Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy
PurposeWhile there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [177Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been pre...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-10-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1275813/full |
| _version_ | 1797662038052306944 |
|---|---|
| author | Sriram Gubbi Mohammad Al-Jundi Sungyoung Auh Abhishek Jha Joy Zou Inna Shamis Leah Meuter Marianne Knue Baris Turkbey Liza Lindenberg Esther Mena Jorge A. Carrasquillo Jorge A. Carrasquillo Yating Teng Karel Pacak Joanna Klubo-Gwiezdzinska Jaydira Del Rivero Frank I. Lin |
| author_facet | Sriram Gubbi Mohammad Al-Jundi Sungyoung Auh Abhishek Jha Joy Zou Inna Shamis Leah Meuter Marianne Knue Baris Turkbey Liza Lindenberg Esther Mena Jorge A. Carrasquillo Jorge A. Carrasquillo Yating Teng Karel Pacak Joanna Klubo-Gwiezdzinska Jaydira Del Rivero Frank I. Lin |
| author_sort | Sriram Gubbi |
| collection | DOAJ |
| description | PurposeWhile there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [177Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated.MethodsThe study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [177Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 – 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed.ResultsAmong the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [177Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [177Lu]Lu-DOTA-TATE dose and peaked within 48 hours.Conclusions[177Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [177Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060. |
| first_indexed | 2024-03-11T18:54:18Z |
| format | Article |
| id | doaj.art-1a998faee69e4db693e7b0732be92100 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-11T18:54:18Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-1a998faee69e4db693e7b0732be921002023-10-11T07:16:40ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-10-011410.3389/fendo.2023.12758131275813Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapySriram Gubbi0Mohammad Al-Jundi1Sungyoung Auh2Abhishek Jha3Joy Zou4Inna Shamis5Leah Meuter6Marianne Knue7Baris Turkbey8Liza Lindenberg9Esther Mena10Jorge A. Carrasquillo11Jorge A. Carrasquillo12Yating Teng13Karel Pacak14Joanna Klubo-Gwiezdzinska15Jaydira Del Rivero16Frank I. Lin17Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, United StatesDepartment of Endocrinology, Eunice Kennedy Shriver National Institute of Child and Human Development, Bethesda, MD, United StatesMetabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, United StatesDepartment of Endocrinology, Eunice Kennedy Shriver National Institute of Child and Human Development, Bethesda, MD, United StatesMolecular Imaging Branch, National Cancer Institute, Bethesda, MD, United StatesMolecular Imaging Branch, National Cancer Institute, Bethesda, MD, United StatesDepartment of Endocrinology, Eunice Kennedy Shriver National Institute of Child and Human Development, Bethesda, MD, United StatesDepartment of Endocrinology, Eunice Kennedy Shriver National Institute of Child and Human Development, Bethesda, MD, United StatesMolecular Imaging Branch, National Cancer Institute, Bethesda, MD, United StatesMolecular Imaging Branch, National Cancer Institute, Bethesda, MD, United StatesMolecular Imaging Branch, National Cancer Institute, Bethesda, MD, United StatesMolecular Imaging Branch, National Cancer Institute, Bethesda, MD, United StatesDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesCenter for Health Professions Education, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesDepartment of Endocrinology, Eunice Kennedy Shriver National Institute of Child and Human Development, Bethesda, MD, United StatesMetabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, United StatesDevelopmental Therapeutics Branch, National Cancer Institute, Bethesda, MD, United StatesMolecular Imaging Branch, National Cancer Institute, Bethesda, MD, United StatesPurposeWhile there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [177Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated.MethodsThe study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [177Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 – 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed.ResultsAmong the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [177Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [177Lu]Lu-DOTA-TATE dose and peaked within 48 hours.Conclusions[177Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [177Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060.https://www.frontiersin.org/articles/10.3389/fendo.2023.1275813/fullDOTATATEPRRT[177 Lu][68 Ga]targeted radiotherapypituitary |
| spellingShingle | Sriram Gubbi Mohammad Al-Jundi Sungyoung Auh Abhishek Jha Joy Zou Inna Shamis Leah Meuter Marianne Knue Baris Turkbey Liza Lindenberg Esther Mena Jorge A. Carrasquillo Jorge A. Carrasquillo Yating Teng Karel Pacak Joanna Klubo-Gwiezdzinska Jaydira Del Rivero Frank I. Lin Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy Frontiers in Endocrinology DOTATATE PRRT [177 Lu] [68 Ga] targeted radiotherapy pituitary |
| title | Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy |
| title_full | Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy |
| title_fullStr | Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy |
| title_full_unstemmed | Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy |
| title_short | Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy |
| title_sort | early short term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with 177lu lu dota tate therapy |
| topic | DOTATATE PRRT [177 Lu] [68 Ga] targeted radiotherapy pituitary |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1275813/full |
| work_keys_str_mv | AT sriramgubbi earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT mohammadaljundi earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT sungyoungauh earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT abhishekjha earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT joyzou earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT innashamis earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT leahmeuter earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT marianneknue earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT baristurkbey earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT lizalindenberg earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT esthermena earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT jorgeacarrasquillo earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT jorgeacarrasquillo earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT yatingteng earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT karelpacak earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT joannaklubogwiezdzinska earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT jaydiradelrivero earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy AT frankilin earlyshorttermeffectsoncatecholaminelevelsandpituitaryfunctioninpatientswithpheochromocytomaorparagangliomatreatedwith177luludotatatetherapy |