Pitfalls in the Diagnosis and Management of Hypercortisolism (Cushing Syndrome) in Humans; A Review of the Laboratory Medicine Perspective
Abstract
:1. Introduction
2. Clinical Syndrome and Steroid Metabolism
2.1. Clinical Syndrome
2.2. Steroid Metabolism
2.2.1. Homeostasis and Diurnal Variation
2.2.2. Steroid Synthesis and Interference
2.2.3. Cortisol Binding Globulin and Interference
2.2.4. Steroid Metabolism and Interference
3. Cortisol Analysis
3.1. Immunoassay
3.2. Structural Assays: Mass Spectrometry and High-Performance Liquid Chromatography
3.2.1. Mass Spectrometry
3.2.2. HPLC
3.3. Specimen Type and Timing
3.3.1. Plasma/Serum (Midnight)
3.3.2. Saliva (Midnight)
3.3.3. Urine (24 h)
3.3.4. Plasma/Serum (Early Morning)
3.3.5. Plasma/Serum (Free)
3.3.6. Hair
4. ACTH
4.1. ACTH Analysis
4.1.1. Techniques
4.1.2. Performance
5. Other Steroid Hormones
5.1. Adrenal Androgens in Women
5.1.1. Dehydroepiandrosterone-Sulfate
5.1.2. Other Female Androgens
5.2. Steroid Profile
5.3. Salivary Cortisone
6. Dynamic Function Tests
6.1. Dexamethasone Tests
6.1.1. 1 mg Overnight Dexamethasone Suppression Test
6.1.2. 2 mg/Day (Low Dose) 48 h Dexamethasone Suppression Test
6.1.3. High Dose Dexamethasone Suppression Test
6.1.4. Dexamethasone-CRH Test
6.1.5. Dexamethasone Analysis in DST Protocol
6.2. CRH Stimulation with ACTH and Cortisol Quantification
6.3. Desmopressin (DDAVP) Test
6.4. Anatomical
7. Other Tests
7.1. Neuroendocrine Markers
7.1.1. Chromogranin A
7.1.2. Serotonin (5-Hydroxyindole Acetic Acid)
7.1.3. Calcitonin
7.1.4. Copeptin
7.2. Electrolytes, Acid Base, Physiological
7.2.1. Hypokalaemic Alkalosis
7.2.2. Metabolome
7.3. Molecular Genetic Techniques
7.4. Others
Anti-Müllerian Hormone and PCOS
8. Testing in Medically Treated Cushing Syndrome
8.1. Steroid Synthesis Inhibition
8.2. Central Inhibition
8.3. Glucocorticoid Receptor Antagonism
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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False Positive | False Negative | ||
---|---|---|---|
Drug | Mechanism; Assay | Drug | Mechanism; Assay |
Carbamazepine | Induction of CYP 3A4 *, accelerates metabolism of dexamethasone; any | Aprepitant | Inhibition of CYP 3A4 *, inhibition of dexamethasone metabolism; any |
Ethosuximide | Cimetidine | ||
Phenobarbital | Diltiazem | ||
Phenytoin | Fosaprepitant | ||
Pioglitazone | Fluoxetine | ||
Primidone | Itraconazole | ||
Rifampin | Ritonavir | ||
Rifapentine | |||
Estrogens | Increase CBG; plasma total | Biotin | Competes for binding; streptavidin-based IA |
Mitotane | |||
Carbamazepine | Overlaps cortisol peak; UFC by HPLC or single transition HPLC MS/MS | Piperacillin | Ion suppression; MS UFC |
Fenofibrate | Interferes with HPLC peak; UFC HPLC | ||
Synthetic glucocorticoids | Cross-reactivity; IA | ||
Carbenoxolone | Inhibition of 11β-HSD2; UFC and salivary; any | ||
Biotin | Competes for binding; streptavidin-based IA | ||
Steroid synthesis inhibitors | Cross-reactivity of steroid precursors; any particularly IA | ||
Mifespristone | Result correct but tissue activity blocked, cortisol analysis should not be performed; any |
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Flowers, K.C.; Shipman, K.E. Pitfalls in the Diagnosis and Management of Hypercortisolism (Cushing Syndrome) in Humans; A Review of the Laboratory Medicine Perspective. Diagnostics 2023, 13, 1415. https://doi.org/10.3390/diagnostics13081415
Flowers KC, Shipman KE. Pitfalls in the Diagnosis and Management of Hypercortisolism (Cushing Syndrome) in Humans; A Review of the Laboratory Medicine Perspective. Diagnostics. 2023; 13(8):1415. https://doi.org/10.3390/diagnostics13081415
Chicago/Turabian StyleFlowers, Kade C., and Kate E. Shipman. 2023. "Pitfalls in the Diagnosis and Management of Hypercortisolism (Cushing Syndrome) in Humans; A Review of the Laboratory Medicine Perspective" Diagnostics 13, no. 8: 1415. https://doi.org/10.3390/diagnostics13081415