Management of Thyroid Dysfunction, Cushing Syndrome Screening, and PCOS in Women with Recurrent Pregnancy Loss

1. Screening for Cushing Syndrome

Perform a 24‑hour urinary free cortisol, late‑night salivary cortisol, or low‑dose dexamethasone suppression test to exclude hypercortisolism; untreated Cushing syndrome is linked to severe metabolic complications, cardiovascular disease, and markedly poor pregnancy outcomes (high miscarriage, preterm delivery, maternal mortality). 1

Check serum TSH and free T4 immediately to verify adequacy of current levothyroxine dosing, because inadequately treated hypothyroidism is strongly associated with recurrent pregnancy loss. 2
Aim for a pre‑conception TSH ≤ 2.5 mIU/L; the Endocrine Society recommends dose adjustment of levothyroxine in all women with known hypothyroidism who are planning conception. 4
Test for thyroid peroxidase antibodies (anti‑TPO); thyroid autoimmunity increases the risk of miscarriage, preterm delivery, and progression of hypothyroidism during pregnancy. 4
Confirm TSH ≤ 2.5 mIU/L on at least two separate occasions 4–6 weeks apart before attempting pregnancy. 4
Document anti‑TPO status; a positive result warrants more intensive monitoring throughout gestation. 4

Increase levothyroxine dose by approximately 30 % (≈ two extra tablets per week) as soon as pregnancy is confirmed, without awaiting laboratory results, because thyroid hormone requirements rise by 4–6 weeks gestation. 2
Measure TSH every 4 weeks; maintain TSH < 2.5 mIU/L in the first trimester and < 3.0 mIU/L in the second and third trimesters. 2
Instruct the patient to contact her clinician promptly after a missed period to reassess TSH and adjust levothyroxine, since untreated or under‑treated hypothyroidism is linked to fetal loss, impaired neurodevelopment, preterm birth, and low birth weight. 2

Reduce levothyroxine back to the pre‑pregnancy dose immediately after delivery, then re‑check TSH at 4–8 weeks postpartum to ensure appropriate dosing. 2

Implement a structured weight‑loss program targeting a 5–10 % reduction in body weight through calorie‑restricted nutrition; even modest loss improves menstrual regularity, ovulation rates, and metabolic parameters in obese women with PCOS. 1
Encourage at least 30 minutes of daily moderate‑to‑vigorous physical activity; exercise enhances metabolic health and lowers diabetes risk independent of weight loss. 1

Metformin is not recommended as first‑line therapy for hirsutism, prevention of pregnancy complications, or obesity management in PCOS. 1
Metformin may be considered only after lifestyle measures fail and if impaired glucose tolerance or type 2 diabetes develops; it should not be used as a primary fertility treatment. 1

Obtain fasting glucose and HbA1c to screen for impaired glucose tolerance or diabetes, conditions that are common in obese women with PCOS and increase pregnancy‑related complications. 1

Do not assume the current levothyroxine dose is sufficient without recent TSH verification; many patients with primary hypothyroidism remain undertreated.
Do not attribute all clinical features to PCOS when Cushingoid signs are present; missing Cushing syndrome can have catastrophic effects on pregnancy outcomes.
Do not delay thyroid optimization while pursuing fertility interventions; inadequate thyroid hormone replacement is a modifiable cause of recurrent pregnancy loss. 2
Do not apply non‑pregnant TSH reference ranges during gestation; pregnancy‑specific targets (first trimester < 2.5 mIU/L, second/third trimester < 3.0 mIU/L) are mandatory. 2
Do not rely on metformin as the primary strategy for PCOS‑related infertility or pregnancy‑loss prevention; weight loss and thyroid optimization have stronger evidence bases. 1