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					Assist.Prof.Dr. Roongsiri Chotpadiwetkul


   Faculty of Associated Medical Sciences
     E-mail: r.muang@chiangmai.ac.th
     Hormonal imbalance

 I. Overproduction

II. Underproduction

III. Nonfunctional receptors that cause target
cells to become insensitive to hormones
http://www.nlm.nih.gov/medlineplus/ency/imagepages/8720.htm
Cortisol = Glucocorticoids




                             - Respond to stress
                             - anti-inflammatory &
                             immunosuppressive properties
Hypothalamic-pituitary-adrenal axis.
(CRH = corticotropin-releasing hormone;
ACTH = adrenocorticotropin hormone)
                                          http://www.aafp.org/afp/20000901/1119.html
  Cushing syndrome

• condition resulting from long term exposure to
excessive glucocorticoids (cortisol)
• „hypercortisolism‟
• intake of exogenous glucocorticoids/overproduction of cortisol
• 10-15 in 1 million people are affected


  Cushing disease

 •caused by excessive secretion of ACTH by pituitary tumor
 (pituitary adenomas)
 • represent most cases of Cushing‟s syndrome
TABLE 1
Clinical Features of Cushing's Syndrome
Sudden weight gain
Central obesity
Hypertension
Facial plethora
Proximal muscle weakness
Glucose intolerance or diabetes mellitus
Decreased libido or impotence
Depression or psychosis
Osteopenia or osteoporosis
Easy bruising
Hyperlipidemia
Menstrual disorders
Violaceous striae wider than 1 cm
Recurrent opportunistic or bacterial
infections
Acne
Hirsutism
The most common symptom of Cushing's syndrome is sudden
weight gain, usually manifested by central obesity.
Multiple wide striae on the abdomen
of a patient with Cushing's disease.
        TABLE 1
        Classification of Cushing's Syndrome


ACTH dependent
   Cushing's disease
   Ectopic ACTH syndrome
   Ectopic corticotropin-releasing
   hormone syndrome*

ACTH independent
   Iatrogenic
   Adrenal adenoma
   Micronodular hyperplasia*
   Macronodular hyperplasia*

ACTH = adrenocorticotropin hormone.
*--Accounts for 1 percent or less of cases.
When Cushing's syndrome is suspected, initial

laboratory testing is usually directed at

confirming excessive glucocorticoid production.


This can be accomplished with a 24-hour urine

collection and analysis for urinary free cortisol

excretion or with a dexamethasone suppression test.
   Urinary free cortisol excretion (UFC)

   • 24-hr urine

   • reference value: < 250 nmole (90 mg)/24hr
            >830 nmol(300 mg)/24hr : Cushing syndrome!

Dexamethasone suppression test

• 1 mg dexamethasone orally (at 11 p.m.), then

    plasma cortisol is measured (at 8 a.m.)

•  5 mg/dL        confirmed with UFC
•  5 mg/dL         re-evaluate within 3-6 months
• distinguish between patients with excess production of ACTH
due to pituitary adenomas from those with ectopic

ACTH-producing tumors
Once hypersecretion of cortisol is confirmed, the

next step is to determine whether the pathologic

state is adrenocorticotropin hormone (ACTH)

dependent or ACTH independent. This is done by

measuring a late-afternoon ACTH level.


       After 4 p.m (normally low)
       10 pg/ml: ACTH dependent
       < 5 pg/ml: ACTH independent
                        CRH stimulation test


  • distinguish between patients with pituitary adenomas and those
  with ectopic ACTH syndrome or cortisol-secreting adrenal tumors


                           CRH (i.v.) 1 mg/kg


        ACTH & cortisol before CRH injection, 15, 30, 45, 60, 90, 120 min


• if cortisol rise > 20% or ACTH rise at least 50% above basal level:


                “pituitary ACTH-dependent lesion”
      ACTH-independent lesion



Abdominal computed tomographic (CT) scan
                   or
    magnetic resonance imaging (MRI)




      Localise the site of lesion
                 Treatment:


 Pituitary adenoma

- surgical removal of the tumor
- radiotherapy
- drug „mitotane‟: suppress cortisol production

Ectopic ACTH syndrome

- surgery, chemotherapy to eliminate cancerous tissues

 Adrenal tumor

 - surgery
       Addison‟s disease


• adrenal glands do not produce enough cortisol

• chronic adrenal insufficiency or hypocortisolism

• 1 in 100,000

• weight loss, muscle weakness, fatigue, low blood
pressure, darkening of skin
http://www-clinpharm.medschl.cam.ac.uk/images/addisons.jpg
                            Causes:

I.    Primary adrenal insufficiency
      (disorders of adrenal glands themselves)

      - gradual destruction of adrenal cortex due to
autoimmune disorders

II.   Secondary adrenal insufficiency
      (inadequate secretion by pituitary gland)

       - lack of ACTH
       - long time taking „prednisone‟,then abruptly stop
       - surgical removal of ACTH-producing tumor of
pituitary gland
       - decrease size of pituitary (infection, loss of blood flow to
       pituitary)
    Symptom: progress slowly


    •Chronic, worsening fatigue
    • Muscle weakness
    • Loss of appetite
    • Weight loss
    • Skin change (dark tanning)

Addisonian crisis (acute adrenal insufficiency)

• Pain in lower back, abdomen, legs
• Severe vomiting
• Diarrheoa
• low blood pressure
• low blood sugar
• loss of conscious
                 Diagnosis:

•Review of patients‟s history + skin tanning
• Biochemical tests (insufficient cortisol)
• X-ray (calcium deposit: TB)

• ACTH stimulation test: most specific

                I. Rapid ACTH test


                Synthetic ACTH (i.v.)


                             30-60 min


              Blood/Urine Cortisol (T0, 30,60)
             II. Long ACTH stimulation test:

                  synthetic ACTH (i.v or i.m)


                                      48-72 hr



                   Blood / urine cortisol (T 0, 48, 72)



Interpretation: - primary adrenal insufficiency: no response

               - secondary adrenal insufficiency: adequate response
Insulin-induced hypoglycemia

   Blood glucose, cortisol at T0




   Fast-acting insulin injection




 Blood glucose, cortisol at T 30,45,90 min




 (Normal: glucose fall, cortisol rise)
Treatment:

Hormone replacement therapy

• hydrocortisone tablets (once/twice a day orally)

				
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