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• Credits

  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

• Associated notes:

  • An overview of the pharmacological uses of Glucocorticoids
  • Major side effects of systemic glucocorticoids

• Abbreviations:

  • HPA axis = hypothalamic-pituitary–adrenal

• Q. Which patients develop Exogenous Cushing syndrome?

  • Patients taking Supraphysiological doses of Steroids for >3 weeks develop exogenous Cushing

• Q. Apart from glucocorticoids which drugs can lead to Cushing's?

  • Megestrol- a progesterone
  • Medroxyprogesterone
  • Fludrocortisone

• #Clinicalpearl

  • Cosmetic skin whiteners' may have glucocorticoids

• Q. How is the diagnosis of Exogenous Cushing syndrome made?

  • Low cortisol in the presence of Cushingoid symptoms

• Q. What is the value of cortisol in exogenous Cushing's?

  • 8 am cortisol < 3.6 ug/dl

• Q. In which cases of exogenous Cushing can the 8:00 am cortisol be normal or high?

  • Use of hydrocortisone- assay interference
  • Use of ACTH
  • Recovering from previous use of exogenous steroids
  • Use of prednisone / prednisolone

• Q. What are the causes of Normal or low 8:00 am cortisol despite endogenous Cushing's?

  • Causes of normal or low baseline cortisol with endogenous Cushing syndrome
    • Normocortisolemic Cushing's – Cortisol hyper-reactive syndrome
    • Pituitary apoplexy
    • bilateral macronodular adrenal hyperplasia (BMAH) with GIP responsive receptors
    • Inactive phase of cyclical Cushing's
    • Ketoconazole therapy inpatient with Cushing syndrome

• Q. What will happen to ACTH in exogenous Cushing's?

  • It will also be low

• Q. Due to the use of exogenous glucocorticoids, what is the level at which suppression occurs?

  • Suppression is mainly seen at the CRH level (Hypothalamus)
  • Eventually, because of the lack of stimulation, the adrenal gland also undergo atrophy

• Q. Why do patients on chronic Glucoritocid therapy fail ACTH stimulation even though the defect is at CRH level and at the level of adrenal cortex?

  • Because of adrenal atrophy

• Q. What are Factitious Cushing's and occult Cushing's?

  • Factitious- patient secretly taking glucocorticoid without the knowledge of the physician
  • Occult Cushing - a patient is taking Glucocorticoids without his/her knowledge

• Q. Which agent used in AIDS cachexia is known to cause Cushing syndrome?

  • Megesterol acetate (ENDACE, UNISTROL)
  • Also medroxyprogesterone

• Q. What are the differences in clinical presentation between Exogenous and Endogenous Cushing's?

  • 

• Q. Which clinical features are more common in Exogenous Cushing compared to endogenous Cushing's?

  • Benign Raised ICT
  • Osteonecrosis of femoral head
  • Posterior subcapsular cataract
  • Glaucoma
  • Panniculitis
  • Pancreatitis
  • Spinal epidural lipomatosis

• Q. Which clinical features as less common in exogenous Cushing's?

  • Hypertension
  • Hypokalemia
  • Hirsustism and virilization

• Q. What is the dreaded ocular complication with exogenous steroids?

  • Glaucoma

• Q. How is a diagnosis of Exogenous Cushing syndrome established?

  • Presence of low morning serum cortisol  and ACTH in the presence of Cushingoid symptoms
  • Low DHEAS is also a practical test for looking at the health of the HPA axis in such patients. It is beneficial for the assessment of the recovery of the HPA axis

• Q. Do exogenous Steroids interfere with endogenous assays?

  • Yes
  • Most do
  • The exception is dexamethasone which does not interfere with the assay
  • Prednisolone is more likely to interfere
  • Glucocorticoid in question can directly be assayed but only in specialized labs

• Q. What happens to ACTH stimulation test in Exogenous Cushing syndrome?

  • There is atrophy of the adrenal cortex
  • Hence there is less plasma cortisol response to ACTH

• Q. What is Occult Cushing syndrome?

  • Patient receives glucocorticoids without their knowledge leading to clinical features of Cushing syndrome

• Q. Which mode of glucocorticoid therapy does not cause Cushing syndrome?

  • There is no mode of therapy that does not cause Cushing
  • All modes of glucocorticoids may cause Cushing syndrome
  • However, it depends on the dose, duration, and many other factors

• Q.  Can hydrocortisone also cause Cushing's?

  • Yes, If given in supraphysiological doses for a long time

• Q. Which clinical features appear within hours of glucocorticoid administration?

  • Insomnia
  • Increased appetite and psychological manifestations

• #Clinicalpearl

  • Cushing syndrome has been described with Intra-articular, Inhaled, and Topical preparations also !!

• Q. Which drugs used along with steroid increases the risk of Cushing's?

  • Itraconazole and ritonavir
  • They inhibit cytochrome p450 hence increasing the half-life of most steroids

• Q. What is "steroid withdrawal syndrome"?

  • Symptoms occurring because of steroids withdrawal even if the HPA axis is intact

• #Clinicalpearl

  • The dose and duration of steroids that can cause HPA axis suppression varies from individual to individual

• Q. What is the typical duration of use of steroids that is known to cause HPA axis suppression?

  • It is unknown
  • Most people believe it is three weeks
  • Some people believe that high doses can cause HPA axis suppression within five days
  • Physiological doses can cause HPA axis suppression after one month
  • HPA axis suppression may not in turn to adrenal insufficiency in all cases
  • Patients receiving frequent short courses of steroids also have significant HPA axis suppression

• Q. Which patients are more likely to have HPA axis suppression with glucocorticoids?

  • Prednisolone > 20 mg for >3 weeks
  • Prednisolone >5mg at night-time > 2 weeks
  • Patient having clinical features of iatrogenic Cushing's

• Q. What prednisolone dose cut-off is considered physiological as far as the HPA axis is concerned?

  • It is believed Prednisolone dose of 7.5 mg of equivalent or less does not cause HPA suppression
  • Dose equivalent to more than this can cause suppression

• Q. What are the physiological doses of steroids described above?

  • Hydrocortisone – 15-20 mg
  • Prednisolone- 5-7.5 mg

• Q. How long with tertiary adrenal insufficiency remain after steroid withdrawal in cases where the HPA axis is affected?

  • They remain for a long time
  • Often, for nine months after withdrawal of steroid

• #Real-life-cases

  • This is a patient taking medications from a local quack for generalized weakness from a quack for a long time. When the patient came to us, he had features of Cushing syndrome. On evaluation, we found he was taking an injection of DEXAMETHASONE from a local quack (Patient permission taken for photographs)

• Investigations:

  1. S. Cortisol - <1.0 mcg/dl
  2. DHEAS- 8.3 mcg/dl (lower limits of normal is 56 mcg/dl)
  3. ACTH <5.0 pg/ml

  • 

  • 

#Updates

• Detailed video and discussion on Exogenous Cushing syndrome

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