Steroid Withdrawal Syndrome and Adrenal Insufficiency Following Unsupervised Steroid Use: A Case Report

ABSTRACT

We report a 65‐year‐old female with prolonged unsupervised corticosteroid use who developed exogenous Cushing syndrome, recurrent infection, and adrenal crisis following abrupt withdrawal.

Key Clinical Message

Careful steroid history, supervised tapering, and early recognition of adrenal insufficiency are essential to prevent life‐threatening complications.

1. Introduction

Steroid withdrawal syndrome (SWS) results from acute glucocorticoid deficiency following abrupt cessation of long‐term corticosteroid therapy. Chronic steroid use suppresses the HPA axis by reducing CRH and ACTH secretion, leading to adrenal atrophy and impaired stress response. This causes secondary adrenal insufficiency, in which the adrenal glands cannot make enough cortisol because ACTH stimulation is inadequate. HPA axis recovery is unpredictable and often takes months. Unrecognized, it can lead to life‐threatening adrenal crisis [1]. Unsupervised or over‐the‐counter steroid use, particularly in low‐resource settings, is a serious concern as it can result in metabolic complications, increased susceptibility to infection, and severe withdrawal symptoms. Here, we report a female with chronic unregulated steroid use for knee pain who developed recurrent infections and metabolic instability, highlighting the diagnostic challenges and the need for careful, supervised steroid tapering.

This case report has been reported in line with the CARE guideline [2].

2. Case Presentation

2.1. Case History/Examination

A 65‐year‐old woman with known hypothyroidism (levothyroxine 88 μg once daily), Type 2 diabetes mellitus (on insulin therapy and oral hypoglycemics), hypertension (amlodipine 10 mg once daily), and bilateral knee osteoarthritis presented with a 6‐month history of recurrent soft‐tissue infections requiring four hospital admissions. Her past surgical history was notable for a laparoscopic cholecystectomy 10 years prior and cataract surgery of the left eye 8 years prior, both uncomplicated. On social history, she was an ex‐smoker having stopped 30 years ago, with no quantified pack‐year history documented, and reported occasional alcohol intake.

On her first admission, she presented with a 7‐day history of right forearm swelling, pain, and erythema, accompanied by fever (100°F) and vomiting. The examination was consistent with cellulitis. She responded to intravenous antibiotics and was discharged on oral antibiotics. Two months later, she was readmitted with cellulitic wound dehiscence and bilateral lower limb edema. Investigations revealed hyperglycemia (FBS 154 mg/dL, PPBS 229 mg/dL) and mild hyponatremia (serum sodium 131 mmol/L). She underwent wound debridement with glycemic optimization (FBS 110 mg/dL, PPBS 130 mg/dL) prior to discharge. A third admission followed 4 weeks thereafter for recurrent right forearm cellulitis, complicated by persistent edema, worsening metabolic instability, and new‐onset hypotension refractory to initial fluid resuscitation. An endocrinology referral was initiated at this point, and re‐debridement of the right forearm cellulitis was done.

Her fourth and most critical admission was for severe lethargy, profuse vomiting, and low blood pressure. On arrival, she was hypotensive (78/52 mmHg), tachycardic (118 bpm), tachypneic (26 breaths/min), and hypoxic (SpO₂ 93% on room air). She was febrile (100.1°F). Anthropometric assessment recorded a weight of 60 kg, height of 148 cm, and BMI of 27.4 kg/m [2]. Examination showed pronounced cushingoid features including moon facies, truncal obesity (Figure 1), a buffalo hump, and thin friable skin with xerotic changes and easy bruising. Bilateral lower limb pitting edema and proximal muscle weakness were additionally noted. The right forearm wound (Figure 2), debrided during her third admission, had not healed. It showed no granulation tissue and was still dehiscent, a finding consistent with impaired wound healing. She was conscious and oriented to person, but disoriented to time and place. Cardiovascular examination demonstrated tachycardia with an otherwise unremarkable precordium, and the chest was clear on auscultation. GCS was 14/15.

FIGURE 1.

Diffuse reticulated hyperpigmentation with xerotic changes and truncal obesity.

FIGURE 2.

Extensive right forearm soft‐tissue defect with pus and slough.

A detailed medication history obtained on this admission revealed that the patient had been self‐administering oral prednisolone 10 mg daily, procured without medical prescription, for over 1 year to manage chronic bilateral knee pain. She had abruptly discontinued the medication approximately 1 month prior to this admission without medical guidance. This history had not been disclosed during any of her three preceding admissions. She denied use of topical corticosteroids, herbal preparations, or traditional medicinal formulations.

3. Methods (Differential Diagnosis, Investigation and Treatment)

The relevant laboratory findings are summarized in (Table 1).

TABLE 1.

Investigation results.

Investigation	Result	Reference range
CBC (complete blood count)
WBC	12,200/μL	4500–11,000/μL
Hemoglobin	10.9 g/dL	12.0–16.0 g/dL
Neutrophils	83%	40%–70%
Platelets	2.92 × 105/μL	1.5–4.0 × 105/μL
LFT (liver function tests)
ALP	122 U/L	44–147 U/L
AST	140 U/L	10–40 U/L
Total bilirubin	1.8 mg/dL	0.2–1.2 mg/dL
Albumin	2.0 g/dL	3.5–5.0 g/dL
Electrolytes
Sodium	133 mEq/L	136–145 mEq/L
Potassium	3.0 mEq/L	3.5–5.0 mEq/L
Chloride	93 mEq/L	98–106 mEq/L
Renal panel
Urea	20 mg/dL	7–20 mg/dL
Creatinine	0.5 mg/dL	0.6–1.2 mg/dL
HbA1c
HbA1c	6.8%	< 5.7% normal; 5.7%–6.4% prediabetes; ≥ 6.5% diabetes
Thyroid profile
FT3	3.15 pg/mL	2.50–3.90 pg/mL
FT4	0.83 ng/dL	0.61–1.12 ng/dL
TSH	2.70 μIU/mL	0.34–5.20 μIU/mL
Microbiology
Wound C&S	Staph. aureus	—
Sensitive to	Amikacin, ceftriaxone, Pip‐Taz, carbapenems	—
Resistant to	Amoxycillin, cipro, cloxacillin, co‐trimoxazole	—
Gram stain	Gram + ve cocci in pairs & chains	—
Imaging
Echocardiography	LVEF 60%; valves normal; no vegetation; no effusion	LVEF ≥ 55%
Color doppler—R. forearm	No DVT; focal collection between fascia & muscle; subcutaneous edema	—
Venous doppler—bilateral LL	No DVT; bilateral subcutaneous edema (R > L)	—
Abdominal USG	Liver 16 cm; Grade II fatty change; post‐cholecystectomy; no peri‐wound collection	Liver ≤ 15 cm
Upper GI endoscopy	Pangastritis—erosions & erythema in fundus, body & antrum; duodenum normal	—

Initially ACTH stimulation test/cosyntropin stimulation test couldn't be performed due to the patient's low socio‐economic status. Based on the history, examination and available tests, we diagnosed exogenous Cushing syndrome from prolonged prednisolone use, with secondary adrenal insufficiency and adrenal crisis after abrupt withdrawal. Emergency management was started with IV hydrocortisone 100 mg bolus, followed by 50 mg six‐hourly, with aggressive IV fluid resuscitation and electrolyte correction. Hemodynamic recovery was achieved within 12 h, with improvement in neurological status within 48 h. Once the patient was clinically stabilized, a morning (AM) serum cortisol level, taken 10 h after her last IV dose, was measured and found to be 18.86 μg/dL (reference range: 8.7–22.4 μg/dL). The patient was transitioned to oral prednisolone 20 mg daily with a structured 8‐week taper to facilitate HPA axis recovery. Oral hypoglycemics were withheld during acute illness and reintroduced cautiously. Piperacillin–tazobactam therapy was administered for the management of the wound infection. Levothyroxine was continued unchanged. Osteoarthritic knee pain was managed with paracetamol, topical NSAID gel, and physiotherapy.

4. Results and Conclusion (Outcomes and Follow‐Up)

At the time of discharge, she had improved functional status with resolution of fatigue, myalgia, and increased appetite and mobility. At the 4‐week outpatient follow‐up, a repeat morning serum cortisol measurement was planned; however, it could not be performed because of the patient's financial constraints. The forearm wound showed marked improvement, with complete resolution of purulent discharge and the presence of healthy granulation tissue. The patient was scheduled for skin grafting at a subsequent visit and was advised to continue regular wound dressing at home. Cushingoid features had gradually decreased, and she had good glycemic control. Oral Prednisolone 5 mg daily was continued with a plan to reassess every 4 weeks.

5. Discussion

Physiologically, cortisol secretion is regulated by the hypothalamic–pituitary–adrenal axis through CRH‐ and ACTH‐mediated stimulation, with cortisol exerting negative feedback on both hormones. Exogenous glucocorticoid administration, even at low doses and for short durations, suppresses this axis by inhibiting CRH and ACTH secretion [1]. Long‐term administration of high‐dose glucocorticoids and other hormones may cause reduced drug responsiveness and physiological dependence, and withdrawal of therapy may precipitate a combination of hormone deficiency and nonspecific withdrawal symptoms [3]. Glucocorticoid withdrawal syndrome is believed to result from physiological dependence on prolonged supraphysiological glucocorticoid exposure. The condition is thought to be mediated by the development of glucocorticoid tolerance and involves factors such as interleukin‐6, corticotropin‐releasing hormone, vasopressin, and central noradrenergic and dopaminergic systems [3, 4].

In our patient, abrupt cessation of over‐the‐counter steroids likely caused her withdrawal symptoms and adrenal crisis, particularly in the background of recurrent infections.

Iatrogenic Cushing syndrome may occur following excessive topical corticosteroid use, particularly in children and infants, and can also lead to adrenal insufficiency. Major risk factors include prolonged use of potent steroids, frequent application, large treatment areas, impaired skin barriers, and occlusive dressings [5, 6]. Although our patient denied the use of topical corticosteroids and traditional medicinal preparations, her prolonged oral corticosteroid use contributed to the development of cushingoid features and adrenal crisis. A 2012 case–control analysis demonstrated that the risk of serious infection associated with taking prednisolone 5 mg daily for 3 years was comparable to that of taking 30 mg daily for 1 month. The study also found that discontinuation of a two‐year course of prednisolone 10 mg daily for 6 months reduced the risk by nearly half compared with continued use [7]. Similarly, our patient had been taking oral prednisolone 10 mg daily for more than 1 year and subsequently developed an infective complication in the form of forearm cellulitis.

The patient's socioeconomic status was a major limiting factor during the diagnostic evaluation. Because of the patient's financial constraints, a cosyntropin stimulation test could not be performed; therefore, the diagnosis was primarily based on clinical history, examination findings, and supportive basic laboratory investigations. Current literature suggests that the 1‐μg cosyntropin stimulation test is more sensitive than the 250‐μg test for diagnosing secondary adrenal insufficiency, particularly in non‐stressed and critically ill patients. However, in primary adrenal insufficiency, the low‐dose test offers no significant diagnostic advantage over the standard high‐dose test [8].

Although the optimal strategy for discontinuing prolonged glucocorticoid therapy remains uncertain, gradual tapering is generally recommended. Patients receiving chronic or high‐dose glucocorticoids should also receive stress‐dose steroid coverage unless normal hypothalamic–pituitary–adrenal axis function has been confirmed [9]. A 2002 systematic review of randomized controlled trials found no significant difference between rapid and slow glucocorticoid tapering in terms of disease exacerbation or relapse rates, suggesting that prolonged withdrawal may not always improve outcomes. However, the review also emphasized the limited evidence regarding the safety and efficacy of glucocorticoid withdrawal across chronic diseases and highlighted the need for further research [10]. In our case, a similar approach was adopted; the patient was commenced on oral prednisolone 20 mg daily, with a gradual taper over 8 weeks involving weekly dose reductions of 5 mg, followed by continuation at a maintenance dose of 5 mg daily. Newer guidelines suggest that patients presenting with unexplained features suggestive of primary adrenal insufficiency—such as hypotension, hyponatremia, hyperkalemia, hypoglycemia, fever, abdominal pain, or volume depletion—should undergo diagnostic evaluation for adrenal insufficiency. Confirmation is recommended with a corticotropin (Synacthen) stimulation test when clinically feasible. However, in suspected adrenal crisis or severe adrenal insufficiency, immediate treatment with stress‐dose intravenous hydrocortisone should be initiated without awaiting diagnostic test results [11]. Unlike the guideline‐based recommendations, cost and poor awareness of steroid risks complicated her care. This highlights the growing healthcare burden associated with inappropriate steroid use and emphasizes the importance of patient education, regular follow‐up, and monitoring.

6. Conclusion

This case highlights the clinical consequences of unsupervised oral corticosteroid use and the diagnostic delays that can arise when patients do not disclose such use. Exogenous Cushing syndrome and secondary adrenal insufficiency should be considered in any patient presenting with cushingoid features, recurrent infections, poor wound healing, or hemodynamic compromise of unclear etiology. A thorough medication history enquiring about over‐the‐counter and non‐prescribed agents is essential. Prompt corticosteroid replacement in confirmed or suspected adrenal crisis, followed by a carefully supervised taper and patient education, is the key to management.

Author Contributions

Samit Kumar Gautam: conceptualization, writing – original draft. Shardul Bhattarai: writing – original draft. Aastha Dhakal: writing – original draft. Kushal Acharya: writing – review and editing. Binay Khadka: writing – review and editing. Ganesh Lama: writing – review and editing. Milan Shakya: writing – review and editing. Alok Dhungel: data curation, supervision, validation.

Funding

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient and the patient's family members to publish this report in accordance with the journal's patient consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.