A Case of Acute Adrenal Insufficiency Unmasked During Sunitinib Treatment for Metastatic Renal Cell Carcinoma

Abstract

Sunitinib has recently become a standard treatment for metastatic renal cell carcinoma. However, various adverse events have been reported. We present the first case of clinically evident adrenal insufficiency during sunitinib therapy. A 72-year-old man began sunitinib therapy for bilateral lung and adrenal metastases of renal cell carcinoma. His adrenocorticotrophic hormone level was 93.6 pg/ml (7.2 -63.3 pg/ml) before sunitinib treatment, indicating that subclinical adrenal insufficiency already existed. Fatigue, which is a frequently seen adverse effect of sunitinib treatment, emerged acutely on Day 24 of the second cycle. Adrenocorticotrophic hormone and free T4 were high and thyroid-stimulating hormone was suppressed. Under the clinical diagnosis of acute adrenal insufficiency with thyrotoxicosis, a low dose of steroid was administered. Fatigue was completely ameliorated by the following morning, although free T4 was still high and thyroid-stimulating hormone was still low. Therefore, hypermetabolism due to thyrotoxicosis unmasked adrenal insufficiency in our case. Physicians should be aware of this rare but potentially fatal complication when severe acute fatigue develops in patients with subclinical adrenal insufficiency.

Sunitinib-Induced Adrenal Crisis in a Patient with Pre-Existing Immunotherapy-Related Hypopituitarism

“…While initial safety studies of sunitinib failed to demonstrate clinical relevance of adrenal toxicity, Yoshino et al [2] have reported a case of possible sunitinib-associated adrenal insufficiency in the setting of mRCC treatment. This patient received sunitinib therapy for mRCC with bilateral adrenal metastases and pre-treatment ACTH and cortisol levels indicating subclinical hypoadrenalism.…”

“…The authors postulated that hypermetabolism secondary to thyroid hormone excess was responsible for unmasking adrenal toxicity. Given the response of adrenal metastases to treatment, the clinical relevance of aforementioned adrenal toxicity was theorised [2].…”

“…The authors postulated that hypermetabolism secondary to thyroid hormone excess was responsible for unmasking adrenal toxicity. Given the response of adrenal metastases to treatment, the clinical relevance of aforementioned adrenal toxicity was theorised [2]. Further to this, Elshimy et al [3] have reported a case of primary adrenal insufficiency in the setting of pazopanib therapy for mRCC.…”

“…Within the product information for this medication, adrenal toxicity is listed as a recognized toxicity, but its clinical significance has yet to be determined [1]. Two previous case reports have been published describing TKI-induced adrenal insufficiency with sunitinib and another TKI, pazopanib [2, 3]. We report a case of presumed sunitinib-induced adrenal crisis in a patient with established hypopituitarism and hypoadrenalism in the setting of previous immunotherapy use.…”

Optimizing Patient Adherence to Targeted Therapies in Renal Cell Carcinoma

“…Like almost all anticancer therapies, fatigue is common among recipients of VEGFr-TKI (Cohen & Oudard, 2012). Instances of severe, acute fatigue in recipients of VEGFr-TKI should be investigated further because rare cases of adrenal insufficiency being unmasked by the effects of VEGFr-TKI therapy have been reported (Yoshino et al, 2012). VEGFr-TKIs are also associated with hypothyroidism (Feldt et al, 2012), and patients who experience fatigue should be evaluated for the need for thyroid hormone replacement therapy.…”