Thyroid Disease (Harrison's)

X-37. The patient described above is started on atenolol and his heart rate slows to 80 beats/min. Which of the fol- lowing additional therapies is indicated? A. Diltiazem B. Itraconazole C. Liothyronine D. Methimazole E. Phenoxybenzamine

X -37. The answer is D. (Chap. 335) Hyperthyroidism is treated by reducing thyroid hor- mone synthesis, using antithyroid drugs, reducing the amount of thyroid tissue with ra- dioactive iodine, or by thyroidectomy. Antithyroid drugs are used more frequently in Japan and Europe, whereas radioactive thyroid is used more frequently in North Amer- ica. Propthiouracil and methimazole are the most commonly used antithyroid drugs and act by inhibiting the function of thyroid peroxidase. In Graves' disease, they also reduce thyroid antibody levels. Thyroid function tests and clinical manifestations are reviewed every 3-4 weeks with dose titrated based on unbound T4 levels. Euthyroidism usually takes 6-8 weeks with this regimen. Agranulocytosis occurs in <1% of patients. Since ra- dioactive iodine is contraindicated in pregnancy, propthiouracil may be used carefully since blocking doses may cause fetal hypothyroidism. Diltiazem may be used to slow heart rate in atrial fibrillation; however, beta blockers are effective in hyperthyroidism to control adrenergic symptoms. Itraconazole is an antifungal agent. Phenoxybenzamine is an α-adrenergic blocker often used to control blood pressure in patients with pheochro- mocytoma. Liothyronine is the oral form of triiodothyronine (T3) and would not be used in hyperthyroidism. Levothyroxine has been used in combination with antithyroid drugs (block-replace regimen) to avoid drug-induced hypothyroidism.

X-1. What is the most common cause of hypothyroidism worldwide? A. Autoimmune disease B. Graves' disease C. Iatrogenic causes D. Iodine deficiency E. Medication side effects

X-1. The answer is D. (Chap. 335) The thyroid produces two related hormones, T3 and T4. These hormones act on nuclear receptors inside cells to regulate differentiation during development and maintain metabolic homeostasis in virtually all human cells. T4 is se- creted in excess of T3 from the thyroid and both are protein-bound in the plasma. Pro- tein binding delays hormone clearance. Unbound protein appears to be more biologically active. T4 is converted to more active T3 in peripheral tissues. Two thyroid hormone receptors are bound to specific DNA sequences; when activated by thyroid hormone, these receptors can act to up-regulate or down-regulate gene transcription. Io- dide uptake by the thyroid is the critical first step of thyroid hormone synthesis. Dietary iodine deficiency leads to decreased production of thyroid hormone and represents the most common cause of hypothyroidism worldwide. In areas of iodine sufficiency, au- toimmune disease such as Hashimoto's thyroiditis and iatrogenic causes are the most common etiologies for hypothyroidism. Paradoxically, chronic iodine excess can also cause goiter and hypothyroidism via unclear mechanisms. This is the mechanism for the hypothyroidism that occurs in up to 13% of patients taking amiodarone. Graves' disease leads to hyperthyroidism.

X-10. A 44-year-old male is involved in a motor vehicle col- lision. He sustains multiple injuries to the face, chest, and pelvis. He is unresponsive in the field and is intubated for airway protection. An intravenous line is placed. The pa- tient is admitted to the intensive care unit (ICU) with multiple orthopedic injuries. He is stabilized medically and on hospital day 2 undergoes successful open reduc- tion and internal fixation of the right femur and right hu- merus. After his return to the ICU, you review his laboratory values. TSH is 0.3 mU/L, and the total T4 level is normal. T3 is 0.6 μg/dL. What is the most appropriate next management step? A. Initiation of levothyroxine B. A radioiodine uptake scan C. A thyroid ultrasound D. Observation E. Initiation of prednisone

X-10. The answer is D. (Chap. 335) Sick-euthyroid syndrome can occur in the setting of any acute, severe illness. Abnormalities in the levels of circulating TSH and thyroid hormone are thought to result from the release of cytokines in response to severe stress. Multiple abnormalities may occur. The most common hormone pattern is a decrease in total and unbound T3 levels as peripheral conversion of T4 to T3 is im- paired. Teleologically, the fall in T3, the most active thyroid hormone, is thought to limit catabolism in starved or ill patients. TSH levels may vary dramatically, from 0.1 to >20 mU/L, depending on when they are measured during the course of illness. Very sick patients may have a decrease in T4 levels. This patient undoubtedly has ab- normal thyroid function tests as a result of his injuries from the motor vehicle acci- dent. There is no indication for obtaining further imaging in this case. Steroids have no role. The most appropriate management consists of simple observation. Over the course of weeks to months, as the patient recovers, thyroid function will return to normal.

X-15. A 29-year-old woman presents to your clinic com- plaining of difficulty swallowing, sore throat, and tender swelling in her neck. She has also noted fevers intermit- tently over the past week. Several weeks prior to her cur- rent symptoms she experienced symptoms of an upper respiratory tract infection. She has no past medical his- tory. On physical examination, she is noted to have a small goiter that is painful to the touch. Her oropharynx is clear. Laboratory studies are sent, and reveal a white blood cell count of 14,100 cells/μL with a normal differ- ential, erythrocyte sedimentation rate (ESR) of 53 mm/h, and a thyroid-stimulating hormone (TSH) of 21 μΙU/mL. Thyroid antibodies are negative. What is the most likely diagnosis? A. Autoimmune hypothyroidism B. Cat-scratch fever C. Graves' disease Ludwig's angina D. Subacute thyroiditis

X-15, E (see 16 for explanation) FIGURE X-15/16 Clinical course of subacute thy- roiditis. The release of thyroid hormones is initially associated with a thyrotoxic phase and suppressed thyroid-stimulating hormone (TSH). A hypothyroid phase then ensues, with low T4 and TSH levels that are initially low but gradually increase. During the recov- ery phase, increased TSH levels combined with reso- lution of thyroid follicular injury leads to normaliza- tion of thyroid function, often several months after the beginning of the illness. ESR, erythrocyte sedi- mentation rate; UT4, unbound T4.

X-16. What is the most appropriate treatment for the patient described above? A. Iodine ablation of the thyroid B. Large doses of aspirin C. Local radiation therapy D. No treatment necessary E. Propylthiouracil

X-15. and. X-16. The answers are E and B. (Chap. 335) Subacute thyroiditis, also known as de Quervain's thyroiditis, granulomatous thyroiditis, or viral thyroiditis, is a multiphase ill- ness three times more frequent in women than men. Multiple viruses have been impli- cated, but none have been definitively identified as the trigger for subacute thyroiditis. The diagnosis can be overlooked in patients as the symptoms mimic pharyngitis, and it fre- quently has a similarly benign course. In this patient, Graves' disease is unlikely given her elevated TSH and negative antibody panel. Autoimmune hypothyroidism should be con- sidered; however, the tempo of her illness, the tenderness of the thyroid on examination, and her preceding viral illness make this diagnosis less likely. Ludwig's angina is a poten- tially life-threatening bacterial infection of the retropharyngeal and submandibular spaces, often caused by preceding dental infection. Cat-scratch fever is a usually benign illness that presents with lymphadenopathy, fever, and malaise. It is caused by Bartonella henselae and is frequently transmitted from cat scratches that penetrate the epidermis. It will not cause an elevated TSH. Subacute thyroiditis can present with hypothyroidism, thyrotoxicosis, or neither. In the first phase of the disease, thyroid inflammation leads to follicle destruction and release of thyroid hormone. Thyrotoxicosis ensues. In the second phase, the thyroid is depleted of hormone and hypothyroidism results. A recovery phase typically follows in which decreased inflammation allows the follicles to heal and regenerate hormone. Large doses of aspirin (such as 600 mg by mouth every 4-6 h) or nonsteroidal anti-in- flammatory drugs are often sufficient for what is usually a self-limited illness. A glucocor- ticoid taper can be used if symptoms are severe. Thyroid function should be monitored closely; some patients may require low-dose thyroid hormone replacement.

X-36. A 62-year-old man presents to a local emergency room complaining of chest pressure and feeling "like my heart is fluttering inside my chest." He experienced similar symp- toms 1 month ago that resolved spontaneously. He did not seek medical attention at that time. He has no significant past medical history. On review of systems he notes some recent weight loss and excessive sweating. He feels as though his appetite has increased lately. His wife adds that he has recently taken some time off work due to fatigue; despite his time off he has not been able to relax and has not been sleeping well. On physical examination his heart rate is irregular at 140-150 beats/minute. Blood pressure is 134/55 mmHg. He is admitted to the hospital and screen- ing tests reveal an undetectable thyroid-stimulating hor- mone level. Which of the following statements is true? A. 50% of hyperthyroid patients will convert from atrial fibrillation to normal sinus rhythm with thyroid management alone. B. A firm, small thyroid on physical examination would be compatible with a diagnosis of Graves' disease. C. Atrial fibrillation is the most common cardiac manifestation of hyperthyroidism. D. His excessive sweating is likely not related to hyper- thyroidism. E. Hyperthyroidism leads to a high-output state for the heart, and narrowing pulse pressure.

X-36. The answer is A. (Chap. 335) Thyrotoxicosis presents with a characteristic set of signs and symptoms. Common signs include tachycardia and atrial fibrillation, tremor, goiter, and warm, moist skin. Common symptoms include hyperactivity, dysphoria, irritability, heat intolerance, excessive sweating, and fatigue. Weight loss occurs frequently; however, some patients will gain weight as they typically have a marked increase in appetite. The most common cardiac abnormality of thyrotoxicosis is sinus tachycardia. In older patients atrial fibrillation is frequently seen. These arrhythmias are a manifestation of a high-output state, which frequently leads to a widened pulse pressure and a systolic mur- mur. This can exacerbate underlying heart failure or coronary disease. Up to 50% of pa- tients with atrial fibrillation related to untreated thyrotoxicosis will convert to normal sinus rhythm with management of their thyroid condition.

X-39. Which of the following statements regarding autoimmune hypothyroidism is true? A. 10% of 40- to 60-year-old adults have subclinical hypothyroidism. B. Absence of a goiter makes autoimmune hypothy- roidism unlikely. C. Family history of autoimmune disorders does not significantly increase risk. D. It is more common in the Pacific Rim where diets are lower in iodine. E. Viral thyroiditis does not induce subsequent au- toimmune thyroiditis.

X-39. The answer is E. (Chap. 335) Autoimmune hypothyroidism is a common diagnosis, present in 4 per 1000 women and 1 per 1000 men. The mean age of diagnosis is 60 years. It is more prevalent in locations with chronic exposure to a high-iodine diet, such as Ja- pan. Subclinical hypothyroidism (elevated thyroid-stimulating hormone, normal un- bound T4) is present in 6-8% of women and 3% of men. It is present in up to 10% of adults >60 years of age. There is an association between autoimmune hypothyroidism and other autoimmune conditions, and there appears to be a heritable familial risk of de- veloping disease. There are likely environmental triggers other than heavy iodine expo- sure that predispose to the disease phenotype in susceptible individuals, but these have not been identified. Autoimmune thyroiditis may present with or without a goiter. When a goiter is present, it is termed Hashimoto's thyroiditis. The goiter is due to lymphocytic infiltration of the thyroid. Eventually atrophy of thyroid follicles leads to shrinkage of the gland. Atrophic thyroiditis likely represents the end stage of Hashimoto's thyroiditis. There is no evidence that viral thyroiditis induces subsequent autoimmune thyroiditis.

X-41. In regard to Graves' disease, which of the following is true? A. It accounts for >90% of all causes of thyrotoxicosis. B. It occurs in 2% of women. C.It typically occurs in patients between 50 and 60 years of age. D. Populations with a low iodine intake have an increased prevalence. E. There is an equal male-to-female prevalence.

X-41. The answer is B. (Chap. 335) Thyrotoxicosis is a state of hormone excess. It is not synony- mous with hyperthyroidism, which is the result of excessive thyroid function. Graves' disease ac- counts for 60-80% of thyrotoxicosis. Graves' disease is caused by the presence of thyroid- stimulating antibodies, which autonomously activate the thyroid-stimulating hormone receptor and cause overproduction of thyroid hormone. Other common causes of thyrotoxicosis include toxic multinodular goiter and toxic thyroid adenoma. Thyrotoxicosis without hyperthyroidism may occur in subacute thyroiditis, thyroid destruction from amiodarone or radiation, or inges- tion of excess thyroid hormone. Graves' disease is common among populations with high io- dine intake and occurs in up to 2% of women. It is one-tenth as frequent in men. It rarely presents in adolescence, and is most prevalent in patients between the ages of 20 and 50 years.

X-46. A 38-year-old woman presents to her primary care doctor complaining of fatigue and irritability. She thinks these symptoms have been worsening over a period of sev- eral months. She has a history of mild intermittent asthma and hypertriglyceridemia. Physical examination reveals a resting heart rate of 105 beats/min, blood pressure of 136/ 72 mmHg, bilateral proptosis and warm, moist skin. Screening tests are sent and reveal a thyroid-stimulating hormone (TSH) level that is undetectable and a normal unbound T4. What should be the next step in diagnosis? A. Radionuclide scan of the thyroid B. Thyroid-stimulating antibody screen C. Thyroid peroxidase (TPO) antibody screen D. Total T4 E. Unbound T3

X-46. The answer is E. (Chap. 335) This patient has signs and symptoms of Graves' disease. In patients with thyrotoxicosis due to Graves' disease, the TSH level is low and total and unbound thyroid hormone levels are increased. In 2-5% of patients, only the T3 levels will be increased. In this patient, with a high pre-test probability of Graves' disease, a sup- pressed TSH and normal T4 supports Graves'; however, testing of T3 should be performed to definitively make the diagnosis. A total T4 level would not provide definitive evidence of Graves' disease. Radionuclide scan of the thyroid is used to evaluate for toxic multinodular goiter and toxic adenoma. Measurement of thyroid-stimulating antibodies and thyroid peroxidase antibodies will help confirm the diagnosis of Graves' but are not routinely used since the diagnosis may be made with a consistent clinical picture com- bined with supportive TSH and thyroid hormone results. Figure x-46 Evaluation of thyrotoxicosis. aDiffuse goiter, positive TPO antibodies, oph- thalmopathy, dermopathy; bcan be confirmed by radionuclide scan. TSH, thyroid-stimulating hormone

X-55. A 62-year-old woman presents to your clinic com- plaining of fatigue and lethargy over a period of 6 months. She cannot recall exactly when these symptoms started, but feels that they are worsening with time. She describes dry skin and has noted that she is losing hair. On examination she is mildly bradycardic at 52 beats/min with normal blood pressure and has dry, coarse skin. There are areas of alopecia and mild lower extremity edema is noted. Which of the following is the most likely clinical diagnosis and which test would be indicated for screening for the diagnosis? A. Hyperthyroidism: thyroid-stimulating hormone (TSH) B. Hyperthyroidism: unbound T4 C. Hypothyroidism: TSH D. Hypothyroidism: unbound T4

X-55. The answer is C. (Chap. 335) The main clinical symptoms of hypothyroidism include tiredness, weakness, dry skin, feeling cold, hair loss, difficulty concentrating, constipation with poor appetite, dyspnea, and hoarse voice. Menorrhagia, amenorrhea, paresthesias, and impaired hearing may also occur. Signs of hypothyroidism include dry coarse skin, puffy hands/face/feet (myxedema), diffuse alopecia, bradycardia, peripheral edema, delayed ten- don reflex relaxation, carpal tunnel syndrome, and serous cavity effusions. The symptoms of hyperthyroidism include hyperactivity, irritability, dysphoria, heat intolerance, sweating, palpitations, fatigue and weakness, weight loss with increased appetite, diarrhea, loss of li- bido, polyuria, and oligomenorrhea. Signs include tachycardia, atrial fibrillation (particu- larly in the elderly), tremor, goiter, warm moist skin, proximal myopathy, lid lag, and gynecomastia. Exophthalmous is specific for Graves' disease. TSH is the most effective screening test for hypothyroidism. If elevated, an unbound T4 is necessary to confirm clini- cal hypothyroidism. Testing of unbound T4 will not detect subclinical hypothyroidism. Subclinical hypothyroidism is present when the TSH is elevated and unbound T4 is normal. Patients may have minor or early symptoms of hypothyroidism in this stage.

X-65. Which of the following is consistent with a diagnosis of subacute thyroiditis? A. A 38-year-old female with a 2-week history of a painful thyroid, elevated T4, elevated T3, low TSH, and an elevated radioactive iodine uptake scan B. A 42-year-old male with a history of a painful thy- roid 4 months ago, fatigue, malaise, low free T4, low T3, and elevated TSH. C. A 31-year-old female with a painless enlarged thy- roid, low TSH, elevated T4, elevated free T4, and an elevated radioiodine uptake scan D. A 50-year-old male with a painful thyroid, slightly elevated T4, normal TSH, and an ultrasound show- ing a mass E. A 46-year-old female with 3 weeks of fatigue, low T4, low T3, and low TSH

X-65. The answer is B. (Chap. 335) Subacute thyroiditis, also known as de Quervain's thy- roiditis, granulomatous thyroiditis, and viral thyroiditis, is characterized clinically by fe- ver, constitutional symptoms, and a painful enlarged thyroid. The etiology is thought to be a viral infection. The peak incidence is between 30 and 50 years of age, and women are af- fected more frequently than are men. The symptoms depend on the phase of the illness. During the initial phase of follicular destruction, there is a release of thyroglobulin and thyroid hormones. As a result, there is increased circulating T4 and T3, with concomitant suppression of TSH. Symptoms of thyrotoxicosis predominate at this point. Radioiodine uptake is low or undetectable. After several weeks, thyroid hormone is depleted and a phase of hypothyroidism ensues, with low unbound T4 levels and moderate elevations of TSH. Radioiodine uptake returns to normal. Finally, after 4 to 6 months, thyroid hormone and TSH levels return to normal as the disease subsides. Patient A is consistent with the thyrotoxic phase of subacute thyroiditis except for the increased radioiodine uptake scan. Patient C is more consistent with Graves' disease with suppression of TSH, an elevated up- take scan, and elevated thyroid hormones as a result of stimulating immunoglobulin. Pa- tient D is consistent with a neoplasm. Patient E is consistent with central hypothyroidism.

X-69. A healthy 53-year-old man comes to your office for an annual physical examination. He has no complaints and has no significant medical history. He is taking an over-the-counter multivitamin and no other medicines. On physical examination he is noted to have a nontender thyroid nodule. His thyroid-stimulating hormone (TSH) level is checked and is found to be low. What is the next step in his evaluation? A. Close follow-up and measure TSH in 6 months B. Fine-needle aspiration C. Low-dose thyroid replacement D. Positron emission tomography followed by surgery E. Radionuclide thyroid scan

X-69. The answer is E. (Chap. 335) Thyroid nodules are found in 5% of patients. Nodules are more common with age, in women, and in iodine-deficient areas. Given their prev- alence, the cost of screening, and the generally benign course of most nodules, the choice and order of screening tests have been very contentious. A small percentage of incidentally discovered nodules will represent thyroid cancer, however. A TSH should be the first test to check after detection of a thyroid nodule. A majority of patients will have normal thyroid function tests. In the case of a normal TSH, fine-needle aspiration or ultrasound-guided biopsy can be pursued. If the TSH is low, a radionuclide scan should be performed to determine if the nodule is the source of thyroid hyperfunction (a "hot" nodule). In the case above, this is the best course of action. "Hot" nodules can be treated medically, resected, or ablated with radioactive iodine. "Cold" nodules should be further evaluated with a fine-needle aspiration. 4% of nodules undergoing biopsy will be malignant, 10% are suspicious for malignancy and 86% are indetermi- nate or benign. FIGURE X-69 Approach to the pa- tient with a thyroid nodule. See text and references for details. *About one-third of nodules are cystic or mixed solid-cystic. US, ultrasound; TSH, thyroid-stimulating hormone; FNA, fine-needle aspiration.

X-7. A 34-year-old woman presents to your clinic with a variety of complaints that have been worsening over the past year or so. She notes fatigue, amenorrhea, and weight gain. She states that her primary physician diagnosed her with hypothyroidism several months ago, and she has been faithfully taking thyroid hormone replacement. Her thyroid-stimulating hormone (TSH) has been in the nor- mal range over the last two laboratory checks. When her symptoms did not improve on synthroid, she was sent to your clinic for further evaluation. A diagnosis of pan- hypopituitarism is considered. All of the following are consistent with normal pituitary function except A. Basal elevation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in a post- menopausal woman B. Elevation of aldosterone after infusion of cosyntropin C. Elevation of growth hormone after ingestion of a glucose load D. Elevation of cortisol after injection of regular insulin E. Elevation of TSH after infusion of thyrotropin- releasing hormone (TRH)

X-7. The answer is C. (Chap. 333) Osteoporosis is a significant public health problem in the United States affecting 8 million women and 2 million men. An additional 18 million individu- als are at risk for development of osteoporosis as measured by low bone density (osteopenia). Most of these individuals are unaware of the presence of osteopenia or osteoporosis. In the United States and Europe, fractures related to osteoporosis are much more common in women than men, although this is not seen in all races. Diagnosis of pituitary insufficiency is made by biochemical demonstration of low levels of trophic hormones in the setting of low target hormone levels. Thus, in a postmenopausal woman, a low FSH and LH would suggest hypopituitarism. Provocative tests may also be used to test reduced pi- tuitary reserve. Growth hormone should elevate during hypoglycemic stress, not during hyperglycemia. Elevation of aldosterone (or cortisol) after cosyntropin, corti- sol after insulin-induced hypoglycemia, or TSH after TRH are consistent with intact pituitary function. A summary of tests of pituitary insufficiency is shown in the fol- lowing table.

X-79. Which of the following statements regarding hypothyroidism is true? A. Hashimoto's thyroiditis is the most common cause of hypothyroidism worldwide. B. The annual risk of developing overt clinical hypothyroidism from subclinical hypothyroidism in patients with positive thyroid peroxidase (TPO) antibodies is 20%. C. Histologically, Hashimoto's thyroiditis is characterized by marked infiltration of the thyroid with activated T cells and B cells. D. A low TSH level excludes the diagnosis of hypothyroidism. E. Thyroid peroxidase antibodies are present in less than 50% of patients with autoimmune hypothyroidism.

X-79. The answer is C. (Chap. 335) Iodine deficiency is the most common worldwide cause of hypothyroidism. Autoimmune, or Hashimoto's, thyroiditis is a common cause in de- veloped countries with dietary iodine supplementation. Histologically, it is characterized by lymphocytic infiltration of the thyroid with activated T cells and B cells. Thyroid cell destruction is thought to be mediated by cytotoxic CD8+ T lymphocytes. Primary hy- pothyroidism is characterized by an elevation in TSH as the feedback inhibition of the anterior pituitary is diminished. However, patients with hypothyroidism may have low TSH in the setting of secondary hypothyroidism. In this case, a clinical and radiologic evaluation of the pituitary is required. Subclinical hypothyroidism is characterized by ab- normalities in the serum levels of TSH but minimal symptoms and often minimal change in the free T4 level. The rate of development of overt, symptomatic hypothyroidism is about 4% per year, especially in the case of positive TPO antibodies, which are present in 90 to 95% of patients with autoimmune hypothyroidism.

X-38. A patient presents to his primary care physician com- plaining of fatigue and hair loss. He has gained 6.4 kg since his last clinic visit 6 months ago but notes markedly decreased appetite. On review of systems, he reports that he is not sleeping well and feels cold all the time. He is still able to enjoy his hobbies and spending time with his family, and does not believe that he is depressed. His ex- amination reveals diffuse alopecia and slowed deep ten- don reflex relaxation. Hypothyroidism is high on the differential for this patient. Which of the statements re- garding that diagnosis is correct? A. A normal thyroid-stimulating hormone (TSH) ex- cludes secondary, but not primary hypothyroidism. B. T3 measurement is not indicated to make the diagnosis. C. The T3/T4 ratio is important for determining response to therapy. D. Thyroid peroxidase antibodies distinguish between primary and secondary hypothyroidism. E. Unbound T4 is a better screening test than TSH for subclinical hypothyroidism.

x-38 The answer is B. (Chap. 335) While hypothyroidism may be strongly suspected from his- tory and physical examination findings, it is definitively diagnosed with serum laboratory measurements. TSH should be the first test sent. A normal TSH level excludes primary, but not secondary, hypothyroidism. Primary hypothyroidism refers to disease caused by hypo- function of the thyroid gland itself. Secondary hypothyroidism typically arises from disease of the anterior pituitary. If the TSH is low or normal and pituitary disease is suspected, a free T4 should be sent. If this test is low, the differential includes anterior pituitary dysfunction, sick euthyroid syndrome, and drug effects. TSH, not unbound T4, is the test of choice for diagnos- ing subclinical hypothyroidism. In these cases, TSH is elevated and T4 is normal. Thyroid per- oxidase antibodies are present in >90% of patients with autoimmune hypothyroidism; this test helps distinguish autoimmune causes of hypothyroidism from other possibilities. Circu- lating T3 levels are normal in ~25% of patients with clinical hypothyroidism and are not indi- cated for diagnosis. A T3/T4 ratio is not helpful for diagnosis or prognosis. FIGURE X-38 Evaluation of hy- pothyroidism. TPOAb+, thyroid peroxidase antibodies present; TPOAb-, thyroid peroxidase anti- bodies not present; TSH, thyroid- stimulating hormone.