2. Adrenal mass

3. Cushing’s Syndrome Taylor Wofford September 18, 2009

4. Diagnosis Excess glucocorticoid Timing of symptoms Severity of symptoms Cause of symptoms

5. Frequency of causes of Cushing’s syndrome ACTH-dependentPercentageACTH- independent Percentage Cushing’s disease (ACTH-secreting pituitary tumor) 68Adrenal adenoma10 Ectopic ACTH syndrome 12Adrenal carcinoma8 Ectopic CRH syndrome <<1Micronodular hyperplasia 1 Macronodular hyperplasia <<1

6. Hypothalamic-Pituitary-Adrenal Axis

7. Cushing’s Syndrome Blood clots?  IOP, cataracts

8. Comparing Obesity vs. Cushing’s Physical exam ObesityCushing’s StriaePinkPurple WeaknessGeneralProximal (squat) DistributionGeneralSupraclavicular, Buffalo hump HirsutismMildMale pattern BruisingNormalVery easily CataractsAnteriorPosterior CortisolMildly elevated>> ULN

9. Diagnostic testing algorithm Testing to establish the diagnosis of Cushing's syndrome* UpToDate

10. Indeterminate ACTH Testing Cortocotropin Releasing Hormone stimulation test –When CRH is given, ACTH-dependent disease should produce an increase in ACTH and cortisol –Draw labs  dose of CRH  measure change 45 min post.

11. ACTH-dependent workup MRI-pituitary CRH stimulation test AND High dose dexamethasone suppression test –Nonpituitary tumors associated with ectopic ACTH are completely resistant to feedback inhibition –8mg dex po at 2300. measure serum cortisol at 0800 next day. <5 μg/dL=pituitary source.

12. ACTH-dependent workup-2 Inferior petrosal sinus sampling –If ACTH secretion is coming from a pituitary source, inferior petrosal sinus ACTH levels will be greater than peripheral ACTH levels –Central-to-peripheral ratio of ≥2.0 pre-CRH or ≥3.0 post-CRH = pituitary source

13. ACTH-independent workup Adrenal CT or MR imaging –Thin cuts –Masses often difficult to differentiate. ?PET. Favor adenomaFavor carcinoma Size <5 cmSize >5 cm HomogeneousHeterogeneous Density <20 HUsDensity >20 HUs Necrosis, hemorrhage, calcifications

14. Adrenal mass

15. Adrenal histology No one characteristic feature Weiss score 0-9 –Nuclear grade –Mitotic rate –Atypical mitosis –Character of cytoplasm –Architecture of tumor cells –Necrosis –Invasion of venous structures –Invasion of sinusoid structures –Invasion of the capsule of the tumor

16. Steroid synthesis pathway

17. Infectious complications of Cushing’s syndrome Cryptococcosis Aspergillosis Nocardiosis Pneumocystis carinii Staph aureus Candida albicans Alternariosis Tinea

18. Bibliography Graham BS, Tucker WS, Opportunistic infections in endogenous Cushing’s syndrome. Ann Intern Med 1984 Sep;101 (3):334-8. http://images.google.com/imgres?imgurl=https://courses.stu.qmul.ac.uk/smd/kb/resources/endocrinologyresource/21- 36.JPG&imgrefurl=http://flipper.diff.org/app/items/info/418&usg http://models.cellml.org/workspace/bingzheng_zhenye_liansong_1990/@@rawfile/f475e016ed033c4b3dda595794addb2c8a6bcdc9/bingz heng_1990.png http://www.scielo.br/img/revistas/abem/v51n8/17f2.gif Up To Date Dr. O’Connell and Dr. DeCherney, UNC Endocrinology