Associated with pernicious anemia and insulin-dependent diabetes through association of those w autoimmune Hashimoto's

Sx:Hair loss, and coarseness; coarse skin; fatigue; swollen tongue with slurred speech; nonpitting edema; menorrhagia; feel cold; lactation from TRH stimulation of prolactin (Ann IM 1976;84:534); constipation; muscle cramps; mental dullness. Worsened or precipitated by smoking since that impairs thyroid hormone secretion and peripheral effect (Nejm 1995;333:969)

Si:Goiter; dry skin; hung-up reflexes (r/o hypothermia, ß-blockers, pregnancy, procainamide); diminished PMI from pericardial effusion (Nejm 1977;296:1); arthritis with synovial thickening and noninflammatory effusions (Nejm 1970;282:1172)

Very slowly progressive; insidious; 25% of atrophic type may revert (Nejm 1992;326:513)

Anemias from folate deficiency in 20%, hypoproliferative, Fe-deficient (Ann IM 1968;68:792); bleeding from diminished platelet stickiness (Ann IM 1974;82:342); cerebellar sx (30%); peripheral neuropathies (25%); coma, confusion, psychoses, seizures; hypothermia; hypoventilation, sleep apnea (Ann IM 1984;101:491); CAD and mortality incr if TSH >/=10 (Jama 2010;304:1365) sss

r/o "EUTHYROID-SICK SYNDROME": low T₃T₄, with normal or low TSH in presence of other severe illness (Nejm 1985;312:546); no specific rx required

Lab:

Chem:TSH elevated in primary hypothyroidism, the earliest test to become abnormal, may be worth using as a screening test in the elderly (Ann IM 1990;112:840); if on thyroid and indications in doubt, may stop and check TSH, T₄ at 5 wk. Total T ₃, free T₄, resin T₃ uptake (a measure of thyroid-binding globulins) all low. In secondary myxedema, TSH stimulation by TRH administration may be slow to respond w delayed peak (Nejm 1985;312:1085)

• Cholesterol elevated >250 mg % in thyroid gland not in pituitary types (“rapid TSH”); triglycerides elevated
• CPK (MM) and liver enzymes often elevated

Xray:Chest may show increased heart size (pericardial effusion)

Rx:

L-Thyroxine (Synthroid, Levoxyl, or generic, all the same—Jama 1997;277:1205) (Nejm 1994;331:174) 0.1-0.2 mg (100-200 µgm) qd po; 0.1 adequate for 2/3 of pts, 0.125 plenty for most (1.7 µgm/kg) (Ann IM 1986;105:11); monitor sensitive TSH (Ann IM 1990;113:450) to keep 0.5 mIU/cc so osteoporosis/hip fx risk minimized (Ann IM 2001;134:560). Use of T₃ w T₄ replacement no benefit by DBCT (Jama 2008;299:769; Ann IM 2005;142:412). No benefit from rx of TSH’s <10 (Jama 2003:291:228, 239); but at age 84 yr, survival better if slightly hypothyroid (Jama 2004;292:2591). Beware of concomitant rx w FeSO₄, which impairs absorption (Ann IM 1992;117:1010), as do proton pump inhibitors, calcium pills like Tums or Os-Cal (Jama 2000;283:2822), or any other condition that decreases gastric acidity (Nejm 2006;354:1787), phenytoin (Dilantin), carbamazepine (Tegretol), rifampin, cholestyramine, sucralfate, and aluminum hydroxide antacids

in coma/confusion: 100-500 µgm iv/po qd, usually w concomitant stress steroid doses in case also hypoadrenal

in elderly, go very slowly, eg, 1/4 or less these doses, and work up slowly because normal T₃ half-life is several days and may be longer in the elderly, and T₄ half-life is nearly twice that of T₃

in pregnancy, dose requirements may increase; monitor with TSH (Nejm 1990;323:91)

in developing countries, I₂ in oil annually to all w euthyroid goiter? (Nejm 1992;326:236) and/or to pregnant women and babies in areas of endemic cretinism (Nejm 1986;315:791)