The endocrine emergencies most commonly discussed by EMS provi.docx

The endocrine emergencies most commonly discussed by EMS
providers typically deal with diabetes mel-litus, a condition
associated with malfunction of the pancreas or its hormones and
improper regulation of the blood glucose level. It is important
to recognize that there are many other emergencies that may be
related to
malfunctioning endocrine glands or hormones. These
emergencies may produce acute life-threatening conditions that
exhibit a wide variety of clinical presentations based on the
gland or hormones involved. Some patients may not readily
recognize, or may ignore, the slow and progressive clinical
changes that are occurring and allow the disease to create an
acute life-threatening condition.
Since EMS providers may be called upon to manage the patient
experiencing this acute and potentially life-threatening
condition, it is prudent for them to possess an awareness and
understanding of other potential life-threatening endocrine
emergencies, such as those involving the thyroid gland and its
related hormones.
By Joseph J. Mistovich, MEd, NREMT-P,
William S. Krost, BSAS, NREMT-P,
& Daniel D. Limmer, AS, EMT-P
Part 1: Hyperthyroidism and Thyroid Storm
This CE activity is approved
by EMS Magazine, an

organization accredited by
the Continuing Education
Coordinating Board
for Emergency Medical
Services (CECBEMS), for
1.5 CEUs.
OBJECTIVES
• Review anatomy of the
thyroid gland
• Discuss metabolic
disturbances
• Review emergency
management of
endocrine emergencies
Sponsored by
CONTINUING
EDUCATION FROM EMS
This article is the first in a two-part series addressing endocrine
emergencies involving thyroid hormone
disorders. The second part will follow in next month’s issue and
cover conditions related to hypothyroid-
ism. The section below on anatomy and physiology of the

thyroid gland pertains to both articles. It will be
important to review this section prior to reading the next article
to completely understand the hypothyroid-
ism conditions covered in part two.
BEYOND THE BASICS:BEYOND THE BASICS:
Part 1: Hyperthyroidism and Thyroid Storm
This CE activity is approve
by EMS Magazine, an
organization accredited by
the Continuing Education
Coordinating Board
for Emergency Medical
Services (CECBEMS), for
1.5 CEUs.
OBJECTIVESJ
• Review anatomy of the
thyroid gland
• Discuss metabolic
disturbances
• Review emergencyThis article is the first in a two part series
addressing endocrine emergencies involving thyroid
hormoneThis article is the first in a two part series addressing

endocrine emergencies involving thyroid hormone
ENDOCRINEENDOCRINE
EMERGENCIESEMERGENCIES
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ANATOMY AND
PHYSIOLOGY OF THE
THYROID GLAND

The thyroid is a butterfly-shaped
endocrine gland located in the ante-
rior neck just inferior to the thyroid
cartilage (Adam’s apple). It consists of
two lateral lobes that are connected
anteriorly by a mass of tissue referred
to as the isthmus. It can be easily pal-
pated just below the cricoid cartilage.
The size of the gland varies in indi-
viduals depending on many factors.
The thyroid gland is the largest pure
endocrine gland in the body and has
a very rich blood supply. Thus, when
performing a needle cricothyrotomy,
it is extremely important to ensure
that the proper landmarks have been
identified to avoid inadvertent lac-
eration of the vascular lateral lobes or
isthmus of the thyroid gland. If these
are lacerated, an excessive amount
of bleeding may occur, complicating
an already dire airway situation. The
gland may also be lacerated and
bleed heavily from blunt or penetrat-
ing trauma to the anterior neck.
The thyroid gland produces and
secretes two distinct hormones: thy-
roid hormone (TH) and calcitonin.
Calcitonin is produced by a differ-
ent group of cells within the thyroid
gland, and is responsible for lowering
the blood levels of calcium and stim-
ulation of bone growth and develop-
ment in childhood. It may also play a

role in reducing bone loss associated
with starvation and in late stages of
pregnancy when the fetus is compet-
ing for calcium being absorbed in the
digestive tract. Otherwise, the role of
calcitonin in the healthy adult is not
well understood; it may serve merely
as a weak hypocalcemic agent.
The thyroid hormone is comprised
of two different iodide-attached mol-
ecules. Thyroxine, also known as tet-
raiodothyronine or T4, makes up the
majority of hormone secreted by the
thyroid cells. It consists of four iodide
ions attached to its molecular struc-
ture. Triiodothyronine, also known as
T3, is the other hormone secreted by
the thyroid gland. It has only three
iodide ions attached to it. Although
only a small amount of T3 is secreted
by the thyroid gland, approximately
10% of the TH secretion, a large
amount is formed from the conver-
sion of T4 through the removal of
one iodine group by enzymes from
the liver, kidneys and other tissues.
Interestingly, though, T3 is primar-
ily responsible for the thyroid hor-
mone effect, which is primarily a very
strong, immediate and short-acting
increase in cellular metabolism.
It is important to review the trans-
port, binding and concentration of
T3 and T4 in the blood in order to

understand a potential trigger for the
disease process involving the thyroid
hormone. Approximately 75% of T4
and 70% of T3 hormones attach
to thyroid-binding globulins, also
known as thyroxine-binding globu-
lins (TBGs), upon entering the blood.
A majority of the remaining T3 and
T4 are attached to the plasma pro-
tein albumin or a thyroid-binding
prealbumin. Very small amounts of
the thyroid hormone, approximately
0.3% of T3 and 0.03% of T4, are left
unbound to diffuse into the periph-
eral tissue. Thus, the only useable
form of thyroid hormone is in an
unbound form.
Both T3 and T4 bind to target
tissue receptors; however, T3 binds
much more readily and is about 10
times more active than T4. Equilibrium
must be maintained in the blood
between the amount of thyroid hor-
mones bound to protein carriers and
the amount being released into the
peripheral tissue. Levels of T4 and
the thyroid-stimulating hormone
(TSH) play a major role in maintain-
ing this blood level equilibrium. It is
interesting to note that more than a
week’s supply of thyroid hormone is
found in the bloodstream.
Thyroid hormones affect many of

the major organ systems and tissues
within the body, with the exception
of only the adult brain, spleen, testes,
uterus and thyroid gland itself. Effects
of the thyroid hormones are to:
• Maintain normal sensitivity of
respiratory centers to changes in oxy-
gen and carbon dioxide concentra-
tions
• Maintain normal cell oxygen use
• Maintain a normal basal meta-
bolic rate (BMR)
• Promote calorigenesis (heat pro-
duction) by increasing the metabolic
rate of cells
• Enhance the effects of the sym-
pathetic nervous system
• Promote glucose metabolism,
fat mobilization and protein synthesis
• Maintain normal adult nervous
system function
• Promote normal cardiac func-
tion to include rate and force of
contraction
• Promote normal muscle devel-
opment and function, and skeletal
growth and maturation

Patients with hyperthyroidism may experience tachycardia and
an
elevated systolic pressure. Pulse pressure may also be widened.
124 OCTOBER 2007 ■ EMS ■ www.emsresponder.com
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ce article
• Promote normal gastrointestinal
(GI) motility and tone, and increase
digestive enzyme secretion
• Maintain hydration and secre-
tory function of the skin.
Hypothyroidism, an insufficient
number of thyroid hormones, or
hyperthyroidism, an excessive num-
ber of thyroid hormones, will cause
metabolic disturbances that disrupt
normal body function and have
an impact on most or all of the
aforementioned hormone effects.
Hypothyroidism results in a decrease
in hormonal effects on the body
systems; hyperthyroidism increases
or accentuates the thyroid hormone
effects on body systems. Both condi-

tions can lead to acute and poten-
tially lethal emergencies.
PATHOPHYSIOLOGY
Hyperthyroidism describes a con-
dition of excessive secretion of thy-
roid hormone resulting from elevated
and inappropriate thyroid function.
Thyrotoxicosis, also associated with
an excessive amount of circulating
thyroid hormone, results from the
patient taking too much thyroid hor-
mone (an exogenous source), or from
an inflamed thyroid gland releasing
too much stored thyroid hormone.
Although these terms are often used
interchangeably to describe an elevat-
ed thyroid hormone level, they have
different etiologies that affect long-
term treatment. Hyperthyroidism and
thyrotoxicosis typically describe the
milder form of the disease process.
Graves’ disease, also known as
diffuse toxic goiter, is the most com-
mon form of hyperthyroidism. It is
typically more common in women
and usually occurs between the ages
of 20 and 40. Graves’ results from an
autoimmune condition that affects
the function of the thyroid-stimulat-
ing hormone, causing the thyroid
gland to increase its production and

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The enlarged thyroid gland in

Graves’ is typically diffuse and
nontender to palpation. This
woman also shows signs of exop-
thalmos, which occurs when the
tissue behind the eyes becomes
edematous and fibrous and the
extraocular muscles degenerate.
For More Information Circle 105 on Reader Service Card For
More Information Circle 106 on Reader Service Card
9/18/2007 3:38:36 PM9/18/2007 3:38:36 PM
secretion of thyroid hormone and
leading to hyperthyroidism.
Thyroid storm, also referred to as
thyrotoxic crisis, represents a severe
and potentially life-threatening con-
dition. Although it is a relatively rare
condition, occurring in only 1% to
2% of patients with hyperthyroid-
ism, if left untreated, thyroid storm
can be fatal, sometimes within days.
It carries an adult mortality rate of
10%–20%. The pathophysiology
of thyroid storm is not completely
understood; however, it is thought
that the excessive levels of thyroid
hormone are not necessarily from the
thyroid gland but from the conver-

sion of bound-thyroid hormone in
the blood to an unbound form. The
unbound form becomes active and
can easily enter peripheral tissue,
producing a dangerous and possibly
life-threatening hypermetabolic state
and increased sympathetic nervous
system activity. The patient may pres-
ent with an excessively high fever
(106°F), tachycardia, nausea, vomit-
ing, diarrhea and hypotension.
Graves’ disease is the most com-
mon underlying cause of thyroid
storm. Other causes include taking
an excessive amount of thyroid hor-
mone (factitious hyperthyroidism)
and administration of amiodarone,
a rich iodine-containing antidysrhyth-
mic agent that can have complex
effects on the thyroid gland and hor-
mone function. Other conditions that
may precipitate thyroid storm in the
patient with hyperthyroidism include:
infection, surgery, burns, trauma,
cardiovascular events, preeclampsia
or eclampsia, diabetic ketoacidosis,
hyperglycemic hyperosmolar non-
ketotic syndrome, insulin-induced
hypoglycemia, pulmonary embolism,
ingestion of thyroid hormone and
drug reactions (Mellaril, Itrumil).
ASSESSMENT
It is important to understand the

history and physical exam findings
in a patient with hyperthyroidism.
A patient who presents with life-
threatening thyroid storm may have
an undiagnosed history of hyper-
thyroidism. Although hyperthyroid-
ism and thyroid storm may present
with a wide clinical array of signs
and symptoms, clinical features of a
hypermetabolic state and increased
sympathetic activity are the most
common. Key findings include agita-
tion, weight loss, nervousness and
palpitations. History findings include:
• Weight loss of approximately
15% of prior weight (often greater
than 40 pounds)
• Cardiac palpitations
• Nervousness
• Anxiety, agitation, restlessness
• Wide mood swings
• Tremors
• Chest pain in the absence of
cardiovascular disease
• Dyspnea
• Edema
• Disorientation
• Psychosis
• Weakness
• Diarrhea and increased bowel
movements

• Increased perspiration
• Fatigue
• Intolerance to heat from the
hypermetabolic state
• Abdominal pain.
Physical exam findings include:
• Fever (excessively high in thy-
roid storm)
• Tachycardia (often 100–170 bpm)
that is out of proportion to the fever
• Wide pulse pressure (40–100
mmHg) due to the increase in cardiac
contractility (inotrope) with an eleva-
tion in systolic blood pressure
• Warm skin
• Diaphoresis
• Dehydration (may be secondary
to diaphoresis and diarrhea)
• Congestive heart failure
• Thyromegaly (enlarged thyroid
gland)
• Exopthalmos (protruded eye-
balls)
• Stare with eyelid retraction
• Atrial fibrillation, atrial flutter, or
premature atrial contractions
• Tremors

• Tender liver
• Shock
• Jaundice
• Coma or obtunded mental
state.
The enlarged thyroid gland in
Graves’ is typically diffuse and non-
tender to palpation. If there is infec-
tion or inflammation, the gland will
present with diffuse enlargement and
pain on palpation.
Exopthalmos occurs when the tis-
sue behind the eyes becomes edem-
atous and fibrous and the extraocular
muscles degenerate. This is thought
to result from the autoimmune dis-
order associated with hyperthyroid-
ism. In some cases, the protrusion
is so severe that the optic nerve
is stretched and vision is impaired.
Severe eyeball protrusion may cause
the eyelids to stretch and not close
completely when the patient blinks
or sleeps. This may lead to drying
and irritation of the outer eye tissue,
causing corneal ulcerations.
It is important for EMS providers
to recognize not only the patient
experiencing a thyroid storm, but
also one who is exhibiting an array
of signs and symptoms that are char-
acteristic of hyperthyroidism. The

hyperthyroid condition may progress
rapidly to thyroid storm or conges-
tive heart failure if not treated.
MANAGEMENT
Thyroid storm is a life-threaten-
ing condition that requires immedi-
ate emergency care and transport.
Severe hyperthyroidism may also
require supportive emergency care.
Consider the following when man-
Photo courtesy Bechara Y. Ghorayeb, MD
Surgery to remove an enlarged
thyroid gland. The thyroid is
normally a butterfly-shaped gland
that lies in the anterior neck
inferior to the thyroid cartilage.
9/18/2007 3:38:38 PM9/18/2007 3:38:38 PM
ce article
aging a patient with an acute and
severe hyperthyroid condition:
• Establish and maintain a pat-

ent airway. If the patient presents
with an altered mental status or is
comatose, it may be necessary to
establish an airway by a manual
maneuver, and potentially with a
mechanical device, including endo-
tracheal intubation, in severely
altered mental states.
• Establish and maintain an
adequate ventilation status. If the
patient’s respiratory rate or tidal vol-
ume is inadequate, it is necessary to
provide positive pressure ventilation.
• Establish and maintain ade-
quate oxygenation. Assess the
patient for evidence of hypoxia.
Apply a pulse oximeter and deter-
mine the SpO
2
reading. If there is
either clinical evidence of hypoxia
or a SpO
2
reading of less than
95% on room air, administer a high
concentration of oxygen via a non-
rebreather mask. If the patient is
exhibiting no signs of hypoxia or
the SpO

2
reading is greater than
95%, supplemental oxygen may
be applied via a nasal cannula at
2–4 lpm, especially if any dyspnea,
chest pain or congestive heart fail-
ure is exhibited during the history
or physical exam.
• Provide continuous ECG moni-
toring. Patients experiencing hyper-
thyroidism or thyroid storm may
present with cardiac dysrhythmias.
Atrial fibrillation is common, espe-
cially in the elderly. Patients may also
experience atrial flutter and prema-
ture atrial contractions. Traditional
management of the ventricular rate
control in atrial fibrillation or conver-
sion to a sinus rhythm may not be
effective until the thyroid levels have
been managed.
• Initiate an intravenous line of
normal saline. Patients may lose
significant amounts of fluid from
excessive sweating and diarrhea.
Aggressive fluid resuscitation may be
necessary in severe cases.
• Initiate cooling measures if high
fever is present. Remove the patient’s
clothing, mist the body with water

and fan aggressively. If antipyretic
therapy is considered, avoid the use
of aspirin. Aspirin may decrease pro-
tein binding of thyroid hormones
and increase the levels of unbound
T3 and T4, thereby increasing the
tissue uptake of thyroid hormone.
Acetaminophen would be preferred
over aspirin since it does not have
this effect.
• Expeditious transport. If the
patient is experiencing a thyroid
storm or a severe hyperthyroid con-
dition, consider rapid transport to an
appropriate medical facility that can
initiate definitive therapy to decrease
the thyroid hormone levels.
• Consider medications.
Blockading the peripheral adrener-
gic hyperactivity with beta blockers
could be a critical factor in man-
aging the thyroid storm patient.
Propranolol (Inderal), the current beta
blocker agent of choice, can reduce
tachydysrhythmias, high body core
temperature, tremors, restlessness,
anxiety and palpitations. Another
major indication for the specific use
of propranolol is its ability to inhibit
the conversion of T4 to T3 in the
peripheral tissue. Keep in mind that
T3 is responsible for the majority
of thyroid hormone activity in the

peripheral tissue. Contraindications
to propranolol’s use include reac-
tive airway disease, atrioventricular
blocks, bradydysrhythmias, cardio-
genic shock, hypersensitivity to the
drug and congestive heart failure. It
is important to note that heart failure
in hyperthyroidism and thyroid storm
is typically a high-output CHF, or
heart failure due to tachydysrhyth-
mias that may respond well to the
beta blocker therapy. However, use
beta blockers with extreme caution
if heart failure is suspected. The
dose of propranolol is 1–2 mg intra-
venously, repeated every 10 to 15
minutes until the symptoms are con-
trolled. Be sure to follow your local
protocol in managing the thyroid
storm patient.
Another medication to consider
is dexamethasone (Decadron), which
also blocks the conversion of T4 to T3
in the peripheral tissue. Administer 2
mg intravenously. Again, it is impor-
tant to follow local protocol when
managing the patient.
CONCLUSION
Even though the chance of
responding to a patient experiencing
a thyroid storm or thyrotoxic crisis is
rare, be prepared to quickly identify

the severity of the condition and initi-
ate rapid supportive emergency care
and transport. Possessing a funda-
mental understanding of the disease
process will better prepare the EMS
provider to rapidly recognize and
manage this potentially acute life-
threatening condition.
Bibliography
Bledsoe BE, Porter RS, Cherry RA. Paramedic Care:
Principles and Practice, Medical Emergencies, 2nd ed.
Upper Saddle River, NJ: Prentice Hall Health, 2006.
Guyton AC, Hall JE. Textbook of Medical Physiology,
10th ed. Philadelphia: W.B. Saunders, 2001.
Marieb EN. Anatomy and Physiology, 2nd ed. San
Francisco: Pearson Education, 2005.
Martini FH. Anatomy and Physiology. San Francisco:
Pearson Education, 2005.
Marx JA, Hockberger RS, Walls RM. Rosen’s Emergency
Medicine: Concepts and Clinical Practice, 5th ed. St.
Louis: Mosby, Inc., 2002.
Schraga ED. Hyperthyroidism, Thyroid Storm, and
Graves Disease. www.emedicine.com/emerg/
topic269.htm.
Joseph J. Mistovich, MEd, NREMT-P, is a
professor and chair of the Department of Health
Professions at Youngstown (OH) State University,
author of several EMS textbooks and a nationally
recognized lecturer.
William S. Krost, BSAS, NREMT-P, is an
operations manager and flight paramedic
with the St. Vincent/Medical University of
Ohio/St. Rita’s Critical Care Transport Network

(Life Flight) in Toledo, OH, and a nationally
recognized lecturer.
Daniel D. Limmer, AS, EMT-P, is a paramedic
with Kennebunk Fire-Rescue in Kennebunk, ME.
He is the author of several EMS textbooks and a
nationally recognized lecturer.
Th yroid storm is a life-threatening
condition that requires immediate
emergency care and transport.
9/18/2007 3:38:38 PM9/18/2007 3:38:38 PM
ce reviewce review
ENDOCRINE EMERGENCIES
1. The “Adam’s apple” is a commonly
used name for the _____.
A. Thyroid gland
B. Thyroid cartilage
C. Cricoid cartilage
D. Isthmus
2. The hormone secreted by the
thyroid cells is made up mostly of
_____.

A. Calcitonin
B. Triiodothyronine
C. Thyroxine
D. Albumin
3. More than _____ supply of thyroid
hormone can be found in the
bloodstream.
A. One week’s
B. Two weeks
C. One day’s
D. One month’s
4. Thyroid hormones affect many of
the body’s major organ systems and
tissues, with the exception of the
_____.
A. Adult brain
B. Spleen
C. Uterus
D. All of the above
5. The effects of thyroid hormone on
body systems are accentuated by
_____.
A. Calorigenesis
B. Thyrotoxicosis
C. Hypothyroidism
D. Hyperthyroidism
6. According to the article, _____ is
the most common underlying cause
of thyroid storm—a potentially

life-threatening condition.
A. Thyrotoxicosis
B. Graves’ disease
C. Hypothyroidism
D. Excessive levels of T3
7. A patient who is suspected of
having thyroid storm may exhibit
all of the following signs, with the
exception of _____.
A. Low-grade fever
B. Congestive heart failure
C. Tremors
D. Atrial fi brillation
8. When examining the patient with
suspected hyperthyroidism, the
EMS provider would not fi nd _____
in the patient’s history.
A. Wide mood swings
B. Edema
C. Signifi cant weight gain
D. Chest pain in the absence of
cardiovascular disease
9. _____ is a condition that occurs
when tissue behind the patient’s
eyes becomes edamatous and the
extraocular muscles degenerate.
A. Thyromegaly
B. Inotrope

C. Exopthalmos
D. Graves’ disease
10. Blockading the peripheral
adrenergic hyperactivity with beta
blockers can be a critical factor in
managing the thyroid storm patient.
According to the article, _____ is
the current beta blocker of choice
for treating hyperthyroidism.
A. Atenolol
B. Propranolol
C. Labetalol
D. Betaxolol
11.The thyroid gland consists of two
lateral lobes that are connected
anteriorly by a mass of tissue, which
is called the ____.
A. Thyroid cartilage
B. Cricoid cartilage
C. Fibrous tissue
D. Isthmus
12. Concerning management of the
patient with thyroid storm, which
one of the following statements is
not correct?
A. It is important to provide
continuous ECG monitoring to
assess for cardiac dysrhythmias.
B. If the patient’s respiratory rate is

inadequate, provide positive
pressure ventilation.
C. If fever is excessive, initiate cooling
measures and administer aspirin to
the patient until the fever subsides.
D. Assess the patient for hypoxia and
administer oxygen as needed.
Sponsored by
The following questions are based on Beyond the Basics:
Endocrine Emergencies, beginning on page 123.
EMS Magazine’s CE Review offers affordable continuing
education credits. Simply read the CE article beginning on page
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then answer the test questions below, marking your answers in
the answer strip on the opposite page. The test is worth 1.5
hours
of credit approved by the Continuing Education Coordinating
Board for EMS (CECBEMS). Upon receiving a grade of 80% or
better,
participants will be issued a CE certificate that attests to a
passing score. The cost per test is $5, or $4 each when you
purchase
CEU vouchers in advance. You must purchase a minimum of
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include a
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Check the correct answers and mail this entire page, along with
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128-129 CE test Oct.indd 128128-129 CE test Oct.indd 128
9/18/2007 3:41:20 PM9/18/2007 3:41:20 PM
RESEARCH AND REPORTS
Salivary Cortisol Levels in Students Challenged with
a Testing Stressor
KATHLEEN KENWRIGHT, PATTY W LIDDELL, LEONARD
BLOOM, AUDREY ZUCKER-LEVIN,
ANN H NOLEN, LAWRENCE W FAULKNER, ROSEMARY E
BATORSKI
OBJECTIVE: The objective was twofold. The focus of
the study was primarily to determine if the stress of a
particularly difficult exam could cause students to lose
the normal diurnal variation seen in human cortisol
levels and secondarily, to validate the use of a
competitive enzyme immunoassay for salivary cortisol.

i nDESIGN: Physical therapy students enrolled
Research Design were asked to participate in the study
by collecting baseline evening and morning salivary
Cortisols during what was regarded as a relatively stress
free time in the Fall of 2009. The following spring, the
same students were asked for samples the evening before
and morning of their first Kinesiology test, traditionally
a stressful time. Method validation was accomplished
using instrumentation owned by the Medical
Laboratory Science (MLS) Program and analysis was
performed by MLS faculty and a second year MLS
student.
SETTING: Participants were enrolled in the College of
Health Sciences at the University of Tennessee in
Memphis. Sample collection and testing was performed
in the student laboratory of the Medical Laboratory
Science Program.
PARTICIPANTS: Physical therapy students in their
first year of a three-year entry level doctorate program,
DPT.
RESULTS: This group of students did not lose their
diurnal variation of cortisol. However, an unexpected
finding was noted: the students' salivary cortisol
specimen collected in the morning of the fall semester
was significantly higher than the salivary cortisol
specimen collected the morning of the test in the spring
semester (p = .019). Method validation was successful
demonstrating a strong correlation ( r = 0.915) when
compared to the reference laboratory.
C O N C L U S I O N S : Cortisol diurnal variation was not
lost in the study participants, but further studies should

be performed due to the low percentage of students
completing the study and the lack of demographic
diversity. Even though the method validation in the
student laboratory setting demonstrates that it is indeed
possible to obtain the same excellent correlation as is
seen in a clinical setting, the student laboratory is not
CLIA certified, so assays can be performed for research
use only.
ABBREVLTIONS: ACTH-adrenocorticotropic hor-
mone, CRH-corticotrophin-releasing hormone, D P T -
Doctorate in Physical Therapy, BS-Baccalaureate of
Science, BA-Baccalaureate of Arts, IRB-Internal Review
Board, GPA-Grade Point Average, EIA-Enzyme
Immunoassay, BMI-Basic Metabolic Index, CLIA-
Clinical Laboratory Improvement Amendments, N D -
none detected
INDEX TERMS: stress, cortisol, exams, students
Clin Lab Sei 2011;24(4):221
Kathleen Kenwright, MS, MT,(ASCP)SL,MB"^,
University of Tennessee Health Science Center, Memphis,
TN38163.
Patty W. LiddellMS, MT(ASCP)SH, Baptist College of
Health Sciences, Memphis, TN 38163
Leonard Bloom MPH, CT(ASCP), The University of
Tennessee Health Science Center, College of Allied Health
Sciences, Memphis, TN.
Audrey Zucker-Levin PT, PhD, MBA, GCS, The
University of Tennessee Health Science Center, College of

Allied Health Sciences, Memphis, TN.
VOL 24. NO 4 FALL 2011 CLINICAL LABORATORY
SCIENCE 221
RESEARCH A N D REPORTS
Ann H. Nolen, Psy.D., OTR, FAOTA, The University of
Tennessee Health Science Center, College o/^Allied Health
Sciences, Memphis, T N .
Lawrence W. Faulkner, Ph.D. OTIL, The University of
Tennessee Health Science Center, College of Allied Health
Sciences, Memphis, TN.
Rosemary E. Batorski, MEd, MOT, OTR, The
University of Tennessee Health Science Center, College of
Allied Health Sciences, Memphis, TN
Address for Correspondence: Kathleen Kenwright, MS,
MT,(ASCP)SI,MB^^, University of Tennessee Health
Science Center, 930 Madison Avenue, Suite 672,
Memphis, TN 38163, 901-448-6338, [email protected]
edu
I N T R O D U C T I O N
Cortisol is a steroid hormone produced by the adrenal
glands in response to adrenocorticotropic hormone
(ACTH) secreted by the pituitary.' The typical ditirnal

variation of cortisoi secretion has been well established.
Cortisol shows an increase in the early morning hours,
peaking at or slightly before the time of waking, and
decreases in the evening.' This hormone plays an
important role in maintaining homeostasis by affecting
multiple organ systems and processes. Under stressful
situations, the body responds by increasing the
production of cortisoi by initiating a series of events
involving the hypothalamus, pituitary and adrenal
cortex called the H PA axis. Specifically, corticotrophin-
releasing hormone (CRH) released by the hypothalamus
triggers release of adrenocorticotropic hormone
(ACTH) from the pituitary which in turn causes the
secretion of glucocorticoids from the adrenal cortex.'
The strength of the stimulus causes some variation in
circadian peak levels and the normal variation has been
shown to be disrupted during times of stress.^
Effect on memory
Though elevated cortisoi in response to stress is a
natural response, it is sometimes detrimental for
students in that some forms of memory are impaired.
There is abundant evidence that the secretion of
glticocorticoid stress hormones may modulate memory
functioning.'* The frontal lobe and hippocampus in
humans contain a high density of glucocorticoid
receptors and are areas for cognition and emotion.
During times of stress there may be a pronounced
deficit in working memory but at the same time,
enhancements may be seen associated with other forms
of memory.'
MATERIAL AND M E T H O D S
Multidisciplinary Project

Four departments within the College of Allied Health at
the University of Tennessee Health Science Center
participated in various aspects of this project. The
following outlines some goals anticipated by the faculty
of the departments involved in the study.
The purposes of this multidisciplinary project were to:
r- Validate salivary cortisoi in our Clinical
Laboratory Science (MLS) student laboratory.
" Determine if the stress of an exam would cause
students to lose their normal diurnal variation
of cortisoi.
'- Determine if there is a correlation between
cortisoi concentration and a test grade.
Determine if there is a correlation between
students' perceived stress and the biological
marker of stress-cortisol.
To serve as a working example of research
design to physical therapy students starting a
research course.
-- Provide opportunities for multi-disciplinary
scholarly activity to tenured and non-tenured
faculty.
This paper will focus on only two aspects of the study:
the method validation and whether or not the students
lose their diurnal variation when challenged with a
Stressor.
Participants
After IRB approval was obtained, the entire student
body, of the first year physical therapy class, was

approached at the beginning of a structured lecture to
ask for their participation in the project. These students
were in their fourth month (4''') of a thirty three (33)
month entry-level Doctor of Physical Therapy (DPT)
program. All students had a BA or BS degree prior to
admission to the program. The study was explained in
detail and informed consent was obtained from 50
students. Of these 50 students, 23 completed the
research protocol. The students who completed the
study were on average 23 (± 1.21) years old; 18 female.
222 VOL 24, NO 4 FALL 2011 CLINICAL LABORATORY
SCIENCE
5 male; 22 Caucasian, 1 Asian, 1 Hispanic with an
average undergraduate GPA of 3.54 (±.27) and an
average GRE score of 1025 (±92.7).
Design
Salivary rather than serum or plasma samples were
obtained because levels measured in saliva agree very
well with the amount of free cortisol in blood.** Studies
have shown that the rate of saliva production does not
affect the level of cortisol present.^ Using saliva also
eliminated the possibility of falsely increased cortisol
due to anxiety associated with venipunctures.
Baseline salivary cortisol samples were obtained during
the beginning of the first semester at a time that was
deemed less academically stressful. Test samples were
collected the second semester, one in which they take

36 credits. This heavy course load makes this semester
particularly difficult for the students and an ideal time
to test how stress influences performance.
Students were given specific instructions to follow
(Table 1) for all collections and asked to refrigerate the
specimens collected in the evening and bring them to
campus the following day. For the baseline samples
collected in November 2009, participants were asked to
collect 1 mL of saliva at home between 7:30 and 8:30
pm. The subjects collected their saliva samples by
drooling, through a straw, into a 2 mL polypropylene
screwcap tube. The specimens were refrigerated
overnight and brought to campus the next morning.
Participants collected a morning sample the day after
their evening collection between 7:30 and 8:00 am.
Table 1. Instructions for students
Sample collection instructions:
Do not collect a sample if you have a fever.
Avoid alcohol for 12 hours before sample collection.
Do not eat a major meal within 60 minutes of sample
collection.
Avoid dairy products for 20 minutes before sample collection.
Avoid foods with high sugar or acidity or high caffeine content
immediately before sample collection.
Rinse mouth with water to remove food residue before sample
collection.
Please refrigerate samples overnight.
In February of 2010, the second semester, the same
participants were again asked to collect an evening saliva
sample at home between 7:30 and 8:30 pm the evening
before their 8:00 am kinesiology exam. Many students

also collected their morning sample at home and
brought it in with them. Specimens were collected
Sunday night and Monday morning before the test.
Exclusion criteria
Students previously diagnosed with a condition related
to variation in cortisol such as Cushing s syndrome or
Addison's disease' were excluded from the study. In
addition, students taking steroid medication either oral,
nasal or topical were not enrolled. Students were asked
to avoid the following situations that have been shown
to affect cortisol levels: excessive exercise, smoking, and
food or alcohol intake immediately prior to obtaining a
sample.'*
Salivary cortisol determination
An enzyme immunoassay method purchased from
Salimetrics* was used to determine the salivary cortisol
levels. This method was chosen because it used a matrix
which accommodated the use of saliva." Other methods
available are designed for serum/plasma but are not
validated for saliva. After samples were brought to
campus, they were stored at -20°C until assayed. Saliva
was thawed, vortexed, and centrifuged at 1500 x g for
15 minutes to spin down any mucus in the sample. The
assay was performed by following the package insert
from Salimetrics" (State College, PA).« A BIO-TEK,
Inc. ELx800 Absorbance Microplate Reader, set at 450
nm wavelength, was used to perform the cortisol assays
in the MLS student chemistry laboratory. Raw data
(absorbance values) was sent to Salimetrics for
interpretation using Gen5™ data analysis software, a
program that was not installed on our instrument at the
time.

Method Verification
Ninety-one salivary cortisol samples from participants
were assayed in-house as previously described. Aliquots
of these samples were also sent, on dry-ice, to
Salimetrics for correlation.
Statistical analysis was performed using SPSS 18.0
PASW Statistics. A paired sample t-test and Pearson
correlation was performed (n=91) on the split samples
performed in the student lab and sent to Salimetrics.
The paired sample correlation r =.915 and p < .001
VOL 24, NO 4 FALL 2011 CLINICAL LABORATORY
SCIENCE 223
showed a very strong correlation between the two
methods (Figure 1).
An intra-assay coefficient of variation was 5.5%.
Cortisol Test Comparison
u
T
H
S
C
L
A
B

1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
Salimetrics
Figure 1. Method Verification - Ninety-one salivary eortisol
samples were assayed at U T H S C and at Salimetrics.
A laboratory offering the salivary eortisol testing for
clinical purposes would be required to perform a more
in-depth verification protocol. Sensitivity, specificity
and lower limit of detection assays were not performed.
RESULTS
Interpretation of the students' eortisol values (n=23)
showed a mean fall evening value of .075 ug/dL, a mean
fall morning value of 0.63 ug/dL, a mean test evening
value of 0.08 ug/dL, and a mean test morning value of
0.41 Ug/dL (Table 2). Ranges are shown on Table 3.
The normal diurnal variation between evening and
morning samples did occur with evening samples
reading lower than morning samples.
A paired samples t-test comparing the difference
between the evening and morning values collected in
the fall (baseline), compared with the difference

between the evening and morning values collected in
February (test) showed a statistically significant
difference (p =.028). There was a greater difference in
the evening and morning values during the non-stressful
Table 2. Salivary eortisol values*
Baseline
Fall eveninj;
Ba.seline
Fall morning
Test
Spring evening
Test
Spring morning
N
23
23
23
23
•"All vaiues are reporrcd in iig/dL.
Table 3. Salivary eortisol ranges*
Range
Minimum
Maximum
Fall evening
.19

.01
.20
Mean
0.075
0.6300
0.0809
0.4117
Fall
- -
Std. deviation
0.05955
0.033694
0.11955
0.26819
Morning
1.47
.19
1.65
Expected value
males
age 21-308

ND-.308
0.112-0.743
ND-.308
0.112-0.743
Test Evening
.47
.02
.49
Expected
value females
age 21-308
ND-0.7403
0.272-1.348
ND-0.7403
0.272-1.348
Test Morning
.95
.04
.99
*Ali values are reported ¡n ug/dl..

semester (mean = .5557), than the difference in the
evening and morning values during the test semester
(mean = .3291). Cohen's d effect size = .4. Interestingly,
this difference was due to lower eortisol values on the
morning of the test than on the morning they were
collected in the fall. A paired samples t-test comparing
the difference in the baseline morning eortisol value
(mean = 0.6300) and test morning eortisol (mean =
0.4117) showed a statistically significant difference p =
.019. Results for the paired samples t-tests are shown in
Table 4.
Power analysis was not performed with this pilot study
because estimates of effect size and sample variance
must be known before conducting a power analysis.''"'
When larger studies are performed, researchers can
224 VOL 24, NO 4 FALL 2011 CLINICAL LABORATORY
SCIENCE
utilize effect size estimates from pilot data such as the
current study. Cohen's d effect size was calculated by
subtracting baseline diurnal differences from test
diurnal differences and dividing by the pooled estimate
of variance.
Table 4. Paired samples t-test
her fall evening value was abnormally high and
inconsistent with the rest of her results. This may have
been due to a collection error, medication, or a personal

issue.
Pair 1
Pair 2
Pair 3
fall difference- test difference
fall evening-test evening
fall morning-test morning
df
22
22
22
S ig. (2-tailed)
.028*
.826
.019*
'denotes statistical significance, p < ,05
DISCUSSION
People are able to maintain relative homeostasis because
the human body naturally responds to stressful
situations in ways that allow us to react appropriately.
Dealing with stress for prolonged periods of time will
eventually affect us adversely." Students deal with the
stress of school individually with some thriving but
others struggling to cope. Helping students learn how
to cope with academic pressures benefits all involved.
In this group of students, the cortisol level prior to the
stressful event did not increase as expected. This may be
due to the fact that the students had an additional day

to study due to weather related closing of the campus.
Another explanation might be that these students have
been coping with this type of Stressor for the last four or
five years resulting in desensitization. Repeated exposure
to the same Stressor can result in desensitization or
failure to respond. This is called adaptation or
habituation." Another explanation could be that these
students as a group have developed skills that allow
them to manage test related stress. The students are
selected through a competitive process using criteria
that would exclude students who succumb easily to the
stress of an exam.
This initial small sample study made the researchers
aware of problems that should be addressed before a
larger study is designed. When participants bring in
specimens collected at home, investigators need to make
sure the specimen is properly labeled before the
participant leaves. Several participants were dropped
from the study because the collection tubes were not
labeled. One sample was lost because the cap was not
tightened properly and the specimen leaked. One
participant's data was deleted from the study because
Cortisol diurnal variation was not lost in the study
participants, but further studies should be performed
due to the low percentage of students completing the
study and the lack of demographic diversity. The
weekend immediately before the test, the students had
an unexpected 3-day weekend due to a weather- related
closure of the university. It is possible that this extra day
to study decreased the stress the students would have
otherwise felt. Also, these physical therapy students tend
to be more physically active, compared to a more
generalized adult population, which could affect the
results.

C O N C L U S I O N S
Diurnal variation of cortisol was not lost in the study
participants but further studies need to be performed
due to the low number of participants completing the
study and the lack of demographic diversity. Other
variables that should be controlled, in future studies,
include: physical activity level, grade point average, and
body mass index (BMI).
Even though the method validation performed in the
student laboratory setting demonstrates that it is indeed
possible to obtain the same excellent correlation as is
seen in a clinical setting, the student laboratory is not
CLIA certified so assays can be performed for research
use only.
The fact that the students' cortisol levels were
significantly higher in the fall semester than the spring
semester has raised some interesting questions that will
be investigated in the future. One such question is,
"Does the stress of life events, including moving to a
new location, affect students more than academic
Stressors"?
A C K N O W L E D G E M E N T S The authors would like to
thank Thomas A. Hughes M.D. at the University of
Tennessee Health Science Center for his advice on this
project. Kametricia N. Derricks is gratefully
acknowledged for her contributions. This project was
supported with a seed grant from the College of Allied
VOL 24, NO 4 FALL 2011 CLINICAL LABORATORY
SCIENCE 225

Health Sciences at the University of Tennessee Health
Science Center.
REFERENCES
1. Burtis CA, Ashwood, E.R., Bruns. D.E. Tietz Textbook of
Clinical Chemistry and Molecular Diagnostics, 4th ed. St.
Louis: Elsevier Saunders; 2006.
2. Kaiman B, Grahn R. Measuring Salivary Cortisol in the
Behavioral Neuroscience Laboratory. The Journal of
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3. Kudielka B, Kirschbam C. Sex differences in HPA axis
responses to stress: a review. Biological Psychology
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4. Smeets T, Dziobek I, Wolf O. Social cognition under stress:
Differential effects of stress-induced cortisol elevations in
healthy young men and women. Hormones and Behavior
2OO9;55:5O7-13.
5. Luethi M, Meier B, Sandi C. Stress effects on working
memory, explicit memory, and implicit memory for neutral
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2009 [cited Jan 14, 2011].
6. Arafah B, Nishiyama F, Tlygeh H, Hejal R. Measurement of
Salivary Cortisol Concentration in the Assessment of Adrenal
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Circulating Free Cortisol. J Clin Endocrinol Metab
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7. Vining R, McGinley R. The measurement of hormones in
saliva: Possibilities and pitfalls. J Steroid Biochem.
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8. Salimetrics'". High Sensitivity Salivary Cortisol Enzyme
Immunoassay Kit. July 2009. State College, PA.
9. Statistical Computing Seminars: Introduction to Power
Analysis. Available from: http://www.ats.ucla.edu/stat/
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