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Thyroid Disease
Women’s Health Symposium
August 1, 2009
Michael Gardner, MD
University of Missouri Columbia
Departments of Internal Medicine and Child Health
Division of Endocrinology
A 24 Year Old Woman With Fatigue
A 24 year old woman complains of fatigue
weight gain and trouble sleeping at night
PMH and PE: unremarkable
TSH is drawn and comes back at 7 mU/L (0.3-5)
What is the diagnosis?
What other test should be ordered?
What is any therapy should be started?
Progression of Hypothyroidism
TSH
Normal
Range
T3
Euthyroid
Subclinical
Primary T4
Hypothyroid Hypothyroid
Hypothyroidism
Primary hypothyroidism
TSH generally >10, low free T4
Treat with levothyroxine
Adjust dose to keep TSH in normal range
Subclinical hypothyroidism
TSH >5 and normal T4
Check for anti-TPO antibodies
Progression of Subclinical to
Overt Hypothyroidism
Progression to overt hypothyroidism
estimated is 4 to 18% per year
Increased likelihood with
Higher TSH
Positive antibodies
(+) antibodies doubles likelihood
History of RAI therapy
Lithium therapy
Age <55yrs
A 24 Year Old Woman With Fatigue
A free T4 is 1.54 (0.71-1.8) Anti TPO Antibodies
are strongly positive
She is diagnosed with Subclinical
Hypothyroidism and started on L-thyroxine
0.075 mg/day
Four months later her TSH is 0.7 mU/L
She is still complaining of fatigue and
trouble sleeping and has not lost any weight.
Says she has been reading on the Internet
that she might need treatment bioequivalent
hormone found in Armour thyroid.
A 24 Year Old Woman With Fatigue
What do you do?
Increase her L-thyroxine dose to treat her
symptoms
Change to Armour 1 grain daily
Screen for other causes of her symptoms
A 24 Year Old Woman With Fatigue
 Excessive doses of thyroid hormone will not fix:
Depression
Metabolic syndrome / increased adiposity
Sleep apnea / Sleep deprivation
Etc.
 No evidence for increased efficacy with the
addition of Liothyronine (T3) to Levothyroxine
Most T3 in humans is produced by peripheral
conversion of T4
Dessicated thyroid is desiccated porcine
thyroid gland.
Dose based on organic iodine not thyroid
hormone content
Other Causes of Increased TSH
Recovery from serous non thyroidal disease
Random pulses of TSH (particularly in evening)
Assay variability (Lab error)
Adrenal insufficiency
Treatment with metoclopramide
TSH producing tumor and thyroid hormone
resistant states
Extremely Rare
Free T4 should be increased
Reasons to Treat Subclinical
Hypothyroidism
 Very Little Evidence of Benefit
 Possible benefits
Stabilize Goiter
Widely accepted, conflicting evidence
Prevent Progression to Overt Hypothyroid
Good association
Improved lipids
Decrease CAD
Only in younger patients
May increase risk >70 yo
Improved non-specific symptoms
Generally patients symptoms unrelated
Potential Disadvantages to Treating
Subclinical Hypothyroidism
Relatively safe in young patients
Cost of life long therapy and monitoring
Generic is $4 at national chains
Over treatment
Atrial fibrillation
Bone loss
Having an asymptomatic patient taking
medication for the rest of life
High TSH in Patients Taking L-Thyroxine
May indicate need for more hormone
Other causes need to be considered
TSH takes longer to come down than the T4
takes to come up
Missed doses
Generally TSH high with high normal or
elevated T4
Medications interfering with absorption
Iron/Calcium supplements
Bile binders
Proton pump inhibitors
32 Year Old Woman With Fatigue
and Cold Intolerance
A 32 y/old woman is seen by her PCP
complaining of fatigue and cold intolerance
ROS: otherwise negative
PE: Normal except for dry doughy skin
Lab:
TSH is 0.9 mU/L (0.3-5.0)
Is this patient hyper, hypo or euthyroid?
What should be done next in the work up of
this patients?
Secondary Hypothyroidism
 TSH can only be used to screen for primary
hypothyroidism
When the TSH is discordant with the symptoms
or physical exam, check the free T4 and
occasionally free T3
Cases were the history or physical exam
suggests hypopituitarism you must also check
Free T4
Amenorrhea / Hypogonadism
Growth Failure (children)
Postpartum hemorrhage
Past head trauma etc.
A 48 Year Old Man With “Nervousness”
A 48 year old man complains of increased
nervousness.
He denies heat or cold intolerance
His weight is stable
There is no hair or skin changes
Lab: TSH 0.1 mU/l
Is this patient
Hyperthyroid?
Euthyroid?
Progression of Graves Hyperthyroidism
T3
T4
Normal
Range
TSH
Euthyroid
Subclinical
Hyperthyroid
T3
Overt
Toxicosis Hyperthyroid
Subclinical Hyperthyroidism
Low TSH with normal free T4 and T3
Log linear relationship between thyroid
hormone and TSH
Very small changes in thyroid hormone
result in dramatic changes in TSH
Subclinical Hyperthyroidism: Importance
Clinical importance
Bone
Thyroid hormone stimulates bone
resorption
Studies are conflicting
Atrial fibrillation
More common in patients with low TSH
Lower the TSH, high the risk
Other areas
Sleep
Exercise
Treatment of Subclinical Hyperthyroidism
Few long term studies
Depends on degree and clinical setting
TSH 0.1-0.3 and no symptoms or atrial
arrhythmias: follow
TSH <0.1
Repeat and if still low consider course of
antithyroid medications
Many patients will be normal after 1-2 years
A 48 Year Old Man With “Nervousness”
Total T4 is 5.9 mcg/dL (5-12)
Free T4 is 0.62 ng/dL (0.58-1.64)
Total T3 is 300 ng/dL (87-178)
Is this patient
Hyperthyroid?
Euthyroid?
Hyperthyroidism due to an Autonomous
Nodule
T3
Or
Normal
Range
T4
TSH
Euthyroid
Subclinical
Hyperthyroid
T3
Overt
Toxicosis Hyperthyroid
Indication for I123 Uptake and Scan
Suppressed TSH with elevated T4 and/or T3
Distinguish Hyperthyroidism from acute
thyroiditis
Distinguish Graves from autonomous
nodules
Some autonomous nodules produce both
T3 and T4
Role in diagnosis of nodules diminishing
Unable to distinguish cyst from “cold” solid
nodule
Ultrasound in skilled hands combined with
FNA better for cancer determination
Thank You
Questions?
56 Year Old Man In ICU
66 year old post MVA with multiple fractures,
pneumonia, respiratory failure on respiratory
failure on respirator
The patients develops atrial fibrillation and a
TSH is 0.08 mU/l (0.3-5)
Is this patient hyperthyroid?
Severe Illness and Thyroid Testing
Several changes are seen in thyroid function
test in patients with acute illnesses
Low T3 levels (decrease T4 to T3
conversion)
Increased Reverse T3 levels
Total T4 is often low
More severe illness
Pituitary TSH secretion is diminished
T4 Peripheral Conversion
5’ Deiodinase
T3
T4
5 Deiodinase
5 Deiodinase
T2
Reverse T3
5’ Deiodinase
Severe Illness and Low T4
Seen in more severely ill patients
Appears to be do to abnormalities in binding
Low TBG, TBPA, and Albumin may be low
Circulating substance the impair binding
High free fatty acids are one possibility
Measurement of free T4 are effected differently
Free thyroid index is usually low
Free T4 by equilibrium is usually elevated
Measurement of free T4 by direct assay may
be low, normal or high
Severe Illness and Thyroid Testing
The lower the T4 in severely ill patients, the
higher the mortality
Thyroid hormone replacement does not help
this
TSH In Severely Ill Patients
In severe illness patients may have transient
central hypothyroidism
TSH may be low
In primary hypothyroidism, TSH may be
normal
Always use ultra sensitive TSH assay
Values 0.01-0.05 suggest hyperthyroidism,
0.05-0.3 will usually be normal later
During recovery from acute illness, TSH levels
may be transiently elevated
In Severely Ill Patients
Testing may make euthyroid patient look
hypothyroid or hyperthyroid
Primary hypothyroidism may be masked
Hyperthyroidism may be masked
Effects of Drugs on Thyroid Tests
The following drugs suppress TSH values in
normal and hypothyroid individuals
Dopamine
Dobutamine
Glucocorticoid
T4 may be displaced from binding sites by
Furosemide
Salsalate
Heparin
Phenytoin
Carbamazepine
Thyroid Testing In Severely Ill Patients
Thyroid function should not be assessed in
severely ill patients unless there is strong
suspicion of underling thyroidal illness
NO SCREENING!
When there is a strong suspicion, TSH (ultra
sensitive), Free T4, Free T3 and Reverse T3
need to be assessed
Physical exam: look for clinical findings and
goiter
History: ask about past history of thyroid
disease and hormone use
FHx: Thyroid problems often run in families
Thyroid Function in Elderly Patients
TSH levels tend to drop with age
Several older patients have low Free T4 with
normal or minimally elevated TSH levels
Several older patients have low TSH and
normal free T4 and free T3 and no evidence of
thyroid disfunction
TSH Cascade
2nd or 3rd Generation TSH Assay
Patient without pituitary or severe illness
Low
Taking
thyroid
Reduce
dose
Check FT4
Normal
Check T3
Normal Follow
Normal
Elevated
No further
testing
Check FT4
High
Hyperthyroid
Normal
Subclinical
Hypothyroid
Low
Primary
Hypothyroid
Taking thyroid
Low/Low normal
Increase dose
Prevalence of Subclinical Hypothyroidism
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*Increased Risk in Whites vs Blacks,
Women vs. Men, and elderly subjects.
Sawin CT et al., Arch Int Med 145:1386, 1985
Bagchi N et al., Arch Int Med 150::785, 1990
32 Year Old Woman With Fatigue
and Cold Intolerance
When seen by endocrinology, the patient
recalled she had required blood transfusions
after the birth of her last child
Free T4 was 0.4
ACTH stimulation test showed pre value of 2
and 30 min value of 4
Prolactin was undetectable
After 10 mg of Provera for 10 days there was
no menstrual bleeding and FSH and LH levels
were undetectable
Growth hormone did not stimulate
32 Year Old Woman With Fatigue
and Cold Intolerance
The patient was started on predinsone 2.5 mg
TID
The next day, she was started on L-Thyroxine
Cyclical estrogen and progesterone were
begun
She was begun on human growth hormone
therapy
Euthyroid Graves Disease