AMA Titer of 1:1,600 Suggested Autoimmune Thyroiditis As the Etiology

Patient 1

A 30-year-old white female reported 1 year of fatigue, apathy, hoarseness, neck swelling, and cold intolerance. She worked as a medical receptionist and experienced increasing difficulty answering phone calls due to deepened voice quality and delayed responses to callers. Prior clinical impressions included depression, job stress, and laryngitis. Acute laryngitis is often a secondary bacterial infection triggered by infecting agents causing such illnesses as colds. There was no response to antibiotics or antidepressant medication. On examination, she was found to have a deep, gruff voice, periorbital edema, 40 gram goiter, and delayed AJRP. Cholesterol, CPK, and MCV were elevated.

Extreme TSH elevation of 417 mU/L and decreased T4 of 1.7 ug/dL confirmed the presence of severe hypothyroidism.

AMA titer of 1:1,600 suggested autoimmune thyroiditis as the etiology.

She received thyroxine 25 ug daily and prednisone 5 mg daily for 1 week, with upward titration of thyroxine every 4 weeks to a maintenance dose of 125 ug daily. Vigor returned, voice improved, and temperature tolerance normalized within 1 month. Cholesterol, CPK, MCV, and TSH normalized within 5 months. She received advanced medical training and was promoted to a nursing position in the same office.

Patient 2

A 38-year-old white male experienced 1 year of progressive fatigue, weakness, lethargy, cold intolerance, mental dullness, and erratic driving while working as a forklift operator. He was evaluated in the Family Medicine Center at the insistence of his wife who had earlier requested clomiphene, a synthetic drug that is used to stimulate ovulation for her inability to conceive a second child.

A thorough medical examination for diagnostic purposes revealed no female etiology.

The husband's fatigue and apathy were attributed to overwork. He had received radioiodine therapy for Graves disease at age 16, with erratic physician follow-up for over 20 years. On evaluation he displayed slow mentation, thick-tongued speech, periorbital edema, and delayed AJRP.

The clinical impression of postirradiation hypothyroidism was confirmed by detection of a TSH of 612 mU/L and T4 less than 1.0 ug/dL. Cholesterol and CPK were elevated. Testosterone was low at 146 ng/dL (normal: 270-1070). Semen analysis revealed extensive abnormalities in sperm anatomy and motility.

He received thyroxine 50 ug daily with prednisone 5 mg daily for 7 days. Within 6 months, energy level rebounded, eyelid edema resolved, mental acuity returned, driving improved, CPK normalized, and T4 rose to 4.9 ug/dL with TSH down to 29 mU/L, on thyroxine 150 ug daily. TSH, testosterone, and semen analysis normalized in 8 months. The couple celebrated the birth of a healthy daughter 11 months later.

Patient 3

A 24-year-old white female had 4 months of fatigue, weakness, irritability, sadness, reduced libido, profuse hair loss, and inability to lose weight, following the birth of her second child 6 months earlier. She assisted her husband with leadership of a large church youth group but found her performance compromised due to worsening fatigue and mood disturbance. She attended a physician-directed weight loss clinic without success and withdrew due to fatigue. Symptoms were attributed to postpartum depression. On initial evaluation, a 30-gram goiter and frontal hair loss were detected, along with normal mentation and AJRP.

The clinical impression of hypothyroidism was confirmed by a TSH of 384 mU/L, T4 less than 1.0 ug/mL, and T3 diminished at 49 ng/mL. Values for CPK, MCV, and cholesterol were normal. AMA titer was 1:102,400, documenting the presence of postpartum autoimmune thyroiditis.

With thyroxine 50 ug daily and upward titration, she regained strength, endurance, and emotional stability within 3 months, and lost 14 pounds with renewed capacity for aerobic exercise. TSH fell to 3 mU/L, T4 rose to 8.4 ug/mL, and AMA titer decreased to 1:25,600. All laboratory values normalized within 6 months, as did mood and functional status.

Patient 4

A 26 year old white female presented to her obstetrician with complaints of heart palpitations. She states that the palpitations have been constant over the past two weeks but seem worse at nighttime. When asked to describe them, she states that they are regular and it feels as if her heart is going to jump out of her chest. She denies chest pain, shortness of breath or lightheadedness. She has felt a bit warm of late. She recently delivered a normal baby boy during an uncomplicated delivery 5 1/2 weeks before this visit. Her review of system is remarkable for loose stools occurring approximately 4 times/day. She complains of feeling tired but unable to get a good night sleep. She states that she feels as if her mind is racing. She denies any nausea, vomiting or abdominal pain. She also denies muscle aches, fevers or chills. She denied heat or cold intolerance.

On physical examination, she presented as a thin, white female in no apparent distress. Her blood pressure was 146/90. Pulse 96 and regular and a normal temperature of 37 degrees taken orally. Her review of systems revealed clear lungs, normal heart rhythm, normal abdomen and a normal neurological response although she showed a fine tremor of the hands. Her neck was supple with no lymphadnopathy however her thyroid was approximately 1.5 times normal in size, symmetrically enlarged, firm, non-tender with carotids palpable bilaterally without bruits.

Her blood work at the time of the clinic visit included a CBC (WBC 14.2, Hct, 38.6, MCV normal, platelet count normal, differential 56% neutrophiles, 7% bands, 34% lymphocytes and 3% monocytes) and a chemistry screen that included electrolytes (NA 142, K 3.6, Cl 101, CO2 22), glucose 86, BUN 26, creatinine 1. She also had a thyroid panel that included thyroxine 16.2 (NL 4-13), T3 resin uptake 34% (NL 25 - 35%) and a TSH of <0.05 (NL 0.3 5.0).

From the physical examination, the patient's history including post partum status and the abnormal thyroid function tests, the working diagnosis was postpartum thyroiditis with hyperthyroidism. The patient had a radioactive iodine uptake scan which was normal and subsequently had thyroid auto-antibodies determined which were positive for anti-thyroglobulin and anti-microsomal antibodies. A thyroid biopsy was also performed and revealed diffuse, lymphocytic infiltration, a characteristic histologic picture of post partum thyroiditis. In this case the patient was simply treated with beta blockers to reduce the heart palpitations. Inside three months, the thyroiditis had resolved and the patients' symptoms disappeared with normal thyroid function test results.

Post partum thyroiditis (PPT) is a relatively common disorder expressed in 5 to 15% of post partum women. This disorder initially presents as thyrotoxicosis in the period from 6 weeks to 3 months post partum, is associated with an auto immune component and usually resolves spontaneously after 1-2 months of expression. In some patients, the thyrotoxic phase can be followed by a hypothyroid phase before spontaneous disease resolution occurs. This thyroid disorder is a distinct variant of silent (painless) thyroiditis and is more prevalent in patients with a family history of Hashimoto's thyroiditis. Over 50% of patients will have a mild goiter condition.

Patient 6

A 61-year-old white female reported 2 years of fatigue, cold intolerance, mental dullness, dyspnea, hoarseness, dry skin, constipation, anemia, and hyperlipidemia (elevated concentrations of any or all of the lipids in the plasma). She had been under the care of five physicians in different specialties, with diagnoses including vocal cord polyps which were resected, diverticulosis- a disorder characterized by the presence of diverticula, which are small, usually multiple saclike protrusions through the wall of the colon- anemia requiring transfusion, and elevated cholesterol refractory to high-dose statin medication. On initial evaluation, she displayed marked psychomotor retardation, cool dry skin, periorbital edema, thick-tongued speech, and delayed AJRP. Cholesterol was elevated despite therapy. CPK was elevated as well.

Extreme TSH elevation of 335 mU/L, with decreased T4 less than 1.0 ug/dL and triiodothyronine. (T3) of 54 ng/mL confirmed the bedside impression of severe hypothyroidism.

She received thyroxine 25 ug daily with prednisone 7.5 mg daily for one week, after which thyroxine was titrated.

Patient 7

A 36-year-old white female was referred to the Family Medicine Inpatient Service for disability evaluation. She had suffered 2 years of progressive fatigue, weakness, and apathy, necessitating a rolling walker to ambulate. She claimed to have had "several strokes" and was seen repeatedly by multidisciplinary specialists at an academic center in a major city. Her husband had to feed her and manage all household chores. On examination, she had a depressed mood, delayed verbal responses, juvenile language, periorbital edema, and absent deep tendon reflexes. She required two assistants to stand and ambulate on her walker. Computed tomography revealed no brain infarcts or demyelinating lesions. An electrocardiogram demonstrated low voltage. Cholesterol and CPK were elevated.

TSH was markedly elevated at 652 mU/L, with T4 less than 1.0 ug/dL and T3 less than 50 ng/dL, confirming the clinical impression of profound hypothyroidism. The AMA titer was less than 1:100, suggesting an idiopathic etiology.

She received thyroxine 25 ug daily with dexamethasone, a synthetic glucocorticoid used primarily as an antiinflammatory in various conditions, including collagen diseases and allergic states; it is the basis of a screening test in the 0.5 mg daily for the first week. Within 2 weeks, she was much stronger, could walk alone, and used adult-level language. T4 rose to 1.5, and TSH decreased to 615. She did not feel a need to pursue disability claims any further and was referred back to her hometown physicians for follow-up care.

Patient 8

A 29-year-old woman presented with a 3-month history of increased sweating and palpitations with weight loss of 7kg. On examination, she was a nervous, agitated woman with an obvious, diffuse, non-tender, smooth enlargement of her thyroid, over which a bruit could be heard. She had a fine tremor of her fingers and a resting pulse rate of 150/minute. A maternal aunt had suffered from 'thyroid disease'.

On investigation, she had a raised serum T3 of 4.8nmol/l (NR 0.8-2.4) and a T4 of 48nmol/l (NR 9-23). Measurement of her thyroid-stimulating hormone showed that this was low normal, 0.4mU/l (NR 0.4-5_mU/l).

The biochemical findings pointed to primary thyroid disease rather than pituitary overactivity. Circulating antibodies to thyroid peroxidase (titre 1/3000; 200iu/ml) were detected by agglutination. A diagnosis of autoimmune thyrotoxicosis (Graves' disease) was made. She was treated with an antithyroid drug, carbimazole, to control her thyrotoxicosis, and surgery was not required.

Patient 9

A 39-year-old woman presented with a large, painless swelling in her neck. The enlargement had been a gradual process over 2 years. She had no other symptoms and felt generally well. On examination, her thyroid was diffusively enlarged and had a rubbery consistency. There were no signs of thyrotoxicosis or of thyroid failure.

Thyroid function tests showed that she was euthyroid; T3 was 1.2nmol/l (NR 0.8-2.4), T4 was 12nmol/l (NR 9-23) and TSH was 6.3mU/l (NR 0.4-5mU/l). However, her serum contained high titre antibodies to thyroid peroxidase (1/64000; 4000iu/ml).

This patient had Hashimoto's thyroiditis. The goitre was huge, and she was treated by partial thyroidectomy; the goitre did not recur, and the patient has remained euthyroid for 12 years.antithyroid drug, carbimazole, to control her thyrotoxicosis, and surgery was not required.

Patient 10

A 41-year-old woman complained to her doctor that she 'always felt cold', and that she had become increasingly clumsy. Although she made no other complaint, her husband had noticed increasing physical and mental lethargy in his wife in recent months. One of her sisters had thyroid disease and her mother suffered from pernicious anaemia. On examination her skin was dry, her voice was hoarse and her hair was coarse and brittle. Her pulse rate was 58/min, with a blood pressure of 140/70. Her tendon reflexes showed a markedly delayed relaxation phase.

Her serum T3 was 0.4nmol/l (NR 0.8-2.4), T4 was 4nmol/l (NR 9-23), and TSH was 12.1mU/l (NR 0.4-5mU/l). High titres of autoantibodies to thyroid peroxidase were found in the patient's serum to a titre of 1/128000 (6400iu/ml).

This patient therefore had primary myxoedema and she was treated with replacement doses of L-thyroxine.