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  • 1
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 107, No. 4 ( 2022-03-24), p. 964-971
    Abstract: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. Objective To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. Design and Setting We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. Patients Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. Intervention Performance (or not) of cytoreductive surgery of the primary tumor. Main outcome and measures A propensity score match was done using age and the number of organs with metastasis (≤2 or & gt;2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. Results Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). Conclusion Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2026217-6
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  • 2
    In: International braz j urol, FapUNIFESP (SciELO), Vol. 43, No. 5 ( 2017-10), p. 841-848
    Type of Medium: Online Resource
    ISSN: 1677-5538
    Language: Unknown
    Publisher: FapUNIFESP (SciELO)
    Publication Date: 2017
    detail.hit.zdb_id: 2160867-2
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  • 3
    In: Clinics, Elsevier BV, Vol. 64, No. 1 ( 2009-01), p. 23-28
    Type of Medium: Online Resource
    ISSN: 1807-5932
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
    detail.hit.zdb_id: 2222974-7
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  • 4
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: A.W. Kuhn: None. D.S. de Melo: None. H.L. Charchar: None. B.M. Mariani: None. M.Y. Nishi: None. F.L. Ledesma: None. F.Y. Tanno: None. V. Srougi: None. J.L. Chambo: None. A. Latronico: None. B.B. Mendonca: None. M.Q. Almeida: None. M.C. Fragoso: None. Background: Carney complex (CNC) is a hereditary syndrome with autosomal dominant inheritance, composed of multiple neoplasms, such as benign and malignant, endocrine and nonendocrine tumors (cardiac, cutaneous and neural). The primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome is the most common endocrine neoplasia in CNC. The most frequent genetic cause is related with the presence of germline pathogenic allelic variants on PRKAR1A. Overall CNC penetrance among carriers of the PRKAR1A allelic variant is approximately 97.5%, however, families with long-term follow up is rarely described in literature. Clinical Case: A 17-year-old male, was referred to our Hospital in 2003 due to weight gain (≈10 Kg), BMI 27.27 Kg/m2, acne, occurrence of abdomen purplish striae ( & gt;1cm), facial plethora and arrest of pubertal development for last 2 years. He has had pigmented facial lesions since 9 years old. Laboratory revealed suppressed ACTH & lt;18.0 pg/mL, failure to suppress cortisol levels after low dose dexamethasone test (DST-1mg): cortisol 29 µg/dL (normal range: & lt;1.8 µg/dL), and total urinary cortisol (TUC), 2809 µg/24 h (normal range: 30-300 µg/24h). Abdominal CT scan showed normal right adrenal gland and a micronodule (0.8 cm) in the left adrenal gland. Bone densitometry showed an important loss of density. Owing to ACTH-independent Cushing's syndrome and adrenal with micronodule, the most plausible diagnostic hypothesis was PPNAD associated to CNC. He underwent bilateral laparoscopic adrenalectomy and the histological data confirmed PPNAD on both adrenal glands. He developed primary adrenal insufficiency and he maintains continuous replacement with gluco and mineralocorticoids. The genetic analysis identified a heterozygous germline nonsense pathogenic variant on PRKAR1A (p.Tyr21X) in exon 2. His relatives, such as father, two younger sisters, one paternal aunt and a female cousin carried the same nonsense variant. All of them also presented facial lentiginous but without Cushing features. In the first investigation, all his relatives showed possible autonomous cortisol secretion. In follow-up of almost 20 years, the index case and his family members did not develop other manifestations of CNC. Only his father developed metabolic syndrome, but all relatives maintained subclinical hypercortisolism due to possible autonomous cortisol secretion without any clinical repercussions. Clinical Lessons: Carney complex is a rare disease and the follow-up of familial cases over the years can show different clinical pattern despite the same germline pathogenic variant. Probably somatic molecular mechanisms as modulators could trigger specifically clinical manifestations. Presentation: Friday, June 16, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
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  • 5
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 15 ( 2024-4-15)
    Abstract: For pheochromocytoma and paraganglioma (PPGL), the efficacy of percutaneous ablative therapies in achieving control of metastatic tumors measuring & lt;3 cm had been demonstrated in only few reports, and intraoperative radiofrequency ablation (RFA) of locally invasive primary PPGLs has not been reported. We presented the case of a 31-year-old man who had a 9-cm functioning unresectable PPGL. He was treated with 13 cycles of cytotoxic chemotherapy without objective tumor response, according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, magnetic resonance imaging revealed a 9.0 × 8.6 × 6.0-cm retroperitoneal mass that extended to the inferior portion of the inferior vena cava, the inferior mesenteric artery, and the infrarenal aorta. Biochemical evaluation demonstrated high level of plasma normetanephrine (20.2 nmol/L, normal range & lt;0.9 nmol/L). Genetic investigation showed the germline pathogenic variant c.1591delC (p. Ser198Alafs*22) in the SDHB gene. I 131 -metaiodobenzylguanidine scintigraphy was negative and Ga 68 -dotatate PET-CT scan showed high tumor uptake without distant metastases. On open laparotomy, tumor debulking was not possible. Therefore, intraoperative RFA was performed by a highly experienced team of interventional radiologists. At 12 months after the RFA, the tumor volume decreased from 208 to 45 mL (78%), plasma normetanephrine decreased from 20.2 to 2.6 nmol/L (87%), and the doxazosin dose was reduced from 16 to 8 mg/day. To our best knowledge, this was the first report on intraoperative RFA that markedly reduced the size of a large primary unresectable PPGL, along with clinical and biochemical responses.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2592084-4
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  • 6
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Background: Aldosterone producing adenomas (APAs) are the most common cause of unilateral primary aldosteronism (PA). In most cases, APAs present as small ( & lt;2 cm in diameter) benign appearing nodules on computed tomography (CT). Up to 70% of APAs may harbor KCNJ5 somatic mutations. Clinical Cases: Case 1. A 33-yr-old man was referred to investigate resistant hypertension (HT). Biochemical evaluation revealed normal K levels, aldosterone (A) of 14.7 ng/dl, renin of 2.1 mUI/L (normal, 4.4-46.1) and A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis. Hypercortisolism investigation revealed a non-suppressible cortisol after an overnight 1 mg low-dose dexamethasone suppression (8.3 μg/dL), abnormal midnight salivary cortisol, and normal urinary free cortisol, plasma DHEAS and ACTH levels. Computed tomography (CT) scan showed a well-limited mass in left adrenal, measuring 5.8 cm with pre-contrast density of 30 HU and absolute wash-out of 72%. After left laparoscopic adrenalectomy, hydrocortisone was started and adrenal insufficiency confirmed by basal cortisol & lt;3 μg/dL. He presented biochemical cure of PA and improvement in HT control. Histologic examination revealed an encapsulated tumor with glomerulosa-like cells predominance and a Weiss score 1 (clear cells & lt;25%). CYP11B2 staining was positive in 10% and Ki67 in 5% of tumor cells. Case 2. A 58 yr-old woman was referred to investigate an adrenal mass. She had resistant HT and hypokalemia since 2010. Biochemical evaluation revealed hypokalemia (2.8 mEq/L), A of 16.9 ng/dl, renin & lt;1.6 mUI/L and A/R ratio of 10.6. Confirmatory testing confirmed PA diagnosis. Hypercortisolism investigation was negative. CT scan showed a heterogeneous solid mass in the right adrenal, measuring 5.5 cm with pre-contrast density of 30 HU and absolute wash-out of 77%. After laparoscopic right adrenalectomy, histologic examination revealed an encapsulated tumor with glomerulosa-like cells predominance and a Weiss score 2 (clear cells & lt; 25% and & gt; 1/3 diffuse architecture). CYP11B2 staining was positive in 30% and Ki67 in 5% of the cells. She presented biochemical cure of PA and improvement in HT control. Genetic investigation for somatic KCNJ5, ATP1A1, ATP2B3 and CTNNB1 was negative in both cases. Conclusion: We describe two rare cases of APAs that presented as large and suspicious tumors, without somatic mutations in genes associated with APAs.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
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  • 7
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: I.P. de Magalhães: None. B.S. Boger: None. N.L. Gomes: None. G.L. Martins: None. L.A. Bomfim Jr: None. G.F. Fagundes: None. A.F. Afonso: None. J. Petenuci: None. F.M. Coelho: None. V. Srougi: None. F.Y. Tanno: None. J.L. Chambo: None. A. Latronico: None. M.B. Fragoso: None. A.O. Hoff: None. B.B. Mendonca: None. M.R. Menezes: None. M.Q. Almeida: None. Background: Metastatic pheochromocytoma and paraganglioma (PPGL) are incurable neuroendocrine tumors. Few reports demonstrated the efficacy of radiofrequency ablation (RFA) in achieving tumor control of metastatic lesions (usually & lt;3 cm). However, intraoperative RFA of large and unresectable primary PPGLs was not previously demonstrated. Case Report: A 31-year-old male patient was diagnosed with symptoms of catecholamine excess, high levels of plasma metanephrines and a 9 cm retroperitoneal tumor. The patient underwent an open laparotomy, which revealed unresectable disease. Anatomopathological and immunohistochemical analysis was compatible with the diagnosis of paraganglioma. The patient was treated with 13 cycles of cytotoxic chemotherapy (cyclophosphamide, vincristine and dacarbazine) without objective tumor response by RECIST. Then, he was referred to our Institution for evaluation of additional therapies. Blood pressured was well controlled with doxazosin 16 mg/d, propranolol 40 mg/d and losartan 100 mg/d. A magnetic resonance imaging (MRI) revealed an extensive retroperitoneal mass with 9.0 x 8.6 x 6.0 cm (208 ml) that involved the inferior portion of the vein inferior vena cava, inferior mesenteric artery and infrarenal aorta. Biochemical evaluation demonstrated very high levels of plasma normetanephrine (20.2 nmol/L; normal range & lt;0.9 nmol/L) and normal metanephrine level (0.2 nmol/L; & lt;0.5 nmol/L). The genetic investigation showed the germline pathogenic variant c.1591delC (p.Ser198Alafs*22) in SDHB gene. I131-metaiodobenzylguanidine scintigraphy was negative and Ga68-dotatate PET-CT scan displayed a high uptake in the abdominal mass without metastatic disease. Unfortunately, lutetium177 treatment is not available in our Institution. Due to the lack of alternative therapies, we proposed a debulking open laparotomy with intraoperative RFA in the remaining tumoral lesion. Nevertheless, the tumor did not present a clear cleavage plane with the large vessels and had a large caliber intratumoral vasculature. Intraoperative RFA was performed by a very experienced team (interventional radiologist and anesthesiologist to control blood pressure during the procedure). After 2 months, the dose of doxazosin decreased from 16 mg to 8 mg (50% reduction), plasma normetanephrines dropped to 4.6 nmol/L (79%), and the largest tumor diameter at MRI reduced to 6.8 cm (88.8 ml, 57% reduction). After 7 months of the RFA procedure, the tumor continues shrinking (4.8 cm, 45 ml, 78% reduction) and plasma normetanephrine completely normalized. Conclusion: This is the first report of intraoperative RFA of a large primary unresectable paraganglioma. The patient presented a striking clinical success, complete biochemical remission and an objective tumor response. Support: Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6 (to M.Q. Almeida). Presentation: Saturday, June 17, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
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  • 8
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). PA subtypes include aldosterone-producing adenomas (APA) and bilateral adrenal hyperplasia. To date, few PA patients with bilateral adenomas have been reported, but only one case was well characterized by anatomopathological analysis and clinical outcome after adrenal sparing surgery (1). Clinical case: A 53-year-old woman was referred to investigate resistant HT and hypokalemia. (3.0 mEq/L). PA screening revealed aldosterone (A) of 37.9 ng/dL, renin (R) & lt; 1.6 (4.4-46.1 mUI/L), A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis: seated saline infusion test (A= 83.3 ng/dL) and intravenous furosemide test (R= 3.1 mUI/L; positive test & lt;13 mUI/L). Hypercortisolism investigation revealed a non-suppressible cortisol after an overnight 1 mg low-dose dexamethasone suppression [cortisol (C)= 2.9 μg/dL and dexamethasone= 701 (˃130 ng/dL)], and normal urinary free cortisol, midnight salivary cortisol, plasma DHEAS and ACTH levels. Computed tomography demonstrated bilateral adrenal nodules without adrenal thickening: 3.5 cm right nodule (pre-contrast density of 7UH density; absolute wash-out of 71%) and 2.5 cm left nodule (pre-contrast density of 8UH density; absolute wash-out of 78%). Sequential adrenal venous (AV) sampling (AVS) under continuous cosyntropin infusion showed a lateralization index of 3.4 (bilateral disease & lt;4). Then, the patient underwent right adrenalectomy and left nodulectomy. In the postoperative period, she presented normalization of K+ levels and complete HT remission. She remained under hydrocortisone replacement for 2 months. After 2 months, biochemical evaluation revealed normal basal cortisol levels (13.3 µg/dL) and biochemical cure of PA (A= 3.1 ng/dL and R= 15.3 mUI/L). Currently, she doesn’t have symptoms of adrenal insufficiency after discontinuation of hydrocortisone. Anatomopathological analysis showed bilateral adenomas (Weiss score of 0) in both sides without adjacent hyperplasia. CYP11B2 immunohistochemistry displayed a strong staining in 50% of cells in the right adenoma and in 30% of cells in the left adenoma. Few aldosterone-producing cell clusters (APCC) were identified in the right zona glomerulosa, which is a frequent finding in normal adrenals. Conclusion: We herein described a very rare case of PA caused by bilateral-producing adenomas, confirmed by AVS and CYP11B2 staining after adrenal sparing surgery.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
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  • 9
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: M.A. Stumpf: None. N.L. Queiroz: None. V.C. Souza: None. A.W. Maciel: None. G.F. Fagundes: None. V. Srougi: None. F.Y. Tanno: None. J.L. Chambo: None. M.A. Pereira: None. A. Pio-Abreu: None. L.A. Bortolotto: None. A. Latronico: None. M.B. Fragoso: None. L.F. Drager: None. B.B. Mendonca: None. M.Q. Almeida: None. Background: Primary aldosteronism (PA) is a very prevalent disease, characterized by an autonomous aldosterone secretion. Unilateral PA accounts for approximately 40% of the cases and is preferentially treated with surgery. Several studies reported decrease in renal function following unilateral adrenalectomy, but the risk factors associated with this decline remain to be better elucidated. Aim: Our aim was to investigate predictive factors of the decrease in renal function after unilateral adrenalectomy for PA. Methods: We retrospectively evaluated 89 PA patients submitted to unilateral adrenalectomy. Serum aldosterone, direct renin concentration, estimated glomerular filtration rate (eGFR), and electrolytes were determined at the pre-operative period and at 1 week, 1, 3 and 6 months (m) after unilateral adrenalectomy. The primary endpoint was the DELTAeGFR (eGFR after surgery at different times – eGFR before surgery). Results: Thirty-seven patients (41.6%) were men and 52 (58.4%) were women, with a median age of diagnosis of 49 years (range, 20 to 74 years). At diagnosis, the median aldosterone and renin levels were 29.8 ng/dl (7.3 - 217) and 4 μIU/mL (4 – 8.2), respectively. Hypokalemia at diagnosis was evidenced in 75 out of 89 (84.3%) of the patients. Unilateral PA was confirmed in 78 out of 89 cases (87.6%) by biochemical cure after adrenalectomy. The mean pre-operative creatinine and eGFR were 1.14 ± 0.48 mg/dL and 53.5 ± 17.1 mL/min, respectively. After adrenalectomy, the DELTAeGFR was −6.7 ± 12.1 mL/min at 1 week (p= 0.001), 0.17 ± 10 mL/min at 1m (p= 0.91), −2 ± 8.7 mL/min at 3m (p= 0.13) and −1.8 ± 10.9 mL/min at 6m (p= 0.24). Interestingly, aldosterone levels at diagnosis were significantly associated with the DELTAeGFR at 1 week (p= 0.024). PA patients with aldosterone levels & gt;50 ng/dL (n= 13) at diagnosis presented a higher deterioration in renal function at 1 week when compared to those with aldosterone & lt;50 ng/dL (n= 76) (αeGFR −12 ± 8.6 mL/min vs. −5.9 ± 12.5 mL/min, respectively; p= 0.032). Moreover, the patients with hypoaldosteronism (aldosterone & lt;5 ng/dl) at 1 week had a lower decrease in renal function (DELTAeGFR −4.4 ± 12mL/min (n= 41) vs. −9.9 ± 11.6 mL/min (n= 42), respectively; p= 0.014) and lower levels of aldosterone at diagnosis (31.5 ± 21.1 ng/dL vs. 50.4 ± 44.4 ng/dL, respectively; p= 0.008). The post-operative decline in renal function did not correlate with age, hypokalemia, number of anti-hypertensive medications at diagnosis, immediate pre-operative and post-operative renin, and hypertension remission after surgery. Conclusion: The renal function decreased precociously after adrenalectomy but returned to basal levels after 1m. Aldosterone levels at diagnosis and at 1 week after surgery were significantly associated with decline in renal function. Support: This work was supported by the Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6. Presentation: Friday, June 16, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
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  • 10
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 108, No. 5 ( 2023-04-13), p. 1143-1153
    Abstract: Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. Objective To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. Methods A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. Results The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level & lt;15 ng/dL, 19.9% had at least 2 aldosterone levels & lt;15 ng/dL, and 16.2% had mean aldosterone levels & lt;15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC & gt;2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. Conclusion Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2026217-6
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