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BACKGROUND: The 2022 WHO Classification categorizes oncocytic (OTC) and follicular thyroid carcinoma (FTC) based on the degree of capsular and vascular invasion into minimally invasive (MI), encapsulated angioinvasive (EA) and widely invasive tumors (WI). While associations with clinical outcomes have been studied extensively in FTC, robust clinical data are lacking for OTC. We aimed to investigate the impact of the reclassification of OTC and FTC by the 2022 WHO Classification on clinical outcomes. METHODS: All adult OTC and FTC patients treated at the Erasmus MC (the Netherlands) between 2000 and 2016 were retrospectively included. All tumors were extensively revised by two independent pathologists, facilitated by Palga: Dutch Pathology Databank. Kaplan-Meier curves were used to study the association of the 2004 and 2022 WHO Classification with overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and radioactive iodine (RAI) refractory disease. RESULTS: Fifty-two OTC and 89 FTC patients were included, of which 15 (28.8%) OTC and 34 (38.2%) FTC tumors were reclassified as EAOTC or EAFTC. The 2022 WHO Classification substantially improved risk stratification in both subtypes for DSS, compared with the 2004 edition. Ten-year DSS rates were 100% for MIOTC, 92.9% for EAOTC and 56.5% for WIOTC, compared to 100% (MIOTC) and 64.2% (WIOTC) following the 2004 WHO Classification. For FTC and RAI-refractory disease, similar trends were observed. CONCLUSION: Classification of OTC and FTC into three subcategories as defined by the 2022 WHO Classification substantially improves discrimination between low, intermediate and high risk patients, especially for DSS and RAI-refractory disease.
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BACKGROUND: Brain metastases (BM) are the most common intracranial neoplasms in adults and are a significant cause of morbidity and mortality. The brain is an unusual site for distant metastases of thyroid cancer, indeed the most common sites are lungs and bones. In this narrative review we discuss about the clinical characteristics, diagnosis and treatment options for patients with BM from differentiated thyroid cancer (DTC). SUMMARY: BM can be discovered before initial therapy due to symptoms, but in most patients, BM is diagnosed during follow-up because of imaging performed before starting tyrosine kinase inhibitors (TKI) or due to the onset of neurological symptoms. Older male patients with follicular thyroid cancer (FTC), poorly differentiated thyroid cancer (PDTC) and distant metastases may have an increased risk of developing BM. The gold standard for detection of BM is magnetic resonance imaging (MRI) with contrast agent administration, which is superior to contrast-enhanced computed tomography (CT). The treatment strategies for patients with BM from DTC remain controversial. Patients with poor performance status are candidates for palliative and supportive care. Neurosurgery is usually reserved for cases where symptoms persist despite medical treatment, especially in patients with favorable prognostic factors and larger lesions. It should also be considered for patients with a single BM in a surgically accessible location, particularly if the primary disease is controlled without other systemic metastases. Additionally, stereotactic radiosurgery (SRS) may be the preferred option for treating small lesions, especially those in inaccessible areas of the brain or when surgery is not advisable. Whole brain radiotherapy is less frequently used in treating these patients due to its potential side effects and the debated effectiveness. Therefore, it is typically reserved for cases involving multiple BM that are too large for SRS. TKIs are effective in patients with progressive radioiodine-refractory thyroid cancer and multiple metastases. CONCLUSIONS: Although routine screening for BM is not recommended, older male patients with FTC or PDTC and distant metastases may be at higher risk and should be carefully evaluated for BM. According to current data, patients who are suitable for neurosurgery seem to have the highest survival benefit, while SRS may be appropriate for selected patient.
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Hypophosphatasia (HPP) is a rare disorder, resulting from loss-of-function variants of the ALPL gene encoding non-tissue specific alkaline phosphatase (TNSALP). Presentation varies largely, with increased severity usually occurring with earlier disease onset. Here we describe the clinical improvement of a 57-year-old woman with childhood onset HPP, after initiating treatment with asfotase alfa (Strensiq®). This was started because of the rapid and progressive radiological deterioration of bone structure after placement of nails in both upper legs for spontaneous atypical femur fracture (AFF) - like fractures. Initiation of treatment, not only resulted in stabilization of bone structure on X-rays, but within a few weeks there was a dramatic reduction of burning pain sensations in the lower legs, attributed in retrospect to neuropathic pain, and also almost complete disappearance of headaches. Additionally, unhealed metatarsal fractures finally healed after almost 10 years. Drug efficacy was further evaluated through -quality of life questionnaires and multiple tests conducted by the physiotherapist, and showed clear improvements. Within 3 months after starting asfotase alfa, the patient was able to carry out her daily tasks indoors without relying on a walker and even started electric bike rides for 20 km/day. In conclusion, treatment with asfotase alfa, halted rapid radiological bone deterioration after bilateral intramedullary femoral pen placement and strongly increased quality of life, marked by rapid disappearance of neuropathic pain, reduction in headaches and musculoskeletal pains, and enhanced muscle strength and mobility. The quick and almost complete disappearance of neuropathic pain and headache suggests a relation with disturbed levels of metabolites in HPP.
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Hipofosfatasia , Inmunoglobulina G , Neuralgia , Proteínas Recombinantes de Fusión , Adulto , Femenino , Humanos , Niño , Persona de Mediana Edad , Fosfatasa Alcalina/uso terapéutico , Hipofosfatasia/complicaciones , Hipofosfatasia/tratamiento farmacológico , Calidad de Vida , Terapia de Reemplazo Enzimático/métodos , Neuralgia/tratamiento farmacológico , Cefalea/tratamiento farmacológicoRESUMEN
INTRODUCTION: Risk factors for radioactive iodine (RAI)-refractory disease in follicular (FTC) and oncocytic thyroid carcinoma (OTC) are unknown. Therefore, the aim of this study is to identify clinical and histopathological risk factors for RAI-refractory disease in FTC and OTC patients, facilitated by an extensive histopathological revision. METHODS: All adult FTC and OTC patients treated at Erasmus MC (the Netherlands) between 2000 and 2016 were retrospectively included. 2015 ATA Guidelines were used to define RAI-refractory disease. An extensive histopathological revision was performed applying the 2022 WHO Classification using Palga: Dutch Pathology Databank. Logistic regression was used to identify risk factors for RAI-refractory disease, stratified for histological subtype. RESULTS: Ninety FTC and 52 OTC patients were included, of which 14 FTC (15.6%) and 22 OTC (42.3%) developed RAI-refractory disease over a follow-up time of 8.5 years. RAI-refractory disease occurred in OTC after fewer cycles than in FTC (2.0 [IQR: 1.0-2.0] vs 2.5 [IQR: 2.0-3.75]), and it substantially decreased the 10-year disease specific survival, especially in OTC (46.4%; FTC 85.7%). In FTC, risk factors were higher age at diagnosis, pT3/pT4-stage, N1-stage, widely invasive tumors and extra-thyroidal extension. N1-stage and M1-stage were the strongest risk factors in OTC, rather than histopathological characteristics of the primary tumor. CONCLUSION: To our knowledge, this is the first study that correlates clinical and histopathological risk factors with RAI-refractory disease in FTC and OTC, facilitated by a histopathological revision. In FTC, risk factors for RAI-refractory disease were foremost histopathological characteristics of the primary tumor, whereas in OTC presentation with lymph node and distant metastasis was associated with RAI-refractory disease. Our data can help clinical decision making, particularly in patients at risk for RAI-refractory disease.
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Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome associated with tumors secreting fibroblast growth factor 23 that can be cured with complete surgical resection of the tumor. However, when these tumors are at difficult locations, less invasive modalities such as thermal ablation (TA) might be a good alternative. A 40-year-old woman was seen for a second opinion because of severe hypophosphatemia with complaints of fatigue, myalgia, and muscle weakness for which she needed IV phosphate for 15 to 18â hours per day in addition to oral alfacalcidol and phosphate. Initial laboratory results revealed hypophosphatemia (0.59â mmol/L [1.83â mg/dL]; reference range, 0.90-1.50â mmol/L [8.40-10.2â mg/dL]), increased fibroblast growth factor 23 levels (137 RU/mL; reference range, <125â RU/mL), and a reduced TmP-GFR (0.47â mmol/L; reference range, 0.8-1.4â mmol/L). Gallium-positron emission tomography/computed tomography (CT) showed moderately increased uptake at thoracic vertebra (Th) 8 and mildly increased uptake at Th7, suggestive of TIO. Complete tumor removal would have required resection of at least 1 vertebral body. Therefore, CT-guided TA was performed at Th8. No complications were observed, and in the months after, treatment with IV phosphate could be discontinued, indicating a satisfying result from the procedure. This extreme TIO case demonstrates that CT-guided TA can be an alternative to extensive or risky classical surgery.
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Neoplasias de la Tiroides , Embarazo , Femenino , Humanos , Progresión de la Enfermedad , Estudios RetrospectivosRESUMEN
BACKGROUND: Hypophosphatasia (HPP) is a rare inherited disorder caused by pathogenic loss-of-function variants in the ALPL gene, encoding the tissue-nonspecific isoenzym of alkaline phosphatase (ALP; TNSALP). Low serum ALP is the biochemical hallmark of HPP, but it is unknown whether ALP levels can increase due to concurring liver disease, which may lead to a missed diagnose of HPP. We present a patient with genetically confirmed HPP, who showed a transient increase of serum ALP levels due to alcohol-induced hepatitis. CLINICAL REPORT: A 71-year old man was seen at our Bone Center for surveillance of HPP. Serum ALP was always low (23 U/L; reference value: <115 U/L). During follow-up, his serum ALP increased (156 U/L, further rising to 204 U/L), with concomitantly elevated serum gamma-glutamyl transferase and transaminases, and a rise in bone specific ALP (18.7 µg/L; reference value: 5.7-32.9 µg/L). This was attributed to alcohol-induced hepatitis. After refraining from alcohol intake, both serum ALP and bone specific ALP levels returned to initial low levels (30 U/L and 4.3 µg/L respectively). CONCLUSIONS: We demonstrated the history of a 71-year old patient with HPP, presenting during routine follow-up with an elevated serum ALP level up to 204 U/L due to alcohol-induced hepatitis. This case illustrates that the diagnosis of HPP can potentially be missed when ALP levels are normal or elevated due to a concomitant liver disease.
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Fosfatasa Alcalina , Hepatitis Alcohólica , Hipofosfatasia , Enfermedades Raras , Anciano , Humanos , Masculino , Fosfatasa Alcalina/sangre , Hipofosfatasia/sangre , Hipofosfatasia/complicaciones , Mutación , Enfermedades Raras/sangre , Enfermedades Raras/complicaciones , Hepatitis Alcohólica/sangre , Hepatitis Alcohólica/complicacionesRESUMEN
Osteosclerotic metaphyseal dysplasia (OSMD) is a very rare autosomal-recessive disease caused by mutations in the leucine-rich repeat kinase 1 (LRRK1) gene. It is a sclerosing skeletal dysplasia characterized by osteosclerosis of the long bones, predominantly at the metaphyses and vertebrae. Phenotypic features can be short stature, pathological fractures, delayed development, and hypotonia, but they are not uniformly present, and relatively few cases are known from the literature. A 40-year-old man was seen at our bone center because of nonspontaneous multiple peripheral low-energy trauma fractures since puberty. He had no other complaints and his family history was negative. Except for a relatively short stature (167 cm; -1.5 SD), there were no abnormalities on examination, including laboratory tests. Initially, a suspicion was raised of osteogenesis imperfecta, but bone mineral density was high and X-rays of the whole skeleton showed osteosclerosis of the metaphyses of long bones and vertebrae. Whole-exome sequencing showed a homozygous, likely pathogenic, variant (American College of Medical Genetics and Genomics criteria class 4) in the LRRK1 gene, fitting the diagnosis of OSMD. In conclusion, we described a 40-year-old patient with osteosclerotic metaphyseal dysplasia caused by a homozygous variant in the LRRK1 gene, resulting in multiple fractures of the long bones without other features of the disease, adding to the phenotypic variation of OSMD. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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BACKGROUND: The Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) were developed to improve risk stratification of indeterminate nodules. Our aim was to assess the clinical utility in a European population with restrictive diagnostic workup. METHODS: Clinical utility of the GEC was assessed in a prospective multicenter cohort of 68 indeterminate nodules. Diagnostic surgical rates for Bethesda III and IV nodules were compared to a historical cohort of 171 indeterminate nodules. Samples were post hoc tested with the GSC. RESULTS: The GEC classified 26% as benign. Surgical rates between the prospective and historical cohort did not differ (72.1% vs. 76.6%). The GSC classified 59% as benign, but misclassified six malignant lesions as benign. CONCLUSION: Implementation of GEC in management of indeterminate nodules in a European country with restrictive diagnostic workup is currently not supported, especially in oncocytic nodules. Prospective studies with the GSC in European countries are needed to determine the clinical utility.
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Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/patología , Estudios Prospectivos , Países Bajos , Perfilación de la Expresión Génica , Estudios Retrospectivos , Expresión Génica , Neoplasias de la Tiroides/diagnósticoRESUMEN
OBJECTIVE: Incidence of thyroid cancer varies widely, even across neighboring countries. Data on this phenomenon are largely lacking but are likely related to differences in health care systems. Therefore, we explored whether there are differences between populations from these 2 countries with respect to the relationship between tumor size and advanced disease. METHODS: We retrospectively studied 2 cohorts of adult differentiated thyroid cancer (DTC) patients from a Dutch and a German university hospital. We analyzed the presence of lymph node metastases with respect to tumor size for papillary thyroid cancer (PTC), and the presence of distant metastases for DTC, and PTC and follicular thyroid cancer (FTC) separately. RESULTS: We included 1771 DTC patients (80% PTC, 20% FTC; 24% lymph node and 8% distant metastases). For PTC, the proportion of patients with lymph node metastases was significantly higher in the Dutch than in the German population for tumors ≤ 1â cm (45% vs. 14%; P < .001). For DTC, distant metastases occurred particularly significantly more frequently in the Dutch than in the German population for tumors ≤ 2â cm (7% vs. 2%; P = .004). CONCLUSION: The presence of lymph node and distant metastases is significantly higher in pT1 DTC cases in the Dutch compared to the German cohort, which might be caused by differences in the indication for and application of diagnostic procedures eventually leading to DTC diagnosis. Our results implicate that one should be cautious when extrapolating results and guidelines from 1 country to another.
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Adenocarcinoma Folicular , Carcinoma Papilar , Neoplasias de la Tiroides , Adulto , Humanos , Estudios Retrospectivos , Metástasis Linfática , Carcinoma Papilar/patología , Neoplasias de la Tiroides/patología , Adenocarcinoma Folicular/patología , Cáncer Papilar Tiroideo , PronósticoRESUMEN
Bisphosphonates are effective and relative safe and cheap drugs, used for the treatment of different bone diseases, such as osteoporosis. Recently, several non-skeletal effects have been described, such as a reduced risk of myocardial infarction, cancer and death. Therefore, the question arises whether there are other, non-skeletal, indications for bisphosphonate treatment. However, there is currently insufficient evidence with respect to cardiovascular endpoints, death, cancer incidence, and infectious diseases for treatment with bisphosphonates. This is primarily caused by relative short follow-up duration, and several kinds of bias in the different studies. Therefore, prescribing bisphosphonates outside the current indications is not appropriate as long as there are no randomized trials showing a positive effect for certain diseases, specific risk groups, or the general population.
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Conservadores de la Densidad Ósea , Enfermedades Óseas , Osteoporosis , Humanos , Difosfonatos/efectos adversos , Conservadores de la Densidad Ósea/efectos adversos , Lagunas en las Evidencias , Osteoporosis/tratamiento farmacológicoRESUMEN
BACKGROUND: Many countries have national guidelines for the management of differentiated thyroid cancer (DTC), including a risk stratification system to predict recurrence of disease. Studies whether these guidelines could also have relevance, beyond their original design, in predicting survival are lacking. Additionally, no studies evaluated these international guidelines in the same population, nor compared them with the TNM system. Therefore, we investigated the prognostic value of 6 stratification systems used by 10 international guidelines, and the TNM system with respect to predicting disease-specific survival (DSS). METHODS: We retrospectively studied adult patients with DTC from a Dutch university hospital. Patients were classified using the risk classification described in the British, Dutch, French, Italian, Polish, Spanish, European Society of Medical Oncology, European Thyroid Association, the 2009 and 2015 American Thyroid Association (ATA) guidelines, and the latest TNM system. DSS was analyzed using the Kaplan-Meier method, and the statistical model performance using the C-index, Akaike information criterion, Bayesian information criterion, and proportion of variance explained. RESULTS: We included 857 patients with DTC (79% papillary thyroid cancer, 21% follicular thyroid cancer). Median follow-up was 9 years, and 67 (7.8%) died because of DTC. The Dutch guideline had the worst statistical model performance, whereas the 2009 ATA/2014 British guideline had the best. However, the (adapted) TNM system outperformed all stratification systems. CONCLUSIONS: In a European population of patients with DTC, of 10 international guidelines using 6 risk of recurrence stratification systems and 1 mortality-based stratification system, our optimized age-adjusted TNM system (8th edition) outperformed all other systems.
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Neoplasias de la Tiroides , Adulto , Humanos , Estados Unidos , Estudios Retrospectivos , Teorema de Bayes , Estadificación de Neoplasias , Neoplasias de la Tiroides/patología , Pronóstico , Medición de Riesgo , Recurrencia Local de Neoplasia/patologíaRESUMEN
Thyroid cancer is one of the most common cancers diagnosed in women of reproductive age and during pregnancy. This leads to important questions about thyroid cancer prognosis and treatment, but also fertility and risk for adverse obstetric and/or fetal and neonatal outcomes. The benefits of thyroid cancer treatment should be weighed against its harms, as various options may adversely impact maternal and fetal health. In the current review, the authors focus on perinatal-specific clinical considerations related to the care of patients with thyroid cancer.
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Complicaciones del Embarazo , Neoplasias de la Tiroides , Femenino , Fertilidad , Humanos , Recién Nacido , Embarazo , Complicaciones del Embarazo/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/terapiaRESUMEN
IMPORTANCE: Papillary microcarcinomas of the thyroid (mPTCs) account for an increasing proportion of thyroid cancers in past decades. The use of radiofrequency ablation (RFA) has been investigated as an alternative to surgery. The effectiveness and safety of RFA has yet to be determined. OBJECTIVE: To evaluate the effectiveness and safety of RFA for low-risk mPTC. DATA SOURCES: Embase, MEDLINE via Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and the top 100 references of Google Scholar were searched from inception to May 28, 2021. STUDY SELECTION: Articles reporting on adult patients with mPTC treated with RFA were included. Studies that involved patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension were excluded. Final article selection was conducted by multiple reviewers based on consensus. The proportion of eligible articles was 1%. DATA EXTRACTION AND SYNTHESIS: This meta-analysis was conducted in accordance with the MOOSE guidelines. Random and fixed-effect models were applied to obtain pooled proportions and 95% CIs. MAIN OUTCOMES AND MEASURES: The primary outcome was the complete disappearance rate of mPTC. Secondary outcomes were tumor progression and complications. RESULTS: Fifteen studies were included in this meta-analysis. A total of 1770 patients (1379 women [77.9%]; mean [SD] age, 45.4 [11.4] years; age range, 42.5-66.0 years) with 1822 tumors were treated with RFA; 49 tumors underwent 1 additional RFA session and 1 tumor underwent 2 additional RFA sessions. Mean (SD) follow-up time was 33.0 (11.4) months (range, 6-131 months). The pooled complete disappearance rate at the end of follow-up was 79% (95% CI, 65%-94%). The overall tumor progression rate was 1.5% (n = 26 patients), local residual mPTC in the ablation area was found in 7 tumors (0.4%), new mPTC in the thyroid was found in 15 patients (0.9%), and 4 patients (0.2%) developed lymph node metastases during follow-up. No distant metastases were detected. Three major complications occurred (2 voice changes lasting >2 months and 1 cardiac arrhythmia). Minor complications were described in 45 patients. CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis suggest that RFA is a safe and efficient method to treat selected low-risk mPTCs. Radiofrequency ablation could be envisioned as step-up treatment after local tumor growth under active surveillance for an mPTC or initial treatment in patients with mPTCs with anxiety about active surveillance.
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Carcinoma Papilar , Ablación por Radiofrecuencia , Neoplasias de la Tiroides , Carcinoma Papilar/patología , Femenino , Humanos , Masculino , Ablación por Radiofrecuencia/efectos adversos , Neoplasias de la Tiroides/patologíaRESUMEN
PURPOSE: To determine whether adoption of radiofrequency (RF) ablation in patients with symptomatic benign thyroid nodules (SBTNs) in a Dutch regional thyroid network resulted in clinical success and improvement in health-related and thyroid-related quality of life (QoL). MATERIALS AND METHODS: The eligibility criteria for RF ablation were as follows: (a) nodule size between 2.0 and 5.0 cm, (b) solid component >20%; (c) benign cytology in 2 separate cytological assessments, and (d) symptoms unequivocally related to mechanical compression. The primary end point of this study was volume reduction 1 year after ablation. The secondary outcomes were health-related and thyroid-related QoL, measured using the short form health survey questionnaire (SF-36) and thyroid-specific patient-reported outcome questionnaire (ThyPRO-39), respectively, as well as adverse event rates. RESULTS: A total of 72 SBTNs in 67 patients were included. Median age was 50.0 (interquartile range, 41.0-56.0) years, and 91.0% were women. The median volume reduction at 6 weeks, 6 months, 1 year, 2 years, and 3 years was 51.0%, 63.9%, 65.2%, 81.3%, and 90.3%, respectively. The patients showed a significant improvement on the SF-36 physical component scale and ThyPRO-39 overall QoL-impact scale. An absolute improvement was seen in goiter and cosmetic complaints, determined using ThyPRO-39. The overall adverse event rate was 9.0%, of which 4.5% were considered major. CONCLUSIONS: RF ablation is an effective treatment option for SBTNs, with a significant volume reduction and improvement in health-related and thyroid-related QoL.
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Ablación por Catéter , Ablación por Radiofrecuencia , Nódulo Tiroideo , Ablación por Catéter/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Calidad de Vida , Ablación por Radiofrecuencia/efectos adversos , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: The joint Union International Contre le Cancer and American Joint Committee on Cancer (UICC/AJCC) Tumor, Node, Metastasis (TNM) staging system for differentiated thyroid cancer (DTC) involves a single age cutoff as a prognostic criterion. Because a single cutoff is a dichotomization of what might be a sliding scale, using multiple age cutoffs might result into a better stage definition. The aim of our study was to investigate if using a two-step age-based cutoff would improve the TNM staging system regarding disease-specific survival (DSS). METHODS: We retrospectively studied two cohorts of adult DTC patients from The Netherlands and Germany. DSS was analyzed for papillary (PTC) and follicular thyroid cancer (FTC) separately, investigating several two-step age-based cutoffs for those with distant metastases; below lower threshold classified as stage I, between lower and upper threshold as stage II, and above upper threshold as stage IV. RESULTS: We included 3074 DTC patients (77% PTC). For PTC, an age cutoff of 45 with 50 years had the best statistical model performance, while this was 25 with 40 years for FTC. However, differences with the optimal single age cutoffs of 50 years for PTC and 40 years for FTC were small. CONCLUSIONS: The optimal two-step age-based cutoff to predict DSS is 45 with 50 years for PTC and 25 with 40 years for FTC, rather than 55 years currently used for DTC. Although these two-step age-based cutoffs were marginally better from a statistical point of view, from a clinical point of view, the recently defined optimal single age cutoffs of 50 years for PTC and 40 years for FTC might be preferable.
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Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/epidemiología , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/epidemiología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/epidemiología , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Bases de Datos Factuales/normas , Supervivencia sin Enfermedad , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Países Bajos/epidemiología , Estudios RetrospectivosRESUMEN
Background: In contrast to the thyroid hormones (TH) 3,3',5-triiodothyronine (T3) and thyroxine (T4), current literature on thyroid hormone metabolite concentrations in the hypothyroid and hyperthyroid states is inconclusive. It is unknown how thyroidectomy affects thyroid hormone metabolite concentrations and if levothyroxine (LT4) replacement therapy after thyroidectomy restores thyroid hormone metabolite concentrations in those without a thyroid gland. The treatment of patients with differentiated thyroid cancer (DTC) covers the euthyroid, hypothyroid, and (subclinical) hyperthyroid states and therefore provides a unique model to answer this. Here, we prospectively studied nine TH and its metabolites (THM) across different thyroid states in a cohort of patients treated for DTC. Also, three potentially important determinants for THM concentrations were studied. Methods: We prospectively included patients aged 18 to 80 years who were scheduled for DTC treatment at the Erasmus MC. Peripheral blood samples were obtained before surgery (euthyroid, endogenous TH production), after surgery just before radioactive iodine therapy (hypothyroid), and six months later on LT4 therapy ([subclinically] hyperthyroid, exogenous T4 supplementation). Nine THMs were quantified in serum with an established liquid chromatography/tandem mass spectrometry method. Repeated measurement analysis was used to compare the three different thyroid states with each other for each THM, while linear regression was used to determine the association between THM concentrations and age, sex, and kidney function. Results: In total, 77 patients (mean age 49 years; 65% women) were eligible for the study. 3,5-diiodothyronine and 3,3',5-triiodothyroacetic acids were below the lower limit of detection. Compared with the euthyroid state, all THMs were significantly decreased in the hypothyroid state and significantly increased in the (subclinically) hyperthyroid state, with T3 concentrations remaining within the reference interval. Higher age was associated with higher 3-monoiodothyronine (3-T1) concentrations (p < 0.001). Women had higher L-thyronine concentrations than men (p = 0.003). A better kidney function was associated with lower 3-T1 concentrations (p < 0.001). Conclusions: All THMs decrease after a thyroidectomy and increase under thyrotropin (TSH)-suppressive LT4-therapy, suggesting that formation of thyroid hormone metabolites is dependent on peripheral extrathyroidal metabolism of T4. This is also reflected by T3 concentrations that remained within the reference interval in patients receiving TSH-suppressive LT4-therapy as T3 has some thyroidal origin.
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Glándula Tiroides/metabolismo , Tiroxina/sangre , Triyodotironina/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipertiroidismo/metabolismo , Hipotiroidismo/metabolismo , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Tiroides/metabolismo , Triyodotironina/sangre , Adulto JovenRESUMEN
CONTEXT: Whilst radioactive iodine (RAI) is often administered in the treatment for differentiated thyroid carcinoma (DTC), long-term data on male fertility after RAI are scarce. OBJECTIVE: To evaluate long-term male fertility after RAI for DTC, and to compare semen quality before and after RAI. DESIGN, SETTING, AND PATIENTS: Multicenter study including males with DTC ≥2 years after their final RAI treatment with a cumulative activity of ≥3.7 GBq. MAIN OUTCOME MEASURE(S): Semen analysis, hormonal evaluation, and a fertility-focused questionnaire. Cut-off scores for 'low semen quality' were based on reference values of the general population as defined by the World Health Organization (WHO). RESULTS: Fifty-one participants had a median age of 40.5 (interquartile range (IQR): 34.0-49.6) years upon evaluation and a median follow-up of 5.8 (IQR: 3.0-9.5) years after their last RAI administration. The median cumulative administered activity of RAI was 7.4 (range: 3.7-23.3) GBq. The proportion of males with a low semen volume, concentration, progressive motility, or total motile sperm count did not differ from the 10th percentile cut-off of a general population (P = 0.500, P = 0.131, P = 0.094, and P = 0.500, respectively). Cryopreserved semen was used by 1 participant of the 20 who had preserved semen. CONCLUSIONS: Participants had a normal long-term semen quality. The proportion of participants with low semen quality parameters scoring below the 10th percentile did not differ from the general population. Cryopreservation of semen of males with DTC is not crucial for conceiving a child after RAI administration but may be considered in individual cases.