THE PARADOX OF PLENTY

WHEN GLUCOCORTICOID RESISTANCE SYNDROME MEETS SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract

INTRODUCTION/BACKGROUND
Glucocorticoid resistance syndrome (GRS) is a rare condition characterized by biochemical hypercortisolism without the typical clinical manifestations of Cushing’s syndrome. Patients with GRS exhibit elevated serum cortisol, increased 24-hour urinary free cortisol, normal to elevated ACTH, non-suppressed low-dose dexamethasone-suppression test results and preserved circadian rhythm, which are findings that help distinguish it from Cushing’s disease. It is associated with various mutations in the NR3C1 gene, which encodes the glucocorticoid receptor. Clinical presentations can vary from being asymptomatic to exhibiting features of mineralocorticoid or androgen excess such as hypertension with hypokalemia or hyperandrogenism.

CASE
A 51-year-old female with type 2 diabetes mellitus, hypertension, and dyslipidemia presented with bilateral lower limb edema and intermittent facial flushing. Her BMI was within normal range, and her blood pressure and blood glucose were well-controlled. Notably, she had persistent hypokalemia and elevated cortisol levels. MRI of the pituitary revealed a partial empty sella with a suspected right-sided pituitary adenoma. Her bone mineral density was also normal. Inferior petrosal sinus sampling confirmed ACTH-dependent hypercortisolism. However, in the absence of clinical features of Cushing’s syndrome, diagnosis of GRS was made.

She was started on dexamethasone, leading to significant reduction in cortisol levels over nine months. However, her condition was complicated by recurrent infections, soft tissue abscesses, and a newly diagnosed systemic lupus erythematosus (SLE) with concomitant lupus nephritis. Frequent steroid adjustments were necessary to manage autoimmune flares, which, in turn, increased her risk for opportunistic infections, culminating in severe Pneumocystis jirovecii pneumonia.

CONCLUSION
This case illustrates the diagnostic and therapeutic challenges of managing GRS, particularly when complicated by autoimmune disease and infection risk. While dexamethasone is effective in suppressing the HPA axis in GRS due to its glucocorticoid receptor affinity and mineralocorticoid-sparing properties, its use in patients with concurrent immunosuppressive conditions like SLE requires careful balance to avoid immunosuppression-related complications. Individualized steroid management is crucial to optimize outcomes and minimize adverse events.