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

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 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

A 23-year-old male presents with complaints of polydipsia and frequent, large-volume urination. Laboratory testing does not demonstrate any evidence of diabetes; however, a reduced urine osmolality of 120 mOsm/L is measured. Which of the following findings on a desmopressin test would be most consistent with a diagnosis of central diabetes insipidus?

Increase in urine osmolality to 400 mOsm/L following desmopressin administration

Reduction in urine osmolality to 60 mOsm/L following desmopressin administration

No detectable change in urine osmolality following desmopressin administration

Increase in urine osmolality to 130 mOsm/L following desmopressin administration

Reduction in urine osmolality to 110 mOsm/L following desmopressin administration

A 29-year-old woman comes to her primary care physician hoping she is pregnant. She reports that she had been taking oral contraceptive pills, but she stopped when she began trying to get pregnant about 7 months ago. Since then she has not had her period. She took a few home pregnancy tests that were negative, but she feels they could be wrong. She says she has gained 4 lbs in the past month, and her breasts feel full. Today, she expressed milk from her nipples. She complains of fatigue, which she attributes to stress at work, and headaches, to which she says “my sister told me she had headaches when she was pregnant.” She denies spotting or vaginal discharge. Her last menstrual period was at age 22, prior to starting oral contraceptive pills. Her medical and surgical history are non-significant. She has no history of sexually transmitted infections. She reports she and her husband are having intercourse 3-4 times a week. Her family history is significant for breast cancer in her mother and an aunt who died of ovarian cancer at 55. On physical examination, no breast masses are appreciated, but compression of the nipples produces whitish discharge bilaterally. A bimanual pelvic examination is normal. A urine pregnancy test is negative. Which of the following is the best initial step in management for this patient?

Serum thyroid-stimulating hormone level

Magnetic resonance imaging of the head

Serum follicle-stimulating hormone/luteinizing hormone ratio

A 40-year-old woman with a past medical history significant for pernicious anemia and vitiligo presents to the physician with the chief complaints of heat intolerance and frequent palpitations. The patient does not take birth control and her urine pregnancy test is negative today. Physical exam reveals a patient that is hyper-reflexive with a non-tender symmetrically enlarged thyroid gland. You order thyroid function tests for workup. What thyroid function values are most expected?

T4 elevated, free T4 elevated, T3 elevated, TSH decreased

T4 decreased, free T4 decreased, T3 decreased, TSH decreased

T4 elevated, free T4 normal, T3 elevated, thyroid stimulating hormone (TSH) normal

T4 elevated, free T4 elevated, T3 elevated, TSH elevated

T4 normal, free T4 normal, T3 normal, TSH elevated

Thyroid function testing for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

Thyroid Axis - The Hormone Tango

Hypothalamus-Pituitary-Thyroid Axis Feedback Loop

A finely tuned negative feedback system controlling metabolic rate.

Hypothalamus releases TRH (Thyrotropin-Releasing Hormone).
Anterior Pituitary releases TSH (Thyroid-Stimulating Hormone).
Thyroid releases T4 (Thyroxine) & T3 (Triiodothyronine).
Peripheral conversion: T4 → T3 (more potent form).

⭐ T3 is 3-4x more potent than T4, but T4 has a longer half-life (~7 days vs. 1 day), acting as a prohormone reservoir.

Initial Screening - TSH is King

Best single screening test for thyroid dysfunction in ambulatory patients due to its high sensitivity and specificity.
TSH has an inverse logarithmic relationship with free T4; small changes in fT4 cause large, inverse changes in TSH, making it an excellent first-line indicator.
Normal TSH range: 0.4-4.0 mIU/L (varies slightly by lab).

⭐ Pearl: TSH is unreliable for central (pituitary) hypothyroidism or during acute illness (sick euthyroid syndrome). Always interpret TSH with fT4 if pituitary dysfunction is suspected.

Hypothalamic-pituitary-thyroid axis feedback loop

Lab Patterns - Decoding the Data

Initial Test: Always start with TSH; it's the most sensitive screening tool.
Reflex Testing: If TSH is abnormal, reflexively measure Free T4 (FT4).
TSH-FT4 Relationship: Think of a seesaw-in primary disorders, one goes up, the other goes down.

Condition	TSH	Free T4 (FT4)	Common Cause
Primary Hypothyroidism	↑	↓	Hashimoto's
Primary Hyperthyroidism	↓	↑	Graves' Disease
Subclinical Hypo	↑	Normal	Early Hashimoto's
Subclinical Hyper	↓	Normal	Early Graves'
Secondary Hypothyroidism	↓ / Normal	↓	Pituitary Failure

⭐ Sick Euthyroid Syndrome: Critically ill patients may show abnormal TFTs (esp. low T3) without true thyroid disease due to altered hormone metabolism. Focus on treating the underlying illness, not the thyroid numbers.

Antibodies & Imaging - The Detectives

Key Antibodies:
- Anti-TPO Ab: Hallmark of Hashimoto's; also in Graves'.
- Anti-Tg Ab: Hashimoto's; monitors thyroid cancer recurrence.
- TSH-R Ab (TSI): Pathognomonic for Graves' disease (stimulating).
Imaging:
- Ultrasound (U/S): Best initial test for nodules/goiter; guides Fine Needle Aspiration (FNA).
- Radioactive Iodine Uptake (RAIU): Differentiates hyperthyroidism causes.
  - ↑ Uptake (Hot): Graves', toxic goiter.
  - ↓ Uptake (Cold): Thyroiditis, exogenous hormone.

Thyroid Scans: Grave's, Normal, Thyroiditis, Nodules, Goiter

⭐ A "cold" nodule on RAIU scan has a ~15-20% malignancy risk and requires FNA. "Hot" nodules are rarely malignant (<5%).

Special Conditions - Test Spoilers

Euthyroid Sick Syndrome (Non-thyroidal Illness): Severe illness can ↓ TSH, ↓ T3/T4. Key finding: ↑ reverse T3 (rT3). Treat the underlying condition first.
Pregnancy: Estrogen ↑ TBG, leading to ↑ total T4/T3. Free T4 and TSH remain normal. hCG can suppress TSH in 1st trimester.
Medications:
- Amiodarone, Lithium: Can cause hypo- or hyperthyroidism.
- Steroids, Dopamine: ↓ TSH.
- Estrogen/OCPs: ↑ TBG.

⭐ In Euthyroid Sick Syndrome, low T3 with an elevated reverse T3 (rT3) is the most characteristic finding, distinguishing it from true central hypothyroidism.

High‑Yield Points - ⚡ Biggest Takeaways

TSH is the single best screening test for suspected thyroid disease.

Always confirm an abnormal TSH with a free T4 (FT4). Free T3 is only useful for diagnosing isolated T3 thyrotoxicosis.

In primary hypothyroidism, expect ↑ TSH and ↓ FT4. In primary hyperthyroidism, expect ↓ TSH and ↑ FT4.

Central hypothyroidism classically presents with ↓ TSH and ↓ FT4.

Subclinical disease involves an abnormal TSH with a normal FT4.

Consider euthyroid sick syndrome in critically ill patients with abnormal TFTs.

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