Parathyroid surgery for hypercalcaemic crisis in primary hyperparathyroidism—a retrospective study

Introduction

Primary hyperparathyroidism (PHPT) is a metabolic disorder resulting in hypercalcaemia (HC) from high or inappropriately normal levels of parathyroid hormone (PTH). Hypercalcaemic crisis (HCC) (adjusted calcium >3.5 mmol/L) is a rare and potentially life threatening complication that is most commonly due to sporadic PHPT (1-3). Patients with HCC are frequently symptomatic and have associated problems which have an impact and increased burden on our healthcare system and are at an increased risk of mortality. Parathyroid carcinoma is also a differential diagnosis which can also cause HCC and an increased mortality risk (1,4).

The first reported known human death attributable to HCC was reported in 1938 by Hanes (5). Since then, multiple studies have reported that early diagnosis, prompt preoperative medical management, and early parathyroidectomy for removal of the adenoma provide the best medical treatment (2,6-16). This is supported by the National Institute for Health and Care Excellence (NICE) guidelines that the surgery is in the best interest of the patient from a medical and psychological perspective, and from a health financial perspective (17). The evidence is clear that expeditious parathyroidectomy is the cornerstone of treatment of HCC secondary to PHPT, however it is far more common for patients with a diagnosis of PHPT to present with normal mild or moderate HC and to be managed conservatively prior to localisation studies and then potential surgery for removal of the adenoma. According to NICE and international endocrine society guidance the medical management of HCC due to parathyroid adenoma involves prompt, short-term interventions to rapidly reduce serum calcium levels (18-20). First-line treatment includes aggressive intravenous rehydration with 0.9% saline, followed by intravenous bisphosphonates to inhibit osteoclastic bone resorption. Calcitonin may be used for more immediate but transient reduction in calcium. In refractory cases, or in patients not suitable for surgical management cinacalcet (a calcimimetic) or dialysis may be considered. Calcimimetics like cinacalcet, reduce serum calcium by suppressing PTH and are used in non-surgical patients with PHPT and renal-related secondary/tertiary hyperparathyroidism (21,22). However, curative treatment requires parathyroidectomy as medical therapy does not address the underlying autonomous PTH secretion. Long-term medical management is avoided due to tachyphylaxis, limited efficacy, and risk of recurrent crisis and complications such as nephrocalcinosis, arrhythmias, and pancreatitis (20,23).

This retrospective study aims to analyse our own patient cohort and by looking at referral pathways and surgical treatment for patients with moderate and mild and severe PHPT we hope to improve and streamline our service for the benefit of our patients and raise this issue with service managers of a benign but often severe condition. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0022/rc).

Methods

A list of patients was collated using the help of the Trust’s Business Intelligence team. The inclusion criteria were patients who underwent parathyroid surgeries from 2018–2025. The exclusion criteria were patients with incomplete documentation, who were lost of follow-up, and patients who were treated for reasons other than PHPT such as secondary, tertiary or familial hyperparathyroidism. All patients were worked up for surgery alongside input from the endocrine medical team and were discussed at our local parathyroid multidisciplinary team (MDT) meeting. Pre-operative ultrasound (US) and sestamibi scan (Tc-99m Sestamibi Scintigraphy) were the standard pre-operative imaging with all patients being imaged prior to surgery. Intra-operative PTH serum levels were only taken at the surgeon’s discretion if there was clinical difficulty in identifying the gland. Demographic, biochemical and operative data were collected and compared between mild moderate and severe HC groups. Main outcome measurements were operative success, operative failure and recurrence.

The parathyroid surgeons at UHSussex comply with the British Association of Endocrine and Thyroid surgeons (BAETS) data collection guidance and as per widely accepted international guidelines we define operative success as a normalisation in adjusted calcium serum levels and PTH drop of by at least 50% 6 months post-surgery (19). Persistent disease was defined as increased PTH levels post-surgery. Recurrence was defined as increased serum calcium and PTH levels after 6 months of normocalcaemia (18,24). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective audit was reviewed and approved by the University Hospitals Sussex (UHS) Audit Office. As this study was conducted as a service evaluation/audit using routinely collected anonymized data, formal research ethics committee approval and individual informed consent were not required.

Statistical analysis

Statistical analysis was done using Microsoft Excel Version 16.97.2. Continuous variables were analysed using the Chi-squared test (to test relationships between categorical data) and ANOVA test (to compare three or more independent groups). A P value of P<0.05 was considered statistically significant.

Results

We retrospectively analysed the 175 patients in our inclusion data set who underwent parathyroidectomy at St Richards Hospital and Worthing Hospital in West Sussex from 2018 to the start of 2025.

We assessed patient’s demographics (Table 1), pre- and post-operative blood test values, histology, cure rates, time from referral to surgery, length of hospital stay and localisation studies within this patient cohort over this period. A total of 7 patients (4%) (4 females, 3 males) in our data set were identified as having a HCC, with a mean calcium blood level of 4.09 mm/L (range, 3.61–5.39 mmol/L). The mean age was 70 years (range, 54–81 years). They had the highest mean concentration of pre-operative PTH at 71 pmol/L (19–234 pmol/L). Forty (23%) patients (28 females, 12 males) had moderate HC with a mean pre op blood calcium level of 3.17 mmol/L (range, 3–3.47 mmol/L). Their pre-operative PTH (Table 2) was a mean of 34 pmol/L (range, 10–95 pmol/L) and their age range was from 21 to 86 years with a mean of 66 years. One hundred twenty-eight (73%) patients (100 females, 28 males) had mild HC with a mean of 2.84 mmol/L (range, 2.6–2.99 mmol/L). They had a pre-operative PTH mean of 20 (range, 7–71) pmol/L, and a mean age of 64 (range, 26–83) years (Table 1). The mean pre-operative serum adjusted calcium and PTH concentrations were significantly greater among crisis than non-crisis patients (P<0.001) (Figures 1,2). There was no statistical correlation between age, sex and level of HC. We had no peri- or post-operative deaths in the 12-month period following surgery.

Figure 1 Pre-operative PTH concentrations across mild, moderate, and severe disease groups. Boxplots display median, interquartile range, and overall distribution, with individual points representing outliers. PTH, parathyroid hormone.

Figure 2 Pre-operative adjusted calcium levels in patients classified as having mild, moderate, or severe disease. Boxplots depict median values, interquartile ranges, and data variability, with individual points indicating outliers.

Pre-operative disease related symptoms of each patient were also collected. Symptoms were reported and documented in clinic notes and letters from the initial referral to subsequent consultations (Table 3). In both the mild and moderate HC group, majority of patients experienced fatigue. However, in the severe HC groups, most patients complained of reduced mobility.

Data was also collected on pre-operative management of patients. Disease related admission was significantly different (P<0.001) with 9% (n=11) of patients with mild, 25% (n=10) with moderate, and 100% of patients (n=7) with severe HC having disease related admission pre or post operatively. The 7 mild HC patients were admitted for a mean of 0.7 days (no admission–4 days) moderate 1.35 days (no admission–16 days) and severe 11.57 days (range, 2–33 days). The use of Vitamin D supplementation and cinacalcet has also been noted for each group (Table 4).

The weight of gland in the severe hypercalcaemic group of patients was statistically significantly higher (P<0.001) with a mean of 10.28 g (range, 0.172–52 g) (Figure 3) which correlates with a higher preoperative PTH output and higher preoperative adjusted calcium levels in this group of patients. Patient’s hospital stay included post-surgical care (e.g., one patient had a parathyroid adenoma removed with a thyroid goiter and required a drain placement), medical management of HC (100% of HCC patients had pre-operative admission for medical management), and social reasons such as no one to help care for them at home post operatively. Of the 7 HCC patients, only 2 were known to have PHPT prior to admission and the remaining 5 (71%) were diagnosed during their stay having presented to the hospital with symptoms of HC. None of the HCC patients had emergency surgery and were all managed medically with subsequent referral for surgery. The HCC group of patients had to wait less time to have their surgery with a mean wait of 3.83 months (range, 0–13 months). The moderate group had a mean wait time of 6.18 months (range, 0–16 months) from referral to surgery and the mild group was 9 months (range, 0–27 months), this was a statistically significant difference (P=0.01).

Figure 3 Mean parathyroid gland weight in patients with mild, moderate, and severe disease. Bar lengths represent average gland weight (g) for each severity group, demonstrating a marked increase in gland size with increasing disease severity.

We define operative success as a normalisation of adjusted calcium to <2.59 mmol/L and normalisation of PTH to 1.6–7.2 pmol/L at 6 months post operation. Our mild HC patients had a 95% cure rate with (n=7) patients having an above normal calcium blood level at 6 months. This was 85% for moderate HC (n=6), and 100% for pre-op severe HC (n=0). This gave us an overall cure rate of 93%. There was no significant statistical variance in cure rates between the 3 HC groups (P=0.09).

We had 13 (7%) patients with a persistently high adjusted calcium at above 2.59 mmol/L (mean 2.7, range 2.6–2.91 mmol/L) and therefore these patients can be defined as having no response to surgery. Five of these patients had parathyroid adenomas, normal parathyroid tissue was found for 5 patients, and the remaining 3 patients had their histology reported as inconclusive. There was no malignant pathology on histology. Nine of the 13 patients had clear localisation from the sestamibi scans and in 4 patients this was unclear. 1 patient went on to have another sestamibi scan which was also inconclusive. Of the 4 patients who had no clear localisation on the sestamibi scan, there was also no clear localisation on the US scan either. These four patients also had redo US scans, which again did not localise any pathology.

Of the 13 patients who had persistently high adjusted calcium at 6 months, 7 of these also had persistently high PTH, the other 6 had a drop in PTH of >50%. The average of adjusted calcium was 2.76 mmmol/L at 6 months (range, 2.63–2.91).

There was no statistical significance in the success rate of operation and level of preoperative HC (P=0.11). These 13 patients had an average of 1.43 glands removed during the surgery (range, 1–4 glands).

For this group set of 13 patients, whilst they had persistently high calcium blood levels at 6 months, by 1 year 7 of these patients had returned to normocalcaemia levels and can therefore be classed as operative success. 1 patient had a potential second parathyroid lesion leading to a diagnosis of parathyroid hyperplasia, 3 had no symptoms and did not require further medical management, and 2 remained under endocrine care with ongoing medical management of their persistent HPT.

Six out of the 7 severe HC patients were operated on within 8 weeks following their parathyroid MDT. One patient had to wait 4 months. Upon further investigation, their surgery was delayed due to industrial action by Resident Doctors’ which is still occurring intermittently since 2022. All 7 of these patients had admissions prior to their surgery for symptomatic management with intravenous (IV) fluids and bisphosphonates. Four of these patients were prescribed cinacalcet as per Table 4. All severe HC patients underwent US neck which showed clear localisation. Six of these patients had sestamibi with clear localisation. The one patient who did not have sestamibi had very clear localisation on their US.

Regarding surgical complications, 2 mild HC patients (1%) had weakness in voice following parathyroidectomy. One patient had left vocal cord palsy on flexible nasal endoscope (FNE) and was referred on for injection thyroplasty, the other patient’s voice recovered after a few months. In the moderate HC groups, 1 patient had right vocal cord palsy and was referred to Speech And Language Therapy. There were no voice complications in the severe group. Another surgical complication investigated was Return to Theatre. One patient in the mild group (1%) was brought back to theatre for Examination under Anaesthesia with swelling concerns. 1 patient in the moderate group (1%) was brought back for bleeding concerns. No Return to Theatre was identified for the HCC group.

Medical complications, no patients in this cohort had reported Hungry Bone Syndrome which can be defined as having adjusted calcium <2.1 mmol/L. However, the Trust’s range of normal adjusted calcium is 2.2–2.6 mmol/L. Three patients (2%) had post-operative adjusted calcium with values between 2.1–2.2mmol/L after 6 months. Only 1 of these 3 patients had symptomatic hypocalcemia and is being currently treated with oral calcium and vitamin D supplements.

Discussion

This study demonstrates that HCC patients exhibited significantly higher pre-operative calcium and PTH concentrations, and had significantly larger glands, consistent with other studies (25,26). Despite their more severe biochemical profile, our cure rates in this cohort were 100% of HCC cases achieving normocalcaemia at 6 months, compared with 95% in the mild group and 85% in the moderate group. Time to surgery was significantly shorter (mean of 3.83 months, range, 0–13 months, P=0.01) for patients with severe HC, reflecting prioritisation of these high-risk and more symptomatic patients within our service, and supports the finding emphasised in guidelines (18,19) that expeditious parathyroidectomy following medical stabilization yields excellent outcomes even in the most biochemically severe cases—particularly important due to current service pressures and waiting list backlogs. The overall cure rate of 93% is comparative to published literature (18,19).

Pre-operative localisation findings emerged as a key finding in the small group with persistent: 69% (9/13) had ‘positive’ sestamibi studies that did not correlate with operative or histological findings, and four had no localisation of the adenoma on either sestamibi or US. This discordance is well recognised—particularly in multi-gland disease—and underscores the value of a structured imaging algorithm and selective use of intra-operative PTH (ioPTH) monitoring where localisation is equivocal or discordant (18,27,28).

This study reinforces the known clinical burden associated with HCC. All HCC patients required admission and prolonged inpatient management prior to surgery, with significantly longer lengths of stay compared to mild and moderate cases. This is consistent with previous reports that HCC is associated with increased morbidity, healthcare resource utilisation, and diagnostic delay (3,29). Our finding that five of seven HCC patients were only diagnosed during their emergency admission underlines the importance of clinician awareness and early referral pathways between acute medicine/endocrinology and parathyroid surgeons.

The absence of parathyroid carcinoma in this cohort is reassuring but contrasts with some published literature where carcinoma accounts for up to 2–5% of crisis presentations (1,4,30). In this dataset, adenomas accounted for the vast majority of cases which is in line with UK experience (30).

Limitations include the retrospective design, single-centre setting, and reliance on electronic documentation. Use of ioPTH was discretionary rather than protocolised, and long-term follow-up beyond 12 months was not uniform, limiting formal recurrence estimates. Future work should incorporate prospective data capture, and consideration of predefined imaging/ioPTH pathways. Furthermore, the study period overlapped with the coronavirus disease 2019 (COVID-19) pandemic, which disrupted elective surgery pathways and may have influenced waiting times and sample size.

Expanding further on the wait times, overall, our data confirms prioritisation of severe HC patients over mild and moderate patients. Having said this, we see patients in the United Kingdom (UK) waiting longer for elective surgeries compared to other European countries. There are several factors attributing to this. The NHS uses a centralised waiting system where patients are added to this queueing system until an appointment becomes available in the hospital. Appointment availability is limited by hospital staffing and workforce size and theatre availability. If a global incident happens, i.e., COVID-19, then pressures will mount further, meaning patients end up waiting months even years to see a specialist. Since COVID-19, we are still trying to clear the backlog. NHS hospitals have tight targets to meet in regard to operating for emergency and cancer cases. Parathyroidectomies are viewed as elective as they can be managed medically. This means these cases can be cancelled at the last minute to accommodate for the emergency/cancer cases. Of course, PHPT patients will be prioritised if they don’t respond to treatment.

Another consideration of this project is that all 175 patients were operated on two Oral and Maxillofacial Consultant Surgeons who work part-time within this unit. The implication of this is the surgeries heavily depend on surgeon availability. Unfortunately, this further adds to the long wait which could negatively affect surgical outcomes. All this can explain the long wait some of our patients experienced.

Conclusions

Parathyroidectomy for PHPT achieves high cure rates across all severities of hypercalcaemia. Patients presenting with hypercalcaemic crisis, despite more severe biochemical disease, were prioritised for earlier surgery and achieved excellent outcomes, with 100% cure at 6 months. Overall cure was 93% at 6 months and 96.6% at 12 months, aligning with BAETS national benchmarks. Discordant localisation was associated with the small proportion of early treatment failures, highlighting the importance of accurate pre-operative imaging and multidisciplinary management. These findings support timely surgical intervention for patients with hypercalcaemic crisis and reinforce the need for streamlined referral pathways to facilitate prompt treatment.

Acknowledgments

The authors thank Marwan Khataan, a Senior House Officer in the department, for his assistance with data collection.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0022/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0022/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0022/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0022/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective audit was reviewed and approved by the University Hospitals Sussex (UHS) Audit Office. As this study was conducted as a service evaluation/audit using routinely collected anonymized data, formal research ethics committee approval and individual informed consent were not required.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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