Clinical Research Directory

Natural History Study of Parathyroid Disorders

Background: Parathyroid disorders are very common in the general population and include disorders of parathyroid excess, deficiency, or defects in parathyroid hormone (PTH) signaling. PTH, the main secretory product of parathyroid glands is responsible for regulation of calcium-phosphate homeostasis. Objective: i) To investigate the cause of parathyroid disorders ii) To describe evolution, natural history, and longitudinal trends of parathyroid and related disorders seen in syndromic presentations like multiple endocrine neoplasia, hyperparathyroidism-jaw tumor syndrome Eligibility: People ages 6 months older who have, are at risk of having, or are related to a person with a parathyroid or related disorder. Design: Participants will be screened with a review of their medical records. Participants will be seen, tested, and treated by doctors based on their condition. Their visits may be in person or via telehealth. Participants will complete questionnaires. They will answer questions about their physical, mental, and social health. Participants may give samples such as saliva, blood, urine, or stool. Participants may give cheek cell samples. They will do this using a cheek swab or by spitting into a cup. Adult participants may give a skin biopsy. For this, a small bit of skin is removed with a punch tool. Participants may have medical photos taken. If participants have surgery during the course of their regular care either at the NIH or at a different hospital or doctor s office, researchers will ask for some of the leftover tissue. Participants will be in the study as long as they are being seen by their doctor.

Accuracy of 18F-Fluorocholine PET/MR and NeuroEXPLORER PET/CT Imaging for Localization of Parathyroid Tumors

Background: People have 4 parathyroid glands near the thyroid gland in the neck. Surgery is needed to remove a parathyroid gland that is too large or has a tumor. These glands can be in different places, so doctors use an imaging scan with contrast dye to help find them before surgery. Researchers want to know if a different type of scan and a new tracer can make it easier to find the tumors in the parathyroid glands. Objective: To see if PET/MRI and NeuroEXPLORER PET-CT scans with a 18F-FCH tracer are better than existing methods for finding the parathyroid glands. Eligibility: People aged 18 years or older who are scheduled for surgery to remove a parathyroid gland. Design: Participants will have up to 4 clinic or hospital visits. They will be screened. They will have a physical exam and give blood samples. Participants will have a 4-dimensional computed tomography (4D-CT) scan. This is the current way doctors look for parathyroid glands. They will be injected with an iodine-based dye for the 4D-CT scan. They will lie on a padded table that slides into a donut-shaped machine. Participants will have a positron emission tomography (PET)-magnetic resonance imaging (MRI) and NeuroEXPLORER PET-CT scan. For these scans, they will be injected with a radioactive tracer (18F-FCH). They will wait about 30 to 60 minutes for their body to absorb the tracer. They will lie on a padded table that slides into a tube. Their vital signs will be monitored during the scan. Participants will have surgery to remove the target gland. They may need to stay in the hospital for up to 3 nights. Participants will have a follow-up visit 6 months after the surgery. This may be done remotely....

Parathyroid Tumor Clonal Status

To define the frequency of monoclonal-X and polyclonal-X tumors in PHPT participants having parathyroidectomy (PTX) and to define the relationship between parathyroid tumor clonal status and multiple gland neoplasia (MGN), we will compare surgical and pathologic outcomes to tumor clonal status in a multicenter cohort of patients having bilateral neck exploration (BNE) and PTX (primary objectives).

Aldosterone Variations in Patients With Primary Hyperparathyroidism After Surgery

Primary hyperparathyroidism is a disorder of calcium and phosphorus metabolism linked to dysfunction of one or more parathyroid glands. The latest recommendations from the American Association of Endocrine Surgeons (7) consider the presence of hypertension as an argument for proposing the removal of a parathyroid adenoma in the context of primary hyperparathyroidism. The renin-angiotensin-aldosterone system is involved in regulating blood pressure. The main objective of this study is to assess aldosterone level in patients with primary hyperparathyroidism before surgery and its variation in the year following surgery for parathyroid disease. Secondary objectives are to assess aldosterone variations after surgery at 3 months * Assess aldosterone variations after surgery at 6 months * Assess aldosterone variations after surgery at 12 months * Blood pressure changes before and after surgery (5 pre- and post-operative measurements) * Assess the number of antihypertensive treatments before and after surgery * Assess antihypertensive treatment according to the WHO-DDD classification before and after surgery Compare aldosterone levels in the 'primary hyperparathyroidism' group with a control group of patients from the general population (using the STANISLAS cohort). * Compare aldosterone levels in the HPT group with aldosterone levels in a group of patients after myocardial infarction (cardiovascular patient group )

Amino Acid Transporter System PET/CT Imaging in AATS-Related Diseases

To evaluate the potential usefulness of 11C/18F-MET/FET positron emission tomography/ computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various amino acid transporter system (AATS)-related disease patients.

Molecular and Immunohistochemical Profiling of Tumors in Patients With Parathyroid Tumors

This trial studies molecular and immunohistochemical profiling of tumors in patients with parathyroid tumors. Studying molecular and immunohistochemical profiling of tumors may help doctors avoid inconsistencies in diagnosis, unnecessary or incomplete surgery, surgical morbidity, psychological stress, and inadequate follow up.

Glycemic Control, Type II Diabetes, Parathyroidectomy

The purpose of this study is to assess glycemic control after parathyroidectomy in patients with primary hyperparathyroidism and concomitant type 2 diabetes mellitus.

Cohort Primary Hyperparathyroidism

CoHPT is a prospective, monocentric, observational cohort including all patients diagnosed with primary hyperparathyroidism in Nantes University Hospital, aiming to study the outcomes associated with parathyroidectomy. Clinical and biochemical evaluation is performed at the inclusion, and 6, 12, 36 and 60 months. A biocollection is collected. The main hypotheses are that parathyroidectomy could improve cardiovascular, renal, bone, and cardiovascular outcomes along with quality of life.

18F-choline Positron-emission-tomography - Computed-tomography Compared to Conventional Imaging for Localizing Diseased Parathyroid Glands in Primary Hyperparathyroidism

The goal of this open, single-center, prospective, randomized, clinical study is to compare imaging with \[18F\]fluoromethyl-dimethyl-2-hydroxyethylammonium (18F-choline) positron-emission-tomography - computed-tomography, 18F-ch-PETCT, to conventional imaging with ultrasonography and sestamibi scintigraphy in localizing diseased parathyroid glands in patients diagnosed with primary hyperparathyroidism, pHPT. The question this study aims to answer is: can 18-F-ch-PET-CT more precisely localize diseased parathyroid glands in patients with pHPT before surgery? The objective of the study is to help improve precision in parathyroid surgery, thereby increasing cure rates, minimizing complications, and shortening operation times.

Bisphosphonate Prior to Parathyroidectomy in Primary Hyperparathyroidism

This study is a randomized, double-blinded, placebo-controlled trial investigating the effects of zoledronic acid (ZOL) versus placebo in patients with primary hyperparathyroidism (PHPT) undergoing parathyroidectomy (PTX). PHPT is a common endocrine disorder associated with hypercalcemia, reduced bone mineral density (BMD), increased fracture risk, renal calcifications, and cardiovascular complications. While PTX remains the definitive treatment, the potential role of bisphosphonates in optimizing post-surgical outcomes remains unclear. This trial aims to evaluate whether a single infusion of ZOL prior to PTX impacts bone health, cardiovascular parameters, and renal function one year post-surgery. The primary endpoint is the change in areal bone mineral density (aBMD) at the lumbar spine one year after PTX. Secondary endpoints include changes in aBMD at other skeletal sites, volumetric BMD, bone microarchitecture, bone turnover markers, coronary artery calcium score, arterial stiffness, and renal calcifications. A total of 140 postmenopausal women and men over 50 years with PHPT and low BMD will be enrolled and randomized to receive either ZOL or placebo 2-4 weeks before PTX. Participants will undergo extensive imaging, biochemical analysis, and cardiovascular assessments at baseline and one year post-surgery. This study seeks to clarify whether ZOL improves post-surgical bone recovery or interferes with the natural bone remodeling process following PTX. Additionally, it will provide insight into the cardiovascular and renal effects of bisphosphonate therapy in PHPT patients. Findings may help guide treatment strategies for optimizing long-term skeletal and systemic health in this patient population.

Is Intraoperative PTH Monitoring Obsolete in Times of Choline PET/CT? a Prospective Multicenter Cohort Study to Determine Whether the Regular Preoperative Use of Choline-PET/CT Scan Obviate the Need for Intraoperative PTH-measurement in Patients with Primary Hyperparathyreoidism

In patients with primary hyperparathyreoidism (pHPT) in 80-90% only one of the four parathyroid glands has developed an autonomy and is causative for the disease. Localisation diagnostics are used to help identify the affected gland or glands in order to enable more focused surgical approaches and reduce morbidity of the surgery, as well as operative time. The gold standard for imaging in Germany and Austria are sonography and scintigraphy. If imaging is not conclusive, Choline-PET/CT, which has been shown to have a higher specificity than the scintigraphy, especially for multiglandular disease, is performed mostly in Austria, but only on special indications in Germany. In Switzerland, as of 2023 the Choline-PET/CT has replaced the scintigraphy and is routinely performed in patients with indication for parathyroidectomy in many hospitals. The current S2k guideline recommends to perform an intraoperative PTH measurement before and 10 minutes after removal of the parathyroid gland in order to assess the success of the surgery. Due to the short half-life of PTH of around three minutes, a PTH drop of 50% or into the normal range within 10 minutes of removal of the suspected gland has a high sensitivity and specificity for cure. If PTH drop is inadequate, further gland exploration is performed. The intraoperative measurement of PTH is associated with waiting time in the OR and uncertainty if the next patient can be anesthetized, prolonging surgeries by 30-60 minutes depending on the local facilities. If the Choline-PET/CT is sufficiently sensitive and specific in detecting both uni- and multiglandular disease, surgery according to Choline-PET/CT findings could make waiting for intraoperative PTH drop unnecessary. The aim of the study is to determine whether the regular use of Choline-PET/CT can obviate the need for intraoperative PTH-measurement with the potential to shorten the length of parathyroid surgeries. This could save considerable costs and justify the regular use of Choline-PET/CT.

Diagnostic Performance of [11C]Choline PET/CT In the Preoperative Assessment of Primary Hyperparathyroidism

Primary hyperparathyroidism (HPT) ranks as the third most common endocrine disorder, characterized by excessive secretion of parathormone (PTH), a hormone crucial for regulating calcium and phosphorus metabolism within the body. The only cure for HPT is surgically removing the hyperfunctioning parathyroid tissue, both in symptomatic and asymptomatic settings. With the advance of preoperative medical imaging techniques, a paradigm shift has taken place in the surgical approach of this condition, evolving from an inpatient bilateral cervical exploration to an outpatient minimally invasive procedure, which has proved to be superior in outcome. Due to the small size of the glands, preoperative visualisation and localisation are mandatory for the surgeon. Several imaging methods have been researched for identifying hyperfunctioning parathyroid glands, including morphological, functional and hybrid techniques, with no clear agreement on the optimal imaging approach.The preoperative localization modalities available are ultrasonography; parathyroid scintigraphy using technetium \[99mTc\]Tc sestamibi (MIBI), multiphase multidetector 4D computed tomography (4DCT); magnetic resonance imaging; and recently, positron-emission tomography/computed tomography (PET/CT) using 11C- and 18F-labelled radiotracers. While ultrasound and \[99mTc\]Tc-MIBI scintigraphy have been long used to diagnose and monitor patients with HPT, they can lead to numerous false negative results and therefore require additional examinations.Choline PET/CT is steadily replacing conventional imaging in many centres, allowing for the localization of adenomas in three quarter of patients with negative previous imaging examinations, but is still considered a relatively new method. \[11C\]C-Choline (\[11C\]CH) PET/CT is gradually gaining ground as a reliable method of localising HPT preoperatively, due to its fast uptake in hyperfunctioning parathyroid tissue, shorter acquisition time and lower radiation exposure compared to other nuclear medicine investigations and conventional methods. \[11C\]CH PET/CT has been suggested to be superior in diagnostic performances, compared to other imaging methods, reaching sensitivities up to 98.9%.The aim of our retrospective, single centre study is to evaluate the diagnostic performances and the inter-observer agreement of \[11C\]CH PET/CT for the preoperative detection of parathyroid adenomas in patients with suspected primary HPT.

Calcitonin Pre-treatment to Improve SPECT-CT Sensitivity

Patients with biochemically confirmed primary hyperparathyroidism and non-localizing SPECT-CT exam within the past year will be included. Subjects will be treated with calcitonin to lower calcium levels immediately prior to reimaging. The goal of this study is to determine whether lowering calcium will improve uptake/retention of sestamibi and improve sensitivity of SPECT-CT to localize parathyroid adenoma.

Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients

Neuroendocrine neoplasms (NENs) are a heterogeneous group of lesions derived from cells with the ability to produce hormones that may arise from multiple different organs. Their clinical behavior is quite variable, encompassing both benign lesions and aggressive tumors that invade surrounding and/or distant structures. NENs may also cause serious morbidity due to hormone oversecretion. NENs are among the most frequently inherited human tumors, presenting either isolated or as part of syndromes in which a single patient or family develops multiple tumors. There are also non-inherited changes in the genetic information of the tumor cells that are potential targets for treatment. Both inherited and non-inherited DNA defects can be identified using modern routine genetic tests which, unfortunately, are not widely available in Mexico. This project seeks to uncover the genetic defects causing NENs in a large cohort of Mexican patients, using three different methods for genetic testing. Adult individuals with various types of NENs from two reference hospitals in Mexico City will be invited to participate. After completing informed consent, blood and, if possible, tissue samples will be obtained from all participants. Clinical details, laboratory results, imaging studies, and histopathological data at disease presentation will be retrieved. An initial screening will be performed by analyzing changes in the sequence of multiple genes that have been associated with the occurrence of NENs. In cases with negative screening, a specific method to assess changes in the number of copies of the same genes will also be employed. Finally, sequences of all DNA regions encoding information required to make proteins will be obtained in selected cases. Analyses will be carried out in blood and, if available, also in tumor tissue samples from study participants. Screening of additional family members will be offered. This project will accurately describe the repertoire of specific defects causing NENs in the study population, and will likely uncover and characterize novel genetic associations. The results will contribute for a better understanding of the alterations within and outside known driver genes that shape syndromic presentations, tumor behaviors, and inheritance patterns in individuals with NENs. These data will contribute to improve the information on the molecular bases of NENs, including alterations that can be used as therapeutic targets.