When first diagnosed during pregnancy, most women will have autoimmune thyroid disease. Lymphocytic infiltration is the cause of the thyroid enlargement (goitrous form), although in some cases, usually late in the disease course, the thyroid may become atrophic and nonpalpable. The majority of the cases not caused by autoimmune thyroiditis are secondary to destruction or removal of the thyroid gland (radio-active iodine ablation or surgery) as part of the treatment for hyperthyroidism, thyroid cancer, suspicious nodules or toxic nodular goiter. Rare causes include the transient hypothyroidism that may be seen in silent (painless) and subacute thyroiditis, drug-induced hypothyroidism, high-dose external neck radiation (e.g. for Hodgkin’s lymphoma), congenital hypothyroidism, inherited metabolic disorders of the thyroid, and thyroid hormone resistance syndromes. Secondary hypothyroidism may be seen in pituitary or hypothalamic diseases. Several drugs may cause hypothyroidism if taken during pregnancy. Iodine, lithium, propylthiouracil, and methimazole interfere with thyroid hormone synthesis and/or its release. Carbamazepine, phenytoin, and rifampin increase thyroxine (T4) clearance. Amiodarone decreases the conversion from T4 to triiodothyronine (T3) and also inhibits T3 action. Aluminum oxide, cholestyramine, sucralfate, and particularly ferrous sulfate interfere with the intestinal absorption of T4. Therefore, it is important to make sure that women on levothyroxine replacement take these medications at least 2 hours apart, and perhaps 4 hours might be even better (especially when taking ferrous sulfate which is very commonly given to pregnant women).

The diagnosis of hypothyroidism is difficult to make on clinical grounds alone and therefore it will remain unsuspected and undiagnosed until it is profound and the symptoms very obvious. In addition, only one-third of hypothyroid pregnant women show the classic symptoms, another third will have moderate symptomatology, and the rest will have few or no symptoms despite very abnormal thyroid function tests. Symptoms may include fatigue, sleepiness, lethargy, mental slowing, depression, cold intolerance (which is very unusual in normal pregnancy), decreased perspiration, hair loss, dry skin, deeper voice or hoarseness, weight gain despite poor appetite, constipation, arthralgias, muscle aching, and stiffness and paresthesias. There might be history of menstrual irregularities before pregnancy. On physical examination, signs that may be present include general slowing of speech and movements, dry and pale (or at times yellowish) skin, sparse thin hair, deep or hoarse voice, bradycardia (also unusual in pregnancy), myxedema (nonpitting edema), hyporeflexia, prolonged relaxation phase of the deep tendon reflexes, carpal tunnel syndrome, and a diffuse or a nodular goiter.

The best laboratory test to diagnose hypothyroidism is the TSH except in the rare cases of hypothalamic or pituitary disease. Current sensitive TSH assays make it possible to diagnose hypothyroidism very early and allow monitoring thyroxine replacement therapy very accurately. Other tests include the total T4 (TT4) and free T4 index (FT4I), FT4, thyroid peroxidase antibodies (TPO-Ab), and antithyroglobulin antibodies (ATG-Ab). The levels of total T4 are higher during pregnancy due to an increase in thyroxine-binding globulin (TBG). The pregnancy range is calculated by multiplying the normal nonpregnant TT4 value (5–12 μg/dL for most laboratories) by 1.5 (e.g. 7.5–18 μg/dL). Caution is needed to interpret the current FT4 levels during pregnancy because the normal ranges have been determined using nonpregnant individuals. In addition, the FT4 assays currently in use are influenced by the changes in TBG and albumin that occur during pregnancy. Therefore, until normal FT4 values that are specific for pregnancy are determined, the utility of present FT4 assays will be limited (see Chapter 23). TT4 and FT4I may provide a more reliable estimate for the time being since they retain an appropriate inverse relationship with TSH throughout pregnancy.

Anemia may be found in 30–40% of patients, usually secondary to decreased erythropoiesis, but at times it may also be due to vitamin B12, folic acid or iron deficiencies. Serum lipids and creatine phosphokinase (CPK – of muscle origin) may be elevated. Mild, reversible abnormalities of liver function have also been described.