Summary and update on the management of differentiated thyroid cancer in 2023.

The 6-fold increase in the incidence of differentiated thyroid cancer over the past 30 years in industrialized countries can be mainly attributed to improved detection. At the same time, in addition to the excellent prognosis for low-risk cancers, improved survival in metastatic forms has been also reported, likely due to the progress made recently in the treatment of aggressive forms, for which there is now an extensive therapeutic arsenal. Today, clinical management of differentiated thyroid cancer represents a paradigm of precision oncology, with personalized, risk-adapted therapeutic strategies. This has led to therapeutic de-escalation in those forms with a good prognosis, while targeted treatments play an increasingly important role in the management of radioiodine-refractory or advanced cancers. While endocrinologists will not always have the opportunity to prescribe these treatments, they will be called on to support and monitor patients during treatment. The aim of this article is to provide an overview of treatment options for differentiated thyroid cancer in 2023.

Patients with prediabetes improve insulin resistance after surgery for primary hyperparathyroidism.

BACKGROUND: The objective of this study was to evaluate the evolution of insulin resistance at 12 months after parathyroidectomy for primary hyperparathyroidism according to the preoperative severity of glucose metabolism abnormalities. METHODS: Observational study of patients who underwent parathyroidectomy between 2016 and 2021. Prediabetes and insulin resistance were defined as fasting glucose ≥1.00 g/L (American Diabetes Association) and homeostatic model assessment of insulin resistance >2.5, respectively. RESULTS: A total of 231 patients were included. Preoperatively, 75 patients (32%) had prediabetes, and 108 patients (47%) had insulin resistance. At 12 months postoperative, homeostatic model assessment of insulin resistance values significantly decreased in patients with prediabetes (-0.69; P = .04) and in patients with insulin resistance (-0.85; P < .001). In patients with prediabetes, 48/75 (64%) decreased their insulin resistance, including 15/48 (31%) with normalization of fasting glucose. In multivariate analysis, preoperative prediabetes (1.82, 1.03-3.21; P = .037) or preoperative homeostatic model assessment of insulin resistance >2.5 (3.90, 2.23-6.75; P < .001) remained independent predictors for insulin resistance reduction observed between preoperative and 12 months postoperative. CONCLUSION: Parathyroidectomy is more likely to reduce insulin resistance in patients with primary hyperparathyroidism and prediabetes or in patients with higher preoperative homeostatic model assessment of insulin resistance values. These data support the use of the preoperative prediabetes criterion in addition to the international workshop criteria for parathyroidectomy to better select patients for surgery.

Factors Associated with Survival in Anaplastic Thyroid Carcinoma: A Multicenter Study from the ENDOCAN-TUTHYREF Network.

Background: Anaplastic thyroid carcinoma (ATC) is a rare and frequently fatal type of thyroid cancer. The degree of heterogeneity in survival rates for ATC is incompletely studied. This study evaluated the factors associated with overall survival (OS) of patients with ATC using multicenter real-world data from a national tertiary care center network in France. Methods: In this multicenter, retrospective cohort study, all patients with ATC diagnosed between 2010 and 2020 were identified from the national database of the French ENDOCAN-TUTHYREF network. Factors associated with OS were examined in multivariable analyses using Cox proportional hazards models. Results: The study included 360 patients. Of these, 220 (61%) were female and the median age was 72 years (interquartile range: 62-80). The percentages of patients with pure and mixed (synchronously-transformed) ATC (p-ATC and st-ATC) were 62.5% and 26.7%, respectively. The median OS was 6.8 months [confidence interval, CI: 5.5-8.1]: not reached for stage IVa, 11.4 months [8.2-17.8] for IVb, and 4.6 months [3.5-5.7] for IVc. Surgery, radiation therapy to the neck, chemotherapy, and best supportive care were administered to 69 (19.2%), 214 (59.4%), 254 (70.6%), and 66 (18.3%) patients, respectively. In a multivariable analysis, including stage IVb-IVc patients, significantly higher OS was observed in patients with Eastern Cooperative Oncology Group performance-status of 0-1 (hazard ratio [HR], 0.6; [CI, 0.4-0.9], p < 0.02), stage IVb [HR, 0.5; CI, 0.4-0.8, p < 0.001], and multimodal treatment (surgery and chemoradiotherapy) [HR, 0.07; CI, 0.04-0.1, p < 0.001]. Variables associated with significantly worse OS included: p-ATC (vs. st-ATC) [HR, 1.83; CI, 1.33-2.51, p = 0.001] and a neutrophil-to-lymphocyte ratio (NLR) >5.05 [HR, 2.05, CI, 1.39-3.05, p < 0.001]. Conclusions: Factors independently associated with improved OS in ATC included: European Cooperative Oncology Group performance status, disease stage, multimodality treatment, synchronously transformed ATC, and lower NLR. Long-term OS was observed in selected patients with ATC who underwent multimodal treatment.

MAST1-related mega-corpus-callosum syndrome with central hypogonadism.

OBJECTIVE: Heterozygous variations in microtubule-associated serine/threonine kinase 1 gene (MAST1) were recently described in the mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM, MIM 618273), revealing the importance of the MAST genes family in global brain development. To date, patients with MAST1 gene mutations were mostly young children with central nervous system involvement, impaired motor function, speech delay, and brain magnetic resonance imaging (MRI) abnormalities. Here, we report the clinical presentation of an adult patient with a rare and de novo MAST1 mutation with central hypogonadism that could extend this phenotype. METHODS: A panel of 333 genes involved in epilepsy or cortical development was sequenced in the described patient. Routine biochemical analyses were performed, and hormonal status was investigated. RESULT: We report a 22-year-old man with a de novo, heterozygous missense variant in MAST1 (Chr19(GRCh37):g.12975903G > A, NP_055790.1:p.Gly517Ser). He presented with an epileptic encephalopathy associated with cerebral malformations, short stature, hypogonadotropic hypogonadism, and secondary osteopenia. CONCLUSION: This is the first patient with MAST1 gene mutation described with central hypogonadism, which may be associated with the phenotype of MCCCHCM syndrome.

e-Health Literacy Skills in People with Chronic Diseases and What Do the Measurements Tell Us: A Scoping Review.

Background: Use of electronic health (e-Health) technologies has increased in the past decade and inadequate e-Health literacy may lead to health-related social inequality. This is especially true for patients living with chronic diseases who are often involved in self-care. However, the measurement of e-Health literacy represents several challenges. Among available instruments, the e-Health Literacy Scale (eHEALS) is the only instrument with available psychometric properties. Aim: To identify studies measuring e-Health literacy in adults living with chronic disease and its relationship to health-related behaviors and other perceptions such as quality of life, self-efficacy, or specific disease biomarkers, and studies analyzing the impact of educational intervention on e-Health literacy. Methods: The authors searched MEDLINE, the Cochrane Library, and Web of Science databases to identify studies published in English language until April 2022. Results: Seventeen studies involving 4,877 participants were included. A majority of the studies were cross-sectional with a lack of appropriate controls. Five of the included studies were experimental, involving 758 participants. All of them reported positive effects of educational interventions on the improvements in self-reported e-Health literacy skills. However, most studies were at risk of bias. Conclusion: Despite these limitations, the findings of this review indicate the positive relationship between e-Health literacy and various health care processes in adults with chronic diseases and highlights a need for prospective controlled studies. Promoting e-Health literacy might give better opportunities for the active involvement of people with chronic diseases in self-care and for the implementation of online interventions into existing system of care.

Prognostic indicators in pituitary adenoma surgery: a comprehensive analysis of surgical outcomes and complications.

Objective: The primary aim of this study was to identify predictive factors associated with onset of de-novo clinically significant pituitary insufficiencies following endoscopic endonasal surgery (EES) for pituitary adenomas. The secondary objective explored the predictive factors of surgical success. Methods: A retrospective analysis was conducted on 211 patients who underwent EES. Logistic regression models were employed for the primary and secondary objectives. Patients were stratified into specific groups based on surgical indications and prolactin levels for nuanced analysis. Results: Significant predictors for de-novo pituitary insufficiencies included male sex (OR 3.3, CI95% 1.3-8.1, p=0.01), immediate postoperative insufficiencies (OR 5.6, CI95% 2.8-11.1, p<0.001), and HYPRONOS criteria (OR 5.7, CI95% 1.6-20.9, p=0.008). For surgical success, preoperative insufficiencies (OR 0.7, CI95% 0.5-0.9, p=0.008), repeat surgeries (OR 0.1, CI95% 0-0.4, p=0.001), and gonadotroph or somatotroph adenomas were significant. Age and adenoma size were not predictive in multivariate analysis. Furthermore, we observed a "dip and recover" effect of prolactin after surgery and lower prolactin levels at follow-up (< 3 ng/ml) are correlated with more anterior pituitary insufficiencies than normoprolactinemic patients (p = 0.004). Conclusion: This study identifies key predictors for outcomes in pituitary surgery. Our research is the first to employ individualized success criteria for EES, challenging existing perceptions about the role of age and adenoma size. These findings open avenues for nuanced, individualized preoperative risk assessment and postoperative management.

Systematic detection of mosaicism by using digital NGS reveals three new MEN1 mosaicisms.

Purpose: Mosaicism is a feature of several inherited tumor syndromes. Only a few cases of mosaicism have been described in multiple endocrine neoplasia type 1 (MEN1). Next-generation sequencing (NGS) offers new possibilities for detecting mosaicism. Here, we report the first study to systematically look for MEN1 mosaicism, using blood DNA, in MEN1-suspected patients but without MEN1 pathogenic variants (PV) in a heterozygous state. Methods: Digital targeted NGS, including unique molecular identifiers (UMIs), was performed in routine practice, and the analytic performance of this method was verified. Results: Among a cohort of 119 patients harboring from 2 to 5 MEN1 lesions, we identified 3 patients with MEN1 mosaic PVs. The allele frequencies ranged from 2.3 to 9.5%. The detection rate of MEN1 mosaicism in patients bearing at least 3 MEN1 lesions was 17% (3/18). No cases were detected in patients with two lesions. Conclusion: We report here three new cases with MEN1 mosaicism. This study examined the performance of UMI in the diagnosis of MEN1 mosaicism in routine practice, and our results underline that the frequency of mosaicism is probably underestimated in patients with suspected MEN1.

Management of Patients with Treatment of Pheochromocytoma: A Critical Appraisal.

The management of pheochromocytomas has significantly evolved these last 50 years, especially with the emergence of new technologies such as laparoscopic procedures in the 1990s. A preoperative blockade using antihypertensive medications to prevent intraoperative hemodynamic instability and cardiocirculatory events is recommended by current clinical guidelines. However, these guidelines are still based on former experiences and are subject to discussion in the scientific community. The aim of this systematic review was to assess the evolution of the management of pheochromocytomas. Laparoscopic procedure is established as the standard of care in current practices. Preoperative medical preparation should be questioned because it does not significantly improve intraoperative events or the risk of postoperative complications in current clinical practice. Current clinical recommendations should be revised and upgraded to current clinical practices.

Adverse effects of gender-affirming hormonal therapy in transgender persons: Assessing reports in the French pharmacovigilance database.

Limited data are available on adverse drug reactions (ADRs) of gender-affirming hormone therapy (HT), mainly due to the lack of population-based studies with adequate controls, thus making spontaneous reporting systems a valuable tool to detect potential side reactions. In this nationwide retrospective study, we aimed to analyze ADRs related to gender-affirming HT reported in the French pharmacovigilance database (FPVD). We requested all the individual case safety reports related to gender-affirming HT recorded in the FPVD before May 27, 2020. We excluded previously published cases and those where gender-affirming HT was not the suspected drug. A total of 28 reports of ADRs were identified. Six concerned transgender men (21-40 years) and 22 transgender women (22-68 years). In transgender men taking testosterone enanthate, all reported ADRs were cardiovascular events, with pulmonary embolism in 50% of cases. Median time to onset (TTO) was 34 months. In transgender women, antiandrogens, mainly cyproterone acetate, were involved in 68% of cases, and estrogens in 77% of cases, mostly in association with progestin or cyproterone acetate. Meningiomas were the principal ADRs, followed by cardiovascular events, with a median TTO of 5.3 months. Our data show a previously unreported, non-negligible proportion of cases indicating cardiovascular ADRs in transgender men younger than 40 years. In transgender women, cardiovascular events were the second most frequent ADR. Further research is necessary to identify risk factors that might help to the individualization of treatment strategies. There is a necessity to increase awareness, implement preventive and education measures.

Multiple endocrine neoplasia type 1 caused by mosaic mutation: clinical follow-up and genetic counseling?

MEN1 is an autosomal dominant hereditary syndrome characterized by several endocrine tumors, in most cases affecting the parathyroid glands, pancreas, and anterior pituitary. It is the result of inactivating mutations in the tumor suppressor gene MEN1. More than 1300 different mutations have been identified in this gene. Mosaic MEN1 mutations have been previously described in only a few patients in the literature. In this paper, we provide a review of six cases of MEN1 mosaicism reported in the literature supplemented with six additional cases described by the French TENgen network of laboratories. This review highlights that (i) MEN1 mosaicism is not associated with a mild phenotype and results in the same natural history as heterozygous MEN1 mutation and (ii) that more systematic detection of MEN1 mosaic mutation enables improvements in both patient monitoring and genetic counseling.

Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.

BACKGROUND: In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS: In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS: Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS: In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).

High prevalence of anterior pituitary deficiencies after cranial radiation therapy for skull base meningiomas.

BACKGROUND: Cranial irradiation represents one of the first line treatment proposed in skull base meningiomas. While cranial irradiation is associated with a high risk of secondary hypopituitarism, few studies focused on the specific location of skull base meningiomas. METHODS: Fifty-two adults receiving photon-beam therapy for skull base meningiomas between 2003 and 2014 in our Institution were included. Anterior pituitary (ACTH, FSH, GH, LH, TSH and prolactin) as well as corresponding peripheral hormones (8 am-Cortisol, IGF-1, fT3, fT4, 17ßestradiol or testosterone) were biologically screened before radiotherapy (baseline), then yearly until March 2019. The pituitary gland (PG) was delineated on CT and the mean dose delivered to it was calculated. RESULTS: Mean age at diagnosis was 56 +/- 14 years. Median follow-up was 7 years. Up to 60% of patients developed at least ≥2 pituitary deficiencies, 10 years after radiotherapy. Gonadotroph, thyrotroph, corticotroph and somatotroph deficiencies occurred in 37, 28, 18 and 15% of patients, respectively. Hyperprolactinemia was found in 13% of patients. None patient had only one pituitary deficiency. In the multivariate analysis, a delivered dose to the PG ≥ 50 Gy or a meningioma size ≥40 mm significantly increased the risk of developing hypopituitarism. CONCLUSIONS: Over a long-term follow-up, cranial radiation therapy used in skull base meningiomas led to a high prevalence of hypopituitarism, further pronounced in case of tumor ≥4 cm. These results advocate for an annual and prolonged follow-up of the pituitary functions in patients with irradiated skull base meningiomas.

Adherence to growth hormone therapy guidelines in a real-world French cohort of adult patients with growth hormone deficiency.

OBJECTIVE: Using real-world data from patients with growth hormone deficiency (GHD), we evaluated whether clinical practice in France adheres to international guidelines regarding somatropin dose adjustment, and assessed the long-term effectiveness and safety of somatropin. METHODS: Data were obtained from a national prospective systematic longitudinal routine follow-up programme of naive/non-naive adults with childhood-onset (CO) or adult-onset (AO) GHD treated with Norditropin® (Novo Nordisk A/S). RESULTS: Between 2003 and 2006, 331 treatment-naive and non-naive adults with severe GHD were enrolled and followed for a median duration of approximately 5 years; 328 patients were available for analysis. At baseline, mean patient age was 39.2 years; median standard deviation score (SDS) for insulin-like growth factor-1 (IGF-1) level was -2.2 in naive patients, subsequently fluctuating between -0.1 and +0.3 SDS during the study period. Mean GH doses ranged between 0.25 and 0.51mg/day (naive patients) and 0.39 and 0.46mg/day (non-naive patients). Despite generally receiving a higher somatropin dose, women (naive/non-naive) tended to have lower IGF-1 levels than men. Median somatropin dose was consistently higher in patients with CO-GHD than patients with AO-GHD. Extreme IGF-1 values (<-2 or >+2 SDS) were not systematically accompanied by somatropin dose adjustments. Waist circumference improved in approximately one third of patients, at a mean 3.5 years. Somatropin was well tolerated; there were no cardiovascular or cerebrovascular events during the 5-year analysis period. CONCLUSION: Current clinical practice of physicians in France follows international guidelines regarding somatropin dose adjustment in adults with GHD. However, dose adjustments are not always sufficient, notably in women, and treatment effects may have been delayed due to low somatropin dose (Clinical trial registration NCT01580605).

Robotic adrenalectomy in patients with pheochromocytoma: a systematic review.

Pheochromocytomas (PHEOs) are neural crest cell tumors producing catecholamines. PHEOS need to be early diagnosed and adequately managed. Adrenalectomy is the gold standard treatment of these type of tumors. There has been major improvement of surgical technologies with the development of laparoscopic and robotic systems these past several years. We conducted a review of the literature to evaluate the robotic approach for adrenalectomy for patients with PHEO.

Robotic adrenalectomy: when and how?

Currently, laparoscopic adrenalectomy is considered as the preferred technique to manage adrenal tumors. However, there are no prospective randomized studies evaluating this strategy. With the recent advances in surgical equipment and the widespread of robotic technology, a robotic approach is considered as an interesting option in some medical centers. This approach seems to be feasible and safe but high-level evidence of its benefits is still lacking. This review summarizes indications, advantages and drawbacks of robotic adrenalectomy and describes its surgical technique.

Ultrasound and cytological characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features compared to papillary carcinomas.

INTRODUCTION: NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features, formerly non-invasive encapsulated follicular variant of papillary thyroid carcinoma) has been removed from the carcinoma category because of its indolent character and good prognosis. This change impacts clinical and surgical management, since these tumors no longer require total thyroidectomy, or complementary radioactive iodine therapy for <4cm tumor. The aim of the present study was to identify preoperative ultrasound and cytological differences between NIFTP and papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: A retrospective study included 81 patients who underwent total thyroidectomy or thyroid lobectomy with histologic diagnosis of PTC, NIFTP or invasive follicular variant of PTC (IFVPTC) between January 1st, 2016 and May 31st, 2018. Ultrasound and cytological data were analyzed and compared between NIFTP and non-NIFTP (PTC and invasive follicular variant of PTC). RESULTS: Fourteen NIFTPs, 67 PTCs, including 20 IFVPTCs, were included. In comparison with non-NIFTP PTC, nodules in NIFTP were more often isoechoic (69.2% vs. 17.4%; P=0.0007), with smooth borders (92.3% vs. 31.1%; P=0.0001) and TI-RADS score 2, 3 or 4a. Cytologically, NIFTPs were mainly in categories AUS/FLUS, FN and SusM of the Bethesda System for Reporting Thyroid Cytopathology. Only nuclear pseudo-inclusions were significantly associated with non-NIFTP (P=0.0031). CONCLUSION: NIFTP appears non-suspect on preoperative ultrasound and indeterminate on cytology. These differences with respect to PTC can guide diagnosis and surgical treatment.

Metastatic Potential and Survival of Duodenal and Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1: A GTE and AFCE Cohort Study (Groupe d'étude des Tumeurs Endocrines and Association Francophone de Chirurgie Endocrinienne).

OBJECTIVE: To assess the distant metastatic potential of duodeno-pancreatic neuroendocrine tumors (DP-NETs) in patients with MEN1, according to functional status and size. SUMMARY BACKGROUND DATA: DP-NETs, with their numerous lesions and endocrine secretion-related symptoms, continue to be a medical challenge; unfortunately they can become aggressive tumors associated with distant metastasis, shortening survival. The survival of patients with large nonfunctional DP-NETs is known to be poor, but the overall contribution of DP-NETs to metastatic spread is poorly known. METHODS: The study population included patients with DP-NETs diagnosed after 1990 and followed in the MEN1 cohort of the Groupe d'étude des Tumeurs Endocrines (GTE). A multistate Markov piecewise constant intensities model was applied to separate the effects of prognostic factors on 1) metastasis, and 2) metastasis-free death or 3) death after appearance of metastases. RESULTS: Among the 603 patients included, 39 had metastasis at diagnosis of DP-NET, 50 developed metastases during follow-up, and 69 died. The Markov model showed that Zollinger-Ellison-related tumors (regardless of tumor size and thymic tumor pejorative impact), large tumors over 2 cm, and age over 40 years were independently associated with an increased risk of metastases. Men, patients over 40 years old and patients with tumors larger than 2 cm, also had an increased risk of death once metastasis appeared. CONCLUSIONS: DP-NETs of 2 cm in size or more, regardless of the associated secretion, should be removed to prevent metastasis and increase survival. Surgery for gastrinoma remains debatable.

Immunoglobulin Preparations Can Mislead Clinical Decision-Making in Follow-Up of Differentiated Thyroid Cancer.

OBJECTIVE: Intravenous and subcutaneous immunoglobulins are commonly used for immune substitution or as immune modulators in a variety of inflammatory and autoimmune disorders. Exogenous thyroid-specific thyroglobulin (Tg) antibodies present in the donor plasma may interfere with the interpretation of measurements of Tg autoantibodies (Tg-Abs) in the recipient's plasma and potentially trigger an immune response in the recipient's immune cells. Levels of antibodies causing bioassay interferences or those leading to clinically relevant changes in patient outcomes are not known. Tg is used as a biomarker in the long-term surveillance of patients with differentiated thyroid cancer (DTC) following total thyroidectomy and radioactive iodine ablation. However, the presence of Tg-Abs in the circulation interferes with Tg measurements. Assessment of levels of Tg-Abs is thus recommended as a part of standard follow-up of DTC together with Tg testing. METHODS: To understand the potential mechanisms and pathophysiologic significance of possible interferences associated with administration immunoglobulin preparations and Tg measurement, we overview the current knowledge on interactions between Tg autoimmunity and immunoglobulin preparations and illustrate diagnostic challenges and perspectives for follow-up of patients with DTC treated with exogenous immunoglobulins. RESULTS: In patients with DTC treated with immunoglobulin preparations, monitoring of thyroid cancer using Tg and Tg-Abs is challenging due to possible analytical interferences through passive transfer of exogenous antibodies from immunoglobulin preparations. CONCLUSION: Analytical interferences must be suspected when a discrepancy exists between clinical examination and diagnostic tests. Collaboration between endocrinologists, biologists, and pharmacologists is fundamental to avoid misdiagnosis and unnecessary medical or radiologic procedures. ABBREVIATIONS: CT = computed tomography; DTC = differentiated thyroid cancer; FNAB = fine-needle aspiration biopsy; HAb = heterophile antibody; IMA = immunometric assay; IVIg = intravenous immunoglobulin; RAI = radioactive iodine; RIA = radioimmunoassay; SCIg = subcutaneous immunoglobulin; Tg = thyroglobulin; Tg-Ab = thyroglobulin autoantibody; Tg-MS = thyroglobulin mass spectrometry; TPO-Ab = thyroid peroxidase autoantibody; TSHR-Ab = thyrotropin receptor autoantibody.