Total adrenalectomy versus subtotal adrenalectomy for bilateral pheochromocytoma: meta-analysis.

BACKGROUND: Bilateral pheochromocytomas are rare and often heritable. Total adrenalectomy leads to a definitive oncological cure, with subsequent definitive hypocortisolism. Subtotal adrenalectomy is a possible alternative. The aim of this study was to assess the effects of total adrenalectomy and subtotal adrenalectomy on bilateral pheochromocytoma in terms of post-surgical rate of recurrence, metastatic disease, and steroid dependence. METHODS: Systematic searches in the bibliographic databases PubMed, Embase, and Europe PMC were performed for 1945 to 1 June 2023. PRISMA guidelines were followed and the PICO strategy was applied to English-language studies comparing subtotal adrenalectomy with total adrenalectomy. A random-effects model was used to assess the different outcomes for studies with high heterogeneity. The Newcastle-Ottawa scale and the Risk Of Bias In Non-randomized Studies of Interventions ('ROBINS-I') tool were used to assess quality and risk of bias. RESULTS: From a total of 12 909 studies, 1202 patients (from 10 retrospective studies) were eligible for the meta-analysis. In six studies, including 1176 patients, the recurrence rate after subtotal adrenalectomy and total adrenalectomy was 14.1 versus 2.6 per cent respectively (OR 4.91, 95 per cent c.i. 1.30 to 18.54; P = 0.020; I2 72 per cent). In nine studies, including 1124 patients, the rate of post-surgical steroid dependence was 93.3 versus 11.6 per cent after total adrenalectomy and subtotal adrenalectomy respectively (OR 0.003, 95 per cent c.i. 0.0003 to 0.03; P < 0.00001; I2 66 per cent). Based on two studies, including 719 patients, no differences were evident regarding the occurrence of post-surgery metastatic disease. CONCLUSION: Subtotal adrenalectomy leads to less post-surgical primary adrenal insufficiency, but leads to a higher postoperative recurrence rate. Future prospective randomized studies, with clear eligibility criteria, are needed to confirm these results.

Long-Term Outcomes after Surgery for Pheochromocytoma and Sympathetic Paraganglioma.

BACKGROUND: The prognosis of pheochromocytoma and sympathetic paraganglioma (PHEO/sPGL) is difficult to predict at the time of diagnosis and long-term follow-up data are scarce, especially for apparently benign and sporadic variants. The aim of the study was to analyze the long-term outcomes in PHEO/sPGL patients. METHODS: A monocentric series of 170 patients who underwent surgery for PHEO/sPGL was analyzed. RESULTS: The study cohort included 91 female and 79 males with a median age of 48 years (range 6-83). The majority of PHEO/sPGL cases were considered apparently benign at the time of diagnosis; evident malignant behavior was found in 5% of cases. The overall 10-year risk of recurrence was 13%, but it rose up to 33% at 30 years. The risk of new tumor recurrence was higher in patients with hereditary tumors, but the risk was still significant in patients with apparently sporadic variants (20-year risk: 38% vs. 6.5%, respectively; p < 0.0001). The risk of metastatic recurrence was higher in patients with locally aggressive tumors at diagnosis, but the risk was present also in apparently benign variants (5-year risk: 100% vs. 1%, respectively; p < 0.0001). CONCLUSIONS: Lifelong follow-up is required not only for hereditary PHEO/sPGL but also for apparently benign and sporadic tumors at diagnosis because of the risk of long-term recurrent disease.

Surgical approaches in hereditary endocrine tumors.

Endocrine tumors of thyroid, adrenal and parathyroid glands may be due to germline and inheritable mutations in 5-30% of patients. Medullary Thyroid Carcinoma, Pheochromocytoma, Paraganglioma, and Familial Primary Hyperparathyroidism are the most frequent entity. Hereditary endocrine tumors usually have a suggestive familial history; they occur earlier than sporadic variants, are multifocal, and have increased recurrence rates. They may be present as isolated variant or associated to other neoplasms in a syndromic setting. Genetic diagnosis should be preferably available before surgery because specific and targeted operative management are needed to achieve the best chance of cure. This review was aimed to discuss the surgical approaches for some of the most frequent hereditary endocrine tumors of thyroid, adrenal and parathyroid glands, focusing on medullary thyroid carcinoma, Pheochromocytoma, Paraganglioma and hereditary primary hyperparathyroidism (pHPT). Hereditary Medullary Thyroid Carcinoma is caused by RET mutations, and may be associated to Pheochromocytomas in MEN 2 setting. Total thyroidectomy and at least central neck nodal dissection is required. The availability of genetic screening allows prophylactic or early surgery in asymptomatic patients, with subsequent definitive cure. Hereditary Pheochromocytomas may be present in several syndromes (MEN 2, VHL, NF1, Paraganglioma/Pheochromocytoma syndrome); it may involve both adrenals; in these cases, a cortical sparing adrenalectomy should be performed to avoid permanent hypocorticosurrenalism. Hereditary Primary Hyperparathyroidism may frequently occur associated to MEN 1, MEN 2A, MEN 4, Hyperparathyroidism-Jaw Tumor Syndrome; it may involve all the parathyroid glands, requiring subtotal parathyroidectomy or total parathyroidectomy plus autotransplantation. In some cases, a selective parathyroidectomy might be performed.

Adrenal ganglioneuroma: The Padua Endocrine Surgery Unit experience.

BACKGROUND: Adrenal ganglioneuroma (AGN) is a rare tumor that originates from the gangliar cells of the sympathetic nervous system. It represents less than 5% of all adrenal masses. AGN occurs as a large mass, with benign behavior and no relevant symptoms and hormonal secretion, but it is often misdiagnosed because the preoperative radiological diagnosis is generally challenging. The aim of the present paper is to report the experience of a tertiary referral academic center regarding the management of AGN and review the relevant literature. METHODS: The demographic, diagnostic, surgical, and pathological findings of 666 consecutive patients who were adrenalectomized at the Padua Endocrine Surgery Unit between 1990 and 2015 were retrospectively reviewed in order to focus on AGN. RESULTS: The pathology confirmed AGN in 10 patients (1.5% of cases; median age 35 years, range 19-73). The diagnosis was incidental and never available before surgery. Eight patients were asymptomatic, two presented lower back and abdominal pain. The mass was non-secreting in all cases. Preoperative imaging techniques were inconclusive about the nature of the mass in all cases. The median size of the tumor was 55 mm (range 30-80). The laparoscopic approach was performed in 60% of cases. No recurrences occurred after surgery at a median follow-up of 10 years (range 1.7-18.2). CONCLUSION: The diagnosis of AGN may be challenging and most often occurs after surgery, since it is frequently confirmed by histological examination. Radical excision may be achieved by laparoscopic adrenalectomy, with a subsequent definitive cure and excellent prognosis at long term follow up.