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.

Alzheimer's Disease and Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models.

Alzheimer's disease (AD) is the most common cause of dementia. Epidemiological studies show the association between AD and type 2 diabetes (T2DM), although the mechanisms are not fully understood. Dietary habits and lifestyle, that are risk factors in both diseases, strongly modulate gut microbiota composition. Also, the brain-gut axis plays a relevant role in AD, diabetes and inflammation, through products of bacterial metabolism, like short-chain fatty acids. We provide a comprehensive review of current literature on the relation between dysbiosis, altered inflammatory cytokines profile and microglia in preclinical models of AD, T2DM and models that reproduce both diseases as commonly observed in the clinic. Increased proinflammatory cytokines, such as IL-1ß and TNF-α, are widely detected. Microbiome analysis shows alterations in Actinobacteria, Bacteroidetes or Firmicutes phyla, among others. Altered α- and ß-diversity is observed in mice depending on genotype, gender and age; therefore, alterations in bacteria taxa highly depend on the models and approaches. We also review the use of pre- and probiotic supplements, that by favoring a healthy microbiome ameliorate AD and T2DM pathologies. Whereas extensive studies have been carried out, further research would be necessary to fully understand the relation between diet, microbiome and inflammation in AD and T2DM.

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.

Clinical and Ultrasound Thyroid Nodule Characteristics and Their Association with Cytological and Histopathological Outcomes: A Retrospective Multicenter Study in High-Resolution Thyroid Nodule Clinics.

INTRODUCTION: Thyroid nodules are a common finding. A high-resolution thyroid nodule clinic (HR-TNC) condenses all tests required for the evaluation of thyroid nodules into a single appointment. We aimed to evaluate the clinical outcomes at HR-TNCs. DESIGN AND METHODS: A retrospective cross-sectional multicenter study including data from four HR-TNCs in Spain. We evaluated fine-needle aspiration (FNA) indications and the association between clinical and ultrasound characteristics with cytological and histopathological outcomes. RESULTS: A total of 2809 thyroid nodules were included; FNA was performed in 82.1%. Thyroid nodules that underwent FNA were more likely larger, isoechoic, with microcalcifications, and in younger subjects. The rate of nondiagnostic FNA was 4.3%. A solid component, irregular margins or microcalcifications, significantly increased the odds of Bethesda IV-V-VI (vs. Bethesda II). Irregular margins and a solid component were independently associated with increased odds of malignancy. Thyroid nodules <20 mm and ≥20-<40 mm had a 6.5-fold and 3.3-fold increased risk for malignancy respectively in comparison with those ≥40 mm. CONCLUSION: In this large multicenter study, we found that the presence of a solid component and irregular margins are factors independently related to malignancy in thyroid nodules. Since nodule size ≥40 mm was associated with the lowest odds of malignancy, this cut-off should not be a factor leading to indicate thyroid surgery. HR-TNCs were associated with a low rate of nondiagnostic FNA.

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.

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.

Ghrelin mitigates ß-cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat.

BACKGROUND: Ghrelin is a peptide hormone with pleiotropic effects. It stimulates cell proliferation and inhibits apoptosis-mediated cell death. It prevents diabetes mellitus in several models of chemical, surgical and biological toxic insults to pancreas in both in vivo and in vitro models and promotes glucose-stimulated insulin secretion under cytotoxic conditions. It has not yet been tested in vivo in an autoimmune model of diabetes with a persistent insult to the ß-cell. Given the immunomodulating effects of ghrelin and its trophic effects on ß-cells, we hypothesized that ghrelin treatment during the early stages of insulitis would delay diabetes onset. METHODS: BioBreeding/Worcester male rats received ghrelin (10 ng/kg/day) before insulitis development. Glucose metabolism was characterized by glucose and insulin tolerance tests. ß-cell mass, islet area, islet number, ß-cell clusters, proliferation and apoptosis and degree of insulitis were analysed by histomorphometry. A Kaplan-Meier survival curve was plotted and analysed applying the log-rank (Mantel-Cox) test. RESULTS: Ghrelin treatment significantly reduced the probability of developing diabetes in our model (p < 0.0001). It decreased islet infiltration and partially prevented ß-cell mass loss, enabling the maintenance of ß-cell neogenesis and proliferation rates. Furthermore, ghrelin treatment did not induce any metabolic perturbations. CONCLUSIONS: These findings support the hypothesis that ghrelin delays the development of autoimmune diabetes by attenuating insulitis and supporting ß-cell mass. GENERAL SIGNIFICANCE: Ghrelin promotes ß-cell viability and function through diverse mechanisms that may have significant implications for diabetes prevention, therapy and also transplant success of both islets and complete pancreas. Copyright © 2016 John Wiley & Sons, Ltd.

Ghrelin's Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on ß-Cell Functionality.

Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for ß-cells known as insulitis, which results in loss of ß-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve ß-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1ß, IFNγ, and TNFα and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on ß-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on ß-cells.

Déficit de hormona de crecimiento por depósitos de hierro hipofisarios en paciente con carencia de piruvato cinasa / Growth hormone deficiency secondary to pituitary iron deposition in a pyruvate kinase deficient patient

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Efectividad y seguridad de un modelo protocolizado de control glucémico en el medio hospitalario / Effectiveness and safety of a blood glucose control protocol in hospital

OBJETIVO: Evaluar la efectividad y seguridad de un protocolo de control glucémico para pacientes con diabetes mellitus (DM) en el medio hospitalario. MATERIAL Y MÉTODOS: Estudio de intervención, prospectivo y abierto realizado en pacientes con DM ingresados en planta de hospitalización convencional. Los pacientes fueron asignados a un grupo de intervención (protocolo de control glucémico), o a un grupo control (tratamiento para la diabetes según práctica habitual) con evaluaciones cada 48 h, estableciéndose como objetivo primario la obtención de glucemias preprandiales entre 80 y 180mg/dl, siendo el objetivo secundario la ausencia de hipoglucemias. RESULTADOS: Se incluyó a 104 pacientes de 67,8±9,2 años de edad, 13,7±10,2 años de evolución de diabetes y HbA1c media de 7,8±1,5%. En el grupo de intervención se observó una mejoría significativa en las glucemias capilares antes del desayuno, almuerzo, cena y media de 24 h tanto con respecto al día 0 como comparativamente con el grupo control, alcanzando el 7.° día de seguimiento una glucemia media de 148,2±30,3mg/dl. El porcentaje de pacientes con glucemia entre 80 y 180mg/dl superó el 50% desde el día 4 para la glucemia en ayunas, desde el día 5 para la glucemia antes del almuerzo y desde el día 7 para la glucemia antes de la cena. Siete pacientes (13,4%) presentaron hipoglucemias leves en el grupo de intervención y 9 (17,3%) en el grupo control (p = 0,817). CONCLUSIONES: La aplicación de un protocolo de control glucémico en el medio hospitalario es efectiva para mejorar el control metabólico y alcanzar los objetivos establecidos, con un bajo número de hipoglucemias asociadas

OBJECTIVE: To evaluate the effectiveness and safety of a glucose control protocol designed to manage patients with diabetes in hospital. MATERIAL AND METHODS: An interventional, prospective and open study was designed for patients with diabetes admitted in a conventional hospital setting. Patients were randomized to an intervention group (glucose control protocol) or to a control group (conventional treatment for diabetes). Blood glucose was performed every 48 hours. The primary endpoint was to obtain a pre-prandial blood glucose between 80 and 180 mg/dl, and the secondary endpoint was the absence of hypoglycemia. RESULTS: The study included a total of 104 patients (51.0% male), with a mean age of 67.8 ± 9.2 years old, 13.7 ± 10.2 years since onset of diabetes, and mean HbA1c of 7.8±1.5%. The patients in the intervention group showed a significant improvement in glucose control before all meals as well as in the 24 hour mean compared to day 0 and with the control group. In the first week, patients achieved a mean blood glucose of 148.2 ± 30.3 mg/dl. The percentage of patients with blood glucose between 80 and 180mg/dl gradually increased, exceeding 50% of patients from day 4 for fasting blood glucose, day 5 for blood glucose before lunch, and day 7 for blood glucose before dinner. Seven patients (13.4%) had mild hypoglycemia in the intervention group, and nine (17.3%) in the control group (P = 0.817). CONCLUSIONS: The use of a blood glucose control protocol in hospital settings is effective for improving metabolic control and to achieve the targets, with a low rate of associated hypoglycemia

Evaluación del grado de consecución de objetivos de control metabólico en pacientes con diabetes mellitus tipo 2 / Evaluation of metabolic control targets in patients with type 2 diabetes mellitus

Objetivo Evaluar el grado de consecución de objetivos metabólicos en diabetes tipo 2 (DM-2) en la Unidad de Gestión Clínica (UGC) de Endocrinología y Nutrición del Hospital Puerta del Mar (Cádiz) de 2005 a 2008.Método Explotación de la base de datos incluida en la aplicación informática HP-Doctor utilizada para todos los pacientes atendidos en nuestra UGC (hospitalización, consultas y centros periféricos). Se incluyeron los pacientes con diagnóstico principal o secundario DM-2. Analizamos características clínicas, complicaciones crónicas, fármacos y porcentaje de pacientes que cumplen los niveles medios anuales de hemoglobina glucosilada (HbA1c) y colesterol asociado a lipoproteínas de baja densidad (LDLc).Resultados De 2005 a 2008 se ha incrementado un 108,7% el número de pacientes con DM-2 en seguimiento con historia informatizada. En 2008, evaluamos 1.177 pacientes, siendo 10,8% fumadores activos y 53% hipertensos, y presentando el 51,2% y 12,6% retinopatía y enfermedad cardiovascular, respectivamente. Durante el periodo de estudio, el porcentaje de pacientes con HbA1c media <7% se mantuvo estable (2005: 31,7%; 2008: 30,4%), aumentaron aquellos con LDLc <100mg/dl y solo el 9,2% de los pacientes alcanzaron el objetivo combinado de HbA1c <7% y LDLc <100mg/dl.Conclusiones En 2008, solo 30% y 25% de los pacientes con DM-2 mantenían niveles medios de HbA1c <7% y de LDLc <100mg/dl, respectivamente. Es necesario optimizar el control metabólico en pacientes con DM-2 (AU)

Objective To evaluate the extent to which metabolic targets in type 2 diabetes (DM-2) are achieved in the Endocrinology and Clinical Nutrition Unit of the Hospital Puerta del Mar in Cadiz (Spain) from 2005 to 2008.MethodThe database included in the computer application HP-Doctor used for all patients attended in our unit (admissions, consultations and peripheral centers) was analyzed. All patients with a principal or secondary diagnosis of DM-2 were included. Clinical characteristics, chronic complications, drug treatment and the percentage of patients who achieved annual mean targets of glycosylated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDLc) were analyzed. Results From 2005 to 2008, the number of DM-2 patients with computerized records increased by 108.7%. In 2008, 1,177 patients were evaluated. A total of 10.8% were active smokers, 53% had hypertension, and 51.2% and 12.6% presented with retinopathy and cardiovascular disease, respectively. During the study period, the percentage of patients with a mean HbA1c <7% was similar (2005: 31.7% 2008: 30.4%), those with LDLc <100mg/dl increased from 19.2% to 25.6% and only 9.2% of patients achieved both targets, HbA1c <7% and LDLc <100mg/dl. Conclusions In 2008, only 30% of DM-2 patients achieved a mean HbA1c < 7% and only 25% had LDLc < 100mg/dl. Metabolic control in DM-2 patients should be improved (AU)

[Evaluation of metabolic control targets in patients with type 2 diabetes mellitus]. / Evaluación del grado de consecución de objetivos de control metabólico en pacientes con diabetes mellitus tipo 2.

OBJECTIVE: To evaluate the extent to which metabolic targets in type 2 diabetes (DM-2) are achieved in the Endocrinology and Clinical Nutrition Unit of the Hospital Puerta del Mar in Cadiz (Spain) from 2005 to 2008. METHOD: The database included in the computer application HP-Doctor used for all patients attended in our unit (admissions, consultations and peripheral centers) was analyzed. All patients with a principal or secondary diagnosis of DM-2 were included. Clinical characteristics, chronic complications, drug treatment and the percentage of patients who achieved annual mean targets of glycosylated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDLc) were analyzed. RESULTS: From 2005 to 2008, the number of DM-2 patients with computerized records increased by 108.7%. In 2008, 1,177 patients were evaluated. A total of 10.8% were active smokers, 53% had hypertension, and 51.2% and 12.6% presented with retinopathy and cardiovascular disease, respectively. During the study period, the percentage of patients with a mean HbA1c <7% was similar (2005: 31.7% 2008: 30.4%), those with LDLc <100 mg/dl increased from 19.2% to 25.6% and only 9.2% of patients achieved both targets, HbA1c <7% and LDLc <100 mg/dl. CONCLUSIONS: In 2008, only 30% of DM-2 patients achieved a mean HbA1c < 7% and only 25% had LDLc < 100 mg/dl. Metabolic control in DM-2 patients should be improved.