1. Family Medicine Refresher Course April 5, 2018
Common Issues in Management of Hypothyroidism
Family Medicine Refresher Course April 5, 2018
Janet A. Schlechte, M.D.

2. Disclosure of Financial Relationships
Janet A. Schlechte, M.D.
has no relationships with any proprietary entity producing health care goods or services consumed by or used on patients.

3. Issues 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.

4. Evaluating the Thyroid
Free T T Reverse T3
TSH Free T3
TPO Ab
TSI

5. Thyroid Ultrasound Skin Strap Muscles Carotid Left Lobe Rt. lobe
Trachea

6. 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
Not assess function

7. Won’t need a scan often
Use when you want to know function of the nodule

8. HOT COLD Hot nodules will have ↓ TSH or signs of hyperthyroidism
Most nodules are cold

9. 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.

10. FT4 0.7 ( )
TSH 25 ( )
Most likely diagnosis is autoimmune hypothyroidism
Levothyroxine 1.6 µg/kg except in heart disease or elderly
Repeat TFT’s in weeks

11. One year later
FT4 1.2 ( )
TSH 4.9 ( )
Two years later
FT ( )
TSH 45 ( )
Three years later
TSH is 2, she is constipated and she can’t lose weight

12. The symptomatic patient with normal TFT’s
“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”
Study in Germany excluded patients with FH, nodules, +TPO or goiter

13. Is the TSH assay wrong?
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?

14. Effect of Targeting High and Low Ends of TSH Normal Range
Double blind randomized trial
TSH
Doses of T4 in random order
- Low dose
- Middle dose
- High dose <0.3
Patients maintained on variable doses for 1 year
JCEM 91:2624, 2006

15. No Significant Treatment Effect
Well being
Hypothyroid symptoms
Quality of life
Cognitive function
Treatment preference
JCEM 91:

16. TSH Levels and Changes in Body Composition
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

17. Take Home Points
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 would increase the number of patients with subclinical hypothyroidism and there is no consensus that subclinical disease (TSH 5-10) requires treatment

18. 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 ( ) and TSH 0.01 ( ).
What is wrong with this picture?

19. What is the best thyroid hormone replacement?
Levothyroxine (T4)
Triiodothyronine (T3)
Combination T4/T3
“Natural” thyroid hormone

20. T4 and T3 Concentrations After Thyroid Hormone. T4 T3 T4 T3
Normal Range
Hours After T3
Hours After T4

21. Avoid T3 in Treatment of Hypothyroidism
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
JAMA 299, 2008

22. A 79 y. o. has taken 1½ grains of Armour thyroid for 20 years
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 ( ), TSH 1.2 ( ), T3 2.1 (0.8-2).
What should you recommend?
Increase dose by ½ grain
Decrease dose by ½ grain
Change to levothyroxine
Continue current therapy

23. “Natural” Thyroid Hormone
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

24. Thyroid makes both T4 and T3 Is combination therapy more effective?
TRH
Hypothalamus
Thyroid makes both T4 and T3
Is combination therapy more effective? +
Anterior
Pituitary
TSH
Thyroid
gland +
T4, T3 T3
Target cells
throughout body

25. Randomized Trials Comparing Combination T4 /T3 vs T4 Alone
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
JCEM 91:2592, 2006

26. Combination Therapy
JCEM 91: 2592, 2006

27. American Thyroid Association
Take Home Points
American Thyroid Association
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
Thyroid 24:1670, 2014

28. How can we help the symptomatic patient who has normal TFT’s?
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

29. A 40 y. o. with longstanding hypothyroidism has a FT4 1. 5 (0. 9-1
A 40 y.o. with longstanding hypothyroidism has a FT4 1.5 ( ) and TSH < 0.01 ( ) 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?”

30. Risk of Fracture in Women with Low TSH
Hip
Vertebral
NonSpine
Ann Intern Med 2001 30

31. Incidence of Atrial Fibrillation in Subclinical Hyperthyroidism30 20
Percent with Atrial Fibrillation 10
TSH ≤ 0.1 mU/L
TSH mU/L
TSH ≥ 0.5 mU/L
NEJM 331:1249, 1994

32. 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.
FT ( )
TSH 5.2 ( )
What is the next step?

33. Subclinical Hypothyroidism
Normal FT4
Mildly  TSH
Asymptomatic
Prevalence higher in women
~30% may develop hypothyroidism

34. Levothyroxine vs placebo
Thyroid Hormone Therapy for Older Adults With Subclinical Hypothyroidism
737 adults
TSH
Levothyroxine vs placebo
Changes in hypothyroid symptoms and tiredness score at 1 year
No apparent benefit in older patients
NEJM 376:2534, 2017

35. Elevated antithyroid antibodies
Whether to Treat Subclinical Hypothyroidism is Controversial One Approach
Enlarged gland
Hyperlipidemia
TSH >10 mU/L
Elevated antithyroid antibodies

36. 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.

37. Today she has the same complaints along with constipation
Today she has the same complaints along with constipation. On exam she has delayed DTR’s. Her TSH is 1 ( ) 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?

38. Secondary Hypothyroidism
FT4 and TSH
Patient may have hypopituitarism
Measuring TSH alone may miss or delay diagnosis

39. 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 ( ) and a repeat TSH is 1.1

40. How can she have such prominent symptoms of hypothyroidism and a normal TSH?
What test will confirm your suspicion of hypothyroidism?

41. 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

42. Screening for Hypothyroidism in Pregnancy
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

43. Hypothyroidism in Pregnancy
Requirements for thyroid hormone may increase by 50%
When hypothyroidism diagnosed, adjust dose and repeat levels every days
Requirements will decrease after delivery
Thyroid 21:1081, 2011

44. Trimester Specific TSH
st trimester
nd trimester
rd trimester

45. Low Maternal Free T4 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)

46. References ATA Guidelines - Thyroid Nodule. Thyroid 26:1200, 2016.
ATA Guidelines - Hypothyroidism. Thyroid 24:1670, 2011.
ATA Guidelines – Pregnancy. Thyroid 21:593, 2011.