT. Pathologic changes in parathyroid glands were demonstrated in 47 (70%) of 67 patients with positive scintigraphy. Pathologic changes in parathyroid glands were not evident in the remaining 20 (30%) patients. Out of nine patients with negative scintigraphy results but with suspected enlargement of the parathyroid gland examined by ultrasound, eight (89%) patients did not show pathologic changes in the parathyroid gland, whereas one (11%) patient had evident changes. Eight (54%) of 15 patients with suspected scintigraphy had positive ultrasound findings, as well as fine needle aspiration cytology (FNAC) findings with parathyroid hormone (PTH) determination in the aspirate. Seven (46%) patients had negative FNAC findings and PTH in the aspirate. The study showed scintigraphy to have high sensitivity (98%) in detecting patients with pathologic changes in the parathyroid glands. In patients with suspected HPT, scintigraphy needs to be combined with FNAC and PTH determination in the aspirate due to its low specificity of 28%.

IODINE STATUS AND THYROID FUNCTION IN LACTATING WOMEN AND INFANTS - A SURVEY IN THE ZAGREB AREA, CROATIA.

Lactating women (LW) and infants have high dietary iodine requirements and are at risk of iodine deficiency. The aim of the study was to assess iodine status and thyroid function in LW and their breastfed infants in Zagreb, Croatia. The study included 133 LW and breastfed infant pairs. Urinary iodine concentration (UIC) and thyroid function parameters were measured in all subjects. In LW, breast milk iodine concentration (BMIC) was measured and iodine and salt rich food frequency questionnaire data were collected. Results of analysis indicated that 99.2% of the LW used iodized salt in household and 20.4% used iodine-containing vitamin and mineral supplements. Median (IQR) UIC was 75 µg/L (19.0-180.5 µg/L) in LW and 234 µg/L (151.0-367.5 µg/L) in infants, whereas BMIC was 121 µg/kg (87.8-170.8 µg/kg). Multivariate regression analysis revealed BMIC to be a significant predictor of infant UIC (p<0.001). Positive correlation was recorded between LW and infant thyroid function. This was the first study in Croatia demonstrating BMIC to be a reliable biomarker of iodine status during lactation and predicting iodine intake in breastfed infants. The study confirmed that mandatory salt iodization in Croatia ensured sufficient dietary iodine for LW and optimal iodine intake for breastfed infants via breast milk.

Association of Triiodothyronine Levels With Prostate Cancer Histopathological Differentiation and Tumor Stage.

BACKGROUND/AIM: The aim of this study was to determine the association between total triiodothyronine (T3), free fraction of thyroxin (FT4), and thyrotropin (TSH) levels with prostate cancer histopathological features. PATIENTS AND METHODS: Blood samples from 140 patients with prostate cancer were analyzed preoperatively and stratified according to postoperative histopathological differentiation. The first group (N=62) included patients with prostate cancer Grade Groups (GG) 1-2, while the second group (N=63) included patients with prostate cancer GG 3-5. RESULTS: T3 levels were significantly higher in patients with prostate cancer GG 3-5 (p=0.047). There was no significant difference in the FT4 and TSH levels between the two groups (p=0.680 and 0.801, respectively). T3 levels were positively correlated with tumor percentage involvement (TPI) (p=0.002), and pT stage (p=0.047) on definitive pathology. CONCLUSION: Higher T3 levels are associated with several indicators of prostate cancer histopathological aggressiveness.

Thyroglobulin Measurement in Needle Aspiration for Detection of Recurrences and Neck Metastases in Patients with Differentiated Thyroid Carcinoma: Significance of Anti-Tg Antibodies.

The worldwide incidence of differentiated thyroid cancer (DTC) has increased in recent decades, likely due to frequent use of cervical ultrasonography (US) and US-guided fine needle aspiration biopsy (FNA)., US is performed during follow-up after thyroidectomy, and US-guided FNA with cytology is used if suspicious cervical lymph nodes (LN) or thyroid bed masses are detected. Knowing that serum anti-Tg antibodies (sTgAb) affect the use of serum Tg (sTg) as a tumor marker, the aim of our study was to assess the usefulness of Tg determination in needle aspirates (FNA-Tg) in presence of sTgAb. This retrospective study included 149 patients with DTC and 159 aspirations of suspicious LN and thyroid bed masses. As expected, there was a negative correlation between sTg and sTgAb levels (p<0.05), while FNA-Tg levels had a positive correlation with FNA-TgAb levels (p<0.05). Furthermore, we found a positive correlation between sTg and FNA-Tg levels (p<0.05), but not between sTgAb and FNA-TgAb or sTgAb and FNA-Tg. In conclusion, these results show that FNA-Tg values were not affected by sTgAb and that FNA-Tg measurement were highly effective in detecting cervical DTC metastases. However, combined use with cytology is suggested for neck evaluation because cytology could reveal metastases from other tumor sites.

Dose-volume derived nomogram as a reliable predictor of radiotherapy-induced hypothyroidism in head and neck cancer patients.

Background The aim of this study was to determine the possible predictive value of various dosimetric parameters on the development of hypothyroidism (HT) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. Patients and methods This study included 156 patients with HNSCC who were treated with (chemo)radiotherapy in a primary or postoperative setting between August 2012 and September 2017. Dose-volume parameters as well as V10 toV70, D02 to D98, and the VS10 to VS70 were evaluated. The patients' hormone status was regularly assessed during follow-up. A nomogram (score) was constructed, and the Kaplan-Maier curves and Log-Rank test were used to demonstrate the difference in incidence of HT between cut-off values of specific variables. Results After a median follow-up of 23.0 (12.0-38.5) months, 70 (44.9%) patients developed HT. In univariate analysis, VS65, Dmin, V50, and total thyroid volume (TTV) had the highest accuracy in predicting HT. In a multivariate model, HT was associated with lower TTV (OR 0.31, 95% CI 0.11-0.87, P = 0.026) and Dmin (OR 9.83, 95% CI 1.89-108.08, P = 0.042). Hypothyroidism risk score (HRS) was constructed as a regression equation and comprised TTV and Dmin. HRS had an AUC of 0.709 (95% CI 0.627-0.791). HT occurred in 13 (20.0%) patients with a score < 7.1 and in 57 (62.6%) patients with a score > 7.1. Conclusions The dose volume parameters VS65, Dmin, V50, and TTV had the highest accuracy in predicting HT. The HRS may be a useful tool in detecting patients with high risk for radiation-induced hypothyroidism.

Corrigendum to: Analytical evaluation of the new Seal Autoanalyzer 3 High Resolution for urinary iodine determination.

[This corrects the article DOI: 10.11613/BM.2019.020711.].

DIFFERENTIATED THYROID CANCER IN PEDIATRIC POPULATION (≤18 YEARS): POSTOPERATIVE TREATMENT WITH RADIOACTIVE IODINE (I-131).

The aim is to present data on the treatment and follow-up in a cohort of patients with pediatric thyroid cancer who underwent total thyroidectomy and received postoperative radioactive iodine (I-131) therapy. The study was conducted in a tertiary high-volume thyroid center, in pediatric patients with differentiated thyroid cancer who were consecutively treated during the 1965-2015 period. A total of 45 patients aged ≤18 years having undergone total thyroidectomy with or without selective neck dissection were included in the study. Decision on postoperative I-131 ablation was based on tumor characteristics, postoperative thyroglobulin level, preablative whole body scintigraphy, and/or neck ultrasound. Median age at diagnosis was 15 years. The presence of cervical lymph node metastases was significantly associated with papillary thyroid cancer, larger tumor size, involvement of two thyroid lobes, and multifocal disease. The presence of distant metastases was significantly associated with larger tumor size. None of the patients died during follow-up period, and the 5-year and 10-year overall survival rates were 100%. The 5-year and 10-year progression-free survival (PFS) rates were 87% and 73%, respectively. Male gender (p=0.046), age ≤15 years (p=0.029) and tumor size >15 mm (p=0.042) were significantly associated with inferior PFS. A significant positive trend of increase in the number of newly diagnosed patients was observed over time (p=0.011). Clinical management of pediatric thyroid cancer is challenging, especially in the light of increasing incidence in this population. Male patients younger than 15 years and with tumors of more than 15 mm in size require additional caution due to lower PFS observed.

Analytical evaluation of the new Seal Autoanalyzer 3 High Resolution for urinary iodine determination.

INTRODUCTION: The aim of the study was to evaluate the analytical performance of the new colorimetric, automatic analyser, Seal AutoAnalyzer 3 High Resolution (Seal AA3 HR) (Seal Analytical, Wisconsin, USA) for urinary iodine measurement. MATERIALS AND METHODS: This study included testing of several analytical features of the method involving: imprecision (within-run %CVr, between-run %CVb and total laboratory precision %CVl), measurement uncertainty, carryover, linearity and method comparison, with 70 urine samples including the measuring range (20 - 700 µg/L). RESULTS: Within-run, %CVb and %CVl of two control levels were 2.03% and 3.04%, 0.51% and 2.61%, and 2.09% and 4.01%, respectively. Carryover effect was less than 1%. The linearity was good in the range of urinary iodine values between 60 and 500 µg/L (R2 = 0.99). Good agreement of urinary iodine values was found between manual technique and Seal AA3 HR, using Passing-Bablok regression (y = 7.84 (- 3.00 to 15.29) + 0.95 (0.90 to 1.00) x) and Blant-Altman test. Cusum test for linearity indicates that there is no significant deviation from linearity (P > 0.1). CONCLUSIONS: The obtained results proved excellent precision, reproducibility and linearity, comparable to the already used, manual method. The New Seal AA3 HR automatic analyser is acceptable for urinary iodine measurement with very good analytical characteristics and can be used for urinary iodine epidemiological studies of the Croatian population.

An Unusual Case of Papillary Thyroid Carcinoma Iodine-131 Avid Metastasis to the Adrenal Gland.

Papillary thyroid carcinoma (PTC) is considered one of the most favorable tumors, indolent, with rare distant dissemination. Lungs and bones are the most common metastatic sites. Unusual sites of PTC distant metastases are extremely rare. Brain, liver, skin, kidney, pancreas, and adrenal gland PTC metastases have been sporadically reported in the literature. An 86-year-old female patient underwent total thyroidectomy and neck dissection due to PTC. Postoperative whole body iodine-131 scintigraphy with I-131 SPECT/CT of the abdomen revealed radioiodne avid left adrenal gland metastasis together with high postoperative serum thyroglobulin (Tg) value of more than 5000 µg/L and high serum Tg antibodies. Considering the above-mentioned findings, patient's age and multiple comorbidities, radioiodine therapy was applied. PTC metastases to the adrenal gland are extremely rare, and to our knowledge, only nine cases have been reported in the literature. This case report complements rare examples of unusual PTC metastases.

THYROGLOBULIN AS A TUMOR MARKER IN DIFFERENTIATED THYROID CANCER - CLINICAL CONSIDERATIONS.

- Initial treatment of the majority of patients with differentiated thyroid cancer (DTC) includes total thyroidectomy. Postoperative ablation therapy with radioactive iodine (I-131) is indicated in all high-risk patients, however, there is disagreement regarding its use in low- and intermediate-risk patients. Over the last few decades, thyroglobulin (Tg) has been established as the primary biochemical tumor marker for patients with DTC. Thyroglobulin can be measured during thyroid hormone therapy or after thyroid-stimulating hormone (TSH) stimulation, through thyroid hormone withdrawal or the use of human recombinant TSH. In many studies, the cut-off value for adequate Tg stimulation is a TSH value ≥30 mIU/L. However, there is an emerging body of evidence suggesting that this long-established standard should be re-evaluated, bringing this threshold into question. Recently, a risk stratification system of response to initial therapy (with four categories) has been introduced and Tg measurement is one of the main components. The relationship between the Tg/TSH ratio and the outcome of radioiodine ablation has also been studied, as well as clinical significance of serum thyroglobulin doubling-time. The postoperative serum Tg value is an important prognostic factor that is used to guide clinical management, and it is the most valuable tool in long term follow-up of patients with DTC.

Bone Mineral Density in Relation to Metabolic Syndrome Components in Postmenopausal Women With Diabetes Mellitus Type 2

Diabetes mellitus type 2 is associated with greater bone mineral density (BMD) due to obesity, although rapid bone loss observed over time could be explained by elevated chronic inflammation. The objective of this study was to investigate the relationship between central adiposity and hyperinsulinemia, as well as inflammation markers with vertebral and femoral BMD and bone turnover markers in postmenopausal women with type 2 diabetes. Femoral and vertebral BMD, osteocalcin, pyrilinks D, beta-CrossLaps (B-CTx), insulin, C-reactive protein (CRP), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) were measured in 114 postmenopausal female patients with diabetes type 2. The patients of similar age, HbA1c levels and diabetes duration were divided into 2 groups based on their body mass index (BMI) values: lower or equal to 27 kg/m(2) (31 patients) and higher than 27 kg/m(2) (83 patients). Lower levels of osteocalcin (p=0.001), B-CTx (p=0.000007) and pyrilinks D (p=0.0365), and higher femoral BMD (p=0.00006), insulin level (p=0.0002), PAI-1 (p=0.00000) and CRP (p=0.002) were found in the overweight group. There were no signifi cant differences in vertebral BMD and fibrinogen. Osteocalcin and B-CTx showed inverse correlation, and femoral BMD positive correlation with waist circumference, insulin level and PAI-1. This suggests that abdominal obesity and hyperinsulinemia as components of the metabolic syndrome could increase femoral BMD by lowering bone rate. In addition, the only inflammation marker linked with femoral BMD was PAI-1, which is associated with increased mineralization of cortical bone in mouse.

Serum Osteoprotegerin in Patients with Calcified Aortic Valve Stenosis in Relation to Heart Failure.

The aim of the study was to assess the role of serum osteoprotegerin (OPG) as a biomarker in patients with aortic valve stenosis (AS) in relation to heart failure and symptomatic status. This was a case control study, which included 51 patients with AS and 39 control subjects. At the time of study enrolment, detailed medical history was obtained and all subjects underwent physical examination, chest x-ray and echocardiography. OPG levels were measured in all subjects, and serum N-terminal of the pro b-type natriuretic peptide (NT pro BNP) levels were determined in patients with AS. Serum OPG levels were elevated in patients with AS compared to control subjects (p=0.001). Patients with heart failure due to AS had elevated serum OPG levels in comparison to patients without heart failure (p=0.001). A significant correlation between OPG and symptomatic status was observed in all patients with AS (p<0.001), however, it was not the case in patients without heart failure (p=0.425). There was a positive correlation between OPG and NT pro BNP concentrations with objective signs of heart failure on chest x-ray (p<0.001). Negative correlation of OPG concentrations with aortic valve area was present (p<0.040), as well as with left ventricular ejection fraction (p<0.001). Serum OPG could be a valuable biomarker in the evaluation of severity of calcified AS and serve as an additional indicator besides clinical presentation and echocardiography in the assessment of surgical treatment or aortic valve replacement.

Neurosyphilis in Anglo-American Composers and Jazz Musicians.

Syphilis is a sexually transmitted, systemic disease caused by the spirochete bacterium Treponema pallidum. The most common mechanism of transmission is sexual intercourse. Although there are several hypotheses, the exact origin of the disease remains unknown. Newly published evidence suggests that the hypothesis supporting the theory of the American origin of the disease is the valid one. Among 1500 analyzed pathographies of composers and musicians, data on ten Anglo-American composers and jazz musicians having suffered from neurosyphilis (tertiary stage of the disease) were extracted for this report. In this group of Anglo-American composers and musicians, most of them died from progressive paralysis while still in the creative phase of life. Additionally, diagnoses of eleven other famous neurosyphilitic composers, as well as basic biographic data on ten less known composers that died from neurosyphilis-progressive paralysis are also briefly mentioned. In conclusion, neurosyphilis can cause serious neurological damage, as well as permanent disability or death, preventing further work and skill improvement.

Melanomas in Renal Transplant Recipients: A Single-center Study.

Skin cancers are the most common malignancies in renal transplant recipients, with squamous-cell and basal-cell cancers accounting for the majority of all skin cancer cases. Melanoma is relatively rare in this group of patients. From 1973 to May 2017, out of 1889 patients who received allografts at our institution, 4 developed melanoma. After the mean follow-up of 11.5 months, 2 patients died and 2 are still alive with functioning allografts. Malignancies were localized in the legs in both female patients, and in the neck and head in 1 male patient each. Compared to the general population of Croatia, renal transplant recipients from our cohort have 6.85 times higher risk for development of melanoma. Regular screenings and patient education are mandatory, especially in Mediterranean countries.

[AMIODARONE AND THE THYROID FUNCTION]. / AMIODARON I FUNKCIJA STITNJACE.

Amiodarone is a benzofuran derivative that contains up to 40% of iodine. Amiodarone is used for treatment and prevention of life threatening supraventricular and ventricular tachyarrhythmias. The effects on thyroid gland vary from abnormalities in thyroid function tests to overt amiodarone induced hypothyroidism (AIH) and thyrotoxicosis (AIT). Patients with AIH are treated with L-thyroxine and may continue treatment with amiodarone. Two different forms of AIT have to be distinguished: amiodarone induced hyperthyroidism (AIT I) and thyroiditis (AIT II). AIT I is treated with antithyroid drugs, while total thyroidectomy and iodine-131 are used for definitive treatment. AIT II is treated with glucocorticoids. Patients with AIT have to stop treatment with amiodarone. Dronedarone is a less potent antiarrhythmic agent with structural and pharmacological properties similar to amiodarone. Dronedarone is devoid of iodine with fewer adverse effects and therefore it may be used in high risk patients for development of AIT or AIH.