A patient with Graves' disease is treated with thiocyanate (a historical antithyroid agent). Thiocyanate helps reduce thyroid hormone production by:

Inhibiting iodide follicular uptake

Inhibiting beta-adrenergic receptors

A 49-year-old woman presents to the office because of tremors for 2 months. She says that her hands have been shaking a lot, especially when she feels stressed. In addition, she has been sweating more than usual and has lost 8 kg (17.6 lb) in the last 2 months. She has a past medical history of vitiligo. Her vital signs are a heart rate of 98/min, a respiratory rate of 14/min, a temperature of 37.6°C (99.7°F), and a blood pressure of 115/75 mm Hg. Physical examination shows a fine, bilateral hand tremor and a diffuse goiter. Which of the following hormonal imbalances is most likely present?

Low TSH, high free T4, and high free T3

High TSH, high free T4, and high free T3

High TSH, normal free T4, and normal free T3

Low TSH, normal free T4, and normal free T3

High TSH, low free T4, and low free T3

A 27-year-old woman presents to her doctor complaining of pain in her neck that radiates to her left ear. The pain has been more or less constant for the last 3 weeks and increases when she chews and swallows. She was in her normal state of health before the pain started. She also mentions that she has been experiencing palpitations, muscle weakness, and increased sweating for the last 2 weeks. Past medical history is significant for a flu-like illness 2 months ago. She currently takes no medication and neither consumes alcohol nor smokes cigarettes. Her pulse is 104/min and irregular with a blood pressure of 140/80 mm Hg. On examination, the physician notices that the patient is restless. There is a presence of fine tremors in both hands. The anterior neck is swollen, warm to the touch, and markedly tender on palpation. Thyroid function tests and a biopsy are ordered. Which of the following deviations from the normal is expected to be seen in her thyroid function tests?

↓ Serum TSH, ↑ Total T4, ↑ Free T4, ↓ I131 Uptake

Normal Serum TSH, ↑ Total T4, Normal Free T4, Normal I131 Uptake

↓ Serum TSH, ↑ Total T4, ↑ Free T4, ↑ I131 Uptake

Normal Serum TSH, ↓ Total T4, Normal Free T4, Normal I131 Uptake

↑ Serum TSH, ↑ Total T4, ↑ Free T4, ↑ I 131 Uptake

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

An 18-year-old girl comes to the clinic because she is concerned about her weight. She states that she is on her school’s cheerleading team and is upset because she feels she is the “fattest” girl on the team despite her healthy diet. She says that in the last 2 weeks since practice began, she has lost 2 lbs. The patient has bipolar disorder I. Her medications include lithium and a combined oral contraceptive that was recently started by her gynecologist, because “everyone is on it." Her mother has hypothyroidism and is treated with levothyroxine. The patient’s BMI is 23.2 kg/m2. Thyroid function labs are drawn and shown below: Thyroid-stimulating hormone (TSH): 4.0 mIU/L Serum thyroxine (T4): 18 ug/dL Free thyroxine (Free T4): 1.4 ng/dl (normal range: 0.7-1.9 ng/dL) Serum triiodothyronine (T3): 210 ng/dL Free triiodothyronine (T3): 6.0 pg/mL (normal range: 3.0-7.0 pg/mL) Which of the following is the most likely cause of the patient’s abnormal lab values?

Surreptitious use of levothyroxine

Thyroid hormone synthesis for USMLE Step 1: High-Yield Physiology Lessons

Thyroid Gland - The Body's Thermostat

Key Player: Thyroid Peroxidase (TPO) orchestrates oxidation, organification, and coupling.
Inhibitors: High iodine levels temporarily inhibit TPO (Wolff-Chaikoff effect).

Thyroid Hormone Synthesis Pathway in Follicular Cell

⭐ Propylthiouracil (PTU) and Methimazole inhibit TPO. PTU also blocks peripheral conversion of $T_4$ to $T_3$.

Hormone Factory - Building T3 & T4

Thyroid Hormone Synthesis and Secretion Pathway

Location: Thyroid follicular cell & colloid space.
Key Enzyme: Thyroid Peroxidase (TPO), involved in oxidation, organification, and coupling.

⭐ Wolff-Chaikoff Effect: High levels of iodide paradoxically inhibit TPO, temporarily shutting down hormone synthesis. This is a protective autoregulatory mechanism.

The Control Tower - HPT Axis

Driver: Hypothalamus releases Thyrotropin-Releasing Hormone (TRH).
Relay: TRH stimulates Anterior Pituitary to secrete Thyroid-Stimulating Hormone (TSH).
Effector: TSH acts on the thyroid gland, stimulating T4 and T3 synthesis and release.

Hypothalamic-Pituitary-Thyroid (HPT) Axis

⭐ High-Yield: T3 is the principal mediator of negative feedback on the pituitary and hypothalamus, despite T4 being the major secreted hormone.

Factory Faults - Clinical Tie-ins

Wolff-Chaikoff Effect: Iodine overload transiently inhibits thyroid peroxidase (TPO) → ↓ T3/T4 synthesis. Healthy glands escape via ↓ NIS expression.
Jod-Basedow Phenomenon: Iodine load induces hyperthyroidism in pre-existing thyroid disease (e.g., nodular goiter).
Dyshormonogenesis: Inherited defects in hormone synthesis enzymes (e.g., TPO deficiency).
- Leads to ↓ T3/T4, causing ↑ TSH stimulation and goiter.
- A key cause of congenital hypothyroidism.

⭐ Pendred Syndrome: An autosomal recessive disorder featuring a defect in pendrin (an iodide-chloride transporter), leading to goiter and sensorineural deafness.

Thyroid Hormone Biosynthesis Pathway

High‑Yield Points - ⚡ Biggest Takeaways

Iodide trapping via the Na+/I- symporter (NIS) is the crucial first step, actively concentrating iodide in the thyroid.

Thyroid peroxidase (TPO) is the key enzyme for both organification (iodination of thyroglobulin) and coupling of iodotyrosines.

Propylthiouracil (PTU) and methimazole are thionamides that inhibit TPO.

PTU also uniquely blocks the peripheral conversion of T4 to T3 by inhibiting 5'-deiodinase.

The Wolff-Chaikoff effect is the transient inhibition of organification by excess iodide.

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