Support us: 1. [Support you by Becoming a YouTube member (Click here)](https://www.youtube.com/channel/UC6zQSf7dLDqfQOeM4mNUBTQ/join).  - Premium Membership- Download PDF version of Notes, Get ad free video and more - Consultant Membership- Above plus Download Powerpoint presentation of the notes and get access to EndoAI for Free 2. Support us by purchasing our book - Click here for more details: - [[Volume 1- THE BEST OF NOTES IN ENDOCRINOLOGY BOOK SERIES]] - [[Volume 2- THE BEST OF NOTES IN ENDOCRINOLOGY - DIABETES SPECIAL]] - 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 - <iframe width="560" height="315" src="https://www.youtube.com/embed/ueD7k9iLraM" title="YouTube video player" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe> ---- Please consider donating to *"Notes in Endocrinology"* to keep us going. Please visit our [[DONATION]] page to know more