1. Interpretation of Thyroid Function Tests
Fadi Nabhan, MD
Assistant Professor of Medicine
Endocrinology, Diabetes & Metabolism

2. At the end of this module, you will learn to:
Learning Objectives
At the end of this module, you will learn to:
Interpret the thyroid function tests in a patient with suspected thyroid hormone excess.
Interpret the thyroid function tests in a patient with suspected thyroid hormone deficiency.
Distinguish primary from secondary thyroid disease
Describe euthyroid sick syndrome.
Describe effect of drugs mainly estrogen and Amiodarone on thyroid function tests.
Discuss which radiological exam is appropriate for the diagnosis of some thyroid disorder.

3. Case #1
This is a 50 year old female who presented to her primary care physician with complaints of fatigue, weight gain, sleepiness, cold intolerance and feeling depressed.
In reviewing her symptoms further she also mentioned symptoms of muscle weakness especially when climbing stairs, shortness of breath on exertion, dry skin and thinning of scalp hair

4. Case #1
Physical exam: BP: 140/95, Heart Rate: 56, RR: 18, T: Exam is unremarkable aside from thyroid that was slightly enlarged without palpable nodules.
Laboratory Studies: TSH 20 uIU/ml (nl ), Free T4: 0.4 ng/dl (nl ).

5. Case #1 Question A
The patient’s elevated TSH is the result of which of the following?
A- TSH producing pituitary adenoma
B- Central Hypothyroidism
C-Loss of the positive feedback that thyroid hormone exerts on the TSH producing cells in the pituitary gland
D- Loss of the negative feedback that thyroid hormone exerts on the TSH producing cells in the pituitary gland

6. Case #1
This is a 50 year old female who presented to her primary care physician with complaints of fatigue, weight gain, sleepiness, cold intolerance and feeling depressed.
In reviewing her symptoms further she also mentioned symptoms of muscle weakness especially when climbing stairs, shortness of breath on exertion, dry skin and thinning of scalp hair

7. Case #1
Physical exam: BP: 140/95, Heart Rate: 56, RR: 18, T: Exam is unremarkable aside from thyroid that was slightly enlarged without palpable nodules.
Laboratory Studies: TSH 20 uIU/ml (nl ), Free T4: 0.4 ng/dl (nl ).

8. Hypothalamic-Pituitary-Thyroid Axis Physiology
TRH
Hypothalamus +
TSH
Anterior Pituitary + T3
T4- T3
Thyroid
The thyroid gland production of thyroid hormone is regulated by Hypothalamus and pituitary. Hypothalamus produces TRH which stimulated the anterior pituitary to produce TSH. TSH then stimulates the thyroid to produce Thyroid hormones (T4 and T3).
Thyroid hormone then exerts negative feedback on hypothalamus and pituitary. T4
Target Tissues T3

9. Case #1 Question A
The patient’s elevated TSH is the result of which of the following?
A- TSH producing pituitary adenoma
B- Central Hypothyroidism
C-Loss of the positive feedback that thyroid hormone exerts on the TSH producing cells in the pituitary gland
D- Loss of the negative feedback that thyroid hormone exerts on the TSH producing cells in the pituitary gland

10. Case #1 Question B
Elevation in Thyroid Peroxidase (TPO) antibodies is possible in this patient?
A- True
B- False

11. Causes of Primary Hypothyroidism
Autoimmune Thyroiditis
Postsurgical
Post ablative
Iodine deficiency
Post neck external beam radiation
Infiltrative Disorders
Medications: Examples: Lithium and Amiodarone

12. Case #2
This is a 28 year old female who presented to her primary care physician with complaints of palpitation, tremors, weight loss despite increased appetite and heat intolerance
In reviewing her symptoms further she also mentioned symptoms of muscle weakness especially when climbing stairs, shortness of breath on exertion, insomnia and mood swings

13. Case #2
Physical exam: BP: 140/60, Heart Rate: 100, RR: 18, T: Exam is unremarkable aside from lid lag and stare in eyes with proptosis, heart with tachycardia but regular, thyroid that was enlarged without palpable nodules and with a bruit.
Laboratory Studies: TSH <0.03 uIU/ml ( ),
Free T4: 4 ng/dl ( ) Free T3: 8 pg/ml (nl ).

14. Case #2 Question A
This patient’s hyperthyroidism is most likely primarily caused by which mechanism?
A- Increased production of thyroid hormones by thyroid follicular cells
B- Increased production of TSH by a pituitary tumor
C- Increased release of stored thyroid hormone by destructed thyroid follicular cells.
D- None of the above

15. Case #2
This is a 28 year old female who presented to her primary care physician with complaints of palpitation, tremors, weight loss despite increased appetite and heat intolerance
In reviewing her symptoms further she also mentioned symptoms of muscle weakness especially when climbing stairs, shortness of breath on exertion, insomnia and mood swings

16. Case #2
Physical exam: BP: 140/60, Heart Rate: 100, RR: 18, T: Exam is unremarkable aside from lid lag and stare in eyes with proptosis, heart with tachycardia but regular, thyroid that was enlarged without palpable nodules and with a bruit.
Laboratory Studies: TSH <0.03 uIU/ml ( ),
Free T4: 4 ng/dl ( ) Free T3: 8 pg/ml (nl ).

17. Case #2 Question A
This patient’s hyperthyroidism is most likely primarily caused by which mechanism?
A- Increased production of thyroid hormones by thyroid follicular cells
B- Increased production of TSH by a pituitary tumor
C- Increased release of stored thyroid hormone by destructed thyroid follicular cells.
D- None of the above

18. Case #2 Question B
What is the next test that you should order to further evaluate this patient’s abnormal thyroid function test?
A- I 123 thyroid uptake and scan
B- MRI of thyroid
C- CT scan of neck with contrast
D- MRI of pituitary
E- Ultrasound of thyroid

19. Thyrotoxicosis HIGH UPTAKE Graves Disease Toxic Nodular Goiter
TSH-producing Pituitary Tumor
LOW UPTAKE
Subacute Thyroiditis
Expanded Iodine Pool
Surreptitious Thyroid Hormone Ingestion
The causes of thyrotoxicosis can be differentiated based on results of iodine uptake and scan to low and high uptake.
Iodine uptake and scan test is essential in evaluating the causes of thyrotoxicosis.

20. Case #3
This is a 28 year old female who presented to her primary care physician with complaints of neck pain, palpitation, tremors, weight loss despite increased appetite and heat intolerance.
In reviewing her symptoms further she also mentioned symptoms of muscle weakness especially when climbing stairs, shortness of breath on exertion, insomnia and mood swings.
The patient also reported a recent history of upper respiratory infection 20

21. Case #3 Physical exam: BP: 120/70, Heart Rate: 100, RR: 18, T: 36.6.
Exam is unremarkable aside from anterior neck tenderness along with enlarged thyroid but without palpable nodules.
Laboratory Studies: TSH <0.03 uIU/ml (nl ), Free T4: 4 ng/dl (nl ) Free T3: 8 pg/ml (nl ). Sed rate: 122 mm/hr (nl 0-19).

22. Case #3
This patient’s hyperthyroidism is most likely primarily caused by which mechanism?
A- Increased production of thyroid hormones by thyroid follicular cells
B- Increased production of TSH by a pituitary tumor
C- Increased conversion of T4 to T3 in the periphery
D- Increased release of stored thyroid hormone by destructed thyroid follicular cells.

23. Case #3
This is a 28 year old female who presented to her primary care physician with complaints of neck pain, palpitation, tremors, weight loss despite increased appetite and heat intolerance.
In reviewing her symptoms further she also mentioned symptoms of muscle weakness especially when climbing stairs, shortness of breath on exertion, insomnia and mood swings.
The patient also reported a recent history of upper respiratory infection 23

24. Case #3 Physical exam: BP: 120/70, Heart Rate: 100, RR: 18, T: 36.6.
Exam is unremarkable aside from anterior neck tenderness along with enlarged thyroid but without palpable nodules.
Laboratory Studies: TSH <0.03 uIU/ml (nl ), Free T4: 4 ng/dl (nl ) Free T3: 8 pg/ml (nl ). Sed rate: 122 mm/hr (nl 0-19).

25. Case #3
This patient’s hyperthyroidism is most likely primarily caused by which mechanism?
A- Increased production of thyroid hormones by thyroid follicular cells
B- Increased production of TSH by a pituitary tumor
C- Increased conversion of T4 to T3 in the periphery
D- Increased release of stored thyroid hormone by destructed thyroid follicular cells.

26. Clinical Course of Subacute Thyroiditis
Serum T4
Serum TSH
Thyroid RAIU
Increased           
Normal       
The graph illustrates typical levels of TSH, thyroid radioactive iodine uptake (RAIU), and serum T4 in a patient for several months after delivery.1
Postpartum thyroid dysfunction typically occurs in three phases.1
Within 2 to 4 months postpartum, mild nonspecific symptoms of hyperthyroidism may appear. These symptoms, which can include enlargement of a preexisting goiter, may be difficult to differentiate from the tiredness, irritability, and weight loss that occur after delivery.1,2 Symptoms usually last 2 to 6 weeks.2
Between 3 and 8 months after delivery, mild hypothyroidism may occur, often with a palpable thyroid gland. This phase also lasts 2 to 6 weeks. Few patients remain permanently hypothyroid; most recover spontaneously within 3 to 9 months postpartum.1,2
The major difference between the toxic phase of PPT and Graves’ disease occurring in the postpartum period is that RAIU is low in the former and high in the latter.
1. Mestman JH et al. Endocrinol Metab Clin N Amer. 1995;24:41.
2. Emerson CH. In: Werner and Ingbar’s The Thyroid, 7th ed. 1996:1021.
Clinical course of Subacute thyroiditis.
First phase is hyperthyroid phase where the thyroid hormone stored in the thyroid is released and this leads to elevated T4 and suppressed TSH. Due to the destructed thyroid gland, iodine uptake is low.
Second phase is hypothyroid phase where the released thyroid hormones are now cleared but the thyroid is still not repaired to be able to produce thyroid hormone. Frequently patients are not symptomatic in this phase and do not require thyroid hormone replacement
The third phase then is when the thyroid is repaired and is able again to produce thyroid hormone and this is the euthyroid phase.    
Decreased       
Hyperthyroid
Hypothyroid
Euthyroid 26

27. Case #4
This is a 28 year old female who is referred to endocrinologist by her primary care physician due to abnormal thyroid function test
The patient denies major complaints. She has mild weight gain and fatigue. This has prompted her primary care physician to order thyroid function tests. Rest of tests including kidney, liver functions and complete blood count were normal.
Medications: Oral contraceptives 27

28. Case #4
Physical exam: BP: 120/70, Heart Rate: 80, RR: 18, T: Exam is unremarkable including normal thyroid exam.
Laboratory Studies: TSH: 1.5 (nl ), Total T4: 14 mcg/dl (nl ) 28

29. Case #4 Which statement is most correct?
A- Ordering free T4 may clarify the thyroid function tests
B- Elevated total T4 could be caused by elevated Thyroxin Binding Globulins which is caused by estrogen in oral contraceptive.
C- No further tests are needed and patient should undergo MRI of pituitary to look for TSH producing adenoma.
D- To further clarify the cause of hyperthyroidism, the patient should undergo I 123 thyroid uptake and scan
E- A and B are both correct

30. Case #4
This is a 28 year old female who is referred to endocrinologist by her primary care physician due to abnormal thyroid function test
The patient denies major complaints. She has mild weight gain and fatigue. This has prompted her primary care physician to order thyroid function tests. Rest of tests including kidney, liver functions and complete blood count were normal.
Medications: Oral contraceptives 30

31. Case #4
Physical exam: BP: 120/70, Heart Rate: 80, RR: 18, T: Exam is unremarkable including normal thyroid exam.
Laboratory Studies: TSH: 1.5 (nl ), Total T4: 14 mcg/dl (nl ) 31

32. Case #4 Which statement is most correct?
A- Ordering free T4 may clarify the thyroid function tests
B- Elevated total T4 could be caused by elevated Thyroxin Binding Globulins which is caused by estrogen in oral contraceptive.
C- No further tests are needed and patient should undergo MRI of pituitary to look for TSH producing adenoma.
D- To further clarify the cause of hyperthyroidism, the patient should undergo I 123 thyroid uptake and scan
E- A and B are both correct

33. Case #5
This is a 28 year old female who is referred to endocrinologist by her primary care physician due to abnormal thyroid exam
The patient denies major complaints. However few weeks ago she felt a lump in her neck. This is in the anterior mid neck and slightly to the right side. It is not tender
She denies changes in weight gain or level of energy. She denies palpitation, muscle weakness, change in bowel movement and heat or cold intolerance. 33

34. Case #5
Physical exam: BP: 120/70, Heart Rate: 80, RR: 18, T: Exam is unremarkable except palpable nodule in the right anterior neck that moves with swallowing and measures about 2 CM. It is not tender.
Laboratory Studies: Normal thyroid function tests. 34

35. Case #5 What is the most appropriate next diagnostic study?
A- Iodine I 123 thyroid uptake and scan
B- Ultrasound of thyroid
C- MRI of neck
D- Repeat thyroid function test
E- B and C are both correct

36. Case #5
This is a 28 year old female who is referred to endocrinologist by her primary care physician due to abnormal thyroid exam
The patient denies major complaints. However few weeks ago she felt a lump in her neck. This is in the anterior mid neck and slightly to the right side. It is not tender
She denies changes in weight gain or level of energy. She denies palpitation, muscle weakness, change in bowel movement and heat or cold intolerance. 36

37. Case #5
Physical exam: BP: 120/70, Heart Rate: 80, RR: 18, T: Exam is unremarkable except palpable nodule in the right anterior neck that moves with swallowing and measures about 2 CM. It is not tender.
Laboratory Studies: Normal thyroid function tests. 37

38. Case #5 What is the most appropriate next diagnostic study?
A- Iodine I 123 thyroid uptake and scan
B- Ultrasound of thyroid
C- MRI of neck
D- Repeat thyroid function test
E- B and C are both correct

39. Case #6 This is a 60 year presents with abnormal thyroid exam
The patient has a long standing history of goiter with normal thyroid function tests and she has never taken any medication for her thyroid before.
She has a history of cardiac arrhythmia controlled on Amiodarone
She has symptoms of fatigue weight loss, muscle weakness and mood changes. 39

40. Case #6
Physical exam: BP: 120/70, Heart Rate: 80, RR: 18, T: Exam is unremarkable except enlarged nodular thyroid.
Laboratory Studies: TSH <0.03 (nl ), Free T4: 3 (nl ). 40

41. Case #6
You suspect that Amiodarone is causing the abnormal thyroid function tests. What will be the potential mechanism by which Amiodarone is causing that in this patient?
A- Increased production of thyroid hormone by thyroid gland due to the iodine content in Amiodarone
B- Increased release of stored thyroid hormone in thyroid follicular cells.
C- Inhibition of thyroid hormone production by iodine content in Amiodarone
D- All of the above
E- A and B

42. Case #6 This is a 60 year presents with abnormal thyroid exam
The patient has a long standing history of goiter with normal thyroid function tests and she has never taken any medication for her thyroid before.
She has a history of cardiac arrhythmia controlled on Amiodarone
She has symptoms of fatigue weight loss, muscle weakness and mood changes. 42

43. Case #6
Physical exam: BP: 120/70, Heart Rate: 80, RR: 18, T: Exam is unremarkable except enlarged nodular thyroid.
Laboratory Studies: TSH <0.03 (nl ), Free T4: 3 (nl ). 43

44. Case #6
You suspect that Amiodarone is causing the abnormal thyroid function tests. What will be the potential mechanism by which Amiodarone is causing that in this patient?
A- Increased production of thyroid hormone by thyroid gland due to the iodine content in Amiodarone
B- Increased release of stored thyroid hormone in thyroid follicular cells.
C- Inhibition of thyroid hormone production by iodine content in Amiodarone
D- All of the above
E- A or B

45. Amiodarone Effect on Thyroid function
Hypothyroidism
Hyperthyroidism:
Type I: Increased synthesis of thyroid hormone
Type II: destructive thyroiditis

46. Case #7
This is a 60 year old male who is currently in the intensive care unit due to hypovolemic shock from GI bleed. He also has complicated urinary tract infection.
Endocrine service was consulted due to abnormal thyroid function tests.
Past Medical and Surgical History include hypertension, and coronary artery disease
Currently in the intensive care unit he is receiving IV fluid and blood transfusion and IV antibiotics. 46

47. Case #7
Physical exam: BP: 100/70, Heart Rate: 92, RR: 20, T: Thyroid is not enlarged and without palpable nodules.
Laboratory Studies: TSH:0.1uIU/ml (nl ), Free T4: 1 ng/dl (nl ), Total T4: 2 ug/dl (nl ). Free T3: 1.5 pg/ml (nl ). 47

48. Case #7
What is the most likely explanation of the patient’s thyroid function tests?
A- Decreased thyroid hormone binding proteins leading to low total T4
B- Hypothyroidism
C- Decreased conversion from T4 to T3 leading to low T3
D- A and C
E- None of the above

49. Case #7
This is a 60 year old male who is currently in the intensive care unit due to hypovolemic shock from GI bleed. He also has complicated urinary tract infection.
Endocrine service was consulted due to abnormal thyroid function tests.
Past Medical and Surgical History include hypertension, and coronary artery disease
Currently in the intensive care unit he is receiving IV fluid and blood transfusion and IV antibiotics. 49

50. Case #7
Physical exam: BP: 100/70, Heart Rate: 92, RR: 20, T: Thyroid is not enlarged and without palpable nodules.
Laboratory Studies: TSH:0.1uIU/ml (nl ), Free T4: 1 ng/dl (nl ), Total T4: 2 ug/dl (nl ). Free T3: 1.5 pg/ml (nl ). 50

51. Case #7
What is the most likely explanation of the patient’s thyroid function tests?
A- Decreased thyroid hormone binding proteins leading to low total T4
B- Hypothyroidism
C- Decreased conversion from T4 to T3 leading to low T3
D- A and C
E- None of the above

52. Sick Euthyroid Syndrome
Decreased Conversion of T4 to T3
Low total T4
Low TSH
Low Free T4 in more severe cases

53. Summary
Interpret the thyroid function tests in a patient with suspected thyroid hormone excess.
Interpret the thyroid function tests in a patient with suspected thyroid hormone deficiency.
Distinguish primary from secondary thyroid disease
Describe euthyroid sick syndrome.
Describe effect of drugs including estrogen and amiodarone on thyroid function.
Discuss which radiological exam is appropriate for the diagnosis of each thyroid disorder.

54. Reference Slide Harrison Online
Clinical Practice Guidelines For Hypothyroidism in Adults. Cosponsored by the American Thyroid Association and the American Association of Clinical Endocrinologists. Endocrine Practice Vol 18 No 6 Nov/Dec 2012
Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologist. Endocrine Practice Vol 17 No 3 May/June 2011

55. Thank You for completing this module
If you have any questions, please contact me.
Fadi Nabhan MD:

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