What is the diagnosis and treatment for a patient with low TSH, elevated T4, and significant unintentional weight loss?

Hyperthyroidism (Graves' Disease)

This patient has overt hyperthyroidism, most likely Graves' disease, requiring immediate treatment with antithyroid medication (methimazole) to prevent life-threatening complications including cardiac arrhythmias, heart failure, and thyroid storm.

Diagnosis

The combination of low TSH with elevated T4 and significant unintentional weight loss definitively indicates overt hyperthyroidism 1, 2. This biochemical pattern—suppressed TSH with elevated free T4—distinguishes overt from subclinical hyperthyroidism and requires urgent treatment 1.

Most Likely Etiology

• Graves' disease is the most probable diagnosis, accounting for 70% of hyperthyroidism cases, with a prevalence of 2% in women and 0.5% in men 1, 2.
• The 60-pound unintentional weight loss is a classic manifestation of the hypermetabolic state caused by excess thyroid hormone 1, 2.
• At age 21, Graves' disease is far more common than toxic nodular goiter (which accounts for only 16% of cases and typically affects older patients) 2.

Confirmatory Testing Needed

• Measure TSH-receptor antibodies (TRAb) to confirm Graves' disease—these are positive in Graves' but absent in toxic nodular disease 2.
• Thyroid ultrasonography can identify diffuse enlargement (Graves') versus nodules 2.
• Thyroid scintigraphy is recommended if nodules are present on examination or ultrasound, or if the etiology remains unclear after antibody testing 1, 2.

Immediate Treatment: Methimazole

Start methimazole immediately as the first-line treatment for Graves' hyperthyroidism 2. Methimazole inhibits thyroid hormone synthesis but does not inactivate existing circulating thyroid hormones, so clinical improvement takes several weeks 3.

Methimazole Dosing and Monitoring

• Initial dose: Typically 10-30 mg daily depending on severity (higher doses for more severe hyperthyroidism with marked T4 elevation and significant weight loss) 3.
• Monitor thyroid function tests periodically during therapy—once clinical hyperthyroidism resolves, a rising TSH indicates the need for dose reduction 3.
• Check complete blood count with differential before starting treatment and if any signs of infection develop, as methimazole can cause agranulocytosis 3.
• Monitor prothrombin time, especially before surgical procedures, as methimazole may cause hypoprothrombinemia 3.

Critical Safety Warnings

• Instruct the patient to report immediately: sore throat, fever, skin eruptions, headache, or general malaise—these may indicate agranulocytosis requiring immediate CBC 3.
• Warn about vasculitis risk: Patients should promptly report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis 3.
• Pregnancy considerations: Methimazole is Pregnancy Category D and can cause congenital malformations, particularly in the first trimester 3. For a 21-year-old woman, counsel about contraception and the need to contact her physician immediately if pregnancy occurs 3.

Adjunctive Symptomatic Treatment

• Beta-blockers (propranolol or atenolol) should be started immediately for symptom control—addressing palpitations, tremor, anxiety, and heat intolerance 4, 1.
• Note: Hyperthyroidism increases clearance of beta-blockers, so higher doses may be needed initially; dose reduction will be required as the patient becomes euthyroid 3.

Treatment Duration and Prognosis

• Standard course: 12-18 months of antithyroid drug therapy 2.
• Recurrence risk: Approximately 50% of patients experience recurrence after stopping a 12-18 month course 2.
• Risk factors for recurrence in this patient include: age <40 years, likely high FT4 (given 60-pound weight loss), and potentially large goiter 2.
• Long-term treatment option: Extended therapy for 5-10 years is associated with lower recurrence rates (15%) compared to short-term treatment 2.

Alternative Definitive Treatments

If antithyroid drugs fail or recurrence occurs, definitive options include:

• Radioactive iodine (¹³¹I) ablation 2, 5.
• Thyroidectomy 2.

Important Caveat About Weight

• Weight gain is expected and often excessive after successful treatment 5.
• Treatment for hyperthyroidism significantly increases the risk of becoming obese (odds ratio 1.3 for women) 5.
• Men gain an average of 8.0 kg and women 5.5 kg during treatment 5.
• Radioactive iodine treatment causes additional weight gain (average 0.6 kg more than antithyroid drugs alone), particularly if hypothyroidism develops 5.
• Counsel the patient proactively about expected weight gain to set realistic expectations and discuss weight management strategies 5.

Monitoring During Treatment

• Thyroid function tests (TSH and free T4) should be monitored periodically to guide dose adjustments 3.
• Once clinical hyperthyroidism resolves, a rising TSH indicates the need to reduce methimazole dose to avoid iatrogenic hypothyroidism 3.
• Target: Normalize free T4 and TSH levels while using the lowest effective methimazole dose 3, 2.

Complications to Monitor

• Cardiac: Atrial fibrillation, heart failure (untreated hyperthyroidism significantly increases these risks) 1, 2.
• Bone: Osteoporosis from prolonged hyperthyroidism 1.
• Mortality: Untreated hyperthyroidism is associated with increased mortality 1, 2.
• Thyroid storm: Rare but life-threatening complication requiring immediate hospitalization 2.

Common Pitfalls to Avoid

• Do not delay treatment while waiting for confirmatory antibody or imaging studies—start methimazole based on biochemical hyperthyroidism and clinical presentation 1, 2.
• Do not assume weight loss is intentional or from other causes in a young woman—always check thyroid function 1.
• Do not overlook drug interactions: Adjust doses of warfarin, digoxin, beta-blockers, and theophylline as the patient becomes euthyroid 3.
• Do not fail to warn about agranulocytosis—this is the most serious acute complication of methimazole therapy 3.