What is the most likely diagnosis for a patient with fatigue, cold intolerance, and weight gain, and a diffusely enlarged, lumpy, tender thyroid gland, with normal eye exam results?

Most Likely Diagnosis: Hashimoto's Thyroiditis (Chronic Autoimmune Thyroiditis)

The clinical presentation of fatigue, cold intolerance, weight gain, and a diffusely enlarged, lumpy, tender thyroid gland in a patient with normal eye examination is most consistent with Hashimoto's thyroiditis, the most common cause of hypothyroidism in developed nations with adequate dietary iodine. 1, 2, 3

Key Diagnostic Features Supporting Hashimoto's Thyroiditis

Clinical Presentation Matches Primary Hypothyroidism

• The triad of fatigue, cold intolerance, and weight gain represents classic hypothyroid symptoms that occur in 68-83% (fatigue), 24-59% (weight gain) of hypothyroid patients 3, 4
• These symptoms result from metabolic slowing characteristic of thyroid hormone deficiency 5, 6

Thyroid Gland Characteristics Point to Hashimoto's

• A diffusely enlarged, lumpy thyroid gland is the hallmark physical finding of chronic lymphocytic thyroiditis (Hashimoto's disease) 2
• The "lumpy" texture reflects lymphocytic infiltration and fibrosis characteristic of autoimmune thyroiditis 7, 6
• Tenderness can occur with Hashimoto's, though it is typically less prominent than in subacute thyroiditis 1

Normal Eye Examination Rules Out Graves' Disease

• The absence of ophthalmopathy (eyelid lag, retraction, or exophthalmos) effectively excludes Graves' disease, which causes 95% of hyperthyroidism cases and presents with distinctive eye findings 1
• Graves' disease would also present with hyperthyroid symptoms (weight loss, heat intolerance, tachycardia) rather than hypothyroid symptoms 1

Diagnostic Confirmation Strategy

Essential Laboratory Tests

• Measure TSH and free T4: expect elevated TSH with low free T4 in overt primary hypothyroidism 1, 4
• Check thyroid peroxidase (TPO) antibodies to definitively establish autoimmune etiology—markedly elevated TPO antibodies confirm Hashimoto's thyroiditis 1, 2

Imaging Has No Role

• The American College of Radiology explicitly states there is no role for thyroid ultrasound, CT, MRI, or radionuclide scanning in the workup of primary hypothyroidism in adults, as imaging does not differentiate among causes of hypothyroidism 1, 2

Alternative Diagnoses to Consider (Less Likely)

Subacute Thyroiditis

• While subacute thyroiditis can present with a tender thyroid, it typically causes thyrotoxicosis initially (not hypothyroid symptoms) and is usually preceded by viral illness 1
• The thyroid is typically very tender and painful in subacute thyroiditis, more so than in Hashimoto's 1

Central Hypothyroidism

• If free T4 is low with normal or low TSH (rather than elevated TSH), this suggests pituitary or hypothalamic dysfunction requiring evaluation of other pituitary hormones 8
• This is rare compared to primary hypothyroidism 3

Critical Management Points

Initiate Levothyroxine Replacement

• Start levothyroxine at 1.6 mcg/kg/day for most adults, or 1.5-1.8 mcg/kg/day 4
• Use lower starting doses (12.5-50 mcg/day) in patients over 60 years or with known coronary artery disease 4
• Target TSH of 0.5-2.0 mIU/L or 0.4-4.0 mIU/L depending on therapeutic goals 2, 7

Monitor Response

• Recheck TSH and free T4 at 6-8 weeks after initiating therapy or dose changes 3, 4
• Once TSH is at goal, monitor annually 3

Common Pitfall to Avoid

• If both adrenal insufficiency and hypothyroidism are present, always start steroids before thyroid hormone replacement to avoid precipitating adrenal crisis 1
• Consider checking morning ACTH and cortisol if symptoms overlap significantly with adrenal insufficiency 8