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Table 3 Cases of immune checkpoint inhibitors-induced thyrotoxicosis and hypothyroidism

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

Variable Thyrotoxicosis Hypothyroidism
Graves’ disease Thyroiditis Primary hypothyroidism Thyrotoxicosis → Hypothyroidism
Reports 7 (2 on same case) 31 16 21
Cases 6 67 29 50
Gender Males = 4; Females = 2 Males = 27; Females = 27; Not reported =13 Males = 12; Females = 11; Not reported = 6 Males = 23; Females = 18; Not reported =9
Age (years) Median = 54.5; Mean + SD = 57.3 + 7.3 Range = 51–67 Median = 61 Mean + SD = 62.1 + 12.8 Range = 24–88 Median = 64 Mean + SD = 64.1 + 7.9 Range = 46–85 Median = 63 Mean + SD = 64.1 + 10.4 Range = 42–86
Pertinent medical history PHx + FHx of ThyD Reported = 2; Not reported = 4 PHx + FHx of AutoD Not reported = 6 PHx ThyD: Reported 4; Not reported 63. FHx ThyD: Reported 3. Not reported 64. HxAutoD: Reported 2; Not reported 65 PHx ThyD: Reported 5; Not Reported 24 FHx ThyD: Reported 0; Not reported 29 HxAutoD: Reported 1; Not reported 28 PHx ThyD: Reported 13; Not reported 37. FHx ThyD. Reported 2; Not reported 48. Hx AutoD: Reported = 1; Not reported 49.
Type of cancer Melanoma = 6 Melanoma = 39, NSCLC =9; Breast Ca =1; Lung Ca = 5; RCC = 4; Multiple myeloma = 1; Esophageal Ca = 1; Not reported = 7 Melanoma = 18; Jaw Sq Ca = 1; Lung Sq Ca =6; RCC = 2; Bladder Ca = 1; Multiple myeloma = 1. Melanoma = 29; NSCLC = 8; RCC = 4; Multiple myeloma = 1; breast CA = 1; Lung Ca = 3; Not reported =3.
Check point inhibitor(s) Ipi = 4; Nivo + Ipi = 1, Tremeli = 1. Ipi + bevacizumab = 2; Nivo = 23; Pembro =14; Anti-PD-1 = 6; Ipili = 6; Nivo + Ipili = 7; Ipili+Pembro =1; Ipili, then Pembro = 8. Ipi = 2; PDL-1 = 1; Nivo = 15; Ipi, then Pembro = 9; Nivo+Ipi =2. Nivo = 17; Pembro = 13; Anti-PD-1 = 6; Ipili = 2; Nivo+Ipili = 7; Ipili then, Pembro = 5.
ICI Drug D/C? Yes = 3; Not reported =3 Yes = 12; No = 15; Not reported = 40 Yes =8; No = 5; Not reported = 16 Yes = 8; No = 14; Not reported = 28
Clinical presentation 2 with Graves’ Eye disease (GED) 4 with thyrotoxicosis Hyperthyroidism symptoms = 43; Asymptomatic = 11; Not reported =13 Hypothyroid symptoms = 14; Asymptomatic = 3; Not reported =12. DKA = 2; cardiac = 2; adrenal insufficiency = 2 Many cases do not describe symptoms of hypothyroidism in contrast to symptoms of hyperthyroidism.
Onset after first dose (weeks) Median = 7 Mean + SD = 75.8 + 166.8 Range 6–416 Median = 6 Mean + SD = 7.2 + 5.6 Range 3–28 Median = 12 Mena + SD = 14.2 + 7.1 Range 7–36 Median = 6 Mean + SD = 7.2 + 3.4 Range 3–15
Biochemical tests All have +ve TRAb/TSI; 4 have +ve TPO/TG Ab 2 have NL TSH, FT4 (Graves’ Eye Disease) 4 ↓TSH,↑FT4, ↑FT3 All had ↓TSH, ↑FT4 &/FT3. 47 had reported TPO/TG Ab; 20 + ve. 22 pts. had reported TRAb/TSI; all –ve. All had ↑TSH, ↓FT4. TPO/TG Ab reported in 14: all +ve. 4 had ↓ACTH & cortisol. 2 had ↑Glu, +ve GAD65 Ab, & ↓ C-peptide, pH. & ↑A1c All had ↓TSH, 46↑FT4 /FT3 initially, 3 NL FT4 19 cases had ↑TSH &↓FT4/ FT3. TPO/TG Ab reported in 28: 19 + ve; TRAb/TSI in 21:1 + ve.33 cases stated just as hypothyroid.
Diagnosis 2 Graves’ eye disease 4 Graves’ disease 3 cases described as “thyroid storm”. 44 had symptoms of hyperthyroidism. 9 were asymptomatic. 11 symptoms not reported Primary hypothyroidism (biochemically) in all. 14 had symptoms of hypothyroidism. 19 cases had primary hypothyroidism with ↑TSH & ↓FT4/FT3. Others stated to be hypothyroid with no tests results.
Imaging MRI, RAI uptake 2 enlarged extraocular muscles; 1 ↑thyroid perfusion,1 ↑RAI uptake. 1 MRI pituitary NL; 1 Not reported. 11 had ↓uptake on thyroid scan; 2 had ↑uptake on PET scan; 14 had thyroid US various findings; 31 not reported. Thyroid US in 7–1 swollen gland, 6 heterogeneous echo-structure. PET scan in 5 (↑uptake in 3). Not reported in 16. Not reported during hypothyroid state.
CTCAE grade reported Not reported in all;. Grade 2 = 1 and not reported. = 66 Not reported in all 29. Grade 2 in one; Not reported in 48.
Therapy at onset at diagnosis 3 high dose steroids; 4 had anti-thyroid drugs(1 had LT4) 36 no treatment for hyperthyroidism; 8 on steroid (1 colitis; 3 adrenal insufficiency; 4 not reported); 16 on β-blockers; 8 had anti-thyroid drugs; 3 had iodine solutions (thyroid storm); 3 not reported. LT4 = 26; No LT4 = 1; LT4 Not reported in 2. Steroids = 3; Insulin = 2. 39 on LT4. 11 not reported.
Outcome All improved; 2 on LT4 (1 had thyroidectomy; 1 became hypothyroid). 42 required LT4; 17 no LT4; 8 not reported. 23 0n LT4; 3 subclinical hypothyroid; 2 not reported; 1 deceased. 44 on LT4. LT4 not reported in 6.