Upfront Ultrasound for Preoperative Localization in Primary Hyperparathyroidism

A Protocolled Implementation of Upfront Ultrasound (Sequential Pre-operative Imaging) in Primary Hyperparathyroidism in the Region of Southern Denmark

Primary hyperparathyroidism is caused by overactive parathyroid glands, leading to elevated calcium levels in the blood. The standard preoperative imaging includes both a radiation-based imaging modality and conventional ultrasound. However, ultrasound alone is a faster, safer, and more patient-friendly alternative. This study evaluates an upfront ultrasound approach, where patients undergo ultrasound first, and only those with certain findings proceed directly to surgery without additional imaging. Patients with uncertain findings proceed to additional imaging. The study is designed as a prospective cohort with a non-inferiority analysis, aiming to confirm whether upfront ultrasound can achieve an acceptable diagnostic sensitivity. If successful, this approach could reduce patient burden, minimize radiation exposure, and optimize healthcare resources

Study Overview

• Status: Completed
• Conditions: Primary Hyperparathyroidism

Detailed Description

This study evaluates the implementation of a stepwise approach using upfront ultrasound for localizing pathological parathyroid glands in patients with primary hyperparathyroidism (PHPT).

PHPT is caused by overactive parathyroid glands, leading to excessive amounts of calcium in the blood, which can result in complications such as kidney stones, osteoporosis, cardiovascular disease, and neurological symptoms. The standard preoperative imaging process currently includes both nuclear medicine scans and ultrasound. However, nuclear imaging is time-consuming, exposes patients to radiation, and may not always provide definitive results.

The proposed approach prioritizes ultrasound as the initial localization tool, with additional imaging reserved for cases where ultrasound findings are inconclusive. This method has the potential to reduce unnecessary hospital visits, minimize radiation exposure, and streamline the diagnostic process. The study aims to ensure that this approach maintains high sensitivity for the localization of pathological parathyroid glands, with a target sensitivity of at least 89.5% for correctly identifying diseased parathyroid glands.

Designed as a prospective cohort study, the project will assess patients using ultrasound first, assigning confidence scores (0-3) to determine whether further imaging is necessary. A confidence-score of 3 indicates a high diagnostic confidence. To gain a score of 3, the potential parathyroid adenoma must meet all predefined criteria, i.e. hypoechogenicity, well-defined margins, location at the anatomically expected position, a polar feeding vessel, and a vascular arc. A diagnostic-score of 2 reflects moderate suspicion, where one or two of these key features are missing. A diagnostic-score of 1 suggests low suspicion, typically characterized by a poorly defined structure with no vascular features. Finally, a diagnostic-score of 0 means that no potential adenoma was detected.

Postoperative findings will confirm the accuracy of the preoperative imaging with the histopathological result of the surgically removed specimen(s) combined with biochemical cure at 6 months as the reference standard.

The study aims to benefit both patients and society as it intends to decrease patient exposure to radiation, reduce costs, and reduce the time patients have to take off from work for the purpose of preoperative imaging. One less hospital visit will also reduce the pollution caused by an extra day of transportation to and from the hospital.

• Study Type: Observational
• Enrollment (Actual): 99

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients 18 years and older with primary hyperparathyroidism referred to the Department of ORL, Head and Neck Surgery at Odense University Hospital for parathyroidectomy.

Description

Inclusion Criteria:

• Patients 18 years and older with primary hyperparathyroidism referred to the Department of ORL, Head and Neck Surgery at Odense University Hospital for parathyroidectomy.

Exclusion Criteria:

• Other causes of hypercalcemia
• Persistent or recurrent hyperparathyroidism.
• Previous surgery to the thyroid or the parathyroid glands.
• Inability to read/speak Danish

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of the sequential imaging regimen (upfront ultrasound)	The primary outcome measure is the sensitivity of the sequential imaging regimen (upfront ultrasound) for localizing one or more pathological parathyroid glands to the correct quadrant of the neck. The reference standard is histopathology combined with biochemical cure.	No residual disease 6 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome re-calculated for a theoretical cut-off at "diagnostic confidence score = 2"	The primary endpoint re-calculated with a theoretical cut-off at "diagnostic confidence score=2" as the criteria that leads to surgery without additional imaging.	No residual disease 6 months after surgery
Primary outcome re-calculated for a theoretical cut-off at "diagnostic confidence score = 1"	The primary endpoint re-calculated with a theoretical cut-off at "diagnostic confidence score=1" as the criteria that leads to surgery without additional imaging.	No residual disease 6 months after surgery
Per gland sensitivity, specificity, positive and negative predictive value of the sequential imaging regimen	Per gland sensitivity, specificity, positive and negative predictive value of the sequential imaging regimen	6 months after surgery
Patients that didn't need supplementary imaging	Fractions of patients that didn't need supplementary imaging.	6 months post-surgery
Surgery duration	Discrepancy between expected and actual duration of surgery.	Immediately after surgery
Unnecessary supplementary imaging	Fraction of unnecessary supplementary imaging	6 months post-surgery
Unnecessarily explored quadrants	Number of unnecessarily explored quadrants	6 months post-surgery
Complication rate	Complication rate in terms of recurrent nerve paralysis, post-operative hemorrhage, or permanent hypoparathyroidism	From surgery until one year after surgery
Cure rate	No hyperparathyroid hypercalcemia	No residual disease 6 months after surgery
Cost	Cost of ultrasound, parathyroid scintigraphy and parathyroid choline PET/CT	Through study completion, from baseline to 6 months post-surgery
Confounding	Is the sensitivity influenced by differences in patient age, sex, BMI, adenoma weight, adenoma depth, adenoma diameter, multiple gland disease, preoperative ionized calcium and preoperative PTH?	Baseline to 6 months post-surgery

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Investigators: Principal Investigator: Sanne H Michaelsen, MD, Odense Universitetshospital; Study Chair: Viveque Egsgaard, MD, PhD, Odense Universitetshospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Actual): September 18, 2025
• Study Completion (Actual): September 18, 2025

Study Registration Dates

• First Submitted: March 13, 2025
• First Submitted That Met QC Criteria: July 7, 2025
• First Posted (Actual): July 16, 2025

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Ultrasound; Endocrine System Diseases; Parathyroid Diseases; Hyperparathyroidism; Hyperparathyroidism, Primary; Preoperative Procedures; Preoperative Localization
• Additional Relevant MeSH Terms: Endocrine System Diseases; Parathyroid Diseases; Hyperparathyroidism; Hyperparathyroidism, Primary; Endocrine System Diseases; Parathyroid Diseases
• Other Study ID Numbers: Acadre project ID: 23/36379; A5992 (Other Grant/Funding Number: OUH Fund for Pre-graduate Stipends)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No