Hypoparathyroidism after parathyroidectomy in patients with Multiple Endocrine Neoplasia Type 1 (MEN1)

• Grant number: 25/04626-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: April 30, 2026
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Fábio Luiz de Menezes Montenegro
• Grantee: Rafaela Mendes Battiferro
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Multiple Endocrine Neoplasia Type 1 (MEN1) is a genetic syndrome characterized by the inactivation of the MEN1 gene, a tumor suppressor gene. Patients with this syndrome have an increased susceptibility to the development of neoplasms, particularly endocrine neoplasms, both malignant and benign, such as parathyroid adenomas. Studies show that 90 to 97% of patients with this disease will develop primary hyperparathyroidism due to hyperplasia or neoplasia of one or more parathyroid glands. The treatment for this condition is surgical, and the techniques used are subtotal or total parathyroidectomy with autografting, as the disease is multiglandular. There is no consensus on the best technique to use. Several factors should be considered, including the risk of recurrence and progression to permanent hypoparathyroidism, a feared complication. A permanent condition is arbitrarily defined when it persists for more than six months after surgery and is characterized by insufficient circulating parathyroid hormone (PTH) levels, even in the presence of hypocalcemia. Paresthesia, asthenia, myalgia, cardiac changes-such as QT interval prolongation on the electrocardiogram-cataracts, and psychiatric disorders (anxiety and depression) are some of the potential consequences of hypocalcemia. Although the clinical repercussions are significant and deserve the attention of healthcare professionals, there is still no in-depth study on the long-term evolution (more than six months) of hypoparathyroidism resulting from the mentioned surgical treatments.In this retrospective analysis with a 2-year follow-up, we aim to assess the percentage of patients with MEN1 who developed hypoparathyroidism after parathyroidectomy, examine whether this percentage changed over a longer follow-up period, and determine whether any surgical technique (subtotal or total parathyroidectomy with autografting) was associated with higher percentages of progression to this clinical outcome at 1 and 2 years of follow-up.To achieve this, we will collect data on demographics and serum analyses of total and ionized calcium, phosphorus, PTH, and creatinine, as well as identify other clinical conditions that could influence the analysis of hypoparathyroidism (use of medications, history of hungry bone syndrome, calcium and vitamin D intake and supplementation, previous malabsorptive surgery, and chronic kidney disease). We will evaluate at 3, 6, 12, and 24 months postoperatively or the last follow-up between 1 and 2 years after surgery.It is important to note that, although the definition of hypoparathyroidism previously mentioned is considered in this work, based on the author's experience, there is a difficulty in characterizing this condition in clinical practice. In this sense, hypoparathyroidism will also be considered as the condition of a patient using more than 1g of calcium and/or any dose of calcitriol, as long as the patient is not hypercalcemic. It will also be necessary to differentiate other possible clinical conditions, such as hungry bone syndrome or iatrogenic hypercalcemia.The collected and analyzed information will contribute to clinical practice, both for medical decision-making and for communication with patients, not only regarding the risk of developing hypoparathyroidism after surgery but also concerning the likelihood of recovering normal parathyroid function over a longer follow-up period (2 years)-an aspect that, despite its clinical relevance, has not yet been studied. (AU)