Incident comorbidities in patients with chronic hypoparathyroidism after thyroidectomy: a multicenter nationwide study.

Purpose: Population-based and registry studies have shown that chronic hypoparathyroidism is accompanied by long-term complications. We aimed to evaluate the risk of incident comorbidity among patients with chronic postsurgical hypoparathyroidism in real-life clinical practice in Spain. Methods: We performed a multicenter, retrospective cohort study including patients with chronic postsurgical hypoparathyroidism lasting ≥3 years with at least a follow-up visit between January 1, 2022 and September 15, 2023 (group H). The prevalence and incidence of chronic complications including chronic kidney disease, nephrolithiasis/nephrocalcinosis, hypertension, dyslipidemia, diabetes, cardiovascular disease, central nervous system disease, mental health disorders, eye disorders, bone mineral density alterations, fracture and cancer were evaluated. Patient data were compared with a group of patients who did not develop hypoparathyroidism, matched by gender, age, and follow-up time after thyroidectomy (group NH). Results: We included 337 patients in group H (median [IQR] age, 45 [36-56] years; median time of follow-up, 8.9 [6.0-13.0] years; women, 84.3%) and 669 in group NH (median age, 47 [37-55] years; median time of follow-up, 8.0 [5.3-12.0] years; women, 84.9%). No significant differences were found in the prevalence of comorbidities at the time of thyroidectomy between both groups. In multivariable adjusted analysis, patients with chronic hypoparathyroidism had significantly higher risk of incident chronic kidney disease (OR, 3.45; 95% CI, 1.72-6.91; P<0.001), nephrolithiasis (OR, 3.34; 95% CI, 1.55-7.22; P=0.002), and cardiovascular disease (OR, 2.03; 95% CI, 1.14-3.60; P=0.016), compared with patients without hypoparathyroidism. On the contrary, the risk of fracture was decreased in patients with hypoparathyroidism (OR, 0.09; 95% CI, 0.01-0.70; P=0.021). Conclusion: This study demonstrates that, in the clinical practice of Spanish endocrinologists, a significant increase in the risk of chronic kidney disease, nephrolithiasis and cardiovascular disease, as well as a reduction in the risk of fractures is detected. These results are of interest for the development of new clinical guidelines and monitoring protocols for patients with hypoparathyroidism.

The Medtronic 780G advanced hybrid closed-loop system achieves and maintains good glycaemic control in type 1 diabetes adults despite previous treatment.

INTRODUCTION: Improvements in continuous glucose monitoring (CGM) in recent years have changed the treatment of type 1 diabetes (T1D) by permitting the automation of glucose control. The Minimed 780G advanced hybrid closed-loop (ACHL) system adapts basal infusion rates and delivers auto-correction boluses in order to achieve a user-decided glucose target (100, 110 or 120mg/dL). This study set out to evaluate the effectiveness of the Medtronic 780G system in real-life conditions over 6 months. MATERIALS AND METHODS: Prospective study that included T1D subjects previously treated with insulin pump without CGM (pump group) or with sensor-augmented pump with predictive low-glucose suspend (SAP-PLGS group) who started with the Minimed 780G system. Sensor and pump data from baseline, and at 1, 3 and 6 months were downloaded and HbA1c was recorded at baseline and at 6 months. RESULTS: Fifty T1D subjects were included; 25 were previous SAP-PLGS 640G users and 25 used 640G without CGM. 66% were female, 48.6 (40-57) years of age with 20 (12-31.5) years of diabetes duration. Time in range (TIR) improved in the total cohort from baseline to 6 months (69% (57.7-76) vs. 74% (70-82); p=0.01 as did HbA1c (7.6% (7.1-7.8) vs. 7.0% (6.8-7.5); p<0.001), with improvement in times <54, >180 and >250mg/dL. Outcomes at 6 months did not differ between groups, although the SAP-PLGS subjects were prone to hypoglycaemia and the pump group mainly presented suboptimal metabolic control. CONCLUSION: The AHCL Medtronic Minimed 780G system achieves and maintains good glycaemic control over 6 months in real-life conditions in different profiles of T1D subjects.

Usefulness of Muscle Ultrasound to Study Sarcopenic Obesity: A Pilot Case-Control Study.

Background and objectives: Sarcopenic obesity (SO) is an emerging problem, especially in candidates for bariatric surgery (BS). We hypothesized that musculoskeletal ultrasound (MUS), a simple and accessible method, could be a reliable index of SO. Materials and Methods: A cross-sectional pilot study including 122 subjects (90 cases and 32 controls, 73% female, mean age: 51.2 years) who underwent BS was conducted at University Hospital Mútua Terrassa. The lean mass (LM) was calculated by bioelectrical impedance analysis (BIA) and the thigh muscle thickness (TMT) by MUS. To identify the subjects with SO by BIA, we used skeletal muscle index (SMI). The validity of MUS was determined using the ROC curve. Results: The mean BMI in the obesity group was 44.22 kg/m2. We observed a correlation between the LM and SMI assessed by BIA and the TMT assessed by MUS (R = 0.46, p < 0.001). This correlation was maintained at significant levels in the SO group (n = 40): R = 0.79; p = 0.003). The TMT assessed by MUS was able to predict SMI using BIA (AUC 0.77; 95% CI: 0.68242 to 0.84281). The optimal cut-off point for maximum efficiency was 1.57 cm in TMT (sensitivity = 75.6% and specificity = 71.1%). Conclusions: The TMT of the quadriceps assessed by US is a useful tool for identifying subjects with SO. Larger studies to validate this simple low-cost screening strategy are warranted.

Familial non medullary thyroid carcinoma: Beyond the syndromic forms.

Familial non-medullary thyroid cancer is defined as the presence of non-medullary thyroid cancer in two or more first-degree relatives, in the absence of other predisposing factors. It represents up to 9% of differentiated thyroid cancers, and only a minority appears in well-known hereditary syndromes that associate thyroid cancer among many other clinical manifestations. However, in more than 95% of cases, thyroid cancer appears isolated, and its genetic causes have yet to be elucidated. We review here the current knowledge of the genetic basis of this pathology, as well as its clinical characteristics. Understanding the genetic mechanisms implied would help to comprehend the metabolic pathways involved, with the consequent potential therapeutic application. In addition, it would allow genetic counseling and to focus our efforts on patients at risk of developing this disorder.

Familial non medullary thyroid carcinoma: Beyond the syndromic forms. / Carcinoma diferenciado de tiroides familiar: más allá de las formas sindrómicas.

Familial non-medullary thyroid cancer is defined as the presence of non-medullary thyroid cancer in two or more first-degree relatives, in the absence of other predisposing factors. It represents up to 9% of differentiated thyroid cancers, and only a minority appears in well-known hereditary syndromes that associate thyroid cancer among many other clinical manifestations. However, in more than 95% of cases, thyroid cancer appears isolated, and its genetic causes have yet to be elucidated. We review here the current knowledge of the genetic basis of this pathology, as well as its clinical characteristics. Understanding the genetic mechanisms implied would help to comprehend the metabolic pathways involved, with the consequent potential therapeutic application. In addition, it would allow genetic counseling and to focus our efforts on patients at risk of developing this disorder.

Ultrasound measures of abdominal fat layers correlate with metabolic syndrome features in patients with obesity.

OBJECTIVE: Abdominal fat ultrasound (US) is a simple clinical tool that may allow measures of fat depots not visible using common dual-energy X-ray absorptiometry (DEXA) or computerized tomography (CT) imaging. The aim of this study was to validate the technique, give measures of superficial and profound subcutaneous, preperitoneal, omental and perirenal (retroperitoneal) fat and correlate them with MS markers. METHODS: Sequential US measures of these five abdominal fat layers were done at 397 adults. Blood pressure (BP), body mass index (BMI), waist, body fat %, HOMA-IR index (homeostatic model assessment of insulin resistance), lipid profile and leptin were recorded. Metabolic syndrome (MS) was defined according to Cholesterol education programme adult treatment panel III (ATPIII) criteria. RESULTS: Subcutaneous and omental fat were increased among people with obesity, whereas preperitoneal and perirenal fat did not show any difference according to BMI or waist. Women showed thicker subcutaneous fat (both superficial and profound), whereas men had bigger omental fat. Both postmenopausal and diabetic patients had changes in omental fat only, whereas patients with fatty liver showed thicker preperitoneal and perirenal fat, as well. MS patients showed both thicker perirenal and omental fat. A cut-off of 54 mm in male (M)/34 mm in female (F) of omental fat and 22.5 mm (M)/12.5 mm (F) of perirenal fat could be predictive of later MS onset. CONCLUSIONS: US is a valid method to measure all different abdominal fat depots. Omental and perirenal fat measures may classify patients at risk for MS. Preperitoneal fat depot may also correlate with fatty liver disease.

Lack of Mutations in POT1 Gene in Selected Families with Familial Non-Medullary Thyroid Cancer.

To date, the genes involved in familial non-medullary thyroid cancer (FNMTC) remain poorly understood, with the exception of syndromic cases of FNMTC. It has been proposed that germline mutations in telomere-related genes, such as POT1, described in familial melanoma might also predispose individuals to thyroid cancer, requiring further research. We aimed to identify germline mutations in POT1 in selected FNMTC families (with at least three affected members) without a history of other cancers or other features, and to describe the clinical characteristics of these families. Sequencing of the 5'UTR and coding regions of POT1 was performed in seven affected people (index cases) from seven families with FNMTC. In addition, we performed whole-exome sequencing (WES) of DNA from 10 affected individuals belonging to four of these families. We did not find germline variants of interest in POT1 by Sanger sequencing or WES. We neither found putative causative mutations in genes previously described as candidate genes for FNMTC in the 4 families studied by WES. In our study, no germline potentially pathogenic mutations were detected in POT1, minimizing the possibilities that this gene could be substantially involved in non-syndromic FNMTC.

NOP53 as A Candidate Modifier Locus for Familial Non-Medullary Thyroid Cancer.

Nonsyndromic familial non-medullary thyroid cancer (FNMTC) represents 3-9% of thyroid cancers, but the susceptibility gene(s) remain unknown. We designed this multicenter study to analyze families with nonsyndromic FNMTC and identify candidate susceptibility genes. We performed exome sequencing of DNA from four affected individuals from one kindred, with five cases of nonsyndromic FNMTC. Single Nucleotide Variants, and insertions and deletions that segregated with all the affected members, were analyzed by Sanger sequencing in 44 additional families with FNMTC (37 with two affected members, and seven with three or more affected members), as well as in an independent control group of 100 subjects. We identified the germline variant p. Asp31His in NOP53 gene (rs78530808, MAF 1.8%) present in all affected members in three families with nonsyndromic FNMTC, and not present in unaffected spouses. Our functional studies of NOP53 in thyroid cancer cell lines showed an oncogenic function. Immunohistochemistry exhibited increased NOP53 protein expression in tumor samples from affected family members, compared with normal adjacent thyroid tissue. Given the relatively high frequency of the variant in the general population, these findings suggest that instead of a causative gene, NOP53 is likely a low-penetrant gene implicated in FNMTC, possibly a modifier.

Impaired awareness of hypoglycaemia: A new risk factor for adverse pregnancy outcomes in type 1 diabetes.

AIM: The aim of this study is to evaluate the impact of impaired awareness of hypoglycaemia (IAH) on metabolic control and pregnancy outcomes in women with type 1 diabetes. MATERIAL AND METHODS: This was a single-centre prospective cohort study of singleton pregnant women with type 1 diabetes. IAH was assessed at the first antenatal visit using Clarke's test (score ≥ 3). Data on metabolic control, hypoglycaemic events, and the lipid profile were collected from prior to pregnancy and in each trimester of gestation. Pregnancy outcomes were also recorded. RESULTS: A total of 77 patients with type 1 diabetes were included; 24 (31.2%) were classified as having IAH. Compared with the normal awareness of hypoglycaemia (NAH) group, the IAH group did not show differences in HbA1c , weight gain, insulin doses, or severe and nonsevere hypoglycaemia events throughout pregnancy. IAH was associated with higher triglyceride concentrations in the second trimester (IAH: 154.8 ± 61.1 mg/dL, NAH: 128.6 ± 31.2 mg/dL, P = .034) and an increased risk of neonatal respiratory distress (odds ratio [OR] 11.24; 95% CI, 1.01-124.9, P = .041) in adjusted models. Increased risk of pre-eclampsia was related to higher second trimester triglyceride concentrations (OR 1.028; 95% CI, 1.004-1.053, P = .023) adjusted for confounders. CONCLUSIONS: The IAH was associated with increased risk of neonatal respiratory distress and pre-eclampsia, despite showing no differences in metabolic control. Hypoglycaemia awareness in the first antenatal visit should be assessed to identify the subgroup of pregnant women with increased risk of complications.

Primary adrenal insufficiency due to hereditary apolipoprotein AI amyloidosis: endocrine involvement beyond hypogonadism.

Several mutations in the gene encoding apolipoprotein AI (apoAI) have been described as a cause of familial amyloidosis. Individuals with apoAI-derived (AApoAI) amyloidosis frequently manifest with liver, kidney, laryngeal, skin and myocardial involvement. Although primary hypogonadism (PH) is considered almost pathognomonic of this disease, until now, primary adrenal insufficiency (PAI) has not been described as a common clinical feature. Here, we report the first kindred with AApoAI amyloidosis in which PAI is well-documented. All family members with the Leu60_Phe71delins60Val_61Thr heterozygous mutation who were regularly followed-up at our centre were considered. Nineteen individuals had the confirmed APOA1 deletion/insertion mutation, with detailed medical records available in 11 cases. Of these, 6 had PAI and 3 (all males) had PH. Among them, one 47-year-old man, not previously diagnosed with PAI, developed adrenal crisis after liver transplantation, precipitated by an opportunistic infection. Transplantation due to organ failure, which necessitates use of immunosuppressive medication such as corticosteroids, is frequently required during the course of hereditary amyloidosis. Consequently, PAI can remain masked, being discovered only when an adrenal crisis develops. Therefore, according to the present evidence, patients with AApoAI amyloidosis should be submitted to regular testing of corticotrophin and cortisol levels in order to avoid delaying corticosteroid replacement.

Utility of proGRP as a tumor marker in the medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor caused by a malignant transformation in the parafollicular C-cells of the thyroid, where calcitonin (CT) is released. Nowadays the main tumor markers (TM) used in the diagnosis and follow-up of MTC patients are CT and carcinoembryonic antigen (CEA). Nonetheless, progastrin releasing peptide (proGRP) has been recently proposed as a TM useful in the MTC. Our aims were to investigate the release of proGRP in thyroid tumors, its role in the assessment of advanced MTC and its utility in the differential diagnosis between MTC and non-MTC thyroid tumors. METHODS: Serum samples from 22 patients with MTC and 16 with non-MTC were collected. Patients were classified into advanced cancer or no evidence of disease (NED). ProGRP was performed by Architect (Abbot Diagnostics), CT by Liaison (Diasorin) and CEA by Cobas E601(Roche Diagnostics). RESULTS: ProGRP median concentration in advanced MTC was significantly higher (1398.4 pg/mL) when compared with non-MTC, either in advanced disease (24.9 pg/mL) or NED (14.6 pg/mL). In non-MTC patients, proGRP median concentration was below its cutoff level (50 pg/mL). Similar to CT, proGRP was able to detect 88.9% of MTC patients, but with a slightly lower specificity of 76.9%. Using proGRP together with CT the sensitivity increased to 100%. CONCLUSIONS: The low prevalence of this malignancy strongly recommends further collaborative studies, mainly focused on monitoring proGRP during tyrosine kinase inhibitors treatment for early detection of resistance and assessing its usefulness to avoid the observed false positive fluctuations that occur with CT and CEA.

Detailed description of a prepregnancy care program and its impact on maternal glucose control, weight gain, and dropouts.

BACKGROUND: The aim of this study was to analyze the clinical and metabolic changes observed during a prepregnancy care (PPC) program. METHODS: We performed a retrospective, observational, cohort study of 104 women with type 1 diabetes initiating a PPC program from 2011 to 2014. The outcomes measured were changes in HbA1c levels, weight and hypoglycemic events during PPC. Risk factors associated with severe hypoglycemia events, achieving the HbA1c target and dropouts were evaluated. RESULTS: HbA1c decreased from 7.2 ± 0.8% (55.3 ± 8.8 mmol/mol) to 6.7 ± 0.9% (49.8 ± 10.3 mmol/mol) (P < .001) within a median of 14.2 months (interquartile interval 5.4-23.2); 71.2% obtained HbA1c  < 7% (53 mmol/mol). HbA1c at the end of PPC was associated with baseline HbA1c (ß = .318, P = .001) and the number of previous pregnancies (ß = .224, P = .038), PPC was accompanied by 1.4 ± 4.0 kg weight gain (P = .003) without changes in severe hypoglycemic events. The risk factors for severe hypoglycemia were severe hypoglycemic events during the 2 years before (odds ratio [OR] 11.99, confidence interval 95% 1.89-75.95) and PPC duration (OR 1.09, 1.03-1.16). A total of 33 patients (31.7%) dropped out from PPC during follow-up, with dropout being associated with age (OR 1.17, 1.04-1.36) and PPC duration (OR 1.06, 1.02-1.11). CONCLUSIONS: Our PPC program was associated with an improvement in glycemic control without a significant increase in severe hypoglycemic events, although with some weight gain. A considerable number of patients dropped out during follow-up, this being related to older age and a longer duration of the program. This information could be of help to design new and more effective PPC approaches. Copyright © 2016 John Wiley & Sons, Ltd.

Metabolic control after years of completing a clinical trial on sensor-augmented pump therapy.

BACKGROUND: Sensor-augmented pump (SAP) therapy has been shown to be effective and safe for improving metabolic control in patients with type 1 diabetes mellitus (T1DM) in a number of trials. Our objective was to assess glycemic control in a group of T1DM patients on insulin pump or SAP therapy after years of participating in the SWITCH (Sensing With Insulin pump Therapy To Control HbA1c) trial and their return to routine medical monitoring. METHODS: A retrospective, observational study of 20 patients who participated in the SWITCH trial at our hospital from 2008 to 2010. HbA1c values were compared at the start, during (at the end of the periods with/without SAP use - Sensor On/Sensor Off period respectively - of the cross-over design), and 3 years after study completion. HbA1c values of patients who continued SAP therapy (n=6) or only used insulin pump (n=14) were also compared. RESULTS: Twenty patients with T1DM (44.4±9.3 years, 60% women, baseline HbA1c level 8.43±0.55%) were enrolled into the SWITCH study). Three years after study completion, HbA1c level was 7.79±0.77 in patients on pump alone, with no significant change from the value at the end of the Off period of the study (7.85±0.57%; p=0.961). As compared to the end of the On period, HbA1c worsened less in patients who remained on SAP than in those on pump alone (0.18±0.42 vs. 0.55±0.71%; p=0.171), despite the fact that levels were similar at study start (8.41±0.60 vs. 8.47±0.45; p=0.831) and at the end of the On period (7.24±0.48 vs. 7.38±0.61; p=0.566). Frequency of CGM use in patients who continued SAP therapy was high (61.2% of the time in the last 3 months). CONCLUSIONS: Our study suggests that the additional benefit of SAP therapy achieved in a clinical trial may persist in the long term in routine clinical care of patients with T1DM.

Metabolic control after years of completing a clinical trial on sensor-augmented pump therapy / Control metábolico años después de completar un ensayo clínico de tratamiento con bomba potenciado con sensor

BACKGROUND: Sensor-augmented pump (SAP) therapy has been shown to be effective and safe for improving metabolic control in patients with type 1 diabetes mellitus (T1DM) in a number of trials. Our objective was to assess glycemic control in a group of T1DM patients on insulin pump or SAP therapy after years of participating in the SWITCH (Sensing With Insulin pump Therapy To Control HbA1c) trial and their return to routine medical monitoring. METHODS: A retrospective, observational study of 20 patients who participated in the SWITCH trial at our hospital from 2008 to 2010. HbA1c values were compared at the start, during (at the end of the periods with/without SAP use - Sensor On/Sensor Off period respectively - of the cross-over design), and 3 years after study completion. HbA1c values of patients who continued SAP therapy (n = 6) or only used insulin pump (n = 14) were also compared. RESULTS: Twenty patients with T1DM (44.4 ± 9.3 years, 60% women, baseline HbA1c level 8.43 ± 0.55%) were enrolled into the SWITCH study). Three years after study completion, HbA1c level was 7.79 ± 0.77 in patients on pump alone, with no significant change from the value at the end of the Off period of the study (7.85 ± 0.57%; p = 0.961). As compared to the end of the On period, HbA1c worsened less in patients who remained on SAP than in those on pump alone (0.18 ± 0.42 vs. 0.55 ± 0.71%; p = 0.171), despite the fact that levels were similar at study start (8.41 ± 0.60 vs. 8.47 ± 0.45; p = 0.831) and at the end of the On period (7.24 ± 0.48 vs. 7.38 ± 0.61; p = 0.566). Frequency of CGM use in patients who continued SAP therapy was high (61.2% of the time in the last 3 months). CONCLUSIONS: Our study suggests that the additional benefit of SAP therapy achieved in a clinical trial may persist in the long term in routine clinical care of patients with T1DM

OBJETIVOS: La terapia bomba-sensor (SAP, del inglés Sensor Augmented Pump) ha demostrado eficacia y seguridad en la mejoría del control metabólico en pacientes con diabetes tipo 1 (DT1) en múltiples ensayos clínicos. Nuestro objetivo ha sido valorar el control glicémico en un grupo de pacientes con DT1 en tratamiento con bomba de insulina/SAP años después de su participación en el estudio SWITCH (Sensing With Insulin Pump Therapy To Control HbA1c) tras el retorno al seguimiento médico habitual. MÉTODOS: Estudio observacional retrospectivo que incluye todos los pacientes que participaron en el estudio SWITCH en nuestro centro entre 2008 y 2010. Se comparó la HbA1c al inicio, durante (al final de los periodos con/sin terapia SAP - periodos Sensor On/Sensor Off respectivamente del diseño cruzado-) y tres años tras la conclusión del estudio. Adicionalmente, se compararon los valores de HbA1c de los pacientes que habían continuado la terapia SAP (n = 6) respecto a los que únicamente utilizaban bomba de insulina (n = 14). RESULTADOS: Se incluyeron 20 pacientes con DT1 (44.4 ± 9.3 años, 60% mujeres, HbA1c al inicio del estudio SWITCH 8.43 ± 0.55%). Tres años después de la conclusión del estudio, la HbA1c en los pacientes que únicamente realizaban tratamiento con bomba fue de 7.79 ± 0.77%, sin cambios significativos desde la finalización del periodo Off del estudio (7.85 ± 0,57%, p = 0.961). En comparación con la conclusión del periodo On, la HbA1c de aquellos pacientes que mantuvieron la terapia SAP al finalizar el estudio empeoró menos que aquellos que únicamente utilizaban bomba (0.18 ± 0.42 vs. 0.55 ± 0.71%; p = 0.171) aun siendo igual tanto al inicio del estudio (8.41 ± 0.60 vs. 8.47 ± 0.45;p = 0.831) como al finalizar el periodo On (7.24 ± 0.48 vs. 7.38 ± 0.61; p = 0.566). Los pacientes que seguían realizando terapia SAP tenían un elevado uso del sensor (61.2% del tiempo durante los últimos 3 meses). CONCLUSIONES: nuestro estudio apunta que el beneficio adicional obtenido por la terapia SAP durante un ensayo clínico puede persistir a largo plazo durante la práctica clínica habitual en los pacientes con DT1