I. Subclinical hypothyroidism
  1. May be associated with hypercholesterolemia and progression to overt hypothyroidism
  2. But then again may be self-limited
    1. In a prospective study of 107 pts > 55yo with subclinical hypothyroidism and no prior h/o thyroid disease, over mean 32mo f/u, 37% normalized their TSH values and 27% developed overt hypothyroidism.  The incidence of overt hypothyroidism was greater with higher baseline TSH levels (J. Clin. Endocrinol. Metab. 89:4890, 2004--abst)
  3. Associated with increased risk for cardiovascular disorders
    1. In a prospective study in a cohort of 2,730 community-dwelling pts 70-79yo, of whom 12.4% had subclinical hypothyroidism (TSH >= 4.5mIU/L), over 4y f/u, the incidence of CHF was sig. higher (RR 2.0) among those with subclinical hypothyroidism and TSH >= 7mIU/mL compared with euthyroid pts (Arch. Int. Med. 165:2460, 2006--JW)
    2. In a prospective study in 2,108 pts of whom 5.6% had subclinical hypothyroidism (TSH >= 4.0 mIU/L), over 20y f/u, incidence of CHD events was sig. higher among those with TSH > 10mIU/L c/w euthyroid pts (HR 2.6) (Arch. Int. Med. 165:2467, 2005--JW)
  4. "Results from randomized trials of treatment to relieve sx have been equivocal...the available evidence is not sufficient to recommend for or against treatment" per ACIP-ASIM (Ann. Int. Med. 129:141, 1998)
    1. "Either treatment or observation is a reasonable approach" in women > 50yo with TSH > 10mU/l
    2. For pts with mildly elevated TSH (< 10 mU/l) or women < 50yo or men, "no strong evidence indicates that treatment is effective or ineffective in relieving symptoms...might consider a trial of therapy in selected, more symptomatic patients and a specified plan for follow-up in the remaining patients...every 2 to 5 years"
    3. "The efficacy of treating pts with subclinical hypothyroidism to prevent progression to overt hypothyroidism is not known"
    4. 63 women with subclinical hypothyroidism (mean baseline TSH 12mIU/L) randomized to L-thyroxine vs. placebo x 48wks; no sig. diff. in change in lipid levels or sx scores (J. Clin. Endoc. Metab. 86:4860, 2001--JW) 
  5. See also: Thyroid Disorders in Pregnancy
II. Overt Hypothyroidism
  1. Clinical features:
  1. Cold intolerance
  2. Weight gain
  3. Hair loss
  4. Fatigue
  5. Decreased appetite
  6. Dry skin
  7. Hoarseness
  8. Constipation
  9. Nonpitting edema
  10. Hypertension
  11. Bradycardia
  12. Hypercholesterolemia
  13. FIT in kids
  14. Psychomotor retardaton
  15. Depressed DTR's with delayed relaxation
  16. Increased serum Cr (can occur in severe hypothyroidism; Arch. Int. Med. 159:79, 1999--AFP)
  17. In children-Delayed bone age but usually normal height age
  1. Prev. of unrecognized hypothyroidism in gen'l pop: 1%
  2. Differential diagnosis
  1. Destructive (surgery, radioiodine, neoplasms)
  2. Autoimmune (most common)-Hashimoto's, Graves'
  3. Thyroiditis-subacute (viral), postpartum
  4. Drug-induced (iodides, lithium, thionamides)
  5. Hereditary (enzyme deficiencies, thyroid agenesis, hormone resistance)
  6. Hypothalamic & pituitary disorders, e.g. Sheehan's
  1. Treatment
  1. L-thyroxine replacement
  1. Tradition is to start at a low dose and gradually build up to avoid cardiac decompensation and adrenal insufficiency from hypopituitarism
  2. In a study in 50 newly-diagnosed hypothyroid pts 22-86yo randomized to initiation of levothyroxine therapy at full-dose (1.6 micrograms/kg/d) vs. low-dose (25ug/d initially increasing by 25ug Q4wks until euthyroid), the full-dose group had faster median time to normalization of TSH levels (4wks vs. 16wks), but there were no sig. differences in symptom or quality of life scores over 48wks (Arch. Int. Med. 165:1714, 2005--JW)
  3. t-1/2 of thyroxine is about 8d, so wait 32-40d before changing dose!
  4. Target for treatment is usually to get TSH in normal range
    1. In a study in 56 pts with primary hypothyroidism, all of who received three randomly ordered 8-wk courses of levothyroxine adjusted to target TSH levels in the low (< 0.3mU/L, low-normal (0.3-1.99 mU/L), and high-normal (2.0-4.8 mU/L) levels, there were no sig. diffs in measures of cognitive function, quality of live, or thyroid-related sx measured at the end of each 8-week course of treatment. (J. Clin. Endocrin. Metab. 91:2624, 2006--JW)
  1. T3 + T4 for hypothyroidism
  1. 33 hypothyroid pts randomized to T4 (their usual dose) vs. reduced T4 dose (50ug less than usual) + 12.5ug/d of T3. There were modest improvements in the T3 group in various tests of cognition, mood, and physical symptoms (NEJM 340:424, 1999--JW)
  2. In a 10-week randomized trial in 110 pts with hypothyroidism on T4-only replacement, randomized to continued T4 or T3/T4 combination therapy, there were no sig. differences in quality-of-life scores, cognitive-function scores, mental health, or physical symptoms (J. Clin. Endoc. Metab. 88:4543, 2003--JW)
  3. In a 15-week randomized trial in 40 pts with depression and hypothyroidism on T4-only replacement, randomized to continued T4 or T3/T4 combination therapy, there were no sig. differences on measures of mood, functional status, or overall well-being (J. Clin. Endoc. Metab. 88:4551, 2003--JW)
  4. In a study in 44 pts with primary hypothyroidism on stable doses of T4, randomly assigned to continue their usual T4 dose or a T3-T4 combination adjusted to normalize TSH levels, over 4mos, no sig. diffs were seen on symptom scores, neuropsychological test results, body weight, or lipid levels (JAMA 290:2952, 2003--JW)
  1. Bioequivalency of l-thyroxine preparations: 22 women with hypothyroidism got 4 thyroxine products in a 4-way crossover trial for 6wks each. Measured AUC and peak concentrations of T3, T4, and fT4i and found no diff. among the 4 thyroxine preparations, which all met FDA criteria for bioequivalence: Synthroid, Levoxyl, and generics distributed by Geneva Generics and Rugby Laboratories. (JAMA 277:1205, 1997)