Objective: To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults. Participants: The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline. Evidence: The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of ...

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Hormonal replacement in hypopituitarism in adults: An endocrine society clinical practice guideline

BackgroundFew data are available regarding the use of tenofovir disoproxil fumarate (TDF) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus (HBV). MethodsIn this trial, we included 200 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per milliliter. Participants were randomly assigned, in a 1:1 ratio, to receive usual care without antiviral therapy or to receive TDF (at an oral dose of 300 mg per day) from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28. All the infants received immunoprophylaxis. The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28. ResultsAt delivery, 68% of the...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1508660

Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load

Cortisol is a steroid hormone produced in response to stress. It is essential for maintaining health and well-being; and leads to significant morbidity when deficient or present in excess. It is lipophillic and is transported bound to cortisol-binding globulin (CBG) and albumin; a small fraction (~10%) of total serum cortisol is unbound and biologically active.

Serum cortisol assays measure total cortisol and their results can be misleading in patients with altered serum protein concentrations. Automated immunoassays are used to measure cortisol but lack specificity and show significant interassay differences. Liquid chromatography – tandem mass spectrometry (LC-MS/MS) offers improved specificity and sensitivity; however cortisol cut-offs used in the short Synacthen and Dexamethasone suppression tests are yet to be validated for these assays.

Urine free cortisol is used to screen for Cushing’s syndrome. Unbound cortisol is excreted unchanged in the urine and 24-hour urine free cortisol correlates well with mean serum free cortisol in conditions of cortisol excess. Urine free cortisol is measured predominantly by immunoassay or LC-MS/MS.

Salivary cortisol also reflects changes in unbound serum cortisol and offers a reliable alternative to measuring free cortisol in serum. LC-MS/MS is the method of choice for measuring salivary cortisol; however, its use is limited by the lack of a single, validated reference range and poorly standardised assays. 

This review examines the methods available for measuring cortisol in serum, urine and saliva, explores cortisol in disease and considers the difficulties of measuring cortisol in acutely unwell patients and in neonates.

https://journals.sagepub.com/doi/pdf/10.1177/0004563216687335

Measuring cortisol in serum, urine and saliva – are our assays good enough?:

This book is promoted as a practical manual and data book for forensic scientists, toxicologists, analytical chemists, pharmacists, biochemists, pathologists, and police surgeons. The problems of identification of drugs and related compounds in biological material grow year by year, with the continual introduction of new drugs, insecticides, food additives, industrial chemicals, etc. In addition, self-poisoning with drugs is assuming epidemic proportions in many countries. Although sedativehypnotic drugs, tranquilisers, antidepressants, and salicylates account for the great majority of drugs taken in overdosage, the clinical chemist and forensic scientist must be able to identify a vast range of other less commonly encountered compounds. This comprehensive text outlines methods for the isolation and identification of drugs and is therefore particularly welcome. It describes a large number of simple and rapid screening tests which can be performed with a minimum of apparatus; at the other end of the scale, it provides standardised reference data

Isolation and Identification of Drugs.

This case study over time describes five years of experience with interventions to improve laboratory test utilization at an academic medical center. The high-frequency laboratory tests showing the biggest declines in order volume post intervention were serum albumin (36%) and erythrocyte sedimentation rate (17%). Introduction of restrictions for 170 high-cost send-out tests resulted in a 23% decline in order volume. Targeted interventions reduced mis-orders involving several “look-alike” tests: 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D; manganese, magnesium; beta-2-glycoprotein, beta-2-microglobulin. Lastly, targeted alerts reduced duplicate orders of germline genetic testing and orders of hepatitis B surface antigen within 2 weeks of hepatitis B vaccination.

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Promoting improved utilization of laboratory testing through changes in an electronic medical record: experience at an academic medical center

Immunoassays are widely used in clinical laboratories for measurement of plasma/serum concentrations of steroid hormones such as cortisol and testosterone. Immunoassays can be performed on a variety of standard clinical chemistry analyzers, thus allowing even small clinical laboratories to do analysis on-site. One limitation of steroid hormone immunoassays is interference caused by compounds with structural similarity to the target steroid of the assay. Interfering molecules include structurally related endogenous compounds and their metabolites as well as drugs such as anabolic steroids and synthetic glucocorticoids. Cross-reactivity of a structurally diverse set of compounds were determined for the Roche Diagnostics Elecsys assays for cortisol, dehydroepiandrosterone (DHEA) sulfate, estradiol, progesterone, and testosterone. These data were compared and contrasted to package insert data and published cross-reactivity studies for other marketed steroid hormone immunoassays. Cross-reactivity was computationally predicted using the technique of two-dimensional molecular similarity. The Roche Elecsys Cortisol and Testosterone II assays showed a wider range of cross-reactivity than the DHEA sulfate, Estradiol II, and Progesterone II assays. 6-Methylprednisolone and prednisolone showed high cross-reactivity for the cortisol assay, with high likelihood of clinically significant effect for patients administered these drugs. In addition, 21-deoxycortisol likely produces clinically relevant cross-reactivity for cortisol in patients with 21-hydroxylase deficiency, while 11-deoxycortisol may produce clinically relevant cross-reactivity in 11β-hydroxylase deficiency or following metyrapone challenge. Several anabolic steroids may produce clinically significant false positives on the testosterone assay, although interpretation is limited by sparse pharmacokinetic data for some of these drugs. Norethindrone therapy may impact immunoassay measurement of testosterone in women. Using two-dimensional similarity calculations, all compounds with high cross-reactivity also showed a high degree of similarity to the target molecule of the immunoassay. Compounds producing cross-reactivity in steroid hormone immunoassays generally have a high degree of structural similarity to the target hormone. Clinically significant interactions can occur with structurally similar drugs (e.g., prednisolone and cortisol immunoassays; methyltestosterone and testosterone immunoassays) or with endogenous compounds such as 21-deoxycortisol that can accumulate to very high concentrations in certain disease conditions. Simple similarity calculations can help triage compounds for future testing of assay cross-reactivity.

https://link.springer.com/content/pdf/10.1186%2F1472-6890-14-33.pdf

Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction

Autoverification in a core clinical chemistry laboratory at an academic medical center

Hepatitis B virus (HBV) is a common cause of viral hepatitis with significant health complications including cirrhosis and hepatocellular carcinoma. Assays for hepatitis B surface antigen (HBsAg) are the most frequently used tests to detect HBV infection. Vaccination for HBV can produce transiently detectable levels of HBsAg in patients. However, the time course and duration of this effect is unclear. The objective of this retrospective study was to clarify the frequency and duration of transient HBsAg positivity following vaccination against HBV. The electronic medical record at an academic tertiary care medical center was searched to identify all orders for HBsAg within a 17 month time period. Detailed chart review was performed to identify all patients who were administered HBV vaccine within 180 days prior to HBsAg testing and also to ascertain likely cause of weakly positive (grayzone) results. During the 17 month study period, 11,719 HBsAg tests were ordered on 9,930 patients. There were 34 tests performed on 34 patients who received HBV vaccine 14 days or less prior to HBsAg testing. Of these 34 patients, 11 had grayzone results for HBsAg that could be attributed to recent vaccination. Ten of the 11 patients were renal dialysis patients who were receiving HBsAg testing as part of routine and ongoing monitoring. Beyond 14 days, there were no reactive or grayzone HBsAg tests that could be attributed to recent HBV vaccination. HBsAg results reached a peak COI two to three days following vaccination before decaying. Further analysis of all the grayzone results within the 17 month study period (43 results out of 11,719 tests) revealed that only 4 of 43 were the result of true HBV infection as verified by confirmatory testing. Our study confirms that transient HBsAg positivity can occur in patients following HBV vaccination. The results suggest this positivity is unlikely to persist beyond 14 days post-vaccination. Our study also demonstrates that weakly positive HBsAg results often do not reflect actual HBV infection, underscoring the importance of confirmatory testing. This study also emphasizes that vaccination-induced HBsAg positives occur most commonly in hemodialysis patients.

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Positive hepatitis B surface antigen tests due to recent vaccination: a persistent problem

A rapid headspace-gas chromatography (HS-GC) method was developed for the analysis of ethylene glycol and propylene glycol in plasma and serum specimens using 1,3-propanediol as the internal standard. The method employed a single-step derivitization using phenylboronic acid, was linear to 200 mg/dL and had a lower limit of quantitation of 1 mg/dL suitable for clinical analyses. The analytical method described allows for laboratories with HS-GC instrumentation to analyze ethanol, methanol, isopropanol, ethylene glycol, and propylene glycol on a single instrument with rapid switch-over from alcohols to glycols analysis. In addition to the novel HS-GC method, a retrospective analysis of patient specimens containing ethylene glycol and propylene glycol was also described. A total of 36 patients ingested ethylene glycol, including 3 patients who presented with two separate admissions for ethylene glycol toxicity. Laboratory studies on presentation to hospital for these patients showed both osmolal and anion gap in 13 patients, osmolal but not anion gap in 13 patients, anion but not osmolal gap in 8 patients, and 1 patient with neither an osmolal nor anion gap. Acidosis on arterial blood gas was present in 13 cases. Only one fatality was seen; this was a patient with initial serum ethylene glycol concentration of 1282 mg/dL who died on third day of hospitalization. Propylene glycol was common in patients being managed for toxic ingestions, and was often attributed to iatrogenic administration of propylene glycol-containing medications such as activated charcoal and intravenous lorazepam. In six patients, propylene glycol contributed to an abnormally high osmolal gap. The common presence of propylene glycol in hospitalized patients emphasizes the importance of being able to identify both ethylene glycol and propylene glycol by chromatographic methods.

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Cory Morris

Papers

Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction

Autoverification in a core clinical chemistry laboratory at an academic medical center

Positive hepatitis B surface antigen tests due to recent vaccination: a persistent problem

A rapid analysis of plasma/serum ethylene and propylene glycol by headspace gas chromatography

Operational impact of using a vanadate oxidase method for direct bilirubin measurements at an academic medical center clinical laboratory.