Mass Spectrometry Based Cutoffs for Cortisol After Stimulation Tests

Mass Spectrometry Based Cutoffs for Cortisol and 17-hydroxy-progesterone (17-OH-progesterone) After Stimulation Tests for Primary and Secondary Adrenal Insufficiency.

There are two main stimulation tests used to decide if a patient has cortisol deficiency. It is the "synacthen test", were we stimulate the patient with intramuscular or intravenous synacthen ( ACTH) to see how much cortisol the adrenals are capable of producing, and it is the "Insulin hypoglycemia test" were we give the patient insulin to provoke a hypoglycemia, and look at the adrenal response to that stimulus. The cut off values for a normal response is based on old immunological assays no longer in use. Assays with a lot of interference and cross reactivity leading to measurement of higher values for cortisol than what we measure on the highly specific LCMS/MS ( Liquid chromatography mass spectrometry methode) that we are using for cortisol today. So, there is a need for new cut off values for a normal response to such tests. The purpose of this study is to produce such new cutoff values by performing the test in 120 healthy controls. We also want to perform the test in patient groups normally going trough this tests according to the same protocol as the control persons, to evaluate the new cutoffs in different patient groups.

Study Overview

• Status: Completed
• Conditions: Adrenal Insufficiency
• Intervention / Treatment: Drug: Synachten

Detailed Description

120 healthy controls will perform an intravenous synacthen test in our out patient clinic. We register anthropometric data, and take basal blood screening to assure they are healthy. We take basal blood and saliva samples right before start of the test ( called 0-samples). Then they get intravenous synacthen, and we take new samples at 30 minutes and 60 minutes. They are observed during the procedure. We will then calculate a new cut off value for cortisol after the test, based on the 2.5 percentile for cortisol in this population. We will also calculate the same for 17-OH-progesterone, a parameter we also look at after synacthen test in som patient groups ( patients with hirsutism, who are suspicious of having an enzyme defect in the cortisol synthesis cascade). The saliva samples will also be analyzed for cortisol and 17-OH-progesterone, to evaluate if it is possible to use saliva instead of blood samples in synacthen tests in the future. The advantage of using saliva samples is that they can be used also in patients with elevated amount of cortisol binding globulin (CBG), because it measure the free hormone that is biological active ( not both the free and the protein bound, as we measure in serum samples). This is important in patients on estrogens , and in pregnant women, that have large amount of CBG.

• Study Type: Interventional
• Enrollment (Actual): 232
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Grethe Åstrøm Ueland, MD; Phone Number: +4790950021; Email: geas@helse-bergen.no
• Study Contact Backup: Name: Eystein Husebye, MD, Prof.; Phone Number: +47559750000; Email: eyhu@helse-bergen.no

Study Locations

• Norway
  • Bergen, Norway, 5019
    • Haukeland University hopsital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy individuals not using any corticosteroids .
• Patients with clinical suspicion of primary or secondary adrenal insufficiency. -Patient suspicious of having an enzyme defect ( 21 hydroxylase deficiency) giving hirsutism.

Exclusion Criteria:

-Use of corticosteroids.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Synacthen; The patient get Synacthen to stimulate the adrenals to produce cortisol	Drug: Synachten; To stimulate the adrenals to increase the cortisol Production as much as possible; Other Names: tetracosactide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Define a cutoff level for serum cortisol after stimulation with synacthen or hypoglycemia in healthy control persons.	s-cortisol	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Define a cutoff level for serum 17-OH-progesterone after stimulation with synacthen or hypoglycemia in healthy control persons.	s-17-OH-progesterone	2 year
Define a cutoff level for saliva cortisol after stimulation with synacthen or hypoglycemia in healthy control persons.	saliva cortisol	2 year
Define a cutoff level for saliva 17-OH-progesterone after stimulation with synacthen or hypoglycemia in healthy control persons.	saliva 17-OH-progesterone	2 year

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Investigators: Principal Investigator: Grethe Åstrøm Ueland, MD, Haukeland University hopsital

Publications and helpful links

General Publications

• Ueland GA, Methlie P, Oksnes M, Thordarson HB, Sagen J, Kellmann R, Mellgren G, Raeder M, Dahlqvist P, Dahl SR, Thorsby PM, Lovas K, Husebye ES. The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1696-1703. doi: 10.1210/jc.2017-02602.
• Ueland GA, Dahl SR, Methlie P, Hessen S, Husebye ES, Thorsby PM. Adrenal steroid profiling as a diagnostic tool to differentiate polycystic ovary syndrome from nonclassic congenital adrenal hyperplasia: pinpointing easy screening possibilities and normal cutoff levels using liquid chromatography tandem mass spectrometry. Fertil Steril. 2022 Aug;118(2):384-391. doi: 10.1016/j.fertnstert.2022.05.012. Epub 2022 Jun 18.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2016
• Primary Completion (Actual): December 21, 2017
• Study Completion (Actual): December 21, 2017

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 27, 2016
• First Posted (Estimated): June 30, 2016

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenal Insufficiency; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Cosyntropin
• Other Study ID Numbers: 2016/174

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO