Evaluation and Management of Hypothyroidism in the Primary Care Setting

1
Evaluation and Management of Hypothyroidism in
the Primary Care Setting

• Christopher P. Paulson, Maj, USAF, MC
• Faculty, Eglin AFB Family Medicine Residency

2
Case Scenario

• While precepting residents the following case is
  presented for your review
• 45 yo female with abnormal thyroid labs
  discovered during an evaluation of mild fatigue
  of several months duration

3
Case Scenario

• Past Med Hx negative for diabetes, autoimmune
  disorders, radiation exposure, and known thyroid
  disease or thyroid surgery
• Medications none
• Family Hx negative for autoimmune disorders and
  thyroid dysfunction

4
Case Scenario

• Labs
• TSH 6.73 (0.46 - 4.68) mIU/ml
• FT4 1.32 (0.71 2.19) ng/dl
• Repeat labs in 6 weeks
• TSH 6.82
• FT4 1.27

5
Case Scenario

• The patient desires thyroid replacement therapy
• The resident inquires about treatment guidelines
  for subclinical hypothyroidism
• How do you respond?

6
Learning Objectives

• Identify common risk factors and etiologies of
  hypothyroidism
• Be able to evaluate and initiate appropriate
  treatment for hypothyroidism
• Use an evidence-based approach for population
  screening and sub-clinical disease management
• Apply management guidelines to your patient
  population

7
Overview of Hypothyroidism

• Epidemiology
• Etiology
• Evaluation and Treatment
• Subclinical Disease and Screening Guidelines
• Conclusion/Key Points

8
Epidemiology

• Incidence of Hypothyroidism
• 1 in areas with adequate iodine (U.S.)
• Female to Male ratio 81
• Incidence increases with age

Vanderpump, MP, Tunbridge, WM. The epidemiology
of thyroid disease. In The Thyroid A
Fundamental and Clinical Text, 8th ed, Braverman,
LE, Utiger, RD (eds). Lippincott Williams and
Wilkins, Philadelphia, 2000. p. 467.
9
Epidemiology

• Risk Factors
• Downs Syndrome
• Turners Syndrome
• Head and neck radiation exposure
• Type 1 Diabetes
• Family history of autoimmune disease

• History of previous thyroid disorder
• Presence of other autoimmune disorders
• Postpartum state
• Family history of thyroid disorders

Larsen PR, Kronenberg HM, Melmed S, Polonsky KS,
editors. Williams textbook of endocrinology.
10th edition. Philadelphia Saunders, 2003
423-55.
10
Epidemiology

• Symptoms
• Fatigue
• Weight gain
• Headache
• Dry Skin
• Hoarseness of voice
• Irregular menses
• Decreased appetite

• Myalgias
• Parasthesias
• Somnolence
• Lethargy
• Depression
• Cold intolerance

Larsen PR, Kronenberg HM, Melmed S, Polonsky KS,
editors. Williams textbook of endocrinology.
10th edition. Philadelphia Saunders, 2003
423-55.
11
Epidemiology

• Symptoms
• Fatigue 90
• Weight gain
• Headache
• Dry Skin
• Hoarseness of voice
• Irregular menses
• Decreased appetite

• Myalgias
• Parasthesias
• Somnolence
• Lethargy
• Depression
• Cold intolerance

Larsen PR, Kronenberg HM, Melmed S, Polonsky KS,
editors. Williams textbook of endocrinology.
10th edition. Philadelphia Saunders, 2003
423-55.
12
Epidemiology

• Signs
• Nonpitting edema
• Constipation
• Memory defects
• Coarse skin
• Dry skin
• Brittle nails
• Bradycardia
• Ataxia

• Diminished libido
• Bleeding tendencies
• Alopecia
• Macroglossia
• Slowed speech
• Dementia
• Psychosis
• Slowed reflexes

Larsen PR, Kronenberg HM, Melmed S, Polonsky KS,
editors. Williams textbook of endocrinology.
10th edition. Philadelphia Saunders, 2003
423-55.
13
Etiology

• Primary hypothyroidism (95 99)
• Chronic autoimmune thyroiditis (Hashimotos)
• Goitrous
• Atrophic
• Iatrogenic
• Thyroidectomy
• Radioiodine treatment
• External beam radiation

Farwell, AP, Ebner, SA, editors. Hypothyroidism.
In Noble Textbook of Primary Care Medicine,
3rd ed, Mosby 2001.
14
Etiology

• Primary hypothyroidism
• Iodine deficiency (most common world-wide)
• Drugs
• Lithium, amiodarone, etc
• Infiltrative disease - rare
• Fibrous thyroiditis (Reidels thyroiditis)
• Hemochromatosis
• Scleroderma
• Others

Farwell, AP, Ebner, SA, editors. Hypothyroidism.
In Noble Textbook of Primary Care Medicine,
3rd ed, Mosby 2001.
15
Etiology

• Primary hypothyroidism
• Congenital
• Transient Hypothyroidism
• Postpartum
• Subacute (granulomatous) thyroiditis
• Subtotal thyroidectomy

Farwell, AP, Ebner, SA, editors. Hypothyroidism.
In Noble Textbook of Primary Care Medicine,
3rd ed, Mosby 2001.
16
Etiology

• Secondary and Tertiary hypothyroidism
• Tumor
• Postpartum pituitary necrosis (Sheehans)
• Hypophysitis
• Infiltrating disease
• TSH or TRH deficiency
• Trauma
• Radiation therapy

Farwell, AP, Ebner, SA, editors. Hypothyroidism.
In Noble Textbook of Primary Care Medicine,
3rd ed, Mosby 2001.
17
Etiology

• Other
• Thyroid hormone resistance very rare

Farwell, AP, Ebner, SA, editors. Hypothyroidism.
In Noble Textbook of Primary Care Medicine,
3rd ed, Mosby 2001.
18
Evaluation

• When to evaluate
• Signs or symptoms suggestive of hypothyroidism
• Periodic assessment for high risk medications
  (amiodarone, lithium, etc.)
• Screening at risk populations?
• Controversial addressed in screening section

19
Evaluation

• Assess risk factors for hypothyroidism
• Medications (lithium, amiodarone, etc)
• History of head or neck radiation exposure
• Presence of Downs or Turners
• Family or personal history of autoimmune or
  thyroid disorders
• Type 1 diabetes

20
Evaluation
Basic Thyroid Labs
TSH
FT4
Primary Hypothyroidism
Subclinical Hypothyroidism
Secondary or Tertiary Hypothyroidism
Thyroid Hormone Resistance (pt is clinically
hypothyroid)
21
Evaluation

• Primary hypothyroidism
• Proceed to treatment
• Further evaluation generally not indicated
• For postpartum hypothyroidism, serial TSH and
  FT4, treat only if significantly symptomatic

22
Evaluation

• Secondary or tertiary hypothyroidism
• Image the sellar and suprasellar regions with MRI
  to evaluate for mass
• Screen for other hypothalamic or pituitary
  disease
• Adrenocortical, posterior pituitary, and gonadal
  dysfunction
• Consider consultation

23
Evaluation

• Thyroid hormone resistance
• Exceedingly rare
• If suspected consultation is appropriate
• Subclinical hypothyroidism
• Addressed in later section

24
Treatment Guidelines

• Standard Replacement Therapy
• Synthetic thyroxine (T4)
• 1.6 mcg/kg/day lean body mass
• 112 mcg in 70kg adult
• Full dose recommended regardless of degree of
  hypothyroidism
• Reassess after 6 weeks with TSH

Roos, A, Linn-Rasker, SP, van Domburg, RT, et al.
The starting dose of levothyroxine in primary
hypothyroidism treatment a prospective,
randomized, double-blind trial. Arch Intern Med
2005 1651714.
25
Treatment Guidelines

• Special situations
• Elderly patients
• Start at 50 mcg/day and increase by 25 mcg/day
  every 6 weeks until TSH is normalized
• Known CAD
• Start at 25 mcg/day and increase by 25 mcg/day
  every 6 weeks until TSH is normalized

Larsen PR, Kronenberg HM, Melmed S, Polonsky KS,
editors. Williams textbook of endocrinology.
10th edition. Philadelphia Saunders, 2003
423-55.
26
Treatment Guidelines

• Special situations
• Postpartum hypothyroidism
• Treat based on moderate or severe clinical
  symptoms not based on labs
• Only 1 in 4 will require treatment
• 50 to 100 mcg per day x 12 weeks
• Discontinue and recheck thyroid labs 6 wks later

Stuckey, BG, Kent, GN, Allen, JR. The biochemical
and clinical course of postpartum thyroid
dysfunction the treatment decision. Clin
Endocrinol (Oxf) 2001 54377.
27
Treatment Guidelines

• What about liothyronine (T3) replacement?
• Physiologically active
• 20 from thyroid directly and 80 from peripheral
  conversion of T4
• Early studies indicated possible beneficial
  effects on mood, quality of life, and
  psychometric functioning

28
Treatment Guidelines

• Systematic review of the literature published in
  2005
• Levothyroxine (T4) compared with levothyroxine
  liothyronine (T3)
• 9 controlled trials included
• Beneficial results in only a single study
• Quality of life, mood, psychometric performance

Escobar-Morreale, HF. Treatment of
Hypothyroidism with Combinations of Levothyroxine
plus Liothyronine. Journal of Clinical
Endocrinology and Metabolism. Vol 90, number 8.
Aug 2005.
29
Treatment Guidelines

• Systematic review of the literature published in
  2005
• Increased incidence of side effects with T3
  including palpitations, irritability,
  nervousness, dizziness, and tremor
• Overall patient preference for T3
• Not explained by outcome measures
• No clear clinical benefit

Escobar-Morreale, HF. Treatment of
Hypothyroidism with Combinations of Levothyroxine
plus Liothyronine. Journal of Clinical
Endocrinology and Metabolism. Vol 90, number 8.
Aug 2005.
30
Subclinical Hypothyroidism

• Generally defined as few or no symptoms of
  hypothyroidism with an elevated TSH and normal
  FT4
• Historically unclear recommendations in the
  literature

31
Subclinical Hypothyroidism

• Possible benefits of treatment
• Symptom improvement
• Prevent progression to overt hypothyroidism
• Reduce lipid levels and subsequently lower risk
  of cardiovascular events
• Prevent poor developmental outcomes in children
  born to women with subclinical disease

32
Subclinical Hypothyroidism

• Possible risk of unnecessary treatment
• Development of osteoporosis
• Increased incidence of atrial fibrillation
• Cost

33
Subclinical Hypothyroidism

• What does the literature show?
• USPSTF review in 2004
• No clear difference in lipid levels or
  cardiovascular outcomes for subclinical disease
• Except for patients with known thyroid disease
• No significant symptom improvement with treatment
• Except for patients with known thyroid disease

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
34
Subclinical Hypothyroidism

• What does the literature show?
• USPSTF review in 2004
• Poor neurodevelopmental outcomes in children born
  to women with elevated TSH values in their first
  trimester
• Increase in fetal demise rate
• Average IQ at age 7 to 9 was 7 points less
  (significant)
• No studies on whether screening or treatment
  would impact outcome

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
35
Subclinical Hypothyroidism

• What does the literature show?
• USPSTF review in 2004
• No increased risk of fracture or diminished bone
  density with levothyroxine treatment
• Except in those patients on suppressive therapy
• No increased risk of atrial fibrillation with
  treatment

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
36
Subclinical Hypothyroidism

• What does the literature show?
• Other considerations
• Annual rate of progression to overt disease
• No autoimmunity lt2
• No prior thyroid disease - lt 2
• Thyroid antibodies 5-7
• Elderly with thyroid antibodies 20-24

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
37
Case Scenario - revisited

• Initial labs
• TSH 6.73
• FT4 1.32
• Repeat labs in 6 weeks
• TSH 6.82
• FT4 1.27

38
Case Scenario - revisited

• The patient desires thyroid replacement therapy
• The resident inquires about treatment guidelines
  for subclinical hypothyroidism
• Now, how do you respond? What is the evidence
  based answer?

39
Case Scenario - revisited

• The evidence-based answer
• There is no clear indication to treat
• Likelihood of progressing on to overt
  hypothyroidism in this case is very low

40
Screening Guidelines

• The American Thyroid Association
• Screen ALL adults at age 35 and then every 5
  years more frequent for high risk or symptoms
• The American College of Physicians
• Screen women older than 50 with at least one
  symptom

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
41
Screening Guidelines

• The American Association of Clinical
  Endocrinologists
• Screen women of childbearing age or during the
  first trimester

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
42
Screening Guidelines

• The American College of Obstetricians and
  Gynecologists
• Be aware if signs and symptoms of postpartum
  thyroid dysfunction and evaluate when indicated

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
43
Screening Guidelines

• AAFP
• Recommends AGAINST routine screening in
  asymptomatic patients younger than age 60
• No recommendation for those over 60

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
44
Screening Guidelines

• USPSTF
• Evidence is insufficient (I) to recommend for or
  against routine screening for thyroid disease in
  adults
• Fair evidence that TSH is useful in detecting
  subclinical disease
• Poor evidence that treatment improves clinically
  important outcomes

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
45
Screening Guidelines

• USPSTF Clinical Considerations
• Clinicians should be aware of subtle thyroid
  dysfunction particularly in high risk groups
• Elderly
• Down Syndrome
• Post-partum women
• Radiation exposure (gt20 mGy)

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
46
Screening Guidelines

• USPSTF Clinical Considerations
• Subclinical hypothyroidism
• Is associated with poor obstetric outcomes and
  poor cognitive development in children
• Evidence for dyslipidemia, atherosclerosis, and
  decreased quality of life is inconsistent and
  less convincing

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
47
Screening Guidelines

• USPSTF Discussion
• No controlled studies showing whether routine
  screening improved symptoms or health outcomes
• 2 of 3 small randomized studies demonstrated no
  benefit in treating subclinical disease
• No trials of treatment of subclinical disease for
  pregnant women

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
48
Screening Guidelines

• USPSTF Discussion
• No clear benefit demonstrated on systematic
  review of the literature for either screening
  asymptomatic adults or treating subclinical
  thyroid disease

www.ahrq.gov/clinic/uspstf/uspsthyr.htm
49
Conclusion/Key Points

• Hypothyroidism is commonly encountered in the
  primary care setting
• Be aware of signs and symptoms of hypothyroidism
  particularly in populations at risk
• There is insufficient evidence to recommend
  treatment with liothyronine (T3) over
  levothyroxine (T4)

50
Conclusion/Key Points

• There is insufficient evidence for screening
  asymptomatic patients without a history of
  thyroid disease
• There is no clear benefit in treating subclinical
  hypothyroidism
• Treatment is indicated in pregnancy due to known
  risk without treatment