Apoptosis: its pathophysiology and monitoring. The role of apoptosis in the radioiodine therapy of hyperthyroidism

The review aims to give an up to date understanding of the mechanisms of apoptosis (programmed cell death), the methods of detecting apoptosis, in particular with regard to imaging such changes non-invasively. Radioiodine (I-131) is a gamma and beta emitting radionuclide and is commonplace in the treatment of hyperthyroidism. I-131 therapy relies on the destruction of thyroid tissue by beta radiation, and such destruction is proposed to be partly as a result of apoptosis. The review undertakes to explore and provoke research into the mechanisms of thyroid cell destruction by I-131, and whether such changes are able to be detected or monitored. Current knowledge concerning apoptosis in the thyroid gland in diseased states (including cancer) are described. The clinical significance of monitoring and modifying apoptosis are emphasized. Furthermore, overt and late destruction of thyroid tissue following I-131 therapy requires elaboration, and the relevance of detecting and modifying thyroid cell apoptosis following I-131 are questioned

Iodine isotope (131I) therapy for toxic nodular goitre: treatment efficacy parameters

BACKGROUND: When planning radioactive iodine therapy, itfrequently happens, both in Poland and world-wide, that inadequateattention is paid to such easily measurable parametersas: 1) the serum concentration of thyrotropin (TSH) beforeadministering radioiodine, which is a key factor for extranodular(non-autonomous) iodine uptake of the thyroid gland, 2) thyroidgland iodine uptake, and 3) the effective half-life of 131I (Teff.). Theaim of the study is to evaluate the impact of the above factorson the efficacy of 131I treatment in hyperthyroid patients.METHODS: The material consisted of 4140 patients: 2190 withautonomous toxic nodules (ATN) and 1950 with toxic multinodulargoitres (TMG). The patients were prepared for treatment insuch a way that the concentration of TSH did not exceed 0.1 mU/land Teff.< 5 days. The therapeutic activity of 131I was calculatedusing Marinelli’s formula. The selection of absorbed dose valuewas determined by the degree of suppression of extranodulartissue. Monitoring was performed every eight weeks.RESULTS: At one year after 131I administration showed thata euthyroid status was achieved in 94%, hypothyroidism was seen observed in 3%, while persistence or recurrence of hyperthyroidismin 3% of ATN patients and, respectively, 89%, 4% and7% of TMG patients.CONCLUSIONS: Patients with toxic nodular goitre who are to betreated with radioiodine should have the lowest possible serumconcentration of TSH. The suppression of extranodular determinesthe optimal value of absorbed dose for Marinelli’s formula

The influence of non-radioactive iodine (127I) on the outcome of radioiodine (131I) therapy in patients with Graves’ disease and toxic nodular goitre

BACKGROUND: The aim of the study was to achieve an effective target dose in the thyroid by increasing the effective half-life (Teff) of 131I by use of iodide (127I) two days after 131I therapy in patients with hyperthyroidism with low Teff. MATERIAL AND METHODS: The study was carried out in two groups. Group A — 41 patients, and Group B — 14 patients, all the patients were with hyperthyroidism with Teff less than 3 days qualified for 131I therapy. Only group A patients received 600 μg of iodide a day for 3 days, two days after 131I therapy. Radioiodine uptake (RAIU) after 24 and 48 hours, thyroid scintiscan and ultrasonography were done before and after 12 months of 131I therapy. RESULTS: In group A a significant increase was seen in the Teff (5 days on average) resulting in an increase in the energy target dose by 28% and 37%, in patients with Graves’ disease (GD) and toxic nodular goitre (TNG), respectively. After one year of therapy 50% of GD and 93% of TNG patients achieved euthyroidism; 28% of GD and 3% of TNG patients were in hypothyroidism. In Group B, all the patients had radioiodine treatment failure and received a second therapeutic dose of 131I. CONCLUSIONS: Administration of 127I after 131I treatment can lead to an increase in its effective half-life. This will also increase the absorbed energy dose in thyroid tissue, thereby improving therapeutic outcome without administration of a higher or second dose of 131I. This may minimize whole-body exposure to radiation and reduces the cost of treatment. Nuclear Med Rev 2011; 14, 1: 9–1

Bone scan in metabolic bone diseases. Review

Metabolic bone disease encompasses a number of disordersthat tend to present a generalized involvement of the wholeskeleton. The disorders are mostly related to increased boneturnover and increased uptake of radiolabelled diphosphonate.Skeletal uptake of 99mTc-labelled diphosphonate depends primarilyupon osteoblastic activity, and to a lesser extent, skeletalvascularity. A bone scan image therefore presents a functionaldisplay of total skeletal metabolism and has valuable role toplay in the assessment of patients with metabolic bone disorders.However, the bone scan appearances in metabolic bonedisease are often non-specific, and their recognition dependson increased tracer uptake throughout the whole skeleton. Itis the presence of local lesions, as in metastatic disease, thatmakes a bone scan appearance obviously abnormal. In theearly stages, there will be difficulty in evaluating the bone scansfrom many patients with metabolic bone disease. However, inthe more severe cases scan appearances can be quite strikingand virtually diagnostic.Metabolic bone disease encompasses a number of disordersthat tend to present a generalized involvement of the wholeskeleton. The disorders are mostly related to increased boneturnover and increased uptake of radiolabelled diphosphonate.Skeletal uptake of 99mTc-labelled diphosphonate depends primarilyupon osteoblastic activity, and to a lesser extent, skeletalvascularity. A bone scan image therefore presents a functionaldisplay of total skeletal metabolism and has valuable role toplay in the assessment of patients with metabolic bone disorders.However, the bone scan appearances in metabolic bonedisease are often non-specific, and their recognition dependson increased tracer uptake throughout the whole skeleton. Itis the presence of local lesions, as in metastatic disease, thatmakes a bone scan appearance obviously abnormal. In theearly stages, there will be difficulty in evaluating the bone scansfrom many patients with metabolic bone disease. However, inthe more severe cases scan appearances can be quite strikingand virtually diagnostic

Parathyroid gland function after radioiodine (131I) therapy for toxic and non-toxic goitre

Wstęp: Efekt terapeutyczny radiojodu (131I) w wolu łagodnym opiera się na emisji niszczącego tkanki promieniowania beta. Maksymalnyzasięg promieniowania beta 131I w tkance wynosi do 2,4 milimetra. Dlatego, też w zasięgu tego promieniowania mogą się znajdowaćsąsiadujące z tarczycą przytarczyce. Celem pracy była ocena czynności przytarczyc u chorych z wolem nadczynnym i normoczynnympoddanych terapii 131I w okresie do 5 lat od zastosowanego leczenia.Materiał i metody: Badania zostały wykonane u 325 chorych z łagodnym wolem (220 z wolem guzowatym nadczynnym (TNG), 25z wolem guzowatym obojętnym (NTNG) i 80 z chorobą Gravesa-Basedowa (GD) poddanych leczeniu 131I. Aktywność lecznicza 131Idla każdego pacjenta wyliczana była z wzoru Marinellego. W trakcie radiojodoterapii oznaczano stężenia fT3, fT4, TSH, iPTH, Ca2+, Cai fosforanów w surowicy tydzień przed podaniem 131I, i następnie w odstępach dwumiesięcznych przez rok po terapii oraz po 3 i 5 latach.Wyniki: U wszystkich chorych po 2 miesiącach od momentu rozpoczęcia leczenia zaobserwowano znamienny statystycznie wzrost stężeniaiPTH ponad normę (do wartości prawie dwukrotnie powyżej normy u pacjentów z TNG), który utrzymywał się aż do 10 miesiąca,a następnie ulegał normalizacji. Stężenia Ca2+, Ca i fosforanów u wszystkich leczonych pozostawały w zakresie normy w trakcie całegobadania. Stężenia fT3 i fT4 w surowicy po podaniu 131I szybko się normalizowały i pozostawały w zakresie normy do końca badania.Wnioski: Radiojodoterapia łagodnych schorzeń tarczycy prowadzi do powstania przejściowej (trwającej maksymalnie do 10 miesiąca odpodania radiojodu) nadczynności przytarczyc. Stan ten istotnie nie wpływa na stężenia wapnia i fosforanów w surowicy.(Endokrynol Pol 2013; 64 (5): 340–345)Introduction: The therapeutic effect of radioactive iodine (131I) on benign goitre consists of the emission of tissue-destructive beta-radiation. Since the range of beta 131I radiation in tissue can reach 2.4 mm, it can affect the adjacent parathyroid glands. The purpose of this paperis to assess parathyroid function in patients with toxic and non-toxic goitres, up to five years following 131I therapy.Material and methods: The study sample consisted of 325 patients with benign goitres (220 with toxic nodular goitre (TNG), 25 withnon-toxic nodular goitre (NTNG), and 80 with Graves’ disease (GD) treated with 131I. The therapeutic activity of 131I for each patient wascalculated using Marinelli’s formula. The serum levels of fT3, fT4, TSH, iPTH and Ca2+, Ca and phosphates were determined one week before131I administration, as well as every two months up to a year following the therapy, and then after three and five years post-treatment.Results: After two months following the administration of 131I, all the treated patients showed a statistically significant above normal increase in iPTH concentrations (amounting to a value almost twice the norm in patients with TNG), which remained stable up to ten months after treatment, to return to normal level in the following months. In all the patients, Ca2+, Ca, phosphates concentration remained within normal range throughout the course of the study. The concentrations of fT3 and fT4 quickly returned to normal after 131I administration, and remained within normal range until the completion of the study.Conclusion: Radioiodine treatment of benign thyroid disorders results in transient (up to ten months after 131I administration) hyperparathyroidism.The condition does not influence the level of calcium and phosphates concentration in any significant way. (Endokrynol Pol 2013; 64 (5): 340–345

Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter

BACKGROUND: Radioiodine therapy (RIT) in patients with large nontoxic multinodular goiter (MNG) recently becomes more common method in comparison to surgery (especially in elderly patients and with contraindications because of severe chronic diseases other systems). Repeatedly low thyroid radioactive iodine uptake (RAIU) decreases effectiveness of RIT or makes it impossible. The recombinant human thyrotropin can increase RAIU and improve the results of RIT. The aim of the study was to assess the influence of a single very low dose (0.03 mg) of rhTSH on RAIU and thyroid function in euthyroid (MNG-EU) and subclinical hyperthyroid (MNG-SC) patients with a large multinodular goiter. MATERIAL AND METHODS: 40 patients (14 male, 26 female, age 57–80 yr) with large non-toxic MNG over 80 grams and with baseline RAIU < 40% were included into the double-blind randomized study and divided into two groups: rhTSH-group and control group. First group received the single intramuscular injection of 0.03 mg rhTSH and the second received placebo. The RAIU were measured 24 and 48 hours after the rhTSH and then all the patients were administered therapeutic doses of I-131. TSH and free thyroxine levels were measured at 1st and 2nd day after the injection of rhTSH and later, at 4 and 8 weeks after the RIT. RESULTS: The mean RAIU increased significantly from 30.44 ± 7.4% to 77.22 ± 8.7% (p < 0.001). There were no statistically significant differences in RAIU between euthyroid (MNG-EU) and subclinically hyperthyroid (MNG-SC) patients. The peak of serum TSH was noticed 24 hours after rhTSH injection and in MNG-EU patients it has remained within normal range, similarly as fT4. In the MNG-SC group the administration of rhTSH resulted in a significant increase in the TSH values after 24 hours, whose mean level slightly exceeded the upper limit of the normal range with normalization at 48 hours. 8 weeks after the RIT, the TSH and fT4 levels did not exceed the normal range and did not differ in a statistically significant way. Conclusions: Even the single very low dose of rhTSH increases the values of RAIU in significant way, in euthyroid and subclinically hyperthyroid patients. The administration of rhTSH is well-tolerated. Neoadjuvant administration of a low dose (0.03 mg) of rhTSH before I-131 seems to be an optimal method of management which may increase the effectiveness of RIT and decrease the exposure of the patients to absorbed doses of ionizing radiation.BACKGROUND: Radioiodine therapy (RIT) in patients with large nontoxic multinodular goiter (MNG) recently becomes more common method in comparison to surgery (especially in elderly patients and with contraindications because of severe chronic diseases other systems). Repeatedly low thyroid radioactive iodine uptake (RAIU) decreases effectiveness of RIT or makes it impossible. The recombinant human thyrotropin can increase RAIU and improve the results of RIT. The aim of the study was to assess the influence of a single very low dose (0.03 mg) of rhTSH on RAIU and thyroid function in euthyroid (MNG-EU) and subclinical hyperthyroid (MNG-SC) patients with a large multinodular goiter. MATERIAL AND METHODS: 40 patients (14 male, 26 female, age 57–80 yr) with large non-toxic MNG over 80 grams and with baseline RAIU < 40% were included into the double-blind randomized study and divided into two groups: rhTSH-group and control group. First group received the single intramuscular injection of 0.03 mg rhTSH and the second received placebo. The RAIU were measured 24 and 48 hours after the rhTSH and then all the patients were administered therapeutic doses of I-131. TSH and free thyroxine levels were measured at 1st and 2nd day after the injection of rhTSH and later, at 4 and 8 weeks after the RIT. RESULTS: The mean RAIU increased significantly from 30.44 ± 7.4% to 77.22 ± 8.7% (p < 0.001). There were no statistically significant differences in RAIU between euthyroid (MNG-EU) and subclinically hyperthyroid (MNG-SC) patients. The peak of serum TSH was noticed 24 hours after rhTSH injection and in MNG-EU patients it has remained within normal range, similarly as fT4. In the MNG-SC group the administration of rhTSH resulted in a significant increase in the TSH values after 24 hours, whose mean level slightly exceeded the upper limit of the normal range with normalization at 48 hours. 8 weeks after the RIT, the TSH and fT4 levels did not exceed the normal range and did not differ in a statistically significant way. Conclusions: Even the single very low dose of rhTSH increases the values of RAIU in significant way, in euthyroid and subclinically hyperthyroid patients. The administration of rhTSH is well-tolerated. Neoadjuvant administration of a low dose (0.03 mg) of rhTSH before I-131 seems to be an optimal method of management which may increase the effectiveness of RIT and decrease the exposure of the patients to absorbed doses of ionizing radiation

Concentration of the Cross-Linked Carboxyterminal Telopeptide of type I Collagen in Serum of Young Growing Rats Fed a Low Calcium and Vitamin D-Deficient Diet

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