Teaming Up to Tackle New Challenges in Endocrinology

Why are more people developing secondary adrenal insufficiency and why is their diagnosis being missed? How should we measure gonadal steroids in transgender patients receiving hormone therapy and how should these results be interpreted? Will multiplexed steroid panels prove to be a game changer for patients with complex endocrine disorders?

Identified as critical topics by clinicians attending the 2019 Endocrine Society annual scientific conference, these questions are answered in the eighth consecutive Endocrine Society-AACC co-sponsored symposium this week, “Clinical Assay Issues: What Endocrinologists Will Ask You.”

Irina Bancos, MD, describes a streamlined approach for diagnosing secondary adrenal insufficiency, an increasing problem brought about by new immune checkpoint inhibitors used in treating many cancers and opioids used in managing pain.

Although seemingly unrelated, both treatment strategies can suppress pituitary adrenocorticotropic hormone (ACTH) production, resulting in insufficient stimulation of the adrenal glands. She notes that “clinicians are not suspicious enough of adrenal insufficiency” and consequently, patients receiving these treatments are undertested and underdiagnosed. Furthermore, she explains that endocrinologists might not be familiar with the strengths and limitations of laboratory tests used in evaluating adrenal function and might wrongly dismiss secondary adrenal insufficiency if a suboptimal testing strategy is followed.

Bancos illustrates this possibility by describing false negative results in the cosyntropin stimulation test, a mainstay for endocrinologists evaluating adrenal function. “If we bombard the adrenal cortex with synthetic ACTH, the adrenal response could be normal, but the real issue is the pituitary is not releasing ACTH at the right time, she notes. Using a case-based approach, Bancos summarizes the ideal testing strategy for each clinical scenario and explains how results should be interpreted to ensure optimal patient care.

Sabine Hannema, MD, PhD, discusses controversies and challenges in monitoring transgender adolescents and adults undergoing hormone therapy. She notes that appropriate care decisions depend on accurately measuring gonadal steroids including estradiol, estrone, and testosterone, which can be technically challenging to perform. She then explains that accurately measuring these steroid hormones is only part of the picture and emphasizes that results must also be correctly interpreted in order to provide any clinical value.

As an example of factors that complicate interpretation of steroid hormone test results, she describes the differential effects of new approaches to administer hormone therapy and notes that the method of medication delivery must be taken into consideration when monitoring patients over time. To accomplish this two-part goal, Hannema advocates for an active partnership involving contributions from both laboratorians and clinicians.

Brian Keevil, MSc, summarizes the advantages and limitations of two analytical techniques for measuring steroid hormones – namely liquid chromatography tandem mass spectrometry (LC-MS/MS) and immunoassay.

While LC-MS/MS is technically challenging, requires large capital investment, and a dedicated pool of specialized technologists, it provides superior sensitivity and specificity—essential attributes for certain clinical applications. On the other hand, automated immunoassays might be adequate or even superior to LC-MS/MS when applied to other clinical scenarios.

After providing guidance to help attendees select the right assay for their specific clinical question, Keevil highlights future developments in steroid hormone testing – namely multiplexed steroid panels to evaluate patients with complex endocrine disorders including polycystic ovary syndrome, congenital adrenal hyperplasia, and adrenal cancer. He suggests that artificial intelligence and other novel data analysis tools will be needed to distill the large data sets generated by this type of analysis into succinct, clinically actionable information.

Endocrinologists frequently consult clinical laboratories for guidance on appropriately selecting and interpreting tests. Attendees at this symposium will be comfortable providing insightful answers to the next generation of questions regarding the evaluation of endocrine function.