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Table 5 Cases of Immune Checkpoint Inhibitors Induced Primary Adrenal Insufficiency, Cushing’s Disease, Hypoparathyroidism and Diabetes Insipidus

From: Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

Variable Primary adrenal insufficiency ACTH-dependent Cushing’s syndrome Hypoparathyroidism Diabetes Insipidus
Reports No. 6 1 1 3
Cases No. 6 1 1 3
Gender Male = 3; Female = 2; Not reported =1 Female = 1 Male = 1 Male = 3
Age (years) Median = 52; Mean + SD = 51.2 + 4.7 Range 43–56 53 73 Median = 62; Mean + SD = 61.7 + 11.5 Range = 50–73
Pertinent medical history PHx EndoD: NR = 6 FHx EndoD: NR = 6 HX AutoD: NR = 6 PHx EndoD: NR FHx EndoD: NR Hx AutoD: NR PHx EndoD: NR FHx EndoD: NR Hx AutoD: No PHx EndoD: NR = 3 FHx EndoD: NR = 3 Hx AutoD: NR = 3
Type of cancer (all metastatic) Melanoma = 3; RCC = 1; Lung adenoCa = 1; NSCLC = 1 Melanoma Melanoma Prostate Ca = 1; Melanoma = 1; Merkel cell Ca = 1.
Check point inhibitor(s) Ipilimumab =2; Nivolumab =3; Pembrolizumab =1 Ipilumumab + Nivolumab Nivolumab +Ipilimumab C1: Ipilimumab. C2: Ipilimumab C3: Avelumab
ICI Drug D/C? Yes = 1; Not reported = 5 Yes = 1 at 12 wks. Not reported =1  
Clinical presentation Fatigue, weight loss, anorexia, nausea, vomiting, headache, etc Anorexia, weakness Paresthesia, weakness, etc C1: Polydipsia, polyuria C2: Polydipsia, polyuria C3: Polydipsia, polyuria.
Onset (weeks) after 1st dose Median = 10 Mean + SD =14.92 + 14 Range = 1.5–36 14 wks 6 wks Median = 12; Mean + SD = 3 + 16; Range = 3–16
Biochemical tests ↑ACTH in 5; ↓cortisol in 4; Synactin test +ve & + ve adrenal Ab in 1 without cortisol. In 1 cosyntropin stimulation test was negative and pt. had enlarged adrenal glands preceded by secondary adrenal \insufficiency. 9wks: slight ↑ in cortisol; 12 wks: ↑ACTH, ↑cortisol, ↑[cortisol]u. Abnormal low dose dexamethasone suppression test. 16 wks: ↓ACTH, cortisol. 6wks: ↓TSH, ↑FT4, FT3. Then ↓TSH, FT4, FT3. ↓LH, estradiol. Normal PRL. ↓Calcium, undetectable PTH, ↑ phosphate4, ↓vitamin D, magnesium 7wks: ↓TSH, ↑FT4, FT3, then ↓TSH, FT4, FT3. C1: ↓ACTH, cortisol, TSH, FT4, FT3, LH & FSH. Normal glucose. C2: ↓ACTH, cortisol, TSH, FT4, FT3, LH & FSH. Normal glucose. Water deprivation test: partial diabetes insipidus C3: ↑[sodium],[osmolality]s, ↓[osmolality]u. Normal glucose
Diagnosis Primary adrenal insufficiency Cushing’s disease, then 2o adrenal insufficiency. Thyroiditis, then hypothyroidism. 2o hypogonadism. Primary hypoparathyroidism Diabetes insipidus
Imaging MRI/CT MRI brain: 2 normal & 2 enlarged pituitary. Abd CT scan: atrophied adrenals; enlarged in 1 MRI pituitary at 12 wks: enlarged EKG: prolonged QT interval MRI pituitary: Normal in all
CTCAE grade reported Severity not reported in all: Not reported Not reported; Not reported in all.
Therapy at onset at diagnosis iv steroids in 4. Oral steroids in 2. Florinef in 2 Wk5: LT4 Wk16: HCT & LT4. iv calcium gluconate, then oral vitamin D & Ca carbonate. LT4. C1: High dose steroidsC2: HCT, LT4 & desmopressin. C3: Desmopressin
Outcome 5 discharged on steroids. 1 NR. HCT & LT4. Calcium carbonate + calcitriol LT4. C1: NR. C2: HCT, LT4 & desmopressin; C3: Desmopressin D/C