Parathyroid CancerNCT04969926
Natural History Study of Parathyroid Disorders
An observational study of Parathyroid Cancer and Primary Hyperparathyroidism, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 6 months to 100 years
- Conditions the study is for
- Parathyroid Cancer, Primary Hyperparathyroidism, Pseudohypoparathyroidism
- How many people
- 3,000 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2021to 22 Jan 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with confirmed, suspected or at risk of developing parathyroid and related disorders.
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Subjects known to have, suspected of having, or at risk of developing a parathyroid or related disorder.
- Age >= 6 months.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Children <= 6 months
- Patients with conditions that in the opinion of the investigators can interfere with the study objectives.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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.
Read more
Objective:
- 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.
Read the detailed description
Study Description:
Patients with confirmed, suspected or at risk of developing parathyroid disorders will be provided standard of care testing for their condition. Data obtained during the testing will be used for research. Additionally, samples may be collected for research.
Objectives:
- To investigate the cause of the disease and its associated manifestations, possibly genetic in participants with parathyroid and related disorder(s)
- To identify biomarkers of the various parathyroid disorder(s) and associated manifestations by performing molecular profiling of available biospecimens
- To describe evolution, natural history and longitudinal trends of parathyroid and related disorders including the associated extra-parathyroid manifestations seen in these disorders, for example, Zollinger-Ellison syndrome, gastro-entero-pancreatic neuroendocrine tumors, kidney, jaw, pituitary, and uterine tumors.
- To investigate the natural history of parathyroid disorders and associated manifestations during pregnancy
- To characterize the morbidity and mortality in participants with parathyroid and related disorders and investigate its association with extra-parathyroidal manifestations.
- To investigate long-term risks and benefits with standard of care testing and therapy for parathyroid and associated extra-parathyroidal manifestations.
- Conditions
- Parathyroid Cancer, Primary Hyperparathyroidism, Pseudohypoparathyroidism, Inheritable Bone Diseases, Multiple Endocrine Neoplasia, Type 1
- Keywords
- Hyperparathyroidism, calcium disorders, Parathyroid Cancer, Inheritable, PSEUDOHYPOPARATHYROIDISM, Natural History
- Medical subject headings
- Parathyroid Neoplasms, Hyperparathyroidism, Primary, Pseudohypoparathyroidism, Multiple Endocrine Neoplasia Type 1, Hyperparathyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with confirmed, suspected or at risk of developing parathyroid disorder | Parathyroid (and related disorders) will be evaluated and their biospecimens collected to define the molecular signature and clinical spectrum of their disorder |
What is being measured
The primary outcome is the main question the study is designed to answer.
To identify biomarkers of the disease and associated manifestations by performing molecular profiling of available biospecimens
Participants will undergo standard clinical evaluations for their condition. Data obtained during these evaluations will be retained for purposes of the primary objective, for analysis of secondary objectives, and for future research. There are no mandatory study procedures for this protocol.
Measured: 5 years
To investigate the cause and molecular mechanism of the disease, possibly genetic in participants with unknown cause of parathyroid and related disorder(s)
Participants will undergo standard clinical evaluations for their condition. Data obtained during these evaluations will be retained for purposes of the primary objective, for analysis of secondary objectives, and for future research. There are no mandatory study procedures for this protocol.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2021
- Study start30 Nov 2021
- Primary completion22 Jan 2031 (estimated)
- Study completion22 Jan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Parathyroid CancerStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 3,000 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Smita Jha, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04969926
- Sponsor's protocol ID
- 10000344
- Other IDs
- 000344-DK
- Status last verified
- 3 Nov 2026
- First submitted
- 20 Jul 2021
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Tepede AA, Lee M, Welch J, Mandl A, Cochran C, Hamimi A, Weinstein LS, Simonds WF, Gharib AM, Millo C, Sadowski SM, Blau JE, Jha S. 18F-FDOPA PET/CT for neuroendocrine tumors in multiple endocrine neoplasia type 1. Front Endocrinol (Lausanne). 2026 Aug 5;17:1849746. doi: 10.3389/fendo.2026.1849746. eCollection 2026.
PubMed 42620272Alkaissi H, Chuki E, Liu Y, Welch J, Bliss L, Shah N, Agarwal SK, Simonds WF, Quezado M, Sakiani S, Andresson T, Pacak K, Nilubol N, Weinstein LS, Febres-Aldana CA, Jha S. Expansion of Germline Variants in Primary Hyperparathyroidism: Fumarate Hydratase Deficiency as a Cause of Parathyroid Adenomas. Endocr Pathol. 2026 Jul 22;37(1):32. doi: 10.1007/s12022-026-09928-w.
PubMed 42484783Worthy CC, Tora R, Uttarkar CN, Welch JM, Bliss L, Cochran C, Ninan A, Kumar S, Wank S, Auh S, Weinstein LS, Simonds WF, Agarwal SK, Blau JE, Jha S. Genotype-phenotype correlation in multiple endocrine neoplasia type 1. JCI Insight. 2025 Feb 13;10(6):e176993. doi: 10.1172/jci.insight.176993.
PubMed 39946193Graf A, Cochran C, Sadowski S, Nilubol N, Simonds WF, Weinstein LS, Chang R, Jha S. Invasive Testing for Preoperative Localization of Parathyroid Tumors. J Endocr Soc. 2024 Jan 2;8(1):bvad158. doi: 10.1210/jendso/bvad158. eCollection 2023 Dec 1.
PubMed 38174154Tora R, Welch J, Sun J, Agarwal SK, Bell DA, Merino M, Weinstein LS, Simonds WF, Jha S. Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome. J Clin Endocrinol Metab. 2023 Nov 17;108(12):3165-3177. doi: 10.1210/clinem/dgad368.
PubMed 37339334Zenno A, Ramamoorthy B, Hammoud DA, Quezado M, Zeiger MA, Jha S. Case Report: Nine-year-old with parathyroid adenoma within the piriform sinus. Front Endocrinol (Lausanne). 2023 May 23;14:1171052. doi: 10.3389/fendo.2023.1171052. eCollection 2023.
PubMed 37288292Chuki E, Graf A, Ninan A, Tora R, Abijo T, Bliss L, Nilubol N, Weinstein LS, Agarwal SK, Simonds WF, Jha S. Long-Term Outcomes of Parathyroid Autografts in Primary Hyperparathyroidism. J Endocr Soc. 2023 Apr 22;7(5):bvad055. doi: 10.1210/jendso/bvad055. eCollection 2023 Mar 6.
PubMed 37284613
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History Study of Parathyroid Disorders
- ClinicalTrials.gov ID
- NCT04969926
- Acronym / sponsor ID
- 10000344
- Conditions
- Parathyroid Cancer, Primary Hyperparathyroidism, Pseudohypoparathyroidism, Inheritable Bone Diseases, Multiple Endocrine Neoplasia, Type 1
- Keywords
- Hyperparathyroidism, calcium disorders, Parathyroid Cancer, Inheritable, PSEUDOHYPOPARATHYROIDISM, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 22 Jan 2031 (estimated)
- Study completion
- 22 Jan 2031 (estimated)
- First posted
- 21 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Detailed description
Study Description:
Patients with confirmed, suspected or at risk of developing parathyroid disorders will be provided standard of care testing for their condition. Data obtained during the testing will be used for research. Additionally, samples may be collected for research.
Objectives:
- To investigate the cause of the disease and its associated manifestations, possibly genetic in participants with parathyroid and related disorder(s)
- To identify biomarkers of the various parathyroid disorder(s) and associated manifestations by performing molecular profiling of available biospecimens
- To describe evolution, natural history and longitudinal trends of parathyroid and related disorders including the associated extra-parathyroid manifestations seen in these disorders, for example, Zollinger-Ellison syndrome, gastro-entero-pancreatic neuroendocrine tumors, kidney, jaw, pituitary, and uterine tumors.
- To investigate the natural history of parathyroid disorders and associated manifestations during pregnancy
- To characterize the morbidity and mortality in participants with parathyroid and related disorders and investigate its association with extra-parathyroidal manifestations.
- To investigate long-term risks and benefits with standard of care testing and therapy for parathyroid and associated extra-parathyroidal manifestations.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with confirmed, suspected or at risk of developing parathyroid disorder | – | –Parathyroid (and related disorders) will be evaluated and their biospecimens collected to define the molecular signature and clinical spectrum of their disorder |
Who may qualify
- Ages
- 6 months to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with confirmed, suspected or at risk of developing parathyroid and related disorders.
Key inclusion criteria (3 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Subjects known to have, suspected of having, or at risk of developing a parathyroid or related disorder.
- Age >= 6 months.
Key exclusion criteria (3 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Children <= 6 months
- Patients with conditions that in the opinion of the investigators can interfere with the study objectives.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To identify biomarkers of the disease and associated manifestations by performing molecular profiling of available biospecimens
Time frame: 5 years
Participants will undergo standard clinical evaluations for their condition. Data obtained during these evaluations will be retained for purposes of the primary objective, for analysis of secondary objectives, and for future research. There are no mandatory study procedures for this protocol.
To investigate the cause and molecular mechanism of the disease, possibly genetic in participants with unknown cause of parathyroid and related disorder(s)
Time frame: 5 years
Participants will undergo standard clinical evaluations for their condition. Data obtained during these evaluations will be retained for purposes of the primary objective, for analysis of secondary objectives, and for future research. There are no mandatory study procedures for this protocol.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Derived from this study: PubMed 42620272Tepede AA, Lee M, Welch J, Mandl A, Cochran C, Hamimi A, Weinstein LS, Simonds WF, Gharib AM, Millo C, Sadowski SM, Blau JE, Jha S. 18F-FDOPA PET/CT for neuroendocrine tumors in multiple endocrine neoplasia type 1. Front Endocrinol (Lausanne). 2026 Aug 5;17:1849746. doi: 10.3389/fendo.2026.1849746. eCollection 2026.
- Derived from this study: PubMed 42484783Alkaissi H, Chuki E, Liu Y, Welch J, Bliss L, Shah N, Agarwal SK, Simonds WF, Quezado M, Sakiani S, Andresson T, Pacak K, Nilubol N, Weinstein LS, Febres-Aldana CA, Jha S. Expansion of Germline Variants in Primary Hyperparathyroidism: Fumarate Hydratase Deficiency as a Cause of Parathyroid Adenomas. Endocr Pathol. 2026 Jul 22;37(1):32. doi: 10.1007/s12022-026-09928-w.
- Derived from this study: PubMed 39946193Worthy CC, Tora R, Uttarkar CN, Welch JM, Bliss L, Cochran C, Ninan A, Kumar S, Wank S, Auh S, Weinstein LS, Simonds WF, Agarwal SK, Blau JE, Jha S. Genotype-phenotype correlation in multiple endocrine neoplasia type 1. JCI Insight. 2025 Feb 13;10(6):e176993. doi: 10.1172/jci.insight.176993.
- Derived from this study: PubMed 38174154Graf A, Cochran C, Sadowski S, Nilubol N, Simonds WF, Weinstein LS, Chang R, Jha S. Invasive Testing for Preoperative Localization of Parathyroid Tumors. J Endocr Soc. 2024 Jan 2;8(1):bvad158. doi: 10.1210/jendso/bvad158. eCollection 2023 Dec 1.
- Derived from this study: PubMed 37339334Tora R, Welch J, Sun J, Agarwal SK, Bell DA, Merino M, Weinstein LS, Simonds WF, Jha S. Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome. J Clin Endocrinol Metab. 2023 Nov 17;108(12):3165-3177. doi: 10.1210/clinem/dgad368.
- Derived from this study: PubMed 37288292Zenno A, Ramamoorthy B, Hammoud DA, Quezado M, Zeiger MA, Jha S. Case Report: Nine-year-old with parathyroid adenoma within the piriform sinus. Front Endocrinol (Lausanne). 2023 May 23;14:1171052. doi: 10.3389/fendo.2023.1171052. eCollection 2023.
- Derived from this study: PubMed 37284613Chuki E, Graf A, Ninan A, Tora R, Abijo T, Bliss L, Nilubol N, Weinstein LS, Agarwal SK, Simonds WF, Jha S. Long-Term Outcomes of Parathyroid Autografts in Primary Hyperparathyroidism. J Endocr Soc. 2023 Apr 22;7(5):bvad055. doi: 10.1210/jendso/bvad055. eCollection 2023 Mar 6.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Smita Jha, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parathyroid Cancer and Primary Hyperparathyroidism, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lynn M Bliss ((301) 435-7921, bonemineralclinic@niddk.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To identify biomarkers of the disease and associated manifestations by performing molecular profiling of available biospecimens (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04969926, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.