Letter to the Editor from Powers Carson and Gronowski: “New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency After ACTH Stimulation Using Specific Cortisol Assays”

Abstract Context The normal cortisol response 30 or 60 minutes after cosyntropin (ACTH[1–24]) is considered to be ≥18 μg/dL (500 nmol/L). This threshold is based on older serum cortisol assays. Specific monoclonal antibody immunoassays or LC-MS/MS may have lower thresholds for a normal response. Objective To calculate serum cortisol cutoff values for adrenocorticotropic hormone (ACTH) stimulation testing with newer specific cortisol assays. Methods Retrospective analysis of ACTH stimulation tests performed in ambulatory and hospitalized patients suspected of adrenal insufficiency (AI). Serum samples were assayed for cortisol in parallel using Elecsys I and Elecsys II immunoassays, and when volume was available, by Access immunoassay and LC-MS/MS. Results A total of 110 patients were evaluated. Using 18 μg/dL as the cortisol cutoff after ACTH stimulation, 14.5%, 29%, 22.4%, and 32% of patients had a biochemical diagnosis of AI using the Elecsys I, Elecsys II, Access, and LC-MS/MS assays, respectively. Deming regressions of serum cortisol were used to calculate new cortisol cutoffs based on the Elecsys I cutoff of 18 μg/dL. For 30-minute values, new cutoffs were 14.6 μg/dL for Elecsys II, 14.8 μg/dL for Access, and 14.5 μg/dL for LC-MS/MS. Baseline cortisol <2 μg/dL was predictive of subnormal stimulated cortisol values. Conclusion To reduce false positive ACTH stimulation testing, we recommend a new serum cortisol cutoff of 14 to 15 μg/dL depending on the assay used (instead of the historical value of 18 μg/dL with older polyclonal antibody assays). Clinicians should be aware of the new cutoffs for the assays available to them when evaluating patients for AI.

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Risk of adrenal insufficiency following intra-articular or periarticular corticosteroid injections among children with chronic arthritis

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0219 ◽

2020 ◽

Vol 33 (10) ◽

pp. 1257-1263

Author(s):

Justine Turmel-Roy ◽

Marc-Antoine Bédard ◽

Maude Millette ◽

David Simonyan ◽

Jean-Philippe Proulx-Gauthier ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Corticosteroid Injection ◽

Significant Risk ◽

Chronic Arthritis ◽

Stimulation Test ◽

Acth Stimulation ◽

Common Procedure ◽

Morning Cortisol ◽

High Prevalence ◽

Risks Factors

AbstractObjectivesIntra-articular and/or periarticular corticosteroid injection (IACI) is a common procedure in pediatric rheumatology. Despite many adult studies demonstrating a significant risk of adrenal insufficiency (AI) following the procedure, very little evidence is available in the pediatric literature regarding this risk. The main goal of this study is to evaluate the prevalence of AI in children with chronic arthritis following IACI.MethodsThis is a retrospective study including children aged 0-18 years who had an IACI from June 2017 to July 2019. An 8:00 morning cortisol (8MC) sample was drawn around two weeks after the injection, and an ACTH 1mcg stimulation test was performed if morning cortisol level was low. AI was defined as an 8MC under 50 nmol/L or an abnormal ACTH stimulation test. Risks factors for AI and its duration were assessed.ResultsSixty patients were included in this study. AI prevalence was 30% with 18 of 60 affected patients. The corticosteroid dose injected was statistically associated with the development of AI. Median duration of AI was 181 days for the nine patients who were followed up until resolution of AI. Four patients developed symptoms of AI, namely fatigue (2 of 4), nausea (2 of 4) and abdominal pain (3 of 4). None were hospitalized or died.ConclusionsIn this cohort of children with chronic arthritis who had an IACI, we found a high prevalence of AI. Monitoring and counseling of such complication is warranted until further evidence is available.

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OR25-04 Over 14% of Inpatients with Euvolemic Hyponatremia Have Undiagnosed Adrenal Insufficiency

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1039 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Amit Kumar ◽

Maria Ghosh ◽

Jubbin Jagan Jacob

Keyword(s):

Adrenal Insufficiency ◽

Hormone Secretion ◽

Stimulation Test ◽

Acth Stimulation Test ◽

Sheehan’S Syndrome ◽

Acth Stimulation ◽

Steroid Use ◽

Inappropriate Antidiuretic Hormone Secretion ◽

Inhaled Steroids ◽

Sheehan's Syndrome

Abstract Background- The commonest cause of euvolemic hyponatremia (EvHNa) is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The diagnosis of SIADH requires the exclusion of secondary adrenal insufficiency (AI) and untreated hypothyroidism. Studies have suggested about 4% of unselected patients presenting to the emergency room with EvHNa have undiagnosed SAI.1 Among patients admitted to specialized endocrine units this prevalence maybe as high as 20%.2Objective- To study the prevalence of undiagnosed AI among inpatients with EvHNa admitted to general medical wards. Methods- This was a prospective, single centre observational study conducted among inpatients with EvHNa. EvHNa was defined as patients with a serum sodium (Na) <135 mEq/L, with no clinical evidence of dehydration or fluid excess, and a urine spot Na >30mmol/L. In addition patients with recent vomiting, renal failure, recent diuretic use, uncontrolled hyperglycemia and patients with history of use of oral or parenteral steroids in the last 6 months were excluded. Adrenal functions were assessed by a modified porcine ACTH stimulation test which has been described recently by Nair et al. A cut off cortisol value of <18mg/dl after 60 minutes of ACTH injection was used to diagnose AI.3Results- One hundred and forty one (141) patients were included after informed consent and all underwent a modified ACTH stimulation test. They had a mean age of 58 years and 52.3% (n=74) were males. Modified ACTH stimulation testing suggested 20/141 (14.2%) had undiagnosed AI. The mean age among those with AI was 55.2 years. In only 25% (5/20) AI was suspected based on clinical presentation by the treating physician. Despite excluding patients with documented steroid use, the commonest cause of AI (9/20) was secondary AI due to exogenous steroid use including high potency inhaled steroids (5/9) and the use of undocumented steroids or steroid containing medicaments by alternative practitioners (4/9). Hypopituitarism was diagnosed as the cause of AI in 5 patients, which included unsuspected Sheehan’s syndrome in post menopausal women (3/5), non functioning pituitary adenoma (1/5) and lymphocytic hypophysitis (1/5). Despite primary AI not commonly presenting as EvHNa, 3/20 patients had primary AI and in the remaining 3 patients the aetiology of AI remained unclear. Conclusions- Undiagnosed AI is much more common in our country among inpatients presenting with EvHNa to medical units. This increase is primarily driven by inhaled and undocumented exogenous steroid use and undiagnosed Sheehan’s syndrome. An assessment of the hypothalamic-pituitary-adrenal axis is mandatory before making a diagnosis of SIADH. References -(1) Diederich et al. Eur J Endocrinol 2003; 148: 609-617. (2) Cuesta et al. Clin Endocrinol (Oxf) 2016; 85: 836-844. (3) Nair A et al. Eur J Endocrinol. 2019 Oct 1. pii: EJE-19-0558.R2.

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Salivary cortisol levels by tandem mass spectrometry during high dose ACTH stimulation test for adrenal insufficiency in children

Endocrine ◽

10.1007/s12020-019-02084-8 ◽

2019 ◽

Vol 67 (1) ◽

pp. 190-197 ◽

Cited By ~ 2

Author(s):

Christina S. Chao ◽

Run-Zhang Shi ◽

Rajiv B. Kumar ◽

Tandy Aye

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Adrenal Insufficiency ◽

Salivary Cortisol ◽

Stimulation Test ◽

High Dose ◽

Tandem Mass ◽

Acth Stimulation Test ◽

Acth Stimulation ◽

Cortisol Levels

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Dexmedetomidine Infusion Associated with Transient Adrenal Insufficiency in a Pediatric Patient: A Case Report

Case Reports in Pediatrics ◽

10.1155/2013/207907 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Elizabeth W. Tucker ◽

David W. Cooke ◽

Sapna R. Kudchadkar ◽

Sybil Ann Klaus

Keyword(s):

Adrenal Insufficiency ◽

Animal Studies ◽

Structural Similarity ◽

Adrenal Suppression ◽

High Dose ◽

Respiratory Compromise ◽

Acth Stimulation ◽

Minute Post ◽

Total Body ◽

Dexmedetomidine Infusion

Dexmedetomidine is a highly selectiveα2-adrenoceptor agonist used for sedation due to its anxiolytic and analgesic properties without respiratory compromise. Due to its structural similarity to etomidate, there has been concern that dexmedetomidine may cause adrenal insufficiency. This concern was initially supported by animal studies, but subsequent human studies demonstrated mixed results. We describe the case of transient adrenal insufficiency in a 1-year-old male who presented with 24% total body surface 2nd degree burns. He required sedation with a prolonged, high-dose dexmedetomidine infusion with a peak infusion dose of 2.7 mcg/kg/hr and duration of 6.5 days. The patient developed lethargy and hypotension four days after discontinuation of his infusion. He had a random cortisol level which was low at 0.4 mcg/dL, and the concern for adrenal suppression was confirmed with an ACTH stimulation test with the baseline cortisol of 0.4 mcg/dL and inappropriate 60 minute post-ACTH stimulation cortisol of 7.8 mcg/dL. While further studies will be needed to clarify the risk of adrenal suppression secondary to dexmedetomidine, this case suggests that caution should be taken when administering dexmedetomidine to pediatric patients and highlights the need for future studies to look at appropriate dosing and duration of dexmedetomidine infusions.

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Transplantation of bovine adrenocortical cells encapsulated in alginate

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1500242112 ◽

2015 ◽

Vol 112 (8) ◽

pp. 2527-2532 ◽

Cited By ~ 31

Author(s):

Mariya Balyura ◽

Evgeny Gelfgat ◽

Monika Ehrhart-Bornstein ◽

Barbara Ludwig ◽

Zohar Gendler ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Hpa Axis ◽

Cell Biology ◽

Treatment Options ◽

Graft Function ◽

3D Cell Culture ◽

Normal Function ◽

Acth Stimulation ◽

Adrenocortical Cells ◽

Tissue Organization

Current treatment options for adrenal insufficiency are limited to corticosteroid replacement therapies. However, hormone therapy does not replicate circadian rhythms and has unpleasant side effects especially due to the failure to restore normal function of the hypothalamic–pituitary–adrenal (HPA) axis. Adrenal cell transplantation and the restoration of HPA axis function would be a feasible and useful therapeutic strategy for patients with adrenal insufficiency. We created a bioartificial adrenal with 3D cell culture conditions by encapsulation of bovine adrenocortical cells (BACs) in alginate (enBACs). We found that, compared with BACs in monolayer culture, encapsulation in alginate significantly increased the life span of BACs. Encapsulation also improved significantly both the capacity of adrenal cells for stable, long-term basal hormone release as well as the response to pituitary adrenocorticotropic hormone (ACTH) and hypothalamic luteinizing hormone-releasing hormone (LHRH) agonist, [D-Trp6]LHRH. The enBACs were transplanted into adrenalectomized, immunodeficient, and immunocompetent rats. Animals received enBACs intraperitoneally, under the kidney capsule (free cells or cells encapsulated in alginate slabs) or s.c. enclosed in oxygenating and immunoisolating βAir devices. Graft function was confirmed by the presence of cortisol in the plasma of rats. Both types of grafted encapsulated cells, explanted after 21–25 d, preserved their morphology and functional response to ACTH stimulation. In conclusion, transplantation of a bioartificial adrenal with xenogeneic cells may be a treatment option for patients with adrenocortical insufficiency and other stress-related disorders. Furthermore, this model provides a microenvironment that ensures 3D cell–cell interactions as a unique tool to investigate new insights into cell biology, differentiation, tissue organization, and homeostasis.

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