Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (208 page)

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DISORDERS OF THE THYROID GLAND

THYROTOXICOSIS/HYPERTHYROIDISM

   Definition

Thyrotoxicosis refers to the classic physiologic manifestations of excessive quantities of the circulating thyroid hormones. The term hyperthyroidism is reserved for disorders that result from sustained overproduction of the hormone by the thyroid itself. Thyrotoxicosis can be caused by hyperthyroidism, or by exogenous thyroid hormone, iatrogenic, or self-administered.

   Overview

The clinical manifestations of thyrotoxicosis are largely independent of its cause. However, the disorder that causes thyrotoxicosis may have other effects. The most common form is Graves disease, comprising 70–80% of the cases.

   Common Causes

  1.  Graves disease (diffuse toxic goiter) is the prototypic autoimmune hyperthyroid condition. Prevalence is approximately 1–2% in women; in men, the prevalence is about one tenth of that. Patients commonly have a family history of thyroid dysfunction (hyperthyroidism or hypothyroidism). It may be accompanied by an infiltrative orbitopathy and ophthalmopathy. In patients and their relatives, there is an increased frequency of other autoimmune disorders, such as DM, pernicious anemia, and myasthenia gravis. The radioactive iodine uptake (RAIU) is typically elevated unless the patient has been exposed to excess iodine or acutely to large dose of glucocorticoids. The circulating autoantibodies specific to Graves disease are directed against the thyroid-stimulating hormone (TSH) receptor and can be measured directly.

  2.  Toxic multinodular goiter (MNG) is a disorder in which hyperthyroidism arises in a multinodular goiter, usually of long standing. The overproduction of thyroid hormone is usually less than in Graves disease and is almost never accompanied by infiltrative ophthalmopathy. All patients with MNG should be screened annually with a serum TSH.

  3.  Toxic adenoma is usually caused by a single adenoma sometimes referred to as hyperfunctioning solitary nodule or toxic nodule. It often shows a suppressed TSH, which appears in a radioiodine thyroid scan as a localized area of increased radioiodine accumulation.

  4.  Chorionic gonadotropin–induced hyperthyroidism can be physiologic during pregnancy (transient gestational thyrotoxicosis) or associated with trophoblastic tumors.

  5.  Iodide-induced hyperthyroidism. Administration of supplemental iodine to subjects with endemic iodine deficiency goiter can result in iodide-induced hyperthyroidism. Amiodarone, an antiarrhythmic medication, is the most common drug that has been reported to be associated with iodine-induced thyrotoxicosis.

  6.  Autoimmune (Hashimoto’s) thyroiditis can be associated with transient thyrotoxicosis, which is caused by thyroid cell breakdown, and the hyperthyroid symptoms are of abrupt onset and short duration.

  7.  Subacute thyroiditis is an acute inflammatory disorder of the thyroid gland, which is caused directly or indirectly by a viral infection. The symptoms of fever, malaise, and neck soreness frequently overshadow the symptoms of hyperthyroidism. Characteristic findings are of a tender thyroid gland, an elevated erythrocyte sedimentation rate (ESR), and a low RAIU.

  8.  Excess thyroid hormone ingestion can be either iatrogenic or factitious. The presence of a low, rather than elevated, serum thyroglobulin level in a patient with thyrotoxic manifestations and a low RAIU is very suspicious for exogenous hormone ingestion rather than thyroid hyperfunction.

  9.  Thyroid storm (accelerated hyperthyroidism) represents an extreme accentuation of thyrotoxicosis. It is an uncommon but serious complication, with a mortality of 10–75%. Manifestations include severe fever, marked tachycardia, cardiac arrhythmias, tremulousness, and altered mental status.

10.   Subclinical (mild) hyperthyroidism refers to the situation that there are no signs or symptoms of thyrotoxicosis, but the serum TSH is subnormal despite normal serum free thyroid hormone concentrations. The diagnosis requires several subnormal TSH concentration results spaced months apart.

11.   Ectopic thyroid hormone excretion from the ovary (struma ovarii).

   Who Should Be Suspected?

Signs and symptoms of thyrotoxicosis include

  1.  Anxiety, emotional lability, nervousness, and irritability

  2.  Heat intolerance and increased perspiration

  3.  Weight loss despite a normal or increased appetite

  4.  Tremor, palpitations, tachycardia, proximal muscle weakness, and exophthalmos

  5.  Oligomenorrhea in women; gynecomastia and erectile dysfunction in men

   Laboratory Findings

The availability of sensitive and reliable assays for serum TSH and free thyroxine (T
₄
) has made the laboratory diagnosis of hyperthyroidism rather straightforward (Figure
6-1
).

   Serum TSH is the most cost-effective screening test. If the value is normal, the patient is very unlikely to have hyperthyroidism. In hyperthyroidism, serum TSH is below normal and frequently <0.1 μIU/mL. TSH may remain decreased for many months in treated formerly hyperthyroid patients; therefore, thyroid hormone levels more accurately reflect the clinical situation.

   Serum free T
₄
is important to confirm and determine the degree of hyperthyroidism in a patient with a low TSH.