15 July 2021>: Articles
Isolated Adrenocorticotropic Hormone Deficiency Associated with Severe Hyperkalemia During Pembrolizumab Therapy in a Patient with Ureteral Cancer and an Ileal Conduit: A Case Report and Literature Review
Unusual clinical course
Yudai Hinata B , Nobumasa Ohara A* , Yuhki Sakurai C , Ryo Koda B , Yuichiro Yoneoka C , Toshinori Takada C , Noboru Hara B , Tsutomu Nishiyama BDOI: 10.12659/AJCR.931639
Am J Case Rep 2021; 22:e931639
Table 4. Summary of reports of patients who exhibited isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) associated with cancer treatment with programmed cell death 1 inhibitors.
Ref. | Age/sex | Target cancer | PD-1 inhibitor administered | Period from drug initiation to IAD onset (months) | Major symptoms at IAD onset | Plasma ACTH (pg/mL) |
---|---|---|---|---|---|---|
[]6 | 50/M | Melanoma | Nivolumab | 3.5 | Anorexia, fatigue, weakness | 4.9 |
[]7 | 55/M | Melanoma | Nivolumab | 3 | Anorexia, nausea, malaise, myalgia | |
[]8 | 76/F | Melanoma | Nivolumab | 6 | Fatigue, appetite loss | 6.7 |
[]8 | 54/M | Poorly differentiated lung carcinoma | Nivolumab | 5 | Fatigue, nausea | 7.0 |
[]8 | 64/M | Lung adenocarcinoma | Nivolumab | 4.5 | Fatigue, appetite loss | |
[]8 | 57/M | Large cell lung carcinoma | Nivolumab | 4.5 | Appetite loss, nausea | 2.9 |
[]9 | 68/M | Melanoma | Nivolumab | 7 | N.D. | |
[]10 | 76/F | Melanoma | Nivolumab | 5 | Anorexia, bradykinesia | 7.2 |
[]11 | 39/M | Melanoma | Nivolumab | 9 | General malaise | 6.9 |
[]11 | 50/F | Melanoma | Nivolumab | 10 | Fatigue, fever, dizziness | |
[]12 | 60/M | Non-small cell lung cancer | N.D. | 5 | Fatigue, anorexia, exertional dyspnea | 6 |
[]12 | 72/M | Non-small cell lung cancer | N.D. | 4.5 | Fatigue, anorexia, vomiting | |
[]12 | 71/M | Small cell lung cancer | N.D. | 5 | Fatigue, anorexia, nausea | 8.5 |
[]13 | 75/M | Lung adenocarcinoma | Nivolumab | 6 | Appetite loss, fatigue | |
[]14 | 74/M | Renal cell carcinoma | Nivolumab | 2.5 | Appetite loss, nausea, fatigue | 14.4 |
[]15 | 60/M | Lung adenocarcinoma | Nivolumab | 5 | Anorexia, fatigue | 1.4 |
[]16 | 80/M | Melanoma | Pembrolizumab | 10.5 | Headache, muscle weakness | |
[]16 | 43/F | Melanoma | Nivolumab | 7 | Asthenia, fever | 5 |
[]17 | 54/M | Renal cell carcinoma | Nivolumab | 6 | Consciousness disturbance, fatigue | 33.2 |
[]18 | 55/M | Pulmonary pleomorphic carcinoma | Nivolumab | 8 | Asthenia, nausea, hypotension | 4 |
[]19 | 63/F | Lung adenocarcinoma | Nivolumab | 8 | Anorexia, fatigue, weakness | 3.1 |
[]20 | 63/F | Melanoma | Nivolumab | 8 | Fatigue | |
[]21 | 58/M | Melanoma | Nivolumab | 8 | Appetite loss, fatigue, weakness | |
[]22 | 55/F | Invasive breast ductal carcinoma | Pembrolizumab | 14 | Chest pain, hypotension | |
[]23 | 79/M | Squamous cell lung cancer | Nivolumab | 7 | Nausea, appetite loss, walking difficulty | |
[]24 | 72/F | Melanoma | Nivolumab | 15 | General malaise, appetite loss | 9.6 |
[]25 | 71/M | Renal cell carcinoma | Nivolumab | 6 | Appetite loss, malaise, consciousness disturbance | 4.5 |
[]26 | 69/F | Lung adenocarcinoma | Nivolumab | 7 | Anorexia, fatigue, weakness | 2.6 |
[]27 | 70/M | Urothelial carcinoma | Nivolumab | 4.5 | Anorexia, nausea, general weakness | 10 |
[]28 | 59/M | Non-small cell lung cancer | Pembrolizumab | 7 | Anorexia, fatigue, slight fever | 17.4 |
[]29 | 85/F | Squamous cell lung carcinoma | Pembrolizumab | 5 | Appetite loss, fatigue | 8.3 |
[]30 | 65/F | Cecal cancer | Pembrolizumab | 1.5 | Fatigue | 3.0 |
Present case | 78/F | Urothelial carcinoma | Pembrolizumab | 4.5 | Anorexia, general weakness, muscle pain | 16.6 |
ACTH – adrenocorticotropic hormone; CKD – chronic kidney disease; HMA – hyperchloremic metabolic acidosis; IRAE – immune-related adverse event; MRI – magnetic resonance imaging; N.D. – not determined; T2D – type 2 diabetes mellitus. * Nivolumab or pembrolizumab. | ||||||
Ref. | Plasma cortisol (μg/dL) | Serum sodium (mEq/L) | Serum potassium (mEq/L) | Morphological abnormality of the pituitary evident on MRI | Other IRAEs | Comorbid conditions |
[]6 | 1.7 | 127 | 3.9 | Mild pituitary enlargement | (–) | (–) |
[]7 | 0.5 | N.D. | N.D. | (–) | Interstitial pneumonia, hypothyroidism | (–) |
[]8 | 123 | N.D. | (–) | (–) | (–) | |
[]8 | 130 | N.D. | (–) | (–) | (–) | |
[]8 | 127 | N.D. | (–) | (–) | (–) | |
[]8 | 137 | N.D. | (–) | (–) | (–) | |
[]9 | N.D. | N.D. | (–) | (–) | (–) | |
[]10 | 123 | N.D. | N.D. | (–) | (–) | |
[]11 | 0.3 | N.D. | N.D. | (–) | (–) | (–) |
[]11 | N.D. | N.D. | (–) | (–) | (–) | |
[]12 | 0.6 | 133 | N.D. | (–) | (–) | (–) |
[]12 | 0.3 | 138 | N.D. | (–) | (–) | (–) |
[]12 | 3.2 | 139 | N.D. | (–) | Type 1 diabetes mellitus | (–) |
[]13 | 0.4 | 133 | 4.5 | (–) | (–) | (–) |
[]14 | 2.3 | 126 | 4.3 | (–) | (–) | (–) |
]15 | 1.5 | N.D. | N.D. | (–) | Primary hypothyroidism | (–) |
[]16 | 0.4 | 132 | 3.6 | (–) | Primary hypothyroidism | (–) |
[]16 | 0.8 | 131 | 4.5 | (–) | Primary hypothyroidism, vitiligo, Type 1 diabetes mellitus | (–) |
[]17 | 3.7 | 131 | 4 | (–) | Primary hypothyroidism | (–) |
[]18 | Undetectable | 130 | Normal | (–) | Type 1 diabetes mellitus | (–) |
[]19 | 1.6 | 117 | 3.9 | Mild pituitary enlargement | (–) | Primary hypothyroidism caused by prior external irradiation of the neck |
[]20 | 3.5 | 137 | N.D. | (–) | Thyrotoxicosis | (–) |
[]21 | 0.3 | 136 | 5.3 | (–) | Thyroiditis, hypercalcemia | Kidney dysfunction, T2D, hypertension |
[]22 | 0.9 | 132 | 4.3 | (–) | Acute pericarditis, primary hypothyroidism | (–) |
[]23 | 0.2 | 129 | 4 | (–) | (–) | (–) |
[]24 | Undetectable | 120–127 | N.D. | (–) | Primary hypothyroidism | (–) |
[]25 | 0.1 | 122 | 3.8 | (–) | (–) | Hypertension, primary hypothyroidism |
[]26 | 124 | 4.8 | Mild pituitary atrophy | Primary hypothyroidism | (–) | |
[]27 | 1.4 | 120 | N.D. | (–) | Guillain-Barré syndrome | Hypertension, nephroangiosclerosis |
[]28 | 0.9 | 137 | N.D. | (–) | Primary hypothyroidism | (–) |
[]29 | 0.9 | 122 | N.D. | (–) | (–) | (–) |
[]30 | 0.5 | N. D. | N.D. | (–) | (–) | (–) |
Present case | 1.4 | 134 | 6.3 | (–) | (–) | HMA due to ileal conduit, CKD, T2D, hypertension |
ACTH – adrenocorticotropic hormone; CKD – chronic kidney disease; HMA – hyperchloremic metabolic acidosis; IRAE – immune-related adverse event; MRI – magnetic resonance imaging; N.D. – not determined; T2D – type 2 diabetes mellitus. * Nivolumab or pembrolizumab. |