common issues in management of hypothyroidism€¢small changes in levothyroxine do not produce...
TRANSCRIPT
Family Medicine
Refresher Course
April 5, 2018
Janet A. Schlechte, M.D.
Common Issues in
Management of
Hypothyroidism
Janet A. Schlechte, M.D.
has no relationships with any
proprietary entity producing
health care goods or services
consumed by or used on
patients.
Disclosure of Financial
Relationships
• The symptomatic patient with normal
thyroid function studies.
• Is there a role for T3 or combination
T4/T3 therapy?
• Thyroid disease during pregnancy.
• Subclinical thyroid disease.
• Recognizing secondary
hypothyroidism.
Issues
• Too sensitive for screening
• Measures size and number of
nodules
• Not a substitute for the physical
exam
• At least 50% of general population
has small nodules by ultrasound
• An ultrasound cannot distinguish
benign and malignant nodules
Thyroid Ultrasound
• A 40 y.o. has developed
fatigue, cold intolerance,
constipation and weight gain
since her last visit.
• Her exam is normal and the
thyroid is not palpable. You
suspect hypothyroidism and
order thyroid function studies.
• FT4 0.7 (0.8-1.8)
• TSH 25 (0.2-4.2)
• Most likely diagnosis is
autoimmune hypothyroidism
• Levothyroxine 1.6 µg/kg
except in heart disease or
elderly
• Repeat TFT’s in 10-12 weeks
One year later
• FT4 1.2 (0.8-1.8)
• TSH 4.9 (0.2-4.2)
Two years later
• FT4 1.3 (0.8-1.8)
• TSH 45 (0.2-4.2)
Three years later
• TSH is 2, she is constipated
and she can’t lose weight
• “Using the wrong tests”
• “The TSH normal range is wrong”
• “I need both T4 and T3”
• “I need natural thyroid hormone”
• “I need a higher dose”
• “My thyroid is not converting T4 to T3”
The symptomatic patient
with normal TFT’s
• Will maintaining TSH at the
upper or lower ends of the
normal range improve
symptoms?
• Should you use symptoms or
TSH levels to guide therapy
with thyroid hormone?
Is the TSH assay wrong?
• Double blind randomized trial
• TSH 0.3-4.8
• Doses of T4 in random order
- Low dose 2.0-4.8
- Middle dose 0.3-1.9
- High dose <0.3
• Patients maintained on variable
doses for 1 yearJCEM 91:2624, 2006
Effect of Targeting High and Low Ends
of TSH Normal Range
No Significant Treatment Effect
• Well being
• Hypothyroid symptoms
• Quality of life
• Cognitive function
• Treatment preference
JCEM 91:2624 2006
Percent change in BMI, percent change in body fat, and
absolute change in LDL cholesterol in patients maintained
for one year with TSH values of approximately 3 mlU/L
(black bars) and approximately 1 mlU/L (gray bars). TSH
differences are significant; differences in other parameters
are non-significant. Thyroid 21: 355, 2011
TSH Levels and Changes in Body Composition
• Small changes in levothyroxine do not
produce measurable changes in
hypothyroid symptoms or well being
• TSH target for hypothyroidism should not
differ from the general reference range
• Changing upper limit of normal TSH to
2.5 would increase the number of
patients with subclinical hypothyroidism
and there is no consensus that
subclinical disease (TSH 5-10) requires
treatment
Take Home Points
A 40 y.o. has been taking thyroid
hormone for 6 months but didn’t bring
the pills to her clinic visit. Because she
is fatigued her dose has been steadily
increased over the last 3 months. Now
her complaints are tachycardia and
heat intolerance.
Labs today: free T4 0.6 (0.8-1.8) and
TSH 0.01 (0.2-4.2).
What is wrong with this picture?
What is the best thyroid hormone
replacement?
• Levothyroxine (T4)
• Triiodothyronine (T3)
• Combination T4/T3
• “Natural” thyroid hormone
T4
T4
T3
T3
No
rmal
Ran
ge
Hours After T3 Hours After T4
T4 and T3 Concentrations After Thyroid Hormone
.T4T3
• Short half-life
• Risky in elderly and in those with
CV disease
• If you must use it monitor TSH to
assess adequacy of dose
• Many labs don’t do routine T3 or
free T3 assays
Avoid T3 in Treatment of
Hypothyroidism
JAMA 299, 2008
A 79 y.o. has taken 1½ grains of Armour
thyroid for 20 years. Now she is fatigued, has
lost weight and has constipation. Her BMI is 26
and her thyroid is not palpable. Her B/P is
120/80 and pulse is 88.
FT4 0.6 (0.8-1.8), TSH 1.2 (0.2-4.2), T3 2.1 (0.8-2).
What should you recommend?
A. Increase dose by ½ grain
B. Decrease dose by ½ grain
C. Change to levothyroxine
D. Continue current therapy
• Armour thyroid extract
• 1 grain contains 38 µg T4 and 9 µg
T3 roughly equivalent to 74 µg of
levothyroxine
• Batch to batch variability
• Not always readily available
• Unless you only measure TSH,
results can be confusing
“Natural” Thyroid Hormone
HypothalamusTRH
TSH
T4, T3
Target cells
throughout body
Anterior
Pituitary
Thyroid
gland
+
+
T3
• Thyroid makes
both T4 and T3
• Is combination
therapy more
effective?
• 8/9 randomized trials showed no
difference in
- quality of life
- cognitive function
- psychometric performance
- treatment preference
• Combinations do not replicate
physiologic T4/T3 production
Randomized Trials Comparing
Combination T4 /T3 vs T4 Alone
JCEM 91:2592, 2006
• Patients with hypothyroidism should
be treated with levothyroxine as
monotherapy
• Levothyroxine is treatment of
choice due to long term experience,
favorable side effect profile, ease of
administration, long half-life and low
cost
American Thyroid Association
Thyroid 24:1670, 2014
Take Home Points
• Be sympathetic but don’t try to fix all
problems with thyroid hormone
• Don’t over replace or change therapy
based on symptoms alone
• Eventual understanding of molecular
regulation of thyroid hormone may lead
to better understanding of how to treat
How can we help the symptomatic
patient who has normal TFT’s?
A 40 y.o. with longstanding
hypothyroidism has a FT4 1.5 (0.9-1.5)
and TSH < 0.01 (0.2-4.2) at a routine visit.
She takes 0.15 mg of levothyroxine daily.
Her pulse is 96, BP 110/80 and she has
hyperactive reflexes.
You recommend lowering the dose but
she is worried about gaining weight.
She asks “is there any harm in letting
TFT’s run a little high?”
1
1.9
3.6
1
2.8
4.5
1
22.3
0
1
2
3
4
5
6
Od
ds R
ati
o
TSH 0.5-5.5
TSH 0.1-0.5
TSH <0.1
Hip Vertebral NonSpine
Risk of Fracture in Women with Low TSH
Ann Intern Med 2001
Incidence of Atrial Fibrillation in Subclinical
Hyperthyroidism
30
Perc
en
t w
ith
Atr
ial F
ibri
llati
on
NEJM 331:1249, 1994
TSH ≤ 0.1 mU/L
20
10
0TSH 0.1-0.4 mU/L TSH ≥ 0.5 mU/L
A 42 y.o. man had these tests at a visit to Neurology for evaluation of headaches.
The headaches have improved, he feels great, his exam is normal and the thyroid is not enlarged.
FT4 1.2 (0.8-1.8)
TSH 5.2 (0.2-4.2)
What is the next step?
Subclinical Hypothyroidism
• Normal FT4
• Mildly TSH
• Asymptomatic
• Prevalence higher in women
• ~30% may develop hypothyroidism
Thyroid Hormone Therapy for Older Adults
With Subclinical Hypothyroidism
• 737 adults
• TSH 4.6-10
• Levothyroxine vs placebo
• Changes in hypothyroid symptoms
and tiredness score at 1 year
• No apparent benefit in older patients
NEJM 376:2534, 2017
Whether to Treat Subclinical
Hypothyroidism is Controversial
One Approach
• Enlarged gland
• Hyperlipidemia
• TSH >10 mU/L
• Elevated antithyroid antibodies
A 40 y.o. complains of fatigue,
amenorrhea, cold intolerance,
dry skin and weight gain. Six
months ago in your office her
TSH was normal.
Today she has the same
complaints along with constipation.
On exam she has delayed DTR’s.
Her TSH is 1 (0.2-4.2) and you
reassure her that her thyroid is ok.
One month later she is back
feeling worse and she also
complains of severe headaches.
What is wrong with this picture?
Secondary
Hypothyroidism
• FT4 and TSH
• Patient may have
hypopituitarism
• Measuring TSH
alone may
miss or delay
diagnosis
A 35 y.o. has had amenorrhea
since the birth of her second child
1½ years ago. She has noted a 10
pound weight gain, constipation
and cold intolerance. On exam
she has dry skin and periorbital
puffiness and her thyroid is smooth
and not enlarged. Her TSH is 0.9
(0.2-4.2) and a repeat TSH is 1.1
How can she have such
prominent symptoms of
hypothyroidism and a normal
TSH?
What test will confirm your
suspicion of hypothyroidism?
Secondary Hypothyroidism
• Symptoms and replacement therapy are the same as in primary hypothyroidism
• Monitor replacement with free T4
• Evaluate the pituitary adrenal axis as patient may also have adrenal insufficiency
• Universal screening is controversial
• Use targeted approach
- history of autoimmune disease
- family history of thyroid disease
- history of elevated TPO antibodies
- recurrent miscarriage
- history of head or neck irradiation
- BMI >40 kg/m2
Screening for Hypothyroidism
in Pregnancy
• Requirements for thyroid hormone
may increase by 50%
• When hypothyroidism diagnosed,
adjust dose and repeat levels every
30-40 days
• Requirements will decrease after
delivery
Hypothyroidism in Pregnancy
Thyroid 21:1081, 2011
• Isolated maternal hypothyroxinemia and normal TSH
• Effect on perinatal and neonatal outcome is unclear
• Isolated low free T4 during second trimester not associated with cognitive dysfunction (JCEM 2012)
• Guidelines do not support treatment (Thyroid 21:1081, 2011)
Low Maternal Free T4