Subclinical Hypothyroidism

Aka: Subclinical Hypothyroidism, Sick Euthyroid Syndrome, Euthyroid Sick Syndrome

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II. Definitions

  1. Subclinical Hypothyroidism
    1. Elevated TSH with normal Free T4

III. Epidemiology

  1. Incidence Older Men: 2-8%
  2. Incidence Older Women: 5-10%

IV. Precautions

  1. Normal TSH range increases with age up to 7.5 mIU/L for an 80 year old patient (see TSH)

V. Labs

  1. Elevated TSH with normal Free T4
  2. TPO Antibody
    1. Associated with increased risk of progression from subclinical to clinical Hypothyroidism

VI. Management: Observation

  1. Treatment is not indicated unless otherwise noted above
    1. Recheck TSH in 6-12 months
    2. See Risk of Progression to Overt Hypothyroidism below
    3. TSH often normalizes spontaneously after 12 months
      1. More than half of patients over age 55 years with TSH <10 mIU/L will normalize without treatment
      2. Diez (2004) J Clin Endocrinol Metab 89(10): 4890-7 [PubMed]

VII. Management: Treatment

  1. See Hypothyroidism
  2. Indications for Treatment
    1. Thyroid Stimulating Hormone (TSH) > 10 mU/ml or
    2. Thyroid peroxidase Antibody positive (TPO Antibody) or
    3. Symptoms with persistent mildly elevated TSH
      1. Major Depression (esp. treatment resistant)
      2. Fatigue, Constipation, Cold intolerance, Hair Loss
      3. Hyperlipidemia
      4. Goiter
      5. Hyperhomocysteinemia
      6. Coronary Artery Disease or Cardiac Risk Factors
      7. Pregnancy or expected pregnancy
  3. Levothyroxine
    1. See Levothyroxine for standard dosing protocol if TSH >10 mIU/L
    2. Dosing (indicated for TSH <10 mIU/L and indications listed above)
      1. Younger than age 50 years
        1. Start at 50 mcg daily and increase by 25 mcg every 6 weeks until goals met
      2. Over age 50 years
        1. Start at 12.5 to 25 mcg daily and increase by 12.5 to 25 mcg every 6 weeks until goals met
    3. Goals for treating Subclinical Hypothyroidism
      1. LDL Cholesterol falls
      2. Hypothyroidism symptoms improve
      3. TSH normalizes <4.0
    4. Monitoring
      1. Aim to lower Serum TSH to mid-normal: 1 to 3 mU/ml
  4. Precautions: Avoid overtreatment with excessive Levothyroxine
    1. Risk of Osteoporosis worsening, Atrial Fibrillation and increased mortality
    2. Stop Levothyroxine if persistently subclinical (TSH <10) and no symptom improvement at 3-6 months

VIII. Complications

  1. Subclinical Hypothyroidism (TSH<10 mIU/L) treatment does not improve clinical outcomes or quality of life in the elderly
    1. Stott (2017) N Engl J Med 376(26): 2534-44 [PubMed]
  2. Thyroid Stimulating Hormone (TSH) >10 mIU/L
    1. Fracture (Osteoporosis)
    2. Ischemic Heart Disease
    3. Heart Failure
  3. Coronary Artery Disease (increased risk in elderly)
    1. Treating patients with Subclinical Hypothyroidism may lower cardiovascular disease risk
    2. Biondi (2002) Ann Intern Med [PubMed]

IX. Course: Risk of longterm progression to overt Hypothyroidism

  1. TSH 4-6 mU/ml: No increased risk of future Hypothyroidism
  2. TSH >6 mU/ml: 27-42% risk of future Hypothyroidism
    1. Annual risk 5.6%
  3. TSH >6 mU/ml and Thyroid Peroxidase Antibody positive: >55% risk of future Hypothyroidism

X. References

  1. (2017) Presc Lett 25(1):4
  2. (2012) Presc Lett 19(6): 34
  3. Svec (2001) CMEA Medicine Lecture, San Diego
  4. Hueston (2001) Am Fam Physician 64(10):1717-24 [PubMed]
  5. Adlin (1998) Am Fam Physician 57(4):776-80 [PubMed]
  6. Vanderpump (1995) Clin Endocrinol 43:55 [PubMed]
  7. Wilson (2021) Am Fam Physician 103(10): 605-13 [PubMed]

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