ADRENAL FLIPPED CLASS

Facilitator: Dra. Honolina Gomez

Group 3B
HPI
A 35-year-old female Balikbayan was brought to the emergency room because of an altered
level of consciousness.
She has dysuria over the past week and has been febrile for the past 3 days. She
self-medicated with paracetamol with some relief of symptoms. Her appetite has dropped and
she feels weak over the past week. She felt lightheaded whenever she stood up.

PE
GS: Thin and weak looking woman who is lethargic but oriented.
VS: BP- 85/50 mmHg PR- 110/min RR- 12/min T- 38C.
Attempt to have patient sit upright makes her very lightheaded.
She has dry skin with hypopigmentation in the forehead, chin, cheeks, hands and lower legs.
Dry lips and buccal mucosa.
Hair is thin, soft and dry with alopecia areata
Heart, lung and abdominal examination are normal, Negative kidney punch

SALIENT FEATURES: (GAMENG)

Can you make a diagnosis based on the HPI?
- Altered sensorium: neurologic problems such as meningitis (febrile, infection)
- Impression: infection in the urinary tract
- Consider sepsis
- Poisoned
- BP: hypotensive; orthostatic
- PR: tachycardic
- RR: normal
- Temp: febrile
- Hypopigmentation (vitiligo) , dry mucosa, dry skin - dehydration
- Alopecia areata in 35 y/o - may point to a thyroid disease
- (-) kidney punch
- Lethargic but oriented (significant finding): possibility of adrenal crisis
QUESTIONS
1. What further information should you ask? (GONZAGA)
○ Vomiting or diarrhea
○ Fatigue
○ Patient is a balikbayan - would ask where she came from to determine possible
endemic diseases
○ Family history: autoimmune disease but rule out other diseases first because
these are uncommon
○ Salt cravings - to determine if primary or secondary AI
○ Weight
○ Hair loss
 ○ Glucocorticoid use
○ Has the patient given birth? - Placental hemorrhage (?) can cause apoplexy

● Consider APSII due to presence of T1DM and Hypothyroidism

2. What is the main endocrine disorder? (GARCIA)

○ Primary Adrenal Insufficiency d/t APS2

3. What is the relationship of the endocrine history years ago to the present endocrine
disorder? (GOMEZ)

○
● Causes of Secondary Adrenal Insufficiency:
○ Pituitary tumors (endocrine active and inactive adenomas)
 ○ Other mass lesion affecting the hypothalamic-pituitary region
○ Pituitary Irradiation
○ Autoimmune hypophysitis
○ Pituitary infiltration
○ Drug-induced
○ Congenital isolated ACTH deficiency
○ Combined pituitary hormone deficiency
○ Proopiomelanocortin(POMC) deficiency
● Autoimmune Polyendocrine Type II
○ Occurs more in female compared to males
○ Combination of autoimmune adrenal insufficiency with autoimmune thyroid
disease and/or type 1 autoimmune DM
○ Conditions may occur in any order and diagnosis is confounded by the
nonspecific nature of symptoms of adrenal insufficiency and hypothyroidism
○ Not common but diagnosis can be overlooked
○ Present in midlife peaks between 20-60 y/o
○ Presence of two or more of the following endocrine deficiencies in the same
patient defines the presence of APS-2
■ Primary adrenal insufficiency
■ Grave’s disease or autoimmune thyroiditis
■ Type 1 DM
■ Primary Hypogonadism
○ Frequently associated autoimmune conditions
■ Celiac disease
■ Myasthenia gravis
■ Vitiligo
■ Alopecia
■ Serositis
■ pernicious anemia
○ Conditions can occur with increased frequency in affected patients but are also
found in their family members

● Adrenal insufficiency
○ ranges from mild to nonspecific symptoms to life-threatening shock conditions.
○ The decreasing or suppressed adrenal function may be masked until stress or
illness triggers an Adrenal Crisis
● Adrenal Crisis
○ Can occur in patients who are receiving physiologic or pharmacologic doses
of synthetic glucocorticoid if their mineralocorticoid requirements are not
met
○ There is almost always a stressor or cause of adrenal insufficiency in patients
with adrenal crisis,
■ In chronic primary adrenal insufficiency, when patients experience serious
infection or other acute major stress, Adrenal crisis may be the initial
presentation in a previously undiagnosed patient
■ Occur in patients with known primary or secondary AI who are
under-replaced, either because of
● 1.) insufficient daily doses of glucocorticoid and/or
mineralocorticoid
● 2.) failure to take more glucocorticoid during an infection or other
major illness
● 3.) Persistent vomiting or diarrhea caused by viral gastroenteritis
leading to dec absorption
■ Acute cause of adrenal gland destruction, such as bilateral infarction or
hemorrhage
■ Development of acute cause of secondary or tertiary adrenal insufficiency,
such as pituitary infarction
■ Unmasking of secondary adrenal insufficiency in patients who are
abruptly withdrawn from supraphysiologic doses of glucocorticoid
 4. What other Physical findings are to be evaluated? (GEROCHE)

After seeing Hx, you are now sure you’re dealing with Primary Adrenal Insufficiency
secondary to APS2, so no need to find for signs related to pituitary tumors/secondary AI
Agree for thyrotoxicosis facticia (?)
U cannot have graves if nagkaroon na ng thyroiditis
Myasthenia - lowe ex weakness
Myocarditis - soft heart sounds

● Based on the patient’s presentation, we are suspecting adrenal insufficiency. Other

physical findings would be weight loss, muscle weakness and orthostatic hypotension
which are signs of glucocorticoid deficiency. Pallor of the palpebral conjunctiva should be
assessed because glucocorticoid deficiency could also present with anemia. Loss of
axillary and pubic hair can also be evaluated due to androgen deficiency. Because there
is hypopigmentation, we are suspecting secondary adrenal insufficiency rather than
primary. To determine possible causes of secondary adrenal insufficiency, we can check
for bitemporal hemianopia and blurring of vision which are signs of a mass compressing
on the optic chiasm, surgical wounds and signs of head trauma. Thyroid lymphoid
nodules and thyroid enlargement should be checked as a sign of possible
hyperthyroidism due to overmedication of hypothyroidism/ grave’s disease due to family
history. Galactorrhea due to hyperprolactinemia is also a possible finding indirectly
caused by glucocorticoid deficiency.

For 5-6

5. Work-ups in the ER will include the following? Why? (FULE)

○ Patient is hypotensive so labs in order of priority
○ Serum cortisol and ACTH levels - not widely available but may request cortisol
immediately
● Electrolytes - hyponatremia, hyperkalemia
● CBC - for possible anemia and RULE OUT SEPSIS
● Random blood sugar - drop in blood sugar hypoglycemia <70
● Urinalysis - rule out kidney etiology cos px presented with dysuria

● BUN and creatinine - increase BUN and creatinine may point to AI, also the px
is in dehydrated state → px may have AKI
● CXR - AI may be due to TB or lung infection
● ECG - needed to know levels of potassium (hyperkalemia)
● Lipase - if increased, can cause pancreatitis
● MonoSpot test - EBV, infectious mononucleosis associated with APS2; not widely
available
● Aldosterone - differentiate primary from secondary
● Abdominal ultrasound
○ May be used to check the adrenal glands.
● BUN/Creatinine
○ For screening/confirmation of diagnosis.
○ Creatinine and BUN would both be increased in primary adrenal
insufficiency.
● Baseline serum cortisol and ACTH levels.
○ For screening/confirmation of diagnosis.
○ Measurement of the basal plasma ACTH concentration can usually
distinguish between these disorders (primary, secondary, tertiary adrenal
 insufficiency). When coupled with simultaneous measurement of basal
serum cortisol, measurement of plasma ACTH may both confirm the
diagnosis of adrenal insufficiency and its cause. (Niemman, Uptodate)
● Chest X-ray
○ Done to determine if patient may have tuberculosis since it can be one of
the infective causes of adrenal insufficiency.
● Complete Blood Count
○ For screening/confirmation of diagnosis.
○ Patients with adrenal insufficiency will present with mild anemia,
lymphocytosis, and eosinophilia.
● Cortisol level after Cosyntropin stimulation test
○ Done for screening/confirmation of diagnosis.
● ECG
○ May help in evaluation of the cause of the patient’s hypotension.
● Lipase
● Na, K, Cl, iCa
○ For screening/confirmation of diagnosis
○ Hyponatremia may cause fatigue, lethargy, hypotension manifested in the
patient. (Amboss)
○ Hyperkalemia may cause muscle weakness which may be the reason
why the patient is feeling weak. (Amboss)
○ Hypercalcemia may cause fatigue, cognitive dysfunction, muscle
weakness, abdominal pain, and anorexia. (Amboss)
● MonoSpot Test
○ Form of heterophile antibody test
○ May be used to determine if the patient has infection.
● Plasma aldosterone
○ Used for differential diagnosis
● Plasma renin
○ Used for differential diagnosis
● RBS
○ May be used to determine if the patient is hypoglycemic due to the
following signs and symptoms:
■ Altered level of consciousness
■ Lethargy
■ Lightheadedness
■ Tachycardia
● SGPT, SGOT
● Thyroid Peroxidase Antibody
○ For differential diagnosis
○ Can be used to determine if there is Hashimoto’s thyroiditis since primary
adrenal insufficiency may manifest together with autoimmune diseases
● Urinalysis
 ○ May be used to determine if patient has infection since she experiences
dysuria and is febrile

6. Choose the labs you will request and explain why? (FIGUEROA)
I would request the plasma aldosterone level of the patient to know the presence
insufficiency then I would also need the BUN/Creatinine levels of my patient to support my
working diagnosis. Because in AI the BUN and Crea would be elevated. I would also request for
baseline serum cortisol and ACTH levels of the patient to be able to know my differential
diagnosis. Because a decrease in cortisol level but at the same time increase in ACTH would
point out a primary adrenal insufficiency.

7. Explain ACTH stimulation test (GIOSKOS)

ACTH stimulation test is used to evaluate cortisol production and help diagnose adrenal
insufficiency. A negative feedback loop is used by our body to regulate production of cortisol.
This feedback loop includes the HPA axis. So normally, in a healthy person, when cortisol levels
fall, the hypothalamus releases CRH. The CRH makes the pituitary gland produce ACTH which
then in turn signals the adrenal glands to release more cortisol. When cortisol rises, the
hypothalamus decreases CRH production.

Decreased levels of cortisol may be visible in adrenal insufficiency, pituitary gland tumor aka
secondary adrenal insufficiency (inhibits ACTH production), damaged adrenal glands (primary
adrenal insufficiency) such as in addison’s disease and etc.

The ACTH stimulation test is used when a cortisol test is done and the result is too low. The
practitioner will conduct the test in order to help confirm the findings and help determine its
cause.
The ACTH test goes like this.
a) Blood is drawn for an initial baseline level (pre-ACTH stimulation)
b) An injection of a manufactured fragment of ACTH is given (cosyntropin, tetracosactide,
and/or synacthen) either parenterally or intramuscularly. This administered ACTH will
stimulate the adrenal glan
 c) ds to produce cortisol.
d) Blood is drawn again at time intervals of 30 minutes and 60 minutes
e) Cortisol level is measured in each time interval including initial blood draw.
f) Check if cortisol level doubles after 60 minutes, if it doesnt then there is a primary
adrenal insufficiency meaning the adrenal glands itself are damaged and unable to
produce cortisol.

Cortisol NV: 6 to 8 a.m.: 10 to 20 micrograms per deciliter (mcg/dL) Around 4 p.m.: 3 to

10 mcg/dL.
ACTH NV: between 10 and 60 pg/mL (2.2 and 13.3 pmol/L) at 8 AM.

8. Briefly discuss the recommended laboratory tests needed for evaluation of APS2?
(FRANCISCO)

’Lifelong disease that needs lifelong lab tests and m onitoring

APS2 or Autoimmune Polyendocrine Syndrome Type 2 (Schmidt Syndrome)
Definition:
- Harrison’s: The presence of 2 or more of the ff endocrine deficiencies in the
same patient defines the presence of APS2:
- Primary adrenal insufficiency (Addison’s disease)
- Grave’s disease or autoimmune thyroiditis
- Type 1 DM
- Primary hypogonadism
- It is also associated with other autoimmune conditions such as celiac
disease, myasthenia gravis, alopecia, serositis, and pernicious anemia.
- There is a controversy as to which tests to use and how often to screen individuals for
disease. A strong family hx of autoimmunity should raise suspicion in an individual with
an initial component diagnosis.
- Tests used to diagnose APS2 should include :
Request for circulating autoantibodies because concomitant dx of Primary
adrenal insufficiency and Thyroid disease or DM does not necessarily
confirm a dx of APSII. An autoimmune basis for the components of the
syndrome must be demonstrated to confirm dx.
 a. Addison’s disease - 21-hydroxylate is highly diagnostic
- highly sensitive and specific for primary adrenal insufficiency of
autoimmune origin
b. Type 1 diabetes - measuring autoantibodies directed against insulin,
GAD65, IA-2, and ZNT8
- Islet cell antibodies can be demonstrated in about 80 percent of patients with
new-onset type 1 diabetes. 2 Glutamic acid decarboxylase autoantibodies are
the marker with the highest diagnostic sensitivity for type 1 autoimmune diabetes.
(https://www.aafp.org/afp/2007/0301/p667.html )
c. autoimmune thyroid conditions - measuring anti-thyroid peroxidase
(TPO) or anti-thyroglobulin autoantibodies
- For each of the endocrine components of the disorder, a positive autoantibody result
should prompt physiologic testing to diagnose clinical or subclinical disease.
● Other tests may include gonadotropin levels, thyroid tests (thyroid-stimulating
hormone [TSH], triiodothyronine [T3] and thyroxine [T4]), plasma renin activity,
serum electrolytes, fasting blood glucose and a complete blood count
Additional Information

- The most frequent cause of primary adrenal insufficiency is autoimmune adrenalitis. 60-70% are part of APs.
Less commonly, it is due to infection (tuberculosis, CMV) or adrenal hemorrhage.
- APS2 is more common than type 1 and it occurs more often in females with a peak incidence between 20 and 60
years.
Screening test
a. Addison’s disease - Cosyntropin test
- Cosyntropin (Cortrosyn) test (synthetic adrenocorticotropic hormone [ACTH]),
which has 95 percent sensitivity and 97 percent specificity. 11 One ampule
(250 mcg) of cosyntropin is given intramuscularly or intravenously, and the
plasma or serum cortisol level is measured 30 to 60 minutes later. 12 In a
normal (negative) test result, the serum cortisol level is usually greater than 14
mcg per dL (390 nmol per L). A serum cortisol level less than 14 mcg per dL is
considered positive and indicates an increased probability of primary or
secondary adrenal insufficiency. The test can be done at any time of day. A
basal cortisol level is not necessary because the percent of change is not used
as diagnostic criteria.
b. Type 1 DM - fasting blood glucose level (>126 mg/dL)

c. Thyroid disease - thyrotropin secreting hormone and serum-free thyroxine

-
 9. How will you treat Acute AI? (GAMBOA)

Thiamine incorporated in the IV line

Definition of Acute Adrenal insufficiency

- Aka Adrenal crisis. Occurs after a prolonged period of non-specific complaints and is
more frequently seen in primary adrenal insufficiency (due to loss of both
glucocorticoid and mineralocorticoid secretion) (harrison’s)
- Primary AI: the major clinical features of adrenal crisis are volume depletion
and hypotension, resulting mainly from mineralocorticoid deficiency.
- Secondary or tertiary AI (isolated GC deficiency) does not cause volume
depletion but results in a decreased vascular tone leading to hypotension.
- Because of this, adrenal crisis is less frequent in this type
Treatment of Acute Adrenal insufficiency
 From Batch 2022 Trans on Adrenal Disorders

A. Initiation of rehydration (due to volume depletion) and correction of imbalances

- Saline infusion is administered with rates of 1L/ hr with continuous cardiac monitoring
(harrison’s)
- Will correct hypovolemia and possible pre-renal failure
- 1L of saline given in the first hour then succeeding intravenous replacements will
be based on the hemodynamic status of the patient (Jeong et al, Adrenal crisis
NCBI)
- 4-6 liters are usually needed in 1st 24 hrs (Jeong et al, Adrenal crisis NCBI)
- In addition to corticosteroid replacement, aggressive fluid replacement with 5% or
10% intravenous dextrose and saline solutions and treatment of hyperkalemia is
mandatory. (Kirkland,L-Adrenal crisis tx and mgt from Medscape)
- Since in primary MI there is low MC, there will be increased urinary sodium
loss, decreased blood volume, and high potassium retention hence the said
treatment.
- In secondary AI, due to the loss of feedback inhibition of ADH, there will be
increase in water retention resulting in dilutional hyponatremia
- Dextrose is utilized due to the hypoglycemia caused by Acute AI.
- No cortisol would mean less insulin resistance causing glucose to enter
the cells.
- Use dextrose 50% as needed for hypoglycemia. (Kirkland,L-Adrenal
crisis tx and mgt from Medscape)
B. Replacement of glucocorticoids
- First, 100 mg of hydrocortisone is given via a bolus injection then this is followed by
200 mg of hydrocortisone for a period of 24 hours (harrison’s)
- History and physical examination that suggest excess or deficient glucocorticoids are the
basis of monitoring of glucocorticoid replacement. (harrison’s)
- Once the patient stabilizes (usually second day), the corticosteroid dose may be reduced
and then tapered. (Klauer,K-Adrenal crisis in Emergency Med tx and mgt from
Medscape)
 - Oral maintenance can usually be achieved by the fourth or fifth day.
- GC is given first because it is able to stimulate mineralocorticoids receptors in itself(mas
common din na GC lang ang deficiency) and once the GC level is <50mg, MC may now
be initiated to have a better response(if sure na primary AI).
C. Replacement of Mineralocorticoids (only for primary adrenal insufficiency)
- Mineralocorticoid replacement is initiated at a dose of 100-150 microgram
fludrocortisone. (harrison’s)
- Mineralocorticoid treatment can be evaluated via the following (harrison’s):
- Blood pressure determination (sitting and standing) to detect a postural drop
indicative of hypovolemia
- Serum sodium and potassium- if hyponatremia and hyperkalemia are improving
- Renin levels- should be maintained in the upper normal reference range
- Dose changes in glucocorticoid may have an effect on mineralocorticoid replacement
since cortisol binds the MR (mineralocorticoid receptor) (harrison’s)

D. Replacement of adrenal androgens

- This is indicated for patients with lack of energy despite glucocorticoid and
mineralocorticoid replacement (harrison’s)
- Indicated also for women with signs and symptoms of androgen deficiency (eg.
loss of libido) (harrison’s)
- Medication for treatment: Dehydroepiandrosterone(DHEA) 20-50mg/day, daily
- Efficacy of treatment is monitored by measuring the following (harrison’s)
- Dehydroepiandrosterone sulfate(DHEAS)
- Androstenedione
- Testosterone
- Sex-hormone binding globulin (SHBG).
Note: These measurements are requested 24 hours after the last DHEA dose.

10. What about Chronic AI? Include patient education and actual treatment (FORONDA)
 A. Glucocorticoid replacement

Physiologic dose of cortisol: 7.5

Primary: maintain at7.5 mg daily
Most important is px education
-sabay na yung tx for infection

a. Hydrocortisone 15-25 mg PO in two or three divided doses with LARGEST dose

in the MORNING, or
b. Prednisone 2.5-7.5 mg PO at bedtime, or
c. Dexamethasone 0.25-0.75 mg PO at bedtime
d.
 i. **Harrisons: 1 mg hydrocortisone = 1.6 mg cortisone acetate = 0.2 mg
prednisolone = 0.25 mg prednisone = 0.025 mg dexamethasone
e. Monitoring of clinical symptoms
B. Mineralocorticoid replacement
a. Fludrocortisone 0.05-0.2 mg PO
i. Must be decreased if given 20mg hydrocort or 50mg prednisone d/t
mineralocorticoid effect
b. Liberal salt intake
c. Monitor BP, pulse, serum K, plasma renin
C. Androgen replacement (in female patients w/ low libido, depressive sx, and low energy)
a. Dehydroepiandrosterone (DHEA) 25-50 mg PO
D. Patient education
a. “Sick day rules”
i. (1) illnesses with fever, need for bed rest, and need for antibiotics; and (2)
minor procedures e.g. dental operations require double of usual oral
glucocorticoid dose for the few days of illness
ii. (1) vomiting/diarrhea, (2) severe illness, (3) trauma, (4) fasting required
for a procedure, and (5) perioperative period require IM/IV
glucocorticoids or suppositories
b. Instruct patient on management of these stresses and proper injection of IM/IV
glucocorticoids
E. Surgical stress
a. Minor: hydrocortisone 25 mg IV on day of procedure
b. Moderate: hydrocortisone 50-75 mg IV on day of procedure and post-op day 1
c. Major: hydrocortisone 100-150 mg IV in 2-3 divided doses on day of procedure,
post-op day 1, and post-op day 2
F. Severe stress/trauma
a. Patient should have injectable steroid on hand, sterile 0.9% NSS, and syringes

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