37-Year-Old Woman With Palpitations and Fatigue

A 37-year-old woman presented to the emergency department with palpitations, fatigue, and exertional dyspnea of 2 months' duration. The palpitations were persistent at rest and were not associated with anxiety. Review of the patient's medical history revealed that a prior pregnancy was complicated by postpartum cardiomyopathy. She was afebrile, had tachycardia (120 beats/min), and had a normal blood pressure of 118/64 mm Hg. Findings on physical examination were unremarkable, apart from trace bilateral lower extremity edema. Cardiac assessment yielded negative results, other than sinus tachycardia revealed on electrocardiography. The patient was referred to the general internal medicine clinic. Ten days later she was seen in the medicine clinic with symptoms of semiformed bowel movements after each meal; progressive fatigue, light-headedness, and diaphoresis associated with palpitations; and a 5.5-kg weight loss over 2 months. Her menstrual cycles were normal, and she denied any fevers, chills, or rigors. She had a regular heart rate of 99 beats/min, a blood pressure of 112/70 mm Hg, and a body mass index of 26.9 kg/m2. A nontender diffusely enlarged and smooth but firm thyroid gland with audible bruit was noted. A soft, midsystolic murmur was present at the left upper sternal border. There was a slight lid lag, but no significant exophthalmos, extraocular muscle weakness, or pretibial dermopathy. Her thyroid-stimulating hormone (TSH) level was suppressed to 0.05 mIU/L (reference ranges provided parenthetically) (0.3-5.0 mIU/L). Which one of the following diagnoses most likely explains this patient's clinical presentation? Graves disease Subacute granulomatous thyroiditis Hashimoto (chronic lymphocytic) thyroiditis Toxic multinodular goiter Papillary carcinoma of the thyroid Graves disease is the most likely diagnosis and is supported by the subacute to chronic course; the symptoms of thyrotoxicosis, including tachycardia, palpitations, diaphoresis, weight loss, and diarrhea; a suppressed TSH level; and physical examination findings of diffuse thyromegaly with thyroid bruit. As opposed to Graves disease, which causes painless thyromegaly, subacute granulomatous thyroiditis usually has a self-limiting course and causes painful and tender thyroid enlargement, often associated with transient hyperthyroidism due to thyroid hormone release from the inflamed thyroid follicles. Hashimoto thyroiditis is a painless chronic thyroid disorder characterized by lymphocytic inflammation of the thyroid. It commonly leads to hypothyroidism, although transient hyperthyroid episodes can occasionally occur early in the disease course. Toxic multinodular goiter has discrete palpable thyroid nodules as opposed to the diffuse thyromegaly observed in this case. Papillary carcinoma usually does not cause any biochemical thyroid hormone abnormalities and can present as an incidentally noted thyroid nodule on imaging, a palpable thyroid nodule with or without fixation to surrounding tissues and ipsilateral cervical lymphadenopathy, or as new-onset hoarseness or vocal cord paralysis.1,2 A complete thyroid profile yielded the following results: TSH, 0.05 mIU/L (0.3-5.0 mIU/L); free thyroxine (T4), 5.3 ng/dL (0.8-1.8 ng/dL); and free triiodothyronine (T3), 15.4 pg/mL (2.0-3.5 pg/mL). An elevation in which one of the following is most specific for Graves disease? TSH receptor antibodies (TRAb) Thyroid-stimulating immunoglobulin (TSI) TSH receptor–blocking antibodies Antithyroid peroxidase antibodies Antithyroglobulin antibodies The TRAb bind to the TSH receptor and have 2 subtypes: TSI and the TSH receptor–blocking antibodies. The TSI subtype is elevated in Graves disease and correlates with thyroid disease activity. Assays for both TRAb and the TSI subtype are elevated in Graves disease, but TSI is more specific for this diagnosis. However, TSI is a bioassay and is thus much more expensive and has a longer turnaround time than TRAb, which is an immunoassay. The TSH receptor–blocking antibody subtype, which can also be measured using a bioassay, can occasionally be present in Graves disease but may also be present in other autoimmune thyroid disorders. Antibodies to antithyroid peroxidase and antithyroglobulin can be nonspecifically elevated in any thyroiditis.1 The patient returned for follow-up 1 week later with worsening palpitations and increasing neck swelling. Her level of TSI was increased at 2.2 TSI index (≤1.3 TSI index). The urine pregnancy test yielded negative results. The patient was prescribed propranolol for symptomatic relief of her palpitations. Which one of the following would be the most appropriate next step in the management of this patient? Endocrinology consultation to discuss treatment of Graves disease Surgical consultation to evaluate for thyroidectomy Initiation of antithyroid drug (ATD) therapy 24-Hour radioactive iodine (RAI) uptake thyroid scan Ultrasonographic evaluation of the neck and thyroid An endocrinology consultation is recommended for the management of Graves disease but would be most appropriate after completing the evaluation. Surgical thyroidectomy and antithyroid medications are among treatment options; however, these should also be discussed after completing the work-up. The next step in management would be to obtain a 24-hour RAI uptake thyroid scan to rule out other causes of hyperthyroidism, especially silent thyroiditis. Graves disease causes diffuse radiotracer uptake by the thyroid gland as opposed to the suppressed uptake seen in thyroiditis. Ultrasonography of the neck and guided fine-needle aspiration for cytology are not helpful in diffuse thyroid enlargement unless there are discrete nodules.1,3 In this case, an I123 uptake thyroid scan showed diffusely increased radiotracer uptake by the thyroid gland consistent with Graves disease. Alternatively, an I131 uptake study could have been performed. Which one of the following is the most appropriate treatment for this patient's hyperthyroidism? Administer saturated solution of potassium iodide Continue propranolol and recheck biochemical thyroid profile in 4 weeks before committing to any treatment Perform RAI ablation Prescribe ATDs (eg, propylthiouracil [PTU] or methimazole) Perform surgical thyroidectomy Saturated solution of potassium iodide or potassium iodide-iodine (Lugol solution) transiently reverses the hyperthyroidism, but its use is limited to a 10-day prethyroidectomy treatment when ATDs cannot be used. Once a diagnosis of Graves disease has been established, waiting has no merit, and treatment should be initiated sooner rather than later. Radioactive iodine, ATDs, and surgical thyroidectomy are all treatment options for Graves disease. The first-choice treatment is usually RAI, and this would be the preferred option in this case. Alternatively, ATDs could be used but have a higher risk of failure or relapse. Surgical thyroidectomy is usually reserved for patients who do not benefit from or are not candidates for RAI and ATDs.1,3,4 After discussion regarding ATDs, RAI, and surgical management, the patient elected to proceed with ATD therapy. She began taking methimazole, and propranolol was continued. Which one of the following recommendations regarding family planning is most appropriate after initiating methimazole treatment? There is no contraindication to pregnancy Pregnancy is contraindicated until biochemical euthyroid status is achieved Use of ATDs is a contraindication to pregnancy Use of ATDs is a contraindication to breast-feeding The fetus is at risk of complications from fetal hyperthyroidism irrespective of Graves status in the mother Maternal hyperthyroidism is associated with risk of miscarriage, placental abruption, preterm delivery, as well as fetal malformations, and pregnancy should be deferred at least until maternal euthyroid status has been achieved. Both methimazole and PTU are classified as pregnancy category D drugs, although the risk of congenital malformations is very low, especially with PTU. Therefore, these drugs are acceptable in the pregnant patient, especially because the risks of untreated hyperthyroidism are much greater. Antithyroid drugs are secreted only in small quantities in breast milk and are considered safe during lactation. Fetal hyperthyroidism is caused by maternal TRAb that cross the placenta and is not a concern when the mother is in remission with negative findings on a serum TRAb assay.4-6 The patient was counseled regarding risks associated with pregnancy while receiving treatment. She continued methimazole and was scheduled for clinical follow-up of her response to therapy.