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Introduction: Thyroid cancer is the main endocrine neoplasia worldwide, for which 131I therapy is the cornerstone treatment. One of the main problems of follow up in patients with this type of cancer, is the need for thyroglobulin stimulation, not to mention the poor availability of 123I or 124I, to perform studies with a higher degree of sensitivity. Prostatic Specific Membrane Antigen (PSMA) PET/CT has demonstrated to be quite useful in a diversified number of neoplasms, on behalf of its capacity of evaluating the extent of type II carboxypeptidase expression in vascular endothelium. The end point of this article is to assess whether this novel image method possesses applicability in thyroid neoplasms follow up, for diagnostic and potentially therapeutic purposes. Methods: We retrospectively evaluated well differentiated metastatic thyroid cancer patients, who underwent a post therapeutic 131I dose whole body scan (WBS) and complementary SPECT/CT, as well as 68Ga-PSMA-11 PET/CT. Results: Ten patients with differentiated thyroid cancer were included, of whom 80% were women and 20% men, mean age was 58 years old (± 11.6). Sixty-four metastatic lesions were analyzed, 67.19% had papillary histology and 32.81% were follicular type, the most affected site of metastases was bone in 57.81%, followed by lung 17.19%, lymph nodes 7.81%, postoperative thyroid bed 4.69%, brain 4.69% and others 7.81%. 68Ga PSMA-11 PET/CT detected 64/64 lesions, all of them also identified by computed tomography (CT), whereas 131I SPECT/CT detected 55/64 lesions. Discrepant lesions were localized in lung 44.4%, brain 22.2%, postoperative thyroid bed 11.1%, lymph nodes 11.1% and bone 11.1%. The degree of correspondence among observers was outstanding for both radiotracers, but close upon perfect for PSMA-11 (κ = 0.98; 95% CI, 0.80 - 0.91), as opposed to 131 I (κ = 0.86; 95% CI, 0.71 - 0.76). Conclusions: 68Ga-PSMA PET/CT showed an utterly superior capability for metastatic lesion detection when compared to 131I SPECT/CT. These findings suggest that PSMA PET/CT could possibly and precociously identify radioiodine refractoriness. PSMA uptake values not only expedite diagnosis, but also award it the ability to be used for therapeutic intents.

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PURPOSE: Thyroid (131)I effective half-life (T(eff)) is an essential parameter in patient therapy when accurate radiation dose is desirable for producing an intended therapeutic outcome. Multiple (131)I uptake measurements and resources from patients themselves and from nuclear medicine facilities are requisites for determining T(eff), these being limiting factors when implementing the treatment planning of Graves' disease (GD) in radionuclide therapy. With the aim of optimizing this process, this study presents a practical, propitious, and accurate method of determining T(eff) for dosimetric purposes. METHODS: A total of 50 patients with GD were included in this prospective study. Thyroidal (131)I uptake was measured at 2-h, 6-h, 24-h, 48-h, 96-h, and 220-h postradioiodine administration. T(eff) was calculated by considering sets of two measured points (24-48-h, 24-96-h, and 24-220-h), sets of three (24-48-96-h, 24-48-220-h, and 24-96-220-h), and sets of four (24-48-96-220-h). RESULTS: When considering all the measured points, the representative T(eff) for all the patients was 6.95 (±0.81) days, whereas when using such sets of points as (24-220-h), (24-96-220-h), and (24-48-220-h), this was 6.85 (±0.81), 6.90 (±0.81), and 6.95 (±0.81) days, respectively. According to the mean deviations 2.2 (±2.4)%, 2.1 (±2.0)%, and 0.04 (±0.09)% found in T(eff), calculated based on all the measured points in time, and with methods using the (24-220-h), (24-48-220-h), and (24-96-220-h) sets, respectively, no meaningful statistical difference was noted among the three methods (p > 0.500, t test). CONCLUSIONS: T(eff) obtained from only two thyroid (131)I uptakes measured at 24-h and 220-h, besides proving to be sufficient, accurate enough, and easily applicable, attributes additional major cost-benefits for patients, and facilitates the application of the method for dosimetric purposes in the treatment planning of Graves' disease.

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In 105 normal volunteers, 52 male and 53 female, mean age 45 (range, 20-68), serum thyroid-stimulating hormone (TSH) (1.46 ± 0.7; range, 0.43-3.87 microUI/mL) and 24-hour thyroid radioactive iodine uptake (RAIU) (16.15% ± 4.78% range, 6.45%-30.08%) were measured. Additionally, TSH was 1.18 ± 0.5 microUI/mL for 20 to 29 year-olds and 1.59 ± 0.9 microUI/mL for 60 to 68 year old (P = 0.037). RAIU was 18.30 ± 4.5 for 20 to 29-year-olds and 14.92 ± 3.1 for 60 to 68 year-olds (P = 0.009). TSH trends positively and RAIU at 24 hours correlates negatively with aging of the pituitary axis.

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BACKGROUND: Iodide has direct effects on thyroid function. Several iodinated lipids are biosynthesized by the thyroid and they were postulated as intermediaries in the action of iodide. Among them 6 iodo-delta-lactone (IL-delta) has been identified and proposed to play a role in thyroid autoregulation. The aim of this study was to compare the effect of iodide and IL-delta on several thyroid parameters. METHODS: Thyroid bovine follicles were incubated with the different compounds during three days. RESULTS: KI and IL-delta inhibited iodide uptake, total protein and Tg synthesis but only KI had an effect on NIS and Tg mRNAs levels. Both compounds inhibited Na+/K+ ATPase and deoxy-glucose uptake. As PAX 8, FOXE 1 and TITF1 are involved in the regulation of thyroid specific genes their mRNA levels were measured. While iodide inhibited the expression of the first two, the expression of TITF1 was stimulated by iodide and IL-delta had no effect on these parameters. CONCLUSION: These findings indicate that IL-delta reproduces some but not all the effects of excess iodide. These observations apply for higher micromolar concentrations of iodide while no such effects could be demonstrated at nanomolar iodide concentrations.

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BACKGROUND: Recombinant human thyroid stimulating hormone (rhTSH) increases the thyroid radioactive iodine uptake (RAIU) in euthyroid and multinodular goiter patients. Furthermore, rhTSH is a well-known complementary tool in the management and treatment of differentiated thyroid cancer patients. OBJECTIVE: To evaluate the effect of rhTSH on RAIU in subjects without thyroid disease exposed to iodinated contrast agent during computed tomography (CT). METHODS: Nine euthyroid patients, seven female and two male, with ages ranging from 22 to 58 years, have signed a consent form approved by the hospital's Ethics Committee and had their TSH levels and RAIU evaluated in three moments: baseline (M1), 96 h after intravenous iodinated contrast agent (M2) and 24 h after intramuscular injection of 0.1 mg of rhTSH (M3). Each patient acted as his own control. RESULTS: There was significant variation throughout the study of TSH (mean+/-SD): M1=2.39+/-0.92 microUI/ml; M2=2.54+/-1.28 microUI/ml; M3=7.54+/-2.96 microUI/ml (P=0.004) and of RAIU (mean+/-SD): M1: 8.76+/-2.4%; M2=6.54+/-1.77%; M3=18.75+/-8.24% (P=0.002). In both cases, there was a significant increment from M1 and M2 to M3. CONCLUSION: It was shown that a single dose of 0.1 mg of rhTSH, given 96 h after the exposure to computed tomography iodinated contrast media, enhances the RAIU in nine euthyroid patients 4 h after 123I administration. These results indicate that rhTSH could be useful for avoiding delay in the treatment of patients with 131I.

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Several methods can be used to determine the activity of (131)I in the treatment of hyperthyroidism. However, many of them do not consider all the parameters necessary for optimum dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: organ mass, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with (131)I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the IRD was used to calibrate a scintillation camera and a uptake probe SCT-13004 at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and a uptake probe SCT-13002, available at the Nuclear Medicine Institute in Goiânia. The biokinetic parameters were determined based on measurements performed in eight voluntary patients. It is concluded that the use of the equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable and feasible procedure for dose optimization in terms of effectiveness, simplicity and cost.

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Previous studies on angiotensin II (AngII) AT(1) receptor function have revealed that the N-terminal residues of AngII may modulate receptor activation by binding at the receptor extracellular site. A remarkable feature of this site is an insertion of 8 amino acids in the middle of the EC-3 loop including the Cys(274) residue that supposedly makes a disulfide bond with N-terminal Cys(18). As demonstrated by assays with Del(267-275)AT(1), the role of the Cys(18)-Cys(274) disulfide bridge is to keep a conformation of the inserted residues that allows a normal binding of the AngII N-terminal residues. C18S AT(1) receptor mutant, supposedly having a dissociated disulfide bridge, but an intact residue insertion, is constitutively activated and can less efficiently bind AngII. Similar results were observed when the S-S disulfide bond was disrupted in (C18S,C274S) AT(1) receptor. The importance of the free N-terminal amino group of Asp(1) and of the Arg(2) guanidino group for the binding of AngII to C18S mutant with EC-3 loop insertion was investigated by means of assays using AngII peptide analogues bearing a single mutation of Asp(1) for Sar(1) or Arg(2) for Lys(2), as ligands. This study showed that like AngII, [Sar(1)]-AngII can bind the C18S mutant receptor with low affinity whereas [Lys(2)]-AngII binding is still more reduced. Interestingly, when (125)I-AngII instead of (3)H-AngII was used, no significant binding of this mutant was observed although wild type AT(1) receptor was shown to bind all AngII analogues.

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AIMS: Retinoic acid is widely used in dermatological treatment and thyroid cancer management; however its possible side-effects on normal thyroid function remains unknown. We aimed to determine the effects of retinoic acid on thyroid function of adult female rats. MAIN METHODS: Female Wistar rats were treated with all-trans-retinoic acid and 13-cis retinoic acid for 14 and 28 days. Then, rats were killed and thyroid function was evaluated. KEY FINDINGS: Serum T4 and thyrotropin levels remained unchanged, while serum T3 increased in animals treated with all-trans-retinoic acid for 14 days. No changes were observed in hepatic or renal type 1 iodothyronine deiodinase (D1) activities, while thyroid D1 was higher in animals treated for 14 days with all-trans-retinoic acid, which could be related to the increased serum T3 levels. 13-cis retinoic acid increased thyroid iodide uptake after 28 days. These results show effects of retinoic acid treatment on these thyroid proteins: sodium/iodide symporter and deiodinase. SIGNIFICANCE: Retinoic acid is able to interfere with normal thyroid function, increasing thyroid type 1 deiodinase activity, serum T3 levels and sodium/iodide symporter function. However, the effects are time- and retinoic acid isomer-dependent. Since serum thyrotropin levels did not change in any group, the effects observed are probably mediated by a direct retinoic acid effect on the normal thyroid.

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Esta investigación propone un protocolo de planificación individualizada de dosis ablativas basado en el metabolismo individual del paciente y en la medida de la masa de los remanescientes tiroideanos. Utilizando SPECT, el metabolismo de I-131 fue estudiado en 9 pacientes tiroidectomizados, y la actividad optima para la terapia fue calculada y comparada con la actividad fija establecida de 3.7 GBq (100 mCi), que és en general administrada. Fue observado que 78 por ciento de las pacientes podrian tener recibido actividades reduzidas de 131I (de 0.8-3.2 GBq (20-87 mCi)). Además, 33 por ciento destes pacientes podrian recibir actividades tan bajas que no necesitarian internamiento hospitalar. Visando facilitar los calculos de la actividad terapeutica optima de 131I hacia pacientes individuales, un programa de planificación de dosis simples y rápido fue criado (PlanDose). Este protocolo de cálculo de actividades de 131I específicas para el paciente permite una mejor determinación de la dosis ablativa necesaria en caso de pacientes con carcinoma diferenciado de la tiroide, y és un ejemplo de optimización de la práctica de protección radiologica.

This investigation proposes a protocol for planning of thyroid ablation therapy for individual patients, based on individual patient metabolic data and measured thyroid remnant masses. Using SPECT, I-131 uptake and clearance was studied in 9 patients who had undergone thyroidectomies, and the optimum activity for their therapy was calculated and compared to the established fixed activity of 3.7 GBq (100 mCi), which normally would have been assigned. It was observed that 7 of the patients could have received reduced activities of 131I (from 0.8-3.2 GBq (20-87 mCi)). In addition, 3 patients could have received low enough activities to have been discharged from the hospital. To facilitate the calculations of the optimum therapeutic activity of 131I for individual patients, a computer program was created (PlanDose). This protocol of calculated optimal patient-specific 131I activities allows a better determination of the necessary ablative dose for patients with differentiated carcinoma of the thyroid, and is an important example of optimization of the practice of radiation protection.

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The relative roles of the types 1 and 2 iodothyronine deiodinases (D1 and D2) in extrathyroidal 3,5,3'-triiodothyronine (T3) production in humans are unknown. We calculated the rate of thyroxine (T4) to T3 conversion by intact cells transiently expressing D1 or D2 at low (2 pM), normal (20 pM), and high (200 pM) free T4 concentrations. Deiodinase activities were then assayed in cell sonicates. The ratio of T3 production in cell sonicates (catalytic efficiency) was multiplied by the tissue activities reported in human liver (D1) and skeletal muscle (D2). From these calculations, we predict that in euthyroid humans, D2-generated T3 is 29 nmol/d, while that of D1-generated T3 is 15 nmol/d, from these major deiodinase-expressing tissues. The total estimated extrathyroidal T3 production, 44 nmol/d, is in close agreement with the 40 nmol T3/d based on previous kinetic studies. D2-generated T3 production accounts for approximately 71% of the peripheral T3 production in hypothyroidism, but D1 for approximately 67% in thyrotoxic patients. We also show that the intracellular D2-generated T3 has a greater effect on T3-dependent gene transcription than that from D1, which indicates that generation of nuclear T3 is an intrinsic property of the D2 protein. We suggest that impairment of D2-generated T3 is the major cause of the reduced T3 production in the euthyroid sick syndrome.

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