Biomarkers in Thyroid Cancer: Emerging Opportunities from Non-Coding RNAs and Mitochondrial Space.

Thyroid cancer diagnosis primarily relies on imaging techniques and cytological analyses. In cases where the diagnosis is uncertain, the quantification of molecular markers has been incorporated after cytological examination. This approach helps physicians to make surgical decisions, estimate cancer aggressiveness, and monitor the response to treatments. Despite the availability of commercial molecular tests, their widespread use has been hindered in our experience due to cost constraints and variability between them. Thus, numerous groups are currently evaluating new molecular markers that ultimately will lead to improved diagnostic certainty, as well as better classification of prognosis and recurrence. In this review, we start reviewing the current preoperative testing methodologies, followed by a comprehensive review of emerging molecular markers. We focus on micro RNAs, long non-coding RNAs, and mitochondrial (mt) signatures, including mtDNA genes and circulating cell-free mtDNA. We envision that a robust set of molecular markers will complement the national and international clinical guides for proper assessment of the disease.

[Post-Thyroidectomy Hypocalcemia: Incidence, Prediction, and Outpatient Management Strategies Based on PTH and Calcium Levels]. / Incidencia de Hipocalcemia Post Tiroidectomía. Factores predictores (PTH, Fósforo, Magnesio) y protocolo de manejo con alta precoz.

INTRODUCTION: PTH measurement has been proposed to predict transient and permanent postoperative hypocalcemia. There is no standard cut-off point or time for sampling. AIM: To report the incidence of post-thyroidectomy hypocalcemia in a high-volume surgical group and propose an outpatient management protocol according to postoperative (PO) calcium levels, iPTH (normal, low, or undetectable), and symptoms. Furthermore, determine postoperative PTH values as predictors of hypocalcemia. METHODS: In 106 patients with total thyroidectomy between 2019 and 2021, pre-and postoperative levels of calcium, magnesium, phosphorus, and iPTH were measured. RESULTS: Transient (< 12 months) and permanent (> 12 months) hypocalcemia was observed in 29% and 1%. Cut-off points to predict hypocalcemia were PTH < 8.8 pg/mL and < 80% decrease in % PTH (d% PTH) the day after surgery. With the proposed management, early discharge is indicated (an average of 1.05 days), and the prescription cost is limited. There is no significant association between PO hypomagnesemia and hyperphosphatemia with PO hypocalcemia. The most widely used treatment is exclusive calcium carbonate (schemes I and II). Patients remain with mild symptoms at two weeks PO in 5% and discontinue oral treatment in 93% in this period. CONCLUSIONS: Protocols for measuring PTH as a hypocalcemia predictor vary. Each center must know and establish its management protocols. With this experience, we demonstrate the usefulness and safety of a management scheme based on calcium, PTH (normal, low, or undetectable), and symptoms with an indication of prophylactic treatment for all patients and a safe outpatient setting at a lower cost than prolonged hospitalization.

[Study and management of thyroid nodes by non specialist physicians: SOCHED consensus]. / Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED.

The thyroid nodule is a frequent cause of primary care consultation. The prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to 67% by the incidental detection of nodules on ultrasound. The vast majority are benign and asymptomatic, staying stable over time. The clinical importance of studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10% of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and Diabetes) asked the Thyroid Study Group to develop a consensus regarding the diagnostic management of the thyroid nodule in Chile, aimed at non-specialist physicians and adapted to the national reality. To this end, a multidisciplinary group of 31 experts was established among university academics, active researchers with publications on the subject and prominent members of scientific societies of endocrinology, head and neck surgery, pathology and radiology. A total of 14 questions were developed with key aspects for the diagnosis and subsequent referral of patients with thyroid nodules, which were addressed by the participants. In those areas where the evidence was insufficient or the national reality had to be considered, the consensus opinion of the experts was used through the Delphi methodology. The consensus was approved by the SOCHED board for publication.

Remifentanil-Induced Secondary Hyperalgesia Is Not Prevented By Preoperative Acetazolamide Administration In Patients Undergoing Total Thyroidectomy: A Randomized Controlled Trial.

PURPOSE: Acute administration of remifentanil may lead to opioid-induced hyperalgesia (OIH). Studies in mice suggest that OIH is mediated by impaired anionic homeostasis in spinal lamina I neurons due to a down-regulation of the K+-Cl- co-transporter KCC2, which was reverted using acetazolamide (ACTZ), a carbonic anhydrase inhibitor. We propose that ACTZ prevents remifentanil-mediated OIH in humans. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial between December 2016 and September 2018. Patients were randomly allocated to receive ACTZ (250 mg of ACTZ 2 h before surgery) or placebo. To detect hyperalgesia, mechanical pain threshold (MPT) were measured before and after surgery using hand-held von Frey filaments in the forearm. Anesthesia was maintained with remifentanil at a target effect site of 4.5 ± 0.5 ng/mL, and sevoflurane at an end-tidal concentration of 0.8 MAC corrected for age. RESULTS: In total, 47 patients completed the study. Both groups were comparable in the baseline characteristics and intraoperative variables. Baseline MPT were similar in both groups. However, MPT in the forearm significantly diminished in the time in both groups. Finally, postoperative pain and morphine consumption were similar between groups. CONCLUSION: Both groups developed remifentanil-mediated OIH at 12-18 h after surgery. However, ACTZ did not prevent the MPT reduction in patients undergoing total thyroidectomy.

Incidencia de Hipocalcemia Post Tiroidectomía. Factores predictores (PTH, Fósforo, Magnesio) y protocolo de manejo con alta precoz

Se ha propuesto la medición de PTH como predictor de hipocalcemia postoperatoria transitoria y permanente. No hay un estándar de punto de corte o tiempo de toma de muestra. El objetivo es reportar la incidencia de hipocalcemia post tiroidectomía en un grupo quirúrgico de alto volumen y proponer un protocolo de manejo ambulatorio (esquemas de I a V) según niveles postoperatorios (PO) de calcemia, PTHi (normal, baja o indetectable) y síntomas. Y determinar valores de PTH postoperatoria como predictores de hipocalcemia. En 106 pacientes con tiroidectomía total entre 2019 y 2021 se realiza medición de niveles pre y postoperatorios de calcio, magnesio, fosforo y PTHi. Se observó 29% y 1% de hipocalcemia transitoria ( 12 meses). Los puntos de corte para predecir hipocalcemia fueron PTH < 8,8 pg/ml y < 80% de descenso de % de PTH (d % PTH) al día siguiente. Con el manejo propuesto se indica el alta precoz (promedio 1.05 días) y el costo de la prescripción es acotado. No hay asociación significativa de hipomagnesemia e hiperfosfemia PO con la hipocalcemia PO. El tratamiento más utilizado es de carbonato de calcio exclusivo (esquemas I y II). Los pacientes se mantienen con síntomas leves a las 2 semanas PO en 5% y logran suspender el tratamiento vía oral en 93% en este mismo período. Los protocolos de medición de PTH como predictor de hipocalcemia son muy variados. Cada centro debe conocer y establecer sus propios protocolos de manejo. Con esta experiencia demostramos la utilidad y seguridad de un esquema de manejo basado en calcemia, PTH (normal, baja o indetectable) y síntomas, con indicación de tratamiento profiláctico para todos los pacientes y ajuste ambulatorio seguro y de menor costo que una hospitalización prolongada.

Introduction: PTH measurement has been proposed to predict transient and permanent postoperative hypocalcemia. There is no standard cut-off point or time for sampling. Aim: To report the incidence of post-thyroidectomy hypocalcemia in a high-volume surgical group and propose an outpatient management protocol according to postoperative (PO) calcium levels, iPTH (normal, low, or undetectable), and symptoms. Furthermore, determine postoperative PTH values as predictors of hypocalcemia. Methods: In 106 patients with total thyroidectomy between 2019 and 2021, pre-and postoperative levels of calcium, magnesium, phosphorus, and iPTH were measured. Results: Transient ( 12 months) hypocalcemia was observed in 29% and 1%. Cut-off points to predict hypocalcemia were PTH < 8.8 pg/mL and < 80% decrease in % PTH (d% PTH) the day after surgery. With the proposed management, early discharge is indicated (an average of 1.05 days), and the prescription cost is limited. There is no significant association between PO hypomagnesemia and hyperphosphatemia with PO hypocalcemia. The most widely used treatment is exclusive calcium carbonate (schemes I and II). Patients remain with mild symptoms at two weeks PO in 5% and discontinue oral treatment in 93% in this period. Conclusions: Protocols for measuring PTH as a hypocalcemia predictor vary. Each center must know and establish its management protocols. With this experience, we demonstrate the usefulness and safety of a management scheme based on calcium, PTH (normal, low, or undetectable), and symptoms with an indication of prophylactic treatment for all patients and a safe outpatient setting at a lower cost than prolonged hospitalization.

Downregulation of the Sonic Hedgehog/Gli pathway transcriptional target Neogenin-1 is associated with basal cell carcinoma aggressiveness.

Basal Cell Carcinoma (BCC) is one of the most diagnosed cancers worldwide. It develops due to an unrestrained Sonic Hedgehog (SHH) signaling activity in basal cells of the skin. Certain subtypes of BCC are more aggressive than others, although the molecular basis of this phenomenon remains unknown. We have previously reported that Neogenin-1 (NEO1) is a downstream target gene of the SHH/GLI pathway in neural tissue. Given that SHH participates in epidermal homeostasis, here we analyzed the epidermal expression of NEO1 in order to identify whether it plays a role in adult epidermis or BCC. We describe the mRNA and protein expression profile of NEO1 and its ligands (Netrin-1 and RGMA) in human and mouse control epidermis and in a broad range of human BCCs. We identify in human BCC a significant positive correlation in the levels of NEO1 receptor, NTN-1 and RGMA ligands with respect to GLI1, the main target gene of the canonical SHH pathway. Moreover, we show via cyclopamine inhibition of the SHH/GLI pathway of ex vivo cultures that NEO1 likely functions as a downstream target of SHH/GLI signaling in the skin. We also show how Neo1 expression decreases throughout BCC progression in the K14-Cre:Ptch1lox/lox mouse model and that aggressive subtypes of human BCC exhibit lower levels of NEO1 than non-aggressive BCC samples. Taken together, these data suggest that NEO1 is a SHH/GLI target in epidermis. We propose that NEO1 may be important in tumor onset and is then down-regulated in advanced BCC or aggressive subtypes.

Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED / Study and management of thyroid nodes by non specialist physicians: SOCHED consensus

The thyroid nodule is a frequent cause of primary care consultation. The prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to 67% by the incidental detection of nodules on ultrasound. The vast majority are benign and asymptomatic, staying stable over time. The clinical importance of studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10% of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and Diabetes) asked the Thyroid Study Group to develop a consensus regarding the diagnostic management of the thyroid nodule in Chile, aimed at non-specialist physicians and adapted to the national reality. To this end, a multidisciplinary group of 31 experts was established among university academics, active researchers with publications on the subject and prominent members of scientific societies of endocrinology, head and neck surgery, pathology and radiology. A total of 14 questions were developed with key aspects for the diagnosis and subsequent referral of patients with thyroid nodules, which were addressed by the participants. In those areas where the evidence was insufficient or the national reality had to be considered, the consensus opinion of the experts was used through the Delphi methodology. The consensus was approved by the SOCHED board for publication.

Establecimiento de la primera línea celular de paratoroides humana / Establishment of first cell line of human parathyroid

Para el manejo de pacientes con hipoparatiroidismo postquirúrgico se ha intentado el transplante de células de paratiroides humanas. Los problemas para este eventual tratamiento han sido mantener cultivos duraderos a largo plazo y mantener cultivos con función endrocina normal. Existe un método de inmortalización celular, descrito por Caviedes y cols. que permite mantener células humanas con la capacidad de proliferar sin perder sus funciones de células diferenciadas. Con este método de inmortalización se logrará establecer una línea celular continua de paratiroides humana con función endrocina normal a largo plazo: esta última definida como la capacidad de respuesta secretoria normal de paratohormona (PTH), frente a distintas concentraciones de calcio extracelular. En este artículo se presenta el procedimiento y sus resultados in vitro.

For the handling of patients with postsurgical hypoparathyroidism, the trasplant of cells of human parathyroid has been tried. The difficulties to establish this type of cultures have been to maintain cultures lasting in the term and to maintain cultures with normal endocrin function. A method of cellular inmortalization, described by Caviedes et al. exists that allow to maintain human parathyroid cells with the capacity to proliferate without losing their differentiated functions. With this method of inmortalization it will be managed in the long term to establish a continuous parathyroid cellular line with normal endocrinal function, defined as the capacity of normal secretion of paratohormona (PTH), as opposed to different extracellular calcium concentrations. We present de procedure and its in vitro results.