Changes in RANKL, OPG, and 25(OH)D Levels in Children with Leukemia from Diagnosis to Remission.

BACKGROUND: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption, and disruptions in this complex can affect bone metabolism. METHODS: This study analyzes the changes in RANKL, OPG, and 25(OH)D levels; the RANKL/OPG ratio; and other bone turnover markers (BTMs) from diagnosis to complete remission in children with acute lymphoblastic leukemia (ALL). This is a prospective observational cohort study, carried out at the Instituto Mexicano del Seguro Social, Mexico City, including 33 patients (4-17 years) with newly diagnosed B-cell ALL. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A peripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. RESULTS: Increased RANKL (p = 0.001) and osteocalcin (p < 0.001) levels and RANKL/OPG ratio (<0.001) and a decreased OPG level (p = 0.005) were observed at remission, predominantly in the high-risk (HR) relapse and vitamin D deficiency groups. A negative association between RANKL and OPG (r = -0.454, p = 0.008) was observed. CONCLUSIONS: we suggest that the RANKL/OPG ratio could serve as a bone remodeling marker in ALL patients.

Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus.

OBJECTIVE: To assess thrombotic risk with PAI-1 levels in patients with COVID-19, to evaluate PAI-1 differences between hyperglycemic and/or Type 2 Diabetes Mellitus (T2DM) versus non-hyperglycemic patients, and to analyze the association of plasminogen activator inhibitor-1 (PAI-1) with hyperglycemia and T2DM. METHODS: A cross-sectional study carried out in 181 patients hospitalized for COVID-19. Two groups were formed: the patients with hyperglycemia at admission and/or previously diagnosed T2DM group and the non-hyperglycemic group. Fibrinolysis was assessed by measuring PAI-1 levels by ELISA. RESULTS: The mean age was 59.4±16.1 years; 55.8% were male 54.1% of patients presented obesity, 38.1% had pre-existing T2DM and 50.8% had admission hyperglycemia and/or pre-existing T2DM. The patients with admission hyperglycemia and/or preexisting T2DM had higher PAI-1 compared with non-hyperglycemic patients [197.5 (128.8-315.9) vs 158.1 (113.4-201.4) ng/mL; p=0.031]. The glucose levels showed a positive correlation with PAI-1 levels (r=0.284, p=0.041). A multivariate logistic regression analysis showed association of PAI-1 level and hyperglycemia and pre-existing T2DM with severity of COVID-19. CONCLUSION: Patients hospitalized for COVID-19 infection with preexisting T2DM or hyperglycemia detected during their hospitalization presented a greater increase in PAI-1 levels, which suggests that hyperglycemia contributes directly to the hypercoagulable state and probably a worse outcome from the patients.

Novel pathogenic variant of DICER1 in an adolescent with multinodular goiter, ovarian Sertoli-Leydig cell tumor and pineal parenchymal tumor of intermediate differentiation.

OBJECTIVES: To present a case of a new pathogenic variant of DICER1. CASE PRESENTATION: 13-year-old female with non-toxic multinodular goiter and ovarian Sertoli-Leydig cell tumor, in whom a pineal parenchymal tumor of intermediate differentiation was diagnosed. Next-generation sequencing revealed a new germline mutation in the DICER1 gene (exon 16, c2488del [pGlu830Serfs*2] in heterozygosis), establishing the diagnosis of DICER1 syndrome. CONCLUSIONS: Mutations in the DICER1 gene cause genetic predisposition to a wide spectrum of benign or malignant tumors from childhood to adulthood.

[Vitamin D and its positive effect on the PTH/vitamin D/calcium-FGF23/klotho/phosphorus axis in kidney transplant recipients]. / Vitamina D y su efecto positivo sobre el eje PTH/vitamina D/calcio-FGF23/klotho/fósforo en pacientes con trasplante renal.

Introduction: Background: hypovitaminosis D is frequent in kidney transplant recipient (KTR) patients and is associated with deleterious effects both at the bone and extraosseous levels. Treatment with cholecalciferol is effective for the normalization of 25(OH)D, demonstrating a beneficial effect on the calcium-tropic axis in other populations; however, its effect on the PTH/vitamin D/calcium and FGF23/klotho/phosphorus axis in RTR has not been reported. The aim of this study was to evaluate the effect of normalization of serum 25(OH)D concentrations on the PTH/vitamin D/calcium-FGF23/klotho/phosphorus axis in KTR treated with cholecalciferol, as well as the association between the components of this axis. Methods: a prospective study in 23 KTR with hypovitaminosis D, with evolution from 1 to 12 months post-transplantation, an estimated glomerular filtration rate > 60 mL/min/1.73 m2 and a history of primary nephropathy treated with cholecalciferol, in whom the PTH/vitamin D/calcium and FGF23/klotho/phosphorus axis was evaluated during the state of hypovitaminosis D and at normalization of 25(OH)D. Results: at the normalization of 25(OH)D, a reduction in PTH [103 (58.5-123.9) vs 45.6 (30.1-65.1) pg/mL; p = 0.002] and an increase in serum phosphorus [3.1 (2.3-3.5) vs 3.3 (3-3.6) mg/dL; p = 0.01] were evident, with no differences in calcium, klotho and FGF23 concentrations. The time to achieve normalization of 25(OH)D was 12 weeks (RIC, 4-12), with a dose of 5000 IU/day (RIC, 4000-6000). A positive association between klotho and PTH was corroborated (r = 0.54; p = 0.008; linear regression, ß = 0.421; B = 0.004; 95 % CI, 0.003-0.007; p = 0.045). Conclusions: treatment with cholecalciferol is effective for the normalization of 25(OH)D, with a beneficial effect on calcium-phosphotropic metabolism characterized by a reduction in PTH concentration, without significant changes in calcemia or calciuria, as well as an increase in phosphatemia, without modifications in FGF23 or klotho concentrations.

Introducción: Introducción: la hipovitaminosis D es frecuente en los receptores de trasplante renal (RTR) y se asocia con efectos deletéreos tanto a nivel óseo como extraóseo. El tratamiento con colecalciferol es eficaz para la normalización de la 25(OH)D, demostrándose un efecto benéfico sobre el eje calciotrópico; sin embargo, su efecto sobre el eje fosfotrópico no se ha reportado. El objetivo de este estudio fue evaluar el efecto de la normalización de las concentraciones séricas de 25(OH)D sobre el eje PTH/vitamina D/calcio-FGF23/klotho/fósforo en RTR tratados con colecalciferol, así como la asociación entre sus componentes. Métodos: estudio prospectivo en 23 RTR con hipovitaminosis D y antecedente de nefropatía primaria tratados con colecalciferol, en quienes se evaluó el eje PTH/vitamina D/calcio y FGF23/klotho/fósforo durante el estado de hipovitaminosis D y a la normalización de la 25(OH)D. Resultados: a la normalización de la 25(OH)D se evidenció una reducción de la PTH [103 (58,5-123,9) vs. 45,6 (30,1-65,1) pg/mL; p = 0,002] y un aumento del fósforo sérico [3,1 (2,3-3,5) vs. 3,3 (3-3,6) mg/dL; p = 0,01], sin diferencias en las concentraciones de calcio, klotho y FGF23. El tiempo para lograr la normalización de la 25(OH)D fue de 12 semanas (4-12), con una dosis de 5000 UI/día (4000-6000). Se corroboró una asociación positiva entre klotho y PTH (r = 0,54; p = 0,008; regresión lineal, ß = 0,421; IC 95 %: 0,003-0,007; p = 0,045). Conclusiones: el tratamiento con colecalciferol es eficaz para la normalización de la 25(OH)D con un efecto benéfico sobre el metabolismo calcio-fosfotrópico caracterizado por una reducción de la PTH y un incremento de la fosfatemia, sin modificaciones de calcemia, calciuria, FGF23 o klotho.

Efficiency and Safety of CyberKnife Robotic Radiosurgery in the Multimodal Management of Patients with Acromegaly.

OBJECTIVE: To analyze, in a cohort of acromegalic patients, the results of the efficiency and safety of radiosurgery (CyberKnife), as well as the prognostic factors associated with disease remission. MATERIAL AND METHODS: Observational, retrospective, longitudinal, and analytical study that included acromegalic patients with persistent biochemical activity after initial medical-surgical treatment, who received treatment with CyberKnife radiosurgery. GH and IGF-1 levels at baseline after one year and at the end of follow-up were evaluated. RESULTS: 57 patients were included, with a median follow-up of four years (IQR, 2-7.2 years). The biochemical remission rate was 45.6%, 33.33% achieved biochemical control, and 12.28% attained biochemical cure at the end of follow-up. A progressive and statistically significant decrease was observed in the comparison of the concentrations of IGF-1, IFG-1 x ULN, and baseline GH at one year and at the end of follow-up. Both cavernous sinus invasion and elevated baseline IGF-1 x ULN concentrations were associated with an increased risk of biochemical non-remission. CONCLUSION: Radiosurgery (CyberKnife) is a safe and effective technique in the adjuvant treatment of GH-producing tumors. Elevated levels of IGF x ULN before radiosurgery and invasion of the cavernous sinus by the tumor could be predictors of biochemical non-remission of acromegaly.

Severity of Fatigue and Its Relationship with TSH before and after Levothyroxine Replacement Therapy in Patients with Primary Hypothyroidism.

BACKGROUND: Fatigue is a common symptom in hypothyroidism; however, the effect of levothyroxine on fatigue has been little studied. The aim of this study was to evaluate the effect of levothyroxine on fatigue in Latino patients with primary hypothyroidism, as well as the association of TSH and free T4 (FT4) with the severity and persistence of fatigue. METHODS: A prospective study was performed in 92 patients with primary hypothyroidism. Fatigue severity scale (FSS) scores and clinical and biochemical characteristics before and at 6 months of levothyroxine were evaluated. RESULTS: After 6 months of levothyroxine, a reduction in FSS (53 (47-57) vs. 36 (16-38); p = 0.001) and fatigue frequency (45.7% vs. 26.1%; p = 0.008) was evident. Both before and after 6 months of levothyroxine, there was a positive correlation of the FSS score with TSH and a negative correlation with FT4. Persistent fatigue was associated with a pretreatment FSS score (r = 0.75; p = 0.001) and diabetes (r = 0.40; p = 0.001). An FSS > 34 (RR 3.9 (95% CI 1.43-10.73; p = 0.008)), an FSS > 36 (RR 3.23 (95% CI 1.21-8.6; p = 0.019)), and diabetes (RR 5.7 (95% CI 1.25-9.6; p = 0.024)) before treatment were risk factors for persistent fatigue. CONCLUSIONS: Levothyroxine improved fatigue in most patients. Diabetes and an FSS score >34 or >36 before treatment were risk factors for persistent fatigue.

Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients / Distúrbio do eixo hipotálamo-hipófise-gonadal e sua associação com resistência à insulina em receptores de transplante renal

Abstract Objective: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. Methods: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. Results: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). Conclusion: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.

Resumo Objetivo: Avaliar as alterações do eixo hipotálamo-hipófise-gonadal (HHG) em 1 e 12 meses após transplante renal (TR) e sua associação com a resistência à insulina. Métodos: Foi realizado um estudo clínico retrospectivo em um centro de cuidados terciários em receptores de transplante renal (RTR) com idade entre 18-50 anos com doença renal primária e função do enxerto renal estável. LH, FSH, E2/T e HOMA-IR foram avaliados em 1 e 12 meses após o TR. Resultados: foram incluídos 25 RTR; 53% eram homens e a média de idade foi de 30,6±7,7 anos. O IMC foi de 22,3 (20,4-24,6) kg/m2 e 36% apresentaram hipogonadismo em 1 mês vs 8% aos 12 meses (p=0,001). A remissão do hipogonadismo foi observada em todos os homens, enquanto nas mulheres, o hipogonadismo hipogonadotrófico persistiu em dois RTR aos 12 meses. Ficou evidente uma correlação positiva entre gonadotrofinas e idade em 1 e 12 meses. Cinquenta e seis por cento dos pacientes apresentaram resistência à insulina (RI) em 1 mês e 36% aos 12 meses (p=0,256). O HOMA-IR mostrou uma correlação negativa com E2 (r=-0,60; p=0,050) e T (r=-0,709; p=0,049) em 1 mês, sem correlação em 12 meses. O HOMA-IR aos 12 meses após TR correlacionou-se positivamente com o IMC (r=0,52; p=0,011) e a dose de tacrolimus (r=0,53; p=0,016). Conclusão: O TR bem-sucedido restaura o eixo HHG no primeiro ano. O hipogonadismo apresentou uma correlação negativa com a RI no período inicial após o TR, mas essa correlação não foi significativa aos 12 meses.

Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients.

OBJECTIVE: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. METHODS: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. RESULTS: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). CONCLUSION: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.

Efficacy of cabergoline therapy in patients with non-functioning pituitary adenomas: A single center clinical experience

ABSTRACT Objective: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.

Van Wyk-Grumbach syndrome and trisomy 21.

The Van Wyk-Grumbach syndrome (VWGS) is characterized by severe hypothyroidism, peripheral precocious puberty, delayed bone age, hyperestrogenism, prepubertal luteinizing hormone, and elevated follicle-stimulating hormone. Patients with Down syndrome have a high susceptibility and prevalence of thyroid disorders. However, the coexistence of VWGS and trisomy 21 is uncommon. We present a case of a 5-year-old Mexican girl with Down syndrome, severe autoimmune hypothyroidism, pituitary enlargement, hyperprolactinemia, peripheral precocious puberty, multiple ovarian cysts, and delayed bone age, with a clinical diagnosis of VWGS. The patient presented with a remission of these manifestations after treatment with levothyroxine. Patients with Down syndrome, precocious puberty, hyperestrogenism, prepuberal luteinizing hormone, high follicle-stimulating hormone, and delayed bone age should be evaluated with a thyroid profile due to the possibility of VWGS.

Efficacy of cabergoline therapy in patients with non-functioning pituitary adenomas: A single center clinical experience.

Introduction: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.

Risk Factors Associated with Mortality among Patients with COVID-19: Analysis of a Cohort of 1213 Patients in a Tertiary Healthcare Center.

The presence of cardio-metabolic and respiratory comorbidities, immunosuppression, and chronic kidney disease have been associated with an increase in mortality from COVID-19. The objective of this study is to establish the risk factors associated with 30-day mortality in a cohort of hospitalized patients with COVID-19. This paper conducts a retrospective and analytical study of patients hospitalized for COVID-19 in a tertiary care center. A Cox proportional hazard analysis was performed to estimate the association of comorbidities with 30-day mortality. A total of 1215 patients with a median age of 59 years were included. In the adjusted Cox proportional hazards regression model, hypothyroidism, D-dimer ≥ 0.8 µg/mL, LHD ≥ 430 IU/L, CRP ≥ 4.83 ng/mL, and triglycerides ≥ 214 mg/dL were associated with an increased risk of death. The presence of a history of hypothyroidism and biomarkers (D-dimer, lactic dehydrogenase, CRP, and triglycerides) were associated with an increase in mortality in the studied cohort.

[Somatropin and final height in Mexican paediatric population with growth hormone deficiency]. / Somatropina y talla final en población pediátrica mexicana con deficiencia de hormona de crecimiento.

Treatment with recombinant growth hormone, or somatropin, increases linear growth and is effective in improving final height in children with isolated growth hormone deficiency (IGHD), however, the available information of these results in the Latin population is scarce. OBJECTIVE: To evaluate the effect of somatropin on growth velocity and final height in Mexican children with IGHD, as well as to determine the factors associated with final height. PATIENTS AND METHOD: A retrospective study was conducted in 50 children with isolated and severe growth hormone deficiency treated with somatro pin. Auxological characteristics were assessed before somatropin and at final height. Only patients with severe GH deficiency, with a peak GH value < 5 µg/L, were included. RESULTS: 40% (n = 20) were girls. The basal height Z-score was -2.6 ± 0.4 vs final height Z-score 1.6 ± 0.7, with a Z-score of height in crease of 1 ± 0.6. Ninety-two percent (n = 46) reached their genetic potential; somatropin dose was 33 ± 0.5 µg/kg/d, with a treatment duration of 4.16 ± 1.5 years. The highest growth velocity was observed during the first year. In the multivariate analysis, the association between final height, mid-parental target height (r = 0.30; p = 0.03, ß = 0.7; p = 0.001), and somatropin dose (r = 0.63; p = 0.001, ß = 0.30; p = 0.028) was observed. CONCLUSIONS: Somatropin treatment allows normalization of linear growth and the achievement of genetic height potential in most Mexican children with IGHD. Final height is associated with mid-parental height and somatropin dose, highlighting the importance of genetic potential and the dose-response effect of somatropin in establishing height prognosis.

Burden in primary informal caregivers of children and adolescents with type 1 diabetes: Is it associated with depression, family dysfunction, and glycemic control?

Objective: The requirement of a chronic treatment and the increase in life expectancy in children with type 1 diabetes (T1D) leads to the possibility of caregiver burden. The aim of our study was to evaluate the burden in primary informal caregivers (PIC) of children and adolescents with type 1 diabetes and its association with depression, family dysfunction, and glycemic control. Materials and methods: A retrospective study was performed in PIC of children and adolescents with T1D. Zarit Burden Interview Scale (ZBIS) was used to evaluate caregiver burden. Beck Depression Inventory (BDI-II) was used to evaluate depression in PIC, and the Family APGAR questionnaire was used to evaluate the family functionality. Results: A total of 100 PIC of children and adolescents with T1D were included. Caregiver burden was found in 33% of caregivers. The total score of the Zarit scale was 41 (34-49); 19% had mild caregiver burden, and 14% had severe caregiver burden. According to the BDI-II, 82% had minimal depression, 11% mild depression, 5% moderate depression, and 2% severe depression. Family function was good in 69%; 13% had moderate dysfunction, and 18% had severe dysfunction. A positive correlation between caregiver burden and BDI-II score (r = 0.84; p = 0.001) and the grade of depression (r = 0.87; p = 0.001) was found. A logistic regression model showed that BDI-II score was associated with caregiver burden (OR 1.14; 95% CI 1.061-1.23; p = 0.001). A BDI-II cut off of 9 or more had a sensibility and specificity of 58% and 28%, respectively, for caregiver burden [AUC 0.751 (0.64-0.85); p = 0.001]. A BDI-II score ≥9 was a predictor of caregiver burden (OR 3.4; 95% CI 1.4-8.1; p = 0.008). Conclusion: Caregiver burden is present in more than one third of the PIC of patients with T1D and is associated with depression. A BDI-II score ≥9 is a predictor of caregiver burden which may be a point to take into account in the integral approach to the patient with T1D and his or her family nucleus.

Risk factors associated with thyroid nodular disease in acromegalic patients: A case-cohort study in a tertiary center.

INTRODUCTION: Goiter is very common in patients with acromegaly; its development is correlated to the duration of the disease. Thyroid cells express the IGF-1 receptor and the TSH/IGF-1 interaction has been demonstrated to have a synergistic effect in thyroid cell growth. There is a correlation between IGF-1 levels and the thyroid volume of patients with acromegaly. The aim of this study was to evaluate, in a retrospective case-cohort study of patients with acromegaly, the associated risk factors for thyroid nodules disease in this population. METHODS: This was a case-cohort study matched by age, gender, and growth hormone at diagnosis. Cases consisted of acromegalic patients that developed thyroid nodules during the follow up, and controls consisted in acromegalic patients without thyroid nodules. A Cox proportional hazard estimation was carried out for measure the associated risk factors for thyroid nodules disease in acromegalic patients. A nodular thyroid disease-free survival analysis was estimated using the Kaplan-Meier analysis. RESULTS: We recruited 49 cases and 56 controls. In a multivariate Cox proportional hazard analysis age and IGF-1 ≥ 2.2 x ULN were significantly related with the presence of thyroid nodules [HR of 2.21 (95% CI; 1.15-4.25, p = 0.01)]. Nodularity-free survival rates in patients who had an IGF-1 X ULN ≥ 2.2 was found to be lower in comparison to those who had IGF-1 X ULN < 2.2, according to a Kaplan-Meier survival analysis. CONCLUSIONS: Our findings support that exist more probability to develop thyroid nodular disease in patients with acromegaly that present IGF-1 X ULN ≥ 2.2, suggesting a possible direct effect between the time of exposure to the IGF-1 axis hyperactivity and the genesis of thyroid nodules.

Pattern of Adiponectin, Osteocalcin, Irisin, FGF-21, and MCP-1 According to the Body Size Phenotype: Could They Be Markers of Metabolic Health in Mexican-Mestizo Middle-Aged Women?

Variations in levels of some adipokines, myokines, osteokines, hepatokines and inflammatory cytokines contribute to abnormal glucose and lipid metabolism. The aim of this study was to determine the pattern of adiponectin, osteocalcin (OCN), irisin, FGF-21, and MCP-1 according to the body size phenotype of middle-aged women, and their associations with BMI, visceral adipose tissue (VAT), and HOMA-IR. A cross-sectional study in 265 women aged from 40 to 65 years was performed. The biochemical characteristics were evaluated in metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy obese, and metabolically unhealthy obese women. There was an association of OCN with BMI (r = -0.107; p = 0.047); adiponectin with BMI (r = -0.217; p = 0.001), insulin (r = -0.415; p = 0.0001), HOMA-IR (r = -0.429; p = 0.0001), and VAT (r = -0.134; p = 0.025); irisin with BMI (r = 0.604; p = 0.001), insulin (r = 0.446; p = 0.0001), HOMA-IR (r = 0.452; p = 0.0001), and VAT (r = 0.645; p = 0.0001); FGF-21 with insulin (r = -0.337; p= 0.030) and HOMA-IR (r = -0.341; p = 0.03); and MCP-1 with BMI (r = 0.481; p = 0.0001), VAT (r = 0.497; p = 0.001), insulin (r = 0.298; p= 0.001), and HOMA-IR (r = 0.255; p = 0.004). A multivariate analysis showed that an elevation of OCN (OR 1.4 (95%CI 1.06-1.81)) and a reduction of adiponectin (OR 0.9 (0.84-0.96)) were associated factors for a metabolic unhealthy phenotype in normal weight participants. Likewise, higher irisin (OR 1.007 (1.003-1.011)) and MCP-1 (1.044 (1.008-1.083)) were risk factors for a metabolic unhealthy phenotype in woman with obesity. OCN, adiponectin, irisin, FGF-21, and MCP-1 are associated with some metabolic parameters such as BMI, HOMA-IR, and VAT, and could be possible biomarkers of an unhealthy metabolic phenotype in middle-aged women.

COVID-19 in a country with a very high prevalence of diabetes: The impact of admission hyperglycaemia on mortality.

Aims: To evaluate the frequency of diabetes and admission hyperglycaemia in Mexican COVID-19 patients, to describe the clinical and biochemical characteristics of patients with admission hyperglycaemia and to determinate the impact of diabetes and admission hyperglycaemia on COVID-19 severity and mortality. Methods: A multicentric study was performed in 480 hospitalized patients with COVID-19. Clinical and biochemical characteristics were evaluated in patients with admission hyperglycaemia and compared with non-hyperglycaemic patients. The effect of diabetes and admission hyperglycaemia on severity and risk of death were evaluated. Results: Age was 50.7 ± 13.6 years; 68.3% were male. Some 48.5% (n = 233) had admission hyperglycaemia; 29% (n = 139) of these patients had pre-existing diabetes. Patients with admission hyperglycaemia had more requirement of invasive mechanical ventilation (IMV), higher levels of urea, D-dimer and neutrophil-lymphocyte ratio (NLR), as well as lower lymphocyte count. An association between admission hyperglycaemia with IMV and D-dimer with glucose was found. Age ≥50 years (OR 2.09; 95%CI 1.37-3.17), pre-existing diabetes (OR 2.38; 95%CI 1.59-5.04) and admission hyperglycaemia (OR 8.24; 95%CI 4.74-14.32) were risk factors for mortality. Conclusions: Admission hyperglycaemia is presented in 48.5% of COVID-19 patients. Diabetes and admission hyperglycaemia are associated with the severity of disease and mortality. This study shows the devastating conjunction of hyperglycaemia and COVID-19. Clinical trial registration: Clinical characteristics of patients with COVID-19, DI/20/204/04/41 (Hospital General de Mexico) and NR-13-2020 (Hospital Regional de Alta Especialidad Ixtapaluca).

Effect of the normalization of TSH and free T4 on lipid profile in a pediatric population with primary hypothyroidism. / Efecto de la normalización de TSH y T4 libre sobre el perfil lipídico en población pediátrica con hipotiroidismo primario.

INTRODUCTION: Hypothyroidism has been associated with dyslipidemia. Its treatment with levothyroxine has shown a positive effect on the lipid profile in adults, however, there is a lack of data on the pediatric popu lation. OBJECTIVE: to evaluate the effect of the thyroid profile normalization on the lipid profile in children with primary hypothyroidism. PATIENTS AND METHOD: Retrospective study in children aged from 6 to 16 years, with diagnosis of primary hypothyroidism due to Hashimoto's thyroiditis, in treatment with levothyroxine, and who had an evaluation of serum lipids before and during their treatment. The lipid profile was evaluated in 2 stages: the first one referred to as "before levothyroxine treatment" (at the diagnosis of primary hypothyroidism) and the second one referred to as " thyroid profile normalization" (when normalization of Thyroid-stimulating hormone [TSH] and free T4 [FT4] was achieved during levothyroxine treatment). Sociodemographic and anthropometric data were recorded. The lipid profile evaluation consisted of the serum determination of total cholesterol (TC), high-density cholesterol (HDL-C), and TG. The phenotype of dyslipidemias was determined according to the Fredrickson's classification. RESULTS: 72 patients were included (61% women; age 11.5 ± 2.9 years), out of which 58.3% (n = 42) presented pre-treatment dyslipidemia. In hypothyroid state, it was evident the correlation of TSH with TC (r = 0.36; p = 0.002), LDL-C (r = 0.46; p = 0.01), and HDL-C (r = -0.33; p = 0.004). The thyroid profile normalization showed the reduction of TC [184 mg/dL (IQR 92-322) vs 147 mg/dL (IQR 92-283); p = 0.05], LDL-C [99 mg/dL (IQR 44-232) vs 82 mg/dL (IQR 41-168); p = 0.02], TG [113 mg/dL (IQR 50-483) vs 88 mg/dL (IQR 16-343); p = 0.03], and the frequency of dyslipidemia [58.3% vs 22.2%; p = 0.001), as well as the TC correction with TG (r = 0.35; p = 0.02) and LDL-C (r = 0.88; p = 0.01). Persistent dyslipidemia was associated with obesity (r = 0.27; p = 0.02), overweight (r = 0.58; p = 0.001), and pre-treatment dyslipidemia (r = 0.53; p = 0.001). CONCLUSIONS: There is an association between TSH, TC, LDL-C, and HDL-C in hypothyroidism. When the thyroid profile was normalized, there was a reduction of TC, TG, LDL- C, and dyslipidemia frequency. Persistent dyslipidemia was associated with obesity, overweight, and pre-treatment dyslipidemia.

Biochemical Characteristics of Bone Mineral Metabolism before and throughout the First Year after Kidney Transplantation, Persistent Hyperparathyroidism, and Risk Factors in a Latin Population.

Bone mineral metabolism disease, which included persistent hyperparathyroidism, is common after successful kidney transplantation (KT) and is related with negative outcomes in kidney transplant recipients. There is a lack of information about bone mineral metabolism, persistent hyperparathyroidism, and its risk factors in Latin kidney transplant recipients (KTRs). Material and Methods: A retrospective study was conducted in 74 patients aged 18-50 years with evolution of 12 months after KT and estimated glomerular filtration rate (eGFR) >60 ml/min; biochemical data of bone mineral metabolism before and at 1, 3, 6, and 12 months of KT were registered. Results. Age was 33 (IQR 27-37) years; 54% (n = 40) were men. Before KT, all patients had hyperparathyroidism, 40% (n = 30) hypocalcemia, 86% (n = 64) hyperphosphatemia, and 42% (n = 31) hyperphosphatasemia. After KT, an increase of calcium and a diminution of PTH, phosphorus, and alkaline phosphatase were corroborated (p=0.001). All patients had hypovitaminosis D (deficiency: 91% (n = 67); insufficiency: 9% (n = 7)); 40% (n = 30) had persistent hyperparathyroidism at 12 months. Hyperphosphatasemia before KT (OR = 4.17 (95% CI: 1.21-14.44); p=0.04), hyperparathyroidism at 6 months (OR = 1.84 (95% CI; 1.67-2.06); p=0.02), hypovitaminosis D at 6 months (OR = 3.94 (95% CI: 1.86-17.9); p=0.01), and hyperphosphatasemia at 6 months (OR = 1.47 (95% CI: 1.07-2.86); p=0.03) were risk factors for persistent hyperparathyroidism at 12 months after KT. Conclusion. Persistent hyperparathyroidism at 6 months, hypovitaminosis D, and hyperphosphatasemia are risk factors for persistent hyperparathyroidism at 1 year of KT in Latin population.

The Testosterone Effect on Metabolic and Urologic Outcomes in Patients with Nonfunctioning Pituitary Macroadenomas and Hypogonadotropic Hypogonadism.

OBJECTIVE: To evaluate cardiovascular risk, metabolic profile, low urinary tract symptoms (LUTS), and sexual function in patients with nonfunctional pituitary macroadenoma (NFPMA) and hypogonadotropic hypogonadism with testosterone therapy (TTh). METHODS: A retrospective clinical study at a tertiary care center was performed in 101 men with NFPMA, HH, and TTh; metabolic profile, cardiovascular risk, International Prostate Symptoms Score (IPSS), and International Index of Erectile Function 5 (IIEF-5) scores were evaluated before initiation of TTh and at the last checkup with TTh. RESULTS: Age was 49.3 ± 8.8 years; T before TTh was 195 ng/mL (101-259) vs. 574 (423-774) at the last checkup. The time of TTh administration was 34 months (12-72). An increase in triglyceride levels (200 (153-294) vs. 174 (134-233) mg/dL; p=0.03), dyslipidemia (40% vs. 52%; p=0.03), and MetS (25% vs. 34%; p=0.05) was corroborated. A statistical difference in the Globorisk score and cardiovascular (CV) risk stratification was not found. IIEF-5 score was 15.5 ± 6.5 vs. 17.8 ± 5.3 (p=0.11). An improvement in penetration quality (2.0 ± 1.5 vs. 2.6 ± 1.3; p=0.05), erection after penetration (1.8 ± 1.2 vs. 2.5 ± 1.6; p=0.02), completion of intercourse (1.8 ± 1.2 vs. 2.4 ± 1.3; p=0.03), and satisfaction of sexual intercourse (1.8 ± 1.3 vs. 2.5 ± 1.5; p=0.01) was evidenced. IPSS score was 6 (IQR 2-10) vs. 7 (IQR 4-12); p=0.30. A lower rate of intermittency (14% vs. 3%; p=0.02), urgency (39% vs. 16%; p=0.01), and episodes of nocturia (18% vs. 4%; p=0.02) was found. An increase of hematocrit (44.1 ± 4.4 vs. 47.3 ± 4.4%; p=0.001), hemoglobin (14.9 ± 1.4 vs. 15.9 ± 1.4 g/dL; p=0.001), and prostatic specific antigen (0.59 (0.43-1.19) vs. 0.82 (0.45-1.4) ng/mL; p=0.02) was evidenced during TTh. CONCLUSION: TTh in young men with NFPMA improves LUTS, sexual function, and some metabolic parameters, and it is relatively safe in the prostatic context.