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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.