Adrenal insufficiency

1. TOPIC:
ADRENAL INSUFFICIENCY
PRESENTED BY: DR MAHNOOR
MD,PGR1

2. LEARNING OBJECTIVES
. DEFINITION
. EPIDEMIOLOGY
. ETIOLOGY
. CLINICAL MANIFESTATION
. DIAGNOSTIC WORKUP
. MANAGEMENT
. COMPLICATIONS
. FOLLOW UP

3. DEFINITION
ADRENAL INSUFFICIENCY
• IT IS A CLINICAL CONDITION CHARACTERIZED BY INADEQUATE
PRODUCTION OR ACTION OF ADRENAL HORMONES, PRIMARILY
CORTISOL AND IN SOME CASES ALDOSTERONE, DUE TO
DYSFUNCTION OF ADRENAL GLANDS (PRIMARY), PITUITARY
GLAND (SECONDARY) OR HYPOTHALAMUS (TERTIARY),

4. EPIDEMIOLOGY
• WORLDWIDE, PERMANENT AI IS FOUND IN 5 IN 10,000
POPULATION. THE MOST FREQUENT CAUSE OF AI IS
HYPOTHALAMIC-PITUITARY DAMAGE WHICH IS CAUSE OF
AI IN 60% OF AFFECTED PATIENTS.
• THE REMAINING 40% OF CASES ARE DUE TO PRIMARY
FAILURE OF ADRENAL TO SYNTHESIZE CORTISOL,
• IN PAKISTAN EXACT PREVALENCE IS UNKNOWN DUE TO
UNDERDIAGNOSIS OR LACK OF NATIONAL DATA.
HOWEVER STUDY CONDUCTED IN LAHORE SUGGESTED
THAT AMONG PATIENTS WITH TB 30% WILL DEVELOP AI.

5. However, aldosterone is
mainly controlled by RAAS
pathway.

6. CLASSIFICATION:
TYPES ACTH LEVEL CORTISOL,
ANDROGENS
ALDOSTERON
E
Primary AI
(Adrenal gland
failure)
High Low Low
Secondary AI
(pituitary failure)
Low Low Normal, due
to intact
RAAS
Tertiary AI
(Hypothalamic
failure, dec CRH)
Low Low Normal

7. CAUSES:
PRIMARY ADRENAL INSUFFICIENCY
A. AUTOIMMUNE ADRENALITIS, OFTEN PART OF AUTOIMMUNE POLYENDOCRINE SYNDROME (APS). APS
TYPE 1-ADDISONS + MUCUCUTANEOUS CANDIDIASIS, HYPOPARATHRYOIDISM AND APS TYPE 2:
ADDISONS + TYPE 1 DM + THYROIDITIS (SCHMIDT SYNDROME)
B. INFECTIOUS: TB MOST COMMON, HIV, MENINGOCOCCAEMIA (WATER HOUSE FRIEDRICHSEN
SYNDROME)
C. INFILTRATIVE DISORDERS: AMYLOIDOSIS, SARCOIDOSIS, HEMOCHROMATOSIS, LYMPHOMA
D. METASTATIC CANCER TO ADRENALS: LUNG, BREAST, MELANOMA, GI CANCERS
E. VASCULAR: ADRENAL HAEMORRHAGE DUE TO TRAUMA, ANTICOAGULATION THERAPY, DIC, SEPSIS
F. SURGICAL: BILATERAL ADRENALECTOMY
G. DRUG INDUCED: RIFAMPICIN, PHENYTOIN (INC CORTISOL METABOLISM), ABIRATERONE,
KETOCONAZOLE, ETOMIDATE.(INHIBITS CORTISOL SYNTHESIS)

8. SECONDARY AI
A. PITUITARY TUMOURS OR SURGERY
B. SHEEHAN SYNDROME: POSTPARTUM ISCHEMIC NECROSIS OF PITUITARY
C. PITUITARY APOPLEXY: SUDDEN HAEMORRHAGE OR INFARCTION OF PITUITARY
TUMOUR.
D. DRUGS THAT SUPPRESS ACTH: HIGH DOSE OPIOIDS, GLUCOCORTICOIDS (
CHRONIC USE CAN SUPPRESS ACTH)
TERTIARY AI
A. Chronic exogenous steriod
either INHALED,TOPICAL,ORAL, IV or INTRA articular.
B. HYPOTHALMIC TUMOURS OR RADIATIONS

9. NEWLY EMERGING CAUSES
• A.IMMUNE CHECKPOINT INHIBITOR THERAPY
• B. COVID 19 RELATED ADRENAL DYSFUNTION
• C.ADRENAL FATIGUE

10. PRESENTATION:

11. QUICK COMPARISON
Feature Primary AI Secondary AI
Hyponatremia yes yes
Hypekalemia yes no
Hypoglycemia yes yes
Skin pigmentation Present (inc Acth ,inc
MSH)
Absent
Hypotension Severe Mild

12. DIAGNOSTIC WORKUP
1. BASELINE LABS
HYPONATREMIA
HYPERKALAEMIA
HYPOGLYCAEMIA
ELEVATED CREATININE, UREA
EOSINOPHILIA

13. 2.
8AM SERUM CORTISOL
<80NMOL/L
SUGGESTS
ADRENAL
INSUFFINCY
>500NMOL/
L
NORMAL
ADRENAL
FUNCTION
B/W 80-500
NMOL/L
INTDERMINATE
RESULT,
DO ACTH
STIMULATION
(SYNACTHEN
TEST)

15. 250mg
Cortisol levels
should rise
btw 500-
600nmol/L

16. . PLASMA ACTH LEVELS:
HIGH IN PRIMARY AI
LOW IN SECONDARY AI
. PLASMA RENIN OR ALDOSTERONE
IN PRIMARY AI: INC RENIN BUT DEC ALDOSTERONE
IN SECONDAY AI: NORMAL RENIN AND NORMAL
ALDOSTERONE (DUE TO RAAS STIMULATING ADRENAL
GLAND)

17. LONG SYNACTHEN TEST
(RARELY NEEDED)
• TO DIFFERENTIATE PRIMARY AI FROM SECOND AI
• WE GIVE 1MG SYNACTHEN IM AND MEASURE SERUM CORTISOL AT 30, 60
AND 120MINS AND AT 4, 8, 12 AND 24 HR FOLLOWING FOR 3 DAYS.
• IF SERUM CORTISOL RISES ABOVE 1000NMOL/L SUGGESTS THAT ADRENAL
GLAND ARE MILDLY ATROPHIC AND NOT PERMANENTLY DAMAGED
(SECONDARY AI )
• IF NO RISE IN SERUM CORTISOL MEANS PERMANENT DAMAGE TO
ADRENALS.(PRIMARY AI).

18. SPECIAL/ADDITIONAL TESTS:
• ANTI 21 HYDROXYLASE ANTIBODIES FOR AUTOIMMUNE
ADRENALITIS
• PITUITARY MRI: IF SECONDARY AI SUSPECTED
• ADRENAL CT SCAN :IF INFECTION, METASTASIS OR TB SUSPECTED

19. CHRONIC MANAGEMENT (MAINTENANCE
THERAPY)
DEFICIENCY DRUG DOSE
Glucocorticoid Hydrocortisone
Or
Prednisone
(20mg Hydrocortisone
equals 4mg on prednisone)
15-25mg can be given tds or
bd
Like for 20mg give 15mg in
morning and 5mg at
midday
Give 3 mg in morning and
1mg midday
Mineralocorticoid Fludrocortisone ,only in
primary AI
Give 0.05 or 0.1mg once a
day.it equals 100-200
micrograms
Androgens (females)
Males have normal bcz it comes
from testes mainly.
DHEA Give 25-50mg/day

20. MONITORING OF THERAPY
CLINICAL
. WATCH FOR SIGNS OF GLUCOCORTICOID EXCESS LIKE WEIGHT GAIN
. BP (INCLUDING POSTURAL CHANGE)
. HYPERTENSION AND EDEMA SUGGESTS EXCESS MC REPLACEMENT, WHEREAS
POSTURAL HYPOTENSION AND SALT CRAVING SUGGESTS INSUFFIENCY.
BIOCHEMICAL
. SERUM ELECTROLYTES
. SERUM CORTISOL TO ASSESS ADEQUACY.

21. SPECIAL CONSIDERATIONS
• CORTISOL REQUIREMENTS INCREASES DURING SEVERE ILLNESS OR SURGERY.
• PATIENT HAVING DIARRHOEA VOMITING OR ANY INFECTION DOUBLE THE DOSES
• FOR MODERATE ELECTIVE PROCEDURES OR INVESTIGATIONS LIKE ENDOSCOPY
,COLONOSCOPY PATIENT SHOULD RECEIVE A SINGLE DOSE OF 100MG
HYDROCORTISONE BEFORE PROCEDURE
• FOR MAJOR SURGERY, PATIENT SHOULD RECEIVE 100MG IV OR IM
HYDROCORTISONE AND 50MG 6 HOURLY FOR 1-2 DAYS UNTIL RECOVERY

22. ADRENAL CRISIS: A LIFE THREATENING EMERGENCY

23. STEP BY STEP EMERGENCY MANAGEMENT: ABCDE OF ADRENAL CRISIS
IF DIAGNOSIS IS SUSPECTED, DO NOT WAIT FOR LABS AND TREAT HOWEVER IT IS BEST TO
DRAW SAMPLES BEFORE STARTING IV MEDICATIONS.
A. ACCESS IV AND AIRWAY SUPPORT
. SECURE AIRWAY AND BREATHING ,OXYGEN IF NEEDED
. IV ACCESS ,1-2 CANNULAS
B. BOLUS FLUIDS
. START IV FLUIDS , 0.9% NS, 1L RAPIDLY THEN 4-5 L IN 24H (MONITOR BP, URINE
OUTPUT)

24. C. CORTISOL , GLUCOCORTICOID REPLACEMENT
• GIVE HYDROCORTISONE 100 MG IV BOLUS IMMEDIATELY THEN
GIVE 50-100 MG IV EVERY 6 HRS OR CONTINUOUS INFUSION
200MG/24 HRS
• HYDROCORTISONE IS PREFERRED AS IT HAS BOTH
GLUCOCORTICOID AND MINERALOCORTICOID ACTIVITY IN HIGH
DOSES. NO FLUDROCORTISONE NEEDED ACUTELY.

25. D. DEXTROSE: 50ML OF 50% DEXTROSE IV IF GLUCOSE
<70
E. EVALUATE AND TREAT UNDERLYING CAUSE

26. RECOVERY PHASE ( AFTER 24-48 HRS)
• ONCE PATIENT STABILIZES
STEP ACTION
Swtich to oral hydrocortisone or
prednisone
15-25mg/day divided in 2/3 morning and
1/3 afternoon like 15mg in morning and
5mg afternoon
Or prednisone 3mg in morning and 1 mg
afternoon
Add fludrocortisone (if primary AI) 0.05 - 0.2 mg/day which equals 100-
200 micrograms one a day

27. MANAGING ADRENAL INSUFFICIENCY WITH
COMORBIDITIES
Comorbidity Special considerations
Diabetes Mellitus Give lowest effective dose, steroids
raises blood sugar.
Hypothyroidism Treat AI before starting levothyroxine
as it can trigger adrenal crisis
without cortisol to meet metabolic
demands.
Sepsis/Icu High risk of crisis ,inc doses
accordingly
Heart Failure Limit fluids ,give fludrocortisone
cautiously to prevent worsening of
edema
Autoimmune diseases Screen for other endocrinopathies