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Difficulty: HardMenstrual Cycle Abnormalities and Contraception

A 29-year-old woman presents to the outpatient clinic to discuss contraception and to be evaluated for absent menstrual periods. Her last menstrual period was 8 months ago. Previously, her cycles were regular, occurring every 28 days. She reports feeling excessively tired, frequently cold, and having gained 6 kg (13 lb) over the past year despite active exercise. She also notes occasional clear fluid expression from her breasts.

Her medical history is notable for migraine headaches accompanied by visual scintillating scotomas, for which she takes sumatriptan as needed. She does not smoke or use illicit drugs.

Vital signs are:
Blood pressure: 105/65 mm Hg
Pulse: 56/min
Respirations: 14/min
Temperature: 36.1 °C (97.0 °F)
BMI: 27 kg/m2

Physical examination reveals a delayed relaxation phase of the deep tendon reflexes. Breast examination confirms bilateral non-bloody galactorrhea. The pelvic examination is normal.

Urine beta-hCG test is negative.

Serum laboratory studies show:
Thyroid-stimulating hormone (TSH): 1.2 mIU/L (Normal: 0.5–5.0 mIU/L)
Free thyroxine (T4): 0.5 ng/dL (Normal: 0.9–1.7 ng/dL)
Prolactin: 65 ng/mL (Normal: < 20 ng/mL)
Follicle-stimulating hormone (FSH): 3.2 mIU/mL (Normal follicular: 3–10 mIU/mL)

The patient requests a prescription for combined oral contraceptive pills to regulate her cycle and prevent pregnancy. Which of the following is the most appropriate next step in management?

  1. Magnetic resonance imaging of the brainAnswer
  2. B
    Prescription of combined oral contraceptive pills
  3. C
    Measurement of serum anti-thyroid peroxidase antibodies
  4. D
    Initiation of levothyroxine therapy
  5. E
    Pelvic ultrasonography

Answer

Magnetic resonance imaging of the brain
This patient presents with secondary amenorrhea, fatigue, weight gain, bradycardia, and delayed deep tendon reflexes, which are classic signs of hypothyroidism. However, her laboratory results show an inappropriately normal TSH in the setting of a frankly low Free T4. This combination indicates central (secondary) hypothyroidism, where the anterior pituitary fails to secrete adequate TSH. Furthermore, she has a low-normal FSH in the setting of amenorrhea (hypogonadotropic hypogonadism) and mild hyperprolactinemia. This constellation of central endocrine deficits combined with mild prolactin elevation (typically less than 100 ng/mL) is highly suspicious for a pituitary or hypothalamic mass (e.g., non-functioning macroadenoma) compressing the pituitary stalk. Stalk compression prevents hypothalamic dopamine from reaching the lactotrophs, leading to uninhibited prolactin secretion (the "stalk effect"). The most appropriate next step is magnetic resonance imaging (MRI) of the brain to visualize the sella turcica and optic chiasm. Furthermore, prescribing combined oral contraceptive pills is absolutely contraindicated (WHO Medical Eligibility Criteria Category 4) in this patient due to her history of migraines with aura, which carries an unacceptable risk of ischemic stroke.

Step-by-Step Solution

1
Evaluate the secondary amenorrhea by verifying a negative pregnancy test and assessing the endocrine laboratory panel.
The urine beta-hCG is negative. Labs show normal TSH, low Free T4, mild hyperprolactinemia, and low/normal FSH.
Pregnancy is the most common cause of secondary amenorrhea. Once ruled out, the hypothalamic-pituitary-ovarian axis must be evaluated.
2
Analyze the thyroid laboratory results in the context of the patient's hypothyroid symptoms (fatigue, cold intolerance, weight gain, bradycardia).
The inappropriately normal TSH in the setting of a frankly low Free T4 establishes a diagnosis of central (secondary) hypothyroidism.
In primary hypothyroidism, the lack of negative feedback causes TSH to be elevated. A normal TSH with low T4 points to a pituitary or hypothalamic failure.
3
Correlate the central hypothyroidism with the mild hyperprolactinemia (65 ng/mL) and low/normal FSH.
This pattern is highly suspicious for a structural mass (e.g., non-functioning pituitary macroadenoma) compressing the pituitary stalk.
Stalk compression disrupts the delivery of hypothalamic dopamine to the lactotrophs, leading to uninhibited prolactin secretion (the 'stalk effect'), while simultaneously compressing functional anterior pituitary tissue.
4
Determine the required diagnostic intervention and address the patient's request for contraception.
An MRI of the brain is required to evaluate the sella turcica. Furthermore, combined oral contraceptives are absolutely contraindicated due to her history of migraines with aura.
Structural imaging is the definitive diagnostic step for a suspected pituitary mass. Migraines with aura carry an unacceptable risk of ischemic stroke (WHO MEC Category 4) with estrogen use.

Key Concept

Diagnosis of secondary amenorrhea due to a pituitary mass (central hypothyroidism and hypogonadism with stalk effect) and recognizing WHO Medical Eligibility Criteria contraindications for hormonal contraception.
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Topics

Menstrual Cycle Abnormalities and Contraception

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