Subclinical hyperthyroidism

Overt Hypothyroidism

I. Clinical features

  1. Tachycardia
  2. Nervousness
  3. Heat intolerance
  4. Tachyarrhythmias Tremors Diaphoresis
  5. CHF Insomnia Diarrhea
  6. Hypertension
  7. Muscle wasting
  8. Inc. appetite
  9. Exopthalmos
  10. Non-pitting edema
  11. Weight loss
  12. Lymphocytosis
  13. Oligomenorrhea
  14. Decreased bone density (if chronic)
II. Differential diagnosis
  1. Diffuse toxic goiter (Graves')
  1. Typically treated with antithyroid medication and thyroid ablation (the latter with I-131)
  2. For I-131 treatment, pre-treatment with antithyroid drugs traditionally done to reduce risk of transiently worsening hyperthyroidism after I-131 tx; however, a randomized trial of 42 pts with Graves' did not show any such benefit using methimazole to normalize T4 levels x 2mos before I-131 (J. Clin. Endocr. Metab. 86:3016, 2001--JW)
  3. Treatment with thyroxine during and after antithyroid drugs postulated to reduce risk of recurrent hyperthyroidism (NEJM 334:220, 1996-JW)
  1. 111 pts with Graves randomized to carbimazole x 18mos vs. (carbimazole x 1mo then carbimazole + thryoxine x 17mos) then thyroxine alone x 18mos
  2. At 3 mos after w/d of carbimazole, recurrent hyperthyroidism occurred in about 30% of each group
  1. Nodular toxic goiter (Plummer's)
  2. Toxic adenoma
  3. Thyrotoxicosis factitia (ingestion of toxic amounts of thyroid hormones)
  4. Thyroiditis
  5. Metastatic thyrocarcinoma (rare)
  6. TSH- or hCG-secreting tumor (rare)
  7. Choriocarcinoma or molar pregnancy (rare)
  8. n.b. You can't get thyrotoxicosis from too much TRH
III. Diagnostic approach
  1. Best initial test is thyroid uptake & scan (Source: UWMC Nuclear Medicine Newsletter Autumn 1998)
    1. Thyroid uptake determines (us.) 6 & 24h retention of radioiodine (is. 5uCi of I-131) by the thyroid; helps to differentiate different causes of hypothyroidism; also helps to gauge dose of I-131 that will be needed for thyroid ablation.
      1. 6h uptake allows identification of pts with rapid I-131 turnover causing 24h to be low (would be false-neg if only did 24h)--these pts require higher dose for I-131 ablation
      2. 24h uptake is the standard measure (normal = 10-35%; low, normal, or high in thyroiditis; high in Graves'; normal-to-high in Toxic multinodular goiter)
    2. Thyroid scan--us. IV technetium pertechnetate; imaging about 15min after injection. Thyroiditis, Grave's, toxic multinodular goiter, and of course, "cold nodules" have characteristic apperances.
IV. Treatment
  1. Radioiodine (I-131)
  1. Contraindicated in kids, pregnant women
  2. Although I-131 was associated with increased mortality for thyroid Ca, there was no evidence of an increase in overall cancer risk for pts tx'd with I-131 (Cooperative Thyrotoxicosis Therapy Follow-Up Study; JAMA 280:347, 1998--JW)
  1. Surgery-sl. less risk (as of 1990) for subsequent hypothyroidism
  2. Antithyroid drugs
  1. Thionamines - inhibitors of thyroidal peroxidase
    1. Propothiouracil, methimazole, carbimazole
    2. Cross the placenta; there may be an association between methimazole and carbimazole with teratogenic effects
    3. Propylthiouracil may be associated with risk of severe liver injury
  2. Beta-blockers
  3. Cholestyramine binds T4 and increases fecal excretion and speeds decrease in serum T4 in pts with Graves' (J. Clin. Endocrinol. Metab. 81:3191, 1996-AFP)