Endocrine Society's Practice Guidelines Research Articles

A self-guided curriculum on endocrinology standard of care for gender diverse youth, including ethical considerations

ObjectiveWhile the field of pediatric endocrinology, and the American Board of Pediatrics, continues expanding training to include gender-affirming care, many pediatric endocrinology fellowship programs do not have formal curriculum for this patient population. Members of the Pediatric Endocrine Society (PES) that have a special interest in transgender health designed a curriculum based on Endocrine Society practice guidelines to expand the knowledge of gender affirming care for medical trainees' and faculty. MethodsPES members designed a 5-part self-guided educational module series with embedded knowledge questions. Uniquely, medical ethical reflections were included within each module. Participants completed baseline demographic and baseline and follow-up knowledge surveys. ResultsMost participants were pediatric endocrinology fellows and 44 % percent (n = 21) completed all study components, including the follow up knowledge survey. Knowledge question data analysis demonstrated knowledge gained in medical management of pubertal youth and surgical interventions. ConclusionThis is the first medical education curriculum in gender-affirming care created by pediatric endocrinologists grounded in the Endocrine Society practice guidelines. This study demonstrates medical knowledge gained in caring for gender diverse youth and is the first to incorporate ethical considerations for this patient population. While initially designed for pediatric endocrinology trainees and faculty, this curriculum may be of great utility for any provider interested in caring for gender diverse youth.

Who should be screened for primary aldosteronism? A comprehensive review of current evidence.

Arterial hypertension is a major risk factor for cardiovascular disease. The prevalence of primary aldosteronism (PA) ranges from 5% to 10% in the general hypertensive population and is regarded as one of the most common causes of secondary hypertension. There are two major causes of PA: bilateral adrenal hyperplasia and aldosterone‐producing adenoma. The diagnosis of PA comprises screening, confirmatory testing, and subtype differentiation. The Endocrine Society Practice Guidelines for the diagnosis and treatment of PA recommends screening of patients at an increased risk of PA. These categories include patients with stage 2 and 3 hypertension, drug‐resistant hypertension, hypertensive with spontaneous or diuretic‐induced hypokalemia, hypertension with adrenal incidentaloma, hypertensive with a family history of early onset hypertension or cerebrovascular accident at a young age, and all hypertensive first‐degree relatives of patients with PA. Recently, several studies have linked PA with obstructive sleep apnea and atrial fibrillation unexplained by structural heart defects and/or other conditions known to cause the arrhythmia, which may be partly responsible for the higher rates of cardiovascular and cerebrovascular accidents in patients with PA. The aim of this review is to discuss which patients should be screened for PA, focusing not only on well‐established guidelines but also on additional groups of patients with a potentially higher prevalence of PA, as has been reported in recent research.

Whom Should We Screen for Cushing Syndrome? The Endocrine Society Practice Guideline Recommendations 2008 Revisited

ContextCushing syndrome (CS) is a rare and serious disease with high mortality. Patients are often diagnosed late in the course of the disease.ObjectiveThis work investigated whether defined patient populations should be screened outside the at-risk populations defined in current guidelines.MethodsAs part of the prospective German Cushing registry, we studied 377 patients with suspected CS. The chief complaint for CS referral was documented. Using urinary free cortisol, late-night salivary cortisol, and the 1-mg dexamethasone suppression test as well as long-term clinical observation, CS was confirmed in 93 patients and ruled out for the remaining 284.ResultsPatients were referred for 18 key symptoms, of which 5 were more common in patients with CS than in those in whom CS was ruled out: osteoporosis (8% vs 2%; P = .02), adrenal incidentaloma (17% vs 8%, P = 0.01), metabolic syndrome (11% vs 4%; P = .02), myopathy (10% vs 2%; P < .001), and presence of multiple symptoms (16% vs 1%; P < .001). Obesity was more common in patients in whom CS was ruled out (30% vs 4%, P < .001), but recent weight gain was prominent in those with CS. A total of 68 of 93 patients with CS (73%) had typical chief complaints, as did 106 of 284 of patients with ruled-out CS status (37%) according to the Endocrine Society practice guideline 2008.ConclusionThe 2008 Endocrine Society Practice guideline for screening and diagnosis of CS defined at-risk populations that should undergo testing. These recommendations are still valid in 2022.

The endocrine society practice guideline revisited: why do nowadays patients undergo screening for cushing' syndrome, and with which outcome?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Late-onset hypogonadism: a concept comes of age.

The term Late-onset hypogonadism (LOH) was coined in 2002 and defined as a disease entity in the ISA, ISSAM, EAU, EAA and ASA endorsed Recommendations for Investigation, Treatment and Monitoring of LOH (2005 and 2008) as 'a clinical and biochemical syndrome associated with advancing age, characterized by symptoms and a deficiency in serum testosterone (T)'. LOH was classified as a combined primary and secondary hypogonadism since the endocrine capacity of the testes and the pituitary are impaired. Symptoms of LOH include loss of libido, erectile dysfunction, loss of muscle mass, increased body fat, anemia, osteoporosis, depressed mood, decreased vitality, sweating, and hot flushes. Since these symptoms may also have origins other than LOH, exclusion of other disease entities and subnormal serum T levels are considered prerequisites for the diagnosis and possible treatment of LOH. However, during following years these guidelines were often neglected and, especially in the USA, indiscriminate prescribing of T was widely practised so that the US FDA warned against such irresponsible behavior. In Europe, T prescribing remained largely restricted to LOH as defined above. Nevertheless, a discussion started whether LOH really exists or is only a consequence of age-related comorbidities. Numerous studies have helped to clarify the situation, in particular, the European Male Aging Study (EMAS) and the US-initiated 7T trials. Consequently, the newest US Endocrine Society Practice Guideline on T treatment (2018) includes advanced age as a cause of organic hypogonadism and recommends that 'in men >65years who have symptoms or conditions suggestive of T deficiency … and consistently and unequivocally low morning T concentrations we suggest that clinicians offer T therapy on an individualised basis after explicit discussion of the potential risks and benefits'. Thus, the concept of LOH as conceived two decades ago has weathered criticism and survived the times.

Longitudinal association of 25-hydroxyvitamin D with adipokines and markers of glucose metabolism among Brazilian pregnant women.

This study aimed to evaluate the longitudinal association of vitamin D status with glycaemia, insulin, homoeostatic model assessment of insulin resistance, adiponectin and leptin. A prospective cohort with 181 healthy, pregnant Brazilian women was followed at the 5th-13th, 20th-26th and 30th-36th gestational weeks. In this cohort, 25-hydroxyvitamin D (25(OH)D) plasma concentrations were analysed using liquid chromatography-tandem MS. Vitamin D status was categorised as sufficient or insufficient using the Endocrine Society Practice Guidelines (≥75/&lt;75 nmol/l) and the Institute of Medicine (≥50/&lt;50 nmol/l) thresholds. Linear mixed-effect regression models were employed to evaluate the association between vitamin D status and each outcome, considering interaction terms between vitamin D status and gestational age (P&lt;0·1). At baseline, 70·7 % of pregnant women had 25(OH)D levels &lt;75 nmol/l and 16 % had levels &lt;50 nmol/l. Women with sufficient vitamin D status at baseline, using both thresholds, presented lower glycaemia than those with insufficient 25(OH)D. Pregnant women with 25(OH)D concentrations &lt;75 nmol/l showed lower insulin (β=-0·12; 95 % CI -0·251, 0·009; P=0·069) and adiponectin (β=-0·070; 95 % CI -0·150, 0·010; P=0·085) concentrations throughout pregnancy than those with 25(OH)D levels ≥75 nmol/l. Pregnant women with 25(OH)D &lt;50 nmol/l at baseline presented significantly higher leptin concentrations than those with 25(OH)D levels ≥50 nmol/l (β=-0·253; 95 % CI -0·044, 0·550; P=0·095). The baseline status of vitamin D influences the biomarkers involved in glucose metabolism. Vitamin D-sufficient women at baseline had higher increases in insulin and adiponectin changes throughout gestation than those who were insufficient.

Response of serum 25(OH)D to Vitamin D and calcium supplementation in school-children from a semi-rural setting in India

The objectives of this study were to: 1) Determine the impact of varying baseline serum 25OHD on increase in vitamin D concentrations after daily supplementation with vitamin D and calcium (1000 IU + 500 mg respectively) for six months in school-children from a semi-rural setting 2) Test the efficacy of daily vitamin D-calcium supplementation on improvement in serum vitamin D concentrations to ≥75 nmol/L. Data collected from 106 subjects (58 boys, 48 girls), aged 6–12 years, included anthropometric measures like height and weight, body composition analysis, three one-day dietary recalls and sunlight exposure (by questionnaire). Blood was collected at baseline and endline and estimated for serum vitamin D by ELISA technique using standard kits. Classification of Vitamin D status was performed according to the 2011 Endocrine Society Practice Guidelines: vitamin D deficiency – <50 nmol/L; insufficiency – 50.0–74.9 nmol/L; sufficiency – ≥75 nmol/L. Statistical analysis was performed using SPSS software. Mean baseline serum vitamin D concentration was 59.7 ± 11.2 nmol/L; this rose to 79.8 ± 23.3 nmol/L with no significant differences between genders at the two time-points. Inverse relationship was obtained between baseline serum 25(OH)D concentrations and change in serum concentrations after supplementation, implying that with increasing baseline serum concentrations of 25(OH)D, increase in vitamin D levels post supplementation were significantly lower (r = − 0.96, p < 0.0001). Greatest benefit of change in serum vitamin D concentrations after supplementation was experienced by children with basal concentrations of <45 nmol/L. Daily vitamin D supplementation was effective in improving serum 25(OH)D to ≥75 nmol/L in 44% of children. Significantly higher percentage of children who were deficient at baseline (64%) were able to attain serum concentrations of ≥75 nmol/L as compared to children who were vitamin D insufficient (43%) (p < 0.001). Thus, daily supplementation with 1000 IU of vitamin D along with 500 mg of calcium helped in improving serum vitamin D concentrations to ≥75 nmol/L. Children who were vitamin D deficient particularly experienced these benefits.

Association between plasma concentrations of vitamin D metabolites and depressive symptoms throughout pregnancy in a prospective cohort of Brazilian women

Plasma concentrations of vitamin D metabolites can be inversely associated with depressive symptoms. However, few longitudinal studies have investigated this association, especially during pregnancy. The aim of this study was to investigate the association between concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxivitamin D [1,25(OH)2D] with the occurrence of depressive symptoms throughout pregnancy. A prospective cohort of 179 women was followed at 5th-13th, 20th-26th and 30th-36th gestational weeks. At each trimester of pregnancy, the plasma concentrations of 25(OH)D and 1,25(OH)2D were analyzed by liquid chromatography tandem mass spectroscopy. Vitamin D status was categorized according to the Endocrine Society Practice Guidelines and the Institute of Medicine. Depressive symptoms were measured at each trimester using the Edinburgh Postnatal Depressive Scale (cutoff ≥13). Statistical analyses included random intercept logistic regression models for longitudinal analyses. In the first trimester, the prevalence of 25(OH)D <75, <50 and <30 nmol/L were 69.3%, 14.0% and 1.7%, respectively. Prevalence of depressive symptoms were 20.1%, 14.7% and 7.8% for the first, second and third trimesters, respectively. The probability of occurrence of depressive symptoms decreased throughout pregnancy (p-value = 0.005). Women with higher concentrations of 25(OH)D in the first trimester presented a lower odds ratio (OR) for the development of depressive symptoms during pregnancy (OR = 0.98; 95%CI: 0.96 to 0.99, p-value = 0.047) in the adjusted model. In conclusion, there was a higher prevalence of vitamin D inadequacy and depressive symptoms during the first trimester. Higher 25(OH)D concentrations in the first trimester were associated with a decrease of 2% in the odds for presenting depressive symptoms throughout pregnancy.

Evidence-based D-bate on health benefits of vitamin D revisited

Vitamin D has received worldwide attention not only for its importance for bone health in children and adults but also for reducing risk for many chronic diseases including autoimmune diseases, type 2 diabetes, heart disease, many cancers and infectious diseases. Vitamin D deficiency is pandemic due to the fact that most humans have depended on sun for their vitamin D requirement which they now either avoid or wear sun protection for fear of skin cancer. There are few foods that naturally contain vitamin D. Some countries permit vitamin D fortification especially dairy products, some cereals and juice products. The Institute of Medicine made its recommendations based on a population-based model; the Endocrine Society's Practice Guidelines on Vitamin D was for the prevention and treatment of vitamin D deficiency, which helps explain the differences in the recommendations. The Guidelines defined vitamin D deficiency as a 25-hydroxyvitamin D < 20 ng/mL, insufficiency as 21–29 ng/mL and sufficiency as 30–100 ng/mL. To prevent vitamin D deficiency The Guidelines recommended vitamin D intake should be: children < 1 y 400–1,000 IU/d, children 1–18 y 600–1,000 IU/d and adults 1,500–2,000 IU/d.

Adrenal venous sampling as a diagnostic procedure for primary hyperaldosteronism: experience from a tertiary referral centre

Adrenal vein sampling (AVS) is recommended in all patients with hyperaldosteronism to whom surgery would be offered if the results indicated unilateral hypersecretion. To assess the performance of AVS against radiological findings and to evaluate the Endocrine Society's Practice Guidelines for diagnostic cut-offs. Retrospective study of 41 patients with hyperaldosteronism who underwent both AVS and computed tomography (CT) imaging. CT and AVS results were concordant in 73.7%. Unilateral lesions on CT had a greater positive predictive value (85%) than non-unilateral lesions (50%). In patients with subsequently confirmed adrenal adenomas, a lateralisation ratio >2 when comparing cortisol-corrected aldosterone ratios from the affected versus unaffected side was 100% sensitive. Patients who were managed surgically experienced significant reductions in blood pressure and medication burden and 46% were cured. AVS is important in establishing unilateral or bilateral adrenal secretion of aldosterone in patients with primary hyperaldosteronism. However, it may not be essential for the work-up in patients below the age of 40, in whom adrenal incidentalomas adrenal incidentalomas are known to be rarer, and a unilateral lesion on CT therefore has a greater positive predictive value.

Vitamin D supplementation

To summarize recommendations from the 2011 US Institute of Medicine report (on vitamin D) and the new guideline from the US Endocrine Society with emphasis on treating and preventing vitamin D deficiency, including patients with inflammatory bowel disease and prior gastric bypass. The US Institute of Medicine Recommended Dietary Allowance of vitamin D is 400 IU per day for children younger than 1 year of age, 600 IU per day for children at least 1 year of age and adults up to 70 years, and 800 IU per day for older adults. The US Institute of Medicine concluded that serum 25-hydroxyvitamin D [25(OH)D] of 20 ng/ml or more will cover the requirements of 97.5% of the population. The US Endocrine Society's Clinical Practice Guideline suggested that 400-1000 IU per day may be needed for children aged less than 1 year, 600-1000 IU per day for children aged 1 year or more, and 1500-2000 IU per day for adults aged 19 years or more to maintain 25(OH)D above the optimal level of 30 ng/ml. Patients with inflammatory bowel disease even in a quiescent state and those with gastric bypass malabsorb vitamin D and need more vitamin D to sustain their vitamin D status. Difference in the recommendations from the US Institute of Medicine and the US Endocrine Society's Practice Guideline reflects different goals and views on current evidence. Significant gaps remain in the literature, and studies of vitamin D treatment assessing changes in outcomes at different 25(OH)D levels are needed.

Commentary on the Endocrine Society Practice Guidelines: Consequences of adjustment of antihypertensive medication in screening of primary aldosteronism

The Endocrine Society guidelines suggest to screen patients with primary aldosteronism (PA) free of hypertensive medications or alternatively to switch to drugs known to have minimal influence on the aldosterone to renin ratio (ARR). We retrospectively investigated the impact of such strategy on clinical outcome. 25 patients with PA and 25 with essential hypertension (EH) were studied. Initially all subjects were evaluated biochemically and received if possible an adjustment of their medication following the guidlines. Mineralocorticoid antagonists were discontinued in all subjects. Only 26 of 50 patients could be studied under optimal conditions (drug free or on medication with minimal influence on ARR) whereas the remaining 24 subjects had to receive additional drugs (such as ACE inhibitor, angiotensin-2 receptor blocker, or betablockers) because of initial blood pressure or comorbidities. Every fifth patient with a switch of the medication experienced a significant increase in blood pressure. 13 of 25 of PA patients needed potassium supplementation (105+/-25 mEq per day; range 8-320 mEq). Nine of these patients remained hypokalemic despite substitution (serum K 2.82+/-0.07 mmol/l), with 7 classified severely hypokalemic (<.3.0). We observed 6 serious adverse events requiring hospitalization including hypertensive crisis (n = 3), atrial fibrillation (n = 1), heart failure (n = 1) and ICD triggered electric shock (n = 1). In conclusion, in our experience the adjustment of the antihypertensive treatment during screening for PA is only possible in approximately half of patients and can cause severe side effect. Such recommendation, therefore, must include a note of caution because of possibly deleterious side effects.