# Parathyroid Tumor Clonal Status as a Biomarker in Primary Hyperparathyroidism

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $634,474

## Abstract

Project Summary/Abstract
Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in ambulatory patients, and
may lead to bone loss and fracture, cardiovascular disease, kidney stones, and neurocognitive impairment (1).
PHPT is the third most common endocrine disorder with an annual incidence between 34 to 120 per 100,000
person-years that is rising, especially among postmenopausal women. Since the first description of PHPT and
its surgical treatment in the 1920s, the pathogenesis of PHPT has been viewed simply: A parathyroid tumor
develops from a single transformed clone (i.e. monoclonal) that expands and secretes excessive PTH causing
hypercalcemia and the symptoms and sequellae of PHPT. This paradigm predicts that PHPT develops from a
single tumor (single gland disease, SGD) and that removal of this single tumor by parathyroidectomy (PTX) cures
the disease. Although conceptually attractive, this simple approach does not explain several observations
including: 1. The presence of multiple gland disease (MGD) in up to 20% of PHPT patients; 2. The observation
that PTH remains elevated following PTX in up to 30% of patients; 3. The reality that symptoms and sequellae
of PHPT often do not improve following PTX; and 4. The development of recurrent PHPT in up to 15% of patients
(2). These observations, combined with data from our laboratory describing the molecular heterogeneity of
parathyroid tumors have led us to suspect that PHPT may represent several different diseases that can be
distinguished based on characteristics of the parathyroid tumor. The foundation for the proposed work has been
published by our group in two studies. Our first study characterized isolated parathyroid cells from parathyroid
adenomas in PHPT and showed that a significant proportion (40%, 5/14) of these tumors were comprised of
multiple clones (i.e. polyclonal). Our second study of 119 patients confirmed that up to 46% of PHPT patients
have polyclonal tumors and that the clonal status (i.e. monoclonal versus polyclonal) of the tumor predicts MGD
that is often missed at surgery. These findings support the premise that parathyroid tumor clonal status reflects
different types of PHPT with different etiologies, disease presentation and treatment outcomes. We now propose
to characterize PHPT patients with these tumor types and test the novel hypothesis that PHPT can better be
understood and treated by classifying the disorder in terms of the clonal status of the underlying
parathyroid tumor.

## Key facts

- **NIH application ID:** 9828630
- **Project number:** 5R01CA228399-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** JOHN A. OLSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $634,474
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828630

## Citation

> US National Institutes of Health, RePORTER application 9828630, Parathyroid Tumor Clonal Status as a Biomarker in Primary Hyperparathyroidism (5R01CA228399-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9828630. Licensed CC0.

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