Macroprolactin: From laboratory to clinical practice.

Prolactin measurement is very common in standard clinical practice. It is indicated not only in the study of pituitary adenomas, but also when there are problems with fertility, decreased libido, or menstrual disorders, among other problems. Inadequate interpretation of prolactin levels without contextualizing the laboratory results with the clinical, pharmacological, and gynecological/urological history of patients leads to erroneous diagnoses and, thus, to poorly based studies and treatments. Macroprolactinemia, defined as hyperprolactinemia due to excess macroprolactin (an isoform of a greater molecular weight than prolactin but with less biological activity), is one of the main causes of such erroneous diagnoses, resulting in poor patient management when not recognized. There is no unanimous agreement as to when macroprolactin screening is required in patients with hyperprolactinemia. At some institutions, macroprolactin testing by polyethylene glycol (PEG) precipitation is routinely performed in all patients with hyperprolactinemia, while others use a clinically based approach. There is also no consensus on how to express the results of prolactin/macroprolactin levels after PEG, which in some cases may lead to an erroneous interpretation of the results. The objectives of this study were: 1. To establish the strategy for macroprolactin screening by serum precipitation with PEG in patients with hyperprolactinemia: universal screening versus a strategy guided by the alert generated by the clinician based on the absence or presence of clinical symptoms or by the laboratory when hyperprolactinemia is detected. 2. To create a consensus document that standardizes the reporting of prolactin results after precipitation with PEG to minimize errors in the interpretation of the results, in line with international standards.

Do the Prostate-Specific Antigen (PSA) Tests That Are Ordered in Clinical Practice Adhere to the Pertinent Guidelines?

Scientific societies have provided guidelines to reduce PSA-specific harms. We studied the potential non-compliance of PSA testing with current guidelines in general practice. A cross-sectional study of a random sample of 1291 patients with a PSA test was performed between January and April 2018 in primary health care. Patients with a previous prostate cancer diagnosis or those who were being followed-up for previous high PSA values were excluded. Two independent researchers classified whether each test was potentially non-compliant with recommendations. We estimated frequencies of potentially non-compliant PSA determinations and calculated prevalence ratios (PR) to assess their relationship with possible explanatory variables. A total of 66% (95% CI: 62-69%) of PSA requests in asymptomatic patients were potentially non-compliant with the current guideline. This was associated with having a previous diagnosis of neoplasm (PR adjusted by age and life expectancy: 1.18; 95% CI: 1.02-1.37) as well as being a current consumer of tobacco, alcohol, or other drugs (PR: 0.80; 95% CI: 0.67-0.97). Real world data shows that patients are still frequently exposed to overdiagnosis risk with a PSA potentially non-compliant with recommendations. Patients diagnosed with another neoplasm or non-consumers of toxic substances were more exposed, probably due to increased contact with doctors or health-seeking behaviour.

Macroprolactin: From laboratory to clinical practice. / Macroprolactina: del laboratorio a la práctica clínica. Recomendaciones del grupo de trabajo de laboratorio de la SEEN y de la comisión de hormonas de la SEQCML sobre la medición e informe del resultado de la macroprolactina.

Prolactin measurement is very common in standard clinical practice. It is indicated not only in the study of pituitary adenomas, but also when there are problems with fertility, decreased libido, or menstrual disorders, among other problems. Inadequate interpretation of prolactin levels without contextualizing the laboratory results with the clinical, pharmacological, and gynecological/urological history of patients leads to erroneous diagnoses and, thus, to poorly based studies and treatments. Macroprolactinemia, defined as hyperprolactinemia due to excess macroprolactin (an isoform of a greater molecular weight than prolactin but with less biological activity), is one of the main causes of such erroneous diagnoses, resulting in poor patient management when not recognized. There is no unanimous agreement as to when macroprolactin screening is required in patients with hyperprolactinemia. At some institutions, macroprolactin testing by polyethylene glycol (PEG) precipitation is routinely performed in all patients with hyperprolactinemia, while others use a clinically based approach. There is also no consensus on how to express the results of prolactin/macroprolactin levels after PEG, which in some cases may lead to an erroneous interpretation of the results. The objectives of this study were: 1. To establish the strategy for macroprolactin screening by serum precipitation with PEG in patients with hyperprolactinemia: universal screening versus a strategy guided by the alert generated by the clinician based on the absence or presence of clinical symptoms or by the laboratory when hyperprolactinemia is detected. 2. To create a consensus document that standardizes the reporting of prolactin results after precipitation with PEG to minimize errors in the interpretation of the results, in line with international standards.

Factors associated with false negative and false positive results of prostate-specific antigen (PSA) and the impact on patient health: Cohort study protocol.

INTRODUCTION: Prostate-specific antigen (PSA) is the main tool for early detection, risk stratification and monitoring of prostate cancer (PCa). However, there are controversies about the use of PSA as a population screening test because of the high potential for overdiagnosis and overtreatment associated. The net benefit of screening is unclear and according to the available recommendations, it should be offered to well-informed men with an adequate health status and a life-expectancy of at least 10 years or to men at elevated risk of having PCa. In addition, the factors that influence test results are unclear, as is impact of false positive or negative results on patient health.Our objective is to assess the clinical and analytical factors associated with the presence of false positive and false negative results and the diagnostic/therapeutic process followed by these patients. METHODS AND ANALYSIS: A prospective observational cohort study will be carried out. We will include a cohort of patients with a positive PSA result (1.081 patients) and a sample of patients with negative results (572 patients); both will be followed for 2 years by reviewing medical records to assess the variables associated with these results, as well as characteristics of patient management after a positive PSA value. We will include those patients with a PSA determination from 2 hospitals in the Valencian Community. Patients who have been previously diagnosed with prostate cancer or who are being followed for previous high PSA values will be excluded. DISCUSSION: The study will estimate the frequency of false positive and false negative PSA results in routine clinical practice, and allow us to quantify the potential harm caused. STUDY REGISTRATION: Clinicaltrials.gov (https://clinicaltrials.gov/): NCT03978299, June 7, 2019.

Valores de referencia de tirotropina durante la gestación / Tirotropine reference intervals during pregnancy

El hipotiroidismo materno clínico y el subclínico tienen consecuencias graves tanto para la madre como para el feto. Debido a la compleja fisiología de la función tiroidea durante el embarazo, debería realizarse la evaluación hormonal según valores de referencia para cada trimestre de gestación y para cada zona y con las técnicas propias de cada laboratorio. Si no se dispone en el laboratorio de estos valores de referencia trimestrales propios, se recomiendan los siguientes valores de referencia de tirotropina: primer trimestre < 2,5 mUI/L; segundo y tercer trimestres < 3,0 mUI/L(AU)

Overt and subclinical maternal hypothyroidism is known to have serious adverse effects for both mother and fetus. Given the complex physiology of thyroid function during pregnancy, hormone assessment should be performed according to reference values for each gestational trimester and generated locally in each reference laboratory. If trimester-specific references intervals are not available in the laboratory, the following reference ranges of tirotropine are recommended: first trimester < 2,5 mUI/L; second and third trimesters < 3,0 mUI/L(AU)

Treatment of Graves' ophthalmopathy with high-dose intravenous methylprednisolone: a comparison of two dosing regimens.

RATIONALE AND OBJECTIVE: The treatment of active moderate-severe Graves' ophthalmopathy (GO) is based on the administration of highdose intravenous glucocorticoids. The present study compares the efficacy and safety of 2 different intravenous methylprednisolone (MTPiv) dosing regimens. MATERIAL AND METHODS: We carry a retrospective descriptive study with sequential sampling of 24 patients (83% females) presenting moderatesevere GO (EUGOGO criteria) and receiving treatment in our center between January 2006 and June 2008. We use 2 dosing regimens: regimen A (12 weeks): 6 doses of 0.5g/week followed by 6 doses of 0.25 g/week, for a cumulative dose of 4.5 g of MTPiv (n=13); and regimen B (16 weeks): 4 cycles of 15 mg/kg, followed by 4 cycles of 7.5mg/kg, for a cumulative dose of 90 mg/kg (range, 4.9-7.4 g) (n=11). Comparisons were made for safety (fasting glucose, cytolysis-cholestasis enzymes, lipid profile) and efficacy data (clinical improvement and recurrence). RESULTS: Mild-moderate liver cytolysis was recorded in four patients, one with associated moderate cholestasis and another with hyperglycemia, leading to treatment suspension - with no differences between the 2 treatment regimens. Percentage clinical improvement with regimen A was 92% (CI, 65-94%) versus 100% with regimen B (CI, 74-100%). The recurrence rate was 43% with regimen A and 63% with regimen B (p>0.05). None of the variables examined in the univariate logistic regression study were associated to a lesser treatment response or increased risk of recurrence of GO. CONCLUSIONS: The treatment of GO with MTPiv is safe and effective, with a lower recurrence rate when using dosing regimen A.

[Lipid profile and hormonal study in the schoolchildren of the province of Alicante]. / Perfil lipídico y estudio hormonal en población escolar de la provincia de Alicante.

INTRODUCTION: Childhood obesity has increased alarmingly in Europe and the USA, with a rise in the consequences of this epidemic, such as type 2 diabetes, hyperlipidemia and cardiovascular disease. OBJECTIVE: To study the lipid and hormonal profile of schoolchildren in the province of Alicante and to analyze the relationship between body mass index (BMI) and the variables of interest in this study. MATERIALS AND METHODS: We performed a cross-sectional epidemiological study of a cohort of schoolchildren (6-11 years) from the province of Alicante (n = 394, 204 boys and 190 girls). Height and weight were measured. We measured the following analytic variables: total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides, leptin, thyrotropin (TSH), free thyroxin (T4), insulin-like growth factor-1 (IGF-1), cortisol, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and estradiol. Obesity was defined as a BMI > or = 2 SD, using the population curves in the longitudinal study of Zaragoza (Spain) as the reference. RESULTS: When studying lipid risk, we observed that 13.5% had cholesterol levels of > 200 mg/dl, 9.4% had triglyceride levels of > 100 mg/dl and 30.5% had LDL-c/HDL-c values of > 2.2. We found a correlation between BMI and plasmatic concentrations of triglycerides (r = 0.23), IGF-1 (r = 0.211), leptin (r = 0.583), androstenedione, DHEAS, testosterone and estradiol (r = 0.35, r = 0.27, r = 0.23 and r = 0.15, respectively). There was a negative correlation between BMI and HDL-c (r = -0.21) and cortisol (r = -0.09). There was no statistically significant correlation between the degree of obesity and concentrations of cholesterol (p = 0.434) and LDL-c (p = 0.452). CONCLUSIONS: We observed a high prevalence of lipid disturbances in children under 11 years old in our population in relation to obesity.

Perfil lipídico y estudio hormonal en población escolar de la provincia de Alicante / Lipid profile and hormonal study in schoolchildren in the province of Alicante (Spain)

Introducción: La obesidad infantil ha alcanzado unas cifras alarmantes en Europa y Estados Unidos y se ha producido un aumento de las consecuencias de dicha epidemia como diabetes mellitus tipo 2, hiperlipemia y enfermedad cardiovascular. Objetivos: Analizar el perfil lipídico y estudio hormonal en población escolar de la provincia de Alicante. Relacionar el índice de masa corporal (IMC) con las variables estudiadas. Material y métodos: Estudio observacional sobre una muestra representativa de la población de la provincia de Alicante de 6 a 11 años de edad (n = 394; 204 niños y 190 niñas). Se determinaron las siguientes variables antropométricas (peso, talla) y analíticas (perfil lipídico, leptina, tirotropina, tiroxina (T4) libre, factor de crecimiento insulínico tipo I (IGFI), cortisol, androstendiona, dehidroepiandrosterona sulfato (DHEA-S), testosterona y estradiol). La obesidad se definió como valores de IMC ≥ 2 desviaciones estándar, tomando como referencia las curvas del estudio longitudinal de Zaragoza. Resultados: Al estudiar el riesgo lipídico hemos observado que el 13,5% de los sujetos presentaron colesterol total > 200 mg/dl; el 9,4%, concentraciones plasmáticas de triglicéridos > 100 mg/dl, y el 30,5%, cociente cLDL/cHDL > 2,2. También hemos encontrado una correlación positiva estadísticamente significativa entre IMC y concentraciones plasmáticas de triglicéridos (r = 0,23), IGF-I (r = 0,211), leptina (r = 0,583), androstendiona, DHEA-S, testosterona y estradiol (r = 0,35, r = 0,27, r = 0,23 y r = 0,15, respectivamente). Hay correlación negativa entre el IMC y los valores plasmáticos de cHDL (r = ¿0,21) y cortisol total (r = ¿0,09). No hay correlación estadísticamente significativa entre grado de obesidad y concentraciones plasmáticas de colesterol (p = 0,434) y cLDL (p = 0,452). Conclusiones: Hemos observado una prevalencia elevada de alteraciones lipídicas en niños menores de 11 años en relación con el aumento de la adiposidad en esta población (AU)

Introduction: Childhood obesity has increased alarmingly in Europe and the USA, with a rise in the consequences of this epidemic, such as type 2 diabetes, hyperlipidemia and cardiovascular disease. Objective: To study the lipid and hormonal profile of schoolchildren in the province of Alicante and to analyze the relationship between body mass index (BMI) and the variables of interest in this study. Materials and methods: We performed a cross-sectional epidemiological study of a cohort of schoolchildren (6-11 years) from the province of Alicante (n = 394, 204 boys and 190 girls). Height and weight were measured. We measured the following analytic variables: total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides, leptin, thyrotropin (TSH), free thyroxin (T4), insulin-like growth factor-1 (IGF-1), cortisol, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and estradiol. Obesity was defined as a BMI ≥ 2 SD, using the population curves in the longitudinal study of Zaragoza (Spain) as the reference. Results: When studying lipid risk, we observed that 13.5% had cholesterol levels of > 200 mg/dl, 9.4% had triglyceride levels of > 100 mg/dl and 30.5% had LDL-c/HDL-c values of > 2.2. We found a correlation between BMI and plasmatic concentrations of triglycerides (r = 0.23), IGF-1 (r = 0.211), leptin (r = 0.583), androstenedione, DHEAS, testosterone and estradiol (r = 0.35, r = 0.27, r = 0.23 and r = 0.15, respectively). There was a negative correlation between BMI and HDL-c (r = ¿0.21) and cortisol (r = ¿ 0.09). There was no statistically significant correlation between the degree of obesity and concentrations of cholesterol (p = 0.434) and LDL-c (p = 0.452). Conclusions: We observed a high prevalence of lipid disturbances in children under 11 years old in our population in relation to obesity (AU)

Tratamiento de la oftalmopatía de graves con metilprednisolona intravenosa a altas dosis: comparación de dos esquemas / Treatment of Graves¿ ophthalmopathy with high-dose intravenous methylprednisolone: a comparison of two dosing regimens

Objetivo: El tratamiento de la oftalmopatía de Graves (OG) moderada-grave se basa en la administración de corticoides por vía intravenosa. El presente estudio compara la eficacia y la seguridad de dos regímenes de tratamiento intravenoso con metilprednisolona (MTPiv).Material y método: Se realizó un estudio descriptivo, retrospectivo, con muestreo secuencial de 24 pacientes (el 83% mujeres) que presentaban OG moderada-grave (criterios EUGOGO) y recibieron tratamiento en nuestro centro entre enero de 2006 y junio de 2008. Se utilizaron los dos regímenes siguientes: A (12 semanas), 6 dosis de 0,5 g/semana seguidas de 6 dosis de 0,25 g/semana, con una dosis acumulada de 4,5 g de MTPiv (n = 13);B (16 semanas), 4 ciclos de 15 mg/kg, seguidos de 4 ciclos de 7,5 mg/kg, para una dosis acumulada de 90 mg/kg (intervalo, 4,9-7,9 g) (n = 11). Se compararon las variables de seguridad (glucemia basal, enzimas de colestasis-citólisis, perfil lipídico) y de eficacia (mejoría clínica y recurrencia).Resultados: Se observó citólisis hepática de leve moderada en 4 pacientes, una de ellas asociada a colestasis moderada y otra a hiperglucemia, que determinaron la suspensión del tratamiento, sin diferencias entre regímenes. Hubo mejoría con el régimen A en el 92% (intervalo de confianza[IC] del 95%, 65-94) frente al 100% con el régimen B (IC del 95%, 74-100). La tasa de recurrencia fue del 43% con el régimen A y el 63% con el B (p > 0,05). Ninguna de las variables analizadas en el estudio univariable de regresión logística se asoció a menor respuesta al tratamiento o mayor recurrencia de OG.Conclusiones: El tratamiento de la OG mediante MTPiv es seguro y efectivo, con menor tasa de recurrencia con la dosificación del régimen A (AU)

Rationale and objective: The treatment of active moderate-severe Graves’ ophthalmopathy (GO) is based on the administration of high-dose intravenous glucocorticoids. The present study compares the efficacy and safety of 2 different intravenous methylprednisolone (MTPiv) dosing regimens.Material and methods: We carry a retrospective descriptive study with sequential sampling of 24 patients (83% females) presenting moderate-severe GO (EUGOGO criteria) and receiving treatment in our center between January 2006 and June 2008. We use 2 dosing regimens: regimen A (12 weeks): 6 doses of 0.5 g/week followed by 6 doses of 0.25 g/week, for a cumulative dose of 4.5 g of MTPiv (n = 13); and regimen B (16 weeks): 4 cycles of 15 mg/kg, followed by 4 cycles of 7.5 mg/kg, for a cumulative dose of 90 mg/kg (range, 4.9-7.4 g) (n = 11). Comparisons were made for safety (fasting glucose, cytolysis-cholestasis enzymes, lipid profile) and efficacy data (clinical improvement and recurrence).Results: Mild-moderate liver cytolysis was recorded in four patients, one with associated moderate cholestasis and another with hyperglycemia, leading to treatment suspension – with no differences between the 2 treatment regimens. Percentage clinical improvement with regimen A was 92% (CI, 65-94%) versus 100% with regimen B (CI, 74-100%). The recurrence rate was 43% with regimen A and 63% with regimen B (p > 0.05). None of the variables examined in the univariate logistic regression study were associated to a lesser treatment response or increased risk of recurrence of GO.Conclusions: The treatment of GO with MTPiv is safe and effective, with a lower recurrence rate when using dosing regimen A (AU)