Common Thyroid Disorders In Women

Lorraine H. Dajani, M.D., FCAE and J. Gary Evans, M.D., FCAE
Lorraine H. Dajani, M.D., FCAE and J. Gary Evans, M.D., FCAE
are with Northeast Florida Endocrine & Diabetes Associates, P.A.

Hypothyroidism

Thyroid gland failure and varying degrees of dysfunction are quite common among the female population. Because initial signs and symptoms are vague, ambiguous, and often seen in various underlying disorders, thyroid disease is often missed in its early stages. Sadly enough, patients may be seen on multiple occasions in their physician's office with similar complaints and may be even treated for the secondary consequences such as infertility, hypercholesterol, anemia or depression. The purpose of this article is to raise the index of suspicion in the highest risk population to enable a timely diagnosis and treatment. The majority of cases of hypothyroidism can be treated in the primary care setting.

Causes

The most common cause of hypothyroidism is autoimmune chronic thyroiditis (Hashimoto's disease). Another cause is postabalative hypothyroidism following radioactive treatment for Grave's disease or toxic multinodular goiter. It can also be due to surgical removal of the thyroid gland or secondary surgery of the pituitary. Less commonly, thyroid failure may be caused by external radiation to head or neck.

Transient hypothyroidism, which may be subclinical or overt, generally occurs in the final phase of either subacute or postpartum thyroiditis.

Incidence

Most studies suggests an average prevalence of hypothyroidism in 10-20 percent of women. The higher range occurs most in women above the age of 65. It is estimated that one out of eleven women will become hypothyroid in their lifetime.

Individuals At Risk

Women in general show a much higher risk of hypothyroidism than men, with a greater than 5:1 ratio (Table 1). Varying degrees of hypothyroidism are even more common in women above the age of 65. Also, any woman with a personal history of other autoimmune diseases such as Type I diabetes, rheumatoid arthritis, pernicious anemia, bitiligo, adrenal insufficiency, premature menopause, etc., would be at higher risk for thyroid dysfunction.

Those patients with elevated serum cholesterol and the simple process of aging place and individual higher at risk. The woman with a history of irregular menses or infertility should be considered at risk for thyroid disease. Also, an evaluation is warranted in those individuals with a history of depression or dementia.

Certain drugs are known to directly affect thyroid function, especially lithium, amiodarone, certain iodine-containing drugs, some expectorants, dexamethsone and hydrocortisone. Iron and sucralfate can alter the GI absorption of exogenous levothyroxine. Several anticonvulsants may alter the serum binding of thyroid hormone and affect the free or biologically active portion (Table 2).⁸

Presentation

At the early stages of thyroid dysfunction, symptoms may be quite vague and nonspecific, especially fatigue, weight gain, swelling, hair loss, and depression. However, as hypothyroidism progresses, cold intolerance, constipation, very dry skin, along with myalgias, and actual proximal muscle weakness (difficulty fixing one's hair or getting up from a squatting position) should alert the physician to possible thyroid dysfunction. These symptoms are especially true in healthy women under the age of 50. (Table 3) In the elderly women, symptoms may be less predictable and actually be mistaken for the simple aging process by both the patient and the physician. (Table 4). The elderly women may simply have no symptoms. They may complain of vague fatigue, cold intolerance, and generalized weakness.

Physical Examination

Findings most suggestive of hypothyroidism include hair that is dry, coarse, and fall easily. The skin can be dry, leathery, and there may be periorbital swelling in the face as well as puffiness in the hands and feet. There may be relative bradycardia present, the patient may feel cold to the touch, and, if the hypothyroidism is significant, a delay in the relaxation phase of DTRs may be appreciated.

Laboratory findings, which should alert the physician to the possibility of concomitant thyroid disease, include elevated serum cholesterol, especially if this is new elevated CPK, or hyponatremia.

Diagnosis

If Thyroid disease is suspected, the initial lab of choice is a sensitive TSH (unless there is a history of pituitary disease). If the TSH is greater than the upper limit of normal (in most labs it is usually 4.5 or 5mU/L), hen it would be helpful to check a fee T₄ (FT₄), which is likely to be affected by thyroid-binding globulins. The cost now of FT₄ is usually less than the free T₄ index. The latter requires that two tests be run, T₄ and T₃, is certainly preferred in women who are on birth control or estrogen replacement since they increase thyroid-binding globulins. Also, antithyroid-peroxidase antibodies (anti TPO) are present in 90% of cases of Hashimoto's. It is important distinguish between Hashimoto's, which leads to chronic permanent hypothyroidism, and milder transient hypothyroid phase in the setting of subacute thyroiditis or postpartum thyroiditis. These latter two may require temporary replacement but generally the gland fully recovers. (See separate discussion below).

Other tests that may be helpful may be an ultrasound if an enlarged gland is palpated or if it is felt to be irregular or asymmetric. Although nodularity is not uncommon in the setting of chronic thyroiditis, cancer is rare. There is a rare association of lymphoma of the thyroid in the setting of chronic thyroiditis. Thyroid scans are usually helpful in this work-up.

Treatment

Prior to dosing any replacement, one must take into consideration the degree of hypothyroidism, overt versus subclinical, the age of the patient, and associated illnesses such as heart disease, arrythmias, malabsorption, or the presence of drugs which may affect the absorption of the thyroid replacement. It is generally recommended that levothyroxine (L-thyroxine) be used for replacement. One should avoid generics (due to the lack of consistent dosing). There is no indication for dessicated bovine thyroid triiodothyronine, or T₄-T₃ combinations. It is recommended that one avoid switching brands as much as possible since this would necessitate re-titration.

Generally, healthy, young adults may start with 1.6 mcg per kilo of body weight daily. In middle-aged adults with possible undiagnosed heart disease, a more moderate initial dose would be 25-50 mcg per day in patients greater than 65, it is generally recommended to start with 12.5-25 mcg per day. FT₄ and TSH should be repeated in six to eight weeks, sooner if the patient is no better. The goal of therapy is to bring the TSH into the low mid-normal range. In profoundly hypothyroid patients, this may take several weeks to completely normalize, therefore, it is important to follow FT, to decide if the patient is truly biochemically euthyroid.

If the TSH drops "below normal", the dose is likely too strong and should be reduced. Excessive thyroid hormone replacement could be associated with increased risk of cardiac events and possibly osteoporosis.

Subacute Thyroiditis

In subacute thyroiditis, there may be a history of recent upper respiratory infection. This may be followed by painful of painless swelling of the anterior neck. Initially, the patient may feel mild hyperthyroid symptoms or may be totally asymptomatic. Laboratory evaluations at that time may show slightly elevated T₄ hyperthyroidism, it would show low uptake, evidence of a "sick"gland. The elevated T₄ and T₃ is due to leakage of stored hormone from the damaged gland. This phase lasts on the average of two to four weeks and may be followed by a fairly euthyroid window of several weeks. The final phase, in which the sick gland is unable to produce adequate thyroid hormone, generally leads to mild clinical hypothyroidism in varying degrees, however.

Laboratory evaluation will reflect the particular stage. The sed rate is usually elevated and is a helpful tool, whereby antithyroid-peroxidase antibodies (anti-TPO) are generally negative. Treatment is indicated only if symptoms are extreme. Initially, during the hyperthyroid phase, the use of low-dose beta blockers may be indicated temporarily. The final phase, if associated with sever hypothyroidism, may also require low-dose thyroid hormone replacement temporarily (from four to twelve weeks). Therapy should the be discontinued and testing performed six to eight weeks later to assure that the gland has fully recovered.

Postpartum Thyroiditis

This entity may occur in as many as 5-10% of all pregnancies. It tends to occur in women with a personal or family history of autoimmune disease. The onset generally occurs after the six-week postpartum checkup, so it is important to warn patients of the symptoms that may occur. The clinical course is similar to the above description of subacute thyroiditis with the initial hyperthyroid phase usually only mildly symptomatic or totally asymptomatic followed by the more clinically significant thyroid phase. As above, treatment is similar and, again, usually only temporary. However, there is a slightly higher chance of recurrence with subsequent pregnancies and a higher risk of permanent hypothyroidism than seen with subacute thyroiditis.

Nodular Thyroid Disease

Nodular thyroid disease, as with other thyroid disorders, appears to be more common in women. Depending on the geographic population studied as well as age distribution, most population studies report the presence of palpable thyroid nodules in 3-7% of adults with a 5:1 female to male ratio. These nodules may be solitary or one or more within a multinodular thyroid. High resolution thyroid ultrasonography has now been able to identify occult thyroid nodules in up to 13-40% of patients undergoing evaluation for nonthyroid problems. Most of these nodules are benign, colloid nodules. However, it is important to rule out the possibility of thyroid carcinoma, which represents 5% of all solitary thyroid nodules. It is important to have a consistent, rational approach in the clinical and diagnostic evaluation on patients with thyroid nodules to help guide appropriate decision-making for intervention or observation.

The initial history and physical examination are essential and may provide clues that may be supportive of benign or malignant scenarios. A family history of a benign thyroid nodular goiter or Hashimoto's disease, clinical pain or tenderness associated with the nodule, or a multinodular goiter without a dominant nodule generally favors benign disease but does not exclude the possibility of thyroid cancer. In contrast, a family history of thyroid cancer, a prior history of external neck irradiation during childhood, the finding of dysphagia or hoarseness in association with a thyroid nodule, and the presence of a firm, fixed nodule with our without cervical lymphadenopathy raises the suspicion of malignant thyroid disease.

Initial laboratory evaluation should include a sensitive thyroid-stimulating hormone (TSH) to rule out the presence of hyperthyroidism. Most individuals, however, with thyroid nodular disease are biochemically euthyroid. Serum antithyroid-peroxidase antibodies (formerly termed antimicrosomal antibodies) may be helpful in diagnosing Hashimoto's thyroiditis. Hashimoto's thyroiditis may be associated with focal nodular changes within the thyroid gland, and though it is more frequently associated with benign thyroid nodules, its presence does not exclude the possibility of thyroid cancer. The diagnosis of thyroid lymphoma should be considered in patients with a previous diagnosis of Hashimoto's thyroiditis in which there is a rapid increase in size of the thyroid. A serum thyroglobulin level is quite nonspecific and is not helpful in the initial screening evaluation of a solitary thyroid nodule. The measurement of serum thyroglobulin is quite helpful, however, in patients with a prior history of thyroid cancer in monitoring for recurrent disease.

Radionuclide thyroid scanning is not necessary or cost effective in the initial evaluation of euthyroid nodular disease. When a thyroid scan is performed, the nodules are characterized based on their pattern of radionuclide uptake. Nodules which accumulate more isotope than normal thyroid tissue are characterized as hot or autonomous. These hot nodules are generally benign and rarely represent malignancy. Most patients with hot nodules are euthyroid but may become thyrotoxic when the nodules are larger than 2-3 centimeters in size. Cold nodules represent hypo- or non-functional thyroid nodules and are seen as photopenic defects on thyroid scanning. The majority of cold nodules are benign, as well, though the risk of malignancy is increased slightly in a range of 5-8% of cases. Hence, thyroid scanning is very rarely helpful in differentiating between benign and malignant thyroid nodular disease.

Thyroid ultrasonography is frequently used to evaluate the thyroid. It is quite helpful in differentiating solid versus cystic lesions, which is important since cystic lesions carry a lower risk of thyroid cancer. It is not uncommon with ultrasound to find multiple nodules in a gland presumed to have a single, palpable nodule. The largest nodule within a multinodular gland is termed the dominant nodule, and, for diagnostic purposes, should be approached similarly to the solitary thyroid nodule. Thyroid ultrasound may also be helpful in monitoring the size of a nodule as well as differentiating a solid versus hemorrhagic acute expansion and fast-growing thyroid lesions. Thyroid ultrasonography should only be conducted by or in the presence of a physician so that the images may be directly correlated to physical findings on thyroid palpation. Thyroid ultrasonography is also quite helpful in guiding fine-needle thyroid biopsies.

Thyroid fine-needle aspiration and biopsy is the single best method to identify malignancy in a thyroid nodule. Biopsies can generally be performed with a fine needle, gauge 21-25. This provides a high incidence of successful sampling with low incidence of complications. Reviews of the literature find results of thyroid fine-needle biopsy findings to be benign in 74%, inadequate or suspicious in 22%, and malignant in 4%. Of suspicious nodules, 10-30% were ultimately malignant. Therefore, suspicious or nondiagnostic nodules should generally be rebiopsied or be considered for resection.

Most solitary thyroid nodules are colloid adenomas (27-60%) or benign follicular adenomas (26-40%). However, a benign follicular adenoma cannot be differentiated from a well-differentiated follicular carcinoma from fine-needle aspiration as this distinction depends on the presence or absence of capsular invasion by the tumor. Clinical judgment and experience, based on the physicians' index of suspicion, is critical in guiding the decision for surgical resection versus a course of observation. Table 5 lists the differential diagnosis of thyroid nodules.

Management Of Benign Thyroid Disease

The three main therapeutic options for patients with benign thyroid nodules are observation versus a trial of thyroid hormone suppression versus surgical resection.

Surgery is generally reserved for patients that are exhibiting compressive symptoms of the trachea or esophagus or with evidence of a growth of a nodule, and recurrence of cystic nodules after repeated aspiration. Surgery may also be considered for suspicious lesions or when thyroid fine needle biopsies are nondiagnostic on repeated sampling. Surgical approach generally is limited to an ipsilateral thyroid lobectomy for single nodules.

The use of thyroid hormone suppression therapy remains somewhat controversial. The goal of suppression therapy is a reduction in the size of the thyroid nodule over time. Most studies have suggested that a complete response to suppression therapy occurs in less than 10% of cases while a 50% reduction may be seen in approximately 30% of cases. There has been increasing concern over the possible risk of cardiac arrhythmias and osteopenia associated with longer-term suppression therapy when baseline TSH values are elevated.

If it is elected to simply observe the thyroid nodule, then a follow-up thyroid ultrasound is recommended in three to six months to assess any change in size. A repeat thyroid fine-needle aspirate biopsy is recommended if there is an increase in size of the nodule.

Management Of The Autonomously Functioning "Hot" Thyroid Nodule

In euthyroid patients with hot thyroid nodules, observation is generally recommended. Over time, approximately 5% of patients will progress to overt hyperthyroidism each year, more often with larger nodules 3 cm in diameter or larger. Occasionally, hot nodules may spontaneously involute, again reinforcing the prudence of observation in the absence of overt thyrotoxicosis. Treatment options for hyperthyroid patients with toxic adenomas include radioiodine therapy or surgical resection. The choice between these modalities remains controversial. We generally recommend radioiodine therapy in middle-aged and older patients since it is highly effective and noninvasive.

Malignant Thyroid Nodules

In general, the ideal surgical approach for patients with confirmed malignant thyroid nodules is a near total thyroidectomy. For patients with follicular and papillary thyroid carcinoma, postoperative high-dose radioactive iodine treatment has been found to be highly effective in reducing the risk of recurrent thyroid carcinoma.

Summary

Thyroid fine needle aspiration biopsy and thyroid ultrasound have greatly enhanced the management approach to thyroid nodular disease. Diagnostic findings must always be correlated to a comprehensive history and thyroid examination by palpation. Routine thyroid scanning is not recommended except in selected cases or in the setting of hyperthyroidism as hallmarked by a suppressed TSH.

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January, 1999/ Jacksonville Medicine

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