Cushing's Syndrome

Cushing's Syndrome

1. Causes

   • ACTH
     • Pituitary Dependent
       • Cushing's Disease
     • ACTH Administration
     • Ectopic ACTH secreting Tumour
       • Impaired GTT (Frank DM)
       • HypoKalaemia
   • NON- ACTH
     • Adrenal
       • Carcinoma
       • Adenoma
     • Alcohol Induced "Psuedo-Cushing's"
       • Cushingoid Appearance due to alcohol consumption
     • Glucocorticoid administration

2. Clincal Presntation

   • Symptoms
     • Weight Gain
     • Depression
     • Insomnia
     • Amenorrhoea/ Oligomenorrhea
     • PoorLIbido
     • Hair Growth
     • Thin Skin
     • Back Pain
     • Polyuria/Polydipsia
   • Signs
     • Moon Face
     • Dorsal Fat Pad
     • Striae (Purple/Red)
     • Acne
     • Pigmentation
       • Only In ACTH causes
     • HTN
       • All Cushing's
     • Central Obesity
     • Pathological Fractures

3. Diagnosis

   • Confirmation
     • Demonstrate Inappropriate secretion of cortisol 
     • 48 Hrs Dexamethasone Test (Low Dose)
       • Measure Day 0 and Day 2
         • Normal <50nmol/L
         • Abnormal: Cortisol not suppressed
     • 24-Hour Urinary Free Cortisol
     • Circadian Rhythm
       • After 48Hrs Cortisol at 09:00 and 24:00
         • High Midnight Cortisol in CUSHING'S
     • Other Tests
       • Insulin Stress Test
       • Desmopressin Stimulation Test
       • CRH Test
         • http://www.pathology.leedsth.nhs.uk/dnn_bilm/Investigationprotocols/Pituitaryprotocols/CorticotrophinReleasingHormoneCRHTest.aspx
   • Differential of Cause
     • ACTH Dependent
       • Ectopic
         • Other tests. Radio-labelled otreotide to locate ectopic ACTH
         • Plasma ACTH >200ng/L
         • Frank Diabetes
         • Hypokalaemia
         • 48 Hr Dexamethasone Test (High Dose)
           • Failure of Significant Cortisol Suppression.
         • Chest X-Ray
           • Bronchial Carcinoid
             • CT-Lung, Mediastinum and Abdomen
       • MRI/CT Scan
         • Bilateral Adrenal Hyperplasia
       • Pituitary
         • Other Tests Catheterization of inferior petrosal sinus to measure ACTH for pituitary lesions.&nbsp;&nbsp;
         • Adenoma
           • MRI/CT Scan
         • Cushing Disease
           • CRH Test
             • In response to exogenous CRH, Exaggerated ACTH and Cortisol Response is soon.&nbsp;
     • NON-ACTH
       • Adrenal
         • CT/MRI Scan
           • Tumour
             • 48 Hr Dexamethasone Test (High Dose)
               • Failure of Significant Cortisol Suppression.
           • Adenoma
           • Nodular Hyperplasia

4. Treatment

   • Pre-operative Control
     • METYRAPONE 750g to 4g Daily (TDS/QDS)
     • KETOCONAZOLE 200mg TDS
     • Monitor Plasma Coritsol
   • Pituitary Dependent
     • Trans-sphenoidal Adenomectomy
     • External Irradiation
       • When surgery fails
     • Medical Therapy
       • Reduce ACTH levels
         • Bromocriptine
         • Cabergoline
     • Bilateral Adrenalectomy (Laparoscopic)
       • Last Resort
       • NELSON SYNDROME
         • Enlarged Pituitary, Increased ACTH production&nbsp; Excessive Pigmentation.&nbsp; Can be reduced by performing a pituitary radiotherapy after bilteral adrenalectomy.&nbsp;&nbsp;
         • Bitemporal Hempianopia
         • Pigementation excess
   • Adrenal
     • Adenomas
       • Resect after Medical remission
         • METYRAPONE
         • KETOCONAZOLE
     • Carcinomas
       • Poor Prognosis
       • Surgery reduces tumor bulk
         • MITOTANE inhibits tumor Growth
         • Radiotherapy after surgery
   • Ectopic
     • KNOWN
       • RESECTION
       • Chemo/Radio if surgery impossible.
       • Medical Control
         • METYRAPONE
         • KETOCONAZOLE
       • Bilateral Adrenalectomy
     • UNKNOWN

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