Short summary

The purpose of this project is to examine, in a non-inferiority study, whether a sequential algorithm applying conventional ultrasound as the primary imaging modality, complemented by further imaging only in case of a nonlocalizing US examination, could be non-inferior to theoretical results from the same department in patients with primary hyperparathyroidism.

Rationale

Primary hyperparathyroidism (PHPT) is an endocrine disorder in which plasma calcium levels are abnormally high due to an autonomous overproduction of parathyroid hormone (PTH) by one or more parathyroid glands. Most patients suffer from a single adenoma, while a minority suffer from double adenomas or from multiple gland hyperplasia. The typical symptoms of the disease are renal stones and bone demineralization with the risk of developing pathological fractures. Other manifestations may be proximal muscle weakness, pancreatitis, hypertension, depression, anxiety, and neurocognitive deficits. The only definite cure for PHPT is surgical excision of all abnormal parathyroid glands. For years, the surgical approach to PHPT was bilateral neck exploration with identification and evaluation of all parathyroid glands prior to removal of those deemed pathological. In recent years, however, minimally invasive surgical approaches that target only one side or quadrant of the neck are increasingly used. A minimally invasive parathyroidectomy (MIP) is made possible by preoperative parathyroid localization imaging along with intraoperative measurement of parathyroid hormone levels (ioPTH), which should drop at least 50% compared to intraoperative baseline values ten minutes after the pathological gland has been resected, at which point no further surgical exploration is necessary. For a focused MIP to be possible, preoperative imaging must correctly localize all hyperactive parathyroid glands. This can be difficult, especially in patients with small adenomas or concurrent nodular thyroid disease. In the Region of Southern Denmark, all patients with PHPT undergo surgery at Odense University Hospital, which is a high-volume tertiary referral center for PHPT. In 2023, the available preoperative localization techniques are SUS, dual-tracer 99mTechnetium-pertechnetate/ 99mTechnetium-sestamibi subtraction scintigraphy with 99mTechnetium-sestamibi SPECT/CT (dtSM SPECT/CT), and radiolabeled choline PET/CT. A recent prospective cohort study from Odense University Hospital found that SUS was non-inferior to dtSM SPECT/CT, with a patient-based sensitivity of SUS of 81.4% compared to 79.1% for dtSM SPECT/CT. The study argued that pre-operative imaging should be sequential instead of parallel and reported that a theoretical algorithm applying conventional ultrasound as the primary imaging modality, complemented by dtSM SPECT/CT only in case of a non-localizing US examination, would have resulted in a per-patient sensitivity of 89.5% while reducing imaging costs by 73% and markedly reducing the strain on nuclear medicine resources. Furthermore, the use of sequential imaging would spare selected patients from unnecessary procedures that are both time consuming and involve radiation. We wish to examine, in a non-inferiority study, whether the per-patient sensitivity of the new sequential imaging regimen remains non-inferior to the theoretical results.

Description of the cohort

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

Data and biological material

Age, gender, body mass index, smoking status, alcohol consumption, co-morbidity, parathyroid hormone levels, ionized calcium levels, vitamin D levels, eGFR, histopathological diagnosis of intraoperatively excised specimens, concomitant thyroid pathology, prior neck surgery, pre-operative symptoms, results of supplementary imaging modality (if performed), surgical record for the parathyroidectomy, duration of surgery, duration of hospital stay, surgical complications, weight, size, depth, and localization of pathological parathyroid glands. The parathyroid hormone and ionized calcium levels from the standard control at the department of endocrinology/blood tests approximately 6 months after surgery.

Collaborating researchers and departments

Department of Nuclear Medicine, Odense University Hospita

• Paw Christian Holdgaard, MD
• Sys Vestergaard, MD

Department of Otorhinolaryngology, Head and Neck Surgery, Odense University Hospital

• Christian Godballe, MD, PhD
• Helle Døssing, MD, PhD
• Marie Westergaard-Nielsen, MD, PhD
• Mette Bay, MD
• Sanne Høxbroe Michaelsen, MD
• Viveque Egsgaard Nielsen, MD, PhD