Subclinical Hyperthyroidism

Aka: Subclinical Hyperthyroidism

advertisement

II. Definition

  1. Euthyroid patient with TSH suppression
    1. Low but detectable TSH: 0.1 to 0.4 mIU/L
    2. Suppressed TSH: <0.1 mIU/L (greatest association with adverse effects, esp. >65 years old)

III. Epidemiology

  1. Prevalence in U.S. (study included patients over age 12 years old)
    1. TSH <0.4 mIU/L: 3.2%
    2. TSH <0.1 mIU/L: 0.7%
    3. Hollowell (2002) J Clin Endocrinol Metab 87(2): 489-99 [PubMed]
  2. More common in older adults
    1. Prevalence in age over 70 years approaches 15% in Iodine deficient regions
    2. Aghini (1999) J Clin Endocrinol Metab 84(2): 561-6 [PubMed]

IV. Causes

  1. Over-treatment of Hypothyroidism (excessive Thyroid Replacement)
    1. Prevalence approaches 20%
  2. Multinodular Goiter (esp. Iodine-deficient regions)
  3. Graves Disease
  4. Functional Thyroid Adenoma
  5. Transient Thyroiditis
    1. Silent Thyroiditis (TSH normalizes within months)
    2. Subacute Thyroiditis
    3. Postpartum Thyroiditis
  6. Pituitary abnormalities (Free T4 also suppressed)
  7. Early Hyperthyroidism in transition
  8. Partially treated Hyperthyroidism
  9. Iodine intake
    1. Recent radiocontrast administration (e.g. IVP)
    2. Amiodarone
    3. Other excessive Iodine intake
  10. Medications that suppress TSH
    1. Corticosteroids
    2. Dopamine
  11. Other conditions
    1. Sick Euthyroid Syndrome
    2. Psychiatric illness (esp. affective disorders)

V. Symptoms

  1. Significant Hyperthyroidism symptoms absent
  2. Nonspecific symptoms may be present
    1. Malaise
    2. Tachycardia
    3. Nervousness or anxiety
    4. Muscle Weakness

VI. Differential Diagnosis

  1. See Hyperthyroidism
  2. See Thyroid Stimulating Hormone (TSH)

VII. Complications: Primarily for TSH <0.1 mIU/L (undetectable)

  1. Overt Hyperthyroidism
    1. TSH 0.1 to 0.4 mIU/L: 1-3% risk per year (in age over 60 years)
      1. Rosario (2010) Clin Endocrinol 72(5): 685-8 [PubMed]
    2. TSH <0.1 mIU/L: 27% 27% risk in 2 years (in age over 65 years)
      1. Rosario (2008) Clin Endocrinol 68(3): 491-2 [PubMed]
    3. Cause of Subclinical Hyperthyroidism impacts risk of progression
      1. Multinodular Goiter is typically stable without progression
      2. Graves Disease is more unpredictable in terms of course
  2. Cardiovascular effects
    1. Atrial Fibrillation (Relative Risk: 3-5 in age > 60 years old)
      1. Auer (2001) Am Heart J 142(5):838-42 [PubMed]
      2. Sawin (1994) N Engl J Med 331(19): 1249-52 [PubMed]
    2. Increased left ventricular mass
    3. Decreased Heart Rate variability
  3. Increased Mortality in older patients
    1. Mortality increased by 20% over 10 years (especially if TSH persistently <0.1)
    2. Haentjens (2008) Eur J Endocrinol 159(3): 329-41 [PubMed]
    3. Sgarbi (2010) Eur J Endocrinol 162(3): 569-77 [PubMed]
  4. Increased Osteoporosis risk in postmenopausal women
    1. Rosario (2008) Arq Bras Endocrinol Metabol 52(9):1448-51 [PubMed]
    2. Uzzan (1996) J Clin Endocrinol Metab 81(12): 4278-89 [PubMed]
  5. Increased Muscle Weakness and atrophy risk

VIII. Labs

  1. Thyroid Stimulating Hormone (TSH) decreased
  2. Serum Free Thyroxine (Free T4) normal
  3. Serum Free Triiodothyronine (Free T3) nornal

IX. Imaging: 24 hour Radioactive Iodine Uptake Scan (RAIU)

  1. Indicated in Overt Hyperthyroidism
  2. Increased >30% at 24 hours
    1. Grave's Disease
    2. Multinodular Goiter
    3. Autonomous Thyroid Nodule
  3. Decreased <5% at 24 hours
    1. Silent Thyroiditis
    2. Postpartum Thyroiditis
    3. Exogenous Thyroid Hormone intake

X. Evaluation

  1. See Hyperthyroidism
  2. Initial lab testing
    1. Thyroid Stimulating Hormone (TSH)
    2. If TSH suppressed, obtain:
      1. Serum Free T4
      2. Serum Free T3
    3. If Free T4 and Free T3 increased then evaluate and treat as overt Hyperthyroidism
    4. Else if Free T4 and Free T3 normal, then continue as Subclinical Hyperthyroidism as below
  3. Subsequent repeat testing at 3 to 6 months
    1. Labs
      1. Thyroid Stimulating Hormone (TSH)
      2. Serum Free T4
      3. Serum Free T3
    2. Overt Hyperthyroidism (increased Free T4 or Free T3)
      1. Evaluate as Hyperthyroidism (including RAIU Scan)
      2. See Hyperthyroidism Management
    3. TSH below 0.1 with normal Free T4, Free T3
      1. Labs
        1. Thyrotropin receptor Antibody or TRab (positive in Graves Disease)
        2. Thyroglobulin (increased in transient Thyroiditis, decreased in excess Thyroid Hormone)
      2. Obtain 24 hour Radioactive Iodine Uptake Scan (RAIU)
        1. Increased uptake in Graves Disease (diffuse uptake) and Toxic Nodular Goiter (focal uptake)
        2. Decreased in transient Thyroiditis (Thyroglobulin high), excess Thyroid Hormone (Thyroglobulin low)
      3. Consider Hyperthyroidism Management
        1. Symptomatic or
        2. Over age 65 years or
        3. Cardiovascular disease or significant risk factors or
        4. Osteoporosis or Osteopenia
    4. TSH between 0.1 to 0.45 with normal Free T4, Free T3
      1. Consider additional evaluation management (esp. if symptomatic) as per TSH <0.1 protocol
      2. Periodic re-evaluation of TSH every 3-12 months

XI. Management

  1. Indications (American Thyroid Association) for Subclinical Hyperthyroidism with TSH persistently <0.1 mIU/L
    1. Age 65 years old or older OR
    2. Age <65 years old with heart disease, Osteoporosis or Hyperthyroidism symptoms
    3. Age <65 years old and postmenopausal and not on Estrogen or Bisphosphonates
    4. Other indications
      1. May consider same management indications as above, for patients with TSH 0.1 to 0.4
  2. Treatment options
    1. Treat underlying cause of Subclinical Hyperthyroidism
    2. Radioactive Iodine (Graves Disease, Toxic Multinodular Goiter, solitary autonomous Nodule)
    3. Antithyroid Drugs

XII. References

  1. Donangelo (2011) Am Fam Physician 83(8): 933-8 [PubMed]
  2. Donangelo (2017) Am Fam Physician 95(11): 710-16 [PubMed]
  3. Marqusee (1998) Endocrinol Metab Clin North Am 27:37-49 [PubMed]
  4. Shrier (2002) Am Fam Physician 65(3):431-8 [PubMed]
  5. Surks (2004) JAMA 291:228-38 [PubMed]
  6. Woeber (1997) Arch Intern Med 157:1065-8 [PubMed]

Images: Related links to external sites (from Bing)

These images are a random sampling from a Bing search on the term "Subclinical Hyperthyroidism." Click on the image (or right click) to open the source website in a new browser window. Search Bing for all related images

Related Studies

Related Topics in Thyroid Disease

advertisement