ENDO 2019: 5 Key Takeaways in Pediatric Endocrinology

Vaneeta Bamba, MD


May 08, 2019

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Vaneeta Bamba, MD

A range of presentations at the 2019 Endocrine Society Annual Meeting focused on issues that affect growth and health in individuals with endocrine disorders. To summarize the key takeaways from this plethora of new information, Medscape asked Vaneeta Bamba, MD, medical director of the Growth Center at the Children's Hospital of Philadelphia (CHOP), to tell us the five most interesting presentations from this year's meeting.

1. Guidelines for Congenital Adrenal Hyperplasia

Clinical practice guidelines for congenital adrenal hyperplasia (CAH) were released during this meeting and include comprehensive recommendations for management of both pediatric and adult CAH. Prenatal dexamethasone therapy remains controversial due to potential adverse side effects. In children, short-acting glucocorticoid tablets remain the recommended therapy, as longer-acting glucocorticoids such as prednisolone and dexamethasone may lead to growth suppression, and hydrocortisone suspensions may have uneven distribution, causing inadequate CAH control.

Of note, while aldosterone deficiency is apparent in those with salt-wasting CAH, all patients with 21-hydroxylase deficiency have some degree of subclinical aldosterone deficiency, best assessed using the aldosterone-to–plasma renin ratio. The addition of oral contraceptives containing drospirenone is useful adjunctive therapy in young women who develop hyperandrogenism. Because drospirenone has minimal impact on cortisol, blood pressure, and renin and potassium levels, those with classic CAH must continue taking glucocorticoid and mineralocorticoid supplements. Note that spironolactone is contraindicated in salt-wasting CAH. Males with CAH often have impaired fertility, probably due to a combination of factors, such as gonadotropin suppression, testicular failure, and testicular adrenal rest tumors.

2. Health Disparities in Reproductive Endocrinology

Polycystic ovary syndrome (PCOS) is associated with comorbidities that vary with phenotype and race, including increased risk for moderate to severe depression and anxiety. In an attempt to better understand racial differences in mood disorders in women with and without PCOS, Snigdha Alur-Gupta, MD, a fellow in the reproductive endocrinology and fertility department at University of Pennsylvania, and colleagues screened women seen at an academic health center. They reported a higher prevalence of depressive and anxiety symptoms in women with PCOS compared with controls, even after adjustment for a range of confounders.

Depressive symptoms were not different but, compared with black women, white women with PCOS and higher weight had higher scores on scales measuring anxiety symptoms. Though individual domains differed, there were no overall differences in quality of life between black and white women with PCOS.

The investigators concluded that we should be screening everyone for symptoms of anxiety and depression, and additional targeted interventions such as weight management may be helpful.

3. Can Genetic Testing Guide Care for Patients With Familial Lipid Disorders?

Kenneth Feingold, MD, from the University of California, San Francisco, and Sergio Fazio, MD, PhD, from Oregon Health and Science University, presented a talk at the ENDO meeting on recent guidelines for management of dyslipidemia. Several studies now suggest that familial hypercholesterolemia may be more common than we thought—in fact, closer to 1 in 200 to 1 in 250 in some populations, rather than 1 in 500 as previously estimated. While severe hypertriglyceridemia may not cause any symptoms in most patients, there is potential for recurrent and severe—even fatal (although rare)—pancreatitis.

Genetic testing may be useful for identification of abnormalities of the five known genes that control triglyceride function. For these individuals, use of a home triglyceride monitor has been useful to guide the acute dietary modifications that may help them avoid hospitalization for pancreatitis.

4. Subcutaneous and Bone Marrow Adiposity

Recent studies have demonstrated a negative association between bone mineral density and bone marrow adiposity. Endocrine and paracrine activities of marrow adipose are not uniform. Its regulation—beneficial, detrimental, or both—is probably driven by multiple factors, such as genetics, environmental factors, tissue type, and even location.

While the clinical utility of bone mineral adiposity measurements still needs to be determined, potential uses for this information are already being considered. For example, data have shown that females with anorexia nervosa, who have low levels of subcutaneous and visceral adipose, have elevated levels of marrow adipose. Could this be associated with an ultimate outcome of low bone density?

Mone Zaidi, MD, PhD, professor of medicine (endocrinology, diabetes and bone disease) at the Icahn School of Medicine at Mount Sinai, is recognized for his work on the role of pituitary hormones in the regulation of the skeleton. Of particular interest is the potential clinical use of antibodies that block the action of follicle-stimulating hormone (FSH) to minimize bone loss and reduce body fat. At ENDO, Gina Woods, MD, from the University of California, San Diego, presented data analyses showing elevated FSH levels correlated with subcutaneous adipose and lower lean body mass in older women.

Further elucidation of physiologic and pathologic functions of adiposity stores throughout the body, and their contributions to successful therapies, continues to be a goal for many research endocrinologists.

5. The Use of Genome Data in the Clinical Setting

The plenary talk by National Institutes of Health Director Francis S. Collins, MD, PhD, on use of whole genome data to better understand disease processes, was a great start to a subsequent presentation by Fernanda de Azevedo Correa, MD, PhD, from the University of São Paulo in Brazil. Correa presented her research on use of whole exome sequencing to identify pathogenic variants in patients with pituitary stalk interruption syndrome (PSIS). Because PSIS is often associated with hypoplasia of the anterior pituitary and pituitary hormone deficiencies, recognition of pathogenic genetic variants has important clinical implications in regard to management of patients, including genetic counseling.

Correa's study involved patients without abnormalities in known genes associated with PSIS. These individuals underwent additional testing, leading to identification of 116 rare allelic variants, all of which were expressed in the pituitary and/or hypothalamus. Of note, 11 of these variants correlated to malformations of the central nervous system, midline defects, or hormonal deficiencies. Correa presented data on novel variants in four genes, of which two were familial cases. This includes a variant in the ELF4 gene (Xp26.1) found in multiple family members with isolated growth hormone deficiency and PSIS, also associated with hypogammaglobulinemia. This example highlights the translation of bench-to-bedside technology.

The physician's challenge is understanding how and when to use this technological tool in proper ways. While much of this is still research based, the role of genetic counselors becomes important as we move forward. In fact, we may even consider the role of subspecialty genetic counselors to specifically explain variances related to endocrine disease.

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