Greene, Dina

Abstract Background The first international clinical standards of care for the gender-diverse population were formulated in the late 1970s. In the last 15 years, multiple subspecialty societies within the United States have developed clinical care guidelines for those with gender dysphoria, including gender-affirming hormone therapy (GAHT) and surgical treatments. To date, there are no pathology- and laboratory medicine–specific recommendations in the United States for the gender-diverse population. Content This document outlines pathology- and laboratory medicine–specific recommendations for providing optimal care to the gender-diverse population, with a predominant focus on the adult population. The scope of this document focuses on the following 5 topics: (a) reference intervals and interpretation of laboratory tests impacted by use of GAHT (testosterone for transgender men; estradiol with or without antiandrogens for transgender women), focusing on those stably on GAHT for 6 months or longer; (b) transfusion medicine considerations for the gender-diverse patient population, (c) consideration of gender diversity in autopsy and death investigation, (d) interpretation of histology from tissues that are impacted by GAHT and surgical procedures; and (e) pathology and laboratory medicine informatics challenges and opportunities. Summary A relatively small group of laboratory tests is significantly impacted by GAHT. The histology of some tissues shows changes attributable to GAHT or to nonhormonal medical procedures. Autopsy and transfusion medicine practices for the gender-diverse population currently lack standardization, although this is evolving. The landscape of pathology informatics related to gender diversity is complicated by varying electronic health record and laboratory informatics systems functionality.

Purpose: Guidelines recommend serum estradiol concentrations of 100–200 pg/mL for transgender women prescribed oral, subcutaneous, or transdermal estradiol with or without adjunct antiandrogen as gender-affirming feminizing hormone therapy (HT). The purpose of this systematic review was to evaluate if the guideline range of 100–200 pg/mL for estradiol concentration is associated with indicators of adequate gender-affirming feminizing HT, specifically feminizing sufficiency, insufficiency, testosterone suppression, or toxicity in transgender women. Methods: The Populations/Intervention/Comparator/Outcome model was applied to the study question, whereby the target population included transgender, gender-diverse, and nonbinary adults using gender-affirming feminizing HT by any route of administration, with or without adjunct antiandrogen use. The comparator was defined as estradiol concentrations within (100–200 pg/mL or 367–734 pM) versus outside (</>100–200 pg/mL) the guideline range; evaluated outcomes were listed by the same clinical guidelines that recommend using the 100–200 pg/mL range. Embase, MEDLINE, and Web of Science were queried over a 24-year time frame (January 1, 1999–April 20, 2023); the search was restricted to English. The extracted outcomes were categorized as indicators of therapeutic insufficiency, sufficiency, toxicity, or hormone concentration. Results: There were 49 studies that met the inclusion criteria, of which 9, 42, 25, and 5 studies included indicators of therapeutic insufficiency, sufficiency, toxicity, or hormone concentration, respectively. The search did not identify articles demonstrating that the 100–200 pg/mL guideline range provides optimal feminizing outcomes or reduces adverse events. Conclusions : Evidence does not support using the guideline range of 100–200 pg/mL to indicate sufficient feminization in transgender women using gender-affirming feminizing HT.

Abstract Background There have been conflicting messages about the influence of female sex hormones on women's health, with historical messaging indicating that use of estrogen and/or progesterone in peri- or postmenopause poses a significant clinical risk to cisgender women. More recent guidance indicates that the benefit of hormone therapy (HT) outweighs the risks for symptomatic women. Exogenous estrogen use is also indicated for contraception and gender-affirming care. Despite the potential for broad applications, robust reference intervals for estradiol, progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are lacking, and guidelines indicate that measurement of 17-β-estradiol (E2), progesterone, LH, or FSH does not facilitate care in women who may be experiencing menopausal symptoms or women taking exogenous HT. Content Here we review the physiological roles of estrogen, progesterone, LH, and FSH. We examine the modes of administration for estrogen and progesterone, clarify the nomenclature related to exogenous hormone use, and comprehensively review the literature for studies evaluating normal concentrations of these female gonadal axis hormones during the menstrual cycle. The content primarily focuses on cisgender women, but some aspects of these hormones in transgender women will also be discussed. Summary Currently, E2, LH, FSH, and progesterone reference intervals for women remain incomplete. Although there are a variety of clinical indications that benefit women using HT, symptoms and shared decision-making should guide care. Collaborative efforts between clinicians and laboratory professionals to better define therapeutic or reference intervals for these hormones can advance women's health globally.

Abstract Background Artificial intelligence (AI) promises to become an important tool in the practice of laboratory medicine. AI programs are available online that can provide concise medical and laboratory information within seconds after a question is submitted. Methods We posed the following contemporary and relevant question for clinical chemists using an AI program: “Should labs eliminate CK-MB testing?” The results of this inquiry were critically reviewed by a cardiologist, emergency department physician, and clinical laboratorians for accuracy and appropriateness. Results An AI report answering this question was generated within 15 s. The experts felt that the information was inaccurate with the statements that CK-MB results are released earlier than cardiac troponin (cTn), and are more useful for detection of myocardial injury in patients with renal insufficiencies. The summary omitted discussion on the ongoing debate for periprocedural detection of acute myocardial infarction (MI), the perceived value for detection of reinfarction, the value in risk stratification compared to cTn, the economic justification for testing both CK-MB and cTn, and medicolegal aspects of testing when results are discordant. Conclusions At this time, AI does not appear to be ready to be used by clinical laboratories for answering important practice questions.

Abstract Background Chronic diarrhea can be categorized as fatty, watery, or inflammatory. Watery diarrhea is further divided into secretory or osmotic types and can be differentiated by measuring fecal electrolytes and osmotic gap. However, with widespread use of endoscopy, it is unclear if these measurements are being used clinically. Furthermore, because stool is not a validated specimen type for Food and Drug Administration–approved electrolyte assays, utilization is a practical concern for laboratories before analytical validation. Here, we determined the clinical utility and validated the performance characteristics of stool electrolytes on the Beckman Coulter AU680. Methods Historical results and literature review were used to determine the clinically relevant ranges for stool electrolytes (Na+, Cl−, K+, phosphate, and Mg2+). Additionally, medical chart review was performed (n = 44 patients) on results to evaluate their clinical utility in chronic diarrhea work-up. Linearity, precision, and stability studies were performed on the AU680. Accuracy was evaluated by comparing results to the Roche Cobas 6000 c501. Results For all cases, stool electrolytes and osmotic gap proved valuable in chronic diarrhea work-up. The imprecision of the assays ranged from 0% to 5.9%. All assays were found to be linear within the instrument's analytical measurement range with appropriate slopes and intercepts. The bias between the AU680 and the Roche c501 ranged from −0.48 to 2.39 (mmol/L or mg/dL). Na+, Cl−, and K+ were stable refrigerated for 5 days and up to 1 freeze-thaw cycle. Phosphate and Mg2+ were stable refrigerated for 48 h, but unstable to freeze-thaw cycles. Conclusions Stool osmotic gap is valuable for evaluating chronic diarrhea and can be calculated using electrolyte concentrations measured on the AU680.

Abstract This document is an essential companion to the third iteration of the National Academy of Clinical Biochemistry [NACB,8 now the American Association for Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG) on cardiac markers. The expert consensus recommendations were drafted in collaboration with the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF-CB). We determined that there is sufficient clinical guidance on the use of cardiac troponin (cTn) testing from clinical practice groups. Thus, in this expert consensus document, we focused on clinical laboratory practice recommendations for high-sensitivity (hs)-cTn assays. This document utilized the expert opinion class of evidence to focus on the following 10 topics: (a) quality control (QC) utilization, (b) validation of the lower reportable analytical limits, (c) units to be used in reporting measurable concentrations for patients and QC materials, (d) 99th percentile sex-specific upper reference limits to define the reference interval; (e) criteria required to define hs-cTn assays, (f) communication with clinicians and the laboratory's role in educating clinicians regarding the influence of preanalytic and analytic problems that can confound assay results, (g) studies on hs-cTn assays and how authors need to document preanalytical and analytical variables, (h) harmonizing and standardizing assay results and the role of commutable materials, (i) time to reporting of results from sample receipt and sample collection, and (j) changes in hs-cTn concentrations over time and the role of both analytical and biological variabilities in interpreting results of serial blood collections.