|Year : 2018 | Volume
| Issue : 6 | Page : 219-222
Acute pancreatitis and primary hyperparathyroidism: Effect of parathyroidectomy
Riju Ramachandran, Gopalakrishnan C Nair, Misha J C Babu, Pradeep Jacob
Department of General Surgery, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala, India
|Date of Submission||06-Oct-2017|
|Date of Decision||19-Jan-2018|
|Date of Acceptance||04-May-2018|
|Date of Web Publication||11-Dec-2018|
Dr. Riju Ramachandran
Department of General Surgery, Amrita Institute of Medical Sciences, Amrita University, AG1, Sterling Sarovar, Kosseri Lane, Edapally, Kochi, Kerala
Source of Support: None, Conflict of Interest: None
Background: The association between primary hyperparathyroidism (PHPT) and acute pancreatitis (AP) is well known. However, the causal association is disputed.
Aims: The present cohort study of PHPT patients was done: (1) to assess the prevalence of AP and (2) to assess the effect of successful parathyroidectomy in preventing further recurrence.
Materials and Methods: Case records of patients admitted with AP during the study period were reviewed. Diagnosis of PHPT among this group was based on serum level of corrected calcium and parathyroid hormone. Review of records of patients who were successfully operated for PHPT was done. Records of patients treated with confirmed diagnosis of AP during the study period were reviewed. Variables used for analysis were serum levels of calcium (adjusted to serum albumin), phosphate, intact parathyroid hormone, 25-OH-Vitamin D, alkaline phosphatase, and estimated glomerular filtration rate (eGFR). For continuous/numerical variables with two groups, Mann–Whitney U-test was applied. Multivariate regression analysis was done if the univariate analysis showed significance (P < 0.05).
Results: There were 13 (7.5%) patients with confirmed diagnosis of AP and serum calcium level significantly elevated in this group. There was a linear association of serum calcium with AP. Successful parathyroidectomy prevented further episodes in 11 (84.6%) of patients. There was 2% prevalence of PHPT among 558 patients with AP.
Conclusions: Hypercalcemia in PHPT patients was significantly associated with AP and early parathyroidectomy prevented further recurrence.
Keywords: Acute pancreatitis, hypercalcemia, primary hyperparathyroidism
|How to cite this article:|
Ramachandran R, Nair GC, Babu MJ, Jacob P. Acute pancreatitis and primary hyperparathyroidism: Effect of parathyroidectomy. Formos J Surg 2018;51:219-22
|How to cite this URL:|
Ramachandran R, Nair GC, Babu MJ, Jacob P. Acute pancreatitis and primary hyperparathyroidism: Effect of parathyroidectomy. Formos J Surg [serial online] 2018 [cited 2019 Jan 18];51:219-22. Available from: http://www.e-fjs.org/text.asp?2018/51/6/219/247307
| Introduction|| |
Conventionally, 80% of acute pancreatitis (AP) is related to alcohol abuse and biliary stone disease and <10% have metabolic causes as etiology., Ever since the association between AP and primary hyperparathyroidism (PHPT) was reported in 1940 by Smith and Cook, many case series have appeared in the literature recording varying prevalence from 1.5% to 15%.,, However, the causal association of PHPT with AP was always debated. Population-based survey did not reveal significant difference in the prevalence of AP in PHPT patients and general population. A recent systematic review emphasized the association between PHPT and AP and implicated hypercalcemia as causal association. However, many case series failed to exclude other concurrent potential causes of AP such as alcohol abuse and biliary stones, and hence, the causal association was doubted.
We also analyzed the case records of patients admitted with confirmed diagnosis of AP during the study period for clinical and biochemical features indicative of PHPT. The aim of the study was to assess the prevalence of AP in PHPT patients and to determine the effect of parathyroidectomy in preventing recurrence.
| Materials and Methods|| |
Patients operated for PHPT during January 2005 and December 2014 were included in the study. Patients with evidence of multiple endocrine neoplasia type 1 were excluded since associated pancreatic tumors could be an etiology. AP patients with other possible etiological features such as alcohol abuse, biliary stones, and elevated serum triglycerides (50.0–150.0 mg/dl) were excluded from the study.
Diagnosis of AP was based on the history of acute abdominal pain with serum lipase level more than 200 U/L (21–67). Contrast-enhanced helical computed tomography (CT) was reviewed for confirmation. A diagnosis of recurrent AP was made if the patient had more than one episode of AP.
Surgical cure of hyperparathyroidism was ensured by intraoperative parathyroid hormone monitoring (Miami criterion) and regular follow-up to exclude recurrent hypercalcemia. All patients were reviewed at 6 monthly intervals. Ultrasonography or CT of the abdomen, serum amylase, and lipase levels was done based on clinical findings. Data regarding clinical features and laboratory values were retrieved from the prospective database maintained in the surgical endocrinology division of the Institution. The details regarding prior treatment were reviewed.
Case records of patients admitted with AP during the study period were reviewed. Diagnosis of PHPT among this group was based on serum level of corrected calcium and parathyroid hormone.
The cohort was further divided into two subgroups based on the association of AP. For the comparison of categorical variables among the different groups, Chi-square test was used. Variables used for analysis were serum levels of calcium (adjusted to serum albumin), phosphate, intact parathyroid hormone, 25-OH-Vitamin D, alkaline phosphatase, and estimated glomerular filtration rate (eGFR). For continuous/numerical variables with two groups, Mann–Whitney U-test was applied because the laboratory parameters values did not follow the parametric assumption. Multivariate regression analysis was done if the univariate analysis showed significance (P < 0.05). SPSS version 11 (SPSS Inc., Chicago) was employed for statistical analysis.
| Results|| |
During the study period, 186 patients were operated for PHPT. Nine patients with clinical and biochemical evidence of MEN-1 syndrome were excluded from the study. Of the remaining 177 patients, 12 patients (6.6%) were asymptomatic and others presented with symptoms related to the skeletal system, kidneys, gastrointestinal system, and metabolic disturbances. There were 16 (8.6%) patients with AP and 9 (4.8%) with chronic calcific pancreatitis (CCP), and hence, a total of 13.4% had complications related to the pancreas. Of the 16 patients with AP, three were excluded in view of associated alcohol abuse (n = 2) and obesity with increased serum level of triglycerides (body mass index [BMI] – 33.4lg/m2 and serum triglycerides level – 491 mg/dl). All the 13 patients had recurrent AP since they had more than one episode of AP.
We analyzed the data of 174 patients with the mean age of 45.66 years (standard deviation [SD]: 14.24) and the mean BMI of 24.6 Kg/m2 (SD: 4.123). The cohort included 59% (n = 103) females. Coincident hypertension was present in 59 (33.3%) and diabetes mellitus in 40 (22%) patients when PHPT was diagnosed. The mean value of creatinine clearance (modification of diet in renal disease study equation) was 78.24 mL/min/1.73 m2 (SD: 35.213) and 20 (12%) had eGFR <40 ml. The profile of cohort is shown in [Table 1].
The cohort that included 13 (7.5%) patients who had recurrent episodes of AP was grouped to analyze clinicopathological features and is noted in [Table 2]. The mean age of the group was 45.24 years included 7 (54%) females. The serum level of calcium was significantly high in patients who developed AP compared to those who did not.
Successful parathyroidectomy was done in all patients, and the mean weight of excised parathyroid lesion was 5.784 g (SD: 6.05). The histology showed adenoma in 135 (77.6%), atypical adenoma in 7 (4%), carcinoma in 13 (7.5%), and hyperplasia in 19 (11%). The patients were followed for a mean duration of 61.46 months (24–132). Of the 13 with AP, 11 (84.6%) were free of further episodes, but 2 developed CCP during follow-up.
We analyzed 558 patients admitted with AP during the same study period (male 416 and female 142) with mean age of 42.71 years (SD: 18.829). Of these, 11 (2%) had confirmed PHPT. The mean serum calcium level was 8.1 mg/dl (SD: 1.342) and 61.2% had values below reference level. The serum calcium levels of patients with PHPT were above normal reference level during hospitalization (mean: 10.32 mg/dl). All PHPT patients underwent successful parathyroidectomy and did not develop further episodes of AP.
| Discussion|| |
In this group, 95% of participants were symptomatic and the serum levels of calcium and PTH were high. We observed 7.5% prevalence of AP in PHPT patients after adjusting to other potential etiologies.
Serum calcium level was significantly high in AP patients, but the PTH level was not. The regression model showed a linear association with serum calcium level with no definite cutoff point. There were no other possible etiologies associated with them and hence we assume that hypercalcemia was an independent triggering factor in the development of AP. AP was noted as the first manifestation in patients with hypercalcemia related to malignancy and sarcoidosis.,, Experimental hypercalcemia by calcium infusion was found to induce trypsinogen activation and pancreatic cellular damage in rats. Hypercalcemia induces pancreatic damage through secretary block, accumulation of secretory products, and activation of proteases. Experimental evidence link elevated acinar cell calcium levels with AP in association with premature trypsinogen activation to trypsin.,
Successful parathyroidectomy prevented further episodes in 84.5% (n = 11) patients. Approximately 10% AP patient's progress to chronic pancreatitis and the significant predictors are continued alcohol abuse and smoking. The progression to chronic form is mostly due to the persistence of the primary etiology. Two patients who had progression of disease suffered more than four episodes of AP requiring hospitalization before the diagnosis of PHPT. The patients with CCP gave multiple episodes of AP in the past.
Of the 558 patients with AP admitted during the study period, 2% patients had confirmed PHPT. All these patients underwent successful parathyroidectomy. The serum calcium levels of all these patients were above normal reference level during the acute phase of the disease. Awareness of this rare combination among the treating physician helps to make an early diagnosis of PHPT and thus preventing progression of the disease to chronic disease.
However, hypercalcemia does not have a temporal relation with AP. Despite having high serum calcium levels, <15% PHPT patients develop AP. Few genetic variables have been identified that increase the susceptibility to develop AP, namely, polymorphisms in serine protease inhibitor Kazal type 1 (SPINK1), polymorphisms in cationic trypsinogen (PRSS1) and chymotrypsinogen C (CTRC) genes in the acinar cells and cystic fibrosis transmembrane conductance regulator (CFTR), and calcium-sensing receptor (CASR genes in the ductal cells). SPINK1 gene governs pancreatic secretory trypsin inhibitor and mutations in SPINK1 N34S allele is associated with acute and chronic pancreatitis, but only <1% carriers develop pancreatitis during their lifetime., SPINK1 mutations are seen in approximately 2% of population and were considered to lower the threshold for pancreatitis from other genetic or environmental factors, but by themselves does not cause disease.,,
Extracellular calcium-sensing receptors were first cloned from bovine parathyroid glands in 1993 and later Rácz et al. documented evidence indicating the presence of CASR in human exocrine pancreas. Recent studies from Germany and India have reported high prevalence of CASR and SPINK1 N34S missense mutation either alone or in combination., Felderbauer et al. found significantly high prevalence of the N34S missense mutation in the SPINK1 gene among PHPT patients with AP. The higher disease severity indices of PHPT and increased incidences of SPINK1 gene mutation can explain significantly high prevalence of AP in PHPT patients in Indian subcontinent.
| Conclusions|| |
Significantly, high prevalence of AP was present among patients with PHPT. Approximately 2% of AP could be related to PHPT. These patients had high serum calcium levels during the acute phase of pancreatitis and awareness of this rare combination increases chances of early diagnosis. Surgical cure of hyperparathyroidism effectively prevents further recurrence of AP.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]