Cushing's Syndrome

1. Pituitary Dependent
   1. Cushing's Disease
2. ACTH Administration
3. Ectopic ACTH secreting Tumour
   1. Impaired GTT (Frank DM)
   2. HypoKalaemia

1. Adrenal
   1. Carcinoma
   2. Adenoma
2. Alcohol Induced "Psuedo-Cushing's"
   1. Cushingoid Appearance due to alcohol consumption
3. Glucocorticoid administration

1. Weight Gain
2. Depression
3. Insomnia
4. Amenorrhoea/ Oligomenorrhea
5. PoorLIbido
6. Hair Growth
7. Thin Skin
8. Back Pain
9. Polyuria/Polydipsia

1. Moon Face
2. Dorsal Fat Pad
3. Striae (Purple/Red)
4. Acne
5. Pigmentation
   1. Only In ACTH causes
6. HTN
   1. All Cushing's
7. Central Obesity
8. Pathological Fractures

Nota:

• Demonstrate Inappropriate secretion of cortisol 

1. 48 Hrs Dexamethasone Test (Low Dose)
   1. Measure Day 0 and Day 2
      1. Normal <50nmol/L
      2. Abnormal: Cortisol not suppressed
2. 24-Hour Urinary Free Cortisol
3. Circadian Rhythm
   1. After 48Hrs Cortisol at 09:00 and 24:00
      1. High Midnight Cortisol in CUSHING'S
4. Other Tests
   1. Insulin Stress Test
   2. Desmopressin Stimulation Test
   3. CRH Test

      Nota:

      • http://www.pathology.leedsth.nhs.uk/dnn_bilm/Investigationprotocols/Pituitaryprotocols/CorticotrophinReleasingHormoneCRHTest.aspx

1. ACTH Dependent
   1. Ectopic

      Nota:

      • Other tests. Radio-labelled otreotide to locate ectopic ACTH
      1. Plasma ACTH >200ng/L
      2. Frank Diabetes
      3. Hypokalaemia
      4. 48 Hr Dexamethasone Test (High Dose)
         1. Failure of Significant Cortisol Suppression.
      5. Chest X-Ray
         1. Bronchial Carcinoid
            1. CT-Lung, Mediastinum and Abdomen
   2. MRI/CT Scan
      1. Bilateral Adrenal Hyperplasia
   3. Pituitary

      Nota:

      • Other Tests Catheterization of inferior petrosal sinus to measure ACTH for pituitary lesions.  
      1. Adenoma
         1. MRI/CT Scan
      2. Cushing Disease
         1. CRH Test

            Nota:

            • In response to exogenous CRH, Exaggerated ACTH and Cortisol Response is soon. 
2. NON-ACTH
   1. Adrenal
      1. CT/MRI Scan
         1. Tumour
            1. 48 Hr Dexamethasone Test (High Dose)
               1. Failure of Significant Cortisol Suppression.
         2. Adenoma
         3. Nodular Hyperplasia

1. METYRAPONE 750g to 4g Daily (TDS/QDS)
2. KETOCONAZOLE 200mg TDS
3. Monitor Plasma Coritsol

1. Trans-sphenoidal Adenomectomy
2. External Irradiation
   1. When surgery fails
3. Medical Therapy
   1. Reduce ACTH levels
      1. Bromocriptine
      2. Cabergoline
4. Bilateral Adrenalectomy (Laparoscopic)
   1. Last Resort
   2. NELSON SYNDROME

      Nota:

      • Enlarged Pituitary, Increased ACTH production  Excessive Pigmentation.  Can be reduced by performing a pituitary radiotherapy after bilteral adrenalectomy.  
      1. Bitemporal Hempianopia
      2. Pigementation excess

1. Adenomas
   1. Resect after Medical remission
      1. METYRAPONE
      2. KETOCONAZOLE
2. Carcinomas
   1. Poor Prognosis
   2. Surgery reduces tumor bulk
      1. MITOTANE inhibits tumor Growth
      2. Radiotherapy after surgery

1. KNOWN
   1. RESECTION
   2. Chemo/Radio if surgery impossible.
   3. Medical Control
      1. METYRAPONE
      2. KETOCONAZOLE
   4. Bilateral Adrenalectomy
2. UNKNOWN