Diagnostic Imaging Pathways - Cushing's Syndrome
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This pathway provides guidance on the imaging of adult patients with Cushing's syndrome.
Date reviewed: January 2012
Date of next review: January 2015
Published: January 2012
Quick User Guide
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The relative radiation level (RRL) of each imaging investigation is displayed in the pop up box.
| SYMBOL | RRL | EFFECTIVE DOSE RANGE |
 | None | 0 |
 | Minimal | < 1 millisieverts |
 | Low | 1-5 mSv |
 | Medium | 5-10 mSv |
 | High | >10 mSv |
Images
Image GalleryNote: These images open in a new page | ||
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| 1a |  |
Cushing's Disease Image 1a and b (Magnetic Resonance Imaging): There is a right sided pituitary adenoma (arrows) measuring up to 14mm with deviation of the stalk to the left. Slight suprasellar extension is noted without impingement of the chiasm or optic nerves. |
| 1b |  |
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| 2a |  |
Pituitary Macroadenoma Image 2a and 2b: Post-mortem specimens showing a circumcribed nodular tumour arising from the anterior pituitary consistent with a macroadenoma. |
| 2b |  |
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| 2c |  |
Image 2c (H&E, x2.5) and 2d (H&E, x20): Histological sections demonstrating a circumscribed lesion composed of sheets of uniform polygonal cells with centrally placed nuclei and amphophilic cytoplasm. The features are consistent with a pituitary adenoma. |
| 2d |  |
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Teaching Points
Teaching Points
- Once Cushing's Syndrome is confirmed biochemically, further imaging is dictated by the ACTH
- ACTH suppressed – Likely primary adrenocortical lesion and CT scan of the adrenals is required
- ACTH normal or high – Either pituitary disease or ectopic source of ACTH. Further biochemical testing with dexamethasone suppression may help differentiate the two causes prior to imaging
acthup
ACTH Dependant Cushing's Syndrome
- Once Cushing's syndrome is confirmed biochemically, imaging is directed by the measurement of ACTH levels 1,2,3,4
- When plasma ACTH and cortisol levels are increased, this suggests an ACTH dependant cause of Cushing's syndrome. Further evaluation is based on the 'High-Dose Dexamethasone Suppression Test'
- If ACTH is suppressed pituitary disease is the most likely diagnosis and MRI of the pituitary is indicated 1,2,3,4
- When the biochemistry data suggests an ectopic ACTH syndrome, a CT scan of the abdomen and chest should be performed as the initial radiographic evaluation for the variety of tumours responsible for this syndrome 1,2,3,4
ct2
Computed Tomography (CT) of the Abdomen and Chest in Ectopic Cushing's Syndrome
- A radiological search for occult ACTH producing tumour should only be made after exclusion of Cushing's disease 14
- 40-50% of functioning pituitary microadenoma's may not be visible on MRI
- Inferior petrosal sampling should be undertaken to exclude a pituitary cause of hypercortisolism (not visible on conventional MRI) prior to a radiological search for an ectopic ACTH-secreting tumour 14
- Imaging of the thorax and abdomen with computed tomography will yield the highest detection rate in searching for an occult ACTH-secreting neoplasm 14
ct
Computed Tomography (CT) of the Adrenal Glands
- Most sensitive method for finding adrenal tumour in a patient with ACTH-independent Cushing's syndrome 1,2,3,4
- As the size of the adrenal mass is the most important feature distinguishing benign adenoma from adrenocortical carcinoma, a CT scan is all that is required in most cases 12
- May differentiate between adenoma and hyperplasia, but hyperplastic adrenal glands have a variable appearance and CT diagnosis of adrenal hyperplasia is not very reliable 1,2,3,4
- Nodularity and bilateral gland enlargement suggests hyperplasia
- Nodule and contralateral atrophy suggests functioning adenoma
- Nodule in otherwise normal gland may be either hyperplasia or functioning adenoma
cushing
Causes of Cushing's Syndrome
- Evaluation of the patient with suspected Cushing's syndrome begins with a 24 hour urinary cortisol 13
- Cushing's disease (excessive production of ACTH) is the most common aetiology, accounting for 65-75% of Cushing's syndrome. Most cases of Cushing's Disease are result of pituitary adenomas 1
- Ectopic production of ACTH from a variety of tumours (bronchial carcinoid, thymoma, oat-cell carcinoma, phaeochromocytoma, islet cell tumour, and prostate cancer) accounts for 10-15% of Cushing syndrome 1
- Primary adrenocortical disease accounts for the remaining 20-30% of Cushing's syndrome, including benign adenoma (10-15%), adrenocortical carcinoma (5-10%) and adenomatous hyperplasia (5%) 1
mri
Magnetic Resonance Imaging (MRI) of the Pituitary Gland
- MRI is the imaging modality of choice for localisation of pituitary adenoma in pituitary-dependent Cushing's disease (53-75% sensitivity for detecting corticotroph tumour) 5-9
- MRI, with the addition of gadolinium, facilitates diagnosis of microadenoma and increases the confidence with which cavernous sinus invasion can be diagnosed or excluded 9,10
- Advantages of MRI - superior soft tissue resolution (depicts the anatomy of the pituitary gland, infundibulum, optic chiasm, cavernous sinuses and neighbouring vascular structures accurately and noninvasively) 5-9
- Disadvantages of MRI - expensive and limited availability
- CT has a 47% sensitivity and 74% specificity for the identification of pituitary microadenomas and most commonly reveals a hypodense lesion that usually fails to enhance with contrast administration 5,6
- Petrosal sinus sampling may be indicated in patients with clinically suspected pituitary microadenoma but normal MRI 1-5,11
References
References
References are graded from Level I to V according to the Oxford Centre for Evidence-Based Medicine, Levels of Evidence. Download the document
- Goldfarb DA. Contemporary evaluation and management of Cushing's syndrome. World J Urol. 1999;17:22-5. (Review article)
- Boscharo M, Barzon L, Fallo F, et al. Cushing's syndrome. Lancet. 2001;357:783-91. (Review article)
- Newell-Price J, Jorgensen JOL, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome. Hormone Research. 1999;51(S3):81-94. (Review article)
- Ross RJM, Trainer PJ. Endocrine investigation: Cushing's syndrome. Clin Endocrinol (Oxf). 1998;49:153-5. (Review article)
- Kaye TB, Crapo L. The Cushing syndrome: an update on diagnostic tests. Ann Intern Med. 1990;112:434-44. (Level II evidence). View the reference
- Buchfelder M, Nistor R, Fahlbusch R, et al. The accuracy of CT and MR evaluation of the sella turcica for detection of adrenocorticotropic hormone-secreting adenomas in Cushing disease. AJNR Am J Neuroradiol. 1993;14:1183-90. (Level III evidence)
- Peck WW, Dillon WP, Norman D, et al. High resolution MR imaging of pituitary microadenomas at 1.5T: experience with Cushing's disease. AJR Am J Roentgenol. 1989;152:145-51. (Level III evidence)
- De Herder WW, Uitterlinden P, Pieterman H, et al. Pituitary tumour localisation in patients with Cushing's disease by magnetic resonance imaging: is there a place for petrosal sinus sampling? Clin Endocrinol (Oxf). 1994;40:87-92. (Level III evidence)
- Colombo N, Loli P, Vignati F, et al. MR of corticotropic-secreting pituitary microadenomas. AJNR Am J Neuroradiol. 1994;15:1591-5. (Level IV evidence)
- Doppman JL, Frank JA, Dwyer AJ, et al. Gadolinium DTPA enhanced MR imaging of ACTH-secreting microadenomas of the pituitary gland. J Comput Assist Tomogr. 1988;12:728-35. (Level IV evidence)
- Oldfield EH, Doppman JL, Nieman LK, et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing's syndrome. N Engl J Med. 1991;325;897-905. (Level III evidence)
- Daitich JA, Goldfarb DA, Novick AC. Cleveland clinic experience with adrenal Cushing's syndrome. J Urol. 1997;158:2051-5. (Level III evidence)
- Mengden T, Hubmann P, Muller J et al. Urinary free cortisol versus 17-hydroxycorticosteroids: a comparative study of their diagnostic value in Cushing's Syndrome. Clinical Invest. 1992; 70(7): 545-8. (Level III evidence)
- Findling J, Raff Hershel. Cushing's syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab. 2006;91(10):3746-53. (Review article)
Further Reading
- Cushing's syndrome. Current Probl Surg. July 2001;489-545. (Review article)
Information for Consumers
Information for Consumers
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Consent to Procedure or Treatment Radiation Risks of X-rays and Scans Magnetic Resonance Imaging (MRI) |
Contrast Medium (Gadolinium versus Iodine) Iodine-Containing Contrast Medium Magnetic Resonance Imaging (MRI) Radiation Risk of Medical Imaging During Pregnancy Radiation Risk of Medical Imaging for Adults and Children |
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