Evaluation & Diagnosis

Increased Suspicion Of Hypercortisolism

Signs and symptoms beyond difficult-to-control type 2 diabetes (T2D) and hypertension may indicate hypercortisolism. The Endocrine Society Guidelines urge providers to increase clinical suspicion in people who have overlapping conditions and features.1

Overlapping conditions and clinical features of Cushing syndromeaCushing syndrome features in the general population that are common and/or less discriminatory
Symptoms
  • Depression
  • Fatigue
  • Weight gain
  • Back pain
  • Changes in appetite
  • Decreased concentration
  • Decreased libido
  • Impaired memory (especially short term)
  • Insomnia
  • Irritability
  • Menstrual abnormalities
Signs
  • Dorsocervical fat pad (“buffalo hump”)
  • Facial fullness
  • Obesity
  • Supraclavicular fullness
  • Thin skinb
  • Peripheral edema
  • Acne
  • Hirsutism or female balding
  • Poor skin healing
Overlapping conditions
  • Hypertensionb
  • Incidental adrenal mass
  • Vertebral osteoporosisb
  • Polycystic ovary syndrome
  • T2Db
  • Hypokalemia
  • Kidney stones
  • Unusual infections
Features that best discriminate Cushing syndrome; most do not have a high sensitivity
  • Easy bruising
  • Facial plethora
  • Proximal myopathy (or proximal muscle weakness)
  • Striae (especially if reddish purple and >1 cm wide)

aFeatures are listed in random order.

bCushing syndrome is more likely if onset of the feature is at a younger age.

Diagnosing Hypercortisolism In The Catalyst Study2

In the CATALYST study, people with difficult-to-control T2D were identified as having hypercortisolism if they had:

  • 1-mg DST >1.8 μg/dL

  • Confirmed dexamethasone level ≥140 ng/dL

The following tests were used to help understand the potential source of hypercortisolism and inform treatment decisions:

Adrenocorticotropic hormone (ACTH) test

≤15 pg/dL or 15-30 pg/dL

Dehydroepiandrosterone sulfate (DHEAS) test

≤100 μg/dL

Computed tomography (CT)

Abnormal abdominal scan

Other Secondary Tests To Consider

Other secondary tests include a repeat of the 1-mg DST, the late-night salivary cortisol (LNSC), and urinary free cortisol (UFC) tests. However1:

  • People with confirmed autonomous adrenal cortisol secretion often have discordant LNSC results3

  • People with confirmed hypercortisolism and comorbidities often have 24-hour UFC levels within the normal range4,5

GUIDANCE FROM THE ENDOCRINE SOCIETY1

“…some patients with Cushing’s syndrome, usually those with mild or cyclic disease, may have discordant results. Also, some patients without Cushing’s syndrome may have only a minimally abnormal but discordant result. The distinction between these groups is difficult, and there is no one correct diagnostic strategy.”

– 2008 ENDO Guidelines

“…referral to endocrinology centers with expertise and interest in Cushing’s syndrome in patients with abnormal initial testing is likely to be associated with better patient outcomes.”

– 2008 ENDO Guidelines

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References

1. Nieman LK, Biller BM, Findling JW, et al. J Clin Endocrinol Metab. 2008;93(5):1526-1540. doi:10.1210/jc.2008-0125 2. DeFronzo RA, Auchus RJ, Bancos I, et al. BMJ Open. 2024;14(7):e081121. doi:10.1136/bmjopen-2023-081121 3. Kuzu I, Zuhur SS, Demir N, Aktas G, Yener Ozturk F, Altuntas Y. Endokrynol Pol. 2016;67(5):487-492. doi:10.5603/EP.a2016.0028 4. Giovanelli L, Aresta C, Favero V, et al. J Endocrinol Invest. 2021;44(8):1581-1596. doi:10.1007/s40618-020-01484-2 5. Chiodini I, Ramos-Rivera A, Marcus AO, Yau H. J Endocr Soc. 2019;3(5):1097-1109. doi:10.1210/js.2018-00382