Why would a female patient with a normal Thyroid-Stimulating Hormone (TSH) level of 2.5 and a history of regular menstrual cycles for over a year suddenly experience menstrual irregularities?

Sudden Menstrual Irregularities with Normal TSH

A TSH of 2.5 mIU/L is completely normal and does not explain sudden menstrual irregularities after a year of regular cycles—you need to look beyond the thyroid for the cause.

Why Thyroid Dysfunction Is Not the Culprit

• TSH of 2.5 mIU/L falls well within the normal reference range of 0.45-4.5 mIU/L, indicating adequate thyroid function 1
• This TSH value represents near the geometric mean of 1.4 mIU/L seen in disease-free populations, making thyroid dysfunction highly unlikely 1
• TSH is the most sensitive test for thyroid dysfunction, with sensitivity above 98% and specificity greater than 92%—a normal value effectively excludes thyroid disease as the cause 1
• The combination of normal TSH with presumably normal free T4 definitively excludes both overt and subclinical thyroid dysfunction 1

Common Causes of Sudden Menstrual Irregularities to Investigate

Pregnancy and Reproductive Causes

• Pregnancy must be ruled out first with a urine or serum beta-hCG test, as this is the most common cause of sudden cycle changes 1
• Polycystic ovary syndrome (PCOS) can present with sudden irregularities, though typically has a more gradual onset 1
• Premature ovarian insufficiency should be considered, particularly if age >35 years, by checking FSH and estradiol 1

Stress and Lifestyle Factors

• Significant weight changes (gain or loss >10% body weight) commonly disrupt menstrual cycles through hypothalamic dysfunction 1
• Excessive exercise or athletic training can suppress the hypothalamic-pituitary-ovarian axis 1
• Major psychological stress, life changes, or trauma can cause functional hypothalamic amenorrhea 1

Medications and Medical Conditions

• Recent medication changes, particularly hormonal contraceptives, antipsychotics, or antidepressants, can alter cycles 1
• Hyperprolactinemia from medications (dopamine antagonists) or pituitary adenomas should be excluded with prolactin level 1
• Uncontrolled diabetes, Cushing's syndrome, or other endocrine disorders can present with menstrual changes 1

Appropriate Diagnostic Workup

Initial Laboratory Testing

• Urine or serum beta-hCG to exclude pregnancy (most important first step) 1
• Prolactin level to screen for hyperprolactinemia 1
• FSH and estradiol if premature ovarian insufficiency suspected 1
• Consider androgen panel (total testosterone, DHEA-S) if signs of hyperandrogenism present 1

When to Recheck Thyroid Function

• Do not recheck TSH based solely on menstrual irregularities when the initial value is normal 1
• TSH should only be rechecked if specific hypothyroid symptoms develop (fatigue, cold intolerance, weight gain, constipation) or if risk factors emerge 1
• Remember that TSH can vary by up to 50% day-to-day due to normal physiological variation, so a single normal value is reassuring 2

Critical Pitfalls to Avoid

• Do not attribute menstrual irregularities to thyroid dysfunction when TSH is normal—this leads to unnecessary thyroid testing and delays diagnosis of the actual cause 1
• Avoid the trap of ordering anti-TPO antibodies in asymptomatic patients with normal TSH, as positive antibodies without thyroid dysfunction do not require treatment (except in pregnancy planning) 1
• Do not initiate levothyroxine therapy for normal TSH values, as this creates iatrogenic hyperthyroidism with risks of atrial fibrillation, osteoporosis, and cardiac complications 1
• TSH levels between 2.5-4.5 mIU/L are not associated with adverse consequences in asymptomatic individuals and do not warrant treatment 1

When Thyroid Would Actually Be Relevant

• If TSH were >4.5 mIU/L with menstrual irregularities, subclinical hypothyroidism could contribute and warrant further evaluation 1
• If TSH were <0.4 mIU/L, subclinical hyperthyroidism could cause oligomenorrhea or amenorrhea 1
• In women planning pregnancy with TSH >2.5 mIU/L, optimization to <2.5 mIU/L is recommended, but this does not apply to menstrual irregularities in non-pregnant women 1