ORIGINAL RESEARCH |
https://doi.org/10.5005/jp-journals-10002-1476 |
Focused Parathyroidectomy in Primary Hyperparathyroidism: Experience in a Tertiary Care Center of North India
1Department of General Surgery, Endocrine and Breast Surgery Division, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2Department of Endocrine Surgery, Fortis Hospital Shalimar Bagh, New Delhi, India
3Department of Endocrinology, Sir Ganga Ram Hospital, Delhi, India
4Department of Radiology, Sri Balaji Action Medical Institute, Paschim Vihar, Delhi, India
Corresponding Author: Satyajit Kundu, Department of General Surgery, Endocrine and Breast Surgery Division, Postgraduate Institute of Medical Education and Research, Chandigarh, India, Phone: +91 9007916623, e-mail: satyajitkundu93@gmail.com
Received: 24 December 2024; Accepted: 16 January 2025; Published on: 06 March 2025
ABSTRACT
Background: Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by dysregulated calcium homeostasis. Currently, there is a growing trend toward diagnosis via routine biochemical screenings. Surgery remains the only curative treatment, with minimally invasive techniques like focused parathyroidectomy (FP) gaining popularity. However, postoperative hypocalcemia, including Hungry Bone Syndrome (HBS), remains a major concern.
Aim: This study seeks to evaluate the surgical outcomes of FP in patients with PHPT, analyze the usefulness of intraoperative parathyroid hormone (IOPTH) assessment, and evaluate the efficacy of postoperative management with calcium and vitamin D supplements.
Materials and methods: One hundred forty-two patients with sporadic PHPT who underwent parathyroidectomy at Fortis Hospital Shalimar Bagh, Delhi, between March 2018 and December 2023 were participants in a retrospective analysis. The abnormal parathyroid glands were identified by high-resolution neck ultrasonography and SestaMIBI scans used in preoperative imaging. After 15 minutes of gland removal, IOPTH was measured and compared with the preoperative PTH levels. Supplementing with calcium carbonate and calcitriol was part of the postoperative care. For a minimum of 6 months, patients were monitored to track serum calcium levels and recurrence rates.
Results: One hundred eighteen of the 142 patients (83.1%) who had concordant imaging underwent successful FP. The average serum calcium level was 11.5 ± 1.2 mg/dL, and the average preoperative parathyroid hormone (PTH) level was 230.2 ± 96 pg/mL. In 17.6% of cases, patients experienced transient hypocalcemia, and 4.9% experienced HBS. There were two recurrent cases, but the overall cure rate was 98.6%.
Conclusion: FP is a highly effective surgical treatment for PHPT, with a success rate similar to standard bilateral exploration. Routine IOPTH assessment is indicated to improve patient outcomes. Empirical calcium and vitamin D treatment after surgery reduced the prevalence of hypocalcemia and HBS. This study emphasizes the possibility for more widespread use of FP and IOPTH in developing nations.
Keywords: Concordant imaging, Focused parathyroidectomy, Hungry bone syndrome, IOPTH monitoring, Primary hyperparathyroidism
How to cite this article: Kundu S, Aggarwal V, Aggarwal A, et al. Focused Parathyroidectomy in Primary Hyperparathyroidism: Experience in a Tertiary Care Center of North India. World J Endoc Surg 2024;16(2):36–41.
Source of support: Nil
Conflict of interest: None
INTRODUCTION
Primary hyperparathyroidism (PHPT) is an endocrinopathy characterized by dysregulated calcium homeostasis and is typically a symptomatic condition with ”stones, bones, moans, and groans.” Nowadays, PHPT is increasingly being identified as a result of hypercalcemia discovered during normal biochemical screening, as reported in Western literature. However, Indian physicians continue to face a mixture of both types of presentations. Felix Mandl is credited with the first successful parathyroidectomy conducted in Vienna in 1925, and surgery has been the sole curative treatment available.1 The initial procedure involved bilateral neck exploration and the removal of a single enlarged gland.
Lately, minimally invasive surgical methods have gained popularity.2 The completeness of parathyroid surgery is determined by intraoperative measurement of parathyroid hormone (IOPTH), and not the actual gland visibility. Preoperative imaging is essential to diagnose aberrant parathyroid glands. Parathyroidectomy is effective in greater than 95% of PHPT patients.3,12 These minimally invasive focused parathyroidectomy (FP) have a success rate of more than 95%, which is similar to bilateral exploration.13,17
For patients with PHPT, hypocalcemia is a frequent postoperative complication. Many studies have found that the incidence of postoperative hypocalcemia following PHPT ranges from 4.1 to 21.3%,18,20 indicating that patients are at significant risk of developing postoperative hypocalcemia. Hungry bone syndrome (HBS) is characterized by severe hypocalcemia that can last for an extended amount of time.
AIMS
In this article, we will present our experience in terms of surgical treatment of PHPT in Indian patients undergoing FP in a corporate hospital. This study was also conducted to determine the most cost-effective method of performing IOPTH by decreasing the number of samples. We will also evaluate the postoperative management of such patients by repletion with calcium and vitamin D.
MATERIALS AND METHODS
Study Design
A retrospective analysis of patients diagnosed with PHPT and who underwent treatment in the Department of Endocrine Surgery at Fortis Hospital Shalimar Bagh, Delhi, between March 2018 and December 2023, was included in this study.
Inclusion and Exclusion Criteria
The inclusion criteria were: (1) patients diagnosed with sporadic PHPT, (2) underwent FP for PHPT, (3) minimum 6 months follow-up period, and (4) patients ≥18 years old.
The exclusion criteria were: (1) patients with discordant imaging, (2) patients diagnosed with multiple endocrine neoplasia (MEN), (3) secondary and tertiary hyperparathyroidism cases, and (4) patients having thyroid lesions also.
Preoperative Biochemical Evaluation
Prior to surgery, a thorough history and clinical examination were performed on each patient. Samples of blood were drawn following an overnight fast. Measurements were made of the serum activity of alkaline phosphatase as well as the blood urea nitrogen, albumin, creatinine, total calcium, inorganic phosphate, and 25-hydroxyvitamin D concentrations. Payne’s formula {calcium concentration (mg/dL) + [4 – albumin (gm/dL)] × 0.8} was used to get the corrected level of calcium. A chemiluminescence test was used to assess the preoperative and IOPTH levels.21
Preoperative Imaging
We used SestaMIBI scan and high-resolution ultrasound (USG) neck as part of our preoperative imaging protocol. A single radiologist performed the high-resolution ultrasound on the neck, and any outside reports were cross-checked by our institute’s radiologist. Finding the gland in the same location on both ultrasound and a SestaMIBI scan is known as concordant imaging. When two imaging modalities show different gland locations, this is known as discordant imaging. The study excluded the patients who had discordant imaging.
The bone mineral density (BMD) of all patients with musculoskeletal symptoms, such as bone pain or fractures, was evaluated using dual-energy X-ray absorptiometry (DEXA). The BMD T or Z-score was calculated using the simply calculated osteoporosis estimation (SCORE) and compared to the mean BMD of a young adult in good health.
Surgical Procedure and Intraoperative Parathyroid Hormone
A concordant finding on imaging allowed us to do FP under general anesthesia (GA). An incision of <2.5 cm was made on the side of the offending gland, followed by its removal and then sending it for frozen section.
Blood was drawn from a peripheral vein 15 minutes after the gland was excised. IOPTH was sent in an EDTA vial and run by a chemiluminescence assay at our central lab, thereby saving time and cost. First, we see the diagnostic PTH value, and if it’s <500 pg/mL, IOPTH fall by 50% as compared to the preoperative value and also in the normal range (<65 pg/mL), it indicated a successful removal of all the diseased parathyroid glands.21,22 If both criteria were not met, a BNE was done. If the diagnostic PTH value is >500 pg/mL, and there is a decrease in the IOPTH by 50% from the preoperative value, FP was the surgical endpoint; otherwise, BNE was done. The summary of the IOPTH assay and further plan for surgery is described in Figure 1. An analysis of the data was done to see how accurate the IOPTH was in determining the success of FP.
Fig. 1: Summary of IOPTH and approach during parathyroid surgery
Postoperative Management and Follow-up
All patients were started on oral calcium carbonate 1250 mg (providing elemental calcium of 500 mg) 6 tablets daily and calcitriol 0.25 µg 4 tablets daily. The doses were tapered by 1 tablet each on every 3rd day. Calcium carbonate was tapered to two tablets twice a day, and it was continued for 3 months. S. ALP was measured at that time, and if it was in the normal range, calcium carbonate tablets were stopped. Calcitriol tablets were stopped 2 weeks after gradually tapering them off. Details of calcium and calcitriol supplementation in the postoperative period are given in Figure 2.
Fig. 2: Postoperative management and follow-up
Postoperative calcium levels were assessed the day following surgery, 1 week later, 3 months later, and 6 months later. Postoperative serum calcium levels and cure rates were the main outcomes. Normocalcemia, or a blood calcium level below 10.5 mg/dL 6 months or more after surgery, was the definition of curative parathyroidectomy. Six months following surgery, hypercalcemia (i.e., serum calcium > 10.5 mg/dL) was considered as recurrence.23,24
Statistical Analysis
All data are represented as mean ± SD and percentages. GraphPad Prism was used for all statistical analyses. Descriptive statistics were used for the analyses.
RESULTS
During the previously stated study period, our center operated on 239 hyperparathyroidism patients, 208 of whom had sporadic PHPT. One hundred forty-two patients had concordant preoperative imaging by USG and SestaMIBI and therefore underwent FP. Table 1 displays the patients’ clinical details. The average age of presentation was 49.5 ± 14.3 years. The study population showed a female dominance, with the male to female ratio being 1:3.06. A large proportion of the patients (38.7%) were diagnosed incidentally during screening tests. Sixty-one point three percent of the patients were symptomatic at the time of presentation, with the majority of them presenting with musculoskeletal symptoms (26.8%) as their presenting complaint (Table 2). The symptomology of the patients is given in Table 2. Mean preoperative PTH was 230.2 ± 96 pg/mL, and the average serum calcium level was 11.5 ± 1.2 mg/dL.
| Age | 49.5 ± 14.3 |
| BMI | 26.2 ± 6 |
| Gender ratio (F:M) | 3.06:1 (107:35) |
| Serum corrected calcium (8.5–10.5 mg/dL) | 11.5 ± 1.2 |
| Serum phosphate (2.5–4.5 mg/dL) | 3.3 ± 0.7 |
| PTH (15–65 pg/mL) | 230.2 ± 96 |
| Serum creatinine (0.5–1.5 mg/dL) | 0.9 ± 0.5 |
| 25-OH vit D (30–50 ng/mL) | 31.4 ± 10 |
| Serum ALP (30–130 U/L) | 115 ± 15 |
| No. of patients with T score <2 | 31 (21.8%) |
| Asymptomatic | 55 (38.7%) |
| Musculoskeletal system | 38 (26.8%) |
| Urinary system | 21 (14.8%) |
| Digestive system | 6 (4.2%) |
| Psychiatric symptoms | 9 (6.3%) |
| Both musculoskeletal and urinary system | 13 (9.2%) |
Under GA, 118 patients had open FP (83.1%), and in 24 patients, FP was converted to BNE (16.9%). No patients were found to have infections or bleeding (requiring reexamination). Nonetheless, two patients had transient recurrent laryngeal nerve (RLN) palsy, which resulted in vocal changes in the initial postoperative phase. Their voice recovered in 2 months postoperatively. There are no recorded cases of vocal cord paralysis in patients. There was transient hypocalcemia in 25 patients (17.6%), and they were managed successfully by oral calcium supplementation. Seven patients (4.9%) experienced HBS, which was effectively managed with the administration of calcium by intravenous and oral routes. The average length of hospital admission was 1.7 ± 1 days. Our current protocol is to perform the surgery on a day care basis or discharge patients the next day after surgery. On histopathology, 138 patients were found to have parathyroid adenoma, while 2 patients were diagnosed with hyperplasia, and 4 patients had an atypical tumor (Table 3). The surgical outcomes after FP are enumerated in Table 3.
| Surgical outcomes | N = 142 |
| Bleeding | 0 |
| Infection | 0 |
| Temporary RLN palsy | 2 (1.4%) |
| Permanent RLN palsy | 0 |
| Transient hypocalcemia | 25 (17.6%) |
| Hungry bone syndrome | 7 (4.9%) |
| Duration of hospital stay (days) | 1.7 ± 1 |
| Recurrence within 6 months | 2 (1.4%) |
| Success rate | 140 (98.6%) |
| Hyperplasia/adenoma/atypical tumor/carcinoma | 2/136/4/0 (1.4%/95.8%/2.8%/0) |
Mean postoperative serum calcium and ALP levels were enumerated in Table 4. Within 6 months after a curative parathyroidectomy, two patients developed PHPT recurrences, and both of these patients were diagnosed with hyperplasia on their histopathological examination. As a result, the total cure rate was 98.6% (Table 3).
| Post-op day | Calcium | ALP |
|---|---|---|
| 1st day | 9.6 ± 0.7 | |
| 1 week | 9.3 ± 0.5 | |
| 1 month | 9.2 ± 0.6 | |
| 3 months | 9.4 ± 0.7 | 92 ± 9 |
| 6 months | 9.4 ± 0.5 |
DISCUSSION
Fewer patients with moderate to severe preoperative serum calcium levels and clinically significant PHPT have been observed, since serum calcium was monitored routinely in many countries worldwide. Moreover, a greater number of asymptomatic (or with minimal symptoms) PHPT patients with normal or slightly increased preoperative calcium levels have been identified.25,26 Our data indicate a trend toward a higher proportion of asymptomatic patients, particularly in affluent people visiting corporate hospitals.
Accurate preoperative identification of the aberrant gland is crucial for a successful FP, which has become the gold standard of treatment for a localized abnormality in PHPT. With a success rate of over 95%, this technique has decreased intraoperative exploration, thereby reducing the trauma caused, as well as providing excellent postoperative outcomes, including enhanced cosmetic outcomes and less pain. FP has a failure rate of 1–5%, which is comparable to that of BNE.27 FP had a 98.6% success rate and a 1.4% recurrence rate in our center, which is comparable to results shown in previous studies.
Preoperative imaging, namely one functional (99mTc SestaMIBI scan) and one anatomical (USG), is required for FP. Finding aberrant parathyroid tissue accurately is the aim of this imaging, and it can minimize needless searching and facilitate minimally invasive surgery. Dual imaging has a higher sensitivity than separate tests. When FP is performed on patients who have only one positive imaging, the success rates are significantly lower than when FP is performed after concordant imaging. Out of 142 individuals in our series with concordant imaging, 118 underwent FP. Twenty-four patients underwent BNE because, in 7 patients, there were intraoperative surprises (6 patients with abnormal glands in different locations, 1 patient with a stony hard gland suspicious of malignancy), and in 17 patients, the IOPTH did not meet the criteria as elaborated in Figure 1.
Excellent Outcome after Intraoperative Parathyroid Hormone-guided Parathyroidectomy
In order to confirm that all abnormal glands are removed during surgery, IOPTH is still a crucial adjunct. Approximately, 5% of patients with concordant imaging will experience unexpected intraoperative observations, such as an adenoma in a different location.28 The Miami criteria, which include a drop in IOPTH level by >50% relative to the highest pre-incision level recorded 10 minutes after removal of the active gland and have an accuracy of 98%, is another element that contributes to the success of FP.29,31 Nevertheless, some studies have observed that this could be deceptive for patients with multiglandular disease.32,33 Errors of up to 16% have also been documented as a result of false-positive and false-negative results.34 According to certain theories, IOPTH is a reliable indicator of prognosis for patients with localized abnormalities in the parathyroid gland. In these patients, a targeted surgical approach can successfully remove the parathyroid gland without the need for an IOPTH test, and it fails when it matters most, that is, in patients with multiglandular disease.35
To counter this drawback, we have introduced a modification wherein we test IOPTH 15 minutes after gland excision. First, we observe the diagnostic PTH value, and if it’s <500 pg/mL, a 50% fall in IOPTH compared to the preoperative value, and also within the normal range (<65 pg/mL), it indicates successful removal of all the diseased parathyroid glands. If both criteria are not met, a BNE was done. If the diagnostic PTH value is >500 pg/mL, and there is a decrease in the IOPTH by 50% from the preoperative value, FP was the surgical endpoint, and otherwise, BNE was done.
Due to financial limitations in India, where IOPTH is only routinely utilized in a limited number of facilities, time and cost-saving measures are always being sought. IOPTH may be made less expensive with the help of two changes. Reducing the quantity of samples is one approach. PTH level is tested once—at the time of presentation preoperatively and again in the intraoperative period, 15 minutes after gland excision. Using the central laboratory to get results quickly is the second change that might be implemented. Afterward, rapid PTH assays were integrated into conventional immunoanalyzers, enabling their execution at central laboratories. These quick IOPTH assays provide diagnostic concordance in terms of patient outcomes and strong analytic correlations with conventional PTH results.36 The IOPTH test can be set up at a central laboratory with minimal expenses. The cost of reagents is low, and lab staff may conduct IOPTH testing along with running other tests.37,39
Post-op Follow-up and Long-term Results
If a patient’s postoperative serum calcium level returned to normal and stayed there for 6 months, the patient was considered clinically cured, and the surgery was considered a success.
PTH overproduction causes osteodystrophy and bone loss in PHPT patients.40,41 Following parathyroidectomy, there is a noticeable decrease in osteoclast activity, a reduction in osteoblast activity, a bone formation rate greater than the bone degradation rate, blood-to-bone calcium transfer, and postoperative hypocalcemia.42
The literature states that 12–30% of people experience HBS following parathyroidectomy. Many risk factors, including advanced age, elevated serum PTH and calcium levels prior to surgery, increased turnover of bone, skeletal deformities, low vitamin D states, and a sharp drop in serum PTH levels following the operation, are likely to play a role in the development of HBS.43,44 To prevent postoperative HBS, our protocol of giving calcium carbonate and calcitriol empirically to all patients has led to decreased numbers of postoperative hypocalcemia and HBS in our study compared to traditional literature.
The single-center design of this study may introduce bias into patient selection, and it failed to account for potential single-center effects. The current study did not evaluate the history of vitamin D supplementation or the duration of vitamin D insufficiency/deficiency, which may have affected the number of postoperative HBS.
CONCLUSION
We recommend the measurement of IOPTH routinely in all FP cases, since this adjunct provides optimum patient safety. Using the central laboratory for rapid results and only obtaining a single preoperative and one postoperative sample within 15 minutes is anticipated to reduce the cost of IOPTH and lead to its widespread adoption in developing nations. The administration of calcium carbonate and calcitriol empirically in all patients has resulted in a lower incidence of postoperative hypocalcemia and HBS.
To our knowledge, this is the first Indian study to include FP in PHPT in a tertiary care corporate hospital and analyze 142 patients.
We feel confident that our initial findings will open the door for comprehensive prospective multicenter research with a large patient population and long-term follow-up to validate or disprove our results.
ORCID
Satyajit Kundu https://orcid.org/0009-0008-1224-2978
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