Interdisciplinary assessment and diagnostic algorithm: The role of the cardiologist.

Patients with diabetes have an increased risk of developing heart failure and those with heart failure are at higher risk of developing diabetes. In patients with diabetes antidiabetic medications and the metabolic alterations of diabetes increase the risk of developing heart failure. In diabetic patients with heart failure and in those with an increased likelihood of developing the disease a stepwise approach based on the use of natriuretic peptides and echocardiography to rule out the presence of heart failure should be used. Once the diagnosis of heart failure is established it will be important to define the phenotype according to the left ventricular function and, where appropriate, use additional tests to identify possible additional underlying causes of heart failure like coronary artery disease. A multidisciplinary heart failure management programs is recommended in all patients with diabetes mellitus and heart failure to enable appropriate investigations, accurate diagnosis, and appropriate agreed evidence-based therapy and care plan. The implementation of a multidisciplinary heart failure management program requires a multidisciplinary team that will have to follow the patients throughout the whole heart failure trajectory and that should consider a holistic approach to the diabetic patient with heart failure rather than focussing merely on either heart failure or diabetes.

Evolution of the Primary Aldosteronism Syndrome: Updating the Approach.

CONTEXT: New approaches are needed to address the evolution of the primary aldosteronism syndrome and to increase its recognition. Herein, we review evidence indicating that primary aldosteronism is a prevalent syndrome that is mostly unrecognized, and present a pragmatic and pathophysiology-based approach to improve diagnosis and treatment. METHODS: Evidence was gathered from published guidelines and studies identified from PubMed by searching for primary aldosteronism, aldosterone, renin, and hypertension. This evidence was supplemented by the authors' personal knowledge, research experience, and clinical encounters in primary aldosteronism. INTERPRETATION OF EVIDENCE: Renin-independent aldosterone production is a prevalent phenotype that is diagnosed as primary aldosteronism when severe in magnitude, but is largely unrecognized when milder in severity. Renin-independent aldosterone production can be detected in normotensive and hypertensive individuals, and the magnitude of this biochemical phenotype parallels the magnitude of blood pressure elevation, the risk for incident hypertension and cardiovascular disease, and the likelihood and magnitude of blood pressure reduction with mineralocorticoid receptor antagonist therapy. Expansion of the indications to screen for primary aldosteronism, combined with the use of a pathophysiology-based approach that emphasizes inappropriate aldosterone production in the context of renin suppression, will substantially increase the diagnostic and therapeutic yields for primary aldosteronism. CONCLUSIONS: The landscape of primary aldosteronism has evolved to recognize that it is a prevalent syndrome of renin-independent aldosterone production that contributes to the pathogenesis of hypertension and cardiovascular disease. Expanding screening indications and simplifying the diagnostic approach will enable implementation of targeted treatment for primary aldosteronism.

Acromégalie : améliorer la prise en charge: Acromegaly: improving care.

Acromegaly is characterized by increased release of growth hormone (GH) and, consequently, Insulin-Like Growth Factor I (IGF-I), most often by a pituitary adenoma. Prolonged exposure to excess hormone leads to progressive somatic disfigurement and a wide range of systemic manifestations that are associated with increased mortality. Transsphenoidal adenomectomy is the treatment of choice of GH-secreting pituitary tumors but surgical cure is not achieved in around 50% of patients, then adjuvant treatment is necessary. Mortality in acromegaly is normalized with biochemical control and has decreased in the last decade with the increased use of adjuvant therapy. Both GH and IGF-I are currently biomarkers for assessing disease activity in patients with acromegaly. However, discordance between GH and IGF-I results is encountered in a quarter of treated patients. The impacts of such a discrepancy over mortality and morbidity and the risk of biochemical and/or clinical recurrence are unclear. Moreover, despite a good biochemical control, some symptoms persist, leading to a decreased quality of life. Back pain due to vertebral fractures seem to be frequent in these patients and underdiagnosed. In patients with acromegaly, bone mineral density is not a reliable predictor of fracture risk. A more accurate evaluation of bone microstructural alterations associated with GH hypersecretion and vertebral fractures may be provided by new radiological devices analyzing alteration of trabecular microarchitecture, leading to a better prevention. © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.

The effect of biotin interference on the results of blood hormone assays.

Approximately 70% of medical decisions are made based on results of laboratory investigations. Immunochemical methods are used most commonly in routine laboratory diagnostics of endocrine disorders. Those methods are limited by susceptibility of the immunochemical reaction to various interferences. Interference may be caused by the presence of autologous antibodies, heterophilic antibodies, or paraproteins in the blood serum, by cross-reactions with similar reagents, haemolysis, significant lipidaemia, or hyperbilirubinaemia. Some recent reports have indicated a significant effect of biotin on the reliability of laboratory investigations. Biotin is a water-soluble vitamin belonging to the B group. It is present in popular dietary supplements - alone or as a component of multi-vitamin formulas - and it is advertised as a remedy to falling out and fragility of hair and nails. Due to its low molecular weight and a strong affinity to streptavidin, biotin is used in many immunochemical tests. Due to a strong and stable bond of streptavidin and biotin, analytical methods using the streptavidin (avidin)-biotin system are characterised by superior sensitivity, and they allow determination of very low levels of the tested substance in biological material. The presence of exogenous biotin in a sample may cause interference when using tests that utilise the streptavidin (avidin)-biotin system. Interference of biotin with immunochemical tests depends on several factors: the construction of the immunochemical test, the dose used by the patient, the biotin concentration in the sample, and most of all - the time from the last dose to the collection of biological material for laboratory testing. In this paper we present some practical recommendations and a procedure to be followed in the case of suspected interference of biotin in immunochemical assays, for clinicians and laboratory diagnosticians.

Evaluation of continuous glucose monitoring system for detection of alterations in glucose homeostasis in pediatric patients with ß-thalassemia major.

BACKGROUND: Disturbances of glucose metabolism are common in ß-thalassemia major (ß-TM). AIM: This study was conducted to assess the pattern of glucose homeostasis in pediatric ß-TM patients comparing oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS). METHODS: Two-hundred ß-TM patients were studied and those with random blood glucose (RBG) ≥7.8 mmol/L (140 mg/dL) were subjected to OGTT, insertion of CGMS and measurement of fasting C peptide, fasting insulin, and hemoglobin A1c (HbA1c). RESULTS: Twenty patients (10%) had RBG ≥ 7.8 mmol/L. Using OGTT, 6 out of 20 patients (30%) had impaired glucose tolerance (IGT) while 7 (35%) patients were in the diabetic range. CGMS showed that 7/20 (35%) patients had IGT and 13 (65%) patients had diabetes mellitus (DM); 10 of the latter group had HbA1c readings within diabetic range. The percentage of diabetic patients diagnosed by CGMS was significantly higher than that with OGTT (P = 0.012). Serum ferritin was the only independent variable related to elevated RBG. All ß-TM patients with DM were non-compliant to chelation therapy. CONCLUSIONS: The use of CGMS in the diagnosis of early glycemic abnormalities among pediatric patients with ß-TM appears to be superior to other known diagnostic modalities.

Diagnostic procedure in suspected Graves' disease.

Diagnostic procedure in suspected Graves' disease has never been studied scientifically and actual practice seems quite variable, notably between countries. Recommendations are few and weak (expert opinion). This article presents the recommendations of an expert consensus meeting organized by the French Society of Endocrinology in 2016. In case of clinically suspected thyrotoxicosis, the first-line biological assessment is of thyroid-stimulating hormone (TSH). Free T4 and possibly free T3 assays assess biological severity and are necessary for treatment efficacy monitoring. Positive diagnosis of Graves' disease after biological confirmation of thyrotoxicosis does not always require complementary etiological examinations if clinical presentation is unambiguous, notably including extra-thyroid signs. Otherwise, first-line anti-TSH-receptor (TSH-R) antibody screening is recommended for its good intrinsic performance (sensitivity and specificity) and ease of access in France. Scintigraphy is reserved to rare cases of Graves' disease with negative antibody findings or when another etiology is suspected. Thyroid ultrasound scan may be contributive, but is not recommended in first line.

Newborn Screening for Primary Congenital Hypothyroidism: Estimating Test Performance at Different TSH Thresholds.

Context: Active surveillance of primary congenital hypothyroidism (CH) in a multiethnic population with established newborn bloodspot screening. Objective: To estimate performance of newborn screening for CH at different test thresholds and calculate incidence of primary CH. Design: Prospective surveillance from June 2011 to June 2012 with 3-year follow-up of outcomes. Relative likelihood ratios (rLRs) estimated to compare bloodspot TSH test thresholds of 6 mU/L and 8 mU/L, with the nationally recommended standard of 10 mU/L for a presumptive positive result. Setting: UK National Health Service. Patients: Clinician notification of children aged <5 years investigated following clinical presentation or presumptive positive screening result. Main Outcome Measure(s): Permanent primary CH status determined by clinician report of continuing T4 requirement at 3-year follow-up. Results: A total of 629 newborns (58.3% girls; 58.7% white ethnicity) were investigated following presumptive positive screening result and 21 children (52.4% girls; 52.4% white) after clinical presentation; 432 remained on treatment at 3-year follow-up. Permanent CH incidence was 5.3 (95% CI, 4.8 to 5.8) per 10,000 infants. With use of locally applied thresholds, sensitivity, specificity, and positive predictive value were 96.76%, 99.97%, and 66.88%, respectively. Compared with a TSH threshold of 10 mU/L, positive rLRs for 8 mU/L and 6 mU/L were 1.20 (95% CI, 0.82 to 1.75) and 0.52 (95% CI, 0.38 to 0.72), and negative rLRs were 0.11 (95% CI, 0.03 to 0.36) and 0.11 (95% CI, 0.06 to 0.20), respectively. Conclusions: Screening program performance is good, but a TSH threshold of 8 mU/L appears superior to the current national standard (10 mU/L) and requires further evaluation. Further research should explore the implications of transient CH for screening policy.

Actualisation sur l'hypoparathyroïdie : un peu de théorie, beaucoup de pratique: Update on hypoparathyroidism: a little theory, a lot of practice.

Parathormone (PTH), produced by parathyroid glands, is the main regulator of calcium homeostasis. Hypoparathyroidism (hypoPT), due to decrease of PTH production, is a rare disease. Symptoms are multiple, altering function of several organs and leading to a decrease of quality of life. Acquired etiologies, including thyroïdectomy, the main cause of hypoPT, can be distinguished from congenital etiologies, including genetic defects. HypoPT, which is classically treated by supplementation by calcium and active vitamin D, can now be treated by recombinant injection in certain indications as a poor control under classical therapy. Here are summarized current knowledge on etiologies, epidemiology, clinical manifestations and management of hypoPT.

Utility of trabecular bone score in the evaluation of osteoporosis.

PURPOSE OF REVIEW: Trabecular bone score (TBS) is a lumbar spine dual-energy absorptiometry texture index which provides information on skeletal quality partially independent of bone mineral density (BMD). A body of work has emerged demonstrating the relationship between TBS and fracture risk, with lower TBS values associated with increased risk for osteoporotic fracture in postmenopausal women and older men. TBS is derived from standard DXA images; however, the information provided by TBS is complementary to that provided by BMD. In this article, we review the current state of TBS and its evolving role in the assessment and management of osteoporosis, with particular emphasis on the literature of the previous year. RECENT FINDINGS: TBS-adjusted The Fracture Risk Assessment tool (FRAX) probabilities enhance fracture risk prediction compared with conventional FRAX predictions. TBS has been found to better categorize fracture risk and assists in FRAX-based treatment decisions, particularly for patients close to an intervention threshold. However, change in lumbar spine TBS while undergoing antiresorptive treatment is not a useful indicator of antifracture effect. SUMMARY: Lumbar spine TBS is a recently developed image-based software technique for skeletal assessment, complementary to conventional BMD, which has been shown to be clinically useful as a fracture risk prediction tool.

Interpretation of plasma PTH concentrations according to 25OHD status, gender, age, weight status, and calcium intake: importance of the reference values.

CONTEXT: Reference values for plasma PTH assessment were generally established on small samples of apparently healthy subjects, without considering their 25-hydroxyvitamin D (25OHD) status or other potential modifiers of PTH concentration. OBJECTIVE: Our objective was to assess ranges of plasma PTH concentration in a large sample of adults, stratifying by 25OHD status, age, gender, weight status, and calcium intake. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey is based on 1824 middle-aged Caucasian adults from the Supplémentation en Vitamines et Minéraux Antioxydants study (1994). MAIN OUTCOME MEASURES: Plasma PTH and 25OHD concentrations were measured by an electrochemoluminescent immunoassay. Extreme percentiles of plasma PTH concentrations were assessed specifically in subjects who had plasmatic values of 25OHD of 20 ng/mL or greater and 30 ng/mL or greater. RESULTS: Among subjects with 25OHD status of 20 ng/mL or greater, the 97.5th percentile of plasma PTH concentration was 45.5 ng/L. By using this value as a reference, 5% of the subjects with plasma 25OHD less than 20 nmol/L had a high plasma PTH level, reflecting secondary hyperparathyroidism. Among vitamin D-replete subjects (25OHD status of 20 ng/mL or greater), the 97.5th percentile of plasma PTH was higher in overweight/obese subjects (51.9 vs 43.5 ng/L among normal weight subjects). CONCLUSIONS: The reference value for plasma PTH defined in this vitamin D-replete population was far below the value currently provided by the manufacturer (65 ng/L) and varied according to overweight status. These results may contribute to improve the diagnosis of primary and secondary hyperparathyroidism and subsequent therapeutic indication.

Development of the Clinic of Endocrinology, diabetes and metabolic disorders.

The Clinic of Endocrinology, diabetes and metabolic disorders was founded in 1975 by Prof d-r Alexandar Plashevski. Healthcare, educational and scientific activities in the Clinic of Endocrinology are performed in its departments. The Department for hospitalized diabetic and endocrine patients consists of the metabolic and endocrine intensive care unit, the department for diagnosis and treatment of diabetics and endocrine patients, day hospital, the department for education of diabetic patients, and the national center for insulin pump therapy. The Center for Diabetes was established in 1972 by Prof d-r Dimitar Arsov. In 1975, Prof d-r Alexandar Plasheski broadened the activities of the Center for Diabetes. It was dislocated in 1980, with new accommodation outside the clinic. Since then the Center has consisted of several organized units: two specialist outpatient clinics for diabetic patients, biochemical and endocrine laboratory, sub-departments for: diabetic foot, cardiovascular diagnosis, ophthalmology, and urgent interventions. The Department of Endocrinology and Metabolic Disorders for outclinic endocrine patients was established in 1980, and it integrates the following sub-departments: thyrology, andrology, reproductive endocrinology, obesity and lipid disorders and sub-department for osteoporosis. The educational staff of the Clinic of Endocrinology organizes theoretical and practical education about Clinical Investigation and Internal Medicine with credit transfer system course of study of the Medical Faculty, Faculty of Stomatology, postgraduate studies, specializations and sub-specializations. Symposiums, 3 congresses, schools for diabetes and osteoporosis and continuous medical education were also organized. The Clinic of Endocrinology was initiator, organizer, founder and the seat of several medical associations.

Variability and reproducibility of circulating vitamin D in a nationwide U.S. population.

CONTEXT: Most studies examining associations between circulating vitamin D and disease are based on a single measure of vitamin D, which may not reflect levels over time, particularly because vitamin D concentrations vary by season. Few studies evaluated how well multiple 25-hydroxyvitamin D [25(OH)D] measures track within the same individual over time. OBJECTIVE: This study examined variability and reproducibility of vitamin D by evaluating repeat measurements of plasma 25(OH)D concentrations while accounting for determinants of circulating concentrations including dietary supplement use and latitude of residence from a population of U.S. radiologic technologists. DESIGN AND PARTICIPANTS: We analyzed circulating 25(OH)D in blood samples taken from 538 men and women from a prospective, nationwide study at two time points within a 1-yr period, most measured in different seasons. Inter- and intra-individual variability, reliability coefficients, and measurement error were examined. RESULTS: The spearman rank correlation between two measurements of 25(OH)D concentrations was moderate (r = 0.75, P < 0.001) and did not vary significantly by participant characteristics including age, race, or latitude. The intraclass correlation coefficient was 0.72 (95% confidence interval = 0.68-0.76). The deattenuation factor of plasma 25(OH)D levels was 1.39, suggesting that a single measure of vitamin D on a continuous scale in regression analyses may result in attenuated relationships of about 40%. CONCLUSION: Our results suggest that a single blood sample obtained in spring or fall provides a reasonable average for 25(OH)D over a 1-yr period, but additional studies are needed to estimate variability and agreement in plasma 25(OH)D measurements over longer intervals and younger populations.

A clinical prediction score to diagnose unilateral primary aldosteronism.

CONTEXT: Adrenal venous sampling is recommended to assess whether aldosterone hypersecretion is lateralized in patients with primary aldosteronism. However, this procedure is invasive, poorly standardized, and not widely available. OBJECTIVE: Our goal was to identify patients' characteristics that can predict unilateral aldosterone hypersecretion in some patients who could hence bypass adrenal venous sampling before surgery. DESIGN AND SETTING: A cross-sectional diagnostic study was performed from February 2009 to July 2010 at a single center specialized in hypertension care. PATIENTS: A total of 101 consecutive patients with primary aldosteronism who underwent adrenal venous sampling participated in the study. The autonomy of aldosterone hypersecretion was assessed with the saline infusion test. INTERVENTION: Adrenal venous sampling was performed without ACTH infusion but with simultaneous bilateral sampling. MAIN OUTCOME MEASURES: Variables independently associated with a lateralized adrenal venous sampling in multivariate logistic regression were used to derive a clinical prediction rule. RESULTS: Adrenal venous sampling was successful in 87 patients and lateralized in 49. All 26 patients with a typical Conn's adenoma plus serum potassium of less than 3.5 mmol/liter or estimated glomerular filtration rate of at least 100 ml/min/1.73 m2 (or both) had unilateral primary aldosteronism; this rule had 100% specificity (95% confidence interval, 91-100) and 53% sensitivity (95% confidence interval, 38-68). CONCLUSIONS: If our results are validated on an independent sample, adrenal venous sampling could be omitted before surgery in patients with a typical Conn's adenoma if they meet at least one of two supplementary biochemical characteristics (serum potassium<3.5 mmol/liter or estimated glomerular filtration rate ≥100 ml/min/1.73 m2).

Ovarian cysts in prepubertal girls.

Visualization of follicles is perfectly physiological during childhood, their diameter generally does not exceed 10 mm. Ovarian cyst in childhood is well defined for a fluid image >20 mm. Generally mild and asymptomatic, ovarian cysts are fluid formations usually discovered incidentally by ultrasound. Some are hormonally active and cause the development of sexual characteristics. The natural history of functional cysts is eventual regression, and persistence is suggestive of organic tumor. The onset of pain is a sign of complication, and an abrupt sharp pain with vomiting is suggestive of ovarian torsion, in which case surgical intervention is urgent. In all cases, the diagnosis is based on pelvic ultrasound. MRI and tumor marker assays are required to determine the nature of an organic cyst before proceeding to surgery. These cysts may appear functional from the fetal period onward and will require management from the first days of life. Certain endocrine disorders such as precocious puberty, hypothyroidism, and aromatase deficiency cause functional cysts in girls. Recurrent bleeding is due to hormonally active cysts and suggests McCune-Albright syndrome. Although the persistence of a cyst suggests a neoplasm, a fluid character indicates benignity. Imagery is a useful aid in the diagnosis of epithelial tumors (cystadenomas) or teratoma (dermoid cyst).

[Budget impact of growth hormone treatment during the transition phase between childhood and adulthood]. / Impacto presupuestario de la utilización de hormona de crecimiento de la edad pediátrica a la adulta.

OBJECTIVE: To estimate the budget impact of somatrophin (Genotonorm) use in growth hormone deficiency (GHD) patients during the transition between childhood and adulthood. METHOD: A budget impact model was designed under the Spanish National Health System with a 5-year time horizon. Calculations of susceptible patients were based on disease prevalence (0.02%) applied to Spanish population. From total GHD cases, 60% was considered persistent and treatment candidates. An expert panel assumed that 20% of candidates would reject the treatment and 8% would withdraw therapy annually. Considered costs included: therapy costs, diagnosis (test and medical visit) and follow-up cost. RESULTS: There would be 49, 93, 132, 186 and 199 patients undergoing treatment each year (2010-2014). The total impact of Genotonorm use during the transition phase would be €367,691, €655,430, €1044,874, €1334,059, and €1594,670 for years 1 to 5. The average annual cost per patient would be €7506, €7059, €7903, €7960, €7995. CONCLUSIONS: GHD treatment during the transition phase in Spain poses an annual average layout of €7684/patient.

El método clínico en las enfermedades tiroideas / The clinical method in thyroid diseases

Se analizan algunos aspectos del método clínico en relación con las enfermedades de la glándula tiroidea, que provocan una mayor concurrencia de los pacientes a las consultas de endocrinología en todo el país, donde se carece en ocasiones de reactivos hormonales, así como también de la posibilidad de realizar estudios y terapéuticas con iodo I 131, entre los medios más importantes para diagnosticar y tratar adecuadamente a quienes padecen esas afecciones(AU)

Some aspects of the clinical method related to the diseases of thyroid gland are analyzed, leading to an increase of patients attending the endocrinology departments throughout the country, where sometimes hormonal reagents are not available, and there is not a possibility for studies or treatment with iodine I 131, among the most important ways to diagnose and adequately treat those suffering from these conditions(AU)

El método clínico en las enfermedades tiroideas / The clinical method in thyroid diseases

Se analizan algunos aspectos del método clínico en relación con las enfermedades de la glándula tiroidea, que provocan una mayor concurrencia de los pacientes a las consultas de endocrinología en todo el país, donde se carece en ocasiones de reactivos hormonales, así como también de la posibilidad de realizar estudios y terapéuticas con iodo I 131, entre los medios más importantes para diagnosticar y tratar adecuadamente a quienes padecen esas afecciones.

Some aspects of the clinical method related to the diseases of thyroid gland are analyzed, leading to an increase of patients attending the endocrinology departments throughout the country, where sometimes hormonal reagents are not available, and there is not a possibility for studies or treatment with iodine I 131, among the most important ways to diagnose and adequately treat those suffering from these conditions.

How should hypomagnesaemia be investigated and treated?

Hypomagnesaemia is relatively common, with an estimated prevalence in the general population ranging from 2·5% to 15%. It may result from inadequate magnesium intake, increased gastrointestinal or renal loss or redistribution from extracellular to intracellular space. Drug-induced hypomagnesaemia, particularly related to proton pump inhibitor (PPI) therapy, is being increasingly recognized. Most patients with hypomagnesaemia are asymptomatic; symptomatic magnesium depletion is often associated with multiple other biochemical abnormalities, including hypokalaemia, hypocalcaemia and metabolic acidosis. Manifestations of symptomatic hypomagnesaemia most often involve neuromuscular, cardiovascular and metabolic features. Patients with symptomatic hypomagnesaemia should be treated with intravenous magnesium, reserving oral replacement for asymptomatic patients.