Ectopic adrenocorticotropic hormone syndrome with Pneumocystis jirovecii pneumonia and pulmonary cryptococcosis: A case report and literature review

Abstract

Ectopic adrenocorticotropic hormone syndrome is a distinct subtype of endogenous Cushing’s syndrome characterized by excessive cortisol secretion, which increases susceptibility to opportunistic infections. Herein, we present the case of a male patient in his early 40s who was admitted with fatigue and bilateral lower-extremity edema. Laboratory tests revealed markedly elevated serum adrenocorticotropic hormone and cortisol levels. Ectopic adrenocorticotropic hormone syndrome was confirmed via dexamethasone suppression testing and somatostatin receptor–targeted positron emission tomography–computed tomography, which localized an ectopic adrenocorticotropic hormone–secreting right pulmonary carcinoid tumor (a neuroendocrine tumor). During hospitalization, the patient was diagnosed with concurrent Pneumocystis jirovecii pneumonia and pulmonary cryptococcosis, and he responded favorably to trimethoprim–sulfamethoxazole and fluconazole. This case, supported by a review of the relevant literature, highlights the importance of early infection diagnosis, prompt management, and appropriate prophylaxis in patients with ectopic adrenocorticotropic hormone syndrome to improve prognosis.

Keywords

Ectopic adrenocorticotropic hormone syndrome infection Pneumocystis jirovecii pneumonia pulmonary cryptococcosis case report

Introduction

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a distinct form of endogenous Cushing’s syndrome (CS) characterized by inappropriate secretion of ACTH from nonpituitary tumors. This results in bilateral adrenal hyperplasia and excessive cortisol production. Hypercortisolism in EAS causes profound immunosuppression and increases susceptibility to opportunistic infections. Prior studies have strongly associated severe endogenous CS with the development of infections, including Pneumocystis jirovecii pneumonia (PJP) and cryptococcosis.¹

This report presents a rare case of EAS complicated by concurrent Pneumocystis jirovecii and cryptococcal infection. Through detailed case analysis and review of the relevant literature, we aimed to highlight the clinical characteristics, diagnostic challenges, treatment strategies, and preventive considerations for such complex presentations.

Case presentation

We retrospectively analyzed the clinical data of a male patient in his early 40s admitted to the Affiliated People’s Hospital of Jiangsu University with EAS complicated by PJP and pulmonary cryptococcosis. The analysis included medical history, laboratory/imaging findings, diagnosis, treatment, and outcome.

The patient presented with a 2‑month history of fatigue and bilateral lower-extremity edema, along with pulmonary lesions detected 1 month earlier. Initial laboratory tests on 10 August 2024 revealed hyperglycemia (glucose, 14.76 mmol/L; reference range: fasting, 3.9–6.1 mmol/L; 2‑h postprandial, <7.8 mmol/L) and severe hypokalemia (potassium, 1.94 mmol/L; reference range: 3.5–5.5 mmol/L), along with elevated 24‑h urinary potassium (147.5 mmol; reference range: 25.0–125.0 mmol/24 h). These findings indicated increased renal tubular potassium excretion, consistent with excess mineralocorticoid or glucocorticoid activity. Concurrently, the patient’s marked hyperglycemia on admission indicated severe insulin resistance, a typical metabolic complication of hypercortisolism. Subsequent testing demonstrated markedly elevated 24-h urinary free cortisol (UFC) (>1658.4 nmol/24 h; reference range: 20–100 μg), morning serum cortisol (>1677.34 nmol/L; reference range: 6.2–19.4 μg/dL), and basal ACTH (504.3 pg/mL; reference range: 7.2–63.3 pg/mL). Neither the 0.5 mg nor the 8 mg overnight dexamethasone suppression test achieved adequate suppression of cortisol and ACTH levels, thereby supporting a diagnosis of ACTH-dependent CS. Pituitary magnetic resonance imaging (MRI) was unremarkable, whereas computed tomography (CT) revealed diffuse bilateral adrenal enlargement, consistent with adrenal hyperplasia due to prolonged excessive ACTH stimulation.

Subsequently, chest CT on 16 August revealed localized bronchial wall thickening, mucus plugging, and a “finger-in-glove” sign in the right upper lobe, suggesting bronchial involvement (Figure 1(a)). A repeat CT on 30 August identified multiple pulmonary nodules, including a high-risk 9 × 7 mm nodule in the right upper lobe that was concerning for neoplasm (Figure 1(b)). On 5 September, functional positron emission tomography–computed tomography (PET/CT) imaging at another hospital demonstrated increased somatostatin receptor (SSTR) expression in the right upper lobe bronchial lesion, raising suspicion for a neuroendocrine tumor (NET) (Figure 2(a)). Two additional SSTR-negative high-risk nodules were tentatively considered potential low-differentiation NETs (Figure 2(b) and (c)). However, serial chest CT on 6 September revealed progression of the indexed nodule into a 14 × 12 mm cavitary lesion (Figure 1(c)), although immediate intervention was deferred. During this period, the patient received oral 10 mg dapagliflozin daily and subcutaneous insulin degludec/aspart (IDegAsp) injections (12 units before breakfast and 10 units before dinner) for glycemic control.

Figure 1.

Chest computed tomography imaging. (a) 16 August. Focal bronchial wall thickening, mucus plugging, and a “finger-in-glove” sign in the right upper lobe; (b) 30 August. Multiple bilateral pulmonary nodules, including a 9 × 7 mm high-risk nodule in the right upper lobe; (c) 6 September. Two low-density nodules in the right upper lobe, one demonstrating cavitary change measuring 14 × 12 mm; (d) 30 September. Ground-glass opacities in both lungs and a cavitary lesion in the right upper lobe; (e) 14 October. Near-complete resolution of bilateral ground-glass opacities, with mild reduction in the size of the irregular cavitary lesion in the right upper lobe compared with prior imaging.

Figure 2.

PET/CT imaging. (a–c) 5 September PET/CT. Increased somatostatin receptor (SSTR) expression in a right upper lobe bronchial lesion, along with two SSTR-negative high-risk pulmonary nodules. PET/CT: positron emission tomography–computed tomography.

Upon formal admission on 30 September 2024, the patient’s vital signs were as follows: temperature, 37.2°C; heart rate, 89 bpm; respiratory rate, 20 breaths/min; and blood pressure, 159/66 mmHg. Physical examination revealed facial acne and mild bilateral lower-extremity edema, without cardiopulmonary or abdominal abnormalities. Laboratory tests demonstrated lymphopenia (0.45 × 10⁹/L; reference range: 1.0–4.0 × 10⁹/L), mild leukopenia, elevated lactate dehydrogenase (628 U/L; reference range: 120–250 U/L), hypokalemia (2.22 mmol/L), elevated serum (1,3)-β-D-glucan (BDG) (1042.175 pg/mL; reference range: <60 pg/mL), reduced cluster of differentiation (CD) 4 (CD4)⁺ T-cell count (165 cells/mm³; reference range: 500–1600 cells/mm³), and hypoxemia, with unremarkable C-reactive protein levels. All pre-transfusion tests (including hepatitis B, hepatitis C, syphilis, and HIV) were negative. Chest CT showed bilateral ground-glass opacities superimposed on the pre-existing right upper cavitary lesion (Figure 1(d)). Bronchoalveolar lavage fluid (BALF) detected Pneumocystis jirovecii (850 sequencing reads). The initial admission diagnoses included combined pulmonary infection (PJP), hypokalemia, and type 2 diabetes. Antibiotic therapy was adjusted to high-dose oral trimethoprim–sulfamethoxazole (TMP–SMX; 400 mg SMX/80 mg TMP, 13 tablets/day) for PJP.

Positive serum cryptococcal capsular antigen (CrAg) detected on hospital days 10 and 11 established concurrent pulmonary cryptococcosis, prompting administration of fluconazole (800 mg daily). Cranial MRI revealed nonspecific white matter changes without meningeal lesions. Negative cerebrospinal fluid assays excluded cryptococcal meningitis, thereby defining isolated pulmonary cryptococcosis. By day 15, repeat chest CT showed radiological improvement, accompanied by normalization of cryptococcal antigen levels (Figure 1(e)). During hospitalization, the patient received approximately 2 weeks of fluconazole for pulmonary cryptococcosis and 3 weeks of TMP–SMX for PJP, resulting in both clinical and radiological improvement. Renal function remained stable during antifungal and anti-PJP combination therapy, whereas a transient mild liver enzyme elevation resolved after hepatoprotective management. The final diagnoses included PJP, pulmonary cryptococcosis, and EAS-related hypercortisolism.

The patient declined surgery for the underlying NET and was discharged on 22 October 2024. He was maintained on oral TMP–SMX (0.48 g daily) and fluconazole (400 mg daily), which he voluntarily discontinued after 2 weeks. Subsequently, he underwent thoracoscopic segmental resection of the right upper lung (segment S3) at another center on 27 December 2024. Immunohistochemical (IHC) staining demonstrated positivity for CD56, synaptophysin (SYN), Chromogranin A (CgA), Ki-67 (1%), insulinoma-associated protein 1 (INSM1), AE1/AE3 (perinuclear punctate), whereas phosphohistone H3 (PHH3), Napsin-A, P40, and thyroid transcription factor-1 (TTF-1) were negative, thereby confirming a 7 mm pulmonary carcinoid tumor. However, the patient did not attend regular longitudinal follow-up appointments, limiting continuous disease surveillance.

A detailed timeline of the patient’s clinical course, including key events and dates, is presented in Table 1. The reporting of this study conforms to Case Report (CARE) guidelines.² We have deidentified all patient details, including age and examination dates, to ensure patient confidentiality.

Table 1.

Timeline with relevant data.

Date	Event
August 2024	The patient presented to an external hospital with fatigue and bilateral lower-extremity edema. Laboratory findings suggested ACTH-dependent hypercortisolism. Chest CT identified a high-risk pulmonary nodule in the right upper lobe.
5 September 2024	PET/CT showed a “finger-in-glove” sign and increased somatostatin receptor expression in the right upper lobe, suggesting an ectopic ACTH-secreting lesion consistent with EAS.
6 September 2024	Chest CT showed low-density nodules with cavitation in the right upper lobe, suggesting possible fungal infection.
30 September 2024	Chest CT showed bilateral ground-glass opacities and a cavitary lesion in the right upper lobe. The patient was hospitalized and received empirical anti-infective therapy.
1 October 2024	BALF detected Pneumocystis jirovecii; therapy was adjusted to TMP–SMX (400 mg SMX/80 mg TMP).
9 and 11 October 2024	Serum cryptococcal capsular antigen (CrAg) was positive on two consecutive occasions, confirming pulmonary cryptococcosis; fluconazole (800 mg daily) was added.
14 October 2024	Chest CT showed near-complete resolution of bilateral ground-glass opacities and mild reduction in the right upper lobe cavitary lesion.
22 October 2024	The patient was discharged after clinical improvement.
27 December 2024	Pathological and immunohistochemical examinations validated a 7 mm pulmonary carcinoid tumor.

ACTH: Adrenocorticotropic hormone; CT: computed tomography; PET/CT: positron emission tomography–computed tomography; EAS: ectopic adrenocorticotropic hormone syndrome; BALF: bronchoalveolar lavage fluid; TMP–SMX: trimethoprim–sulfamethoxazole.

Discussion

EAS is a rare subtype of endogenous CS, predominantly caused by NETs, including small-cell lung cancer, thoracic carcinoid tumor, and medullary thyroid carcinoma.³ In the present case, combined dexamethasone suppression testing and SSTR-targeted PET/CT confirmed an ectopic ACTH-secreting pulmonary NET as the underlying etiology. Notably, SSTR-targeted PET/CT facilitated accurate localization of the ACTH source,⁴ which was particularly useful given unremarkable pituitary MRI findings. Compared with ¹⁸F-fluorodeoxyglucose (FDG) PET, SSTR-targeted PET demonstrates higher sensitivity for small or occult NETs,⁵ making it particularly valuable in patients with suspected infection or in those for whom biopsy is contraindicated. These key advantages are highlighted by the present case.

The most notable clinical feature of this case is the coexistence of EAS with dual opportunistic pulmonary infections (PJP and pulmonary cryptococcosis), which, to the best of our knowledge, has not been previously reported in the literature. This unique presentation underscores the clinical significance of this case, as it expands the spectrum of EAS-related complications and provides practical insights for clinical management. The core pathogenic mechanism linking EAS to these infections involves profound immunosuppression induced by excessive cortisol secretion.^6,7 Sustained elevation of glucocorticoid levels impairs both innate and adaptive immunity, suppressing the proliferation and function of T lymphocytes (evidenced by the patient’s reduced CD4⁺ T-cell count of 165 cells/mm³). Concurrently, elevated cortisol levels inhibit macrophage function, fostering a “double immunosuppressive” environment via impairment of innate and adaptive immunity.⁸ This immunosuppressive state not only predisposes patients with EAS to cryptococcosis but also facilitates superinfection with PJP.

To further contextualize the clinical significance of this case, we compiled data from 23 reported cases of EAS complicated by PJP (including the present case; Table 2).^1,6,7,9–24 The cohort included patients aged 20–82 years (median: 56 years), with varied underlying tumors including lung, thymic, pancreatic, and prostatic NETs. In seven cases, the primary lesion was unidentified. Baseline plasma cortisol levels ranged from 3.0 to 8800 nmol/L, plasma ACTH from 3.85 to 7986 pmol/L, and UFC up to 106,632 μg/24 h. Most patients received cortisol-lowering therapy with steroidogenesis inhibitors, octreotide, or surgery. Notably, two patients developed PJP before cortisol reduction, whereas most others presented 2–14 days after therapy initiation. PJP onset typically followed a decrease in cortisol levels to a mean of approximately 943.9 nmol/L, and the overall mortality was 52%, consistent with previous reports indicating that PJP mortality in patients with CS (60%–65%) is significantly higher than in patients with HIV (10%–40%).²³ This findings highlight the critical importance of early recognition and prevention of PJP in patients with EAS, particularly given the positive association between hypercortisolemia severity and PJP risk.

Table 2.

Clinical features of patients with ectopic ACTH syndrome and PJP.

Author	Age	Sex	PJP confirmed	Etiology of CS	Cortisol (μg/dL)	ACTH (pg/mL)	Urinary cortisol (μg)	Onset of PJP (before or after anticortisolic treatment)	Time between initiation and onset of symptoms	Cortisol during PJP (μg/dL)	Anticortisolic therapy	Prophylaxis	Coinfections	Treatment of PJP	Outcome
Yoshihara et al.⁹	78	F	Suspicion only	Pancreatic neuroendocrine tumors	134.2	134.2	6550.0	NA	NA	NA	Metyrapone, Hydrocortisone	No	Escherichia coli, Pseudomonas aeruginosa, Cytomegalovirus, Candida	TMP–SMX	Death
Cristante et al.¹⁰	82	M	Yes	Prostate adenocarcinoma	59.3	363,000	1110.1	After	30 days	NA	Metyrapone	No	Cytomegalovirus	TMP–SMX	Death
Gabalec et al.¹¹	60	F	Yes	NA	114.1	250	4938.4	After	4 days	44.3	Ketoconazole, Etomidate	No	Cytomegalovirus	TMP–SMX	Recovered
Gabalec et al.¹¹	20	M	Yes	High-grade endocrine carcinoma	50.0	300	430.4	After	Few days	15.4	Ketoconazole, Etomidate	No	/	TMP–SMX	Recovered
Arlt et al.¹²	36	M	Yes	Metastatic neuroendocrine tumor of the right kidney	79.0	1118	3300.0	After	10 days	34.6	Metyrapone, Hydrocortisone	No	/	TMP–SMX	Death
Keenan et al.⁶	26	F	Yes	NA	66.9	204.5	11,231.9	After	14 days	10.9–14.5	Ketoconazole, Metyrapone	No	/	TMP–SMX, Methylprednisolone	Recovered
Kim et al.¹³	60	F	Yes	NA	80.0	460	2509	After	3 days	16.2	Octreotide, Ketoconazole	No	/	TMP–SMX	Death
McQuillen et al.¹⁴	73	F	Yes	Pancreatic islet cell carcinoma	67.0	194	528	After	19 days	86.5	Somatostatin	No	/	TMP–SMX	Death
Graham and Tucker⁷	50	M	Yes	Small-cell lung carcinoid	190.0	NA	NA	After	NA	NA	Steroidogenesis inhibitors	No	Serratia marcescens	/	Death
Fulkerson and Newman¹⁵	38	F	Yes	Metastatic thymic carcinoid	114.0	17.5	NA	After	2 days	NA	Metyrapone, Aminoglutethimide	No	Listeria monocytogenes	TMP–SMX	Death
Chan and Roberts¹⁶	63	F	Yes	NA	>58.9	239.07	5797.1	After	4 days	NA	Ketoconazole	No	Cytomegalovirus	/	Recovered
Oosterhuis¹⁷	62	F	Yes	Carcinoid of the lung	70.5	296	18,628.3	After	Few days	NA	Mifepristone	No	/	TMP–SMX	Recovered
Oosterhuis¹⁷	57	F	Yes	Pancreatic neuroendocrine tumors	85.9	318	10,6632.6	After	2 days	NA	Ketoconazole, Mifepristone	TMP–SMX	/	TMP–SMX	Recovered
Bakker¹	56	M	Yes	NA	197.5	315	18,644.9	After	4 days	36.2	Ketoconazole	No	Herpes simplex virus, Staphylococcus aureus, Aspergillus	TMP–SMX	Death
Zhen et al.¹⁸	52	F	Yes	Carcinoid of the lung	>75.0	198	3826.3	After	3 days	29.1	Surgery	TMP–SMX	Klebsiella pneumoniae	TMP–SMX	Recovered
Natale et al.¹⁹	24	M	Yes	Bronchial carcinoid	0.11	902	11.8	After	40 days	NA	NA	No	/	Cephalosporins, Gentamicin	Recovered
Sieber et al.²⁰	66	M	Yes	Small-cell lung carcinoid	115.9	431.78	NA	Before	NA	NA	NA	No	Cytomegalovirus, Invasive aspergillosis	TMP–SMX	Death
Chowdry et al.²¹	48	F	Yes	High-grade endocrine carcinoma	106.2	296	16,340	After	NA	NA	Ketoconazole, Octreotide	No	Nocardia, Escherichia coli	TMP–SMX	Death
Oda et al.²²	44	M	Yes	Large cell neuroendocrine carcinoma of the thymus	49.1	354.1	NA	After	3 months	NA	Chemotherapy	No	/	TMP–SMX	Recovered
Van Halem et al.²³	70	F	Yes	Thymic carcinoid	318.8	NA	19,179.0	After	NA	NA	NA	No	/	/	Death
Van Halem et al.²³	61	F	Yes	Small-cell lung carcinoid	58.0	NA	5830.0	After	NA	NA	NA	No	/	/	Death
Monte Armenteros et al.²⁴	56	M	Yes	Thymic neuroendocrine carcinoma	NA	NA	NA	After	4 days	NA	Ketoconazole	No	Cytomegalovirus	TMP–SMX	Recovered
Our patient	43	M	Yes	Carcinoid of the lung	>60.8	504.3	>600.9	Before	NA	NA	NA	No	Cryptococcus, Human herpes virus	TMP–SMX	Recovered

ACTH: adrenocorticotropic hormone; CS: Cushing syndrome; F: female; M: male; NA: not available; PJP: Pneumocystis jirovecii pneumonia; TMP–SMX: positron emission tomography–computed tomography.

Based on this case and the existing literature, we summarized key clinical recommendations for managing EAS complicated by opportunistic infections. PJP prophylaxis should be considered in high-risk patients with CS. Guidelines recommend initiation when UFC exceeds 5–10 times the upper normal limit, plasma cortisol is >2500 nmol/L, CD4⁺ T cells are <200/mm³, or patients are about to undergo cortisol-lowering therapy.^16,25,26 TMP–SMX is the preferred prophylactic agent, reducing PJP incidence by approximately 85% in non-HIV immunocompromised patients.²⁷ For diagnosis, BDG ≥80 ng/L and detection of Pneumocystis jirovecii DNA in BALF via polymerase chain reaction/next-generation sequencing (PCR/NGS) or silver staining are reliable tools.²⁸ Oral TMP–SMX remains the first-line treatment for confirmed PJP per European Conference on Infections in Leukemia (ECIL) guidelines.²⁹

This case also highlights diagnostic challenges in patients with EAS with concurrent NETs and infections. Initial radiological findings of lesions were misclassified as suspicious for malignancy, underscoring the difficulty in distinguishing opportunistic infections from tumor progression, particularly when NET-related lesions coexist with infectious changes. Furthermore, Cryptococcus was not detected by NGS of BALF, suggesting that early screening with serum CrAg testing is necessary even when NGS results are negative but imaging shows a cavity or nodule. Lumbar puncture is essential to rule out central nervous system (CNS) dissemination. For isolated pulmonary cryptococcosis, fluconazole is sufficient, whereas CNS involvement requires amphotericin B combined with flucytosine.³⁰

Beyond infection management, resolving hypercortisolism via surgical resection of the ACTH-secreting NET is the cornerstone of improving long-term prognosis in patients with EAS. CS is often associated with hypertension, hyperglycemia, hyperlipidemia, obesity, and hypokalemia,³¹ all of which increase the risk of perioperative complications, including infections, thromboembolism, metabolic disorders, and cardiovascular events.³² Therefore, individualized perioperative optimization is essential. Preoperative medical therapy (PMT)³³ helps control hypercortisolism, thereby reducing complications and improving postoperative wound healing and infection risk. Steroidogenesis inhibitors such as ketoconazole, metyrapone, osilodrostat, and etomidate are commonly used,³² along with glucocorticoid replacement to prevent adrenal insufficiency caused by high-dose steroidogenesis inhibitors. Excess cortisol can cause hypertension and hypokalemia by activating mineralocorticoid receptors, the sympathetic nervous system, and the renin–angiotensin–aldosterone system in EAS. Treatment includes aldosterone receptor antagonists, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs), beta-blockers, and diuretics for hypertension,²⁵ whereas oral potassium chloride is used to correct hypokalemia and prevent arrhythmias. Perioperative hyperglycemia impairs wound healing and overall recovery, necessitating enhanced glycemic control. Medications such as metformin, sodium–glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists are commonly used, with insulin added when necessary to maintain an glycated hemoglobin (HbA1c) level <7%.³⁴ Hypercortisolism also induces a hypercoagulable state, and factors including endothelial damage, atherosclerosis, obesity, hypertension, hyperlipidemia, and diabetes further increase the risk of thrombosis. Deep vein thrombosis and pulmonary embolism are common early postoperative complications.²⁵ Therefore, preoperative thrombosis risk assessment and prophylactic anticoagulation are essential. Prevention of perioperative infections, including urinary tract infections, skin and soft tissue infections, pneumonia, and sepsis,³⁵ can be achieved through strict glycemic control and vaccination. PJP, the most common opportunistic infection in patients with CS, has been discussed above. Overall, the management of EAS should integrate infection control, correction of hypercortisolism, and perioperative optimization to reduce treatment-related risk.

This case report described the clinical course and management of a patient with EAS coexisting with PJP and pulmonary cryptococcosis. However, the absence of long-term follow-up limits the assessment of disease progression, and treatment decisions were based on clinical diagnosis. Additional therapeutic approaches warrant further exploration.

Conclusions

To the best of our knowledge, this is the first report of EAS complicated by both PJP and pulmonary cryptococcosis, thereby expanding the clinical spectrum of EAS-related complications. The timely identification of PJP via BALF testing and cryptococcosis through serum capsular antigen detection, coupled with targeted antimicrobial therapy (TMP–SMX for PJP and fluconazole for cryptococcosis), contributed to the patient’s radiological and clinical improvement. This underscores the importance of maintaining a high index of suspicion for opportunistic infections in patients with EAS, even in the presence of NET-related imaging abnormalities, as delayed diagnosis and treatment can result in severe respiratory failure and adverse clinical outcomes. These findings further reinforce the need for individualized prophylaxis, accurate diagnostic differentiation, and comprehensive perioperative management to improve the prognosis of patients with EAS.

Footnotes

Acknowledgments

The authors thank the patient and his family for providing consent to publish this case. We also appreciate the support of the Department of Respiratory and Critical Care Medicine, Affiliated People’s Hospital of Jiangsu University.

Author contributions

Junlan Zhou drafted the manuscript. Tao Yang, Defei Tan, and Ying Zhou conceived and designed the study. Chenyang Liu and Lingling Li analyzed the data. Tao Yang provided financial support and critically revised the manuscript. All authors read and approved the final version of the manuscript.

Availability of data and materials

The data used to support the findings of this study are included in the article.

Consent for publication

Informed consent for treatment was obtained from the patient. Written informed consent was obtained from the individual for the publication of any potentially identifiable images or data included in this article. On request, a copy of the written consent is available for review by the Editor-in-Chief of this journal.

Declaration of conflicting interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

The study involving humans was approved by the Ethics Committee of the Affiliated People’s Hospital of Jiangsu University (No. K–2025146–W). The study was conducted in accordance with local legislation and institutional requirements. The participant provided written informed consent to participate in this study.

Funding

This work was supported by the Scientific Research Project of the Health Commission of Jiangsu, China (No. M2024034), and the Social Development Foundation of Zhenjiang, China (Nos. SH2020047 and SH2025005).

Generative AI statement

The authors declare that no generative AI was used in the creation of this manuscript.

ORCID iD

Tao Yang

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