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

Yudai Hinata; Nobumasa Ohara; Yuhki Sakurai; Ryo Koda; Yuichiro Yoneoka; Toshinori Takada; Noboru Hara; Tsutomu Nishiyama

doi:10.12659/AJCR.931639

15 July 2021 : Case report Japan

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^1BCD, Nobumasa Ohara^1ABCDEF*, Yuhki Sakurai^1CD, Ryo Koda^2BCD, Yuichiro Yoneoka^3CD, Toshinori Takada^4CD, Noboru Hara^5BD, Tsutomu Nishiyama^5BD

DOI: 10.12659/AJCR.931639

Am J Case Rep 2021; 22:e931639

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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	<1.0
[]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	<2.0
[]⁸	57/M	Large cell lung carcinoma	Nivolumab	4.5	Appetite loss, nausea	2.9
[]⁹	68/M	Melanoma	Nivolumab	7	N.D.	<1.0
[]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	<1.0
[]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	<2.0
[]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	<1.0
[]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	<5
[]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	<1.0
[]²¹	58/M	Melanoma	Nivolumab	8	Appetite loss, fatigue, weakness	<2.0
[]²²	55/F	Invasive breast ductal carcinoma	Pembrolizumab	14	Chest pain, hypotension	<1.6
[]²³	79/M	Squamous cell lung cancer	Nivolumab	7	Nausea, appetite loss, walking difficulty	<1.0
[]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	<1.0	123	N.D.	(–)	(–)	(–)
[]⁸	<1.0	130	N.D.	(–)	(–)	(–)
[]⁸	<1.0	127	N.D.	(–)	(–)	(–)
[]⁸	<1.0	137	N.D.	(–)	(–)	(–)
[]⁹	<0.8	N.D.	N.D.	(–)	(–)	(–)
[]¹⁰	<1.0	123	N.D.	N.D.	(–)	(–)
[]¹¹	0.3	N.D.	N.D.	(–)	(–)	(–)
[]¹¹	<1.0	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	<0.2	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.

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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

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