What is causing the recent weight gain and moon‑face in a multiple sclerosis patient, and how should it be managed?

Weight Gain and Moon Face in Multiple Sclerosis: Corticosteroid-Induced Cushing's Syndrome

The recent weight gain and moon face in this MS patient is almost certainly iatrogenic Cushing's syndrome from corticosteroid therapy used to treat MS relapses, and management requires immediate evaluation of the hypothalamic-pituitary-adrenal axis, gradual steroid tapering if possible, and optimization of disease-modifying therapy to minimize future steroid exposure. 1

Primary Cause: Corticosteroid Exposure

The clinical presentation of weight gain with moon face represents classic Cushingoid features that develop from exogenous corticosteroid administration. 1 In MS patients, this typically occurs from:

• Systemic corticosteroids for acute relapses: MS patients frequently receive high-dose methylprednisolone or oral prednisone during inflammatory relapses, which can produce rapid Cushingoid changes including central obesity, moon face, dorsal and supraclavicular fat pads, and wide violaceous striae. 1

• Cumulative steroid burden: Even intermittent pulse-dose steroids for MS relapses can accumulate sufficient exposure to cause iatrogenic Cushing's syndrome, particularly if relapses are frequent or if maintenance low-dose steroids are used. 2, 3

Diagnostic Evaluation

Confirm iatrogenic Cushing's syndrome with the following tests:

• Overnight 1-mg dexamethasone suppression test as the initial screening test 1
• 24-hour urinary free cortisol excretion (preferably multiple collections) 1
• Morning ACTH level to distinguish iatrogenic (suppressed ACTH) from endogenous causes 2, 4

Critical pitfall: Do not assume all Cushingoid features in a steroid-treated patient are iatrogenic—rare cases of concurrent endogenous Cushing's syndrome from adrenal adenoma have been reported in patients on chronic corticosteroids for autoimmune diseases. 2, 3 If cortisol levels remain elevated after steroid discontinuation, pursue imaging with abdominal CT scan to exclude adrenal pathology. 1, 3

Management Strategy

Immediate Actions

Taper corticosteroids gradually rather than abrupt discontinuation to prevent adrenal crisis, as prolonged steroid exposure suppresses the hypothalamic-pituitary-adrenal axis. 4, 5 The recovery period can take 4 months or longer after cessation. 4

Assess for complications of hypercortisolism:

• Hypertension (target <130/80 mmHg) 1
• Hyperglycemia and impaired glucose tolerance 2
• Hypokalemia (can cause arrhythmias, especially atrial fibrillation) 1
• Osteoporosis and fracture risk 1
• Venous thromboembolism risk (pulmonary embolism and deep vein thrombosis have been reported with iatrogenic Cushing's) 5

Optimize MS Disease-Modifying Therapy

The fundamental solution is preventing future relapses through effective disease-modifying therapy (DMT) to eliminate the need for repeated corticosteroid courses. 6, 7

• Escalate to higher-efficacy DMT if the patient is experiencing breakthrough relapses requiring frequent steroids. Nine classes of DMTs reduce annualized relapse rates by 29-68% compared to placebo. 6, 7

• Consider high-efficacy options such as monoclonal antibodies (natalizumab, ocrelizumab, alemtuzumab) or autologous hematopoietic stem cell transplantation for patients with highly active disease requiring repeated steroid exposure. 6

• Monitor treatment response with annual brain MRI using contrast-enhanced T1 sequences to detect acute inflammation and T2 sequences for new or enlarging lesions. 6

Nutritional and Metabolic Management

Address weight gain and metabolic complications:

• MS patients should undergo regular monitoring of nutritional and vitamin status, with particular attention to changes in body weight. 1
• Supplement vitamin D and calcium as per local guidelines, as MS patients have lower vitamin D levels and reduced bone mineral density. 1
• Screen for and treat cardiovascular risk factors including hypertension, diabetes, hyperlipidemia, and metabolic syndrome. 1
• Encourage a diet lower in saturated fat and higher in polyunsaturated fatty acids from food sources. 1

Important caveat: Weight gain in MS can have multiple causes beyond steroids, including reduced mobility, fatigue, and changes in eating behavior. 1 However, the specific combination of weight gain with moon face strongly indicates Cushingoid features rather than simple deconditioning. 1

Monitoring During Recovery

• Serial cortisol measurements to document recovery of adrenal function after steroid withdrawal 4
• Blood pressure monitoring as hypertension may persist and require treatment 1, 2
• Bone density assessment if prolonged steroid exposure occurred 1
• Weight and body composition tracking as recovery from Cushingoid features can take several months 4, 5

Prevention of Recurrence

Minimize future corticosteroid exposure by:

• Using the lowest effective dose and shortest duration when steroids are necessary for acute relapses 1
• Optimizing DMT to reduce relapse frequency 6, 7
• Avoiding concurrent use of other corticosteroid formulations (topical, inhaled, intra-articular) that can contribute to cumulative exposure 4, 5