Usporedba različitih doza joda 131 u ablaciji ostatnog tkiva štitnjače zbog papilarnog karcinoma, te uloga rekombinantnog humanog tireotropina (rhTSH) kod ablacije

Despite many years of experience in thyroid cancer treatment the agreement about the optimal I-131 activity needed for successful thyroid remnant ablation, has not yet been established. Some authors advocate a dosimetric approach to I-131 therapy, but most centers prefer to give standard activities which can range from as low as 1110 GBq (30 mCi) of I-131 to as high as 5550 GBq (150 mCi). During past decades the activity of 4440 (120 mCi) of I-131 used to be applied in our Department as standard ablative activity with excellent outcome. Encouraged with the results of quantitative dosimetric investigations in our patients we recently reduced the amount of administered radioiodine trying to be more rationale considering radiation burden for patients and staff as well as the cost of treatment. Therefore, we started to practice a lower activity regime by administration of 888 MBq (24 mCi) to 1850 MBq (50 mCi) of I-131. Successful application of radioiodine requires hypothyroid state (TSH level higher than 30 mIU/L) achieved either by stimulation of endogenous TSH production after withdrawal of suppressive therapy or by administration of human recombinant TSH (rhTSH). The aim of this study was to compare ablation rates obtained with different I-131 activities in large group of patients. The first study included 466 patients divided into four groups according to I-131 activities given after total thyroidectomy for papillary thyroid cancer: 888 MBq/24 mCi (group A, n =168), 1480 MBq/40 mCi (group B, n = 125), 1850 MBq/50 mCi (group C, n = 65) and 4440 MBq/120 mCi (group D, n = 108). Second goal, in smaller selected group of patients was to evaluate the successfulness of thyroid remnant ablation after application of 1850 MBq (50 mCi) of radioiodine in hypothyroid patients as well as in euthyroid patients previously prepared with human recombinant thyrotropin. Those study included patients with intrathyroid papillary carcinoma, smaller than 1.5 cm, without any sign of metastatic disease. Patients were divided into two groups according to method of preparation for thyroid remnant ablation (hypothyroid group 42 pts, rhTSH group 35 pts), and the rate of ablation was compared. Ablation outcome was assessed by whole body scan in hypothyroid state 6-9 months after ablation and finally 18-21 months after the treatment. The rate of successful ablation was similar in the group of patients who received 24 and 40 mCi (75% and 71.2%, respectively). The higher rate of ablation (87.69% and 90.74%) was achieved in the groups treated with 50 and 120 mCi of radioiodine. The ablation rates at the first follow-up examinations (59.5%, 67.2%, 73.9%, 80.6%) were lower than at second control study (75.0%, 71.2%, 87.7%, 90.7%) in all groups, respectively. Time required for thyroid remnant ablation appears to be ≥18 months. There was no significant difference between rates of ablation in two groups of patients received 1850 MBq (50 mCi) of radioiodine prepared by recombinant human TSH or by hormone withdrawal, neither at first nor at the second control. Radioablation was considered successful in 88.6% of patients prepared by recombinant human TSH, and 88.1% of those prepared by hormone withdrawal. No serious adverse events were related to recombinant TSH administration. The study indicates that activity of 1850 MBq (50 mCi) seems to be optimal to achieve a successful ablation rate (~ 90%). Low I-131 activities are acceptable for lower risk patients because of satisfactory ablation rate (> 70%), lower expenses, and minimal radiation burden to patients as well as lower radiation exposure to clinical staff. The ablative use of high activities seems neither justified nor optimized. Also, study demonstrates comparable remnant ablation rates in patients prepared for radioiodine remnant ablation with 1850 MBq (50 mCi) by either administering rhTSH or withholding thyroid hormone. In both cases 1850 MBq (50 mCi) dose of radioiodine was sufficient for a satisfactory thyroid ablation rate

Diffuse sclerosing variant of thyroid carcinoma presenting as Hashimoto thyroiditis: a case report [Difuzno sklerozirajući oblik papilarnog karcinoma štitnjače nalik Hashimoto tireoiditisu: prikaz slučaja]

The aim of report is to present a case of a rare diffuse sclerosing variant of a papillary thyroid carcinoma. A 15-year old girl referred for ultrasound examination because of painless thyroid swelling lasting 10 days before. An ultrasound of the neck showed diffusely changed thyroid parenchyma, without nodes, looking as lymphocytic thyroiditis Hashimoto at first, but with snow-storm appearance, predominantly in the right lobe. Positive thyroid peroxidase antibodies (TPO-AT) also suggested Hashimoto thyroiditis. Repeated US-FNAB (fine needle-aspiration biopsy) of the right lobe revealed diffuse sclerosing variant of papillary thyroid carcinoma and patient underwent total thyreoidectomy. Patohistologic finding confirmed diffuse sclerosing variant of a papillary thyroid carcinoma in the both thyroid lobes and several metastatic lymph nodes. Two months later patient recived radioablative therapy with 3700 MBq (100 mCi) of 1-131 followed by levothyroxine replacement. At the moment, patient is without evidence of local or distant metastases and next regular control is scheduled in 6 months. In conclusion, a diffuse sclerosing variant is rare form of papillary thyroid carcinoma that echographically looks similar to Hashimoto thyroiditis and sometimes could be easily overlooked

Diffuse Sclerosing Variant of Thyroid Carcinoma Presenting as Hashimoto Thyroiditis: A Case Report

The aim of report is to present a case of a rare diffuse sclerosing variant of a papillary thyroid carcinoma. A 15- year old girl referred for ultrasound examination because of painless thyroid swelling lasting 10 days before. An ultrasound of the neck showed diffusely changed thyroid parenchyma, without nodes, looking as lymphocytic thyroiditis Hashimoto at first, but with »snow-storm« appearance, predominantly in the right lobe. Positive thyroid peroxidase antibodies (TPO-AT) also suggested Hashimoto thyroiditis. Repeated US-FNAB (fine needle-aspiration biopsy) of the right lobe revealed diffuse sclerosing variant of papillary thyroid carcinoma and patient underwent total thyreoidectomy. Patohistologic finding confirmed diffuse sclerosing variant of a papillary thyroid carcinoma in the both thyroid lobes and several metastatic lymph nodes. Two months later patient recived radioablative therapy with 3700 MBq (100 mCi) of I-131 followed by levothyroxine replacement. At the moment, patient is without evidence of local or distant metastases and next regular control is scheduled in 6 months. In conclusion, a diffuse sclerosing variant is rare form of papillary thyroid carcinoma that echographically looks similar to Hashimoto thyroiditis and sometimes could be easily overlooked

Primjena inhibitora kinaza u liječenju bolesnika s uznapredovalim rakom štitnjače

Although most patients with thyroid cancer have a favorable clinical course, some patients develop a more aggressive type of cancer and exhibit more rapid disease progression with worse prognosis. Those patients usually exhibit mutations of proteins such as tyrosine kinase enzymes that play a significant role in regulation of tumor proliferation and spreading. Development of targeted therapies is based on the inhibition of mutated kinases which are involved in the MAPK signaling pathway. The aim of this study was to present the initial results of clinical experience with kinase inhibitors in patients with metastatic differentiated thyroid cancer (DT C), poorly differentiated thyroid cancer (PDT C), and medullary thyroid cancer (MTC) who exhibited rapid disease progression. A total of 17 adult patients (11 women, mean age 53.3 years) managed for progressive, metastatic disease were included in the study. Twelve patients with DT C and PDT C were previously tested for BRAF mutations, of whom nine that had tumor tissue negative for the BRAF V600E mutation received sorafenib, while three patients with tumors harboring the BRAF V600E mutation were treated with vemurafenib. Patients with MTC were treated with sunitinib, vandetanib, and sorafenib. Two patients with tumors harboring the BRAF mutation treated with vemurafenib showed restoration of radioiodine uptake. Most of patients showed significant improvement in disease status but of limited duration until disease progression. Although there was an improvement in progression-free survival, future research has to achieve a greater and longer-lasting response, probably by utilizing combined targeted therapy.Iako većina bolesnika s karcinomom štitnjače ima povoljan klinički tijek, ipak neki bolesnici pokazuju agresivniji tijek bolesti s razvojem uznapredovalih formi tumora i lošijom prognozom. Razlog su vjerojatno mutacije proteina, uglavnom enzima tirozin kinaza koji imaju značajnu ulogu u proliferaciji i rastu tumora. Razvoj ciljanih terapija zasnovan je na inhibiranju mutiranih kinaza BRAF, MEK, NRAS, c-KIT koje su uključene u signalni put MAPK. U radu su predstavljeni preliminarni rezultati liječenja inhibitorima kinaza u bolesnika s metastatskim diferenciranim karcinomom štitnjače (DT C), slabo diferenciranim karcinomom štitnjače (PDT C) i medularnim karcinomom štitnjače (MTC). U izvješće je uključeno ukupno 17 odraslih bolesnika (11 žena, prosječna dob 53,3 godine) liječenih zbog progresivne, metastatske bolesti. Dvanaest bolesnika s DT C i PDT C prethodno je testirano na BRAF mutacije. Devet bolesnika kod kojih je tumorsko tkivo bilo negativno na mutaciju BRAF V600E primali su sorafenib, dok su tri bolesnika s tumorima koji nose mutaciju BRAF V600E liječena vemurafenibom u cilju rediferencijacije tumora, a u dva bolesnika došlo je do ponovne akumulacije radiojoda na scintigramu tijela. Bolesnici s MTC-om liječeni su sunitinibom, vandetanibom i sorafenibom. U većine bolesnika došlo je do pozitivnog terapijskog odgovora uz poboljšanje stanja, ali ograničenog trajanja. Buduća istraživanja bi trebala osigurati bolji i trajniji terapijski odgovor, vjerojatno primjenom kombinirane ciljane terapije

Dezmoidni tumor u ležištu štitnjače: prikaz bolesnika

SAŽETAK Dezmoidni tumori su rijetke benigne tvorbe podrijetla vezivnog tkiva koje sporo rastu, ne metastaziraju, ali mogu invadirati okolna tkiva. Cilj izvješća je prikaz bolesnice s dezmoidnim tumorom razvijenim u ležištu lijevog režnja štitnjače nakon prethodnoga operacijskog zahvata totalne tireoidektomije zbog multinodularne guše s ekstirpacijom adenoma paratireoidne žlijezde u istom aktu. Zbog promuklosti i osjećaja bolnosti u ležištu štitnjače dvije godine nakon inicijalnog zahvata kod bolesnice je učinjen kontrolni ultrazvuk vrata koji verificira slabo ograničen, nehomogen, pretežno izoehogen čvor tvrde konzistencije u ležištu lijevog režnja štitnjače koji je po svojim ehografskim karakteristikama bio suspektan na malignu promjenu. Ciljana citološka punkcija opisuje rijetke vretenaste stanice, ali bez drugih elemenata za pobližu diferencijaciju. Stoga je ultrazvučni pregled dopunjen drugim slikovnim radiološkim metodama (kompjutorizirana tomografija i magnetska rezonancija) koje postavljaju sumnju na paragangliom ili adenom paratireoidne žlijezde, ali se nije mogla sa sigurnošću isključiti ni promjena druge etiologije. Zbog navedenog kod bolesnice je preporučena kirurška ekscizija koja je bila zahtjevna zbog tvrdoće navedene tvorbe. Patohistološki nalaz je odgovarao ekstraabdominalnoj fibromatozi, odnosno dezmoidnom tumoru s mogućom pojavom recidiva. Iako je dezmoidni tumor općenito benigna bolest, ponekad može biti lokalno invazivan s infiltracijom okolnih struktura oponašajući sliku malignog procesa uz otežanu potpunu kiruršku eksciziju koja je terapija izbora. Štoviše, unatoč potpunom uklanjanju čest je recidiv bolesti pa bolesnike s dezmoidnim tumorom treba povremeno kontrolirati

Are kidney malformations an additional feature of MEN2B syndrome? – Case report and literature review

Sindrom multiple endokrine neoplazije 2B (MEN2B) rijetka je autosomno dominatno nasljedna bolest uzrokovana mutacijama protoonkogena RET. Karakteriziran je pojavom medularnog karcinoma štitnjače već od rane, nerijetko dojenačke dobi, feokromocitoma koji je najčešće obostran, sluzničkim neuromima te drugim ekstraendokrinim manifestacijama i specifičnim fenotipskim značajkama koje mogu pomoći u prepoznavanju ovih bolesnika. Prikazujemo pacijenta sa sindromom MEN2B, dijabetesom melitusom tipa 1, inverznim položajem organa te prirođenim malformacijama bubrega i mokraćnog sustava. Pregledom literature uočeno je da se malformacije mokraćnog sustava opisuju i u drugih bolesnika sa sindromom MEN2B. Prepoznata uloga gena RET u razvoju anomalija mokraćnog sustava čini moguću etiološku poveznicu sa sindromom MEN2B. Predlažemo da se malformacije bubrega razmotre kao jedno od obilježja sindroma MEN2B. Budući da se osobine bolesnika sa sindromom MEN2B postupno razvijaju s dobi, prepoznavanje prirođene mane, uz prve znakove ostalih fenotipskih značajki, moglo bi pomoći ranom postavljanju dijagnoze i liječenju ovih bolesnika.Multiple endocrine neoplasia type 2B (MEN2B) is a rare familial syndrome caused by autosomal dominant mutations in the RET proto-oncogene. The disease is characterized by aggressive, early-onset medullary thyroid carcinoma, pheochromocytoma, most often bilateral, and mucosal neuromas together with other distinctive extra-endocrine manifestations and phenotypic features that can help in recognizing the patients and diagnosing the disease. We present the patient with MEN2B syndrome, type 1 diabetes mellitus, situs inversus and congenital kidney and urinary tract malformation. Reviewing the literature revealed other reports on urinary tract malformations in patients suffering from MEN2B. The recognized role of RET gene in kidney development and urinary tract malformations suggests a possible etiological link with MEN2B syndrome. We suggest that urinary tract malformations might be a feature of MEN2B syndrome. As most of the phenotype characteristics of the syndrome develop with age, recognizing congenital malformation might help in early diagnosing and treating the patients

Platelet serotonin concentration and monoamine oxidase activity in hypothyroid patients

BACKGROUND/AIM: The relationship between the hypothalamic-pituitary-thyroid (HPT) axis and the serotonergic (5-hydroxytryptamine, 5-HT) system is not clear. The aim of the study was to determine platelet biochemical markers (5-HT concentration and monoamine oxidase B, MAO-B, activity) in hypothyroid patients. ----- METHODS: The study included 25 medication-free female hypothyroid patients in postoperative follow-up after total thyroidectomy due to papillary thyroid carcinoma, who had not been treated with synthetic thyroxine (T(4)) for 4 weeks, and 44 age-matched euthyroid healthy women. The platelet 5-HT concentration, platelet MAO-B activity, total T(4) and thyroid-stimulating hormone (TSH) levels were determined using spectrofluorimetric methods, radioimmunoassay and fluoroimmunoassay, respectively. ----- RESULTS: Hypothyroid patients had significantly higher TSH, significantly lower T(4) levels and platelet 5-HT concentrations, and unchanged platelet MAO-B activity than healthy subjects. A positive correlation was found between the 5-HT concentration and platelet MAO-B activity, and between the platelet MAO-B activity and T(4) in control subjects. ----- CONCLUSIONS: Reduced platelet 5-HT concentrations in hypothyroid patients suggests a complex interaction between the 5-HT system and HPT axis activity, which could be related to the frequent occurrence of depressive symptoms in hypothyroid patients. The determination of platelet 5-HT concentrations should be considered a diagnostic tool for the evaluation of depressive symptoms in hypothyroid patients during the hormone withdrawal procedure

Efficacy of long-term ultrasonography in follow-up of patients with papillary thyroid carcinoma: a case of neck metastasis developed 19 years following primary treatment

The cases of relapse in papillary thyroid cancer patients who were initially considered low-risk and for many years were without signs of the disease are extremely rare, but exist. This is supported by the clinical case of a patient who underwent a total thyroidectomy due to papillary thyroid cancer and 19 years later metastasis with extracapsular spreading in a presumed thyroid place was revealed. Due to such cases, the importance of long-term ultrasound monitoring is emphasized

Jesu li bubrežne malformacije jedno od obilježja sindroma MEN2B? – prikaz bolesnika i pregled literature

Sindrom multiple endokrine neoplazije 2B (MEN2B) rijetka je autosomno dominatno nasljedna bolest uzrokovana mutacijama protoonkogena RET. Karakteriziran je pojavom medularnog karcinoma štitnjače već od rane, nerijetko dojenačke dobi, feokromocitoma koji je najčešće obostran, sluzničkim neuromima te drugim ekstraendokrinim manifestacijama i specifičnim fenotipskim značajkama koje mogu pomoći u prepoznavanju ovih bolesnika. Prikazujemo pacijenta sa sindromom MEN2B, dijabetesom melitusom tipa 1, inverznim položajem organa te prirođenim malformacijama bubrega i mokraćnog sustava. Pregledom literature uočeno je da se malformacije mokraćnog sustava opisuju i u drugih bolesnika sa sindromom MEN2B. Prepoznata uloga gena RET u razvoju anomalija mokraćnog sustava čini moguću etiološku poveznicu sa sindromom MEN2B. Predlažemo da se malformacije bubrega razmotre kao jedno od obilježja sindroma MEN2B. Budući da se osobine bolesnika sa sindromom MEN2B postupno razvijaju s dobi, prepoznavanje prirođene mane, uz prve znakove ostalih fenotipskih značajki, moglo bi pomoći ranom postavljanju dijagnoze i liječenju ovih bolesnika