Diagnostic Utility of Procalcitonin for Sporadic Medullary Thyroid Carcinoma in Patients with Nodular Disease and Mild or Moderate Hypercalcitoninemia.

Many authors recommend the measurement of serum calcitonin (Ctn) to screen for sporadic medullary thyroid carcinoma (MTC) in patients with thyroid nodules. In this situation, procalcitonin (pro-Ctn) would have greater utility in patients with hypercalcitoninemia<100 pg/ml. The aim of this study was to evaluate the utility of pro-Ctn in patients with thyroid nodules and without a suspicion of familial MTC or type 2 multiple endocrine neoplasia who had mild or moderate hypercalcitoninemia without an apparent cause. Consecutive patients with nodular thyroid disease assessed routinely by Ctn measurement were selected. Sixty patients with basal Ctn>10 pg/ml but<100 pg/ml were included. Nine patients (15%) had MTC, with cytology being diagnostic in only four. Among the 51 patients without MTC, pro-Ctn was<0.1 ng/ml in 46 (90.2%). All patients with MTC had pro-Ctn>0.1 ng/ml. Basal Ctn was>24.6 pg/ml in all patients with MTC and in 42 patients (82.3%) without MTC. It is noteworthy that among patients with basal Ctn>24.6 pg/ml (n=18) pro-Ctn>0.1 ng/ml identified all patients with MTC and 64.2% of subjects with these pro-Ctn concentrations had this tumor. In conclusion, we did not find superiority of pro-Ctn over Ctn for the diagnosis of sporadic MTC in patients with nodular disease and mild or moderate hypercalcitoninemia. However, in the case of patients with hypercalcitoninemia in the gray zone, pro-Ctn has an excellent negative predictive value while the data regarding its positive predictive value are not uniform.

Natural history, predictive factors of apparent disease (structural or biochemical) and spontaneous excellent response in patients with papillary thyroid carcinoma and indeterminate response to initial therapy with radioiodine.

BACKGROUND: About 20% of patients with papillary thyroid carcinoma (PTC) submitted to total thyroidectomy followed by radioactive iodine (RAI) exhibit an indeterminate response to therapy. The aim was to evaluate the natural history, predictive factors of apparent disease (structural or biochemical), and spontaneous excellent response in patients with PTC and an initial indeterminate response to RAI therapy defined based on unstimulated Tg (u-Tg). METHODS: We evaluated 164 patients who were initially treated with total thyroidectomy and RAI and who had an indeterminate response to therapy (u-Tg between 0.2 and 1 ng/ml, undetectable anti-Tg antibodies [TgAb], and neck ultrasonography [US] without anomalies). None of the patients received empirical therapy with RAI. The patients were followed up for 24 to 144 months (median 72 months). RESULTS: Apparent disease occurred in 16 patients (9.7%), including 13 with structural disease and 3 with u-Tg elevation > 1 ng/ml, but no tumor was detected by the imaging methods (biochemical disease). A higher frequency of disease was observed in patients with >3 lymph node metastases (LNM) and initial u-Tg >0.35 ng/ml. The frequency was only 2% among patients with ≤3 LNM and u-Tg ≤0.35 ng/ml and 9.7% among patients with > 3 LNM or u-Tg >0.35 ng/ml, while the frequency was 27% in patients with >3 LNM and u-Tg >0.35 ng/ml. In the absence of any additional therapy, u-Tg was <0.2 ng/ml (excellent response) in the last assessment in 70 patients (42.7%). Only initial u-Tg was associated with a higher probability of spontaneously achieving an excellent response: 40/72 patients (55.5%) with u-Tg ≤0.35 ng/ml versus 30/92 patients (32.6%) with u-Tg >0.35 ng/ml. CONCLUSIONS: A minority of patients with PTC and an initial indeterminate response to RAI defined based on u-Tg develop apparent disease (structural or biochemical) and many spontaneously achieve an excellent response. The risk of disease can be refined based on parameters such as the extent of lymph node involvement and initial Tg concentration.

Follow-up of patients with thyroid cancer and antithyroglobulin antibodies: a review for clinicians.

Antithyroglobulin antibodies (TgAb) are present in up to 25% of patients with differentiated thyroid carcinoma on initial postoperative assessment. Detectable concentrations of TgAb even below the manufacturer's cut-off can interfere with serum thyroglobulin (Tg) determination. When Tg is quantified using an immunometric assay (IMA) (hereafter referred to as Tg-IMA), this interference results in underestimated values of Tg. Although promising, more clinical trials evaluating the capacity of liquid chromatography/tandem mass spectrometry and of new assays to detect elevated Tg in patients with TgAb and structural disease are necessary, particularly when Tg is undetectable by a second-generation IMA (Tg-2GIMA). Neck ultrasonography (US) should be performed in patients submitted to total thyroidectomy and with negative Tg-IMA but with detectable TgAb more than 6 months after initial therapy. In patients treated with 131I, comparison of TgAb concentrations obtained before this treatment is useful to estimate the risk of disease and to guide the investigation. If initial assessment does not reveal any persistent tumor, the repetition of US is recommended while TgAb persist. Significant elevation of TgAb requires extended investigation. On the other hand, patients with negative Tg-IMA and US without abnormalities who exhibit a reduction > 50% in TgAb generally do not require investigation. Although TgAb can interfere with Tg, the management and follow-up of patients submitted to total thyroidectomy with borderline TgAb can probably be the same as those recommended for patients without TgAb if Tg-2GIMA and US indicate an excellent response to therapy. Currently, the presence/absence or the trend of TgAb levels cannot be considered in the follow-up of patients submitted to lobectomy.

Response to: Could thyroidectomy be excluded if 18F-FDG-PET suggests benignity for TNIC?

No abstract.

The value of ultrasonography for the indication of fine-needle aspiration in autonomous thyroid nodules.

BACKGROUND: The risk of malignancy in autonomous thyroid nodules is considered to be very low in adults and fine-needle aspiration (FNA) is not recommended in these cases; however, some studies contest this. Just as ultrasonography (US) has been used to select nonautonomous nodules with initial benign cytology that deserve FNA repetition, this method may also be useful to select autonomous nodules that are candidates for FNA. METHODS: In this prospective study, FNA was obtained in 48 adults patients with autonomous solitary nodules >1 cm with suspicious US features (at least two of the following findings: hypoechogenicity, microcalcification, irregular margins, taller than wider shape, predominantly or exclusively central vascularization). RESULTS: Cytology was benign in 28 patients (58.3%). Six patients (12.5%) had nondiagnostic cytology and histology revealed benign nodules in these cases. Cytology was indeterminate in nine other patients (18.5%). Of these, seven were adenomas and two were follicular carcinomas on histology. Finally, cytology suspicious for malignancy or malignant cytology was detected in five patients (10.4%), all of them confirmed histologically to be papillary carcinomas (the follicular variant in three). Thus, the frequency of malignancy was 14.6% (two follicular carcinomas and five papillary carcinomas), 8.3% in nodules with two suspicious findings vs 33.3% in nodules with ≥3 suspicious findings (P = .055). CONCLUSION: The results suggest that the presence of ultrasonographic findings suspicious for malignancy in autonomous thyroid nodules >1 cm is a criterion for the indication of FNA.

Usefulness of accessible imaging methods in thyroid nodules with indeterminate cytology.

In thyroid nodules (TN) submitted to fine-needle aspiration (FNA), Bethesda categories III and IV are considered 'indeterminate' cytology. This result corresponds to 10-25% of all FNAs and the risk of malignancy (RoM) ranges from 10% to 30% for category III and from 15% to 40% for category IV. This review analyzed the practical applicability of accessible imaging method in the management of patients with cytologically indeterminate TN > 1 cm (ITN). When ITN are highly suspicious on ultrasonography (US), the RoM supports surgical indication even in the absence of additional tests. The same can be applied to ITN of intermediate suspicion but with elevated stiffness on elastography. Follow-up without additional tests is acceptable in the case of ITN with low-risk cytology and low-suspicion appearance on US and elastography (if obtained). In the case of ITN without highly suspicious US appearance, 123I scintigraphy may be obtained in patients with TSH < 1-1.5 mIU/L to rule out hyperfunctioning nodules before requesting diagnostic methods that are more expensive and less accessible. In addition, in ITN with not very suspicious US appearance, 18FDG-PET may be obtained. If this method does not reveal nodular uptake, the risk of the nodule corresponding to a macrocarcinoma is sufficiently low in order to allow follow-up. The positive predictive value of focal nodular uptake on 18FDG-PET depends on the pre-test RoM, cytological findings, and maximum SUV. There is currently no evidence for the use of CT, MRI or imaging using 99mTc-MIBI to define the nature of ITN.

Can patients with papillary thyroid carcinoma and low postoperative thyroglobulin in the presence of clinically apparent lymph node metastases (cN1) be spared from radioiodine?

BACKGROUND: The study evaluated the recurrence rate in patients with papillary thyroid carcinoma (PTC) and clinically apparent lymph node metastases (LNM) (cN1) who had low thyroglobulin (Tg) after total thyroidectomy and who were not submitted to adjuvant therapy with 131I. METHODS: This was a prospective study. It included 82 cN1 patients (≤3 LNM ≤1.5 cm without macroscopic extracapsular extension) with tumors ≤4 cm without macroscopic extrathyroid invasion (T1-2) and who after thyroidectomy had unstimulated Tg (u-Tg) < 0.3 ng/ml, negative antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) showing no anomalies. The patients were not submitted to therapy with 131I. RESULTS: The time of follow-up ranged from 24 to 156 months (median 84 months). Seventy-nine patients (96.3%) continued to have u-Tg < 0.3 ng/ml and negative US. Three patients (3.6%) exhibited an increase in Tg and structural recurrence was detected in two. After treatment, these patients achieved u-Tg < 1 ng/ml and the imaging methods revealed no apparent tumor. CONCLUSIONS: The results suggest that even cN1 patients, given the absence of extensive LNM or other adverse findings, who have low Tg and neck US showing no anomalies after thyroidectomy do not require radioiodine.

Usefulness of Serum Calcitonin in Patients with Thyroid Nodules ≤ 1 cm Without an Indication for Fine-Needle Aspiration.

Fine-needle aspiration (FNA) is not necessary in adults with nodules ≤ 1 cm without apparent extrathyroidal extension (ETE) or lymph node (LN) involvement on ultrasonography (US). In the absence of FNA and serum calcitonin (Ctn) measurement, medullary thyroid microcarcinomas (microMTC) are not diagnosed. The aim of this prospective study was to evaluate Ctn levels in adults with a low clinical risk of MTC and nodules ≤ 1 cm without ETE or LN involvement on US. A total of 506 consecutively seen adults who had nodules with two or more suspicious features were included. Patients with elevated basal Ctn underwent a calcium stimulation test and FNA. Basal Ctn was normal in 490 patients (96.8%). In the 16 patients with elevated basal Ctn, FNA revealed MTC in only one patient and MTC was not suspected in the 15 patients with elevated basal Ctn. Three patients with stimulated Ctn<100 pg/ml and benign cytology were not submitted to surgery. MTC was excluded by histology in three patients with stimulated Ctn<100 pg/ml and indeterminate or suspicious cytology and in eight patients with stimulated Ctn>100 pg/ml. One patient with stimulated Ctn>100 pg/ml had MTC. Ctn was undetectable 6 months after surgery in two patients with MTC. Although uncommon, even subjects without a suspicious history and with nodules ≤ 1 cm without ETE or LN involvement on US, but with suspicious findings, can have microMTC. The measurement of Ctn permits the diagnosis of these cases.

Subclinical Hypothyroidism with TSH>7 mIU/l and≤10 mIU/l and Coronary Artery Disease.

The association of subclinical hypothyroidism (SCH) with increased cardiovascular risk is controversial when thyroid-stimulating hormone (TSH) concentration is<10 mIU/l, as well as its association with a higher coronary artery calcium score (CACS) in individuals with low cardiovascular risk. This study evaluated coronary artery disease (CAD) by CACS in asymptomatic, low-cardiovascular risk women with SCH and TSH>7 mIU/l and≤10 mIU/l untreated for 5 years after diagnosis. The CACS was obtained for two groups of women with low cardiovascular risk. Group A consisted of 32 women with mild SCH (TSH>7 mIU/l and≤10 mIU/l) who remained untreated for 5 years, and group B consisted of 32 euthyroid women matched for age and body mass index to group A. The CACS ranged from 0 to 350 (median 0, 25-75% interval: 0-10) in group A and from 0 to 280 (median 0, 25-75% interval: 0-0) in group B. Scores>0 and≥10 were significantly more frequent in group A (40.6 vs. 12.5% and 25 vs. 3.1%, respectively). A CACS≥100 was also more frequent in group A (18.75 vs. 3.1%), but the difference was not significant (p=0.1). The results of the study suggest that long-term SCH with TSH>7 mIU/l and ≤ 10 mIU/l is associated with a higher risk of CAD in individuals≤65 years, even in those with low cardiovascular risk.

Celiac disease as differential diagnosis of normocalcemic hyperparathyroidism / Doença celíaca como diagnóstico diferencial do hiperparatireoidismo normocalcêmico

ABSTRACT There is no recommendation to investigate celiac disease (CD) in patients with elevated parathyroid hormone (PTH) and normal blood calcium if they are asymptomatic, especially if they do not have hypovitaminosis D. CD was diagnosed in a 30-year-old asymptomatic man without vitamin D deficiency, who had total calcium 9.2 mg/dl, 25-hydroxyvitamin D 36 ng/dl, PTH 112 pg/ml, total IgA 42 mg/dl, anti-tissue transglutaminase (tTG) IgA 22 U/ml. Duodenal biopsy by endoscopy confirmed CD. The patient started a gluten-free diet that was maintained. After six months, the patient had total calcium 9.5 mg/dl, 25-hydroxyvitamin D 42 ng/dl, and PTH 48 pg/ml. In most patients with elevated PTH and normal blood calcium, clinical history, assessment of renal function, vitamin D and phosphorus measurement, and calciuria define the cause of secondary hyperparathyroidism. However, in the few cases in which this initial investigation is negative, even asymptomatic individuals should be tested for CD antibodies before the diagnosis of normocalcemic primary hyperparathyroidism is made.

RESUMEN No hay recomendaciones para investigar enfermedad celíaca (EC) en pacientes con niveles elevados de hormona paratiroidea y calcio sérico normal si ellos son asintomáticos, principalmente si no tienen hipovitaminosis D. Reportamos un caso de EC diagnosticada en un hombre de 30 años, asintomático, sin deficiencia de vitamina D. Sus niveles séricos: calcio total 9,2 mg/dl, 25-hidroxivitamina D 36 ng/dl, hormona paratiroidea 112 pg/ml, inmunoglobulina A (IgA) total 42 mg/dl y anticuerpos anti-transglutaminasa tisular (tTG) IgA 22 U/ml. Biopsia duodenal por endoscopia confermó el diagnóstico de EC. El paciente empezó una dieta libre de gluten. Después de seis meses, el paciente presentó calcio total 9,5 ml/dl, 25-hidroxivitamina D 42 ng/dl y hormona paratiroidea 48 pg/ml. En la mayor parte de los pacientes con hormona paratiroidea elevada y calcio sérico normal, el historial clínico, la evaluación de la función renal y las mediciones de vitamina D, fósforo y calciuria definen la causa del hiperparatiroidismo secundario. No obstante, en los pocos casos en los cuales esa investigación inicial es negativa, incluso los individuos asintomáticos deben ser examinados para anticuerpos para EC antes que el diagnóstico de hiperparatiroidismo primario normocalcémico sea establecido.

RESUMO Não há recomendação para investigar doença celíaca (DC) em pacientes com paratormônio (PTH) elevado e cálcio sérico normal se eles são assintomáticos, principalmente se não têm hipovitaminose D. Relatamos um caso de DC diagnosticada em um homem de 30 anos, assintomático, sem deficiência de vitamina D. Os exames apresentaram cálcio total 9,2 mg/dl, 25-hidroxivitamina D 36 ng/dl, PTH 112 pg/ml, imunoglobulina da classe A (IgA) total 42 mg/dl e antienzima transglutaminase tecidual (tTG) IgA 22 U/ml. Biópsia duodenal por endoscopia confirmou o diagnóstico de DC. O paciente iniciou dieta sem glúten. Após seis meses, apresentou cálcio total 9,5 mg/dl, 25-hidroxivitamina D 42 ng/dl e PTH 48 pg/ml. Na maioria dos pacientes com PTH elevado e cálcio sérico normal, a história clínica, a avaliação da função renal e as dosagens de vitamina D, fósforo e calciúria definem a causa do hiperparatireoidismo secundário. Porém, nos poucos casos em que essa investigação inicial é negativa, até os indivíduos assintomáticos deveriam ser testados para anticorpos para DC antes de o diagnóstico de hiperparatireoidismo primário normocalcêmico ser firmado.

TRH stimulation test in patients with repeatedly elevated TSH and normal FT4 / Teste de estímulo com TRH em pacientes com TSH repetidamente elevado e T4L normal

ABSTRACT Subclinical hypothyroidism (SCH) is defined by elevated thyroid-stimulating hormone (TSH) with normal free thyroxine (FT4). We aimed to evaluate the thyrotropin-releasing hormone (TRH) stimulation test in patients with repeatedly elevated TSH (up to 10 mIU/l) and normal FT4, but without apparent thyroid disease. Women with TSH > 4.5 and ≤ 10 mIU/l (in two measurements) and normal FT4 were selected. Women with a known non-thyroid cause of TSH elevation, those treated with anti-thyroid drugs, amiodarone, lithium, and those with a history of thyroidectomy, neck radiotherapy and 131I treatment were excluded. Seventy women had negative antithyroperoxidase antibodies. Ultrasonography revealed a eutopic thyroid, usual echogenicity, and a volume ≤ 15 ml, and they underwent the TRH stimulation test during initial evaluation. After stimulation with TRH, TSH > 30 mIU/l was observed in 38 women (expected response), while 32 women had TSH < 20 mIU/l (inadequate response). Age, basal TSH or thyroid volume did not differ between both groups, but FT4 concentrations were significantly lower in the first group. Follow-up was available for 66/70 women. Seven women developed a need for levothyroxine, all of them in the group with an adequate response to TRH [7/36 (19.4%) versus 0/30]. The results suggest that some cases of TSH elevation (even persistent) do not represent the early stage of thyroid insufficiency.

RESUMEN El hipotiroidismo subclínico (HSC) es definido por la elevación de los niveles de hormona tiroestimulante (TSH) con los niveles de tiroxina libre (T4L) dentro de rangos de normalidad. El objetivo de este reporte fue evaluar la prueba de estímulo con hormona liberadora de tirotropina (TRH) en pacientes con TSH persistentemente elevado (hasta 10 mUI/l) y T4L normal, pero sin enfermedad tiroidea aparente. Se eligieron mujeres con TSH > 4,5 y ≤ 10 mUI/l (en dos medidas) y T4L normal. Se excluyeron aquellas con causa no tiroidea conocida de alza de TSH además de las tratadas con medicamentos antitiroideos, amiodarona, litio y con historia de tiroidectomía, radioterapia cervical y tratamiento con 131I. Setenta mujeres presentaron anticuerpos antitiroperoxidasa negativos. La ecografía mostró tiroides eutópica, ecogenicidad usual y volumen ≤ 15 ml; todas se sometieron a la prueba de estímulo con TRH en la evaluación inicial. Tras estímulo con TRH, TSH > 30 mUI/l se observó en 38 mujeres (respuesta esperada), mientras 32 mujeres presentaron TSH < 20 mUI/l (respuesta inadecuada). El seguimiento estuvo disponible para 66/70 mujeres. Siete pacientes evolucionaron con necesidad de levotiroxina, todas ellas en el grupo con respuesta adecuada al TRH [7/36 (19,4%) versus 0/30]. Los resultados sugieren que algunos casos de alza de TSH (aunque persistente) no representan la fase inicial de una insuficiencia tiroidea.

RESUMO O hipotireoidismo subclínico (HSC) é definido pela elevação dos níveis de hormônio tireoestimulante (TSH) com os níveis de tiroxina livre dentro da normalidade (T4L). O objetivo deste relato foi avaliar o teste de estímulo com hormônio liberador de tirotrofina (TRH) em pacientes com TSH repetidamente elevado (até 10 mUI/l) e T4L normal, mas sem doença tireoidiana aparente. Mulheres com TSH > 4,5 e ≤ 10 mUI/l (em duas medidas) e T4L normal foram selecionadas. Foram excluídas aquelas com causa não tireoidiana conhecida de elevação do TSH, além das tratadas com medicamentos antitireoidianos, amiodarona, lítio e com histórico de tireoidectomia, radioterapia cervical e tratamento com 131I. Setenta mulheres apresentaram anticorpos antitireoperoxidase negativos. A ultrassonografia revelou tireoide eutópica, ecogenicidade usual e volume ≤ 15 ml; todas foram submetidas ao teste de estímulo com TRH na avaliação inicial. Após estímulo com TRH, TSH > 30 mUI/l foi observado em 38 mulheres (resposta esperada), enquanto 32 mulheres apresentaram TSH < 20 mUI/l (resposta inadequada). Idade, TSH basal ou volume da tireoide não diferiram entre os dois grupos, mas as concentrações de T4L foram significativamente menores no primeiro grupo. O acompanhamento foi disponível para 66/70 mulheres. Sete pacientes evoluíram com necessidade de levotiroxina, todas elas no grupo com resposta adequada ao TRH [7/36 (19,4%) versus 0/30]. Os resultados sugerem que alguns casos de elevação do TSH (mesmo persistente) não representam a fase inicial de uma insuficiência tireoidiana.

Active Surveillance in Adults with Low-Risk Papillary Thyroid Microcarcinomas: A Prospective Study.

The acceptance and results of active surveillance in patients with low-risk papillary thyroid microcarcinomas (PTMC) are unknown in populations other than the Japanese population. This was the objective of the present prospective study. We selected patients ≥20 years who had thyroid nodules ≤1.2 cm with intermediate or high suspicion for malignancy on ultrasonography (US), not located near the recurrent laryngeal nerve and without extrathyroidal invasion or apparent lymph node metastases, whose cytology was suspicious (Bethesda V) or diagnostic (Bethesda VI) of papillary thyroid carcinoma. Patients who opted for active surveillance were followed up by biannual US. Fifteen patients (18.7%) readily opted for surgery and 12 (15%) for active surveillance. Fifty-three patients (66.2%) delegated the decision or wished to know the doctor's preference before deciding. After the doctor had declared his/her preference for active surveillance, 50 patients decided to have this management and three to have surgery. Only 1/70 patients exhibited tumor progression (growth associated with a suspicion of extrathyroidal invasion) after 30 months of follow-up. Two patients decided to have surgery during follow-up, although the indication was not defined by the study. A>50% reduction in tumor volume was observed in three patients. The study shows that active surveillance can be well accepted if doctors were convinced that it is the best option for patients with low-risk PTMC. At least the short-term results reproduced those observed in other populations, with tumor progression being uncommon.

Definition of the Response to Initial Therapy with Radioiodine in Patients with Differentiated Thyroid Carcinoma: Basal or Stimulated Thyroglobulin?

Basal thyroglobulin (b-Tg) measured with second-generation assay or stimulated Tg (s-Tg) can be used to define the response to therapy of differentiated thyroid carcinoma. However, they do not always define the same category and guidelines do not establish "if" or "when" s-Tg needs to be obtained. We studied 304 patients without clinically apparent disease or disease detected by neck ultrasonography and without anti-Tg antibodies 9-12 months after therapy. Based on b-Tg, 196 patients had an excellent response and 108 had an indeterminate response. Based on s-Tg, a change in category occurred in 10.2% of the patients with an initial excellent response (all to indeterminate response) and in half the patients with an initial indeterminate response (44.4% to excellent response and 5.5% to biochemical incomplete response). One case of recurrence was observed among patients with an initial excellent response but whose response changed to indeterminate after s-Tg, while no disease was detected among those who remained in the initial category; however, this difference was not significant. In patients with an initial indeterminate response, no recurrence was detected among those whose response changed to excellent after s-Tg, while 11.1 and 33.3% of those who remained in the initial category or whose response changed to biochemical incomplete, respectively, had structural disease. This study suggest that, in low- or intermediate-risk patients, s-Tg better defines the response to therapy with 131I when it is classified as indeterminate based on b-Tg using second-generation assay. However, s-Tg is not necessary when b-Tg defines the response as excellent.

Thyroid nodules ≤ 1 cm and papillary thyroid microcarcinomas: Brazilian experts opinion

ABSTRACT The indolent evolution of low-risk papillary thyroid microcarcinoma (mPTC) in adult patients and the consequences of thyroidectomy require a revision of the management traditionally recommended. Aiming to spare patients unnecessary procedures and therapies and to optimize the health system in Brazil, we suggest some measures. Fine-needle aspiration of nodules ≤ 1 cm without extrathyroidal extension on ultrasonography should be performed only in nodules classified as "very suspicious" (i.e., high suspicion according to ATA, high risk according to AACE, TI-RADS 5) and in selected cases [age < 40 years, nodule adjacent to the trachea or recurrent laryngeal nerve (RLN), multiple suspicious nodules, presence of hypercalcitoninemia or suspicious lymph nodes]. Active surveillance (AS) rather than immediate surgery should be considered in adult patients with low-risk mPTC. Lobectomy is the best option in patients with unifocal low-risk mPTC who are not candidates for AS because of age, proximity of the tumor to the trachea or RLN, or because they opted for surgery. The same applies to patients who started AS but had a subsequent surgical indication not due to a suspicion of tumor extension beyond the gland or multicentricity. Molecular tests are not necessary to choose between AS and surgery or, in the latter case, between lobectomy and total thyroidectomy. The presence of RAS or other RAS-like mutations or BRAFV600E or other BRAF V600E-like mutations should not modify the management cited above; however, the rare cases of mPTC exhibiting high-risk mutations, like in the TERT promoter or p53, are not candidates for AS.