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Pneumocystis pneumonia in patients with Cushing's syndrome: A French multicenter retrospective study - 12/02/23

Doi : 10.1016/j.ando.2022.09.020 
Alexandre Lugat a, b, Hélène Lasolle c, d, e, Maud François f, Nesrine Benhenda g, Léopoldine Bricaire h, Erika Cornu i, Justine Cristante j, Anne Gitton f, Julien Hadoux k, Véronique Kerlan l, Maëlle Le Bras m, Vincent Mezzaroba c, d, e, Marie Puerto n, Caroline Storey o, Sophie Ouzounian p, Bruno Donadille p, Gérald Raverot c, d, e, Delphine Drui m, 1, Magalie Haissaguerre n, , 1
a Medical Oncology Department, CHU de Nantes, 44000 Nantes, France 
b Nantes Université, Inserm 1307, CNRS 6075, Université d’Angers, CRCI2NA, Nantes, France 
c Endocrinology Department, Reference Centre for Rare Pituitary Diseases HYPO, “Groupement Hospitalier Est”, Hospices Civils de Lyon, Bron, France 
d Lyon 1 University, Villeurbanne, France 
e INSERM U1052, CNRC UMR5286, Cancer Research Centre of Lyon (CRLC), Lyon, France 
f Endocrinology, Diabetology and Nutrition, Centre Hospitalier Universitaire de Reims, Reims, France 
g Private practice, Anglet, France 
h Department of Endocrinology and National Reference Center for Rare Adrenal Disorders, Hôpital Cochin, Assistance publique–Hôpitaux de Paris, 75014 Paris, France 
i Hypertension Unit, Hôpital Européen George-Pompidou, Paris, France 
j Endocrinology Unit, CHU Grenoble Alpes, 38043 Grenoble, France 
k Department of Endocrine Oncology and Nuclear Medicine, Gustave-Roussy and University Paris-Saclay, Villejuif, France 
l Department of Endocrinology, Diabetes and Metabolic Diseases, Hôpital de la Cavale-Blanche, Brest, France 
m Department of Endocrinology, Diabetology and Nutrition, l’institut du thorax, CHU Nantes, Nantes, France 
n Department of Endocrinology, Haut Levêque University Hospital, Bordeaux, France 
o Department of Paediatric Endocrinology and Diabetology, Robert-Debré Teaching Hospital, Assistance publique–Hôpitaux de Paris, Paris, France 
p Endocrinology Department, Saint-Antoine Hospital, Sorbonne Université, Assistance publique–Hôpitaux de Paris, Paris, France 

*Corresponding author. Department of Endocrinology, Haut Levêque University Hospital, avenue de Magellan, 33604 Pessac cedex, France.Department of Endocrinology, Haut Levêque University Hospitalavenue de MagellanPessac cedex33604France

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Abstract

Objective

Pneumocystis pneumonia (PcP) is an opportunistic infection occurring in immunocompromised patients. Cushing's syndrome (CS) impairs the immune system, and several authors have reported PcP in patients with CS. The present study aimed to characterize PcP occurring in a CS context and its management in French tertiary centers, in order to highlight the similarities in clinical presentation and treatment according to whether prophylaxis is implemented or not.

Methods

This was a multicenter retrospective study conducted in several French University Hospitals and Cancer Centers. Patients with PcP and confirmed CS regardless of etiology were included. We excluded patients with other known causes of acquired immunodeficiency with increased risk of PcP.

Results

Twenty-five patients were included. CS etiology was neoplastic in 84.0% of cases. CS clinical presentation associated predominant catabolic signs (76.0%), hypokalemia (91.7%) and lymphopenia (89.5%). CS was intense in most patients, with mean plasma cortisol levels at diagnosis of 2.424±1.102nmol/L and urinary free cortisol>10× the upper limit of normal in 85.0%. In all patients, PcP onset followed introduction of cortisol blockers, at a median 5.5 days. Patients were treated with 1 to 3 cortisol blockers, mainly metyrapone (88%), which significatively lowered plasma cortisol levels to 667±541nmol/L at the onset of PcP (P<0.001). PcP occurred in 7 patients despite prophylaxis. Finally, 60.0% patients were admitted to intensive care, and 20.0% died of PcP.

Conclusion

High mortality in patients with PcP implies that clinicians should be better informed about this rare infectious complication. Prophylaxis remains controversial, requiring comparative studies.

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Keywords : Cushing's syndrome, Ectopic ACTH secretion, Pituitary adenoma, Pneumocystis pneumonia, Pneumocystis jirovecii


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