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

Free T4 T3 Reverse T3

TSH Free T3

TPO Ab

TSI

Evaluating the Thyroid

Trachea

Carotid

Strap Muscles

Rt. lobe Left Lobe

Skin

Thyroid Ultrasound

• 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

HOT COLD

• 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

JCEM 91: 2592, 2006

Combination Therapy

• 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

0.1-2.5 1st trimester

0.2-3.0 2nd trimester

0.3-3.0 3rd trimester

Trimester Specific TSH

• 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

ATA Guidelines - Thyroid Nodule. Thyroid

26:1200, 2016.

ATA Guidelines - Hypothyroidism. Thyroid

24:1670, 2011.

ATA Guidelines – Pregnancy. Thyroid

21:593, 2011.

References