SUN-334 - An Unexpected Thyroid Detour in Reproductive Care

Introduction
Leuprolide is widely used in the management of infertility, uterine leiomyomas, and precocious puberty. Thyroid dysfunction associated with leuprolide is rare and often reported as painless autoimmune thyroiditis occurring months after therapy initiation, typically in patients with positive thyroid autoantibodies. Awareness of this association remains limited, particularly in individuals without autoimmune predisposition.
Case
A 37-year-old woman with a history of infertility and uterine leiomyoma presented with two weeks of worsening anterior neck pain and swelling associated with odynophagia, with symptoms unresponsive to acetaminophen and naproxen. She started leuprolide injections 3 months prior.
Examination revealed midline neck tenderness with no thyromegaly. Pertinent labs showed TSH < 0.01 μIU/mL, free T4 7.69 ng/dL, and free T3 14.7 pg/mL, along with elevated inflammatory markers (CRP 5.56 mg/dL, ESR 89 mm/hr), and WBC count 11.7 ×10⁹/L with lymphocyte predominance (14%). Thyroid autoantibodies screen was negative. CT imaging of the neck showed mild thyroid heterogeneity with slight right lobe enlargement. Thyroid ultrasound demonstrated a normal-sized heterogeneous gland with increased vascularity and no discrete nodules.
She was treated with propranolol 10 mg TID and a 7-day prednisone taper, with advice to defer further infertility treatment until euthyroidism was achieved. At outpatient follow-up, she reported marked symptomatic improvement. Repeat thyroid function tests one month later showed biochemical improvement with free T4 1.4 ng/dL, total T3 134 ng/dL, and TSH 0.008 μIU/mL.
Discussion
Leuprolide-induced thyroiditis is a rare adverse effect, most often described as painless thyroiditis occurring 4–8 months after therapy initiation and frequently associated with positive thyroid autoantibodies. The proposed mechanism involves estrogen suppression by GnRH agonists, which may unmask or exacerbate autoimmune thyroid disease. Estrogen plays an important role in thyroid physiology, including iodide uptake, thyroid peroxidase activity, and immune regulation. Additionally, GnRH agonists may induce proinflammatory T-lymphocyte changes, contributing to thyroid inflammation even in the absence of overt autoimmunity.
This case is notable for painful thyroiditis, absence of thyroid autoantibodies or family history, and relatively early onset following leuprolide exposure. It highlights leuprolide-induced thyroiditis as an underrecognized complication of GnRH agonist therapy, particularly in patients undergoing fertility treatment, where thyroid dysfunction may affect reproductive outcomes. Clinicians should maintain a high index of suspicion for thyroid dysfunction after leuprolide exposure, and baseline thyroid evaluation with close biochemical monitoring may facilitate early recognition and management.

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