Background and Aims: Increased urinary sodium-to-potassium (Na/K) ratio has been associated with ... more Background and Aims: Increased urinary sodium-to-potassium (Na/K) ratio has been associated with chronic kidney disease. However, we demonstrated that urinary Na/K ratio does not accurately reflect dietary Na/K ratio. Rhythmic patterns of sodium storage and release from the skin interstitium are associated with aldosterone and cortisol levels and previous studies linked tissue sodium accumulation to water conservation. Therefore, we investigated whether the discrepancy between urinary and dietary Na/K ratio could be explained by these factors. Method: For this post-hoc analysis, we used data from the long-term sodium balance studies Mars105 and Mars520. These studies collected 24-hour urine samples and controlled dietary salt intake for 105 (4 men) and 205 days (6 men) at levels of 6, 9 and 12 grams per day. We calculated the difference between urinary and dietary Na/K ratio. We tested whether this difference varied across salt intake levels in a linear mixed-effects model. Furthermore, we fitted two linear mixed-effect models to explain discrepancies between urinary and dietary Na/K ratio. In the first model, sodium intake, potassium intake, urinary aldosterone and urinary cortisol were fixed effects and for each factor random slopes per participant were allowed. In the second model, sodium intake, potassium intake and urine volume were fixed effects and for each factor random slopes per participant were allowed. Each salt intake level was assessed separately. The median difference between 24-hour urinary and dietary Na/K ratio was -0.21 (IQR -0.47 to 0.09). At higher salt intake levels the underestimation was significantly larger (mean difference -0.11, -0.22 and -0.36 for 6, 9 and 12 grams salt intake, respectively; P<0.001). At each salt intake level, higher urinary aldosterone was associated with underestimation of the dietary Na/K ratio (Figure ). In contrast, higher urinary cortisol and higher urine volume were associated with relative overestimation of the dietary Na/K ratio (Figure and C, respectively). The discrepancy between dietary and urinary Na/K ratio can be explained by sodium intake, aldosterone, cortisol and urine volume. This suggests that tissue sodium accumulation contributes to the inaccuracy of a single 24-hour urine collection for estimation of dietary sodium and potassium intake.
Objective There is hardly any information on the consumption of healthcare resources by older peo... more Objective There is hardly any information on the consumption of healthcare resources by older people with differentiated thyroid cancer (DTC). We analyzed these consumptions in older patients with DTC and compared patients 75 years and older with subjects aged 60–74 years. Methods A multicenter, retrospective analysis was designed. We recorded three groups of health resources consumption (visits, diagnostic procedures, and therapeutic procedures) and identified a subgroup of patients with high consumption of resources. We compared elderly patients (group 1, 60–74 years) with very old patients (group 2, ≥ 75 years). Results We included 1654 patients (women, 74.4%), of whom 1388 (83.9%) belonged to group 1 and 266 (16.1%) to group 2. In group 2, we found a higher proportion of patients requiring emergency department visits (7.89% vs 4.32%, P < 0.05) and imaging studies (24.1% vs. 17.3%; P < 0.05) compared to group 1. However, we did not find any significant difference between bo...
Purpose The objective of this study was to determine the association between hypothyroidism and o... more Purpose The objective of this study was to determine the association between hypothyroidism and overall and site-specific cancer in Spanish population. Methods A cross-sectional study was performed using the population-based database BDCAP (Base de Datos Clínicos de Atención Primaria, primary care clinical database) to analyze the relative risk of cancer in Spanish population with hypothyroidism. Results In a total of 2,414,165 patients diagnosed with hypothyroidism in BDCAP in 2019, the relative risk (OR) of cancer, compared to the non-hypothyroid population, was 1.73 (1.72–1.74) (P<0.0001). The higher risk was observed in both men (OR 2.15 [2.13–2.17]; P<0.0001) and women (OR 1.67 [1.636–1.68]; P<0.0001). However, hypothyroid persons aged 65 years or older had a reduced risk of cancer (OR 0.98 [0.97–0.98]; P<0.0001). In addition, hypothyroid patients aged 65 or over showed a decreased risk of cancers of the bladder, colorectal, gastric, pancreatic and prostate. Socioec...
Background: Most pituitary adenomas (PAs) are considered to have a soft tumor consistency. Howeve... more Background: Most pituitary adenomas (PAs) are considered to have a soft tumor consistency. However, there is a non-negligible percentage (5-13%) of tumors presenting or exhibiting a fibrous consistency that would entail a more difficult and complicated surgical excision with higher surgical morbidity and mortality rates.Purpose: To analyze the clinical consequences of PA tumor consistency on the surgical outcomes in patients undergoing endonasal endoscopic transsphenoidal (EET) pituitary surgery.Methods: An ambispective study of patients with PAs operated on through an EET approach in two Spanish tertiary hospitals over the last 12 years. A total of 226 consecutive interventions were carried out in the Neurosurgery Departments of the Hospital Universitario Ramón y Cajal (HURC) and the Hospital Universitario Puerta del Sur by the same neurosurgeon. PAs were grouped into soft (n = 150) and fibrous (n = 76). All patients underwent hormonal and magnetic resonance imaging (MRI) studies b...
Background: Total thyroidectomy is the standard initial surgery for differentiated thyroid carcin... more Background: Total thyroidectomy is the standard initial surgery for differentiated thyroid carcinoma (DTC), but the extent of the thyroidectomy remains controversial. Thyroid lobectomy (TL) has been widely used in eastern countries; however, its use has not been generalized in western countries, including Spain. Our aims were to analyse the clinical outcome of a multicentre nation-wide cohort of DTC patients treated by TL and to assess the proportion of patients who required completion of the thyroidectomy and who presented disease recurrence. We retrospectively analyzed patients who underwent TL for DTC and were followed-up for ≥12 months. We collected demographic, clinical, and histopathological data. Dynamic risk stratification (DRS) was performed at 12 months and at last visit. Results: One hundred and sixty-four patients (128 women, mean age 50.8 years, median follow-up 45.4 months) from 9 hospitals were included. There were 158 cases of papillary and 6 of follicular thyroid carcinoma (FTC). Remission of the disease (excellent response) was shown in 71.6% of the patients at 12 months and in 74.4% at the end of follow-up. At that time, there were 34 patients (20.7%) with indeterminate response, 6 (3.7%) with biochemical incomplete response, and 2 (1.2%) with structural incomplete response. Completion of the thyroidectomy was necessary in 8 patients (4.9%), but only 3 of them (1.8%) had disease recurrence. Conclusions: These results, obtained in real clinical practice, suggest that TL is a safe operative option for selected patients with DTC and that the intensity of the treatment must be tailored according to the presurgical tumor-associated risk, in line with a personalized medicine.
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio, 2021
Objectives Graves’ disease is secondary to the presence of anti-thyrotropin receptor antibodies (... more Objectives Graves’ disease is secondary to the presence of anti-thyrotropin receptor antibodies (TRAb), which stimulate thyroid hormones. TRab determination is crucial for etiological diagnosis. The objectives of this study were (i) to compare two methods for determining TRab by chemoluminiscence vs. standard TRACE-immunofluorescence; (ii) to determine the diagnostic validity of the three methods. Methods A retrospective study in 194 patients with a TRAb determination request. TRAb were determined by immunofluorescence (Kryptor, ThermoFisher) and chemiluminescence (Immulite, Siemens and Maglumi, Snibe). Clinical validation: medical records were reviewed and categorized according to thyroid function. Statistical analysis: Differences in quantitative variables were assessed by intraclass correlation coefficient, Bland–Altman plot, and mean differences (mD). Qualitative variables were dichotomized by cut-off points; Kappa coefficient was calculated. Correlations were evaluated by Pears...
Objetive: To assess the clinical features of incidental clinically non-functioning pituitary aden... more Objetive: To assess the clinical features of incidental clinically non-functioning pituitary adenoma (NFPA) and to analyze its natural history. Methods: A multicenter retrospective study in patients with NFPA followed-up from 1992 to 2015 was performed. Results: Fifty-seven patients were studied (29 women (50.9%); age 55.8±16.7 years. 43.9% were older than 60 years, 40.3% belonged to the age group of 40-60 years and 15.8% were younger than 40 years. Most patients (n=55, 96.5%) were diagnosed by magnetic resonance imaging (MRI). 71.9% (n=41) were macroadenomas; 2 of them (3.5%) were giant adenomas (≧4 cm). Patients with macroadenomas were older than those with microadenomas (59.5±16.7 vs 46.4±18.1 years, P=0.007). Microadenomas were more common in women (41.3 vs 14.3%, P=0.023). About half of them (n=28; 49.1%) showed suprasellar extension; of these, 19 (33.3%) were accompanied by chiasmatic compression. Invasion of the cavernous sinuses was present in 28.1% (n=16). Hypopituitarism was present in 14 (24.6%) patients. Twenty-four patients (42.1%) underwent surgery. Twenty-six non-operated patients were evaluated after a median follow-up of 15.5 months (interquartile range, 5.7-32.7). No significant changes were found in the maximum tumor diameter at the end of follow-up (1.2±0.6 vs 1.2±0.7 cm; NS). The majority of NFPAs evaluated (n=23, 88.5%) did not show any changes in size. In two cases (7.7%) tumor size decreased and in one patient (3.8%) increased. Conclusion: Incidental NFPA is diagnosed by MRI preferably from the 5th decade of life without sex predilection. Most of them are macroadenomas, more commonly diagnosed in men and at an older age, compared to microadenomas. The suprasellar extension with chiasmatic compression and hypopituitarism are frequent at diagnosis. Most of the non-operated NFPAs remain with stable tumor size over time, being growth an unusual event.
Cardiovascular disease (CVD) is the most common cause of morbidity and mortality in developed cou... more Cardiovascular disease (CVD) is the most common cause of morbidity and mortality in developed countries. The prevalence of CVD is much higher in patients with type 2 diabetes mellitus (T2DM), who may benefit from lifestyle changes, which include adapted diets. In this review, we provide the role of different groups of nutrients in patients with T2DM and CVD, as well as dietary approaches that have been associated with better and worse outcomes in those patients. Many different diets and supplements have proved to be beneficial in T2DM and CVD, but further studies, guidelines, and dietary recommendations are particularly required for patients with both diseases.
Central adrenal insufficiency (AI) due to isolated adrenocorticotropic hormone (ACTH) deficiency ... more Central adrenal insufficiency (AI) due to isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) has been recently associated with immune checkpoint inhibitor (ICI) therapy. Our aim was to analyze the prevalence, clinical characteristics, and therapeutic outcomes in cancer patients with IAD induced by ICI therapy. A retrospective and multicenter study was performed. From a total of 4447 cancer patients treated with ICI antibodies, 37 (0.8%) (23 men (62.2%), mean age 64.7 ± 8.3 years (range 46–79 years)) were diagnosed with IAD. The tumor most frequently related to IAD was lung cancer (n = 20, 54.1%), followed by melanoma (n = 8, 21.6%). The most common ICI antibody inhibitors reported were nivolumab (n = 18, 48.6%), pembrolizumab (n = 16, 43.2%), and ipilimumab (n = 8, 21.6%). About half of the patients (n = 19, 51.4%) had other immune-related adverse events, mainly endocrine adverse effects (n = 10, 27.0%). IAD was diagnosed at a median time of 7.0 months (IQR, 5–12) after st...
Global Journal of Obesity, Diabetes and Metabolic Syndrome, 2017
The present study was intended to establish the role of bone in grade III obese women with and wi... more The present study was intended to establish the role of bone in grade III obese women with and without type 2 diabetes mellitus (T2DM). Material & Methods: Serum osteocalcin (OC), Beta Cross-Laps (Beta-CTx), parathormone (PTH) separar and y 25-hydroxyvitamin D (25OHD) concentrations were measured in 48 morbid obesity women (11 with T2DM and 37 control group). Insulin resistance and insulin secretion was assessed by measuring the HOMA-IR and the HOMAβ index and its association with OC and Beta-CTx. Results: Serum OC was signifi cant lower in the diabetic group compared with non-diabetic patients 15.4 ± 3.6 ng/ml vs 22.1 ± 3.5 ng/ml, p<0.001 without signifi cant differences in Beta-CTx (0.24 ± 0.1 vs 0.31 ± 0.2 ng/ml, ns). Both bone biomarkers, OC and Beta-CTx, showed a positive correlation (r=0.76; p<0.01) in the whole group subjects and in the control group (r=0.80, p<0.00), but no in the T2DM group (r=0.50, p ns). In the whole group of patients, OC correlated signifi cantly with HOMA-IR (r=0.36; p<0.01) and HOMA-ß (r=0.36, p<0.01). Beta-CTx also correlated with HOMA-IR (r= 0.40, p<0.01) and HOMA-ß (r= 0.41, p<0.001. OC also signifi cantly correlated with HOMA-IR (r=0.41, p<0.01) in non-diabetic patients and almost reached statistical signifi cance with HOMA-ß (r=0.32, p=0.053), but was not signifi cantly correlated with HOMA-ß (r= -0.53, ns) and with HOMA-IR index (r=0.52, ns) in the T2DM group. When we performed the multivariate logistic regression the serum level of OC was the only covariate found signifi cantly with DM2 with a coefi cient -6.65 , (95% CI, -12.75049 -.5674469 ); p = 0.03). Both groups showed secondary hyperparathyroidism (T2DM, 78.4 ± 19.4 pg/ml vs non-diabetic group, 75.4 ± 35.6 pg/ ml; ns). The majority of the patients showed 25OHD defi ciency 62.5%, followed by 25OHD insuffi ciency 27.1% and normal 25OHD levels in only 10.4%. The 25OHD defi ciency was present in both study groups (T2DM patients, 18.3 ± 7.4 pg/ml and nondiabetic group, 19.7 ± 9.6 pg/ml; ns). OC and Beta-CTx could play a role in glucose metabolism and insulin resistance. Serum OC concentrations are signifi cantly reduced in T2DM morbidily obese women compared with nondiabetic group, and add new evidence on the possible role of bone as an endocrine organ with metabolic implications specially the levels of OC.
Experimental and Clinical Endocrinology & Diabetes, 2020
Background Giant pituitary adenoma (≥4 cm) is a rare tumor whose clinical features and prognosis ... more Background Giant pituitary adenoma (≥4 cm) is a rare tumor whose clinical features and prognosis are not well known. Aim To evaluate the clinical characteristics and therapeutic outcomes of giant non-functioning PA (gNFPA). Patients and Methods A retrospective multicenter study of gNFPA patients diagnosed in a 12-year period was performed. In each patient, clinical data and therapeutic outcomes were registered. Results Forty patients (24 men, age 54.2 ± 16.2 years) were studied. The maximum tumor diameter [median (interquartile range)] was 4.6 cm (4.1–5.1). Women had larger tumors [4.8 cm (4.2–5.4) vs. 4.5 cm (4.0–4.9); p=0.048]. Hypopituitarism [partial (n=22, 55%) or complete (n=9, 22.5%)] at diagnosis was present in 77.5% of the patients. Visual field defects were found in 90.9%. The most used surgical technique was endoscopic endonasal transsphenoidal (EET) surgery (n=31, 77.5%). Radiotherapy was used in 11 (27.5%) patients (median dose 50.4 Gy, range 50–54). Thirty-seven patien...
The concept of aggressive pituitary tumor (APT) has been precisely defined in recent years. These... more The concept of aggressive pituitary tumor (APT) has been precisely defined in recent years. These tumors are characterized by morphological (radiological or histopathological) data of invasion, proliferative activity superior to that of typical adenomas and a clinical behavior characterized by resistance to standard therapies and frequent recurrences. The absence of cerebrospinal or distant metastases differentiates them from the pituitary carcinoma. APTs account for about 10% of all pituitary neoplasm. Proper diagnostic implies participation not only of radiological and hormonal investigation but also a thorough pathological assessment including proliferation markers and immunohistochemistry for hormones and transcription factors. Surgical resection, aiming gross total resection or tumor debulking, is the mainstay initial therapy in most patients. Most patients with APTs need more than one surgical intervention, pituitary radiation, sometimes on more than one occasion, and multiple sequential or combined medical treatments, to finally be doomed to unusual treatments, such as alkylating agents (temozolomide alone or in combination), molecular targeted therapies, or peptide receptor radionuclide therapy. Multimodal therapy, implemented by experts, preferably in specialized centers with high volume caseload, is the only way to improve the prognosis of patients with these uncommon tumors. The research needs in this area are multiple and include a greater knowledge of the molecular biology of these tumors, establishment of protocols for monitoring and sequencing of treatments, development of multicenter studies and international registries.
European journal of internal medicine, Jan 4, 2017
To assess clinical features, diagnostic procedures, therapies and outcomes in patients with clini... more To assess clinical features, diagnostic procedures, therapies and outcomes in patients with clinically non-functioning pituitary adenomas (NFPAs) surgically treated over the last four decades. A multicenter retrospective study in NFPA patients periodically followed up in specialized neuroendocrinology units who underwent surgery in the period 1977-2015 was performed. A total of 131 patients were studied [66 women (50.4%); mean age 52.6±14.8years (range, 15-82)]. Median diameter of the adenoma was 2.6cm (interquartile range, 2.0-3.1). The most frequently type of surgery used was endoscopic endonasal surgery (58.5%) followed by microscopic transsphenoidal surgery (37.4%). Radiation therapy was used in 19 patients (14.5%). Ki-67 labeling index performed in 54 patients was ≤2% in 70% samples. After a median follow-up time of 57months (25 to 128months), tumor diameter significantly decreased to 0.9cm (0-1.8cm), p<0.001. Multivariant analysis showed that endoscopic endonasal surgery (H...
Rapid Nelson's syndrome development after bilateral adrenalectomy is a rare event. A 34-year-old ... more Rapid Nelson's syndrome development after bilateral adrenalectomy is a rare event. A 34-year-old man was referred in 2012 with suspected Cushing's syndrome (CS). Hormonal investigations showed hypercortisolism [serum cortisol 49.2 lg/dl (normal range, NR: 5-25); 24 h urinary-free cortisol, UFC 1903 lg/24 h (NR: <140); serum cortisol after 1 mg dexametasone 23:00 h, 42.1 lg/dl (N < 1.8)] with increased plasma ACTH concentration (120 pg/ml; NR: 5-46)]. Magnetic resonance imaging (MRI) of the pituitary gland was normal (Figure 1A). Inferior petrosal sinus sampling (IPSS) with plasma ACTH quantification before and after 100 lg of corticotropin-releasing hormone (CRH) showed no gradient of central/peripheral plasma ACTH both baseline (IPS:peripheral ratio < 2) and post-CRH (IPS:peripheral ratio <3) suggesting ectopic ACTH secretion (EAS). Localizing studies by chest radiography, thoracoabdominal CT scan, abdominal MRI, octreoscan, bronchoscopy, echo-endoscopy, colonoscopy and 18
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio
Resumen Objetivos La enfermedad de Graves (EG) es una enfermedad secundaria a la presencia de aut... more Resumen Objetivos La enfermedad de Graves (EG) es una enfermedad secundaria a la presencia de autoanticuerpos anti-receptor de TSH (TRAb) que estimulan la producción de hormonas tiroideas. La medida de la concentración de TRAb es crucial para su diagnóstico etiológico. Los objetivos de este estudio fueron 1. Comparar dos métodos de medida de TRAb por quimioluminiscencia con el método habitual del laboratorio (TRACE-inmunofluorescencia). 2. Determinar la validez diagnóstica de los tres métodos. Métodos Estudio retrospectivo de 194 pacientes con petición de TRAb, analizado por: inmunofluorescencia (Kryptor, ThermoFisher) y quimioluminiscencia (Immulite, Siemens y Maglumi, Snibe). Validación clínica: revisión de historias clínicas y clasificación según función tiroidea. Análisis estadísticos: Variables cuantitativas, coeficiente de correlación intraclase (CCI) y gráfica de Bland-Altman, diferencia de medias (Dm). Variables cualitativas, dicotomizadas según puntos de corte, coeficiente ...
Reviews in endocrine and metabolic disorders, Nov 18, 2016
Thyroid hormones influence renal development, kidney hemodynamics, glomerular filtration rate and... more Thyroid hormones influence renal development, kidney hemodynamics, glomerular filtration rate and sodium and water homeostasis. Hypothyroidism and hyperthyroidism affect renal function by direct renal effects as well as systemic hemodynamic, metabolic and cardiovascular effects. Hypothyroidism has been associated with increased serum creatinine and decreased glomerular filtration rate. The reverse effects have been reported in thyrotoxicosis. Most of renal manifestations of thyroid dysfunction are reversible with treatment. Kidney disease may also cause thyroid dysfunction by several mechanisms. Nephrotic syndrome has been associated to changes in serum thyroid hormone concentrations. Different forms of glomerulonephritis and tubulointerstitial disease may be linked to thyroid derangements. A high prevalence of thyroid hormone alteration has been reported in acute kidney injury. Thyroid dysfunction is highly prevalent in chronic kidney disease patients. Subclinical hypothyroidism and low triiodothyronine syndrome are common features in patients with chronic kidney disease. Patients treated by both hemodialysis and peritoneal dialysis, and renal transplantation recipients, exhibit thyroid hormone alterations and thyroid disease with higher frequency than that found in the general population. Drugs used in the therapy of thyroid disease may lead to renal complications and, similarly, drugs used in kidney disorders may be associated to thyroid alterations. Lastly, low thyroid hormones, especially low triiodothyronine levels, in patients with chronic kidney disease have been related to a higher risk of cardiovascular disease and allcause mortality. Interpretation of the interactions between thyroid and renal function is a challenge for clinicians involved in the treatment of patients with thyroid and kidney disease.
We studied a 55-year-old woman with remarkable cushingoid features, which presented biochemical e... more We studied a 55-year-old woman with remarkable cushingoid features, which presented biochemical evidence of suppression of the hypothalamus-hypophysis-adrenal axis. In the detailed anamnesis, we discovered that the patient had used during more than two years a nasal spray containing dexamethasone. In the initial assessment of the suprarenal function, in addition to suppressed concentrations of cortisol and ACTH, we observed the absence of response to acute stimulus (insulinic hypoglycemia and short ACTH test), as well as a normal response to sustained ACTH stimulus. After discontinuing the intranasal administration of dexamethasone, the patient remained asymptomatic; the basal concentrations of ACTH and cortisol, as well as the levels of urinary free cortisol, were normal at 3 months and the responses of cortisol and ACTH to their stimulus were restored to normal levels at 6 months. We conclude that in the cases of Cushing's syndrome with suppression of the hypothalamus-hypophysis-adrenal axis, it is necessary to conduct a detailed investigation on the consumption of glucocorticoids through unusual ways. The presence of a normal response to the sustained stimulus with ACTH may be a quick recovery index of the suprarenal function.
Background and Aims: Increased urinary sodium-to-potassium (Na/K) ratio has been associated with ... more Background and Aims: Increased urinary sodium-to-potassium (Na/K) ratio has been associated with chronic kidney disease. However, we demonstrated that urinary Na/K ratio does not accurately reflect dietary Na/K ratio. Rhythmic patterns of sodium storage and release from the skin interstitium are associated with aldosterone and cortisol levels and previous studies linked tissue sodium accumulation to water conservation. Therefore, we investigated whether the discrepancy between urinary and dietary Na/K ratio could be explained by these factors. Method: For this post-hoc analysis, we used data from the long-term sodium balance studies Mars105 and Mars520. These studies collected 24-hour urine samples and controlled dietary salt intake for 105 (4 men) and 205 days (6 men) at levels of 6, 9 and 12 grams per day. We calculated the difference between urinary and dietary Na/K ratio. We tested whether this difference varied across salt intake levels in a linear mixed-effects model. Furthermore, we fitted two linear mixed-effect models to explain discrepancies between urinary and dietary Na/K ratio. In the first model, sodium intake, potassium intake, urinary aldosterone and urinary cortisol were fixed effects and for each factor random slopes per participant were allowed. In the second model, sodium intake, potassium intake and urine volume were fixed effects and for each factor random slopes per participant were allowed. Each salt intake level was assessed separately. The median difference between 24-hour urinary and dietary Na/K ratio was -0.21 (IQR -0.47 to 0.09). At higher salt intake levels the underestimation was significantly larger (mean difference -0.11, -0.22 and -0.36 for 6, 9 and 12 grams salt intake, respectively; P<0.001). At each salt intake level, higher urinary aldosterone was associated with underestimation of the dietary Na/K ratio (Figure ). In contrast, higher urinary cortisol and higher urine volume were associated with relative overestimation of the dietary Na/K ratio (Figure and C, respectively). The discrepancy between dietary and urinary Na/K ratio can be explained by sodium intake, aldosterone, cortisol and urine volume. This suggests that tissue sodium accumulation contributes to the inaccuracy of a single 24-hour urine collection for estimation of dietary sodium and potassium intake.
Objective There is hardly any information on the consumption of healthcare resources by older peo... more Objective There is hardly any information on the consumption of healthcare resources by older people with differentiated thyroid cancer (DTC). We analyzed these consumptions in older patients with DTC and compared patients 75 years and older with subjects aged 60–74 years. Methods A multicenter, retrospective analysis was designed. We recorded three groups of health resources consumption (visits, diagnostic procedures, and therapeutic procedures) and identified a subgroup of patients with high consumption of resources. We compared elderly patients (group 1, 60–74 years) with very old patients (group 2, ≥ 75 years). Results We included 1654 patients (women, 74.4%), of whom 1388 (83.9%) belonged to group 1 and 266 (16.1%) to group 2. In group 2, we found a higher proportion of patients requiring emergency department visits (7.89% vs 4.32%, P < 0.05) and imaging studies (24.1% vs. 17.3%; P < 0.05) compared to group 1. However, we did not find any significant difference between bo...
Purpose The objective of this study was to determine the association between hypothyroidism and o... more Purpose The objective of this study was to determine the association between hypothyroidism and overall and site-specific cancer in Spanish population. Methods A cross-sectional study was performed using the population-based database BDCAP (Base de Datos Clínicos de Atención Primaria, primary care clinical database) to analyze the relative risk of cancer in Spanish population with hypothyroidism. Results In a total of 2,414,165 patients diagnosed with hypothyroidism in BDCAP in 2019, the relative risk (OR) of cancer, compared to the non-hypothyroid population, was 1.73 (1.72–1.74) (P<0.0001). The higher risk was observed in both men (OR 2.15 [2.13–2.17]; P<0.0001) and women (OR 1.67 [1.636–1.68]; P<0.0001). However, hypothyroid persons aged 65 years or older had a reduced risk of cancer (OR 0.98 [0.97–0.98]; P<0.0001). In addition, hypothyroid patients aged 65 or over showed a decreased risk of cancers of the bladder, colorectal, gastric, pancreatic and prostate. Socioec...
Background: Most pituitary adenomas (PAs) are considered to have a soft tumor consistency. Howeve... more Background: Most pituitary adenomas (PAs) are considered to have a soft tumor consistency. However, there is a non-negligible percentage (5-13%) of tumors presenting or exhibiting a fibrous consistency that would entail a more difficult and complicated surgical excision with higher surgical morbidity and mortality rates.Purpose: To analyze the clinical consequences of PA tumor consistency on the surgical outcomes in patients undergoing endonasal endoscopic transsphenoidal (EET) pituitary surgery.Methods: An ambispective study of patients with PAs operated on through an EET approach in two Spanish tertiary hospitals over the last 12 years. A total of 226 consecutive interventions were carried out in the Neurosurgery Departments of the Hospital Universitario Ramón y Cajal (HURC) and the Hospital Universitario Puerta del Sur by the same neurosurgeon. PAs were grouped into soft (n = 150) and fibrous (n = 76). All patients underwent hormonal and magnetic resonance imaging (MRI) studies b...
Background: Total thyroidectomy is the standard initial surgery for differentiated thyroid carcin... more Background: Total thyroidectomy is the standard initial surgery for differentiated thyroid carcinoma (DTC), but the extent of the thyroidectomy remains controversial. Thyroid lobectomy (TL) has been widely used in eastern countries; however, its use has not been generalized in western countries, including Spain. Our aims were to analyse the clinical outcome of a multicentre nation-wide cohort of DTC patients treated by TL and to assess the proportion of patients who required completion of the thyroidectomy and who presented disease recurrence. We retrospectively analyzed patients who underwent TL for DTC and were followed-up for ≥12 months. We collected demographic, clinical, and histopathological data. Dynamic risk stratification (DRS) was performed at 12 months and at last visit. Results: One hundred and sixty-four patients (128 women, mean age 50.8 years, median follow-up 45.4 months) from 9 hospitals were included. There were 158 cases of papillary and 6 of follicular thyroid carcinoma (FTC). Remission of the disease (excellent response) was shown in 71.6% of the patients at 12 months and in 74.4% at the end of follow-up. At that time, there were 34 patients (20.7%) with indeterminate response, 6 (3.7%) with biochemical incomplete response, and 2 (1.2%) with structural incomplete response. Completion of the thyroidectomy was necessary in 8 patients (4.9%), but only 3 of them (1.8%) had disease recurrence. Conclusions: These results, obtained in real clinical practice, suggest that TL is a safe operative option for selected patients with DTC and that the intensity of the treatment must be tailored according to the presurgical tumor-associated risk, in line with a personalized medicine.
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio, 2021
Objectives Graves’ disease is secondary to the presence of anti-thyrotropin receptor antibodies (... more Objectives Graves’ disease is secondary to the presence of anti-thyrotropin receptor antibodies (TRAb), which stimulate thyroid hormones. TRab determination is crucial for etiological diagnosis. The objectives of this study were (i) to compare two methods for determining TRab by chemoluminiscence vs. standard TRACE-immunofluorescence; (ii) to determine the diagnostic validity of the three methods. Methods A retrospective study in 194 patients with a TRAb determination request. TRAb were determined by immunofluorescence (Kryptor, ThermoFisher) and chemiluminescence (Immulite, Siemens and Maglumi, Snibe). Clinical validation: medical records were reviewed and categorized according to thyroid function. Statistical analysis: Differences in quantitative variables were assessed by intraclass correlation coefficient, Bland–Altman plot, and mean differences (mD). Qualitative variables were dichotomized by cut-off points; Kappa coefficient was calculated. Correlations were evaluated by Pears...
Objetive: To assess the clinical features of incidental clinically non-functioning pituitary aden... more Objetive: To assess the clinical features of incidental clinically non-functioning pituitary adenoma (NFPA) and to analyze its natural history. Methods: A multicenter retrospective study in patients with NFPA followed-up from 1992 to 2015 was performed. Results: Fifty-seven patients were studied (29 women (50.9%); age 55.8±16.7 years. 43.9% were older than 60 years, 40.3% belonged to the age group of 40-60 years and 15.8% were younger than 40 years. Most patients (n=55, 96.5%) were diagnosed by magnetic resonance imaging (MRI). 71.9% (n=41) were macroadenomas; 2 of them (3.5%) were giant adenomas (≧4 cm). Patients with macroadenomas were older than those with microadenomas (59.5±16.7 vs 46.4±18.1 years, P=0.007). Microadenomas were more common in women (41.3 vs 14.3%, P=0.023). About half of them (n=28; 49.1%) showed suprasellar extension; of these, 19 (33.3%) were accompanied by chiasmatic compression. Invasion of the cavernous sinuses was present in 28.1% (n=16). Hypopituitarism was present in 14 (24.6%) patients. Twenty-four patients (42.1%) underwent surgery. Twenty-six non-operated patients were evaluated after a median follow-up of 15.5 months (interquartile range, 5.7-32.7). No significant changes were found in the maximum tumor diameter at the end of follow-up (1.2±0.6 vs 1.2±0.7 cm; NS). The majority of NFPAs evaluated (n=23, 88.5%) did not show any changes in size. In two cases (7.7%) tumor size decreased and in one patient (3.8%) increased. Conclusion: Incidental NFPA is diagnosed by MRI preferably from the 5th decade of life without sex predilection. Most of them are macroadenomas, more commonly diagnosed in men and at an older age, compared to microadenomas. The suprasellar extension with chiasmatic compression and hypopituitarism are frequent at diagnosis. Most of the non-operated NFPAs remain with stable tumor size over time, being growth an unusual event.
Cardiovascular disease (CVD) is the most common cause of morbidity and mortality in developed cou... more Cardiovascular disease (CVD) is the most common cause of morbidity and mortality in developed countries. The prevalence of CVD is much higher in patients with type 2 diabetes mellitus (T2DM), who may benefit from lifestyle changes, which include adapted diets. In this review, we provide the role of different groups of nutrients in patients with T2DM and CVD, as well as dietary approaches that have been associated with better and worse outcomes in those patients. Many different diets and supplements have proved to be beneficial in T2DM and CVD, but further studies, guidelines, and dietary recommendations are particularly required for patients with both diseases.
Central adrenal insufficiency (AI) due to isolated adrenocorticotropic hormone (ACTH) deficiency ... more Central adrenal insufficiency (AI) due to isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) has been recently associated with immune checkpoint inhibitor (ICI) therapy. Our aim was to analyze the prevalence, clinical characteristics, and therapeutic outcomes in cancer patients with IAD induced by ICI therapy. A retrospective and multicenter study was performed. From a total of 4447 cancer patients treated with ICI antibodies, 37 (0.8%) (23 men (62.2%), mean age 64.7 ± 8.3 years (range 46–79 years)) were diagnosed with IAD. The tumor most frequently related to IAD was lung cancer (n = 20, 54.1%), followed by melanoma (n = 8, 21.6%). The most common ICI antibody inhibitors reported were nivolumab (n = 18, 48.6%), pembrolizumab (n = 16, 43.2%), and ipilimumab (n = 8, 21.6%). About half of the patients (n = 19, 51.4%) had other immune-related adverse events, mainly endocrine adverse effects (n = 10, 27.0%). IAD was diagnosed at a median time of 7.0 months (IQR, 5–12) after st...
Global Journal of Obesity, Diabetes and Metabolic Syndrome, 2017
The present study was intended to establish the role of bone in grade III obese women with and wi... more The present study was intended to establish the role of bone in grade III obese women with and without type 2 diabetes mellitus (T2DM). Material & Methods: Serum osteocalcin (OC), Beta Cross-Laps (Beta-CTx), parathormone (PTH) separar and y 25-hydroxyvitamin D (25OHD) concentrations were measured in 48 morbid obesity women (11 with T2DM and 37 control group). Insulin resistance and insulin secretion was assessed by measuring the HOMA-IR and the HOMAβ index and its association with OC and Beta-CTx. Results: Serum OC was signifi cant lower in the diabetic group compared with non-diabetic patients 15.4 ± 3.6 ng/ml vs 22.1 ± 3.5 ng/ml, p<0.001 without signifi cant differences in Beta-CTx (0.24 ± 0.1 vs 0.31 ± 0.2 ng/ml, ns). Both bone biomarkers, OC and Beta-CTx, showed a positive correlation (r=0.76; p<0.01) in the whole group subjects and in the control group (r=0.80, p<0.00), but no in the T2DM group (r=0.50, p ns). In the whole group of patients, OC correlated signifi cantly with HOMA-IR (r=0.36; p<0.01) and HOMA-ß (r=0.36, p<0.01). Beta-CTx also correlated with HOMA-IR (r= 0.40, p<0.01) and HOMA-ß (r= 0.41, p<0.001. OC also signifi cantly correlated with HOMA-IR (r=0.41, p<0.01) in non-diabetic patients and almost reached statistical signifi cance with HOMA-ß (r=0.32, p=0.053), but was not signifi cantly correlated with HOMA-ß (r= -0.53, ns) and with HOMA-IR index (r=0.52, ns) in the T2DM group. When we performed the multivariate logistic regression the serum level of OC was the only covariate found signifi cantly with DM2 with a coefi cient -6.65 , (95% CI, -12.75049 -.5674469 ); p = 0.03). Both groups showed secondary hyperparathyroidism (T2DM, 78.4 ± 19.4 pg/ml vs non-diabetic group, 75.4 ± 35.6 pg/ ml; ns). The majority of the patients showed 25OHD defi ciency 62.5%, followed by 25OHD insuffi ciency 27.1% and normal 25OHD levels in only 10.4%. The 25OHD defi ciency was present in both study groups (T2DM patients, 18.3 ± 7.4 pg/ml and nondiabetic group, 19.7 ± 9.6 pg/ml; ns). OC and Beta-CTx could play a role in glucose metabolism and insulin resistance. Serum OC concentrations are signifi cantly reduced in T2DM morbidily obese women compared with nondiabetic group, and add new evidence on the possible role of bone as an endocrine organ with metabolic implications specially the levels of OC.
Experimental and Clinical Endocrinology & Diabetes, 2020
Background Giant pituitary adenoma (≥4 cm) is a rare tumor whose clinical features and prognosis ... more Background Giant pituitary adenoma (≥4 cm) is a rare tumor whose clinical features and prognosis are not well known. Aim To evaluate the clinical characteristics and therapeutic outcomes of giant non-functioning PA (gNFPA). Patients and Methods A retrospective multicenter study of gNFPA patients diagnosed in a 12-year period was performed. In each patient, clinical data and therapeutic outcomes were registered. Results Forty patients (24 men, age 54.2 ± 16.2 years) were studied. The maximum tumor diameter [median (interquartile range)] was 4.6 cm (4.1–5.1). Women had larger tumors [4.8 cm (4.2–5.4) vs. 4.5 cm (4.0–4.9); p=0.048]. Hypopituitarism [partial (n=22, 55%) or complete (n=9, 22.5%)] at diagnosis was present in 77.5% of the patients. Visual field defects were found in 90.9%. The most used surgical technique was endoscopic endonasal transsphenoidal (EET) surgery (n=31, 77.5%). Radiotherapy was used in 11 (27.5%) patients (median dose 50.4 Gy, range 50–54). Thirty-seven patien...
The concept of aggressive pituitary tumor (APT) has been precisely defined in recent years. These... more The concept of aggressive pituitary tumor (APT) has been precisely defined in recent years. These tumors are characterized by morphological (radiological or histopathological) data of invasion, proliferative activity superior to that of typical adenomas and a clinical behavior characterized by resistance to standard therapies and frequent recurrences. The absence of cerebrospinal or distant metastases differentiates them from the pituitary carcinoma. APTs account for about 10% of all pituitary neoplasm. Proper diagnostic implies participation not only of radiological and hormonal investigation but also a thorough pathological assessment including proliferation markers and immunohistochemistry for hormones and transcription factors. Surgical resection, aiming gross total resection or tumor debulking, is the mainstay initial therapy in most patients. Most patients with APTs need more than one surgical intervention, pituitary radiation, sometimes on more than one occasion, and multiple sequential or combined medical treatments, to finally be doomed to unusual treatments, such as alkylating agents (temozolomide alone or in combination), molecular targeted therapies, or peptide receptor radionuclide therapy. Multimodal therapy, implemented by experts, preferably in specialized centers with high volume caseload, is the only way to improve the prognosis of patients with these uncommon tumors. The research needs in this area are multiple and include a greater knowledge of the molecular biology of these tumors, establishment of protocols for monitoring and sequencing of treatments, development of multicenter studies and international registries.
European journal of internal medicine, Jan 4, 2017
To assess clinical features, diagnostic procedures, therapies and outcomes in patients with clini... more To assess clinical features, diagnostic procedures, therapies and outcomes in patients with clinically non-functioning pituitary adenomas (NFPAs) surgically treated over the last four decades. A multicenter retrospective study in NFPA patients periodically followed up in specialized neuroendocrinology units who underwent surgery in the period 1977-2015 was performed. A total of 131 patients were studied [66 women (50.4%); mean age 52.6±14.8years (range, 15-82)]. Median diameter of the adenoma was 2.6cm (interquartile range, 2.0-3.1). The most frequently type of surgery used was endoscopic endonasal surgery (58.5%) followed by microscopic transsphenoidal surgery (37.4%). Radiation therapy was used in 19 patients (14.5%). Ki-67 labeling index performed in 54 patients was ≤2% in 70% samples. After a median follow-up time of 57months (25 to 128months), tumor diameter significantly decreased to 0.9cm (0-1.8cm), p<0.001. Multivariant analysis showed that endoscopic endonasal surgery (H...
Rapid Nelson's syndrome development after bilateral adrenalectomy is a rare event. A 34-year-old ... more Rapid Nelson's syndrome development after bilateral adrenalectomy is a rare event. A 34-year-old man was referred in 2012 with suspected Cushing's syndrome (CS). Hormonal investigations showed hypercortisolism [serum cortisol 49.2 lg/dl (normal range, NR: 5-25); 24 h urinary-free cortisol, UFC 1903 lg/24 h (NR: <140); serum cortisol after 1 mg dexametasone 23:00 h, 42.1 lg/dl (N < 1.8)] with increased plasma ACTH concentration (120 pg/ml; NR: 5-46)]. Magnetic resonance imaging (MRI) of the pituitary gland was normal (Figure 1A). Inferior petrosal sinus sampling (IPSS) with plasma ACTH quantification before and after 100 lg of corticotropin-releasing hormone (CRH) showed no gradient of central/peripheral plasma ACTH both baseline (IPS:peripheral ratio < 2) and post-CRH (IPS:peripheral ratio <3) suggesting ectopic ACTH secretion (EAS). Localizing studies by chest radiography, thoracoabdominal CT scan, abdominal MRI, octreoscan, bronchoscopy, echo-endoscopy, colonoscopy and 18
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio
Resumen Objetivos La enfermedad de Graves (EG) es una enfermedad secundaria a la presencia de aut... more Resumen Objetivos La enfermedad de Graves (EG) es una enfermedad secundaria a la presencia de autoanticuerpos anti-receptor de TSH (TRAb) que estimulan la producción de hormonas tiroideas. La medida de la concentración de TRAb es crucial para su diagnóstico etiológico. Los objetivos de este estudio fueron 1. Comparar dos métodos de medida de TRAb por quimioluminiscencia con el método habitual del laboratorio (TRACE-inmunofluorescencia). 2. Determinar la validez diagnóstica de los tres métodos. Métodos Estudio retrospectivo de 194 pacientes con petición de TRAb, analizado por: inmunofluorescencia (Kryptor, ThermoFisher) y quimioluminiscencia (Immulite, Siemens y Maglumi, Snibe). Validación clínica: revisión de historias clínicas y clasificación según función tiroidea. Análisis estadísticos: Variables cuantitativas, coeficiente de correlación intraclase (CCI) y gráfica de Bland-Altman, diferencia de medias (Dm). Variables cualitativas, dicotomizadas según puntos de corte, coeficiente ...
Reviews in endocrine and metabolic disorders, Nov 18, 2016
Thyroid hormones influence renal development, kidney hemodynamics, glomerular filtration rate and... more Thyroid hormones influence renal development, kidney hemodynamics, glomerular filtration rate and sodium and water homeostasis. Hypothyroidism and hyperthyroidism affect renal function by direct renal effects as well as systemic hemodynamic, metabolic and cardiovascular effects. Hypothyroidism has been associated with increased serum creatinine and decreased glomerular filtration rate. The reverse effects have been reported in thyrotoxicosis. Most of renal manifestations of thyroid dysfunction are reversible with treatment. Kidney disease may also cause thyroid dysfunction by several mechanisms. Nephrotic syndrome has been associated to changes in serum thyroid hormone concentrations. Different forms of glomerulonephritis and tubulointerstitial disease may be linked to thyroid derangements. A high prevalence of thyroid hormone alteration has been reported in acute kidney injury. Thyroid dysfunction is highly prevalent in chronic kidney disease patients. Subclinical hypothyroidism and low triiodothyronine syndrome are common features in patients with chronic kidney disease. Patients treated by both hemodialysis and peritoneal dialysis, and renal transplantation recipients, exhibit thyroid hormone alterations and thyroid disease with higher frequency than that found in the general population. Drugs used in the therapy of thyroid disease may lead to renal complications and, similarly, drugs used in kidney disorders may be associated to thyroid alterations. Lastly, low thyroid hormones, especially low triiodothyronine levels, in patients with chronic kidney disease have been related to a higher risk of cardiovascular disease and allcause mortality. Interpretation of the interactions between thyroid and renal function is a challenge for clinicians involved in the treatment of patients with thyroid and kidney disease.
We studied a 55-year-old woman with remarkable cushingoid features, which presented biochemical e... more We studied a 55-year-old woman with remarkable cushingoid features, which presented biochemical evidence of suppression of the hypothalamus-hypophysis-adrenal axis. In the detailed anamnesis, we discovered that the patient had used during more than two years a nasal spray containing dexamethasone. In the initial assessment of the suprarenal function, in addition to suppressed concentrations of cortisol and ACTH, we observed the absence of response to acute stimulus (insulinic hypoglycemia and short ACTH test), as well as a normal response to sustained ACTH stimulus. After discontinuing the intranasal administration of dexamethasone, the patient remained asymptomatic; the basal concentrations of ACTH and cortisol, as well as the levels of urinary free cortisol, were normal at 3 months and the responses of cortisol and ACTH to their stimulus were restored to normal levels at 6 months. We conclude that in the cases of Cushing's syndrome with suppression of the hypothalamus-hypophysis-adrenal axis, it is necessary to conduct a detailed investigation on the consumption of glucocorticoids through unusual ways. The presence of a normal response to the sustained stimulus with ACTH may be a quick recovery index of the suprarenal function.
Uploads
Papers by Pedro Iglesias