The Uncharted Landscape of Rare Endocrine Immune-Related Adverse Events
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Data Sources and Search Strategy
2.2. Eligibility Criteria for Articles of Inclusion
3. Literature Review Results
3.1. Primary Adrenal Insufficiency (PAI)
3.1.1. Background
3.1.2. Case Studies
3.1.3. Pathophysiology
3.1.4. Clinical Presentation
3.1.5. Diagnosis
3.1.6. Management
3.2. Diabetes Insipidus (DI)
3.2.1. Background
3.2.2. Case Studies
3.2.3. Pathophysiology
3.2.4. Clinical Presentation
3.2.5. Diagnosis
3.2.6. Management
3.3. Hypoparathyroidism
3.3.1. Background
3.3.2. Case Studies
3.3.3. Pathophysiology
3.3.4. Clinical Presentation
3.3.5. Diagnosis
3.3.6. Management
3.4. Lipodystrophy
3.4.1. Background
3.4.2. Case Studies
3.4.3. Pathophysiology
3.4.4. Clinical Presentation
3.4.5. Diagnosis
3.4.6. Management
3.5. Osteoporosis
3.5.1. Background
3.5.2. Case studies
3.5.3. Pathophysiology
3.5.4. Clinical Presentation
3.5.5. Diagnosis
3.5.6. Management
3.6. Hypergonadotropic Hypogonadism
3.7. Cushing Disease (CD)
4. Future Aspects
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Reference | Type of Study, (n) | Age (y) | Sex (M, Male and F, Female) | Malignancy | Drug | ICI Category | Previous Therapies | Laboratory Evaluation | Adrenal Imaging Findings after ICI Initiation (Method) | Grade of AE | Onset after ICI Initiation (Days) | Outcome of AE | Follow-Up (Days) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Abdallah et al., 2020 [20] | Case report (n = 1) | 70 | F | Pancreatic adenocarcinoma | Nivolumab | PD-1 Ab | ND | Normal sodium and potassium levels, low F and increased ACTH levels, 21-OH Abs (-) | Normal (ND) | IV | After 3rd dose | ND | 90 |
Agrawal et al., 2019 [15] | Case report (n = 1) | 59 | M | SCLC | Ipilimumab + Nivolumab | CTLA-4+PD-1 Ab | Lung radiotherapy and chemotherapy | Low F and increased ACTH levels | ND | II | 120 | ND | ND |
Akarca et al., 2017 [14] | Case report (n = 1) | 52 | M | NSCLC | Nivolumab | PD-1 Ab | ND | Hyponatremia and hyperkalemia, low F and increased ACTH levels | Normal (ND) | IV | 14 | ND | ND |
Bacanovic et al., 2015 [30] | Case report (n = 1) | 79 | ND | ND | Ipilimumab | CTLA-4 Ab | ND | ND | Symmetrically and smoothly enlarged, hypermetabolic (FDG-PET/CT) | ND | ND | ND | ND |
Bischoff et al., 2022 [23] | Case report (n = 1) | 53 | F | Melanoma | Pembrolizuma | PD-1 Ab | Surgery | Hyponatremia, hyperkalemia, low F and increased ACTH levels, ACA (+), 21-OH Abs (+) | Normal (FDG-PET/CT) | III-IV | 168 | ND | ND |
Coskun et al., 2016 [32] | Case report (n = 1) | 50 | M | Lung adenocarcinoma | Nivolumab | PD-1 Ab | ND | Hyponatremia, hyperkalemia, low F and increased ACTH levels | Normal (Ultrasound) | III | 10 | ND | ND |
Dasgupta et al., 2022 [28] | Case report-APS-2 (n = 1) | 14 | F | Hepatocellular carcinoma | Nivolumab | PD-1 Ab | Chemotherapy | Normal morning F and ACTH levels, 21-OH Abs (+) a | ND | I | ND | ND | ND |
Deligiorgi et al., 2020 [26] | Case report (n = 1) | 42 | M | Rectal adenocarcinoma | Nivolumab | PD-1 Ab | Surgery and chemotherapy | Hyponatremia, low F and increased ACTH levels, low PAC levels, 21-OH Abs (+) | Normal (CT) | III–IV | 112 | Recovery after 12 weeks | 630 |
Figuerora-Perez et al., 2021 [29] | Case report (n = 1) | 73 | M | Renal cell carcinoma | Pembrolizumab | PD-1 Ab | Surgery and axitinib | Low F and increased ACTH levels, low PAC levels, high PRA, 21-OH Abs (-) | ND | II | ND | ND | ND |
Gaballa et al., 2020 [34] | Case report (n = 1) | 76 | M | Melanoma | Ipilimumab | CTLA-4 Ab | None | Hyponatremia with normal potassium, low F and elevated ACTH levels, PAC levels undetectable, increased PRA levels | Normal (CT) | III | After 4 cycles | Recovery | 16 cycles of nivolumab |
Galliazzo et al., 2022 [38] | Case report (n = 1) | 74 | M | NSCLC | Nivolumab | PD-1 Ab | ND | Hyponatremia, low F and increased ACTH levels, low PAC levels, 21-OHAbs (-) | Normal (CT) | ND | ND | ND | ND |
Gunjur et al., 2019 [16] | Case report- APS-2 (n = 1) | 78 | F | Melanoma | Pembrolizumab | PD-1 Ab | None | Hyponatremia with normal potassium, Pathological cosyntropin stimulation test (Synacthen), HLA-DRB1*04 genotype (DR4 serotype) | Normal (FDG-PET/CT) | III–IV | 63 | Persistence | 365 |
Hanna et al., 2018 [37] | Case report (n = 1) | 70 | M | Lung adenocarcinoma | Pembrolizumab | PD-1 Ab | None | Pathological cosyntropin stimulation test (Synacthen) | ND | III–IV | ND | ND | ND |
Harsch et al., 2020 [21] | Case report (n = 1) | 62 | F | Melanoma | Pembrolizumab | PD-1 Ab | None | Hyponatremia with normal potassium, low F and increased ACTH levels | Inconspicuous adrenal glands (CT) | III–IV | 365 | ND | ND |
Hescot et al., 2018 [39] | Case report (n = 1) | 33 | F | Cervical squamous cell cancer | Pembrolizumab | PD-1 Ab | ND | Hyponatremia with normal potassium, low F and increased ACTH levels, 21-OH Abs (+) | Adrenal hypoplasia (CT) | III–IV | 147 | Recurrence | 365 |
Hobbs et al., 2020 [33] | Case report (n = 1) | 58 | M | ND | Ipilimumab + Nivolumab | CTLA-4 Ab+ PD-1 Ab | ND | Hyponatremia with hyperkalemia, low F and increased ACTH levels | ND | III | After 4 cycles | ND | ND |
Iqbal et al., 2019 [18] | Case report (n = 1) | 65 | F | NCSLC | Nivolumab | PD-1 Ab | ND | Hyponatremia with hyperkalemia, low F and increased ACTH levels, low PAC levels with increased PRA | Normal (CT) | III | ND | Persistence | ND |
Kagoshima et al., 2019 [19] | Case report (n = 1) | 57 | F | Tongue squamous cell carcinoma | Nivolumab | PD-1 Ab | Surgery, radiotherapy and chemotherapy | Low F and normal ACTH levels, CRH test in favor of PAI | ND | II | ND | ND | ND |
Knight et al., 2021 [31] | Prospective study (n = 1) | 59 | M | Renal cell carcinoma | Ipilimumab + Nivolumab | CTLA-4 Ab+ PD-1 Ab | ND | Hyponatremia, low F and increased ACTH levels | ND | III–IV | ND | ND | ND |
Kojadinovic et al., 2021 [36] | Case report (n = 1) | 64 | Μ | Colorectal cancer | Pembrolizumab (9 cycles), pembrolizumab+ Ipilimumab | PD-1 Ab +CTLA-4 Ab | Surgery and multiple cycles of chemotherapy | Hyponatremia and low F levels, pathological cosyntropin stimulation test (Synacthen) | ND | II | 14 after initiation of dual therapy | Persistence | 567 |
Lanzolla et al., 2019 [17] | Case report- APS-2 (n = 1) | 50 | M | Lung adenocarcinoma | Atezolizumab | PD-L1 Ab | Chemotherapy | Hyponatremia with normal potassium, low F and increased ACTH levels, low PAC levels with increased PRA, 21-OH Abs (+), HLA typing: DRB1*04 and DQB1*03 haplotypes | Normal (CT) | III | 84 | ND | ND |
Min et al., 2013 [25] | Case report- mixed AI (PAI + SAI) (n = 1) | 56 | F | Melanoma | Ipilimumab | CTLA-4 Ab | ND | Low F and increased ACTH levels | Reversible bilateral enlargement (CT) | II | After 4 doses | ND | ND |
Ozyurt et al., 2021 [22] | Case report (n = 1) | 66 | M | Renal cell carcinoma | Nivolumab | PD-1 Ab | Sunitinib | Hyponatremia with hyperkalemia, low F and increased ACTH levels, (under steroids) | ND | II | 21 | Persistence | 60 |
Paepegaey et al., 2017 [13] | Case report-APS-2 (n = 1) | 55 | F | Melanoma | Pembrolizumab | PD-1 Ab | Surgery, chemotherapy and sorafenib | Hyponatremia with hyperkalemia, low F and increased ACTH levels, PAC undetectable with increased PRA levels, ACA (+), 21-OH Abs (+) | Atrophied adrenal glands (CT) | IV | 258 | ND | ND |
Salinas et al., 2020 [27] | Case series (n = 3) | 60, 65, 76 | M(all) | Renal cell carcinoma(all) | Ipilimumab + nivolumab (n = 1) Nivolumab (n = 2) | -CTLA-4 Ab+ PD-1 Ab -PD-1 Ab (n = 2) | Cabozantinib (n = 1), none (n = 2) | Hyponatremia and pathological cosyntropin stimulation test (Synacthen) (n = 2) Pathological cosyntropin stimulation test (Synacthen) (n = 1) | Normal (n = 3) (CT) | IV IV III | 140 183 150 | ND | ND |
Shariff et al., 2018 [35] | Case report (n = 1) | 49 | M | Melanoma | Ipilimumab + nivolumab | CTLA-4 Ab+ PD-1 Ab | Chemotherapy | Hyponatremia with hypokalemia, low F levels and increased ACTH levels, low PAC with increased PRA levels, 21-OH Abs (-) | Normal (ND) | III | 74 | Persistence | 420 |
Trainer et al., 2016 [24] | Case study (n = 1) | 43 | F | Melanoma | Nivolumab | PD-1 Ab | Surgery | Hyponatremia, low F and increased ACTH levels, low PAC with increased PRA levels | Symmetrically and smoothly enlarged, increased FDG activity in both adrenal glands (FDG-PET/CT) | III | 56 | Persistence | 365 |
Reference | Type of Study, (n) | Age (y) | Sex (M, Male and F, Female) | Malignancy | Drug | ICI Category | Previous Therapies | Dysfunction of Pituitary | Dysfunction of Hypothalamus | Onset after Initiation of ICI (Days) | Outcome of AE | Laboratory Evaluation | MRI Findings | Grade of AE | Follow-Up (Days) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Amereller et al., 2021 [65] | Retrospective study (n = 2) | ND | M (n = 1), F (n = 1) | ND | Ipilimumab | CTLA-4 Ab | ND | ND | ND | ND | ND | Serum and urine osmolarity, serum Na, water deprivation test (+) | ND | ND | ND |
Angelousi et al., 2022 [64] | Case report (n = 1) | 53 | F | Melanoma | Nivolumab | PD-1 Ab | Multiple surgeries | Panhypopituitarism | ND | 240 | Persisted | Low urine osmolality, increased plasma osmolality, water deprivation test (+), low baseline copeptin levels | Absent bright spot | II | 180 |
Barnabei et al., 2020 [59] | Case report (n = 1) | 64 | M | Melanoma | Ipilimumab | CTLA-4 Ab | Ocular proton beam radiotherapy | Panhypopituitarism | No | 60 | Transient (5 days) | Low urine osmolality, increased plasma osmolality, normal serum Na | Absent bright spot | I | 1230 |
Brage et al., 2022 [53] | Case report (n = 1) | 46 | M | Adenocarcinoma of the lung | Nivolumab | PD-1 Ab | Whole brain radiotherapy, erlotinib osimertinib and chemotherapy | Panhypopituitarism | No | 62 | ND | Low urine osmolarity, water deprivation test (+) | ND | I | 0 |
Brilli et al., 2020 [52] | Case report (n = 1) | 68 | M | Mesothelioma | Tremelimumab and durvalumab | CTLA-4 Ab + PD-L1 Ab | None | Isolated posterior pituitary | No | 60 | Persisted | Normal levels of serum sodium, plasma osmolality and urinary specific gravity test, water deprivation test (+) | Normal | ND | 570 |
Deligiorgi et al., 2020 [60] | Case report (n = 1) | 71 | M | Adenocarcinoma of the lung | Nivolumab | PD-1 Ab | Surgery and chemotherapy | Isolated posterior pituitary | No | 90 | ND | Hypernatremia, high plasma osmolarity and hyposthenuria, undetectable serum AVP | Normal | IV | ND a |
Dillard et al., 2009 [55] | Case report (n = 1) | 50 | M | Adenocarcinoma of prostate | Ipilimumab | CTLA-4 Ab | ND | Panhypopituitarism | No | 84 | Transient (3 weeks) | ND | Normal | III | ND |
Fosci et al., 2021 [62] | Case report (n = 1) | 62 | M | Hypopharynx cancer | Nivolumab | PD-1 Ab | Surgery and chemotherapy | Panhypopituitarism | No | 35 | 50 days b | Low urine osmolarity, high plasma osmolality, response to desmopressin | Enlarged stalk | I | 50 b |
Grami et al., 2019 [54] | Case report (n = 1) | 30 | M | Acute myeloid leukemia | Ipilimumab + nivolumab | CTLA-4 Ab + PD-1 Ab | Chemotherapy and allogenic stem cell transplant | Panhypopituitarism | No | ND | ND | Low urine osmolarity, high serum Na, response to desmopressin | ND | III | ND |
Gunawan et al., 2018 [57] | Case report (n = 1) | 52 | M | Melanoma | Ipilimumab+ nivolumab | CTLA-4Ab + PD-1 Ab | Small bowel resection | Isolated posterior pituitary | No | 28 | ND | High serum Na, response to desmopressin | ND | I | ND |
Nallapanemi et al., 2014 [56] | Case report (n = 1) | 62 | M | Melanoma | Ipilimumab | CTLA-4 Ab | Vemurafenib+IL-2 | Panhypopituitarism | No | 121 | 5mo | Water deprivation test (+) | ND | II | 180 |
Tshuma et al., 2018 [58] | Case report (n = 1) | 74 | F | Bladder cancer | Atezolizumab | PD-L1 Ab | Surgery + neoadjuvant chemotherapy | Panhypopituitarism | Yes | 270 | ΝD | High serum Na, low urinary Na | Hypothalamic mass | I | 365 |
Yu et al., 2021 [61] | Case report (n = 1) | 60 | M | Hodgkin lymphoma | Sintilimab | PD-1Ab | Chemotherapy | Isolated posterior pituitary | No | Immediate | Transient (3 months) | High serum osmolality, high serum Na, low urine-specific gravity, response to desmopressin | Nodular signal | II | 90 |
Zhao et al., 2017 [63] | Case report (n = 1) | 73 | M | Merkel cell carcinoma | Avelumab | PD-L1 Ab | None | Isolated posterior pituitary | No | 112 | Transients (6 weeks) | High serum os- molarity, low urine osmolarity, low urine specific gravity, high serum Na, response to desmopressin | Normal | I | 240 |
Reference | Type of Study | Age (y) | Sex (M, Male and F, Female) | Malignancy | Drug | ICI Category | Previous Therapies | Laboratory Evaluation | Grade of AE | Onset after Initiation of ICI (Days) | Outcome of AE | Follow-Up (Days) |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Dadu et al., 2020 [71] | Case report (n = 1) | 73 | M | Melanoma | Ipilimumab + nivolumab | CTLA-4Ab + PD-1 Ab | None | Low Ca, P and Mg levels, undetectable PTH levels, low 25-OHD3 CaSR-Abs (+), NALP5 Abs (-), Cytokine Abs (-) | IV | 28 | Persisted | 1185 |
Horinouchi et al., 2015 [79] | Phase I study (n = 1) | ND | ND | NSCLC | Ipilimumab | CTLA-4 Ab | Chemotherapy | ND | I/II | ND | ND | ND |
Kawkgi et al., 2020 [72] | Case report (n = 1) | 76 | M | Melanoma | Ipilimumab + nivolumab | CTLA-4Ab + PD-1 Ab | ND | Low Ca, P and Mg levels, undetectable PTH levels, normal 25-OHD3 levels, anti-PTH Abs (-) | III | 220(combination therapy), 160 (nivolumab monotherapy) | Persisted | 77 |
Lupi et al., 2020 [77] | Case report (n = 1) | 53 | M | Lung adenocarcinoma | Pembrolizumab | PD-1 Ab | ND | Low Ca, normal P and Mg levels, inappropriate normal PTH levels, low25-OHD3 CaSR Abs (+) | IV | 510 | Persisted | 270 |
Mahmood et al., 2020 [78] | Case report (n = 1) | 71 | M | Lung adenocarcinoma | Pembrolizumab | PD-1 Ab | Surgery and lung radiotherapy | Low Ca and PTH levels | II | 45 | Persisted | 210 |
Piranavan et al., 2018 [74] | Case report (n = 1) | 61 | F | SCLC | Nivolumab | PD-1 Ab | Chemotherapy and radiotherapy | Low Ca, P and Mg levels, low PTH levels, normal 25-OHD3 levels, CaSR Abs (+), NALP5 Abs (-), Cytokine Abs (-) | IV | 120 | ND | ND |
Trinh et al., 2019 [75] | Case report (n = 1) | 53 | ND | Melanoma | Ipilimumab + nivolumab | CTLA-4Ab + PD-1 Ab | ND | Low Ca and Mg levels, normal P, normal 25-OHD3 levels, low PTH levels, CaSR Abs insignificant titers | IV | 28 | Persisted | 14 |
Umeguchi et al., 2018 [76] | Case report (n = 1) | 64 | M | NSCLC | Pembrolizumab | PD-1 Ab | Chemotherapy and lung radiotherapy | Low Ca levels, increased P levels, normal 1,25-(OH)2 D3, low PTH levels, CaSR Abs (+) | III | 42 | Persisted | ND |
Win et al., 2017 [73] | Case report (n = 1) | 73 | M | Melanoma | Ipilimumab + nivolumab | CTLA-4Ab +PD-1 Ab | Local excision | Low Ca and Mg levels, low 25-OHD3 levels, low PTH levels | IV | 45 | Persisted | 120 |
Reference | Type of Study, (n) | Age(y) | Sex (M, Male and F, Female) | Malignancy | Drug | ICI Category | Previous Therapies | Type of Lipodystrophy | Laboratory Evaluation | Onset after Initiation of ICI (Days) | Grade of AE | Treatment of AE | Outcome of AE |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Bedrose et al., 2020 [88] | Case report (n = 1) | 67 | M | Melanoma | Pembrolizumab | PD-1 Ab | None | Generalized | Hyperglycemia and hypertriglyceridemia, normal values of liver enzymes, low leptin and adiponectin levels | 42 | II | Insulin + pioglitazone, Statin + fibrate+ omega-3 fatty acids | ND |
Drexler et al., 2021 [90] | Case report (n = 1) | 41 | F | Melanoma | Nivolumab | PD-1 Ab | Inguinal lymph node dissection and local excision | Facial | Normal values of cholesterol, triglycerides, HbA1C | 474 | II | Steroids | Persistence |
Eigentler et al., 2019 [93] | Case report (n = 1) | 45 | F | Melanoma | Nivolumab | PD-1 Ab | Local excision and IFN-a | Generalized | Hyperglycemia, hypertriglyceridemia, increased liver enzymes | 360 | II | Steroids, insulin and then, overlapping courses of empagliflozin, liraglutide and pioglitazone | Improvement in metabolic abnormalities |
Gnanendran et al., 2020 [89] | Case report (n = 1) | 34 | F | Melanoma | Nivolumab | PD-1 Ab | Local excision | Generalized | Normal values of glucose, HbA1C, LDL high leptin levels | 270 | II | Steroids | Persistence |
Haddad et al., 2019 [87] | Case report (n = 1) | 47 | F | Melanoma | Pembrolizumab | PD-1 Ab | None | Generalized | Prediabetes, low leptin and adiponectin levels, hypertriglyceridemia | 60 | III | Treatment for metabolic abnormalities | Persistence |
Jehl et al., 2019 [91] | Case report (n = 1) | 62 | F | Melanoma | Nivolumab | PD-1 Ab | Local excision | Generalized | DM, hypertriglyceridemia, increased liver enzymes, low leptin and adiponectin levels | 540 | III | Insulin + metfromin | Improvement in metabolic abnormalities |
Kruschewsky Falcao et al., 2019 [92] | Case report (n = 1) | 57 | F | Renal cell carcinoma | Nivolumab | PD-1 Ab | Local excision and sunitinib, pazobanib | Generalized | DM, hypertriglyceridemia, high LDL, low leptin levels | 60 | II | Steroids | Improvement in metabolic abnormalities |
Reference | Type of Study | Age (y) | Sex (M, Male and F, Female) | Malignancy | Drug/ICI Category | Previous Therapies | Skeletal AE | Laboratory Evaluation | Grade of AE | Onset after ICI Initiation |
---|---|---|---|---|---|---|---|---|---|---|
Filippini et al., 2021 [97] | Case series (n = 4) | 67.8 (mean age) | M (n = 1), F (n = 3) | Squamous cell carcinoma (n = 4) | Anti-PD-1 Ab (n = 2) Anti-PD-L1 Ab (n = 2) | ND | Dorsal vertebral (D12) fracture Calcaneal fracture Lumbar vertebral (L1) fracture Multiple vertebral (D7-L5) fractures | ND | II | From 2.5 to 15.5 months |
Moseley et al., 2018 [96] | Case series (n = 6) | 59.3 (mean age) | M (n = 5), F (n = 1) | Melanoma (n = 4), RCC (n = 1), lung adenocarcinoma (n = 1) | Pembrolizumab/PD-1 Ab (n = 2), Nivolumab/PD-1 Ab (n = 2), Nivolumab + ipilimumab/PD-1 Ab + CTLA-4 Ab (n = 2) | Wide local excision + axillary lymph node dissection + GM-CSF secreting allogeneic melanoma cell vaccine (n = 1) wide local excision + IFN-a+IL-2 (n = 1), none (n = 4) | 1st patient: compression vertebral fractures (T6, T7, T10, T11, and T12); rib and pelvic fractures 2nd patient: compression vertebral fractures (T6–12, L1) 3rd patient: compression vertebral fracture (T11); lumbar osteomalacia 4th patient: Resorptive bone lesion of left shoulder 5th patient: Resorptive bone lesion of right wrist 6th patient: Resorptive bone lesion of right clavicle | Elevated or high normal CTX and/or bsALP levels (n = 5), Elevated CRP and/or ESR (n = 6) | II | 1st patient: After 20 doses of pembrolizumab therapy 2nd patient: 8 cycles of nivolumab and IL-21 3rd patient: 10 months 4th patient: 8 months 5th patient: 18 months 6th patient: ND |
Pantano et al., 2022 [98] | Case series (n = 4) | ND | ND | ND | ND | ND | Lumbar fractures | Relatively increased CTX-1 levels 1 Relatively decreased PINP levels 1 | II | ND |
Reference | Type of Study, (n) | Age (y) | Sex (M, Male and F, Female) | Malignancy | Drug | ICI Category | Previous Therapies | Clinical Presentation | Laboratory Evaluation | Testicular Biopsy | Onset after Initiation of ICI (Days) | Duration of AE (Days) | Follow up (Days) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Brunet-Possenti et al., 2016 [103] | Case report (n = 1) | 54 | M | Melanoma | Ipilimumab + nivolumab | CTLA-4 Ab+ PD-1 Ab | ND | Bilateral orchitis | Low testosterone with high LH levels | ND | 14 | 7 | 28 |
Quach et al., 2019 [104] | Case report (n = 1) | 69 | M | Melanoma | Pembrolizumab | PD-1 Ab | Partial hepatectomy and RFA of liver lesions. | Bilateral epididymo-orchitis | ND | ND | 60 | 35 | 80 |
Rabinowitz et al., 2021 [105] | Case report (n = 1) | 30 | M | Melanoma | Ipilimumab + nivolumab | CTLA-4 Ab+ PD-1 Ab | None | Infertility | Spermogram: Azoospermia, Hormone profile: Low testosterone levels with high FSH and normal LH levels | Sertoli-only pathology | 730 (time of evaluation) | Persisted | 180 |
Salzamann et al., 2021 [106] | Cross-sectional pilot study (n = 4) | 44, 51, 30, 36 | M | ND | Ipilimumab + nivolumab (n = 2), Pembrolizumab(n = 1), PD-L1 Ab (n = 1) | CTLA-4 Ab+ PD-1 Ab (n = 2), PD-1 Ab (n = 1), PD-L1 Ab (n = 1) | RT to inguinal lymph nodes (n = 1), Chemotherapy (4 years before) (n = 1), ND (n = 2) | None | Spermogram: Azoospermia (n = 3), Oligoasthenoteratozoospermia (n = 1) Hormone profile: normal (n = 2), high FSH levels (n = 2) | No signs of inflammation (n = 2), Inflammation infiltrate (n = 2) | >120 | ND | ND |
Scovell et al., 2020 [107] | Cohort study (n = 6) | ND | M | Melanoma | Ipilimumab/nivolumab/pembrolizumab | CTLA-4 Ab/ PD-1 Ab | None | ND | ND | Sertoli-only syndrome (n = 3), focal active spermatogenesis (n = 1), hypospermatogenesis (n = 2) | ND | ND | ND |
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Mytareli, C.; Ziogas, D.C.; Karampela, A.; Papalexis, P.; Siampanopoulou, V.; Lafioniatis, A.; Benopoulou, O.; Gogas, H.; Angelousi, A. The Uncharted Landscape of Rare Endocrine Immune-Related Adverse Events. Cancers 2023, 15, 2016. https://doi.org/10.3390/cancers15072016
Mytareli C, Ziogas DC, Karampela A, Papalexis P, Siampanopoulou V, Lafioniatis A, Benopoulou O, Gogas H, Angelousi A. The Uncharted Landscape of Rare Endocrine Immune-Related Adverse Events. Cancers. 2023; 15(7):2016. https://doi.org/10.3390/cancers15072016
Chicago/Turabian StyleMytareli, Chrysoula, Dimitrios C. Ziogas, Athina Karampela, Petros Papalexis, Vasiliki Siampanopoulou, Alexandros Lafioniatis, Olga Benopoulou, Helen Gogas, and Anna Angelousi. 2023. "The Uncharted Landscape of Rare Endocrine Immune-Related Adverse Events" Cancers 15, no. 7: 2016. https://doi.org/10.3390/cancers15072016