Iatrogenic Cushing’s syndrome Caused by Artri Ajo King and Literature Review

Lee JS, Lim SH and Mikhail N

Published on: 2025-10-07

Abstract

Health supplements are widely used but remain largely unregulated, contributing to thousands of emergency visits each year, with health effects ranging from mild to life-threatening. Of these supplements, Artri Ajo King is a popular supplement marketed for pain relief and joint support, and has been associated with iatrogenic Cushing’s syndrome, adrenal insufficiency, and glucocorticoid withdrawal syndrome. We report a case of a 63-year-old male patient with an extensive 15-year history of daily Artri Ajo King use, found to have chronic iatrogenic Cushing’s syndrome. A review of the literature identified 30 published cases of iatrogenic adverse effects associated with Artri Ajo King. Collectively, these cases underscore the critical importance of obtaining a comprehensive history of all medications and supplements to ensure accurate diagnosis, guide appropriate management, and minimize the risk of adverse outcomes.

Keywords

Health effect; Accurate diagnosis; Iatrogenic cushing’s syndrome

Introduction

More than half of Americans report using health supplements [1], a trend driven by the widespread availability and marketing of these products. Unlike prescription medications, health supplements are not subject to the rigorous regulation and approval processes by the US Food and Drug Administration. As a result, there are serious concerns regarding the quality of the health supplements, including the potential for contamination, mislabeling, drug-drug interactions, or undisclosed ingredients. According to FDA investigations, over 700 health supplements contained unapproved pharmaceutical ingredients, with approximately 20% containing more than one substance [2]. Approximately 23,000 emergency department visits in the US each year are attributed to the harmful effects of health supplements [3]. Among these, health supplements marketed for joint pain and arthritis have been reported to contain undisclosed amounts of glucocorticoids, raising significant health concerns [4,5]. Long-term glucocorticoid use can suppress the hypothalamic-pituitary-adrenal (HPA) axis, potentially leading to adrenal insufficiency upon abrupt discontinuation and/or the development of Cushingoid features [6]. Prolonged use is also associated with osteoporosis, increased susceptibility to infections, and new-onset hyperglycemia [6]. In 2022, the FDA advised against the purchase and consumption of a popular joint supplement called Artri Ajo King after it was found to contain undisclosed amounts of dexamethasone and diclofenac [5,7]. Despite these warnings, the supplement remains widely available and is still commonly used, largely due to limited awareness of its potential health risks. This case report presents a patient with chronic steroid exposure from long-term Artri Ajo King use for gout, resulting in cushingoid features and clinical findings consistent with iatrogenic Cushing’s syndrome.

Case Presentation

A 63-year-old Hispanic male with a past medical history of gout, metabolic dysfunction-associated steatotic liver disease, uncontrolled diabetes with HbA1C of 10.2%, and nephrolithiasis presented with worsening lower back pain, fever, nausea, and myalgia. He had been discharged two days earlier following a hospitalization for bilateral pyelonephritis complicated by Escherichia coli bacteremia. On physical examination, he exhibited facial plethora, central obesity, abdominal striae, and a swollen, tender right knee demonstrating a moderate suprapatellar fluid effusion. Given leukocytosis, fever, hypotension, and tachycardia despite initiating appropriate antibiotic therapy, subsequent management focused on evaluating for unresolved pyelonephritis versus an alternative infectious source. Patient had elevated blood glucose to 180 mg/dL and mild hyponatremia of 134 mmol/L (normal range 133- 144 mmol/L). Imaging studies and blood and urine cultures were unrevealing. An arthrocentesis of the right knee to assess for possible septic arthritis or a gout flare was performed. By hospital day six, the patient was clinically stable with a primary concern of gout flare. Upon obtaining further history, the patient reported chronic use of an over-the-counter supplement for gout. He had been taking one to two pills daily for the past 15 years for the relief of his gout symptoms. After running out of his supply, he had discontinued the supplement three weeks prior to admission.

The supplement was later identified as Artri Ajo King, which contains undisclosed pharmacologic agents, including dexamethasone and diclofenac [4]. Knowledge of this chronic glucocorticoid use and recent discontinuation shifted the clinical interpretation of the patient’s hypotension, fever, fatigue, and myalgia towards the differential diagnosis of iatrogenic adrenal insufficiency, glucocorticoid withdrawal syndrome, or Cushing’s syndrome. The patient’s morning cortisol level of 6.5 µg/dL was indeterminate for adrenal insufficiency. Cosyntropin stimulation testing showed a baseline ACTH of 13 pg/mL (normal range 6 - 50 pg/mL), with cortisol levels of 14.9 µg/dL at 30 minutes and 18.1 µg/dL at 60 minutes, which is at the diagnostic threshold for adequate adrenal function. The case was discussed with the endocrinologist. Given the discontinuation of the health supplement approximately one month prior, the patient's clinical improvement, and the normal response to cosyntropin, glucocorticoid replacement therapy was not required.

Discussion

Glucocorticoids are commonly prescribed for autoimmune, inflammatory, allergic, dermatologic, endocrine, respiratory, hematologic, and nervous system disorders [19,20]. The dosage and duration of treatment are important in determining the efficacy of treatment and the risk of adverse effects. There are many risks associated with long-term glucocorticoid use, even at low doses, such as hypertension, diabetes mellitus, hyperlipidemia, osteoporosis, increased fracture risk, increased susceptibility to infections, adrenal insufficiency, and Cushingoid features [21,22]. Of these adverse effects, adrenal insufficiency (AI) and glucocorticoid withdrawal syndrome (GWS) are precipitated by abrupt discontinuation or rapid tapering of glucocorticoids. Exogenous glucocorticoids suppress the hypothalamic-pituitary-adrenal axis, resulting in reduced responsiveness of the anterior pituitary gland and atrophy of the adrenal cortex [23]. Gradual, appropriate tapering of glucocorticoid therapy typically enables the adrenal glands to recover and resume normal cortisol production. However, the recovery response is variable depending on the potency, dose, and duration of glucocorticoid therapy, with large inter-individual variability [23].

The patient presented with fever, hypotension, leukocytosis, and myalgia, initially raising concern for unresolved infection following recent hospitalization for pyelonephritis. However, the persistent symptoms despite appropriate antibiotic therapy and an unrevealing infectious workup prompted evaluation for alternative etiologies. Initially, the patient’s central adiposity and abdominal striae were attributed to obesity, and the facial flushing to fever. The diagnosis pivoted upon the patient’s disclosure of his 15-year history of daily use of Artri Ajo King, which he had abruptly discontinued after running out of supply. Given the abrupt discontinuation of chronic dexamethasone use and clinical presentation, the differential diagnoses included AI, GWS, and Cushing’s syndrome.

Clinically, AI and GWS may present with similar features, including malaise, fatigue, myalgias, arthralgias, fever, gastrointestinal symptoms, dizziness, and recurrence of underlying autoimmune disease

[24]. AI is further characterized by recurrent infections, hyponatremia, and hypoglycemia due to inadequate cortisol production. In contrast, GWS is characterized by flu-like symptoms, irritability, mood swings, and psychiatric manifestations. AI is characterized by biochemical evidence of HPA axis suppression, and most patients with GWS have concomitant AI [23]. In AI and GWS, glucocorticoid therapy with gradual tapering is recommended and should be continued until recovery of the HPA axis is confirmed by clinical stability or biochemical testing [23].

The patient’s clinical improvement without reinitiation or tapering of glucocorticoid therapy, along with an appropriate adrenal response on cosyntropin stimulation testing, effectively excluded AI [25]. GWS was also considered unlikely, as it typically manifests within 1 to 2 weeks of glucocorticoid discontinuation, and our patient had discontinued the supplement approximately one month earlier [23]. GWS is frequently associated with concomitant adrenal insufficiency, which was not observed in this case. Diffuse arthralgias and myalgias may occur with AI and GWS; this patient’s pain was localized primarily to the right knee and improved significantly following arthrocentesis, more consistent with a gout flare than AI or GWS. The patient exhibited facial plethora, central obesity, and abdominal striae, characteristic cushingoid features from chronic supraphysiologic glucocorticoid exposure [26]. Long-term use of Artri Ajo King containing dexamethasone likely contributed to both the development of Cushing’s syndrome and poor glycemic control of his diabetes [6]. Overall, the combination of overt cushingoid features, preserved adrenal function, and prolonged exogenous glucocorticoid exposure supports iatrogenic Cushing’s syndrome as the most likely diagnosis.

Our review of published case reports of exogenous Cushing’s syndrome, AI, and GWS due to adulterated over-the-counter supplements, specifically Artri Ajo King, included 31 patients. To our knowledge, this represents the largest review of Artri Ajo King, summarizing all reported cases to date. Patients ranged from 12 to 69 years of age, with a nearly even distribution between females (48%) and males (52%) (Table 1). The reported duration of supplement use varied widely, from as little as a few weeks to over 10 years, showing that even a short-term exposure to surreptitious glucocorticoids can result in clinically significant adverse effects. Despite heterogeneity in age, sex, and duration of exposure, 26 out of 31 (84%) patients presented with overt cushingoid features, including moon facies, central obesity, buffalo hump, and abdominal striae. Among the patients in the literature review, only one patient experienced Cushingoid features without any evidence of AI or GWS after four months of Artri Ajo King use [9]. Our patient represents the first reported case of Cushing’s syndrome without AI or GWS resulting from an extensive 15-year course of Artri Ajo King. Adrenal testing has been documented in less than 1% of patients in routine clinical practice, with over 70% of cases of AI identified during hospitalizations where nonspecific symptoms may often obscure or delay the diagnosis [27]. Upon cosyntropin stimulation test, 20 out of 31 (65%) patients had biochemical evidence of hypothalamic-pituitary-adrenal axis suppression, with 16 (80%) of these patients requiring a hydrocortisone taper to prevent glucocorticoid withdrawal symptoms. Many of these cases required a thorough history to uncover the patients’ Artri Ajo King use, as the patients did not recognize the supplement as a medication or a potential contributing factor to their presentation. These cases emphasize the need for a thorough medication history, including all supplements and herbal medications, as undisclosed use may obscure the diagnosis and put patients at risk for drug-drug interactions or adverse effects.

Conclusion

Chronic or unrecognized use of unregulated supplements can pose significant health risks [2-6]. In this case, the knowledge of the patient’s extensive use of Artri Ajo King, a supplement containing undisclosed dexamethasone, shifted the diagnostic focus and medical workup. The symptom onset, preserved adrenal function on cosyntropin testing, and clinical improvement without glucocorticoid therapy effectively ruled out both adrenal insufficiency and glucocorticoid withdrawal syndrome. The diagnosis of iatrogenic Cushing’s syndrome was supported by classic Cushingoid features, long-term dexamethasone use, intact adrenal function, and symptom improvement without glucocorticoid therapy. Thorough documentation of all medications and supplements is critical to guide accurate diagnosis and effective treatment.

To our knowledge, this report represents the largest review of Artri Ajo King use, summarizing 31 cases, including our present case. A key limitation of this review is the inconsistent reporting of critical patient details, including supplement duration, cushingoid features, and adrenal testing.

Conflict Of Interest

The authors have no conflict of interest to declare.

Literature Review of Patients Taking Artri King in Existing Literature

Table 1: Literature Review Of Published Cases Of Artri Ajo King Use, Including Patient Age, Sex, Duration Of Use, Presence Of Cushingoid Features, Cosyntropin Test Results, And Administration Of Glucocorticoid Therapy.

Article	Age (years)	Sex	Duration of Use (months)	Presence of Cushingoid Features	Adrenal Insufficiency per Cosyntropin Test	Hydrocortisone treatment
Boncompagni 2023 (8)	52	male	18	yes	yes	yes
Morales 2023 (9)	59	female	4	yes	no	no
Saad-Omer 2023 (10)	40	female	>36	no	yes	no
Mikhail 2022 (11)	54	male	12	yes	yes	no
Patel 2022 (12)	49	female	3	yes	yes	yes
Patel 2022 (12)	61	female	24	yes	yes	yes
Dunn 2023 (13)	35	female	36	yes	yes	yes
Dani 2023 (14)	12	male	10	yes	not tested	no
Berg 2023 (15)	58	female	>6	yes	yes	yes
	55	female	not reported	yes	yes	yes
	59	male	0.5	yes	yes	no
	58	female	not reported	yes	yes	yes
Wei 2024 (4)	56	male	not reported	no	yes	yes
	53	male	not reported	yes	yes	yes
	60	male	not reported	no	yes	yes
	51	male	not reported	yes	no	no
	32	male	not reported	yes	not tested	yes
	50	female	not reported	yes	yes	yes
	42	male	not reported	yes	yes	yes
	36	female	not reported	yes	yes	yes
	69	female	not reported	yes	yes	yes
	50	male	not reported	yes	no	yes
	62	male	not reported	yes	no	no
Ishola 2025 (16)	47	male	120	yes	yes	yes
Pena 2024 (17)	66	male	not reported	yes	yes	yes
Pena 2024 (17)	66	male	not reported	yes	yes	Not reported
Chun 2025 (18)	46	female	8	yes	not tested	yes
	66	female	not reported	no	not tested	no
	21	female	12	no	not tested	yes
	54	female	12	yes	not tested	yes
Present case	63	male	180	yes	no	no

Journal of Aging Science and Gerontology