CASE REPORT
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Pediatric adrenocortical carcinoma complicated by uric acid nephrolithiasis: a unique case report
Mao Zhang1, Wenping Guo1, Hengping Li1 and Xinsheng Xi1*
Abstract
Background Adrenocortical carcinoma (ACC) is an exceedingly rare malignancy in children, typically presenting with Cushing’s syndrome due to excessive hormone secretion. The occurrence of uric acid nephrolithiasis in pediatric ACC patients is exceptionally uncommon.
Case presentation We report the case of a 5-year-old boy who exhibited symptoms of Cushing’s syndrome over a period of 10 months, including rapid weight gain, moon face, and increased chest and back hair growth. Laboratory tests revealed elevated cortisol, 17-hydroxyprogesterone, and testosterone levels. Imaging studies identified a 6.6x5.6 cm mass in the left adrenal gland, which was confirmed as ACC through biopsy and immunohistochemistry. One day prior to the scheduled adrenalectomy, the patient developed renal colic due to multiple kidney stones, as evidenced by emergency CT scans showing bilateral nephrolithiasis and a stone in the left upper ureter with mild hydronephrosis. Postoperatively, the patient spontaneously expelled brick-red uric acid stones. With glucocorticoid replacement therapy, his hormonal levels and clinical symptoms normalized within a year. A four-year follow-up revealed no recurrence of ACC or urolithiasis, and his hormonal parameters remained within normal ranges.
Conclusion This case highlights the rare association between ACC and uric acid nephrolithiasis in children. The spontaneous passage of uric acid stones provides insights into the link between stone formation and metabolic disorders, emphasizing the need for comprehensive endocrine and metabolic assessments in pediatric ACC management.
Keywords Adrenocortical carcinoma, Uric acid nephrolithiasis, Cushing syndrome, Pediatric, Case report
*Correspondence:
Xinsheng Xi xixsh05@163.com
1Department of Urology, Gansu Provincial Hospital, 204 Donggang West Road, Chengguan District, Lanzhou 730000, China
☒ BMC
@ The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creati vecommons.org/licenses/by-nc-nd/4.0/.
Introduction
Adrenocortical carcinoma (ACC) is a rare and aggressive form of cancer that originates in the adrenal cortex. It affects approximately 0.2-0.3 per million children under 20 years of age, accounting for 0.2% of pediatric cancers [1, 2]. This disease primarily targets young children, with 48% of cases occurring before the age of 3. It typically manifests as large tumors, with a median size of 9.5 cm [3]. Patients often exhibit symptoms of hormone hyper- secretion, such as Cushing’s syndrome and virilization [4]. The prognosis for children with ACC is significantly influenced by age: those aged 4 years and younger have a 5-year survival rate of 95.2%, whereas this rate drops to15.61% for those aged 5-19 years [5], other factors that affect prognosis include tumor size, the stage of the dis- ease, and the status of surgical margins.
Pediatric ACC demonstrates a strong association with hereditary disorders, particularly Li-Fraumeni syndrome (LFS), an autosomal dominant cancer predisposition syndrome caused by germline mutations in the TP53 tumor suppressor gene. Individuals with LFS exhibit sig- nificantly elevated lifetime risks of developing multiple primary malignancies [6]. Notably, germline TP53 muta- tions are identified in approximately 50% of pediatric ACC cases [7], highlighting the substantial genetic com- ponent of this disease. The prevalence of these mutations shows marked geographical variation, with southern Brazil representing a notable hotspot where the founder mutation R337H TP53 occurs in approximately 0.3% of the population [8]. This genetic association underscores the critical importance of comprehensive genetic coun- seling and testing in the clinical management of pediatric ACC patients, as these findings have significant implica- tions for both treatment strategies and familial cancer risk assessment.
| Parameter | Value | Reference Range |
|---|---|---|
| Cortisol Profile | ||
| AM serum cortisol(nmol/L) | 549.00 | 102.00-536.00 |
| PM serum cortisol(nmol/L) | 497.50 | 80.00-478.00 |
| Midnight cortisol(nmol/L) | 496.60 | - |
| 24 h urinary free cortisol(nmol/L/24 h) | 1957 | 100.00-379.00 |
| ACTH(pg/mL) | <1.00 | 7.20-63.30 |
| Androgen/Thyroid Profile | ||
| 17-hydroxyprogesterone(ng/ml) | 3.86 | <2.32 |
| Progesterone(ng/ml) | 0.70 | <0.20 |
| TSH( mIU/L) | 0.51 | 0.67-4.50 |
| T3(nmol/L) | 1.39 | 1.63-3.13 |
| Basic Metabolic Panel | ||
| Sodium(mmol/L) | 142.00 | 137.00-147.00 |
| Potassium(mmol/L) | 4.00 | 3.50-5.30 |
| Calcium(mmol/L) | 2.41 | 2.50-3.00 |
| Phosphorus(mmol/L) | 1.23 | 1.45-2.10 |
Nephrolithiasis is a common but often overlooked complication in individuals with Cushing’s syndrome. Research shows that up to 50% of patients with active Cushing’s syndrome may develop kidney stones, and this prevalence remains around 25% even after the condition is in remission [9]. Among all types of urinary stones, uric acid stones account for approximately 4.9% [10]. The for- mation of uric acid stones is influenced by several factors, particularly urinary pH, urine volume, and metabolic disorders [11]. Notably, uric acid solubility significantly decreases when urinary pH drops below 5.5. In pediat- ric patients, uric acid stones are relatively rare, making up only 1-4% of all urinary stones in this age group [12]. However, metabolic conditions such as metabolic syn- drome and hyperuricemia can greatly increase the risk of stone formation [13]. Clinical case reports indicate that patients with Cushing’s syndrome may face severe com- plications related to urolithiasis, such as acute kidney injury (AKI) [14]. Therefore, it is essential to closely mon- itor pediatric patients with ACC, especially those with Cushing’s syndrome, for signs of kidney stone formation.
Herein, we present a rare case of a 5-year-old boy with ACC in whom uric acid kidney stones were identified during preoperative evaluation and spontaneously passed during postoperative follow-up. The patient exhibited crystalline material in his urine, accompanied by elec- trolyte imbalances and secondary adrenal insufficiency requiring hormone replacement therapy. These postoper- ative complications are uncommon in pediatric patients with adrenocortical carcinoma.
Case presentation
A 5-year-old boy presented with classic features of Cush- ing’s syndrome, which included a 10-month history of rapid weight gain, moon facies, and hirsutism. Physi- cal examination revealed central obesity with a buffalo hump, thin skin with purple striae, growth failure, and severe hypertension, all strongly indicating glucocor- ticoid excess. Initial laboratory tests confirmed hyper- cortisolism, suggesting adrenal-dependent Cushing’s syndrome. Serial cortisol measurements showed a loss of the normal diurnal rhythm. Further endocrine evalu- ation revealed hyperandrogenism and suppressed thy- roid function, consistent with central hypothyroidism induced by glucocorticoids. The basic metabolic panel indicated hypocalcemia and hypophosphatemia, while sodium and potassium levels remained normal (Table 1). These findings led to a primary diagnosis of ACTH-inde- pendent Cushing’s syndrome, accompanied by second- ary hyperandrogenism and central hypothyroidism. The combination of ACTH-independent cortisol excess and hyperandrogenism strongly suggests an adrenal tumor as the underlying cause. Further imaging studies are needed
to confirm the presence and characteristics of the sus- pected adrenal mass.
Imaging studies revealed a mass measuring 6.6× 5.6 cm in the left adrenal region, with a density of 41 Hounsfield Units (HU). The mass exhibited homogeneous enhance- ment and had well-defined margins, along with a relative washout of 51% (Fig. 1A). While these imaging features suggested an adrenal adenoma, the size of the mass (greater than 4 cm) raised concerns for adrenocortical carcinoma.
On day 8 of hospitalization, the patient experienced acute left-sided renal colic. An emergency urological CT scan revealed bilateral kidney stones, as well as a left upper ureteral stone with a density of 134 HU, accompa- nied by mild hydronephrosis (Fig. 1B-D ). The following day, the patient underwent a left adrenalectomy, which revealed a well-encapsulated tumor without local inva- sion.Postoperatively, glucocorticoid replacement ther- apy was initiated with oral prednisone tablets at a dose of 5 mg administered once daily in the morning. Histo- pathological examination revealed that the tumor was composed of epithelioid cells arranged in an irregular pattern. The nuclei demonstrated coarse chromatin pat- terns and prominent nucleoli. The tumor met two crite- ria of the Wieneke scoring system (2 points): presence of atypical mitotic figures and increased mitotic count (>15/20 HPF) (Fig. 2). Immunohistochemical analysis
showed diffuse Ki-67 positivity with a proliferation index of 20%. Based on the NCCN Guidelines for Neuroendo- crine and Adrenal Tumors, integration of clinical presen- tation, radiological findings, and pathological features established the diagnosis of ACC (Table 2). Integration of multiple diagnostic parameters, particularly the sub- stantial tumor size and markedly elevated Ki-67 prolif- eration index, supported the diagnosis of ACC, despite the relatively low Wieneke score. This multi-dimensional diagnostic approach proved more reliable than the appli- cation of a single scoring system in establishing the final diagnosis.
Preoperative CT scans revealed the presence of bilat- eral renal and ureteral stones. On postoperative day 3, as illustrated in Figure 3, the patient passed brick-red crys- talline material in the urine. Microscopic examination confirmed that these were uric acid stones, likely result- ing from post-surgical stress and metabolic changes. A follow-up urological CT on postoperative day 10 showed complete clearance of the stones. Laboratory tests (Table 3) indicated significant electrolyte imbal- ances, including hypokalemia and hypocalcemia, which required electrolyte replacement. Urinalysis suggested urolithiasis, with mild proteinuria and marked micro- scopic hematuria. Additionally, the patient developed secondary adrenal insufficiency, as indicated by low cor- tisol levels, necessitating glucocorticoid replacement
A
B
Calculus
Adrenal tumor
C
D
Calculus
Hydronephrosis
Calculus
| Parameters | Findings | Clinical Implications |
|---|---|---|
| Biochemical Profile | Hypercortisolism, Hyperandrogenism | Cushing's Syndrome |
| Radiological Features | Tumor Size:6.6x5.6 | Exceeds NCCN threshold (>4-5 cm) for malignancy risk |
| Wieneke Score | presence of atypical mitotic figures and increased mitotic count (> 15/20 HPF) | Wieneke Score: 2/9, demonstrates limited adverse pathological features, indicating low risk of aggressive behavior |
| Ki-67 Index | Ki-67 Index=20% | Ki-67 Index> 10: Indicates aggressive proliferative activity |
A
B
0
HUAWEI P30 Pro LEICA QUAD CAMERA
| Parameter | Value | Reference Range |
|---|---|---|
| Urine | ||
| Occult blood | 3+ | Negative (-) |
| Erythrocyte count | 2077 | 0-17 |
| Unclassified crystallization | 3049 | 0-28 |
| Urinary protein | +- | Negative (-) |
| Serum | ||
| Creatinine (umol/L) | 29.10 | 57.00-97.00 |
| Potassium (mmol/L) | 3.10 | 3.50-5.30 |
| Chloride (mmol/L) | 110.80 | 99.00-110.00 |
| Calcium (mmol/L) | 2.19 | 2.50-3.00 |
| Cortisol(nmol/L) | 3.40 | 102.00-536.00 |
due to the suppression of contralateral adrenal function. The glucocorticoid management protocol incorporated a methodical dose-reduction schedule, decreasing the prednisone dosage by 1 mg biweekly until therapy cessa- tion. This incremental tapering approach was designed to mitigate adrenocortical insufficiency risk while facili- tating hypothalamic-pituitary-adrenal axis recovery. Throughout the postoperative monitoring period, no adverse clinical events, including adrenal crisis or phar- macotherapy-related complications, were observed.
Given the established correlation between pediat- ric ACC and TP53 mutations, comprehensive molecu- lar genetic testing was performed to investigate the
genetic basis (Supplementary material). As summarized in Table 4, analysis of archived FFPE tissue revealed no pathogenic somatic mutations in the TP53 gene. Germline testing identified two benign variants (TP53 c.376-91G>A and P72R), with no pathogenic or likely pathogenic mutations detected. Despite ACC diagnosis at age 5, the family history of gastrointestinal malignan- cies (gastric, colorectal, and liver cancers) did not align with the characteristic tumor spectrum of LFS (Fig. 4). The patient met neither the Classic LFS criteria nor the complete Chompret criteria for LFS diagnosis.
During the four-year postoperative follow-up period, the patient demonstrated significant clinical improve- ment, characterized by normalization of serum corti- sol levels. Serial imaging studies showed no evidence of tumor recurrence or stone reformation. The patient’s par- ents expressed satisfaction with the treatment outcomes, confirming that the clinical results met the expected goals, including complete tumor resection, absence of complications or sequelae, and the child’s return to nor- mal academic performance and activities of daily liv- ing. Based on these findings, our recommendations for surveillance include biannual follow-up for the first 5 postoperative years, followed by annual monitoring comprising physical examination, endocrine evaluation, and imaging studies. Additionally, given the family his- tory of gastrointestinal malignancies, appropriate cancer
| Analysis Type | Gene | Variant | Classification | Location | Nucleotide Change | Amino Acid Change |
|---|---|---|---|---|---|---|
| Somatic mutation | TP53 | None detected | - | - | - | - |
| Germlinemutation | TP53 | Variant 1 | Benign | Intron 4 | c.376-91G>A | - |
| Germline mutation | TP53 | Variant 2 | Benign | Exon 4 | c.215 C>G | p.P72R |
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35y
61y
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screening protocols should be considered in long-term follow-up planning.
Discussion
ACC is a rare endocrine cancer, accounting for just 0.2% of pediatric cancers [1]. Unlike adult ACC, the pediatric form exhibits distinct biological characteristics: approxi- mately 90% of cases involve mixed hormone secretion, and prognosis is closely related to the age of the patient [15]. About 42.1% of children with pediatric ACC expe- rience postoperative complications, primarily metabolic disorders [16]. These complications are strongly asso- ciated with tumor size and the surgical approach used; functional tumors are particularly susceptible to electro- lyte and metabolic imbalances [17]. In this context, the preoperative presence of uric acid stones is noteworthy, as it is infrequently reported in the literature. Postopera- tive hyperuricemia-likely linked to tumor burden and surgical stress-may worsen the formation and progres- sion of uric acid stones. The observed sequence of events (preoperative uric acid stones, surgery, and subsequent stone passage) indicates ongoing dysregulation of uric acid levels during the perioperative period. This high- lights the importance of monitoring uric acid levels and implementing individualized management strategies for ACC patients who have concurrent uric acid stones.
The relationship between pediatric ACC, LFS, and TP53 mutations presents a complex genetic and clini- cal paradigm in pediatric oncology. LFS, which involves germline TP53 mutations, is strongly associated with pediatric ACC. This association is particularly evident in southern Brazil, where a specific mutation, identified as R337H, has been recognized as a significant contributor to the development of the disease [18]. In TP53 muta- tion carriers, the age-specific tumor spectrum includes ACC, choroid plexus carcinoma, and rhabdomyosarcoma during childhood (ages 0-15), highlighting the criti- cal role that TP53 mutations play in the pathogenesis of pediatric ACC [19]. Research has shown that germline TP53 mutations can be found in pediatric ACC cases even in the absence of a classic LFS family history, sug- gesting that ACC may serve as an early manifestation of LFS [20]. However, our case, along with other reported TP53-negative pediatric ACC instances, indicates that there are alternative pathogenic mechanisms at play. The lack of TP53 mutations does not necessarily correlate with an improved prognosis, as other genetic or epigen- etic alterations-especially those affecting chromosome 11p15-can significantly impact disease progression [21]. This genetic complexity extends beyond TP53 mutations, emphasizing the necessity for comprehensive genetic screening and molecular profiling to identify other potential molecular drivers and optimize patient man- agement strategies. These findings collectively highlight
the importance of genetic counseling and testing in ACC- affected families for identifying high-risk individuals and implementing appropriate surveillance protocols.
The development of uric acid stones in ACC represents a complex pathophysiological process involving mul- tiple mechanisms. In pediatric ACC, approximately 90% of cases exhibit mixed hormone secretion, significantly exacerbating metabolic instability [22]. The relation- ship between tumor progression and uric acid metabo- lism follows distinct pathological pathways. Tumor cells demonstrate enhanced proliferation and metabolic activity, leading to accelerated nucleic acid catabolism and increased uric acid production. During tumor cell necrosis, the breakdown of cellular components releases purines, which are subsequently metabolized to uric acid, resulting in elevated serum uric acid levels [23]. The pathogenesis of uric acid stone formation in ACC involves complex endocrine-metabolic cascade reactions. Excessive hormone production, particularly cortisol [24], induces insulin resistance, significantly impairing renal ammonium excretion [25]. As ammonia serves as a cru- cial urinary buffer, its reduced excretion leads to urinary acidification [26]. This acidic environment markedly decreases uric acid solubility, promoting crystallization and subsequent stone formation [27, 28]. While surgical intervention is necessary, it may exacerbate these condi- tions through multiple mechanisms. Surgery can trigger inflammatory responses and tissue breakdown, particu- larly in extensive resections, leading to postoperative hyperuricemia [29]. However, in our case, spontaneous stone passage was observed following tumor removal, which may be attributed to several mechanisms: First, the correction of excessive hormone secretion post-tumor removal improved insulin resistance, thereby restoring renal ammonium excretion; Second, improved postop- erative fluid management and metabolic balance elevated urinary pH, enhancing uric acid solubility. This surgical stress response, combined with pre-existing metabolic derangements and subsequent metabolic environment improvement, collectively influenced the stone’s fate. These risks are particularly pronounced in children under 5 years of age, who have limited regulatory capac- ity and often present with more aggressive tumors [30]. This complex interplay between tumor-related metabolic alterations and surgery-induced changes emphasizes the importance of comprehensive perioperative management strategies in ACC patients.
Pediatric ACC presents with distinct clinical features, prognosis, and treatment approaches. Approximately 95% of pediatric ACC cases are functional, character- ized by abnormal hormone secretion [31]. The clinical manifestations can vary widely, with precocious puberty, Cushing’s syndrome, and virilization being among the most common symptoms [32]. Notable individual cases
include a 4-year-old boy diagnosed with ACC who pre- sented with gynecomastia, an 18-month-old boy exhibit- ing signs of virilization, and a rare case of a 10-month-old infant, highlighting the diversity of clinical presentations in pediatric ACC [33, 34].The prognosis for pediatric ACC largely depends on age; children under three years old generally experience better outcomes, with fewer hormone-related postoperative complications and a lower risk of recurrence [3]. In contrast, adult ACC often yields poorer outcomes, a higher metastatic potential, and more frequent postoperative complications such as circulatory instability and renal failure, with common metastases primarily to the liver and lungs [35, 36]. Nota- bly, there are no reports in the literature of ACC coex- isting with kidney stones in pediatric cases, suggesting that kidney stones are not a common complication in this population.
Effective management is vital for pediatric adrenocor- tical carcinoma, especially with uric acid stones. Even though the stone passed spontaneously after surgery without intervention, the treatment approach merits careful consideration. Perioperative care should include hydrocortisone replacement therapy to prevent adrenal crisis [37], along with age-appropriate fluid management: 2% glucose isotonic fluids for children over six and 5% glucose for younger patients [38]. Preoperative evalua- tion should screen for urinary metabolic risk factors, as conditions like hypercalciuria and hyperuricosuria affect many first-time pediatric stone formers [39]. Postopera- tively, close monitoring of water and electrolyte balance is crucial, with early enteral nutrition being important for young patients. Long-term follow-up should involve checks on blood pressure, electrolytes, hormone lev- els, and urinalysis to prevent recurrence, while ensuring the child’s growth and development are adequately sup- ported with timely hormone adjustment.
Several limitations must be acknowledged when inter- preting our genetic findings. The initial molecular analy- sis relied on FFPE tissue specimens collected five years prior, potentially introducing technical challenges due to DNA degradation. To enhance the reliability of our results, we propose to validate our findings using fresh peripheral blood samples obtained from the proband and family members during subsequent follow-up visits. This supplementary whole-exome sequencing analysis of high-quality specimens will serve to corroborate our preliminary findings and strengthen the validity of our conclusions. The implementation of this comprehensive approach, integrating both archived tissue analysis and blood sampling, will substantially improve the robust- ness of our genetic analysis. Furthermore, as a single case report, this study has inherent limitations in represent- ing the complete clinical spectrum, while the relatively short follow-up period constrains our ability to assess
long-term outcomes. Additional research is needed to elucidate the underlying mechanisms of stone formation in pediatric ACC cases.
Conclusions
This report presents a rare case of pediatric adrenocor- tical carcinoma complicated by renal uric acid stones. During preoperative evaluation, the patient was found to have renal uric acid stones, which resolved spontane- ously with increased fluid intake to maintain adequate urine output and sodium bicarbonate therapy. This underscores the importance of thorough preoperative screening and early detection of metabolic abnormalities in pediatric adrenocortical carcinoma, suggesting that appropriate conservative management may yield favor- able outcomes. However, as a single case report, its abil- ity to represent the full clinical spectrum is limited, the relatively short follow-up impedes long-term outcome assessment, and further study of the underlying mecha- nisms of stone formation is needed.
Supplementary Information
The online version contains supplementary material available at https://doi.or g/10.1186/s12894-025-01801-y.
Supplementary Material 1
Supplementary Material 2
Acknowledgements None.
Author contributions
WPG collected and organized the patient data. MZ performed data analysis and wrote the initial draft. HPL provided expert consultation and XSX revised the manuscript critically for important intellectual content. All authors read and approved the final version of the manuscript.
Funding
This study was supported by the Natural Science Foundation of Gansu Province (Grant No. 21JR7RA640) and the Research Project of Gansu Provincial Hospital (Grant Nos. 23GSSYF-20 and 23GSSYA-8).
Data availability
All data supporting the findings of this study are available within the paper and its Supplementary Information.
Declarations
Ethics approval and consent to participate
This study was approved by the Ethics Committee of Gansu Provincial People’s Hospital (approval number: 2024-742). Written informed consent was obtained from the patient’s parents for this case report.
Consent for publication
Written informed consent was obtained from the patient’s parents for publication of this case report and any accompanying images.
Competing interests
The authors declare no competing interests.
Received: 1 January 2025 / Accepted: 22 April 2025
Published online: 30 April 2025
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