Blood Tests to Assess Pituitary Function
The essential blood tests to assess pituitary function in a female patient with amenorrhea and weight gain are: prolactin, LH, FSH, TSH, and mid-luteal progesterone. 1, 2
Core Pituitary Hormone Panel
Prolactin
- Measure morning resting serum prolactin levels (not post-seizure or post-stress) 1, 2
- Prolactin >20 μg/L is abnormal and indicates hyperprolactinemia 1, 2
- Hyperprolactinemia causes amenorrhea, oligomenorrhea, galactorrhea, and infertility 1
- If prolactin is elevated, first rule out hypothyroidism with TSH before pursuing pituitary imaging 2
- Medications (antipsychotics, metoclopramide, opioids) can elevate prolactin, requiring medication review before extensive workup 2
Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH)
- Measure serum LH and FSH on days 3-6 of the menstrual cycle using an average of three samples taken 20 minutes apart for accuracy 1, 2
- LH/FSH ratio >2 suggests polycystic ovary syndrome (PCOS) 1, 2
- FSH >35 IU/L indicates primary ovarian insufficiency (premature ovarian failure) 1, 2
- LH <7 IU/mL with low FSH indicates hypothalamic amenorrhea (hypogonadotropic hypogonadism) 1, 2
- Low LH and FSH warrant pituitary MRI to evaluate for structural abnormalities 3
Thyroid Stimulating Hormone (TSH)
- TSH assessment is mandatory because thyroid dysfunction disrupts the hypothalamic-pituitary-gonadal axis 4
- Hypothyroidism can cause hyperprolactinemia and must be excluded before attributing elevated prolactin to a pituitary adenoma 2, 4
- Hyperprolactinemia with thyroid dysfunction may be a contributory hormonal factor in amenorrhea 4
Additional Hormonal Assessment
Progesterone
- Measure mid-luteal phase progesterone (day 21 of a 28-day cycle) 1, 2
- Progesterone <6 nmol/L indicates anovulation 1, 2
- Anovulation is commonly caused by PCOS, hypothalamic amenorrhea, or hyperprolactinemia 1, 2
Metabolic Screening (if PCOS suspected)
- Obtain fasting morning glucose and insulin levels 2
- Fasting glucose >7.8 mmol/L and glucose/insulin ratio >4 are associated with obesity and PCOS 2
- Measure free testosterone or calculate free testosterone index (total testosterone/SHBG ratio) if hirsutism or virilization is present 2
Diagnostic Algorithm
When LH/FSH ratio >2 with anovulation (progesterone <6 nmol/L):
- Diagnose PCOS and proceed with metabolic screening 2
- Weight gain is a known trigger for PCOS development 1
When prolactin >20 μg/L:
- Rule out hypothyroidism first with TSH 2, 4
- Review medications that can elevate prolactin 2
- Consider pituitary MRI if persistently elevated after excluding secondary causes 1, 2
When FSH >35 IU/L:
- Diagnose primary ovarian insufficiency 1, 2
- This occurs prematurely in approximately 4% of women with epilepsy in their third decade versus 1% in the general population 1
When LH and FSH are both low (<7 IU/mL):
- Diagnose hypothalamic amenorrhea (hypogonadotropic hypogonadism) 1
- Obtain pituitary MRI to exclude structural lesions 3
- This affects 12% of women with temporal lobe epilepsy versus 1.5% of the general population 1
Critical Pitfalls to Avoid
- Never rely on a single prolactin measurement - obtain multiple baseline measurements over several weeks, as prolactin secretion is pulsatile 5
- Always check TSH when prolactin is elevated - hypothyroidism is a common reversible cause of hyperprolactinemia 2, 4
- Dynamic stimulation tests (TRH, metoclopramide, L-Dopa) provide no additional clinical information beyond mean basal prolactin levels and should not be routinely performed 5
- Normal ranges vary significantly between laboratory assays - always use laboratory-specific reference ranges 2
- In women with epilepsy, antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, valproate) can affect sex hormone levels and cause menstrual disturbances 1