1. Adrenal Dr Sohail Inam FRCP(Ed), FRCP Consultant Endocrinologist
Prince Sultan Military Medical City
Riyadh, Saudi Arabia

3. CRH
AVP
Renin
substrate
Kidney
Renin
ACTH
Angiotensin I
Angiotensin II
Cortisol
Aldosterone
Androgens

4. Cortisol Energy metabolism Maintain circulation
Increases glucose
Increases fat breakdown
Protein breakdown
Maintain circulation
Increasing blood volume
Increase in vascular tone
Control of inflammation

5. Aldosterone Mineralocorticoid
Increase blood volume
Kidney & GIT
Na reabsorption
K excretion
Vascular endothelium
Cardiac

6. Adrenal Andogrens DHEAS, Androstenedione
Axillary & pubic hair
Libido
Muscle strength
Immune modulation
Bone health

7. X CRH AVP Renin substrate Kidney Renin ACTH Angiotensin I
Angiotensin II
Cortisol
Aldosterone
Androgens

8. X ↑Renin CRH AVP Renin substrate Kidney ACTH Angiotensin I
Angiotensin II
Cortisol
Aldosterone
Androgens

9. Primary Adrenal Insufficiency
Damage to adrenal gland
All 3 hormones are affected
Increase compensation due to lack of feed back
High ACTH levels
High Renin levels

10. X ↓ACTH CRH AVP Renin substrate Kidney Renin Angiotensin I
Angiotensin II
↓Cortisol
Aldosterone
↓Androgens

11. Central Adrenal Insufficiency
Damage to pituitary/hypothalamus
ACTH levels are low
Only cortisol & androgens are affected

12. Causes Primary Adrenal Insufficiency
Autoimmune
Infection
TB, CMV, HIV, Fungal
Hemorrhage or infarction
Malignancy
Infiltrative
Sarcoidosis, hemochromatosis, amyloidosis
Adrenal leukodystrophy
Drugs

13. Causes Central Adrenal Insufficiency
Exogenous steroid (commonest)
Pituitary tumors
Infection
Inflammation
Hemorrhage & infarction
Infiltrative
Trauma
Radiation

14. Clinical presentation
Adrenal Insufficiency
Clinical presentation

15. Chronic Presentation Asthenia Weight loss GIT Postural dizziness
Anorexia
Nausea, vomiting and abdominal pain
Diarrhea
Postural dizziness
Pigmentation (primary)

17. Chronic Presentation Become very unwell with stress
Low BP with postural drop and tachycardia
Electrolyte disturbances
Hypoglycemia

18. Acute Adrenal Insufficiency Presentation
Adrenal crisis (Non-specific)
Hypotension
Postural
Recumbent
Abdominal pain
Electrolyte disturbances
Hypoglycemia

19. Electrolyte Abnormalities Adrenal Insufficiency
Primary
Central Na
Low K
High or high normal
Normal or low normal
Urea
High
Normal or high
Creatinine
Low normal
Calcium

20. Acute Adrenal Insufficiency Precipitating factors
Omission of corticosteroids
Increased requirements
Infection
Physical stress
Drugs

21. Diagnosis Measurement of adrenal hormones Cortisol, DHEAS, Aldosterone
Primary versus central
ACTH, Renin
Determine cause

22. Diagnosis Cortisol
Random
8-9 am level
Level during stress
Stimulated

23. ACTH Stimulation Test Standard (250 mcg)
Can be performed any time though preferably 8-9 am.
0, 30, 60 minute
Any value  550 nmol/l excludes adrenal insufficiency in non-critically ill patients
Test is abnormal in almost all patients with primary adrenal insufficiency & 90% individuals with central adrenal insufficiency

24. Pituitary Stimulation Tests
Insulin tolerance test (ITT)
Gold standard for central disease
Risk from hypoglycemia
CRH
Metyrapone
Other

25. Determine Cause Careful history of previous steroid use Radiology
Adrenal CT (Primary)
Pituitary MRI (Central)
Autoantibody
Tests specific for suspected etiology

26. Acute AI Management Fluids Glucocorticoids Treat underlying cause
Resuscitate
0.9% NaCl
Glucose
Glucocorticoids
Treat underlying cause
Precipitation event
Etiology

27. Steroid Therapy Acute crisis Chronic Stress dose adjustment
IV Hydrocortisone drug of choice
Natural compound & mineralocorticoid activity
50 mg 6-8 hourly
Taper dose early
No additional benefit of mineralocorticoids
Chronic
Maintenance glucocorticoid ± mineralocorticoid
Stress dose adjustment

28. Cushing's Syndrome

29. Cushing’s Syndrome Chronic tissue exposure to excess cortisol
Exogenous
Endogenous

30. Clinical features Weight gain Skin changes Proximal muscle weakness
Central fat distribution
Skin changes
Thinning
Striae
Easy bruising
Proximal muscle weakness
Osteoporosis

31. Cushing’s Syndrome Clinical features
Hypertension
Glucose intolerance
Psychiatric disturbance
Hypogonadism
Infections

34. Cushing’s Syndrome Cause
ACTH dependent 75-80%
Pituitary adenoma (Cushing’s disease) 60-70%
Ectopic 10-15%
ACTH independent
Exogenous steroids
Adrenal adenoma & carcinoma (18-20%)
Bilateral adrenal hyperplasia

35. Ectopic ACTH Secretion
Lung
Carcinoid
Small cell carcinoma
Pancreas
Neuroendocrine tumors
Thymus
Other carcinomas

36. Diagnosis Clinical suspicion Documenting hypercortisolism
Symptoms & signs
Documenting hypercortisolism
Determining the cause

37. Diagnosis of Cushing’s Syndrome Documenting Excess Cortisol
Exclude exogenous steroid use
Excess cortisol
24 Hour urine for free cortisol (>3 x Normal)
Loss of diurnal variation
Midnight or late night cortisol (3 samples)
Abnormal regulation
Dexamethasone suppression test
At least 2 out of 3 should be abnormal

38. Diagnosis of Cushing’s Syndrome Falsely Abnormal Tests
Patients who are physically stressed
Sick patients
Patients with severe obesity
Malnutrition, Anorexia nervosa, Severe exercise
Patients with psychological stress
Severe major depressive disorder
Chronic alcoholism
Drugs

39. Determining the cause ACTH
ACTH suppressed (Independent)
Adrenal tumors
Exogenous steroids
ACTH normal or elevated (Dependent)
Cushing’s disease
Ectopic Cushing’s

40. Determining the Cause ACTH Dependent
MRI pituitary
Inferior petrosal venous sampling
CT chest and abdomen
High dose dexamethasone suppression test
Functional nuclear scans

41. Treatment Adrenal tumors Cushing’s disease Surgical resection Surgery
Medical therapy
Radiotherapy
Bilateral adrenalectomy

42. Treatment Ectopic ACTH secretion
Treat the underlying tumor (surgical resection)
Medical therapy
Somatostatin analogues
Adrenal blocking drugs
Bilateral adrenalectomy

43. Treatment Medical Therapy
Inhibit ACTH release
Somatostatin receptor analogues
D2 receptor analogues (cabergoline)
Block cortisol synthesis
Ketaconozole, Metyrapone, Mitotane
Block the cortisol receptor
Mifepristone

44. Thank You