Pulmonary alveolar proteinosis diagnosed during leuprorelin acetate therapy for ovarian endometrioma: a case report.
A 29-year-old woman developed pulmonary alveolar proteinosis during leuprorelin therapy for ovarian endometrioma, but causality cannot be established due to the lack of baseline imaging.
Where it sits
this study against the rest of the leuprorelin corpusSummary and findings
This case report describes a 29-year-old woman diagnosed with pulmonary alveolar proteinosis (PAP) during leuprorelin acetate therapy for ovarian endometrioma. The patient underwent surgery in August 2025 and started leuprorelin therapy three days postoperatively, with CT imaging revealing ground-glass opacities one month later. The relationship between the therapy and the diagnosis is noted, but causality cannot be established.
Abstract
<h4>Background</h4>Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder characterized by impaired surfactant clearance due to alveolar macrophage dysfunction. Leuprorelin acetate, a gonadotropin-releasing hormone agonist, is widely used in the treatment of ovarian endometriosis; however, pulmonary findings associated with this therapy have not been well characterized. We report a case of PAP diagnosed during leuprorelin acetate therapy for ovarian endometrioma and describe its temporal relationship with treatment.<h4>Case presentation</h4>A 29-year-old woman underwent laparoscopic surgery for an ovarian endometrioma in August 2025 and initiated leuprorelin acetate therapy three days postoperatively. A routine chest computed tomography (CT) performed one month later revealed scattered bilateral ground-glass opacities (GGOs), which persisted on repeat CT in November 2025. Although the patient remained asymptomatic, video-assisted thoracoscopic surgery (VATS) lung biopsy was performed to obtain a histopathological diagnosis and confirmed PAP. Serum anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody testing was negative (3.2 µg/mL; reference range, ≤ 5 µg/mL), not supporting autoimmune PAP. During treatment, the patient developed transient Common Terminology Criteria for Adverse Events (CTCAE) grade 2 leukopenia (white blood cell nadir, 2.94 × 10⁹/L), which resolved spontaneously after completion of leuprorelin acetate therapy without intervention. Hematological evaluation did not suggest an underlying clonal disorder, including myelodysplastic syndrome. Because baseline chest imaging was unavailable, pre-existing subclinical PAP could not be excluded. Follow-up CT performed three months after completion of therapy showed regression of GGOs.<h4>Conclusion</h4>This case shows a temporal relationship between leuprorelin acetate therapy and non-autoimmune PAP. However, causality cannot be inferred in the absence of baseline imaging. Only a temporal association can be observed. This observation is hypothesis-generating and highlights a potential rare pulmonary finding observed in the context of gonadotropin-releasing hormone agonist therapy.
Background
Pulmonary alveolar proteinosis (PAP) is characterized by impaired surfactant clearance due to alveolar macrophage dysfunction. Leuprorelin acetate is a gonadotropin-releasing hormone agonist commonly used for ovarian endometriosis, but the pulmonary effects associated with this treatment are not well understood. This case report aims to explore the potential relationship between leuprorelin therapy and the development of PAP.
Methods
This is a case report involving a 29-year-old woman who underwent laparoscopic surgery for an ovarian endometrioma and started leuprorelin acetate therapy three days post-surgery. The primary outcome was the diagnosis of PAP confirmed via video-assisted thoracoscopic surgery (VATS) lung biopsy, with secondary outcomes including imaging findings and hematological evaluations.
Results
The primary endpoint was the diagnosis of PAP, confirmed by VATS lung biopsy. One month after starting leuprorelin therapy, CT imaging revealed scattered bilateral ground-glass opacities. The patient experienced transient leukopenia with a nadir of 2.94 × 10⁹/L, which resolved after therapy completion. Follow-up imaging three months post-therapy indicated regression of the ground-glass opacities.
Interpretation
This case adds to the limited literature on potential pulmonary effects of leuprorelin therapy. While the findings are statistically notable, the clinical significance is uncertain due to the lack of baseline imaging and the single-case nature of the report. The absence of autoimmune markers further complicates the interpretation of causality, suggesting that further research is needed to explore this association.
Key findings
- Ground-glass opacities observed on CT one month after initiating leuprorelin therapy.
- Negative serum anti-GM-CSF antibody testing at 3.2 µg/mL; reference range, ≤ 5 µg/mL.
- Transient CTCAE grade 2 leukopenia with a white blood cell nadir of 2.94 × 10⁹/L.
- Follow-up CT three months post-therapy showed regression of GGOs.
Limitations
- Single case report limits generalizability.
- Absence of baseline chest imaging prevents confirmation of PAP onset.
- Findings are hypothesis-generating and not conclusive.