Download Thyroid Storm - UNM Hospitalist Wiki

Facilitator Version
Module #8 – Endocrine Emergencies
Adrenal Insufficiency
Objectives:
By the end of this module, you should be able to:
1. Recognize signs and symptoms of adrenal insufficiency
2. Differentiate between primary vs secondary adrenal insufficiency
3. Understand and recognize relative adrenal insufficiency
4. Understand the utility and limitations of diagnostic tests in adrenal insufficiency
5. Understand reasons for different treatment regimen in primary vs secondary vs
relative adrenal insufficiency
CASE
A 74 yom with past medical history of oxygen dependent COPD presents to the ER with
fatigue, sob and productive cough present for three days. His outpatient medications are
atrovent and albuterol MDIs and nebulizers. He has had four hospitalizations in the past
year for COPD exacerbations. On review of systems, patient reports that he has lost ~15
lbs over the past 6 mos.
On physical examination, temperature 99.0 F, BP 88/52, HR 114 (after Duoneb was
given), RR 20 with O2 sat 88% while on 4L of oxygen. Weight is 115 lbs, BMI 21.
Physical examination is significant for a thin man with globally diminished breath sounds
without any crackles or wheezing. He is breathing with pursed lips with contraction of
accessory respiratory muscles. Remainder of the exam is normal.
Labs:
Na 131, K 4.0, Cl 92, CO2 40, BUN 6, Cr 0.4, Glu 55
WBC 12.1 (42% N, 46%L, 4%M, 6%E), Hgb 13m Hct 40, Plt 225
Lactate wnl, Coags wnl, LFTs wnl, trop wnl
Imaging:
PA/LAT CXR reveals no evidence of infiltrate or nodules. There is flattening of the
diaphragms bilaterally.
Hospital Course:
A diagnosis of COPD exacerbation is made. The patient is admitted to the hospital and
started on atrovent and albuterol nebs Q6H, doxycycline, and prednisone 60mg taper.
His breathing and oxygenation improves over the course of 3 days.
What is your differential diagnosis for his weight loss?
Malignancy, chronic infections ie fungal, HIV, adrenal insufficiency and malnutrition
What lab values are abnormal and not explained by COPD exacerbation?
Hyponatremia, lymphocytosis, eosinophilia and hypoglycemia
What diagnosis would explain the weight loss, hypotension and the abnormal lab
findings?
Adrenal insufficiency, given patient has a history of recurrent steroid treatment in the past
year along with symptoms/signs of adrenal insufficiency (hypotension, weight loss,
hyponatremia, lymphocytosis, eosinophilia and hypoglycemia).
Would you suspect this to be primary, secondary or relative adrenal insufficiency?
Secondary adrenal insufficiency since we are suspecting that recurrent steroid treatment
led to it.
Definitions:
Primary adrenal insufficiency: Failure of adrenal glands resulting in insufficient
production of BOTH glucocorticoids (cortisol) and mineralocorticoids (aldosterone).
Etiologies: autoimmune adrenalitis (70%), bilateral adrenal hemorrhage, TB,
Histoplasmosis, N. meningitides, medications (eg etomidate, ketoconazole), metastatic
disease, Addison’s disease
Secondary adrenal insufficiency: Due to insufficient pituitary ACTH production
resulting in decreased production of cortisol. Aldosterone production usually not
affected.
Etiologies: pituitary disease (adenoma, empty sella, tumors), chronic steroid use (i.e.
prednisone), history of cranial irradiation
Relative adrenal insufficiency: Transient insufficiency of adrenal glucocorticoid
(cortisol) production associated with critical illness/septic shock.
Etiologies: critical illness, septic shock
How would you work it up?
Cosyntropin stimulation is best test for the diagnosis of adrenal insufficiency and it can
be done any time of day!!!
How do you perform Cosyntropin stimulation test?
-Check baseline cortisol level
-Give Cosyntropin 0.25 mg IV push
-Check cortisol at 30 and 60 min post-Cosyntropin
-Check baseline ACTH level only if trying to determine/distinguish primary vs secondary
adrenal insufficiency (ACTH high in primary AI and low in secondary AI)
How is the interpretation of the results of cosyntropin stim test different in
critically-ill patients vs non-critically ill patients?
In non-critically ill patients: 60 min cortisol < 20 ug/dl after a cosyntropin stimulation is
diagnostic of adrenal insufficiency.
In critically-ill patients: baseline cortisol levels are already increased from being
critically-ill, but the patient may still have diminished response and capacity to stress,
referred to as relative adrenal insufficiency. Therefore a new reference has to be applied
to diagnose relative adrenal insufficiency. Relative adrenal insufficiency is defined by an
increase in cortisol ≤ 9 ug/dl following a 250 ug cosyntropin stim test. A cortisol
increment ≤ 9 ug/dl suggests diminished adrenal reserve and diminished capacity to
respond to stress. Diagnosing relative adrenal insufficiency in critically ill patients is
important because probability of survival decreases in this population if not treated for
the relative adrenal insufficiency.
What is the value of random cortisol level?
The value of random cortisol level is very limited. Random cortisol level is seldom used
to diagnose adrenal insufficiency because normal cortisol level fluctuates significantly
throughout the day. Therefore there is no way of setting up normal parameters for
random cortisol level since it depends on time of day it is drawn. Sometimes, 8am
cortisol level is used because cortisol peaks in early morning so level <3 ug/dl may be
suggestive but not diagnostic of adrenal insufficiency.
Results of Cosyntropin stimulation test are as follows:
Baseline:
ACTH 5 (normal 10-65)
Cortisol 16 ug/dl
30-minute stimulated cortisol: 22 ug/dl
60-minute stimulated cortisol: 26 ug/dl
How do you interpret these values? Does the patient have adrenal insufficiency?
It is not clear whether patient has adrenal insufficiency because the cosyntropin stim test
was done while the patient was taking prednisone. Prednisone and hydrocortisone crossreacts with the assay for cortisol and can raise cortisol values and therefore the results
cannot be interpreted. Dexamethasone does not cross-react with the cortisol assay and
the results of a cosyntropin-stimulation test can be interpreted when dexamethasone is
used.
What should you do now?
Consult with Endocrinology so that a plan is in place after discharge for a repeat
consyntropin stim test and the timing of that test relative to the prednisone taper.
Patient is seen by Endocrinology as outpatient and cosyntropin stim test is repeated,
off prednisone. Results are as follows:
Baseline cortisol: 10 ug/dl
60-minutes stimulated cortisol: 16 ug/dl
Does the patient have adrenal insufficiency?
Yes. In non-critically ill patients, a peak cortisol < 20 ug/dl is diagnostic of adrenal
insufficiency.
How would you treat this patient now?
The average daily cortisol secretion is about 15-25 mg/day with peaks in secretion in the
early morning and early evening. The patient is started on Hydrocortisone 15mg QAM
and 5mg QPM.
Does this patient need fludrocortisone?
No. Fludrocortisone is a mineralocorticoid and is similar to aldosterone. In secondary
adrenal insufficiency, secretion of aldosterone is preserved as the renin-angiotensinaldosterone axis is still able to respond to increases in potassium. If the patient had
primary AI, then fludrocortisone would probably be necessary.
Over the next 2 months, patient reports increased energy and weight gain of 3 lbs.
He is seen in the Pulmonary Clinic for a follow-up of his recurrent COPD
exacerbations (5 episodes in one year) and is started on Prednisone 10mg daily for
his COPD.
What should you do with the hydrocortisone?
Stop the hydrocortisone. Prednisone is a more potent steroid than hydrocortisone. It is
thought that prednisone is ~4-5x more potent than hydrocortisone. In this patient, a dose
of prednisone of 10mg would be about equivalent to a hydrocortisone dose of 40mg
daily. Thus, the prednisone would be sufficient to treat his secondary adrenal
insufficiency, and the hydrocortisone can be stopped.
The patient is readmitted to the hospital 1 year later for RLL pneumonia. He is
febrile, tachycardic, hypotensive, and requires 40% ventimask to maintain his
oxygen saturation. The patient is diagnosed with community-acquired pneumonia
and started on appropriate antibiotics. What would you do with his outpatient
prednisone?
His outpatient prednisone should be discontinued and patient should be placed on stress
dose steroids while he is critically ill. Don’t forget the patient has secondary adrenal
insufficiency. Usually hydrocortisone IV is used, 200-300 mg/d in divided doses, 50mg
IV Q6h or 100mg IV Q8h. Alternative to IV hydrocortisone is Dexamethasone 4mg IV
qd.
When would you taper the stress dose steroids in this patient?
Usually, stress dose steroids can be tapered slowly over the course of several days or
weeks back to the patient’s maintenance dose.
Will the patient need steroids for life for his secondary adrenal insufficiency?
No, the adrenals can recover in secondary adrenal insufficiency, but this may take months
or years.
MKSAP 16:
Question #25: Management of adrenal insufficiency
Question #39: Manage newly diagnosed adrenal insufficiency
Question #48: Evaluate adrenal function during critical illness
Question #55: Manage adrenal function during critical illness
Question # 60: Diagnose the cause of acute adrenal insufficiency
*****YOU MAY STOP HERE OR PROCEED TO THYROID STORM*****
Thyroid Storm
Objectives:
By the end of this module, you should be able to:
1) Recognize three signs and symptoms of thyroid storm and why they occur
2) Be able to appropriately evaluate a patient with suspected thyroid storm
3) List three treatments for thyroid storm
CASE
A 19 yom was involved in a low speed motor vehicle accident. At the scene, he complained of
neck pain. A C-collar was placed and he was transferred by ambulance to the local Emergency
room. On exam, he was generally anxious, warm to touch, had mild tremor. Vitals show patient
was tachycardic with heart rate of 125. Patient had tenderness over the c-spine, but no focal
neurological deficits were noted. X-ray of the c-spine was ordered. Over the course of his ER
stay he became progressively agitated, confused and combative. His heart rate increased to 160
and temperature rose to 40◦ C. He was visibly shaking and unable to sit still. He required
sedation and restraints. He was intubated for airway protection and respiratory support and was
transferred to a tertiary care center and admitted to an ICU bed.
What is your differential diagnosis for his deterioration in mental status (initially anxious
and mildly tremulous to agitation, confusion and combativeness) and increase in heart rate
and temperature?
Sepsis, intoxication, alcohol withdrawal, thyroid storm, organophosphate poisoning, autonomic
insufficiency, psychosis, intracranial hemorrhage.
What is your next step in the work-up and management?
A full metabolic panel, CBC, blood and urine cultures, toxicology screen, and thyroid panel were
ordered. EKG, CXR, CT head. Manage with IVF.
Patient received IV fluids with no improvement in his heart rate. His labs were all WNL,
white count wnl, no toxic granulation, no left shift. Tox screen was negative. UA was
negative and blood culture was drawn, thyroid panel pending. EKG showed sinus
tachycardia, CXR was negative, C-spine x-ray was difficult to interpret so a C-spine CT
was ordered, head CT was negative.
Patient remained tachycardic at 160 and febrile to 41◦C, BP 160/90, with no obvious source
of infection identified. What is the most likely diagnosis now?
A diagnosis of thyroid storm should be made now and treatment started immediately, even when
the thyroid panel results are still pending. The diagnosis of thyroid storm is made by clinical
suspicion based on patient history, signs and symptoms and physical exam findings. Waiting for
thyroid function tests to return leads to unnecessary treatment delays and can be catastrophic.
What are the clinical manifestations of thyroid storm?
Thyroid storm is a medical emergency that includes hyperthyroidism, cardiovascular instability,
thermogenic instability, and neurogenic instability. The diagnosis of thyroid storm is based on
signs and symptoms and is a clinical diagnosis. Being able to recognize the manifestations of
thyroid storm is essential to expedite treatment and prevent morbidity and mortality.
What would you look for in history if thyroid storm was suspected?
Most patients will report a history of symptoms consistent with hyperthyroidism including
unexplained weight loss, insomnia, heat intolerance, tremors, and palpitations.
They will present with an acute worsening of those symptoms in addition to severe agitation.
What would you look for in physical exam if thyroid storm was suspected?
Significant physical exam findings include agitation and inability to sit still. Temperature is
usually elevated, significant tachycardia is present and blood pressure is labile. Skin is moist and
warm to touch. Eye examination may demonstrate stare, lid lag, or exopthalmos if Graves’
disease is present. Thyroid exam findings depend on the etiology of hyperthyroidism (Table 3).
Muscle weakness and hyperreflexia may be present. Additionally, patients perform poorly on the
mini mental status exam.
What is the mortality rate for this condition?
Even with appropriate treatment mortality rates for thyroid storm remain high at 25%.
How would you treat this patient?
Patients should be admitted to an intensive care unit. Treatment is multifactorial and includes
supportive care and pharmacologic intervention. Pharmacologic treatment is aimed at blocking
thyroid hormone synthesis, release, conversion to T3, and action on cells.
 Fluid as patients are volume deplete
 Cooling blankets if hyperthermia is present
 Beta blockade to minimize catecholamine excess
o Propranolol 20-40 mg q 6 hours to decrease heart rate to < 100 bpm
o Esmolol if concern regarding cardiac output (fast acting/short t ½ life.)
 Thionamides:
o Propothyouricil (PTU) 150 mg po q 6 hours if patient is able to take p.o.
Or
o Methimazole 10-20 mg pr q 6 hours
 SSKI or Lugol's solution: administer 1-2 hours following thionamide administration.
 Steroids: Dexamethasone 1 mg q 6-8 hours
 Treat underlying precipitating stressor if present
 If no response consider emergent thyroidectomy or plasmaphoresis.
 Aviod aspirin; it increases free thyroid hormone levels by competing with binding sites
on Thyroid binding globulin
Where do these pharmacologic agents work?
T-4
Synthes
is
Thionamides
T-4
T-4
Iodine
PTU
Propranolol
Steroid
T3 activity
β-blockers
Steroids
Patient received: Propranolol 60 mg iv q 6 hours, PTU 150 mg po q 6 hours,
Dexamethasone 1 mg iv q 6 hours. SSKI 6 drops po q 6 hours (started 2 hours after the
first dose of PTU).
The following day, his thyroid panel results were available and showed TSH was
undetectable and his Free T4 was >6 mg/do. A diagnosis of thyroid storm was confirmed.
Once his c-spine was cleared by CT scan, the c-collar was removed. A diffusely enlarge
thyroid gland was visible on gross inspection. Three days after admission the patient’s
heart rate was 92, Temp was 37.3, he was mentating normally, and was able to report a 20
pound weight loss over the preceding 3-months, insomnia and heat intolerance.
What precipitated this patient into thyroid storm?
Patient’s motor vehicle accident caused an acute catecholamine surge, in the presence of
untreated hyperthyroidism lead to thyroid storm. Thyroid storm typically occurs in a patient with
underlying hyperthyroidism, either previously known or unknown, who develops a second
illness or stressor. The second stressor results in an acute catecholamine surge. The
catecholamine surge in the presence of hyperthyroidism leads to tachyarythmias, high output
cardiac failure and cardiovascular instability. Elevated catecholamine in the setting of
hyperthyroidism causes hyperthermia leading to thermodynamic instability. The combination
also causes tremors, hyperreflexia, mania, concentration and memory disturbances and
culminates in neuropsychiatric instability.
What are common precipitants of thyroid storm?
Table 1. Causes of hyperthyroidism
Graves’ Disease
Toxic Multinodular Goiter
Toxic Adenoma
Thyroiditis
Exogenous Thyroid Hormone
Thyroiditis
Jod Basedow
TSH Secreting Pituitary Adenoma
Molar Pregnancy
Struma Ovarii
Table 2. Precipitants of Thyroid Storm
Pregnancy
Trauma
Infection
Myocardial Infarction
Surgery
Intoxication
ETOH
Cocaine
Amphetamines
Iodine ( in MNG, Toxic adenoma)
Radioactive Iodine
IV Contrast
Amiodarone
MKSAP 16:
Question #72: Diagnose thyroid storm
*****YOU MAY STOP HERE OR PROCEED TO MYXEDEMA COMA*****
Severe hypothyroidism/Myxedema Coma
Objectives:
By the end of this module, you should be able to:
1) Recognize three signs and symptoms of severe hypothyroidism/myxedema coma and
why they occur
2) Be able to appropriately evaluate a patient with suspected of severe
hypothyroidism/myxedema coma
3) List three treatments for severe hypothyroidism/myxedema coma
CASE
72 yo obese female with history of overactive thyroid gland s/p radioactive iodine therapy and
hypertension is brought in to the ED by her husband for cough productive of green sputum,
lethargy and confusion. Husband reports that cough started about a week ago, but patient has
been really weak, unable to get out of bed much and sleeping a lot for the past month. Outpatient
medications are levothyroxine and losartan, although patient has not been taking these for at least
several months. Patient does not take any over the counter medications, herbs or supplements.
Vitals, T 35.2, BP 80/55, HR 70, rr 9, O2 sat 80% on RA. Exam shows an obese female, arouses
intermittently but falls back asleep again, unable to answer questions appropriately, appears
lethargic and has dry skin and dry mucous membranes. Lungs with bibasilar diminished breath
sounds and crackles most notably on R side mid-lung fields. Abdominal exam is normal.
Extremities with mild bilateral edema. Neuro exam, patient unable to follow commands, moves
all 4 extremities spontaneously, and has slow reflexes.
Labs:
WC 21, 000, 90% neutrophils, h/h 15/43, plts 230
Na 131, K 3.5, Cl 102, bicarb 25, bun 8, cr 0.7, Glucose 45
CXR shows RLL consolidation and small bilateral pleural effusions.
CT head without contrast is negative.
Urine toxicology is negative.
Patient is admitted for SIRS/Sepsis, and started on appropriate antibiotics for the pneumonia and
receives IVF to support blood pressure. Patient’s pneumonia appears to be improving over the
next 24 hours as WC decreases to 9,000 and oxygenation improves to 89% on RA. You initially
thought that patient’s altered mental status was due to sepsis and or delirium, and therefore
expected it to improve over the next 24 hours, although it has not. Patient remains really sleepy,
confused and lethargic and this is not a waxing and waning pattern.
What is your differential diagnosis for her confusion, sleepiness, delayed reflexes, low BP,
low respiratory rate, low sodium, and low glucose?
Severe hypothyroidism/myxedema coma
What studies would you send to work this up?
TSH, Free T4 and Total T3
Results return as follows:
TSH 155
Free T4 0.2 (nl range
Total T3 <20
What is your diagnosis?
Severe hypothyroidism/myxedema coma. The clinical picture is often that of an elderly obese
female who has come increasingly withdrawn, lethargic, sleepy and confused. The presentation
is one of severe hypothyroidism, with or without coma (the term myxedema coma, may
therefore, be a misnomer)
What precipitated this patient’s presentation?
In this patient’s case the precipitating event was the pneumonia. Myxedema coma is most
frequently associated with discontinuation of thyroid hormone therapy and rerely is the first
manifestation of hypothyroidism. Myxedema coma may be precipitated by an illness such as a
CVA, infection, GI bleeding acute trauma, excessive hydration, or administration of a sedative,
narcotic, or potent diuretic drug.
What is the most appropriate initial treatment of this patient?
Myxedema coma/severe hypothyroidism is considered a medical emergency, and appropriate
supportive measures (treatment of precipitating factor ie infections or AMI, ventilator support if
necessary, and assessment and treatment of cardiac issues) are very important. Typically, the
patient is severely ill and usually is admitted to the ICU for intubation and ventilator support.
No consensus exists about the most efficacious thyroid hormone replacement regimen to use for
myxedema coma. Oral medications are poorly absorbed (due to ileus), and all medications
should be given intravenously (IV). Typically, a loading dose of 200 to 500 ug of T4 IV is given
initially to saturate T4 binding sites in plasma binding proteins. The patient is then maintained on
50ug to 100ug of IV T4 daily until oral administration is feasible. The high doses of
levothyroxine are recommended to replenish the depleted tissue stores of thyroid hormone.
However, high doses of levothyroxine may be associated with cardiac irregularities and should
be used cautiously, especially in patients with known or suspected cardiac disorders.
Decreased intracellular T3 leads to change in fluid balance with increased water retention due to
impaired renal perfusion as well as increased vascular permeability. These changes result in
effusions and hyponatremia, which in turn contributes to coma.
Water restriction is necessary to correct the hyponatremia and avoid fluid overload.
IV glucose to treat the hypoglycemia.
The use of hydrocortisone is prudent because patients may have hypopituitarism or autoimmune
polyglandular failure that can lead to secondary adrenal insufficiency. Patients with myxedema
coma should be checked for possible adrenal insufficiency and treated with a stress-dose
glucocorticoid, such as hydrocortisone, until adrenal insufficiency is excluded and appropriate
adrenal function confirmed. Usually hydrocortisone IV is used, 200-300 mg/d in divided doses,
50mg IV Q6h or 100mg IV Q8h. Alternative to IV hydrocortisone is Dexamethasone 4mg IV
qd. This is usually tapered over the next 5-7 days.
Once myxedema coma is suspected in a hypothermic patient, external rewarming should be
avoided, because this may cause redistribution of blood flow to subcutaneous tissues and
cardiovascular collapse.
What is the mortality rate in treated vs untreated myxedema coma?
Prior to recognition of the need for IV T4 and for respiratory support, the mortality from
myxedema coma was about 80%. Currently, the mortality is about 20% and is mostly due to the
underlying or precipitation illness.
Higher mortality is associated with increased age, cardiac complications and high-dose thyroid
hormone replacement (> 500ug/d of levothyroxine). Persistent hypothermia and bradycardia,
despite therapy, are associated with a poor prognosis.
MKSAP 16:
Question #49: Treat myxedema coma
Post Module Evaluation
Please place completed evaluation in an interdepartmental mail envelope and address to Dr.
Wendy Gerstein, Department of Medicine, VAMC (111).
1) Topic of module:__________________________
2) On a scale of 1-5, how effective was this module for learning this topic? _________
(1= not effective at all, 5 = extremely effective)
3) Were there any obvious errors, confusing data, or omissions? Please list/comment below:
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________
4) Was the attending involved in the teaching of this module? Yes/no (please circle).
5) Please provide any further comments/feedback about this module, or the inpatient curriculum
in general:
6) Please circle one:
Attending
Resident (R2/R3)
Intern
Medical student