What are the next best investigations for a patient with irregular periods and normal Thyroid-Stimulating Hormone (TSH) levels?

Next Best Investigations for Irregular Periods with Normal TSH

For a patient with irregular periods and normal TSH levels, the next best investigations should include free T4, free T3, gonadal hormones (estradiol, FSH, LH), and prolactin levels to rule out subclinical thyroid dysfunction and evaluate for other hormonal causes of menstrual irregularity. 1, 2

Thyroid Function Testing Beyond TSH

• Measure free T4 to distinguish between subclinical and overt thyroid dysfunction, as TSH alone may miss cases of central hypothyroidism or thyroid hormone resistance 1, 3
• Include free T3 testing, as some patients may have normal TSH and free T4 but abnormal free T3 levels (T3 toxicosis) 4, 5
• Consider thyroid antibody testing (TPO antibodies) to identify autoimmune thyroid disease, which can cause subtle thyroid dysfunction despite normal TSH 1

Gonadal Hormone Evaluation

• Test for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol to assess ovarian function and identify potential causes of irregular periods 6
• These hormones should be measured preferably in the morning (around 8 am) for most accurate results 6
• Consider testing testosterone levels to rule out polycystic ovary syndrome (PCOS), a common cause of menstrual irregularity 6

Additional Hormonal Testing

• Measure prolactin levels to rule out hyperprolactinemia, which can cause menstrual irregularities even with normal thyroid function 6
• Consider morning cortisol and ACTH levels to evaluate for adrenal insufficiency, which can present with menstrual irregularities 6

Pitfalls in Thyroid Testing Interpretation

• Normal TSH does not completely rule out thyroid dysfunction, as measurement variability and non-thyroidal conditions can affect TSH secretion 6
• Free thyroid hormone assays are more reliable than total hormone measurements, as the latter are influenced by variations in thyroid hormone-binding proteins 3, 7
• Laboratory reference intervals for TSH are based on statistical distribution rather than clinical outcomes, making interpretation challenging 6
• Consider repeating thyroid function tests after 3-6 months if initial results are inconclusive, as 30-60% of abnormal TSH levels normalize on repeat testing 1

Special Considerations

• If hypophysitis is suspected (headache, fatigue with abnormal thyroid function), consider MRI of the sella with pituitary cuts 6
• For patients with discrepancies between thyroid function results and clinical symptoms, consider testing for heterophile antibodies or thyroxine-binding globulin (TBG) abnormalities 7
• In cases where immunoassay results are questionable, liquid chromatography-tandem mass spectrometry (LC-MS/MS) may provide more accurate measurement of thyroid hormone levels 5

When to Consider Referral

• Consider endocrinology consultation if initial investigations reveal abnormal results or if symptoms persist despite normal laboratory findings 6
• Referral is particularly important if multiple hormonal abnormalities are detected, suggesting possible pituitary dysfunction 6