Further Evaluations

IDENTIFYING HYPERCORTISOLISM REQUIRES ADDITIONAL TESTING

Clinical suspicion of hypercortisolism should increase when other related comorbidities are present.1-3

Patients with difficult-to-control type 2 diabetes (T2D) who are on 3 or more medications and/or have comorbidities should be evaluated further for hypercortisolism.3

It is recommended that excess cortisol should be evaluated in patients with1-3:

  • A combination of poorly controlled T2D and hypertension
  • T2D and microvascular and/or macrovascular complications
  • Poorly controlled T2D or hypertension who are <50 years of age
  • Onset of T2D who are <40 years with no family history and/or β cell autoimmunity

THE 2008 ENDOCRINE SOCIETY GUIDELINES4

The Guidelines urge providers to increase clinical suspicion in patients who have overlapping conditions and features.

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.

“More often patients have a number of features that are caused by cortisol excess but that are also common in the general population, such as obesity, depression, diabetes, hypertension, or menstrual irregularity…consider Cushing’s syndrome as a secondary cause of these conditions…”

– ENDO 2008 Guidelines
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References

1. Giovanelli L, Aresta C, Favero V, et al. J Endocrinol Invest. 2021;44(8):1581-1596. doi:10.1007/s40618-020-01484-2 2. Chiodini I, Albani A, Ambrogio AG, et al. Endocrine. 2017;56(2):262-266. doi:10.1007/s12020-016-1017-3 3. Aresta C, Soranna D, Giovanelli L, et al. Endocr Pract. 2021;27(12):1216-1224. doi:10.1016/j.eprac.2021.07.014 4. Nieman LK, Biller BM, Findling JW, et al. J Clin Endocrinol Metab. 2008;93(5):1526-1540. doi:10.1210/jc.2008-0125