Disease-free survival and response to therapy of clinically node- negative Papillary Thyroid Cancer treated without central neck dissection: Retrospective study of 321 patients.

BACKGROUND AND OBJECTIVE: Nodal metastases in the central compartment are frequent in papillary thyroid cancer (PTC). However, they are mostly micrometastases with no impact on survival and their relevance on the risk of locoregional relapse is controversial. There is no consensus regarding optimal management of the central neck in patients with PTC cN0. In our center, we do not perform prophylactic central neck dissection (pCND). The objective of this study is to review our long-term results and compare them with the most recent literature. PATIENTS AND METHODS: Retrospective review of patients with PTC who underwent total thyroidectomy (TT) without CND between 2005 and 2017. Primary result was disease-free survival in the neck (DFS). RESULTS: 321 patients were identified, mostly T1-T2 tumors (94.1%). Median follow-up was 90 months. DFS in the central compartment was excellent (96.1% at 10 year's follow-up). 19 patients had cervical recurrence, of which 15 underwent salvage surgery. On their last visit, including salvage surgery when appropriate, 77% of patients had excellent response, 18.7% had indeterminate response, 3.1% had biochemically incomplete response and 1.2% had morphologically incomplete response. Recurrent laryngeal nerve (RLN) paralysis after TT was transient in 4.7% of patients and permanent in 0.9% of patients. There were no RLN paralysis after salvage surgery. Permanent hypoparathyroidism occurred in 3.4% of patients. Only one patient had hypoparathyroidism after salvage surgery and it was permanent. CONCLUSIONS: Based on long-term results and low rate of complications associated with salvage surgery in our experience, we consider routine pCND is not justified.

Therapeutic Management and Long-Term Outcome of Hyperthyroidism in Patients with Antithyroid-Induced Agranulocytosis: A Retrospective, Multicenter Study.

BACKGROUND: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism. METHODOLOGY: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. RESULTS: The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA. CONCLUSIONS: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously.

Mortality in Acromegaly Diagnosed in Older Individuals in Spain Is Higher in Women Compared to the General Spanish Population.

CONTEXT: There are no data on mortality of acromegaly diagnosed in older individuals. OBJECTIVE: This work aimed to compare clinical characteristics, growth hormone-related comorbidities, therapeutic approaches, and mortality rate of patients diagnosed before or after 2010 and to assess overall mortality rate compared with the general Spanish population. METHODS: A retrospective evaluation was conducted among Spanish tertiary care centers of 118 patients diagnosed with acromegaly at age 65 or older. Kaplan-Meier curves were constructed to trace survival, and Cox proportional hazard models were used to assess the risk factors associated with mortality. We also compared mortality with that of the Spanish population by using age- and sex-adjusted standardized mortality ratios (SMRs). RESULTS: No differences were found in first-line treatment or biochemical control, between both periods except for faster biochemical control after 2010. Twenty-nine (24.6%) patients died, without differences between groups, and had a median of follow-up 8.6 years (103, [72.3] months). Overall SMR was 1.02 (95% CI, 0.57-1.54), (0.60; 95% CI, 0.35-1.06) for men and (1.80; 95% CI, 1.07-2.94) for women. The most common cause of death was cardiovascular disease (CVD). CONCLUSION: The mortality in patients with acromegaly diagnosed in older individuals was no different between both periods, and there was no overall SMR difference compared with the general Spanish population. However, the SMR was higher in women. As CVD is the leading cause of mortality, it seems advisable to initiate an intense CVD protective treatment as soon as acromegaly is diagnosed, particularly in women, in addition to tight acromegaly control to prevent excess mortality.

Endocrine and multiple sclerosis outcomes in patients with autoimmune thyroid events in the alemtuzumab CARE-MS studies.

Background: Alemtuzumab is an effective therapy for relapsing multiple sclerosis. Autoimmune thyroid events are a common adverse event. Objective: Describe endocrine and multiple sclerosis outcomes over 6 years for alemtuzumab-treated relapsing multiple sclerosis patients in the phase 3 CARE-MS I, II, and extension studies who experienced adverse thyroid events. Methods: Endocrine and multiple sclerosis outcomes were evaluated over 6 years. Thyroid event cases, excluding those pre-existing or occurring after Year 6, were adjudicated retrospectively by expert endocrinologists independently of the sponsor and investigators. Results: Thyroid events were reported for 378/811 (46.6%) alemtuzumab-treated patients. Following adjudication, endocrinologists reached consensus on 286 cases (75.7%). Of these, 39.5% were adjudicated to Graves' disease, 2.5% Hashimoto's disease switching to hyperthyroidism, 15.4% Hashimoto's disease, 4.9% Graves' disease switching to hypothyroidism, 10.1% transient thyroiditis, and 27.6% with uncertain diagnosis; inclusion of anti-thyroid antibody status reduced the number of uncertain diagnoses. Multiple sclerosis outcomes of those with and without thyroid events were similar. Conclusion: Adjudicated thyroid events occurring over 6 years for alemtuzumab-treated relapsing multiple sclerosis patients were primarily autoimmune. Thyroid events were considered manageable and did not affect disease course. Thyroid autoimmunity is a common but manageable adverse event in alemtuzumab-treated relapsing multiple sclerosis patients.ClinicalTrials.gov Registration Numbers: CARE-MS I (NCT00530348); CARE-MS II (NCT00548405); CARE-MS Extension (NCT00930553).

Factors associated with therapeutic response in acromegaly diagnosed in the elderly in Spain.

Context: Some reports suggest that acromegaly in elderly patients has a more benign clinical behavior and could have a better response to first-generation long-acting somatostatin receptor ligands (SRL). However, there is no specific therapeutic protocol for this special subgroup of patients. Objective: This study aimed at identifying predictors of response to SRL in elderly patients. Design: Multicentric retrospective nationwide study of patients diagnosed with acromegaly at or over the age of 65 years. Results: One-hundred and eighteen patients (34 men, 84 women, mean age at diagnosis 71.7 ± 5.4 years old) were included. Basal insulin-like growth factor type 1 (IGF-1) above the upper limit of normal (ULN) and growth hormone (GH) levels (mean ± SD) were 2.7 ± 1.4 and 11.0 ± 11.9 ng/ml, respectively. The mean maximal tumor diameter was 12.3 ± 6.4 mm, and up to 68.6% were macroadenoma. Seventy-two out of 118 patients (61.0%) underwent surgery as primary treatment. One-third of patients required first-line medical treatment due to a rejection of surgical treatment or non-suitability because of high surgical risk. After first-line surgery, 45/72 (63.9%) were in disease remission, and 16/34 (46.7%) of those treated with SRL had controlled disease. Patients with basal GH at diagnosis ≤6 ng/ml had lower IGF-1 levels and had smaller tumors, and more patients in this group reached control with SRL (72.7% vs. 33.3%; p < 0.04) [OR: 21.3, IC: 95% (2.4-91.1)], while male patients had a worse response [OR: 0.09, IC 95% (0.01-0.75)]. The predictive model curve obtained for SRL response showed an AUC of 0.82 CI (0.71-0.94). Conclusions: The most frequent phenotype in newly diagnosed acromegaly in the elderly includes small adenomas and moderately high IGF-1 levels. GH at diagnosis ≤6 ng/ml and female gender, but not age per se, were associated with a greater chance of response to SRL.

Recovery of parathyroid function in patients with thyroid cancer treated by total thyroidectomy: An analysis of 685 patients with hypoparathyroidism at discharge of surgery.

OBJECTIVE: We aimed to study the predictive factors for recovery of parathyroid function in hypoparathyroid patients after total thyroidectomy for thyroid cancer. METHODS: We designed a retrospective, multicentre and nation-wide analysis of patients with total thyroidectomy who were seen in twenty endocrinology departments from January to March 2018. We selected patients with histologically proven thyroid cancer and retrieved information related to surgical procedure and thyroid cancer features. Survival analysis and Cox regression analysis were used to study the relationship between these variables and the recovery of parathyroid function. RESULTS: From 685 patients with hypoparathyroidism at discharge of surgery, 495 (72.3%) recovered parathyroid function over time. Kaplan-Meier analysis showed that this recovery was significantly related to the presence of specialized surgical team (P<0.001), identification of parathyroid glands at surgery (P<0.001), papillary histopathology (P=0.040), and higher levels of postoperative calcium (Ca) (P<0.001) and parathyroid hormone (PTH) (P<0.001). Subjects with gross extrathyroidal extension (P=0.040), lymph node metastases (P=0.004), and surgical re-intervention after initial surgery (P=0.024) exhibited a significant risk of persistence of hypoparathyroidism. Multivariate Cox regression analysis showed that the significant and independent factors for recovery of parathyroid function were postoperative concentrations of Ca (P=0.038) and PTH (P=0.049). The presence of lymph node metastases was a negative predictor of recuperation of parathyroid function (P=0.042) in this analysis. CONCLUSION: In patients with thyroid cancer, recovery of parathyroid function after total thyroidectomy was directly related to postoperative Ca and PTH concentrations, and inversely related to lymph node metastases.

Late Recovery of Parathyroid Function After Total Thyroidectomy: A Case-Control Study.

The clinical characteristics of patients with postoperative hypoparathyroidism who recover parathyroid function more than 12 months after surgery have not been studied. We aimed to evaluate whether the intensity of replacement therapy with calcium and calcitriol is related to the late recovery of parathyroid function. We compared the demographic, surgical, pathological, and analytical features of two groups of patients: cases, i. e., late recovery patients (those who recover parathyroid function>1 year after thyroidectomy, n=40), and controls, i. e., patients with permanent hypoparathyroidism (n=260). Replacement therapy with calcium and calcitriol was evaluated at discharge of surgery, 3-6 months, 12 months, and last visit. No significant differences were found in clinical, surgical, pathological, or analytical characteristics between cases and controls. The proportion of cases who required treatment with calcium plus calcitriol at 12 months was significantly lower than that found in controls (p<0.001). Furthermore, daily calcium and calcitriol doses in controls were significantly higher than those in cases at 3-6 months (p=0.014 and p=0.004, respectively) and at 12 months (p<0.001 and p=0.043, respectively). In several models of logistic regression analysis therapy with calcium and calcitriol at 12 months was negatively related to late recovery of parathyroid function. Although delayed recuperation of parathyroid function after total thyroidectomy is uncommon (13%), follow-up beyond 12 months is necessary in patients with postoperative hypoparathyroidism, especially in those whose needs of treatment with Ca and calcitriol are reducing over time.

Permanent postoperative hypoparathyroidism: an analysis of prevalence and predictive factors for adequacy of control in a cohort of 260 patients.

BACKGROUND: Recent guidelines for the treatment of hypoparathyroidism emphasize the need for long-term disease control, avoiding symptoms and hypocalcaemia. Our aim has been to analyze the prevalence of poor disease control in a national cohort of patients with hypoparathyroidism, as well as to evaluate predictive variables of inadequate disease control. METHODS: From a nation-wide observational study including a cohort of 1792 patients undergoing total thyroidectomy, we selected 260 subjects [207 women and 53 men, aged (mean ± SD) 47.2±14.8 years] diagnosed with permanent hypoparathyroidism. In every patient demographic data and details on surgical procedure, histopathology, calcium (Ca) metabolism, and therapy with Ca and calcitriol were retrospectively collected. A patient was considered not adequately controlled (NAC) if presented symptoms of hypocalcemia or biochemical data showing low serum Ca levels or high urinary Ca excretion. RESULTS: Two hundred and twenty-one (85.0%) patients were adequately controlled (AC) and 39 (15.0%) were NAC. Comparison between AC and NAC patients did not show any significant difference in demographic, surgical, and pathological features. Rate of hospitalization during follow-up was significantly higher among NAC patients in comparison with AC patients (35.9% vs. 10.9%, P<0.001). Dose of oral Ca and calcitriol were also significantly higher in NAC subjects. In a subgroup of 129 patients with serum parathyroid hormone (PTH) levels available, we found that NAC patients exhibited significantly lower postoperative PTH concentrations than AC patients [median (interquartile range) 3 (1.9-7.8) vs. 6.9 (3.0-11) pg/mL; P=0.009]. CONCLUSIONS: In a nation-wide cohort of 260 subjects with definitive hypoparathyroidism, 15% of them had poor disease control. These patients required higher doses of oral Ca and calcitriol, had higher rate of hospitalization during follow-up and showed lower PTH concentrations in the postoperative period.

Diagnóstico y tratamiento del nódulo tiroideo en España. Resultados de una encuesta nacional / Diagnosis and treatment of thyroid nodules in Spain. Results of a national survey

INTRODUCCIÓN: El nódulo tiroideo (NT) es un motivo de consulta frecuente en la práctica diaria. El objetivo de este estudio es conocer el proceso diagnóstico y terapéutico del NT en nuestro medio y evaluar el estado actual sobre la existencia y estructura de las consultas de alta resolución de NT. MATERIAL Y MÉTODOS: Los miembros de la Sociedad Española de Endocrinología y Nutrición fueron invitados en el año 2018 a participar en una encuesta online sobre los procesos diagnósticos y terapéuticos del NT. RESULTADOS: Se recibieron 211 encuestas válidas. El 30,8% de los encuestados indicaron que existía consulta de alta resolución de NT en su medio, siendo el endocrinólogo el responsable mayoritario de realizar la ecografía (87,7%) y la punción-aspiración con aguja fina (PAAF) (69,2%). Respecto a la clasificación ecográfica, el 32,7% utilizaban criterios ATA y el 32,2% criterios TI-RADS (el 22,7% no utilizaba ninguna clasificación). El 35,5% comprobaban in situ la idoneidad de la muestra y el análisis molecular en el 8,1%. El 65,4% plantearían alta del NT tras 5 años de seguimiento y PAAF benigna. Ante un Bethesda III, el 50,2% de los encuestados repetirían la PAAF y un 35,5% optarían por cirugía; ante un Bethesda IV, el 95,8% optarían por cirugía. CONCLUSIONES: La consulta de alta resolución de NT es una estructura con una creciente introducción en nuestro medio, siendo el endocrinólogo el responsable fundamental de realizar la ecografía y la PAAF. La práctica clínica habitual en nuestro medio es concordante con la mayoría de las recomendaciones de las guías de práctica clínica de NT

INTRODUCTION: Thyroid nodule (TN) is a common reason for consultation in daily practice. The purpose of this study was to evaluate the diagnosis and treatment of TNs in our environment and to assess the current status regarding the existence and structure of high-resolution TN clinics. MATERIAL AND METHODS: Members of the Spanish Society of Endocrinology and Nutrition were invited in 2018 to participate in an online survey on the diagnostic and therapeutic processes of TN. RESULTS: A total of 211 valid surveys were received. Of all respondents, 30.8% stated that there were high-resolution TN clinics in their environment, with the endocrinologist being the main person responsible for performing ultrasonography (87.7%) and fine needle aspiration (FNA) (69.2%). For ultrasound classification of TNs, 32.7% used the ATA criteria, 32.2% the TI-RADS criteria, and 22.7% no classification. In situ verification of sample suitability was performed in 35.5% of the cases, and molecular analysis in 8.1%. With regard to clinical discharge, 65.4% would consider it after 5 years of follow-up and with a benign FNA. In the event of a Bethesda III result, 50.2% of respondents would repeat FNA and 35.5% would opt for surgery; if a Bethesda IV result was found, 95.8% would opt for surgery. CONCLUSIONS: High-resolution TN clinics are structures increasingly implemented in our environment where the endocrinologist is the main person responsible for performing ultrasonography and FNA. The standard clinical practice in our specialty is consistent with most recommendations concerning clinical practice guidelines for TNs

Adenomas hipofisarios no funcionantes: epidemiología, clínica y evolución posquirúrgica / Non-functioning pituitary adenomas: epidemiology, clinical and postoperative outcome

INTRODUCCIÓN: Los adenomas hipofisarios no funcionantes son el grupo tumoral más frecuente en la región selar. Suelen ser neoplasias benignas diagnosticadas por síntomas visuales u hormonales, aunque no es infrecuente detectarlos como un hallazgo casual. OBJETIVO: Analizar los aspectos clínicos hallados en esta enfermedad y su respuesta tras el tratamiento quirúrgico. PACIENTES Y MÉTODOS: En una serie de 100 casos, se analizaron datos epidemiológicos, clínicos, endocrinológicos, visuales y radiológicos antes y después del tratamiento quirúrgico, y se recogen las complicaciones relacionadas con la cirugía y el seguimiento a largo plazo. RESULTADOS: El síntoma más frecuente en el momento del diagnóstico fue la afectación del campo visual (62%), y sólo el 7% de los adenomas se trataba de un hallazgo casual. El déficit hormonal más frecuente era el hipogonadismo hipogonadótropo (48%). Tras la cirugía se observó recuperación completa del defecto campimétrico en el 54,8% de los pacientes, con sólo un 1% de empeoramiento tras la cirugía, y la incidencia de diabetes insípida fue del 4%. La resección fue superior al 95% en el 63% de los casos, a pesar de que el porcentaje de adenomas con invasión del seno cavernoso en grados altos fue elevado (45%). CONCLUSIONES: Aunque el síntoma más frecuente de los adenomas hipofisarios no funcionantes es la afectación campimétrica, ésta tiene una excelente respuesta a la cirugía si se realiza dentro del tiempo adecuado. El grado de invasión del seno cavernoso parece el factor más limitante para una resección quirúrgica completa

INTRODUCTION: Non-functioning pituitary adenomas are the most frequent tumor group in the sellar region. They are usually benign neoplasms diagnosed after visual or hormonal symptoms, although it is not uncommon to detect them as a casual finding. AIM: To analyze the clinical aspects found in this disease and its response after surgical treatment. PATIENTS AND METHODS: In a series of 100 cases, epidemiological, clinical, endocrinological, visual and radiological data were analyzed before and after surgical treatment, as well as the complications related to surgery and long-term follow-up. RESULTS: The most frequent symptom at the time of diagnosis was visual field involvement (62%), and only the 7% of adenomas were a casual finding. The most common hormonal deficit was hypogonadotropic hypogonadism (48%). After surgery, complete recovery of the visual field defect was observed in 54.8% of the patients, only 1% worsening after surgery, and the incidence of diabetes insipidus was 4%. The resection was superior to 95% in 63% of cases, although the percentage of adenomas with invasion of the cavernous sinus in Knosp grades 3 and 4 it was high (45%). CONCLUSIONS: Although the most frequent symptom of non-functioning pituitary adenomas is campimetric involvement, it has an excellent response to surgery if it is performed within the appropriate time. The grade of invasion of the cavernous sinus is the most limiting factor for a complete surgical resection

Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders: An Updated Practical Tool for Physicians and Patients.

Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care.

Identification of Resistance to Exogenous Thyroxine in Humans.

Background: Thyroxine (T4) to triiodothyronine (T3) deiodination in the hypothalamus/pituitary is mediated by deiodinase type-2 (D2) activity. Dio2(-/-) mice show central resistance to exogenous T4. Patients with resistance to exogenous thyroxine (RETH) have not been described. The aim of this study was to identify hypothyroid patients with thyrotropin (TSH) unresponsiveness to levothyroxine (LT4) and to characterize the clinical, hormonal, and genetic features of human RETH. Methods: We investigated hypothyroid patients with elevated TSH under LT4 treatment at doses leading to clinical and/or biochemical hyperthyroidism. TSH and free T4 (fT4) were determined by chemiluminescence, and total T4, T3, and reverse T3 (rT3) by radioimmunoassay. TSH/fT4 ratio at inclusion and T3/T4, rT3/T4, and T3/rT3 ratios at follow-up were compared with those from patients with resistance to thyroid hormone (RTH) due to thyroid hormone receptor-ß (THRB) mutations. DIO2, including the Ala92-D2 polymorphism, selenocysteine binding protein 2 (SECISBP2), and THRB were fully sequenced. Results: Eighteen hypothyroid patients (nine of each sex, 3-59 years) treated with LT4 showed elevated TSH (15.5 ± 4.7 mU/L; reference range [RR]: 0.4-4.5), fT4 (20.8 ± 2.4 pM; RR: 9-20.6), and TSH/fT4 ratio (0.74 ± 0.25; RR: 0.03-0.13). Despite increasing LT4 doses from 1.7 ± 1.0 to 2.4 ± 1.7 µg/kg/day, TSH remained elevated (6.9 ± 2.7 mU/L). Due to hyperthyroid symptoms, LT4 doses were reduced, and TSH increased again to 7.9 ± 3.2 mU/L. In the euthyroid/hyperthyrotropinemic state, T3/T4 and T3/rT3 ratios were decreased (9.2 ± 2.4, RR: 11.3-15.3 and 2.5 ± 1.4, RR: 7.5-8.5, respectively) whereas rT3/T4 was increased (0.6 ± 0.2; RR: 0.43-0.49), suggesting reduced T4 to T3 and increased T4 to rT3 conversion. These ratios were serum T4-independent and were not observed in RTH patients. Genetic testing was normal. The Ala92-D2 polymorphism was present in 7 of 18 patients, but the allele dose did not correlate with RETH. Conclusions: Human RETH is characterized by iatrogenic thyrotoxicosis and elevated TSH/fT4 ratio. In the euthyroid/hyperthyrotropinemic state, it is confirmed by decreased T3/T4 and T3/rT3 ratios, and elevated rT3/T4 ratio. This phenotype may guide clinicians to consider combined T4+T3 therapy in a targeted fashion. The absence of germline DIO2 mutations suggests that aberrant post-translational D2 modifications in pituitary/hypothalamus or defects in other genes regulating the T4 to T3 conversion pathway could be involved in RETH.

Diagnosis and treatment of thyroid nodules in Spain. Results of a national survey. / Diagnóstico y tratamiento del nódulo tiroideo en España. Resultados de una encuesta nacional.

INTRODUCTION: Thyroid nodule (TN) is a common reason for consultation in daily practice. The purpose of this study was to evaluate the diagnosis and treatment of TNs in our environment and to assess the current status regarding the existence and structure of high-resolution TN clinics. MATERIAL AND METHODS: Members of the Spanish Society of Endocrinology and Nutrition were invited in 2018 to participate in an online survey on the diagnostic and therapeutic processes of TN. RESULTS: A total of 211 valid surveys were received. Of all respondents, 30.8% stated that there were high-resolution TN clinics in their environment, with the endocrinologist being the main person responsible for performing ultrasonography (87.7%) and fine needle aspiration (FNA) (69.2%). For ultrasound classification of TNs, 32.7% used the ATA criteria, 32.2% the TI-RADS criteria, and 22.7% no classification. In situ verification of sample suitability was performed in 35.5% of the cases, and molecular analysis in 8.1%. With regard to clinical discharge, 65.4% would consider it after 5 years of follow-up and with a benign FNA. In the event of a Bethesda III result, 50.2% of respondents would repeat FNA and 35.5% would opt for surgery; if a Bethesda IV result was found, 95.8% would opt for surgery. CONCLUSIONS: High-resolution TN clinics are structures increasingly implemented in our environment where the endocrinologist is the main person responsible for performing ultrasonography and FNA. The standard clinical practice in our specialty is consistent with most recommendations concerning clinical practice guidelines for TNs.

Oseltamivir-induced toxic epidermal necrolysis in a patient with Cushing's disease.

We report a case of a patient with Cushing's disease with oseltamivir-induced toxic epidermal necrolysis, who was treated with cyclosporine with favorable evolution. There is only one case reported of Cushing's disease and toxic epidermal necrolysis and very few oseltamivir-induced toxic epidermal necrolysis cases in literature. This report also discusses the role that the preexisting hypercortisolism condition may have played in the development and favorable resolution of the toxic epidermal necrolysis.

Correction to: Prevalence and risk factors for hypoparathyroidism following total thyroidectomy in Spain: a multicentric and nation-wide retrospective analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy.

Thyroid dysfunction (TD) frequently occurs as an autoimmune complication of immune reconstitution therapy (IRT), especially in individuals with multiple sclerosis treated with alemtuzumab, a pan-lymphocyte depleting drug with subsequent recovery of immune cell numbers. Less frequently, TD is triggered by highly active antiretroviral therapy (HAART) in patients infected with human immunodeficiency virus (HIV), or patients undergoing bone-marrow/hematopoietic-stem-cell transplantation (BMT/HSCT). In both alemtuzumab-induced TD and HIV/HAART patients, the commonest disorder is Graves' disease (GD), followed by hypothyroidism and thyroiditis; Graves' orbitopathy is observed in some GD patients. On the contrary, GD is rare post-BMT/HSCT, where hypothyroidism predominates probably as a consequence of the associated radiation damage. In alemtuzumab-induced TD, the autoantibodies against the thyrotropin receptor (TRAb) play a major role, and 2 main aspects distinguish this condition from the spontaneous form: (1) up to 20% of GD cases exhibit a fluctuating course, with alternating phases of hyper- and hypothyroidism, due to the coexistence of TRAb with stimulating and blocking function; (2) TRAb are also positive in about 70% of hypothyroid patients, with blocking TRAb responsible for nearly half of the cases. The present guidelines will provide up-to-date recommendations and suggestions dedicated to all phases of IRT-induced TD: (1) screening before IRT (recommendations 1-3); (2) monitoring during/after IRT (recommendations 4-7); (3) management of TD post-IRT (recommendations 8-17). The clinical management of IRT-induced TD, and in particular GD, can be challenging. In these guidelines, we propose a summary algorithm which has particular utility for nonspecialist physicians and which is tailored toward management of alemtuzumab-induced TD. However, we recommend prompt referral to specialist endocrinology services following diagnosis of any IRT-induced TD diagnosis, and in particular for pregnant women and those considering pregnancy.

Orbital Radioiodine Uptake on Scintigraphy in a Patient with Thyroid Cancer.

Background: Orbital radioiodine uptake in patients with thyroid cancer is very uncommon with only a few reported cases, most of them being metastasis. The accumulation of 131I in nonthyroidal tissues and body fluids can lead to false-positive results in scintigraphy, which are sometimes difficult to differentiate from true metastases. Case Report: A post-therapy 131I whole-body (WBI) scintigraphy in an asymptomatic 57-year-old female with papillary thyroid carcinoma (PTC) previously treated with total thyroidectomy and 6 ablative radioiodine doses showed a focal uptake in the right eyeball region. The lesion, placed in the orbital space, was surgically removed, and histology revealed a conjunctival inclusion cyst. Discussion: Ocular and orbital metastases from thyroid cancer, as well as some non-neoplastic disorders or contamination, are possible causes for 131I uptake in the orbital region in scintigraphy. Conjunctival inclusion cyst is a condition associated with incidental 131I uptake that had not been reported before and should be ruled out as a non-metastatic cause of orbital radioiodine uptake in patients with PTC.

Prevalence and risk factors for hypoparathyroidism following total thyroidectomy in Spain: a multicentric and nation-wide retrospective analysis.

PURPOSE: The prevalence of postoperative hypoparathyroidism has been studied in registries and in surgical series with highly variable and imprecise results. However, the frequency of this hormonal deficiency in the clinical practice of endocrinologists is not known with accuracy. We aimed to assess the prevalence and risk factors of hypoparathyroidism in patients undergoing total thyroidectomy in Spain. METHODS: We designed a retrospective, multicentre and nation-wide protocol including all patients with total thyroidectomy who were seen in the endocrinology clinic of the participant centers from January to March 2018. Prevalence of hypoparathyroidism was evaluated at discharge of surgery, 3-6 months after surgery, 12 months after surgery and at last visit. Twenty hospitals participated in the study. RESULTS: Of 1792 patients undergoing total thyroidectomy, 866 (48.3%) developed postoperative hypoparathyroidism at discharge of surgery. Most of them recover parathyroid function over time. Prevalence of hypoparathyroidism at 3-6 months, 12 months and at last visit was 22.9%, 16.7% and 14.5%, respectively. The risk of developing definitive hypoparathyroidism was related to the presence of parathyroid tissue at histology, lymph node dissection, and two-stage thyroidectomy. Patients with thyroid cancer, with higher postoperative calcium levels and treated by expert surgical teams exhibited lower risk of developing permanent hypoparathyroidism. CONCLUSIONS: Although most patients with postsurgical hypoparathyroidism recover parathyroid function, the prevalence of permanent disease in clinical practice is non negligible (14.5%). Postoperative calcium, extent and timing of surgery, the presence of cancer, expert surgical team, and parathyroid tissue at histology are predictors of permanent hypoparathyroidism.

Implicaciones en pediatría del primer consenso internacional para el diagnóstico y asistencia a pacientes con pseudohipoparatiroidismo y enfermedades relacionadas / Implication in Paediatrics of the First International Consensus Statement for the Diagnosis and management of pseudohypoparathyroidism and related disorders

Desde que en 1942 Albright y colaboradores describieran por primera vez el pseudohipoparatiroidismo como la existencia de hipocalcemia e hiperfosfatemia asociadas a resistencia tisular a la hormona paratiroidea (PTH) en presencia de una función renal normal, se han realizado grandes avances en la caracterización clínica y genética de los pacientes afectos de esta enfermedad. De hecho, no solo se han identificado las alteraciones moleculares responsables, sino que se ha podido establecer que variantes en otros genes de la misma vía de señalización, PTH/PTHrP a través de la proteína Gsα, son la causa de enfermedades que comparten determinadas manifestaciones clínicas con el pseudohipoparatiroidismo. En el ámbito pediátrico, los primeros síntomas o signos que deben hacernos pensar en alteraciones en esta vía son la presencia de osificaciones subcutáneas, la braquidactilia y/o la obesidad de inicio precoz, seguidas en el tiempo por la posible aparición de resistencia a la PTH. Esta sospecha clínica deberá ser confirmada mediante un diagnóstico molecular que permita el correcto seguimiento clínico coordinado y multidisciplinar. Entre los aspectos a tener en cuenta en la atención de estos pacientes se incluye la evaluación al diagnóstico y seguimiento de la eventual presencia de resistencia a la PTH y a la hormona tirotropa (TSH), deficiencia de hormona de crecimiento (GH), hipogonadismo, alteraciones esqueléticas, alteraciones de la salud dental, obesidad, resistencia a la acción de la insulina, intolerancia a la glucosa o diabetes mellitus tipo 2 e hipertensión, así como osificaciones ectópicas (subcutáneas o con afectación de tejidos más profundos) y alteración del desarrollo neurocognitivo

Since Albright and co-workers described pseudohypoparathyroidism in 1942 as the combined presence of hypocalcaemia and hyperphosphataemia associated with the existence of tissue resistance to parathyroid hormone (PTH) action upon normal renal function, great advances have been made in the clinical and genetic profile of patients affected by this condition. Furthermore, not only have genetic bases of pseudohypoparathyroidism been unravelled, but also variants in other genes involved in the PTH/PTHrP signalling pathway through Gsα, have been identified as the cause of diseases that share clinical features with pseudohypoparathyroidism. In the paediatric setting, the first symptoms suggesting the impairment of this signalling pathway are the presence of subcutaneous ossifications, brachydactyly and/or early onset obesity, followed by the possible development of PTH resistance. This clinical suspicion should be confirmed by an accurate molecular diagnosis to allow for coordinated multidisciplinary clinical management. Among the features of this group of disorders, physicians should pay attention to evaluation of PTH and/or thyrotropin (TSH) resistance at diagnosis and throughout follow-up, as well as growth hormone deficiency, hypogonadism, skeletal deformities, dental impairment, obesity, insulin resistance, impaired glucose tolerance or type 2 diabetes mellitus and hypertension, as well as ectopic ossifications (either subcutaneous or affecting deeper tissues) and impairment of neurocognitive development