Hypothyroidism

The prevalence of hypothyroidism in women is approximately 1%–2%, with about 0.3% being overt. Up to 4.6% of women have been found to have biochemical or subclinical disease.[2, 3] The high proportion of subclinical disease and the variation in symptoms requires a high degree of awareness and willingness to test among women’s health providers.

Hypothyroidism has several important clinical associations. These include use of amiodorone, lithium, or interferon and age greater than 65, at which point prevalence rises to 10%. It is also more common in the postpartum period. Women over 65 with loss of appetite, weight changes, or other changes suggestive of physical deterioration or mental status changes should be screened for hypothyroidism.

Most hypothyroidism is autoimmune in origin. Hypothyroidism associated with goiter is Hashimoto’s disease.[4] Iatrogenic hypothyroidism, caused by use of radioactive iodine or surgery for hyperthyroidism, must also be considered.

Presentation can be quite variable (see Table 32-1). In addition to specific gynecologic problems, symptoms also include many common complaints for women, such as constipation, weight gain, and fatigue. Myalgias should also prompt evaluation. Physical examination findings are typically nonspecific. Dry, dull hair and skin and decreased deep tendon reflexes may be seen. Table 32-1 lists several common presenting complaints.

Initial screening with TSH alone is adequate, since subclinical hypothyroidism is defined as an elevated TSH with normal thyroid function. Adding free T4 allows definitive diagnosis of the degree of thyroid dysfunction without additional visits or lab draws for the patient and with little added cost. When TSH alone is abnormal it should be repeated in two to three weeks, since various conditions may cause transient TSH elevation (see Table 32-2). Other evaluation may include prolactin screening, EKG, and lipids when indicated.

Management is with T4 (levothyroxine) replacement. The required dose is approximately 1.6 mcg/Kg, with the typical range being 75 mcg–150 mcg daily. Obesity, medication usage, and age all can have a substantial effect, and dosing is always individualized. Requirements are reduced by about 30% in elderly women. Dosing should be started at 50 mcg daily and then raised in two weeks, especially in the elderly, to avoid cardiovascular complications.[5] Patients with a complex, multisystem presentation, or those who respond inappropriately to replacement management, should be referred to a medical endocrinologist.

Empiric treatment with T4 in the absence of an elevated TSH is not indicated. Weight gain is not a prominent symptom of hypothyroidism, and empiric treatment is especially not indicated for either weight loss or infertility management. Conversely, evaluation of all women with recurrent pregnancy loss should include TSH elevation.

TSH falls only slowly, and should be checked in 8–12 weeks but not sooner. Treatment is most effective when TSH is in the lower range of normal (<2.0 mIU/L).[4] Once a stable dose is established, monitoring can be done with TSH alone every 3–12 months. Return of function of the pituitary-thyroid axis can occur as the degree of inflammatory thyroid damage may change. Variation in thyroid function is not uncommon given the autoimmune nature of most hypothyroidism. Replacement may be discontinued after a prolonged period of treatment to evaluate this possibility.

Pregnancy presents minor variations in management of hypothyroidism. Thyroid replacement doses rise about 20%, the consequence of increased body water and serum protein binding capacity as well as a decrease in iodine availability. TSH should be measured upon presentation, and again at the end of the first trimester. It should be measured monthly for the remainder of the pregnancy. A new diagnosis of hypothyroidism is rare in pregnancy; hypothyroidism is associated with anovulatory infertility. Women’s health providers should be alert for postpartum changes in thyroid function, especially new onset symptoms. Liberal use of screening is appropriate.[6, 7]

Hyperthyroidism

Hyperthyroidism is less common than hypothyroidism. In addition, gynecologists and other women’s health providers are typically less involved in its management because its manifestations are primarily cardiac, in contrast to the multiple gynecologic symptoms of hypothyroidism.

Hyperthyroidism can be both overt and subclinical, as in hypothyroidism. Family history, especially of Graves’ disease, is an important association. Amiodorone can also be associated with hyperthyroidism.

The two most common causes of hyperthyroidism are Graves’ disease and toxic multinodular goiter. Graves’ disease is a specific clinical syndrome; the eponym is not a synonym for hyperthyroidism. Toxic goiter may be simple or multinodular. Hyperthyroidism may also arise from a solitary nodule or, rarely, from iodine excess. Gestational trophoblastic disease must be considered in the pregnant patient. (See Table 32-3 for a list of causes of hyperthyroidism.)

Symptoms, although variable, are more common and more consistent than in hypothyroidism. Graves’ disease has a specific symptom triad of exophthalmos, pretibial edema, and hyperthyroidism. Other symptoms are listed in Table 32-4. Common symptoms include tachycardia, tremor, sweating, and heat intolerance. Marked hyperthyroidism can lead to cardiac failure and thyroid storm. Thyroid storm is a marked exacerbation of hyperthyroidism, usually the result of nontreatment or occasionally by exacerbation secondary to an acute illness. Thyroid storm is an acute medical emergency requiring hospitalization. Symptoms include high fever, marked tachycardia or cardiac arrhythmias, vomiting, diarrhea, and agitation. Symptoms have been scored using a scale developed by Burch and Wartofsky.[8] The use of this scale and management of patients with advanced degrees of hypothyroidism are generally outside the scope of general gynecology practice.

Unlike hypothyroidism, which is associated with amenorrhea and anovulation, patients with hyperthyroidism typically ovulate. Such women are thus capable of becoming pregnant, and therefore become at risk for hyperemesis gravidarum. Gynecologic manifestations of hyperthyroidism are less common, but gynecologic care providers need to be aware of the symptoms of hyperthyroidism and to investigate and test liberally, given the higher incidence of thyroid disease in women. Table 32-4 lists symptoms associated with hyperthyroidism.

Diagnosis is made by hormonal testing. Like hypothyroidism, subclinical disease can occur. These patients have a TSH <0.4 but normal T4. No treatment for asymptomatic patients with a normal T4 is necessary; however, most of these women will progress to overt hyperthyroidism, and close serologic monitoring is essential.[9] Further, subclinical hyperthyroidism is a significant risk factor for atrial fibrillation, and all women’s health providers should be aware of this association.[10] TSH below 0.4 mIU/L and elevated T4 or T3 establish the diagnosis of hyperthyroidism. In overt disease, evaluation of the thyroid gland itself is necessary, utilizing radioactive iodine. Management from this point is based on results of the iodine uptake. The fundamental choice is between medical suppression, radioactive thyroid ablation and surgery.

Toxic goiter with diffuse uptake can be managed with medication or radioactive ablation. A solitary nodule may be managed with radioactive iodine, but surgery is often preferred as nodules may recur, leading to high doses of radiation exposure. Both radioactive iodine and surgery have a risk of secondary, iatrogenic hypothyroidism.

Methimazole and propylthiouracil (PTU) are both used for the medical management of hyperthyroidism. They are equivalent in effectiveness, but methimazole is the drug of choice because it has fewer side effects. Typical initial oral dose is 10 mg–20 mg daily, falling to 5 mg–10 mg daily. PTU dosing is typically 50 mg–100 mg TID. The half-life of T4 is one week; thus TSH rises and T4 falls relatively slowly. Maximum effect of medication on thyroid function tests is at eight weeks.[9]

Thyroid storm is a life-threatening medical emergency. Hospitalization and often intensive care are necessary. Management includes Tylenol and cooling blankets for fever, beta blockers for arrhythmias and tachycardia, and inorganic iodine (Lugol’s iodine) and methimnazole to reduce thyroid hormone production.[11]

Gynecologic surgeons and other women’s health providers should be aware of Struma Ovarii as a cause for hyperthyroidism. A struma is a benign cystic teratoma composed completely or nearly completely of thyroid tissue. Patients typically present with hyperthyroidism without other cause or association. A pelvic ultrasound can rapidly direct management appropriately. Thyroid carcinoma can arise rarely within a struma, and even more rarely can metastasize out of the dermoid into the pelvis. Should this be found, oncologic management is indicated.

The management of established hyperthyroidism in pregnancy is well within the scope of general ob/gyn care providers. Methimazole should not be used in the first trimester. It is discontinued in women using it, and PTU substituted. Once out of the first trimester, patients should be converted back to methimazole. TSH and T4 should be measured monthly, and care taken to avoid iatrogenic hypothyroidism.[12]

Hyperthyroidism and thyroid storm may be caused by gestational trophoblastic disease. Patients presenting with new onset hyperthyroidism in pregnancy should be evaluated for hydatidiform mole, and patients with a partial molar pregnancy and a viable fetus are at risk for hyperthyroidism and thyroid storm. Such patients require a multidisciplinary team, including perinatology and internal medicine. Unless the labor floor has the capability of providing intensive treatment including hemodynamic monitoring, these patients typically require management off the labor floor in an intensive care unit. Thyroid storm in pregnancy has in particular increased risks of cardiac failure, pulmonary edema, and fetal death.

Hyperthyroidism may also present in pregnancy as hyperemesis. All patients with hyperemesis should be screened with a TSH.[13, 14]

Aside from established disease in pregnancy, the choices and managements for hyperthyroidism are generally outside the purview of general ob/gyn providers. Patients newly diagnosed with hyperthyroidism by an ob/gyn provider should be referred promptly to a medical endocrinologist.