Updated Diagnostic Cortisol Values for Adrenal Insufficiency

Официальное название

Re-assessment of Diagnostic Cortisol Values for Adrenal Insufficiency Using a Highly Specific Cortisol Assay

Обзор

The purpose of this study is to determine the cortisol levels that most accurately diagnose a patient with adrenal insufficiency, a condition in which cortisol levels are too low for daily living.

Подробное описание

In this study, a cosyntropin (ACTH) stimulation test will be conducted by administering intramuscular cosyntropin into a subject's arm and measuring cortisol levels before and after injection. Cosyntropin tests are routine medical tests that are done in doctors' offices to diagnose adrenal insufficiency. Cosyntropin is a synthetic version of a hormone, called ACTH, that is secreted by our bodies to help produce cortisol. Participation in this research will last about two hours.

Aim # 1:

The primary aim is to accurately re-define the cortisol threshold to diagnose adrenal insufficiency with cosyntropin stimulation test using the Alinity, monoclonal antibody, cortisol assay.

Aim # 2:

The secondary aims are to determine a basal, morning, cortisol level above which adrenal insufficiency can be ruled out using the Alinity cortisol assay and to compare diagnostic cortisol thresholds within the cosyntropin stimulation test between the Abbott Alinity assay and the Roche 2 assay.

Вмешательства

• Диагностический тест Cosyntropin stimulation test
  In this test, Cosyntropin is administered as an intramuscular injection into the arm. Cortisol levels are measured before and after injection. Cosyntropin tests are routine medical tests that are done in doctors' offices to diagnose adrenal insufficiency. Cosyntropin is a synthetic version of a hormone, called ACTH, that is secreted by our bodies to help produce cortisol.

Первичные конечные точки

• Cortisol threshold with cosyntropin stimulation test [Срок оценки: 0 minutes (pre-cosyntropin administration) and 30 and 60 minutes post-cosyntropin administration; up to 2 hours participation time]

Вторичные конечные точки (1)

• Cortisol threshold with basal, morning level [Срок оценки: 0 minutes (pre-cosyntropin administration) and 30 and 60 minutes post-cosyntropin administration; up to 2 hours participation time]

Критерии участия

Inclusion Criteria for healthy volunteers:

\- Male and female outpatients 18 years or older without prior diagnosis of primary or central adrenal insufficiency

Inclusion Criteria for patients with known adrenal insufficiency:

\- Males and females 18 years or older with established diagnosis of primary or central adrenal insufficiency as previously documented in the electronic medical record by a failed CST (peak cortisol level < 18 μg/dL) or morning serum cortisol < 3 mcg/dL with an appropriate clinical circumstance (e.g., Sheehan's syndrome, pituitary surgery and/or irradiation, bilateral adrenalectomy, etc.) that strongly supports a true diagnosis of primary or central adrenal insufficiency, and current use of physiologic, replacement dose glucocorticoids. Inpatients with non-critical illness and outpatients are eligible

Inclusion Criteria for patients with suspected adrenal insufficiency:

\- Males and females 18 years or older with suspected diagnosis of primary or central adrenal insufficiency by any cause based on clinical evaluation by a study team member. Inpatients with non-critical illness and outpatients are eligible

Exclusion Criteria for all groups:

• Moderate to severe liver impairment or abnormal albumin or cortisol binding globulin concentrations
• Renal impairment with estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73m2 and/or diagnosis of nephrotic syndrome
• Pregnancy or nursing mothers
• Use of estrogen preparations
• Uncontrolled major depressive disorder or psychiatric diseases, severe malnutrition, eating disorders, chronic fatigue syndrome (disorders that alter hypothalamic-pituitary-adrenal (HPA) axis function)
• Use of any medications that induce hepatic cytochrome P-450 enzymes, e.g., barbiturates, phenytoin, rifampin, aminoglutethimide and mitotane
• Active medical treatment of Cushing's syndrome (status-post surgical treatment is acceptable)
• Uncontrolled hypo- or hyperthyroidism
• Use of biotin within the past 72 hours
• Regular alcohol and/or cannabis use
• History of bilateral adrenalectomy
• Treatment for validated primary adrenal insufficiency for greater than 6 months
• Be assessed by the investigators as unsuitable for participation in this study for any reason

Additional Exclusion Criteria for healthy volunteers only:

• Regular use of any oral glucocorticoid (e.g. hydrocortisone, prednisone, dexamethasone) within 6 weeks of the screening visit
• Use of oral or nasal steroid (glucocorticoid) inhalers in the past 2 weeks
• Regular use of any steroid creams, gels, ointments, or lotions
• Use of steroid (glucocorticoid) injections in the past 6 months (healthy volunteers)
• Regular use of opioids
• Regular use of suboxone
• Regular use of megestrol acetate

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

США · 1 центр

• Montefiore Medical Center — The Bronx

Публикации

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• Giordano R, Marzotti S, Balbo M, Romagnoli S, Marinazzo E, Berardelli R, Migliaretti G, Benso A, Falorni A, Ghigo E, Arvat E. Metabolic and cardiovascular profile in patients with Addison's disease under conventional glucocorticoid replacement. J Endocrinol Invest. 2009 Dec;32(11):917-23. doi: 10.1007/BF03345773. Epub 2009 Jul 20. PMID 19620820
• Oelkers W. Adrenal insufficiency. N Engl J Med. 1996 Oct 17;335(16):1206-12. doi: 10.1056/NEJM199610173351607. No abstract available. PMID 8815944
• Dorin RI, Qiao Z, Qualls CR, Urban FK 3rd. Estimation of maximal cortisol secretion rate in healthy humans. J Clin Endocrinol Metab. 2012 Apr;97(4):1285-93. doi: 10.1210/jc.2011-2227. Epub 2012 Feb 15. PMID 22337905
• Reimondo G, Bovio S, Allasino B, Terzolo M, Angeli A. Secondary hypoadrenalism. Pituitary. 2008;11(2):147-54. doi: 10.1007/s11102-008-0108-4. PMID 18418713
• Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, Husebye ES, Merke DP, Murad MH, Stratakis CA, Torpy DJ. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 Feb;101(2):364-89. doi: 10.1210/jc.2015-1710. Epub 2016 Jan 13. PMID 26760044
• Raverot V, Richet C, Morel Y, Raverot G, Borson-Chazot F. Establishment of revised diagnostic cut-offs for adrenal laboratory investigation using the new Roche Diagnostics Elecsys(R) Cortisol II assay. Ann Endocrinol (Paris). 2016 Oct;77(5):620-622. doi: 10.1016/j.ando.2016.05.002. Epub 2016 Jul 19. No abstract available. PMID 27449530
• Vogeser M, Kratzsch J, Ju Bae Y, Bruegel M, Ceglarek U, Fiers T, Gaudl A, Kurka H, Milczynski C, Prat Knoll C, Suhr AC, Teupser D, Zahn I, Ostlund RE. Multicenter performance evaluation of a second generation cortisol assay. Clin Chem Lab Med. 2017 May 1;55(6):826-835. doi: 10.1515/cclm-2016-0400. PMID 27898397

Идентификаторы

NCT: NCT05149638 · 2021-13420

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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