A 48-year-old woman is brought to the emergency department by her family at her psychiatrist's recommendation. According to her family, she has been more restless than her baseline over the past week. The patient herself complains that she feels her mind is racing. Her past medical history is significant for bipolar disorder on lithium and type 1 diabetes mellitus. The family and the patient both assert that the patient has been taking her medications. She denies any recent illness or sick contacts. The patient's temperature is 100°F (37.8°C), blood pressure is 100/60 mmHg, pulse is 130/min, and respirations are 20/min. She appears diaphoretic, and her cardiac exam is notable for an irregularly irregular rhythm with a 2/6 early systolic murmur. Blood counts and metabolic panel are within normal limits. The patient's lithium level is within therapeutic range. Which of the following laboratory tests would be the most useful to include in the evaluation of this patient?

Thyroid stimulating hormone and free thyroxine levels

Thyroid stimulating hormone and total thyroxine levels

Thyrotropin-releasing hormone stimulation test

Triiodothyronine and thyroxine levels

A 27-year-old G1P0 at 12 weeks estimated gestational age presents for prenatal care. The patient says she has occasional nausea and vomiting and a few episodes of palpitations and diarrhea this last week. Physical examination is unremarkable, except for a heart rate of 145/min. Basic thyroid function tests are shown in the table below. Which of the following additional laboratory tests would be most useful in assessing this patient's condition? Thyroid-stimulating hormone (TSH) 0.28 mIU/L (0.3–4.5 mIU/L) Total T4 12 µg/dL (5.4–11.5 µg/dL)

Thyrotropin receptor antibodies (TRAb)

Total triiodothyronine (T3) levels

Thyroid peroxidase (TPO) antibodies

Thyroxine-binding globulin (TBG) levels

A 32-year-old Caucasian woman presents with a three-month history of weight loss, anxiety, and tremors. She recalls frequent heart palpitations and new discomfort while being outside in the heat. Her labs include a TSH level of 0.1 mIU/L. Additionally, the patient’s serum is positive for antibodies that stimulate the TSH receptor. What process is unique to this patient’s diagnosis?

Stimulation of retroorbital fibroblasts

Elevated levels of cholesterol and low density lipoprotein (LDL)

Binding of thyroid hormones to cardiac myocytes

Hyperplasia of thyroid follicular cells

Lymphocyte-mediated destruction of the thyroid gland

A 26-year-old African-American woman presents to the clinic for a routine check-up. Review of systems reveals that she often feels nervous and has recently developed a slight tremor. Of note, she has lost 15 pounds in the past 3 months, despite an increased appetite. The patient’s temperature is 99°F (37.2°C), blood pressure is 130/78 mmHg, pulse is 85/min, and respirations are 14/min with an oxygen saturation of 98% on room air. On physical exam, her skin is warm and she has mild exophthalmos. Which of the following is the direct mechanism causing the patient's ophthalmologic findings?

Anti-thyroid peroxidase antibodies

A 25-year-old woman comes to the physician because of a 4-month history of anxiety and weight loss. She also reports an inability to tolerate heat and intermittent heart racing for 2 months. She appears anxious. Her pulse is 108/min and blood pressure is 145/87 mm Hg. Examination shows a fine tremor of her outstretched hands. After confirmation of the diagnosis, the patient is scheduled for radioactive iodine ablation. At a follow-up visit 2 months after the procedure, she reports improved symptoms but new-onset double vision. Examination shows conjunctival injections, proptosis, and a lid lag. Slit-lamp examination shows mild corneal ulcerations. The patient is given an additional medication that improves her diplopia and proptosis. Which of the following mechanisms is most likely responsible for the improvement in this patient's ocular symptoms?

Decreased production of proinflammatory cytokines

Replacement of thyroid hormones

A 52-year-old male presents to clinic with complaints of anxiety and fatigue for 4 months. He has also been experiencing palpitations, muscle weakness, increased sweating, and an increase in the frequency of defecation. Past medical history is insignificant. He neither consumes alcohol nor smokes cigarettes. His pulse is 104/min and irregular, blood pressure is 140/80 mm Hg. On examination, you notice that he has bilateral exophthalmos. There are fine tremors in both hands. Which of the following results would you expect to see on a thyroid panel?

Normal TSH; Low total T4; Normal Free T4 and T3

Hyperthyroidism and thyroiditis for USMLE Step 3: High-Yield Internal Medicine Lessons

Hyperthyroidism - Gland on Overdrive

Clinical Picture: Weight loss despite ↑ appetite, heat intolerance, palpitations, anxiety, fine tremor, hyperreflexia, lid lag.
Labs: ↓ TSH, ↑ free T4 & T3. TSH is the most sensitive initial test.
Common Causes:
- Graves' Disease: Autoimmune (Type II HSR). Diffuse goiter. Labs show (+) Thyroid-Stimulating Immunoglobulin (TSI).
- Toxic Multinodular Goiter (TMNG): Patchy uptake on RAIU scan.
- Toxic Adenoma: Single "hot" nodule on RAIU scan.

Graves' disease: exophthalmos and goiter

⭐ Thyroid Storm: A life-threatening thyrotoxicosis crisis, often precipitated by stress (surgery, infection). Presents with fever, delirium, tachycardia, and jaundice.

Diagnostic Workup - The Thyroid Detective

Initial Test: ↓ TSH is the most sensitive marker.
Confirmation: ↑ Free T4 (thyrotoxicosis) or ↑ Free T3 (T3 toxicosis).
Etiology: Radioactive Iodine Uptake (RAIU) scan is crucial.

Thyroid scans: Normal, Graves', Toxic MNG, Toxic Adenoma

⭐ A low RAIU with high thyroid hormones points towards preformed hormone release (thyroiditis) or exogenous intake, not active synthesis.

Graves' Disease - Eyes on the Prize

Patho: Type II hypersensitivity. Autoantibodies (Thyroid-Stimulating Immunoglobulin, TSI) agonize TSH receptors, leading to excess thyroid hormone.
Classic Triad:
- Hyperthyroidism (diffuse, non-tender goiter, bruit)
- Ophthalmopathy (proptosis, exophthalmos, lid lag)
- Dermopathy (pretibial myxedema - orange peel texture)
Labs: ↑ free T4 & T3, ↓ TSH. TSI is pathognomonic.
RAIU Scan: Diffusely high uptake.

Graves’ ophthalmopathy and pretibial myxedema

⭐ Exophthalmos results from retro-orbital fibroblast stimulation by autoantibodies, leading to glycosaminoglycan deposition and inflammation.

Thyroiditis Types - Painful, Silent, Postpartum

Subacute (de Quervain's): Painful, tender goiter, often follows viral URI. Marked by ↑ESR.
Silent/Lymphocytic: Painless, non-tender goiter. Autoimmune basis, often (+)TPOAb.
Postpartum: A variant of silent thyroiditis occurring within 1 year of delivery.

All types typically present with a transient hyperthyroid phase (preformed hormone release), followed by a hypothyroid phase, and eventual recovery.

⭐ The hallmark of all thyroiditis forms is a decreased radioactive iodine uptake (↓RAIU), distinguishing them from Graves' disease (which has ↑RAIU).

Thyroiditis: Granulomatous vs. Lymphocytic Infiltrate

Thyroid Storm - The Endocrine Emergency

A life-threatening exacerbation of thyrotoxicosis, often precipitated by stressors like infection, surgery, or trauma. Presents with high fever (>39.4°C), tachycardia, delirium, and GI distress. Diagnosis is clinical, aided by the Burch-Wartofsky Point Scale.
Management Sequence:

⭐ Always give a thionamide (e.g., PTU) at least 1 hour before an iodine solution. Giving iodine first provides more substrate for T4/T3 synthesis, worsening the storm.

High‑Yield Points - ⚡ Biggest Takeaways

Graves' disease is the most common cause of hyperthyroidism, driven by TSH receptor antibodies (TSI).

A thyroid storm is a life-threatening exacerbation of thyrotoxicosis presenting with fever, tachycardia, and delirium.

Subacute (de Quervain's) thyroiditis is distinguished by a painful, tender thyroid, often after a viral illness.

Radioactive iodine uptake (RAIU) is key for diagnosis: diffusely high in Graves', but low in thyroiditis.

PTU is preferred over methimazole in the first trimester of pregnancy and thyroid storm.

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