1. Adrenal Insufficiency
Haley Minnehan, MD

2. Adrenal Insufficiency Definition
A disease state that is caused by lack of glucocorticoids(GC) and/or mineralcorticoids (MC) by interruption at any level of the hypothalamus-pituitary- adrenal axis.

3. Hypothalamus-Pituitary-Adrenal Axis

4. Adrenal Insufficiency
Primary?
Secondary?
Tertiary?

5. Primary (Addisons)
Destruction
Of the Adrenal
Cortex

6. Primary=Primary Gland Failure = No cortisol or MC
1. Autoimmune
2. Infectious
3. Drugs
>Most Common
>Lymphocytic infiltration destroys entire adrenal cortex
>Antibodies are detectable TB
CMV
Histoplasmosis
Ketoconazole
Rifampin
Etomidate

7. Primary Causes continued…..
4.Deposition Diseases
5. Metastatic Disease
7. Adrenal Surgery
Sarcoidosis
Amyloidosis
Hemochromatosis
6. Congenital Adrenal Hyperplasia
8. Bilateral adrenal gland hemorrhage

8. Secondary= Lack of ACTH =Pituitary Problem

9. Secondary Causes Autoimmune - Lymphocytic hypophysitis
Postpartum hemorrhage-Sheehan’s syndrome
Head Trauma
Tumor
Infiltrative Process
Pituitary surgery

10. Tertiary Causes 3. Opiates 1. Exogenous 2. Megestrol Glucocorticoids
Prolonged therapy that is withdrawn
Has some GC properties so will affect the axis
Affects the axis at the CRH level.

11. What does cortisol do? MAINTAINS GLYCOGEN (cause of hypoglycemia)
REGULATES IMMUNE FUNCTION (more infections)
PART OF HEPATIC NEOGENESIS (gut absorption, nausea, diarrhea, vomiting)
VASCULAR TONE (cause of hypotension)

12. What does MC =Aldosterone do?
Regulates Na and K at the level of the kidney/ renin-angiotensin system
(Very little aldosterone secretion comes from ACTH stim)
Lack of aldosterone as in Primary AI
a) renal wasting of Na
b) retention of K
c)volume loss >>severe intravascular depletion>>>hyptotension and shock

13. Renin-Angiotensin-Aldosterone Loop

14. What does AI feel like?

15. Chronic AI Symptoms GI CNS OTHER Fatigue Weakness Chills
Unexplained abdominal pain
Weight loss
Chronic Nausea
Constipation
Vomiting
Headache
Cognitive clouding
Hypersomnia
Depression
Anxiety
Fatigue
Weakness
Chills
Recurrent infxns
Tan skin (Primary)
Hypotension

16. Normal vs SAI Cortisol Pattern

17. JFK had Addisons
Hyperpigmented
Chronically ill
How sick was JFK?

18. Acute Adrenal Crisis Always be in your differential of SHOCK Look foR:
1.Hypoglycemia
2. Acidosis
3. Hyponatremia
4. Hyperkalemia
Primary=low NA, High K

19. ACUTE ADRENAL CRISIS CAUSES
#1 IS gi FROM VOMITING/DIARRHEA
SURGERY
HEAT
EMOTIONAL DISTRESS
TRAUMA
PREGNANCY
INFECTION
ACUTE ADRENAL CRISIS CAUSES

20. ACUTE ADRENAL CRISIS TREATMENT
STEROIDS AND FLUIDS
100 mg IV Hydrocortisone stat then Q8 hours x 24 hours
Normal Saline
Correct hypoglycemia D5 with 100 mg IV HC if needed

21. Laboratory Diagnosis 8-9 am cortisol with ACTH
Cortisol Level:
>18 mcg/dl excludes AI
<3 is virtually diagnostic
< or =10 is suggestive and should start therapy before get further testing
11-18 hold therapy and obtain ACTH stim test (cosyntropin)
Sepsis workup without AI baseline cortisol < or = to 10 think AI
ACTH Level:
>or = to 22 is virtually diagnostic of primary AI

22. ACTH STIM TEST (Cosynotropin)
Give 250 mcg IV Cosynotropin
Measure serial cortisol serum levels at 30 and 60 minutes
Cortisol < 5 = Adrenal Failure
Cortisol >20 = Normal
Cortisol 5-20 = Pituitary Failure

23. Goals of Treatment #1 #2 #3 Physiological Replacement Of GC/MC
Improve QOL
Prevent Adrenal
Crisis

24. Glucocorticoid Replacement Options
Hydrocortisone
Prednisone
dexamethasone

25. Glucocorticoids are not all created equal
None are ideal in avoidance of risks of over or under replacement
Most physiological = hc
Prednisone potency= 4xHC
Dexamethasone=no effect on vascular tone last hrs

26. Chronic AI Treatment Primary Secondary Hydrocortisone 20-30 mg/day
Most physiologic
Divide doses up to TID
10/5/5=7am/12 pm/5 pm
Fludocortisone mg/day
Hydrocortisone mg/day
Divide doses up to TID
7.5/5/2.5 (all combinations)
No need for fludocortisone because aldosterone not under ACTH influence

27. Chronic AI Treatment cont…
Tertiary
Removal of the offending drug with a taper if possible (reversible)
Treat with maintenance HC if not able to d/c drug
As little as 20 mg/day prednisone for 7 days can cause AI
Be suspicious in asthmatics, COPD, rheumatology pts

28. Hydrocortisone GOOD BAD Restores physiology and relieves some symptoms
Nausea, weakness, headache, abdominal pain, hypotension
Allowed longer life span of AI patients
Prior to GC pts lived max 2 years after diagnosis
Cannot replace the physiology- circadian rhythm ie TIMING
Side effects: depression, irritability, insomnia, bone metabolism
Short acting- peaks at 1-2 hours then rapid decline until next dose at hr 4-5
Absorption rate variable

29. Treatment is Challenging
Physiological demands change throughout the day depending on the day.
No objective measurement of cortisol that is “normal” for that individual.
Ideal world = fingerstick rapid test so with symptoms know what to treat
Symptoms checklist: bp, fluids, low blood sugar, stress not accouneted for, infection, sleep deprived

30. Treatment is often trial and error
Despite treatment morbidity is high and life expectancy is reduced
WHY? Non-physiological nature of replacement therapy
Compliance with twice-three times daily dosing is difficult
Overexposure to GC> 30 mg per day=Cardiovascular Complications, Osteoporosis, Infections, Glucose Intolerance, Insomnia, Obesity
Underexposure= Infections, adrenal crisis, feel “post call” all the time, hypersomnia, significant impairment in physical, emotional and cognitive functioning affecting work, family, social

31. Stress Dosing! Ideal to “anticipate” the upcoming stressful event
Travel, holidays, call, prolonged exercise (football game), emotional distress, illness, surgery, pregnancy
Double or Triple the maintenance dose for 3 days then taper for 3 days until reach maintenance doses
Challenging- again
How much?
How long?

32. Stress dose for prolonged exercise

33. Patient and Family Education on Management
Life threatening disease that requires lifelong replacement
Educate and Reiterate the importance of stress dosing and how to avoid v adrenal crisis
ID Emergency bracelet>>”Adrenal Failure- Need steroids”
Emergency kit with 100 mg HC vials, needles, syringes for vomiting/diarrhea or other illness and cannot keep oral down
Give Prevnar and Pneumovax to prevent recurrent sinusitis/bronchitis

34. Despite treatment…. Patients report poor QOL
Worldwide survey of pts:
64% reported compromised health status
40% missed school or work in last 3 months
38% hospitalized in last yr
25% Disability
Despite treatment….

35. Patients need support Support groups
NADF (National adrenal disease foundation)
Website: provides information on emergency kits, patient information, newsletter and online support group- inspire.com
Quality of Life Discussions:
stress, exercise, routine, dosing compliance, sleep (no dosing after 6 pm), relationships, family life, work
Journaling dosing times, bp, hours of sleep, stress

36. What is in the Pipeline?
Cortisol pumps
Long acting/IR Cortisol

37. Adrenal Insufficiency after 4 years of Treatment

38. Thank you IAFP.