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 elevatad TSH
      1. Major Depression (esp. treatment resistant)
      2. Fatigue, Consgtipation, 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

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Ontology: Euthyroid Sick Syndromes (C0015190)

Definition (NCI) Abnormal thyroid function tests, low triiodothyronine with elevated reverse triiodothyronine, in the setting of non-thyroidal illness.(NICHD)
Definition (MSH) Conditions of abnormal THYROID HORMONES release in patients with apparently normal THYROID GLAND during severe systemic illness, physical TRAUMA, and psychiatric disturbances. It can be caused by the loss of endogenous hypothalamic input or by exogenous drug effects. The most common abnormality results in low T3 THYROID HORMONE with progressive decrease in THYROXINE; (T4) and TSH. Elevated T4 with normal T3 may be seen in diseases in which THYROXINE-BINDING GLOBULIN synthesis and release are increased.
Concepts Disease or Syndrome (T047)
MSH D005067
ICD9 790.94
ICD10 E07.81
SnomedCT 237542005
English Euthyroid Sick Syndrome, Euthyroid Sick Syndromes, EUTHYROID SICK SYNDROME <LOW T3/ LOW T4 SYNDROME>, Euthyroid sick syndrome, euthyroid sick syndrome, euthyroid sick syndrome (diagnosis), EUTHYROID SICK SYNDROME LOW T3 LOW T4 SYNDROME, Euthyroid sick-syndrome, Euthyroid Sick Syndromes [Disease/Finding], sick euthyroid syndrome, Sick-euthyroid syndrome, Sick-euthyroid syndrome (disorder), sick-euthyroid; syndrome, syndrome; sick-euthyroid, Non Thyroidal Illness Syndrome, Non-Thyroidal Illness Syndrome, Sick Euthyroid Syndrome, Syndrome, Non-Thyroidal Illness, Syndrome, Sick Euthyroid, Syndromes, Non-Thyroidal Illness
Italian Sindrome tireopatica eutiroidea, Sindrome del malato non-tiroideo, Sick Euthyroid Syndrome, Euthyroid Sick Sindromes
Japanese 甲状腺機能正常症候群, コウジョウセンキノウセイジョウショウコウグン, 低T3状態, 甲状腺機能正常な病的症候群, 低T3T4症候群, 低T3症候群, トリヨードサイロニン低下状態, 高テトラヨードサイロニン症候群, 高T4症候群, 甲状腺機能正常患者症候群
Swedish Euthyroid-sick syndromes
Finnish Korkea T4 -oireyhtymä
Czech Eutyreoidní sick syndrom, sekundární thyreoidální dysfunkce, syndrom eutyreoidního nemocného, eutyreoidální 'sick' syndromy, euthyreózní sick syndrom, euthyroid sick syndrome
Polish Zespoły z nieprawidłowym poziomem hormonów tarczycy, Nieprawidłowy poziom T3 i T4 w eutyreozie
Hungarian Euthyroid betegség syndroma
Portuguese Síndromes do Eutireóideo Doente, Síndrome de doença eutiróide
Norwegian Euthyroid-Sick Syndromes
Spanish Síndromes de Eutiroidismo Enfermo, síndrome del enfermo eutiroideo (trastorno), síndrome del enfermo eutiroideo, Síndrome del enfermo eutiroideo, Síndromes del Eutiroideo Enfermo
Dutch sick-euthyroid; syndroom, syndroom; sick-euthyroid, euthyroid sick syndrome, Syndroom, sick euthyroid
French Syndrome des maladies générales chez un euthyroïdien, Syndrome euthyroïdien, Syndrome normothyroïdien
German Euthyroid Sick Syndrom, Euthyroid-Sick-Syndrome