Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Adrenal Hyperfunction (Cushing Disease) Testing Algorithm
Clinical Background
Clinical Hyperfunction
Adrenal hyperfunction (Cushing disease) is manifested as excess cortisol secretion by the adrenal gland.
Epidemiology
- Incidence - 10/1,000,000
- Age - uncommon in children; peak age 20-60 years
- Gender - F:M; 4-6:1
Etiology
- Endogenous
- Pituitary
- Adrenal
- Ectopic production of ACTH
- Tumors (carcinoid, small cell lung cancer)
- Exogenous
- Glucocorticoid administration
Pathophysiology
- Corticotropin-releasing hormone (CRH) in the hypothalamus stimulates release of ACTH from the pituitary gland
- ACTH acts on the adrenal glands to produce cortisol
- Most cases are caused by hypersecretion of pituitary ACTH or ectopic production of ACTH from non-pituitary source
Clinical Presentation
- Amenorrhea
- Centripetal obesity, moon facies, buffalo hump, hirsutism, striae
- Emotional changes
- Fatigue, weakness
- Hypertension
- Impaired glucose tolerance
- Osteoporosis
- Proximal myopathy
Treatment - Surgical Removal
- Transsphenoidal removal of pituitary adenoma or carcinoma
- Removal of adrenal adenoma or carcinoma
- Removal of ectopic source of ACTH
Prognosis
- Untreated Cushing disease is associated with excess morbidity/mortality secondary to cardiovascular disease
- If tumor is benign and removed, may normalize mortality
- Malignant tumors have poor prognosis
See Also
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Adrenal Hyperfunction (Cushing Disease) Testing Algorithm
Diagnosis
Diagnosis
- Indications for testing - suspicion based on clinical presentation
- Laboratory testing
- Initial testing - 24-hour free urine cortisol or salivary cortisol between 11 and midnight; if positive, follow up with dexamethasone suppression testing
- Differentiate etiology of Cushing disease - ACTH measurements
- Inferior petrosal sinus ACTH
- Imaging studies
- CT/MRI to visualize adenomas/hyperplasia
Differential Diagnosis
- Obesity
- Type 2 diabetes
- Depression
- Polycystic ovarian disease
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Adrenal Hyperfunction (Cushing Disease) Testing Algorithm
Tests generally appear in the order most useful for common clinical situations
| Test name: Cortisol, Saliva
|
| ARUP #: 0081117 |
| Methodology: Enzyme immunoassay
|
| Use:
Screen for endogenous Cushing syndrome
|
| Limitations: |
| Follow-up:
|
| Test name: Cortisol Urine Free by LC-MS/MS
|
| ARUP #: 0097222 |
| Methodology: Tandem Mass Spectrometry
|
| Use:
Screen for endogenous Cushing syndrome
|
| Limitations: |
| Follow-up:
|
| Test name: Dexamethasone
|
| ARUP #: 0078010 |
| Methodology: High Performance Liquid Chromatography/Tandem Mass Spectrometry
|
| Use:
Secondary screen for endogenous Cushing syndrome
|
| Limitations: |
| Follow-up:
|
| Test name: Adrenocorticotropic Hormone
|
| ARUP #: 0070010 |
| Methodology: Chemiluminescent Immunoassay
|
| Use:
Differentiate source of cortisol hypersecretion
|
| Limitations: |
| Follow-up:
|
| Test name: Cortisol, Serum Free
|
| ARUP #: 0098391 |
| Methodology: Equilibrium Dialysis/Enzyme Immunoassay
|
| Use:
Screen for endogenous Cushing syndrome
|
| Limitations: |
| Follow-up:
|
| Test name: Cortisol, Serum or Plasma
|
| ARUP #: 0070030 |
| Methodology: Chemiluminescent Immunoassay
|
| Use:
Screen for endogenous Cushing syndrome
|
| Limitations: |
| Follow-up:
|
| Test name: Immunohistochemistry Stain Offering
|
| ARUP #: arup005 |
| Methodology: Immunohistochemistry
|
| Use: For fixed tissue samples, consultative services as well as immunohistochemical staining for ACTH are available |
Additional Tests Available
| Test name: Adrenocorticotropic Hormone Stimulation, 0 Minutes
|
| ARUP #: 0070031 |
| Methodology: Chemiluminescent Immunoassay
|
| Comments: |
| Test name: Adrenocorticotropic Hormone Stimulation, 30 Minutes
|
| ARUP #: 0070032 |
| Methodology: Chemiluminescent Immunoassay
|
| Comments: |
| Test name: Adrenocorticotropic Hormone Stimulation, 60 Minutes
|
| ARUP #: 0070033 |
| Methodology: Chemiluminescent Immunoassay
|
| Comments: |
| Test name: 17-Hydroxycorticosteroids
|
| ARUP #: 0070490 |
| Methodology: Porter-Silber
|
| Comments: |
| Test name: 17-Ketosteroids, Urine |
| ARUP #: 0080650 |
| Methodology: Spectrophotometry (Zimmerman)
|
| Comments: |
| Test name: Androstenedione
|
| ARUP #: 0070020 |
| Methodology: Chemiluminescent Immunoassay
|
| Comments: |
References
Guidelines
Arnaldi G, Mancini T, Kola B, Appolloni G, Freddi S, Concettoni C, Bearzi I, Masini A, Boscaro M, Mantero F. Cyclical Cushing's syndrome in a patient with a bronchial neuroendocrine tumor (typical carcinoid) expressing ghrelin and growth hormone secretagogue receptors. J Clin Endocrinol Metab.
2003;
88(
12):
5834-5840.
General References
Batista DL, Riar J, Keil M, Stratakis CA. Diagnostic tests for children who are referred for the investigation of Cushing syndrome. Pediatrics.
2007;
120(
3):
e575-e586.
Brown RL, Weiss RE. An approach to the evaluation and treatment of Cushing's disease. Expert Rev Anticancer Ther.
2006;
6 Suppl 9:
S37-S46.
Findling JW, Raff H. Cushing's Syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab.
2006;
91(
10):
3746-3753.
Labeur M, Theodoropoulou M, Sievers C, Paez-Pereda M, Castillo V, Arzt E, Stalla GK. New aspects in the diagnosis and treatment of Cushing disease. Front Horm Res.
2006;
35:
169-178.
Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing's syndrome. Lancet.
2006;
367(
9522):
1605-1617.
Nieman LK, Ilias I. Evaluation and treatment of Cushing's syndrome. Am J Med.
2005;
118(
12):
1340-1346.
Oldfeld EH. Cushing disease. J Neurosurg.
2003;
98(
5):
948-951.
Shibli-Rahhal A, Van Beek M, Schlechte JA. Cushing's syndrome. Clin Dermatol.
2006;
24(
4):
260-265.
Simard M. The biochemical investigation of Cushing syndrome. Neurosurg Focus.
2004;
16(
4):
E4-.
References from the ARUP Institute for Clinical and Experimental Pathology Research®
Kushnir MM, Rockwood AL, Nelson GJ, Terry AH, Meikle AW. Liquid chromatography-tandem mass spectrometry analysis of urinary free cortisol. Clin Chem.
2003;
49(
6 Pt 1):
965-967.
Medical Reviewers
Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah
Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah
Comprehensive Review: January 2008
Last Update: January 2008
