HYPOTHYROIDISM














  • Subclinical hypothyroidism defined as TSH > 4.5 mU/L and T4 ≥ 57.9 nmol/L
  • Clinical hypothyroidism defined as TSH > 4.5 mU/L and T4 < 57.9 nmol/L
  • Data from NHANES III Study
Prevalence of hypothyroidism in U.S. population ≥ 12 years old
Total White Black Mexican-American Remaining races
Subclinical hypothyroidism
(% of population)
4.3% 4.8% 1.6% 3.9% 4.0%
Clinical hypothyroidism
(% of population)
0.3% 0.4% 0.1% 0.2% 0.2%




  • Reference [1,6,23]
RISK FACTORS FOR PRIMARY HYPOTHYROIDISM
Risk factor Notes
Iodine deficiency
  • Most common cause worldwide
  • Rare in developed countries
Female sex
  • Females are affected more than males
Advancing age
  • Prevalence increases with age
Ethnicity
  • Whites are affected more than blacks and Mexican-Americans
Family history of autoimmune thyroid disease
Thyroid peroxidase antibodies (TPOAb)
  • In patients with subclinical hypothyroidism and elevated TPOAb titers, 4.3%/year will develop hypothyroidism
  • See autoimmune thyroiditis
Pregnancy
  • Postpartum thyroiditis - may see period of hyperthyroidism (1 - 6 months postpartum) followed by a period of hypothyroidism for 4 - 6 months
History of thyroid disease/treatment
  • Radioactive iodine
  • Thyroid surgery
  • External beam radiation treatment
Medications
Presence of other autoimmune disease
  • Type 1 diabetes (10% of patients with Type 1 diabetes have hypothyroidism)
  • Addison's disease
  • Pernicious anemia
  • Myasthenia gravis
  • Celiac disease
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Vitiligo
Genetic disorders
  • Down's syndrome
  • Turner's syndrome


  • Reference [1]
RISK FACTORS FOR SECONDARY HYPOTHYROIDISM
Cause Notes
Pituitary or hypothalamic tumors
  • Craniopharyngioma
Infiltrative inflammatory diseases
  • Granulomatous (ex. Sarcoidosis)
  • Lymphocytic (ex. lymphocytic hypophysitis)
Medications
Iatrogenic
  • Brain surgery
  • External beam radiation
Hemorrhagic necrosis
  • Sheehan's syndrome






  • Reference [1,10]
Screening recommendations for asymptomatic hypothyroidism
Organizations Screening recommendation
  • USPSTF
  • American Academy of Family Practice
  • Insufficient evidence to make recommendation for screening nonpregnant, asymptomatic adults
  • American Thyroid Association
  • American Assoc of Clinical Endocrinologist
  • Consider screening patients ≥ 60 years old
  • Association for Clinical Biochemistry
  • British Thyroid Association
  • British Thyroid Foundation
  • Do not screen







  • Data from NHANES III Study. Ranges are from a subpopulation of 13,344 patients without thyroid disease or detectable thyroid antibodies.
  • Reference [15]
TSH Values in Thyroid Disease-free Population
2.5th - 97.5th percentile TSH (mIU/L) values
Age range 20 - 29
(Median)
30 - 39
(Median)
40 - 49
(Median)
50 - 59
(Median)
60 - 69
(Median)
70 - 79
(Median)
≥ 80
(Median)
Black 0.36 - 3.30
(1.10)
0.33 - 3.24
(1.10)
0.42 - 3.74
(1.30)
0.44 - 3.99
(1.40)
0.35 - 4.20
(1.58)
0.39 - 5.20
(1.50)
0.42 - 4.60
(1.50)
Mexican-American 0.47 - 3.62
(1.33)
0.40 - 3.75
(1.30)
0.40 - 3.99
(1.49)
0.55 - 4.85
(1.50)
0.51 - 5.54
(1.80)
0.59 - 7.12
(2.13)
0.55 - 7.84
(1.91)
White 0.46 - 3.60
(1.30)
0.46 - 3.76
(1.37)
0.57 - 3.95
(1.49)
0.52 - 3.97
(1.58)
0.56 - 4.31
(1.66)
0.46 - 5.60
(1.80)
0.41 - 6.56
(1.99)




  • Reference [19]
Hyperthyroidism Hypothyroidism High TBG Low TBG
Total T4 High Low High Low
T3 resin uptake High Low Low High



  • Data from NHANES III Study. Ranges are from a subpopulation of 16,533 who did not report thyroid disease, goiter, or taking thyroid medications.
  • Positive TPOAb defined as ≥ 0.5 U/ml
Percent of Thyroid Disease-free Patients with Positive TPOAb
Age range 20 - 29 30 - 39 40 - 49 50 - 59 60 - 69 70 - 79 ≥ 80
Female 10.4 12.6 15.8 17.1 23 26.2 26.5
Male 5.5 8.4 10.6 10.1 10.2 12 10.6


  • Data from NHANES III Study. Ranges are from a subpopulation of 16,533 who did not report thyroid disease, goiter, or taking thyroid medications.
  • Positive TgAb defined as ≥ 1.0 U/ml
Percent of Thyroid Disease-free Patients with Positive TgAb
Age range 20 - 29 30 - 39 40 - 49 50 - 59 60 - 69 70 - 79 ≥ 80
Female 8.5 13.6 16 16.4 19.6 20.6 25.2
Male 5 6.6 6.8 7.9 9.6 12.9 10.1












  • Reference [1,20]
Initial dosing recommendations
Patient factor Recommendation
Little residual thyroid function or markedly elevated TSH
  • Dosing should be based on ideal body weight (IBW)
    • IBW (male) = 110 lbs + 5 lbs for each inch over 5 feet (50 kg + 2.27 kg for each 2.54 cm over 152.4 cm)
    • IBW (female) = 100 lbs + 5 lbs for each inch over 5 feet (45.45 kg + 2.27 kg for each 2.54 cm over 152.4 cm)
  • Start therapy at approximately 0.73 mcg/lb/day or 1.6 mcg/kg/day
  • Patients who have had thyroidectomy or radioiodine therapy may require higher doses
TSH ≤ 10 mIU/L
  • Lower doses are typically adequate
  • Starting dose of 25 - 50 mcg once daily may be appropriate in most patients
Dosing based on TSH level
  • One study found the following dosing regimen based on TSH level alone to be effective in most patients:
    • TSH 4 - 8 mUI/L: 25 mcg once daily
    • TSH 8 - 12 mUI/L: 50 mcg once daily
    • TSH > 12 mUI/L: 75 mcg once daily
Elderly patients
  • Lower doses (20 - 25% less) are typically adequate because of decreased lean body mass
  • Goal TSH values may be higher (see TSH values)
Patients with coronary artery disease
  • Start with lower doses (12.5 - 25 mcg once daily)
  • Increase dose gradually
  • Monitor for symptoms of angina
Pregnancy
Food
  • Food decreases the absorption of levothyroxine
  • Levothyroxine should be taken on an empty stomach, preferably 60 minutes before breakfast or ≥ 3 hours after the evening meal
Intravenous levothyroxine
  • Intravenous dose of levothyroxine should be 70% of oral dose













  • A study published in the NEJM in 2017 found that treating subclinical hypothyroidism in elderly patients (N=737, average age 74 years) had no effect on hypothyroid symptoms or tiredness. [PMID 28402245]
  • Reference [28,23]
2013 ETA recommendations for treating subclinical hypothyroidism
Age TSH value Recommendation
≤ 70 years < 10
  • If hypothyroid symptoms are present, treat for 3 months and assess response to therapy
  • If hypothyroid symptoms are absent, observe and repeat TSH and free T4 in 6 months
≤ 70 years ≥ 10
  • Treat with levothyroxine
> 70 years < 10
  • Observe and repeat TSH and free T4 in 6 months
> 70 years ≥ 10
  • Consider treatment if clear symptoms of hypothyroidism or high vascular risk





  • Reference [11,12,13]
Screening for thyroid disease in asymptomatic pregnant females
Organization Screening recommendation
American Endocrine Society No consensus agreement on whether or not to screen
American Thyroid Assoc See below
American College of Obstetricians and Gynecologists Does not recommend universal screening
European Thyroid Assoc Does not recommend routine, universal screening