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: August 2017
Date of next review: August 2020
Published: April 2018
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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. |
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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
- A thorough clinical assessment and biochemical analysis along with imaging studies are required in the work up of Cushing’s Syndrome
- 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
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Causes of Cushing's Syndrome
- Successful evaluation of Cushing’s syndrome requires specialist endocrinology review 1
- Evaluation of the patient with clinically suspected Cushing's syndrome begins with a 24 hour urinary cortisol 1, 2
- 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 3, 4
- Ectopic production of ACTH from a variety of tumours (bronchial carcinoid, thymoma, small-cell lung carcinoma, phaeochromocytoma, islet cell tumour, and prostate cancer) accounts for 10-15% of Cushing syndrome 4
- 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%) 4
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ACTH Dependant Cushing's Syndrome
- Once Cushing's syndrome is confirmed biochemically, imaging is directed by the measurement of ACTH levels 4-6
- 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, 4-6
- 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, 4-6
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Suppressed ACTH Levels
- A low or undetectable level of ACTH suggests primary adrenocortical disease and in such cases, CT of the adrenals is the investigation of choice 4-6
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Computed Tomography (CT) of the Adrenal Glands
- Not required for ACTH-dependent Cushing’s but is the most sensitive method for finding adrenal tumour in a patient with ACTH-independent Cushing's syndrome 3-6
- 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 1, 4, 5
- May differentiate between adenoma and hyperplasia, but hyperplastic adrenal glands have a variable appearance and CT diagnosis of adrenal hyperplasia is not very reliable 4-6
- 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
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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) 1, 3, 7-10
- MRI, with the addition of gadolinium, facilitates diagnosis of microadenoma and increases the confidence with which cavernous sinus invasion can be diagnosed or excluded 3, 9, 11
- 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) 7-10
- Disadvantages of MRI - expensive and limited availability 1
- 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 7, 8
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Inferior Petrosal Sinus Sampling (IPSS)
- If the pituitary MRI is negative or the initial biochemical workup is inconclusive, then bilateral inferior petrosal sinus sampling should be considered 3, 12
- Petrosal sinus sampling may be indicated in patients with clinically suspected pituitary microadenoma but normal MRI 4, 5, 7, 12, 13
- The success rate of IPSS is dependent on the level of expertise and experience of the operator 12
- Complications of IPSS may include vascular damage to the brainstem, deep venous thrombosis, pulmonary embolus and cranial nerve palsies 3
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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, 15
- 40-50% of functioning pituitary microadenomas 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
References
References
Date of literature search: July 2017
References are graded from Level I to V according to the Oxford Centre for Evidence-Based Medicine, Levels of Evidence. Download the document
- Sahdev A, Reznek RH, Evanson J, Grossman AB. Imaging in Cushing's syndrome. Arq Bras Endocrinol Metabol. 2007;51(8):1319-28. (Review Article). View the reference
- Mengden T, Hubmann P, Muller J, Greminger P, Vetter W. Urinary free cortisol versus 17-hydroxycorticosteroids: a comparative study of their diagnostic value in Cushing's syndrome. Clin Investig. 1992;70(7):545-8. (Level III evidence). View the reference
- Wagner-Bartak NA, Baiomy A, Habra MA, Mukhi SV, Morani AC, Korivi BR, et al. Cushing Syndrome: Diagnostic Workup and Imaging Features, With Clinical and Pathologic Correlation. AJR Am J Roentgenol. 2017;209(1):19-32. (Review article). View the reference
- Goldfarb DA. Contemporary evaluation and management of Cushing's syndrome. World J Urol. 1999;17(1):22-5. (Review article). View the reference
- Boscaro M, Barzon L, Fallo F, Sonino N. Cushing's syndrome. Lancet. 2001;357(9258):783-91. (Review article). View the reference
- Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states. Endocr Rev. 1998;19(5):647-72. (Review article). View the reference
- Kaye TB, Crapo L. The Cushing syndrome: an update on diagnostic tests. Ann Intern Med. 1990;112(6):434-44. (Level II evidence). View the reference
- Buchfelder M, Nistor R, Fahlbusch R, Huk WJ. 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(5):1183-90. (Level III evidence). View the reference
- Colombo N, Loli P, Vignati F, Scialfa G. MR of corticotropin-secreting pituitary microadenomas. AJNR Am J Neuroradiol. 1994;15(8):1591-5. (Level IV evidence). View the reference
- de Herder WW, Uitterlinden P, Pieterman H, Tanghe HL, Kwekkeboom DJ, Pols HA, et al. Pituitary tumour localization in patients with Cushing's disease by magnetic resonance imaging. Is there a place for petrosal sinus sampling? Clin Endocrinol (Oxf). 1994;40(1):87-92. (Level III evidence). View the reference
- Doppman JL, Frank JA, Dwyer AJ, Oldfield EH, Miller DL, Nieman LK, et al. Gadolinium DTPA enhanced MR imaging of ACTH-secreting microadenomas of the pituitary gland. J Comput Assist Tomogr. 1988;12(5):728-35. (Level IV evidence). View the reference
- Zampetti B, Grossrubatscher E, Dalino Ciaramella P, Boccardi E, Loli P. Bilateral inferior petrosal sinus sampling. Endocr Connect. 2016;5(4):R12-25. (Review article). View the reference
- Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA, 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(13):897-905. (Level III evidence). View the reference
- Findling JW, Raff H. Cushing's Syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab. 2006;91(10):3746-53. (Review article). View the reference
- Guo Q, Young WF, Erickson D, Erickson B. Usefulness of dynamic MRI enhancement measures for the diagnosis of ACTH-producing pituitary adenomas. Clin Endocrinol (Oxf). 2015;82(2):267-73. (Level III evidence). View the reference
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