-
Frontiers in Endocrinology 2023While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with...
PURPOSE
While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [Lu]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.
METHODS
The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [Lu]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.
RESULTS
Among 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 [Lu]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 [Lu]Lu-DOTA-TATE dose and peaked within 48 hours.
CONCLUSIONS
[Lu]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 [Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Pheochromocytoma; Retrospective Studies; Prolactin; Hydrocortisone; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Follicle Stimulating Hormone; Catecholamines; Thyrotropin
PubMed: 37886645
DOI: 10.3389/fendo.2023.1275813 -
Cancers Apr 2024Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed...
Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed between 1974 and 2023. The mean age of diagnosis was 48.8 years (range 10 to 82) with 69.0% female and 26.5% patients with multiple PGLs. Among 119 patients undergoing genetic testing, 70 (58.8%) patients had mutations, with SDHB (30) and SDHD (26) being the most common. The rates of metastasis and recurrence were higher among patients with SDHB mutations or SDHD mutations associated with multiple PGLs. Metabolic evaluation showed elevated plasma dopamine levels were the most common derangements in HNPGL. MRI and CT were the most common anatomic imaging modalities and DOTATATE was the most common functional scan used in this cohort. Most patients (81.5%) received surgery as the primary definitive treatment, while 22.5% patients received radiation treatment, mostly as an adjuvant therapy or for surgically challenging or inoperable cases. Systemic treatment was rarely used in our cohort. Our single-center experience highlights the need for referral for genetic testing and metabolic evaluation and for a team-based approach to improve the clinical outcomes of patients with HNPGLs.
PubMed: 38672605
DOI: 10.3390/cancers16081523 -
Journal of the Endocrine Society Apr 2024
PubMed: 38660142
DOI: 10.1210/jendso/bvae070 -
Frontiers in Endocrinology 2023
Topics: Humans; Adrenal Gland Neoplasms; Pheochromocytoma; Endocrinology
PubMed: 37810878
DOI: 10.3389/fendo.2023.1291582 -
British Journal of Haematology Mar 2024We report a large series of 40 patients presenting EPAS1-mutated paraganglioma (PGL) in whom we investigated a cause underlying chronic hypoxia. Four patients suffered...
We report a large series of 40 patients presenting EPAS1-mutated paraganglioma (PGL) in whom we investigated a cause underlying chronic hypoxia. Four patients suffered from hypoxaemic heart disease. In patients with available haemoglobin electrophoresis results, 59% presented with a haemoglobin disorder, including six with sickle cell disease, five with sickle cell trait and two with heterozygous haemoglobin C disease. Histological and transcriptomic characterization of EPAS1 tumours revealed increased angiogenesis and high similarities with pseudohypoxic PGLs caused by VHL gene mutations. Sickle haemoglobinopathy carriers could thus be at increased risk for developing EPAS1-PGLs, which should be taken into account in their management and surveillance.
Topics: Humans; Adrenal Gland Neoplasms; Hemoglobinopathies; Hemoglobins; Hypoxia; Mutation; Paraganglioma
PubMed: 38195958
DOI: 10.1111/bjh.19278 -
World Journal of Clinical Cases Jun 2024Paragangliomas (PG) are rare neoplasms of neuroendocrine origin that tend to be highly vascularized, slow-growing, and usually sporadic. To date, common treatment...
BACKGROUND
Paragangliomas (PG) are rare neoplasms of neuroendocrine origin that tend to be highly vascularized, slow-growing, and usually sporadic. To date, common treatment options are surgical resection (SR), with or without radiation therapy (RT), and a watch-and-wait approach.
AIM
To evaluate the local control and effectiveness of exclusive fractionated stereotactic RT (FSRT) treatment in unresectable PG (uPG).
METHODS
We retrospectively evaluated patients with uPG (medically inoperable or refused SR) treated with FSRT with a Cyberknife System (Accuray Incorporated, Sunnyvale, California). Toxicity and initial efficacy were evaluated.
RESULTS
From May 2009 to January 2023, 6 patients with a median age of 68 (range 20-84) were treated with FSRT. The median delivered dose was 21 Gy (range 20-30 Gy) at a median isodose line of 75.5% (range 70%-76%) in 4 fractions (range 3-5 fractions). The median volume was 13.6 mL (range 12.4-65.24 mL). The median cumulative biological effective dose and equivalent dose in 2-Gy fractions were 70 Gy and 37.10 Gy respectively. Site of origin involved were the timpa-nojugular glomus (4/6), temporal bone, and cervical spine. In 1 of the 6 patients, the follow-up was insufficient; 5 of 6 patients showed a 5-year overall survival and 5-year progression-free survival of 100%. We observed negligible toxicities during and after RT. The majority of patients showed stable symptoms during follow-up. Only 1 patient developed spine metastases.
CONCLUSION
Our preliminary results on this small cohort of patients suggest that FSRT could be an effective and safe alternative to SR.
PubMed: 38899289
DOI: 10.12998/wjcc.v12.i16.2729 -
The Veterinary Record Aug 2023The contrast-enhanced ultrasound (CEUS) features of adrenal lesions are poorly reported in veterinary literature.
BACKGROUND
The contrast-enhanced ultrasound (CEUS) features of adrenal lesions are poorly reported in veterinary literature.
METHODS
Qualitative and quantitative B-mode ultrasound and CEUS features of 186 benign (adenoma) and malignant (adenocarcinoma and pheochromocytoma) adrenal lesions were evaluated.
RESULTS
Adenocarcinomas (n = 72) and pheochromocytomas (n = 32) had mixed echogenicity with B-mode, and a non-homogeneous aspect with a diffused or peripheral enhancement pattern, hypoperfused areas, intralesional microcirculation and non-homogeneous wash-out with CEUS. Adenomas (n = 82) had mixed echogenicity, isoechogenicity or hypoechogenicity with B-mode, and a homogeneous or non-homogeneous aspect with a diffused enhancement pattern, hypoperfused areas, intralesional microcirculation and homogeneous wash-out with CEUS. With CEUS, a non-homogeneous aspect and the presence of hypoperfused areas and intralesional microcirculation can be used to distinguish between malignant (adenocarcinoma and pheochromocytoma) and benign (adenoma) adrenal lesions.
LIMITATIONS
Lesions were characterised only by means of cytology.
CONCLUSIONS
CEUS examination is a valuable tool for distinction between benign and malignant adrenal lesions and can potentially differentiate pheochromocytomas from adenocarcinomas and adenomas. However, cytology and histology are necessary to obtain the final diagnosis.
Topics: Dogs; Animals; Pheochromocytoma; Contrast Media; Adrenal Gland Neoplasms; Adenoma; Adenocarcinoma; Ultrasonography; Diagnosis, Differential; Dog Diseases
PubMed: 37138528
DOI: 10.1002/vetr.2949 -
Journal of the Endocrine Society Apr 2024Pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors arising from chromaffin cells, present a significant diagnostic challenge due to their clinical...
Pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors arising from chromaffin cells, present a significant diagnostic challenge due to their clinical rarity and polymorphic symptomatology. The clinical cases demonstrate the importance of an integrated approach that combines clinical assessment, biochemical testing, and imaging to distinguish PPGLs from mimicking conditions, such as obstructive sleep apnea and interfering medication effects, which can lead to false-positive biochemical results. Although a rare condition, false-negative metanephrine levels can occur in pheochromocytomas, but imaging findings can give some clues and increase suspicion for a pheochromocytoma diagnosis. This expert endocrine consult underscores the critical role of evaluating preanalytical conditions and pretest probability in the biochemical diagnosis of PPGLs. Moreover, a careful differentiation of PPGLs from similar conditions and careful selection and interpretation of diagnostic tests, with focus on understanding and reducing false positives to enhance diagnostic accuracy and patient outcomes, is crucial.
PubMed: 38737592
DOI: 10.1210/jendso/bvae078 -
Operative Neurosurgery (Hagerstown, Md.) Dec 2023This approach is intended for tumors centered in the jugular foramen with extensions between intracranial and extracranial spaces, possible spread to the middle ear, and...
INDICATIONS CORRIDOR AND LIMITS OF EXPOSURE
This approach is intended for tumors centered in the jugular foramen with extensions between intracranial and extracranial spaces, possible spread to the middle ear, and variable bony destruction. 1,2.
ANATOMIC ESSENTIALS NEED FOR PREOPERATIVE PLANNING AND ASSESSMENT
Jugular foramen paragangliomas are complex lesions that usually invade and fill related venous structures. They present complex relationships with skull base neurovascular structures as internal carotid artery, lower cranial nerves (CNs), middle ear, and mastoid segment of facial nerve. In this way, it is essential to perform an adequate preoperative vascular study to evaluate sinus patency and the tumor blood supply, besides a computed tomography scan to depict bone erosion.
ESSENTIAL STEPS OF THE PROCEDURE
Mastoidectomy through an infralabyrinthine route up to open the lateral border of jugular foramen, allowing exposure from the sigmoid sinus to internal jugular vein. Skeletonization of facial canal without exposure of facial nerve is performed and opening of facial recess to give access to the middle ear in way of a fallopian bridge technique. 2-10.
PITFALLS/AVOIDANCE OF COMPLICATIONS
If there is preoperative preservation of lower CN function, it is important to not remove the anteromedial wall of the internal jugular vein and jugular bulb. In addition, facial nerve should be exposed just in case of preoperative facial palsy to decompress or reconstruct the nerve.
VARIANTS AND INDICATIONS FOR THEIR USE
Variations are related mainly with temporal bone drilling depending on the extensions of the lesion, its source of blood supply, and preoperative preservation of CN function.Informed consent was obtained from the patient for the procedure and publication of his image.Anatomy images were used with permission from:• Ceccato GHW, Candido DNC, and Borba LAB. Infratemporal fossa approach to the jugular foramen. In: Borba LAB and de Oliveira JG. Microsurgical and Endoscopic Approaches to the Skull Base. Thieme Medical Publishers. 2021.• Ceccato GHW, Candido DNC, de Oliveira JG, and Borba LAB. Microsurgical Anatomy of the Jugular Foramen. In: Borba LAB and de Oliveira JG. Microsurgical and Endoscopic Approaches to the Skull Base. Thieme Medical Publishers. 2021.
Topics: Humans; Jugular Foramina; Skull Base; Glomus Jugulare Tumor; Temporal Bone; Cranial Nerves
PubMed: 37350587
DOI: 10.1227/ons.0000000000000775 -
Internal Medicine Journal Apr 2024
Topics: Humans; Pheochromocytoma; Adrenal Gland Neoplasms
PubMed: 38637287
DOI: 10.1111/imj.16372