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All Journal Open Access Indonesian Journal of Medical Reviews
Devina Ravelia Tiffany Subroto
General Practitioner, Wangaya Regional General Hospital, Denpasar, Indonesia
Health Professions Medicine & Pharmacology

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Severe Hyponatremia with Normokalemia in Pembrolizumab-Lenvatinib Combination Therapy for Metastatic Renal Cell Carcinoma: A Case of Suspected Secondary Adrenal Insufficiency and Clinical Differentials Devina Ravelia Tiffany Subroto; Steven Jonathan; I Putu Bayu Triguna
Open Access Indonesian Journal of Medical Reviews Vol. 6 No. 1 (2026): Open Access Indonesian Journal of Medical Reviews
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/oaijmr.v6i1.826

Abstract

The combination of Pembrolizumab and Lenvatinib has become the standard first-line treatment for advanced renal cell carcinoma (RCC). However, the overlapping toxicity profiles of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) create significant diagnostic challenges, particularly regarding electrolyte disturbances. Differentiating ICI-induced secondary adrenal insufficiency from TKI-induced toxicity or syndrome of inappropriate antidiuretic hormone (SIADH) is critical, especially in resource-limited settings where rapid hormonal assays are unavailable. A 67-year-old male with metastatic clear cell RCC presented with confusion, fatigue, and nausea 14 days after initiating palliative Pembrolizumab and Lenvatinib. He had a history of partial nephrectomy and was on Candesartan. Evaluation revealed severe hypotonic hyponatremia (113 mmol/L), acute kidney injury (Creatinine 2.2 mg/dL), and a hypertensive crisis (BP 229/138 mmHg). Notably, despite renal impairment and angiotensin receptor blocker therapy, potassium levels were normal (4.2 mmol/L). The hyponatremia was refractory to 3% hypertonic saline. Suspecting secondary adrenal insufficiency, empiric high-dose corticosteroids were administered, resulting in rapid normalization of serum sodium and resolution of symptoms. In conclusion, in patients receiving ICI-TKI therapy, the specific profile of severe hyponatremia with normokalemia—particularly in the context of renal insufficiency and RAAS blockade—serves as a high-value clinical indicator of preserved mineralocorticoid function. This points toward secondary adrenal insufficiency rather than primary adrenal injury or TKI-induced renal tubular acidosis. This case underscores the utility of deductive physiology in oncology practice.
Severe Erythema Nodosum Leprosum Complicated by Warm Autoimmune Hemolytic Anemia: Navigating the Immunosuppressive Paradox Devina Ravelia Tiffany Subroto; Kadek Cahya Adwitya; I Putu Bayu Triguna
Open Access Indonesian Journal of Medical Reviews Vol. 6 No. 1 (2026): Open Access Indonesian Journal of Medical Reviews
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/oaijmr.v6i1.834

Abstract

Erythema nodosum leprosum (ENL) is a severe, systemic immune-complex mediated complication of multibacillary Hansen’s disease. While anemia of chronic disease is frequently observed in leprosy, the concurrent development of Warm Autoimmune Hemolytic Anemia (wAIHA) is an exceptionally rare and precarious clinical entity. This comorbidity creates a therapeutic paradox wherein the high-dose corticosteroids required to halt hemolysis may exacerbate the risk of sepsis in patients with necrotic skin lesions and compromised barrier function. We report the case of a 42-year-old male with multibacillary Hansen’s disease on multidrug therapy who presented with high-grade fever, progressive fatigue, and necrotic cutaneous lesions. Laboratory evaluation revealed life-threatening normocytic normochromic anemia (Hemoglobin 3.5 g/dL) and a leukemoid reaction (WBC 42,540/µL). Hemolysis was confirmed by elevated lactate dehydrogenase (564 U/L), indirect hyperbilirubinemia, and a strongly positive direct Coombs test (IgG). A diagnosis of wAIHA secondary to severe necrotic ENL was established. Standard high-dose pulse steroid therapy was deemed high-risk due to the patient’s extreme neutrophilia (NLR 80.25) and open necrotic ulcers. Consequently, a tailored regimen of intermediate-dose intravenous methylprednisolone (62.5 mg twice daily) combined with broad-spectrum antibiotics was initiated. This strategy successfully suppressed hemolysis and resolved the ENL reaction without precipitating secondary opportunistic infections. In conclusion, the coexistence of wAIHA and ENL suggests a shared mechanism of dysregulated T-cell immunity and molecular mimicry. This case demonstrates that in scenarios involving high infectious risk, an individualized, intermediate-dose corticosteroid protocol can achieve remission while mitigating the dangers of profound immunosuppression.
Co-Authors I Putu Bayu Triguna Kadek Cahya Adwitya Steven Jonathan