1. What is the clinical diagnosis? What clinical manifestations help to determine this diagnosis?
Cushing's syndrome.

The clinical features that help are 

• weight gain (with centripetal fat distribution in the subcutaneous tissues of face and neck, mediastinum, peritoneum,) 

• depression

• mild hirsutism

• muscle weakness 

• hypertension

• hyperglycemia

• skin changes, etc.
  
  

2. What initial test(s) can be done to assess this condition?

• 24-hour urine free cortisol (UFC) which assesses the integrated plasma free cortisol centrations during a 24-hour period that is filtered by the kidney. 

• Normal is less than 100 mcg/24 hours (although in assays of greater specificity it is less than 50 mcg/24 hours). UFC is normal in the obese although it may slightly increased in <5%. 

• False positives in alcoholism and severe depression (pseudo Cushing states).

• Overnight 1 mg Dexamethasone suppression test whereby 1 mg DEXA given p.o. at 11 p.m. and an 8 a.m. plasma cortisol > 5 mcg/dl suggests Cushing's syndrome.
•  Problems: false positives in intermittent Cushing's syndrome, intake of drugs which increase DEXA metabolism (phenytoin, rifampin, Phenobarbital), estrogen therapy (increased CBG), endogenous depression, obesity, non-compliance with taking DEXA, etc.

3. What is the differential diagnosis after the screening test(s) has confirmed your clinical diagnosis.

ACTH dependent Cushing's syndrome.

-Cushing's disease (pituitary)
-Ectopic ACTH syndrome (small cell lung carcinoma, carcinoids, neuroendocrine tumors)
-Ectopic CRH syndrome (bronchial carcinoid)

ACTH independent Cushing's syndrome.

-Adrenocortical neoplasm (benign or malignant)
-Nodular adrenal hyperplasia (micro-, macro-, PPNAD)
-Food dependent (gastric inhibitory polypeptide mediated)
-Factitious

Pseudo Cushing's syndrome

-Alcoholism
-Major depression, severe stress
-Anorexia/bulimia

4. With this information what is the diagnosis in this patient?

• After two days of high dose DEXA (this can also be performed by overnight 8 mg DEXA p.o.), suppression of 17/(OH)CS by > 64% of baseline and UFC by > 90% of baseline indicating pituitary dependent Cushing's disease.

•  Results that are inconclusive may need further testing such as peripheral CRH stimulation test, inferior petrosal sinus sampling, etc. 

• In this patient, 17(OH)CS suppresses by 72% on day 4 and UFC suppresses by 90% on day 4. ACTH > 52 pg/ml suggests ACTH dependent Cushing's syndrome.
  
  

5. What therapeutic strategy would you recommend?

a) diagnostic

• High resolution MRI of sella turcica with and without gadolinium enhancement. No tumor was identified (only 50% of the microadenomas that cause Cushing's disease are detected). 

• If there was no suppression with high-dose DEXA and ACTH was measurable, a chest +/- abdominal CT/MRI should be done to rule out ectopic ACTH-producing tumor. 

• If ACTH was suppressed, a thin section CT/MRI of adrenals should be done to rule out adrenal adenoma/carcinoma.

b) treatment

• Transsphenoidal hypophysectomy with 85% resection of anterior pituitary was done.

•  Immmunostain were strongly positive for ACTH. 

• Patient was placed on anterior pituitary replacement hormones.