What is the most appropriate next step in management for a 34‑year‑old woman with primary hypothyroidism (elevated TSH, normal free T4), hyperprolactinemia, galactorrhea, menstrual irregularities, fatigue, and intermittent headaches?

Begin Levothyroxine Immediately

The most appropriate management is to begin levothyroxine (Option B). This patient has primary hypothyroidism (TSH 16 mIU/L with normal free T4) causing secondary hyperprolactinemia and pituitary hyperplasia, which will resolve with thyroid hormone replacement alone 1, 2, 3.

Why Levothyroxine is the Correct First Step

Primary hypothyroidism is the root cause of all her symptoms. Her elevated TSH of 16 mIU/L with normal free T4 defines overt hypothyroidism requiring immediate treatment 1. The constellation of galactorrhea, menstrual irregularities, fatigue, malaise, and headaches are all explained by untreated hypothyroidism 2, 3, 4.

The Hyperprolactinemia is Secondary to Hypothyroidism

Prolactin of 1000 pmol/L (approximately 46 ng/mL) is entirely consistent with hypothyroidism-induced hyperprolactinemia 2, 3. While primary hypothyroidism typically causes modest prolactin elevations, levels can reach 100 ng/mL or higher in severe cases 2. The mechanism involves:

• Elevated TRH (from hypothyroidism) directly stimulating lactotroph cells to produce prolactin 3, 4
• Thyrotroph hyperplasia causing pituitary enlargement and potential stalk compression 3, 4, 5

Levothyroxine treatment will normalize prolactin levels within 6-8 weeks 3, 4. In documented cases with similar presentations, prolactin returned to normal, galactorrhea resolved, and menstrual cycles resumed after 6-12 weeks of thyroid hormone replacement 3, 4, 5.

Why Other Options Are Incorrect

Cabergoline (Option A) is Unnecessary and Potentially Harmful

Starting a dopamine agonist before treating the underlying hypothyroidism is a critical error 2, 3, 4. The hyperprolactinemia is secondary to hypothyroidism, not a primary prolactinoma 2, 3. Cabergoline would:

• Treat a symptom rather than the underlying disease 3, 4
• Expose the patient to unnecessary medication side effects 3
• Delay appropriate treatment of her hypothyroidism 4, 5
• Fail to address her other hypothyroid symptoms (fatigue, menstrual irregularities) 3, 4

Pituitary MRI (Option C) Should Wait Until After Levothyroxine Trial

While pituitary imaging may eventually be indicated, it should not delay thyroid hormone replacement 3, 4, 5. The clinical and biochemical picture strongly suggests hypothyroidism-induced pituitary hyperplasia 3, 4. The appropriate sequence is:

1. Start levothyroxine immediately 1, 3, 4
2. Recheck TSH, free T4, and prolactin in 6-8 weeks 1, 3
3. Order pituitary MRI only if prolactin remains elevated after thyroid function normalizes 3, 4, 5

In documented cases, pituitary enlargement completely regressed within 8-12 weeks of levothyroxine therapy, confirming the diagnosis of thyrotroph hyperplasia 3, 4, 5. Ordering MRI first would waste resources and delay definitive treatment 4, 5.

Observation (Option D) is Unacceptable

Delaying treatment for 6 months with a TSH of 16 mIU/L is inappropriate 1. This patient has:

• Overt hypothyroidism requiring immediate treatment 1
• Symptomatic disease (fatigue, malaise, menstrual irregularities, galactorrhea) 1, 3
• TSH >10 mIU/L, which mandates levothyroxine therapy regardless of symptoms 1

Untreated hypothyroidism carries significant morbidity, including cardiovascular dysfunction, adverse lipid profiles, and impaired quality of life 1. The 5% annual risk of progression to more severe hypothyroidism makes observation unacceptable 1.

Specific Treatment Protocol

Initial Levothyroxine Dosing

Start levothyroxine at 1.6 mcg/kg/day for this 34-year-old woman without cardiac disease 1, 6. For a patient with BMI 28 kg/m², this typically translates to 100-125 mcg daily 1, 6. The full replacement dose is appropriate because:

• She is young (<70 years) 1
• No cardiac disease is mentioned 1
• TSH is significantly elevated (16 mIU/L) 1

Administer levothyroxine as a single daily dose on an empty stomach, 30-60 minutes before breakfast 1, 6.

Monitoring and Expected Outcomes

Recheck TSH and free T4 in 6-8 weeks after starting levothyroxine 1, 7. Target TSH within the reference range of 0.5-4.5 mIU/L 1, 7. Also measure prolactin at this visit to confirm it is decreasing 3, 4.

Expected timeline for symptom resolution 3, 4:

• Prolactin normalization: 6-8 weeks 3, 4
• Galactorrhea resolution: 6-12 weeks 3, 4
• Menstrual cycle resumption: 8-12 weeks 3, 4
• Fatigue improvement: 6-8 weeks 1
• Headache resolution: Variable, but should improve as thyroid function normalizes 4

Dose Titration Strategy

If TSH remains elevated at 6-8 weeks, increase levothyroxine by 12.5-25 mcg increments 1, 7. Continue adjusting every 6-8 weeks until TSH normalizes 1, 7. Once stable, monitor TSH annually 1.

Critical Pitfalls to Avoid

Never start cabergoline or pursue pituitary surgery before treating primary hypothyroidism in patients with hyperprolactinemia and pituitary enlargement 2, 3, 4, 5. This combination almost always represents thyrotroph hyperplasia, which resolves completely with levothyroxine alone 3, 4, 5.

Do not assume every patient with galactorrhea, hyperprolactinemia, and headaches has a prolactinoma 3, 4, 5. Always check thyroid function first 4, 5.

Avoid the temptation to order extensive pituitary imaging before addressing the obvious biochemical abnormality 4, 5. The TSH of 16 mIU/L is the key finding that explains everything 3, 4, 5.