Lecture form PARM 2223

1. Adrenal Issues
PARRM 2223
This Photo by Unknown Author is licensed under CC BY-NC-ND

2. Objectives
• Awareness of the pathophysiology of Primary and Secondary Acute
adrenal failure
• Awareness of the pathophysiology of Cushing's Syndrome
• Recognition of the possible clinical presentation that the patient in
Addisonian Crisis may present with.
• Provide education on the optimal treatment for an apparent
Addisonian Crisis.

3. Introduction
• Adrenal emergencies in the pre hospital field are rare but when
encountered the outcome can be fatal if it is not recognized and
treated rapidly.
• The greatest challenge for pre hospital clinicians is to recognize this
elusive condition. Signs and symptoms may be non-specific early on
in the presentation and the diagnosis may not be suspected or
immediately clear in the course of treatment.

4. A rose by any other name
• When dealing with a patient who is aware they
are steroid dependent they may refer to their
condition using a variety of names, for example:
• I am a / have:
• Cortisol Dependent/ Steroid Dependent
• Pituitary Patients
• Addison's Disease
• Adrenal deficient
• Hypercortisolism

5. Epidemiology
• While some studies report to an incidence of adrenal insufficiency of 50
per million, though some studies point to as high as 120 per million.
(Simmons -Holcomb 2006).
• Secondary Adrenal insufficiency is more common than primary adrenal insufficiency
• Most often due to steroid withdrawal
• Approximately 6,000,000 persons in the United States are considered to
have undiagnosed adrenal insufficiency, which is clinically significant only
during times of physiologic stress
• Research also points out that 60% of patients had seen two or more clinicians before
the diagnosis was made.
• While easily treated, mortality for untreated Adrenal Crisis is very high.

6. EMS dropping the
ball…

8. Pathophysiology

9. Discovery and
Innovation
• Adrenocortical insufficiency was first
recognized by Thomas Addison in 1844.
• Prior to the invention of
glucocorticosteroids in the late 1940s
most patients died before reaching
adulthood.
• Adrenocortical insufficiency is an
uncommon life threatening condition
that is readily treated if recognized.
• Adrenal insufficiency may be
categorized as primary, secondary,
congenital or acquired.

10. Etiology
• The adrenal glands sit at the top of the kidneys,
• one on each side of the body
• inner core (known as the medulla)
• surrounded by the outer shell (known as the cortex).
• The inner medulla produces epinepherine, the “fight or
flight” stress hormone.
• The Cortex produces the steroid hormones that are
essential for life: cortisol and aldosterone.
• Cortisol mobilises nutrients, it enables the body to fight
inflammation, it stimulates the liver to produce blood sugar and it
also helps control the amount of water in the body.
• Aldosterone regulates salt and water levels which affect blood
volume and blood pressure.
• The adrenal cortex also produces sex hormones known as adrenal
androgens; the most important of these is DHEA
(Dehydroepiandrosterone).

11. Did you know…
Where the word Adrenal Comes from?

12. Adrenal Glands
• The normal adrenal
cortex has an
enormous functional
reserve.
• This is called upon by
the body especially in
times of intense stress,
such as surgery,
trauma or serious
infection.

13. Cortisol helps the
body respond to
stress.
• Among its other vital tasks,
cortisol:
• helps maintain blood
pressure and
cardiovascular function;
• helps slow the immune
systems inflammatory
response;
• helps balance the effects
of insulin in breaking
down sugar for energy;
and
• helps regulate the
metabolism of proteins,
carbohydrates, and fats.

14. KEY POINT
One of the most significant
consequences of Addison's disease is
the body's failure to adapt to such
stresses.
This combined with inadequate
steroid reserves result in a state of
shock, known as an Addisonian crisis,
which is a medical emergency.

15. Primary vs. Secondary
• In primary adrenal insufficiency glucocorticoid and
frequently mineral corticoid hormones are lost.
• In the United States 80 - 85% of cases are caused by
autoimmune destruction.
• A substantial portion is caused by steroid use.
• Glandular infiltration by tuberculosis is the second
most frequent etiology. In developing countries
Tuberculosis is the most frequent cause.
• Other, much rarer causes of Addison’s include certain
fungal infections, adrenal cancer and adrenal
hemorrhage (for example, following a car accident).

16. In developing countries and underserved
populations, Tuberculosis is the most
frequent cause of adrenal insufficiency.
What does this mean for EMS in the
US?
In developing countries and underserved
populations, Tuberculosis is the most
frequent cause of adrenal insufficiency.
What does this mean for EMS in the US?

17. Secondary adrenal
insufficiency
• Secondary adrenal
insufficiency is adrenal
hypofunction due to a lack of
adrenocorticotropic hormone
(ACTH) and other conditions of
the pituitary gland and
hypothalamus.

18. Adrenal Hyperplasia
• Whilst the main focus of this module is Addisonian Crisis it is important to
also mention Congenital adrenal hyperplasia.
• Congenital adrenal hyperplasia is a genetic condition causing swelling of
the adrenal glands.
• The condition is associated with a decrease in the blood level of cortisol
(the stress hormone) and an increase in the level of androgens (male sex
hormones) in both sexes.
• This can be so severe that females are misdiagnosed at birth as males, or
very mild.
• Advanced bone age
• Predisposes to “salt wasting” (hyponatremia)

19. Steroids as a cause
• Synthetic Glucocorticoid Steroids have been around since 1940’s.
• Synthetic Glucocorticoid Therapy is a common intervention for:
• COPD
• Asthma
• Arthritis
• Lupus
• Certain auto-immune conditions
• Organ Transplantation
• “Critical illness-related cortisol insufficiency“
• 20% incidence,
• Up to 60% in septic shock
• VSE Therapy
• Chronic use suppresses Cortisol production
• Sudden stopping of SGT can precipitate Addison's disease and lead to adrenal crisis.

20. Unrelated but
interesting: VSE
Therapy

21. Classic Presentation
• Early stages symptoms of Addison’s disease are similar to other more
common health conditions such as depression or flu.
• The patient may experience:
• fatigue (lack of energy or motivation)
• lethargy (abnormal drowsiness or tiredness)
• muscle weakness
• low mood (mild depression) or irritability
• loss of appetite and unintentional weight loss
• the need to urinate frequently
• increased thirst
• craving for salty foods

22. Darkened Skin????

24. Presentations
• If the patient is experiencing an
Addisonian crisis, they may
experience a range of symptoms.
• Some symptoms resemble those
of other conditions.
• nausea or abdominal pain
• vomiting
• fever
• joint pain
• loss of appetite
• dramatic changes in blood
pressure
• weakness
• chills
• rashes of the skin
• an irregularly high heart rate
Some patients may experience a craving for salt, for example.
Others may feel fatigued, experience darkening of the skin,
or have unintentional weight loss. Many of these symptoms
can develop over time as part of Addison's disease.

25. Clinical
Presentation of
Adrenal
Insufficiency
• Patients with acute adrenal insufficiency
generally present with acute
dehydration, hypotension,
hypoglycaemia or altered mental status.
• Treat these conditions accordingly IN
ADDITION TO the suspected adrenal
crisis.
• Remember your differential Dx.
• Shock (all causes)

26. Adrenal Insufficiency vs. Adrenal Crisis
Adrenal Insufficiency:
• Chronic condition
• Adrenal glands fail to produce
specific stress hormones
• The student will take daily
medications
• Will not be hypotensive, etc
Adrenal Crisis:
• Acute
• This is an exacerbation of a
patient’s adrenal insufficiency
which can be caused by:
• Illness
• Injury
• Stress
• Missing daily medications

27. Good to know
• One third of adrenal crises occur outside of
the home.
• Vomiting and diarrhea account for most
adrenal crisis events because it interferes
with the absorption of their daily, prescribed
medication.

28. Adrenal Crisis Triggers

29. Quick and Sudden
• Steroid withdrawal is most common cause in the US and industrial
countries
• Other Causes:
• A precipitating illness (severe infection, acute myocardial infarction, stroke)
• Surgery without “adrenal support”,
• pregnancy,
• any acute or chronic disease,
• acute trauma

30. Treatment

31. Treatment Strategies
• KEY POINT #1: Steroid use is a
bridge therapy, may not be
definitive
• KEY POINT #2: Providers should
have a very low threshold to give
steroids to a patient with a hx of
Addison's Crisis
• KEY POINT #3: Overall strategy is
similar as Septic Shock + Steroids
• KEY POINT #4: Treat adjacent
conditions simultaneously

32. Stress Dose of
Glucocorticosteroids
• When a person who does NOT suffer from adrenal
insufficiency suffers significant physical or emotional stress,
they produce up to 10X the normal amount of hormones
needed in response to the event.
• Patients with Adrenal Insufficiency cannot produce these
hormones and must be given an extra dose of medication
(on top of their daily prescribed dose) when their body
experiences physical or emotional stress.
• This is called a “STRESS DOSE.” Depending on the severity of
the event, a stress dose may be given orally or via injection.
•32

34. Hydrocortisone (Solu-
Cortef)
• Dosage: 100mg
• Ped 2 mg/kg
• Route: Intravenous is the preferred
route of administration but
Intramuscular can be used if IV access
is not available.
• Administration: Titrate over a 2
minute period to avoid side effects.
• Contraindications: Known allergy
(which will be to the sodium
succinate or sodium phosphate rather
than the hydrocortisone itself).

35. Methyl
Prednisone (Solu-
Medrol)
• DOSEAGE: 125-250 mg
IV/IO/IM
• Peds 2 mg/kg
• Most common
prehospital steroid

36. Dexamethasone
• Dosage: 4-8 mg/IV/IO/IM
Q 12 hours
• Peds dose 4 mg IV q
8-12 hours
• Dexamethasone is
preferred because it does
not interfere with the
diagnostic testing, unlike
hydrocortisone.
• Must be supplemented
with IVF and electrolyte
replacement

37. Mineral corticosteroids
• Essential adjunctive therapies
• Fludrocortisone most commonly used (0.2 mg PO)

38. Fluids
• 10-20 cc/kg over 1
hour
• Saline preferred.
• Hypertonic saline
may be used if
Hyponatremic
• Titrate for 24 hours to
urine output

39. Hyperkalemia Treatment
• Calcium gluconate
(carbonate)
• 2-4 mg/kg
• Sodium Bicarbonate
• 1 meq/kg
• Insulin/glucose
• 10 U Humalog + 25 GM
D10, Adjusted PRN for
effect
• Kayexalate
• Po 15 g q 6 -12
HOURS
• Pr 30-50 g q 6 HR
• Lasix
• 40-120 mg -
Controversial
• Albuterol
• 10 MG nebulized or
ET
• Hemodialysis

40. Hypoglycemia
• Oral Glucose
• Dextrose containing solutions IV
12.5-25 G
• D10%
• D50%
• Glucagon 1 U IM
• Only, no treat and release

41. Hyponatremia
• Suspect strongly in cases with neurological
instability (Seizures, etc)
• Unless severe, will resolve with
Glucocorticosteroid treatment.
• Treatment focused on restoring fluid and salt
balance
• Acute treatment threshold is typically with
neurological involvement.
• Treatment may include:
• Fluids
• Hypertonic Saline (100-150 ml of 3% HS?)

42. Pitfalls
• Adrenal insufficiency should be considered in any patient
with known chronic steroid use plus acute illness.
• Don't forget that chronic steroid use is the most common cause
of adrenal insufficiency, leaving these patients at risk for adrenal
crisis due to acute stress (e.g. severe infection).
• Adrenal crisis should be considered in any patient who
appears to be septic, but doesn't have an obvious source
of infection. This is a classic sepsis-mimic.

43. Eugene Shoemaker
• World Renown Astro-Geologist
• Pioneered the idea that Craters on the moon and earth were
made by meteorites!
• Helped train the Apollo Astronauts
• Was scheduled to be an astronaut on a future Apollo
moon flight.
• Was “disqualified” when he developed…Addison's
Disease
• Died in July 18, 1997 in a fatal head on auto accident
in Australia, exploring impact craters.
• On July, 1999, his ashes were carried to the moon,
fulfilling his lifelong dream of a lunar mission.
Biggest disappointment in his life was “not going to the moon and banging on it with my
own hammer.”