In a reproductive‑age woman with an ovarian cyst, what is the significance of Anti‑Müllerian hormone (AMH), anti‑thyroid peroxidase antibodies (anti‑TPO), thyroid‑stimulating hormone (TSH), and serum ferritin?

Significance of AMH, Anti-TPO Antibodies, TSH, and Serum Ferritin in Ovarian Cysts

In a reproductive-age woman with an ovarian cyst, AMH helps assess ovarian reserve (particularly if bilateral cysts are present), TSH and anti-TPO antibodies screen for thyroid dysfunction that may affect fertility, while serum ferritin has no established diagnostic role in ovarian cyst evaluation.

Anti-Müllerian Hormone (AMH)

AMH primarily reflects ovarian reserve rather than characterizing the cyst itself. 1

• Bilateral ovarian cysts significantly reduce AMH levels (median 1.3 ng/mL) compared to unilateral cysts (2.0 ng/mL) or intact ovaries (1.9 ng/mL), indicating compromised ovarian reserve when both ovaries are affected. 2

• Unilateral benign ovarian cysts (endometriomas or non-endometriotic) do not significantly alter serum AMH compared to women without ovarian pathology. 2

• AMH does not correlate with cyst size or histologic type (endometriotic versus non-endometriotic), so the measurement cannot distinguish between different cyst etiologies. 2

AMH in PCOS Diagnosis

• If polycystic ovarian morphology is suspected, AMH ≥35 pmol/L (5 ng/mL) shows 92% sensitivity and 97% specificity for PCOS, though it should not replace ultrasound or serve as a standalone diagnostic test due to lack of assay standardization. 1, 3

• AMH is elevated 2–3 times higher in women with PCOS compared to normal ovulatory women and correlates primarily with androgen status. 3

• Do not use AMH as an alternative for detecting polycystic ovarian morphology or as a single test for PCOS diagnosis because of significant overlap between women with and without PCOS, inconsistent cut-off values (ranging 24.29–100 pmol/L across studies), and assay variability. 1, 3

Thyroid-Stimulating Hormone (TSH)

TSH measurement is mandatory to exclude thyroid disease as a cause of menstrual irregularity and to assess its impact on ovarian reserve. 1, 4

• Elevated TSH is associated with decreased ovarian reserve: with each 1-unit increase in TSH, the odds of having AMH <1.1 ng/mL increase by 25%. 5

• In women over 35 years, a TSH cut-off of 1.465 mIU/L identifies decreased AMH levels, and median TSH is significantly higher in those with AMH <1.1 ng/mL. 5

• The optimal TSH for maximal AMH is approximately 2.88 mIU/L; both lower and higher TSH values correlate with reduced AMH in a polynomial relationship. 6

• TSH screening is essential in the differential diagnosis of ovarian cysts because hypothalamic amenorrhea (characterized by low LH and no hyperandrogenism) can present with polycystic ovarian morphology in 17–22% of cases and must be distinguished from PCOS. 7, 1

Anti-Thyroid Peroxidase Antibodies (Anti-TPO)

Anti-TPO antibodies identify autoimmune thyroid disease but show conflicting evidence regarding direct effects on ovarian reserve.

• In euthyroid infertile women with normal TSH, anti-TPO positivity does not independently reduce serum AMH levels; no significant difference in AMH exists between TPOAb-positive and TPOAb-negative women. 8

• However, in TPOAb-positive or TgAb-positive women, serum AMH negatively correlates with TSH levels, suggesting that elevated TSH (even within the normal range) may mediate ovarian reserve decline in the presence of thyroid autoimmunity. 8

• Women with PCOS have a 3.15-fold increased risk of hyperprolactinemia, and functional hyperprolactinemia can mimic PCOS with oligomenorrhea and hirsutism, making prolactin measurement essential alongside thyroid screening. 1, 4

Anti-Thyroglobulin Antibodies (TgAb)

• Elevated TgAb levels are associated with lower AMH: women with AMH below the 10th percentile have higher TgAb levels (median 37.62 IU/mL) and a 35.4% TgAb positivity rate versus 19.6% in those with normal AMH. 9

• Serum AMH inversely correlates with TgAb levels (r = –0.114), suggesting that high TgAb may cause autoimmune damage to the ovaries. 9

• The prevalence of TgAb positivity is significantly higher in women with the lowest AMH levels, indicating a potential direct ovarian effect beyond thyroid dysfunction. 9

Serum Ferritin

Serum ferritin has no established role in the diagnostic evaluation of ovarian cysts or ovarian reserve assessment. No guideline or high-quality evidence supports measuring ferritin for ovarian cyst characterization, PCOS diagnosis, or ovarian reserve evaluation. Ferritin is a marker of iron stores and inflammation but does not inform cyst etiology, hormonal function, or reproductive potential in this clinical context.

Practical Diagnostic Algorithm

1. Measure AMH to assess ovarian reserve, particularly if bilateral cysts are present or if fertility is a concern; interpret in the context of age-specific norms. 1, 2

2. Obtain TSH to exclude thyroid disease and assess its impact on ovarian function; a TSH >1.465 mIU/L in women over 35 warrants closer monitoring. 1, 5, 6

3. Measure anti-TPO and anti-TgAb if TSH is abnormal or if autoimmune thyroid disease is suspected; elevated TgAb may independently signal reduced ovarian reserve. 8, 9

4. If PCOS is suspected (irregular cycles, hyperandrogenism, polycystic ovarian morphology on ultrasound with ≥20 follicles per ovary or ovarian volume >10 mL), measure total testosterone by LC-MS/MS (74% sensitivity, 86% specificity) and consider AMH as supportive but not diagnostic. 1, 4

5. Exclude other causes: measure morning resting prolactin (>20 µg/L is abnormal), assess for Cushing's syndrome if clinical features are present, and consider androgen-secreting tumors if rapid-onset severe virilization occurs. 1, 4

6. Do not measure serum ferritin unless anemia or iron-deficiency symptoms are present; it does not contribute to ovarian cyst evaluation.

Common Pitfalls

• Do not diagnose PCOS based on ultrasound alone: up to one-third of reproductive-aged women without PCOS have polycystic ovarian morphology. 1

• Avoid ultrasound for PCOS diagnosis in adolescents (<8 years post-menarche or <20 years) due to high false-positive rates from normal multifollicular ovaries. 1, 4

• Do not rely on AMH as a standalone PCOS diagnostic test: lack of standardization, no validated cut-offs, and significant overlap with unaffected women limit its utility. 1, 3

• Recognize that normal testosterone does not exclude PCOS: 30% of women with confirmed PCOS have normal testosterone levels, and clinical hyperandrogenism plus irregular cycles suffice for diagnosis under Rotterdam criteria. 1

• Confirm prolactin elevation with 2–3 samples at 20–60 minute intervals via indwelling cannula to exclude stress-related spurious elevation. 1