Severe Exogenous Cushing’s Syndrome with Femoral Avascular Necrosis and Pulmonary Embolism Following Use of an Unregulated “Herbal” Weight-Gain Powder: A Case Report

Technical Summary: Severe Exogenous Cushing's Syndrome from Unregulated Herbal Supplements

Problem Statement
Exogenous Cushing's Syndrome (ECS) is a well-documented consequence of prescribed glucocorticoid therapy; however, an emerging and dangerous source involves unregulated "herbal" or "natural" products adulterated with potent, undisclosed corticosteroids. These products, often marketed for weight gain or traditional remedies, pose a significant public health risk because their contamination is invisible to the consumer. This lack of regulation can lead to delayed diagnosis and severe, life-threatening complications, including metabolic derangements, musculoskeletal destruction (such as avascular necrosis), and thromboembolic events. The specific challenge lies in the diagnostic uncertainty when patients present with classic Cushingoid features but have no history of prescribed steroid use, particularly in contexts where reliance on traditional remedies and limited access to regulated healthcare are prevalent.

Methodology
This study is a single-patient case report adhering to the CARE guidelines. The methodology involved the comprehensive clinical evaluation of a 27-year-old male presenting with rapid weight gain, neuropsychiatric disturbances, and progressive hip pain following the ingestion of an unlabeled weight-gain powder purchased from a local herbalist.

The diagnostic approach included:

• Clinical Assessment: Evaluation of physical signs (violaceous striae, obesity, weakness) and psychiatric status (agitation, disorganized thoughts).
• Imaging: Spiral CT angiography of the chest to assess respiratory symptoms and 3D pelvic CT reconstruction to evaluate hip pathology.
• Laboratory Analysis: Measurement of morning plasma cortisol, adrenocorticotropic hormone (ACTH), and 24-hour urine-free cortisol to assess hypothalamic–pituitary–adrenal (HPA) axis function. Bone mineral density testing was also performed.
• Comparative Analysis: The authors contextualized the patient's presentation by reviewing existing literature on similar cases involving contaminated supplements (e.g., "Artri King" and herbal ointments containing dexamethasone or clobetasol).
• Limitation Note: The authors explicitly state that chemical analysis (mass spectrometry or chromatography) of the herbal powder was not performed due to resource and laboratory constraints, relying instead on the clinical phenotype and exclusion of other causes.

Key Results
The patient presented with a constellation of severe complications attributed to chronic, high-dose glucocorticoid exposure:

• Endocrine Profile: Marked suppression of the HPA axis was confirmed, with morning plasma cortisol <0.05 µg/dL, ACTH <5 pg/mL, and 24-hour urine-free cortisol at 1.1 µg/24 h. These findings are consistent with prolonged exogenous steroid exposure.
• Musculoskeletal Complications: Imaging revealed multifragmentary fracture and dislocation of the femoral head without trauma, consistent with avascular necrosis (osteonecrosis). Bone density testing confirmed osteoporosis.
• Thromboembolic Events: CT angiography confirmed acute pulmonary thromboembolism with central filling defects in the left lower lobe, accompanied by pleural effusion and ground-glass opacities.
• Neuropsychiatric and Metabolic Effects: The patient exhibited rapid 35-kg weight gain, hepatic steatosis (Grade I), and severe psychiatric instability (diagnosed with features of paranoid disorder, OCD, and personality disturbances), which required antipsychotic therapy.
• Clinical Course: Following the discontinuation of the suspected powder and initiation of supportive care (anticoagulation, antipsychotics), the patient's psychiatric and acute respiratory symptoms stabilized. However, the femoral head collapse progressed, necessitating planned orthopedic intervention, and HPA axis suppression persisted three months post-discontinuation.

Key Contributions

• Documentation of Severe Multisystem Toxicity: The report details a rare and severe convergence of complications—simultaneous avascular necrosis, pulmonary embolism, and severe psychiatric decompensation—resulting from a single source of unregulated herbal ingestion.
• Highlighting Diagnostic Challenges: The case underscores the difficulty in diagnosing ECS when the source is an unlabeled product, particularly in the absence of chemical confirmation. It demonstrates how clinical phenotyping and hormonal suppression patterns can strongly suggest the etiology even without direct product analysis.
• Contextualizing Social Determinants: The authors link the case to broader social determinants of health, noting how reliance on traditional remedies and the availability of unmonitored supplements in specific communities increase the risk of accidental steroid exposure.

Significance and Claims
The paper claims that this case serves as a critical warning regarding the dangers of unregulated "herbal" weight-gain supplements. While the authors acknowledge the limitation of not being able to chemically verify the powder's contents, they assert that the clinical presentation, combined with the suppression of the HPA axis and the similarity to previously documented cases of contaminated supplements, provides strong evidence for exogenous Cushing's syndrome caused by hidden glucocorticoids.

The significance of the work lies in its call for:

1. Clinical Vigilance: Clinicians must consider hidden glucocorticoid exposure in patients presenting with unexplained Cushingoid features, especially those using non-prescription supplements.
2. Regulatory Oversight: There is an urgent need for greater regulatory control over over-the-counter herbal products to prevent adulteration.
3. Public Awareness: Education is essential to inform the public about the potential toxicity of unverified "natural" products.

The authors conclude that while their specific case could not be chemically proven, it adds to the growing body of evidence that unregulated formulations can contain potent corticosteroids capable of inducing life-threatening systemic complications.