Sendhil Rajan1, Ghazala Zaidi2, Gaurav Agarwal3, Anjali Mishra1, Amit Agarwal1, Saroj Kanta Mishra1, Eesh Bhatia2. 1. Department of Endocrine & Breast Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Rae Bareilly Road, Lucknow, 226014, Uttar Pradesh, India. 2. Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India. 3. Department of Endocrine & Breast Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Rae Bareilly Road, Lucknow, 226014, Uttar Pradesh, India. gaurav@sgpgi.ac.in.
Abstract
INTRODUCTION: Pheochromocytoma (PCC) manifests in up to 50% of MEN2 patients. We correlated the clinico-pathological features of MEN2-associated PCC (MEN-PCC) with RET mutations and compared them with non-MEN adrenal-PCCs. METHODS: In this retrospective single institution study on a large PCC database (n = 208, 1997-2014) 24 MEN-PCC patients with known RET mutations were reviewed. Excluding 7 with incomplete data, the study cohort of 17 MEN-PCC patients from 11 kindreds (M:F::7:10) was identified. Clinical, biochemical, pathological attributes, and outcomes in the MEN-PCC group were correlated with the genotype, and further compared with non-MEN, apparently sporadic adrenal-PCCs (n = 132, excluding 37 extra-adrenal and 15 VHL/NF1/SDH-associated PCC). RESULTS: Components of MEN2 encountered included MTC in 13(76.5%), Marfanoid habitus in 2, and PHPT, cutaneous lichen amyloidosis and mucosal neuromas in 1 patient each. In 11(64.7%), PCC was the first detected MEN2 component (Symptomatic:8, Incidentaloma:3). Four (23.5%) were normotensive; 8(47.1%) had bilateral PCC (7 synchronous, 1 metachronous). Surgery for PCC included laparoscopic adrenalectomy in 12; and cortical-sparing adrenalectomy in 2 of 8 bilateral PCC patients. Mean MEN-PCC tumor size was 6.9 ± 3.9 cm, and 6(35%) had additional adrenal medullary hyperplasia. Four different genotypes were encountered, commonest involving codon 634, others being 804 and 918. Mean age in MEN-PCC (27.7 ± 12.2 years) was lower than non-MEN PCC (39.4 ± 15.7, p = 0.018). Proportion of pediatric patients (35.3% in MEN-PCC vs. 12.9% in non-MEN-PCC, p = 0.007), bilateral tumors (47.1% in MEN-PCC, 4.5% in non-MEN-PCC, p < 0.001), and adrenal medullary hyperplasia (35.2% in MEN-PCC, 0.7% in non-MEN-PCC, p < 0.001) were different. Median 24-hour urinary metanephrines was significantly higher in index MEN-PCC patients, than non-MEN-PCC (634 vs. 214 mcg/24 h, p value = 0.006), but was non-significantly higher in non-index MEN-PCC patients. Mean tumor sizes were comparable in the two groups. None of MEN-PCC patients had malignant PCC, compared to 7(5.3%) in non-MEN-PCC. CONCLUSIONS: In this cohort of MEN-PCC from India, the commonest causative RET mutations for MEN-PCC involved codon 634. MEN-PCC patients were younger, and more frequently had bilateral PCC than non-MEN disease. MEN-PCC patients in India are diagnosed with large tumors and extremely high catecholamine/metanephrine levels.
INTRODUCTION:Pheochromocytoma (PCC) manifests in up to 50% of MEN2 patients. We correlated the clinico-pathological features of MEN2-associated PCC (MEN-PCC) with RET mutations and compared them with non-MEN adrenal-PCCs. METHODS: In this retrospective single institution study on a large PCC database (n = 208, 1997-2014) 24 MEN-PCC patients with known RET mutations were reviewed. Excluding 7 with incomplete data, the study cohort of 17 MEN-PCC patients from 11 kindreds (M:F::7:10) was identified. Clinical, biochemical, pathological attributes, and outcomes in the MEN-PCC group were correlated with the genotype, and further compared with non-MEN, apparently sporadic adrenal-PCCs (n = 132, excluding 37 extra-adrenal and 15 VHL/NF1/SDH-associated PCC). RESULTS: Components of MEN2 encountered included MTC in 13(76.5%), Marfanoid habitus in 2, and PHPT, cutaneous lichen amyloidosis and mucosal neuromas in 1 patient each. In 11(64.7%), PCC was the first detected MEN2 component (Symptomatic:8, Incidentaloma:3). Four (23.5%) were normotensive; 8(47.1%) had bilateral PCC (7 synchronous, 1 metachronous). Surgery for PCC included laparoscopic adrenalectomy in 12; and cortical-sparing adrenalectomy in 2 of 8 bilateral PCC patients. Mean MEN-PCC tumor size was 6.9 ± 3.9 cm, and 6(35%) had additional adrenal medullary hyperplasia. Four different genotypes were encountered, commonest involving codon 634, others being 804 and 918. Mean age in MEN-PCC (27.7 ± 12.2 years) was lower than non-MEN PCC (39.4 ± 15.7, p = 0.018). Proportion of pediatric patients (35.3% in MEN-PCC vs. 12.9% in non-MEN-PCC, p = 0.007), bilateral tumors (47.1% in MEN-PCC, 4.5% in non-MEN-PCC, p < 0.001), and adrenal medullary hyperplasia (35.2% in MEN-PCC, 0.7% in non-MEN-PCC, p < 0.001) were different. Median 24-hour urinary metanephrines was significantly higher in index MEN-PCC patients, than non-MEN-PCC (634 vs. 214 mcg/24 h, p value = 0.006), but was non-significantly higher in non-index MEN-PCC patients. Mean tumor sizes were comparable in the two groups. None of MEN-PCC patients had malignant PCC, compared to 7(5.3%) in non-MEN-PCC. CONCLUSIONS: In this cohort of MEN-PCC from India, the commonest causative RET mutations for MEN-PCC involved codon 634. MEN-PCC patients were younger, and more frequently had bilateral PCC than non-MEN disease. MEN-PCC patients in India are diagnosed with large tumors and extremely high catecholamine/metanephrine levels.
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