Subclinical Hyperthyroidism

Aka: Subclinical Hyperthyroidism

1. 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
2. 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
   2. More common in the elderly
      1. Prevalance in age over 70 years approaches 15% in iodine deficient regions
      2. Aghini (1999) J Clin Endocrinol Metab 84(2): 561-6
3. Causes
   1. Over-treatment of Hypothyroidism (excessive Thyroid Replacement)
      1. Prevalence approaches 20%
   2. Multinodular Goiter
   3. Silent Thyroiditis (TSH normalizes within months)
   4. Pituitary abnormalities (Free T4 also suppressed)
   5. Early Hyperthyroidism in transition
   6. Partially treated Hyperthyroidism
   7. Iodine
      1. Recent radiocontrast administration (e.g. IVP)
      2. Other excessive iodine intake
   8. Medications
      1. Corticosteroids
      2. Dopamine
4. Symptoms
   1. Significant Hyperthyroidism symptoms absent
   2. Nonspecific symptoms may be present
      1. Malaise
      2. Tachycardia
      3. Nervousness or anxiety
      4. Muscle Weakness
5. Differential Diagnosis
   1. See Hyperthyroidism
   2. See Thyroid Stimulating Hormone (TSH)
6. Complications
   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
      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
      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)
         1. Auer (2001) Am Heart J 142(5):838-42
         2. Sawin (1994) N Engl J Med 331(19): 1249-52
      2. Increased left ventricular mass
      3. Decreased Heart Rate variability
   3. Increased Mortality in older patients
      1. Haentjens (2008) Eur J Endocrinol 159(3): 329-41
      2. Sgarbi (2010) Eur J Endocrinol 162(3): 569-77
   4. Increased Osteoporosis risk in postmenopausal women
      1. Rosario (2008) Arq Bras Endocrinol Metabol 52(9):1448-51
      2. Uzzan (1996) J Clin Endocrinol Metab 81(12): 4278-89
   5. Increased Muscle Weakness and atrophy risk
7. Labs
   1. Thyroid Stimulating Hormone (TSH) decreased
   2. Serum Free Thyroxine (Free T4) normal
   3. Serum Free Triiodothyronine (Free T3) nornal
8. Imaging: 24 hour Radioactive Iodine Uptake Scan (RAIU)
   1. Increased >30% at 24 hours
      1. Grave's Disease
      2. Multinodular Goiter
      3. Autonomous Thyroid Nodule
   2. Decreased <5% at 24 hours
      1. Silent Thyroiditis
      2. Postpartum Thyroiditis
      3. Exogenous Thyroid hormone intake
9. Evaluation
   1. See Hyperthyroidism
   2. Initial lab testing
      1. Thyroid Stimulating Hormone (TSH)
      2. Serum Free T4
      3. Serum Free T3
      4. Complete Blood Count (CBC)
      5. Chemistry panel
   3. Subsequent monthly testing for 3 months
      1. Thyroid Stimulating Hormone (TSH)
      2. Serum Free T4
      3. Serum Free T3
   4. Three month assessment
      1. Overt Hyperthyroidism (increased Free T4 or Free T3)
         1. Evaluate as Hyperthyroidism (including RAIU Scan)
         2. See Hyperthyroidism Management
      2. TSH below 0.1 with normal Free T4, Free T3
         1. Obtain 24 hour Radioactive Iodine Uptake Scan (RAIU)
         2. Consider Hyperthyroidism Management
      3. TSH between 0.1 to 0.45 with normal Free T4, Free T3
         1. Obtain 24 hour Radioactive Iodine Uptake Scan (RAIU)
            1. Evaluate for endogenous disease (e.g. Destructive Thyroiditis, Grave's Disease)
         2. Periodic re-evaluation of TSH every 3-12 months
10. References
    1. Donangelo (2011) Am Fam Physician 83(8): 933-8
    2. Marqusee (1998) Endocrinol Metab Clin North Am 27:37-49
    3. Shrier (2002) Am Fam Physician 65(3):431-8
    4. Surks (2004) JAMA 291:228-38
    5. Woeber (1997) Arch Intern Med 157:1065-8