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

An otherwise healthy 47-year-old woman comes to the physician for the evaluation of a 4-month history of worsening fatigue and constipation. She has also noticed that her cheeks appear fuller and her voice has become hoarse. Her temperature is 36.3°C (97.3°F) and pulse is 59/min. Examination of the neck shows a painless, mildly enlarged thyroid gland. Her skin is dry and cool and her nails appear brittle. Serum studies show antibodies against thyroid peroxidase. A biopsy of the thyroid gland is most likely to show which of the following?

Lymphocytic infiltration, Hürthle cells, and germinal centers

Tall follicular cells, scalloped colloid, and vascular congestion

Large, irregular nuclei, nuclear grooves, and Psammoma bodies

Spindle cells, pleomorphic giant cells, and mitotic figures

Multinucleated giant cells, macrophages, and degenerated follicular cells

A 33-year-old woman comes to the physician because of a 4-day history of fever, anterior neck pain, and throat swelling. She has no history of serious illness. Her temperature is 38.1°C (100.6°F) and pulse is 109/min. Physical examination shows diaphoresis and a fine tremor of the outstretched hands. The thyroid gland is enlarged, firm, and tender to palpation. Serum thyroid stimulating hormone level is 0.06 μU/mL and erythrocyte sedimentation rate is 65 mm/h. 123I scan shows an enlarged thyroid gland with diffusely decreased uptake. Histologic examination of a thyroid biopsy specimen is most likely to show which of the following findings?

Noncaseating granulomas with multinucleated giant cells

Undifferentiated giant cells with areas of necrosis and hemorrhage

Lymphocytic infiltration with germinal follicle formation

Follicular epithelial cell hyperplasia

Concentric intracellular lamellar calcifications

A 50-year-old woman comes to the physician for the evaluation of fatigue over the past 6 months. During this period, the patient has also had a 5 kg (11-lb) weight loss. She has a history of Hashimoto thyroiditis. She is sexually active with her husband only. She does not smoke. She drinks one glass of wine per day. She does not use illicit drugs. Her only medication is levothyroxine. Temperature is 37°C (98.6°F), pulse is 70/min, and blood pressure is 110/70 mm Hg. Abdominal examination shows tenderness in the right upper quadrant with no rebound or guarding. Laboratory studies show a serum alanine aminotransferase level of 190 U/L, serum aspartate aminotransferase level of 250 U/L, and serum total bilirubin level of 0.6 mg/dL. Liver biopsy shows plasma cell infiltration and areas of periportal piecemeal necrosis. Further evaluation of this patient is most likely to show which of the following findings?

Positive anti-smooth muscle antibodies

Elevated serum transferrin saturation

Positive anti-mitochondrial antibodies

A 43-year-old woman comes to the physician because of a 6-week history of hoarseness and difficulty swallowing. She also has a history of lower back pain treated with ibuprofen. She is 162 cm (5 ft 4 in) tall and weighs 77 kg (169 lb); BMI is 29 kg/m2. Her pulse is 64/min and blood pressure is 130/86 mm Hg. Physical examination shows dry skin, swelling of the lower extremities, and a hard nontender anterior neck swelling that does not move with swallowing. Femoral and pedal pulses are decreased bilaterally. A biopsy of the neck swelling is most likely to show which of the following findings?

Collagen deposition and decreased number of follicles

Atypical nuclei and concentric lamellar calcifications

Giant cells and noncaseating granulomas

Lymphocytic infiltrate and germinal center formation

Spindle cells and areas of focal necrosis

A 50-year-old man presents to a clinic with oliguria. Four weeks ago, he had a kidney transplant. Postoperative follow-up was normal. He is currently on cyclosporine and admits that sometimes he forgets to take his medication. On physical examination, the vital signs include: temperature 37.1°C (98.8°F), blood pressure 165/110 mm Hg, heart rate 80/min, and respiratory rate 16/min. There is mild tenderness on renal palpation. His serum creatinine level is 4 mg/dL, well above his baseline level after the transplant. Which of the following best describes the histological finding if a biopsy is taken from the transplanted kidney?

Lymphocytic infiltration of graft vessels and endothelial damage

Thrombosis and occlusion of vessels

Necrosis with granulation tissue

Thickening of blood vessels, fibrosis of graft vessels, and parenchymal atrophy

Two hours after undergoing allogeneic kidney transplantation for polycystic kidney disease, a 14-year-old girl has lower abdominal pain. Examination shows tenderness to palpation in the area the donor kidney was placed. Ultrasound of the donor kidney shows diffuse tissue edema. Serum creatinine begins to increase and dialysis is initiated. Which of the following is the most likely cause of this patient's symptoms?

Preformed antibodies against class I HLA molecules

Immune complex deposition in donor tissue

T-lymphocyte activation by donor HLA peptides

Irreversible intimal fibrosis and obstruction of vessels

Proliferation of donor T lymphocytes

Thyroiditis for USMLE Step 2 CK: High-Yield Pathology Lessons

Thyroiditis Overview - The Gland on Fire

Thyroiditis is inflammation of the thyroid gland, leading to transient or permanent dysfunction. It's classified by onset, duration, and the presence or absence of pain.

Thyroiditis: Lymphocytic Infiltrate and Germinal Centers

⭐ Subacute (de Quervain's) thyroiditis is the most common cause of a painful thyroid gland and often follows a viral upper respiratory infection.

Hashimoto's Thyroiditis - Autoimmune Attack

Most common cause of hypothyroidism in iodine-sufficient areas.
Pathogenesis: Autoimmune destruction of thyroid follicles.
- Genetic predisposition: HLA-DR3 & HLA-DR5.
- Key antibodies: Anti-thyroid peroxidase (anti-TPO) & anti-thyroglobulin (anti-Tg).
Histology: Intense lymphoplasmacytic infiltrate with germinal centers, and Hurthle cells (enlarged eosinophilic follicular cells).

⭐ Increased risk of developing primary B-cell lymphoma of the thyroid.

Clinical course: Initially may cause transient hyperthyroidism (hashitoxicosis) from follicle rupture, followed by progressive hypothyroidism.

Subacute Granulomatous Thyroiditis - de Quervain's Pain

Often follows a viral upper respiratory infection.
Primary Symptom: A very PAINFUL and tender thyroid gland; pain can radiate to the jaw or ear.
Key Labs: Markedly ↑ ESR (often >100 mm/hr) and ↑ CRP.
Clinical Course: Triphasic thyroid function:
- Transient hyperthyroidism (hormone release from damaged follicles).
- Followed by hypothyroidism.
- Spontaneous recovery to euthyroidism is common.
Histology: Granulomatous inflammation with multinucleated giant cells.

⭐ Radioactive Iodine Uptake (RAIU) is dramatically decreased, typically <5%.

Granulomatous thyroiditis with giant cells

Rarer Forms - Rock-Hard & Silent

Riedel's Thyroiditis
- An IgG4-related systemic disease causing intense fibrosis.
- Presents as a painless, "rock-hard," fixed goiter, mimicking malignancy.
- May compress local structures (e.g., trachea, esophagus).
- Patients are typically euthyroid.
Subacute Lymphocytic (Silent/Painless) Thyroiditis
- A self-limited variant of Hashimoto's, often occurring post-partum.
- Presents with a small, non-tender goiter.
- Brief hyperthyroid phase followed by hypothyroidism, then recovery.

⭐ Riedel's thyroiditis can be associated with IgG4-related fibrosis in other locations, such as retroperitoneal fibrosis.

Riedel's Thyroiditis: Dense Fibrous Tissue and Lymphocytes

Diagnostic Workup - Thyroid Detective

Condition	Key Labs & Antibodies	RAIU Scan	Biopsy Buzzwords
Hashimoto's	↑ TSH, ↓ T4 Anti-TPO, Anti-Tg Ab+	Variable	Lymphocytic infiltrate, germinal centers, Hürthle cells
Subacute (de Quervain's)	↓ TSH, ↑ T4 (early) ↑ ESR, CRP	↓ (painful)	Granulomatous inflammation, multinucleated giant cells
Riedel's	Euthyroid/Hypo IgG4-related	↓ ("cold")	Dense "rock-hard" fibrosis, fibrous tissue
Silent/Postpartum	Transient thyrotoxicosis then hypo	↓	Lymphocytic infiltrate (similar to Hashimoto's)

⭐ Subacute (de Quervain's) thyroiditis is the most common cause of a painful thyroid gland.

High‑Yield Points - ⚡ Biggest Takeaways

Hashimoto's thyroiditis: The most common cause of hypothyroidism in iodine-sufficient areas, marked by anti-TPO antibodies.

Subacute (de Quervain) thyroiditis: Presents with a painful goiter, often following a viral infection.

Riedel's thyroiditis: Characterized by a rock-hard, painless goiter from extensive fibrosis, mimicking malignancy.

Postpartum thyroiditis: A self-limited condition occurring within 1 year of delivery.

Subacute and postpartum types can cause transient hyperthyroidism followed by hypothyroidism.

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Thyroiditis