CASE REPORT

Pancreatitis in Primary Hyperparathyroidism

M Abdullah, FRCS

Department of Surgery, University of Malaya, 50603 Kuala Lumpur

Introduction

Pancreatitis is known to be associated with primaryhyperparathyroidism (pHPT). However therelationship of cause and effect between the twodiseases continues to be debated in the medicalliterature in determining whether one leads to theother. Besides, other causes of acute pancreatitislike gallstone disease and alcoholism in Malaysiaare far more common. For this reason theappearance of a raised serum calcium level, in the"routine" biochemical profiles of a patient firstpresenting with acute pancreatitis, does not raisemuch alarm. To our embarrassment, it took thefollowing case report to learn a lesson.

Case Report

We report a 49 years old Malay man whopresented to the University of Malaya Medical

Centre, Kuala Lumpur with one-day history ofsevere upper abdominal pain and vomiting. Pasthistory, revealed occasional episodes of loin pains.He had never consumed alcohol in his life.Investigations revealed serum amylase of 2285IU/L (n=25-150), mild hyperglycemia andcrystalluria. Serum calcium level was 2.65 mmollL(n=2.20- 2.60). Ultrasound examination and CTscans showed a normal gallbladder andinflammation of pancreatic tail. The hypercalcemiawas ignored on this occasion and the patientdischarged home when the symptoms settled.

In the next six months he had two furtheradmissions with clinical and biochemical featuresof acute pancreatitis. On both occasions he settledspontaneously and requested for discharge. Onceagain,"routine calcium" of 2.80 mmollL did notraise any alarm.

Thisarticle was accepted: 19 February 2003Corresponding Author: MuhammadAbdullah, Department of Surgery, University of Malaya, 50603, Kuala Lumpur

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It wasn't until nearly ten months after his firstpresentation on his third admission with acutepancreatitis (serum amylase: 1354 lUlL) that thehypercalcemia was noted and acted upon. On thisadmission the serum calcium was 2.89-mmollLand serum phosphate, 0.94 mrnol/L (n= 0.9-1.5).He was also hyperglycemic, (Glucose = 13.6mmol/L), Repeat checks confirmed persistenthypercalcemia (3.09mmollL), hypophosphatemia(0.7 mmol/L), a normal albumin (43 g/L) and aurinary calcium of 55 mmol/L (n=2.2-75). Theinitial suspicion of primary hyperparathyroidismwas confirmed when his intact parathyroidhormone level (iPTH) level was found to be 99.8pg/ml (n=I1.0- 54.0).

The patient then underwent an open bilateral neckexploration, which showed a lcm left inferiorparathyroid adenoma (Fig. 1). Frozen sectionshowed that the other three parathyroid glandswere normal. Postoperatively the calcium camedown to 2.16 mmol/L before the patient wasdischarged home.

Two months after his parathyroid surgery he hadone further episode of documented acutepancreatitis with serum amylase of 4727 ru/r,calcium of 2.39 mmollL and albumin of 49 g/L(n=35-50). He settled spontaneously. After thishe did not have any further attack of pancreatitisand has been symptom-free till his last review 18months post-surgery. On this occasion, the serumcalcium was 2.32 mmollL and phosphate, 1.3mmol/L.

Discussion

Pancreatitis related to hyperparathyroidism (HPT)was first reported in 1947 by Martin and Canseco inthe Journal of American Medical Association.But it was 10 years later that pancreatitis as afeature of primary HPT became well knownthrough the writing of Cope in the Annals ofSurgery in 1957. Since then, individual cases andseries have been reported periodically in the beliefthat pancreatitis is just one of the manifestations of

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Pancreatitis inPrimary Hyperparathyroidism

Fig 1:The operative

pHPT and that recurrent pancreatitis can be curedby treating the cause of pHPT.

However not everyone accepts this. Some suggestthat the association of pancreatitis with pHPT isincidental or in fact pancreatitis may be the resultof parathyroid surgery for some other reason. Themain challenge has come from Bess' andcolleagues from Mayo clinic in 1980. Reviewing1153 patients with proven pHPT they found only17 patients with pancreatitis. They suggested thatthe association of HPT and pancreatitis was due tobias in patient selection or just chance alone sincethe incidence of pancreatitis in their series was toolow.

These objections by Bess and his colleagues havebeen challenged with counter arguments. Evenbefore the Mayo clinic report, Kelly in 1968published an experimental study in the Archives ofSurgery, demonstrating that persistenthypercalcemia increases the calcium content of the

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CASE REPORT

pancreatic JUIce leading to acceleratedintrapancreatic conversion of trypsinogen totrypsin, the latter causing pancreatic damage.

Sitges-Sera' and co-authors in 1988, have alsostressed the point that hypercalcemia per se isbehind the causation of pancreatitis. Theyhighlighted the association of pancreatitis withnon-hyperparathyroid causes of hypercalcemialike parenteral nutrition, calcium infusion,myeloma, disseminated breast cancer or severehyperthyroidism. They have also criticized thereport by Bess and eo-workers, pointing out thatthe apparently low incidence of pancreatitis in theMayo clinic series of pHPT patients is not true. Inis only apparent because in that institution manypatients with asymptomatic hyperparathyroidismand/or slight hyper-calcaemia are submitted toparathyroid surgery (before they have a chance todevelop pancreatitis). Presenting their own 10cases in support they have stressed thatpancreatitis is more likely to develop in patientswho exhibit moderate to severe hypercalcemiawhile patients with asymptomatichyperparathyroidism and/or with mildhypercalcemia are less prone to developpancreatitis.

Carnille' and colleagues reported from France in1998 after reviewing 1435 consecutive patientsoperated for hyperparathyroidism. Of these, 1224patients had biochemically proven pHPT, theremaining 211 had renal hyperparathyroidism(RHPT). They found that a total of 40 patients(3.2%) with pHPT had pancreatitis, 18 having anacute attack. This rate of pancreatitis was higherthan in their random hospital population.Spontaneous healing of 17 out of 18 patients withacute pancreatitis followed surgical cure of pHPT.A single diseased gland was found in 27 (out of 40patients with pancreatitis), which is in favour ofprimary parathyroid disease being responsible for,and not a consequence of pancreatitis. In 78% ofcases, pancreatitis preceded the diagnosis of pHPTand that no pancreatitis was recorded either in theRHPT group or after parathyroidectomy. Theirlaboratory data suggest that pancreatitis is an effect

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of hypercalcaemia and not of high intactparathyroid hormone levels (iPTH) levels per se.

A controversial aspect of the Pancreatitis-HPTassociation is the suggestion that pancreatitis maybe caused by parathyroid surgery or at least shouldbe accepted as an uncommon complication of it.Supporters of this theory, Reeve and Delbridge,had postulated in 1982 that the mechanism was therelease of parathyroid hormone and an acute risein serum calcium consequent on operativemanipulation of a parathyroid tumour. In theirexperience, this complication was much morecommon when thyroid lobectomy or bilateralsubtotal thyroidectomy was performed in additionto parathyroidectomy.

This has been contested by Robertson andassociates in the Annals of the Royal Collefje ofSurgeons of England. They reported a study in1995 to test the hypothesis that up to 35%ofpatients may experience hyperamylasaemia afterparathyroidectomy indicating subclinicalinflammation of the pancreas. A series of 26patients undergoing parathyroidectomy werestudied by preoperative and post operativebiochemical analysis and CT scan of the pancreasafter operation. However postoperatively, therewas no evidence in any patient of acute pancreaticinflammation or hyperamylasaemia. Theypostulated that any amylase elevation in otherreports might reflect an increase in salivaryisoamylase as a result of extensive neck dissection

Shepard' from Tasmania in 1996 has also disagreedwith the theory of post-parathyroidectomypancreatitis. Reviewing the literature on thesubject, Shepard suggests that it is the surgicalstress rather than manipulation of the parathyroidgland, which is responsible for excessiveparathyroid hormone release in patients afterparathyroidectomy.

In conclusion, acute pancreatitis is one of thesymptoms of primary hyperparathyroidism, oftencaused by a parathyroid adenoma and curable byits excision. Calcium and parathyroid profiles

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should be scrutinized in all fresh cases of acutepancreatitis even though primaryhyperparathyroidism is a rare cause. Anyoversight will result in diagnostic delays like theone that we had in our case.

Pancreatitis in Primary Hyperparathyroidism

Acknowledgement

I thank Associate Professor K TOng for theoperative findings and photograph.

lill el_mIll 111/I11'IlIII 10' '911 iI I !'IlIII! ,_,,'IfIj'l/jI-

1. Bess MA, Edis AJ, von Heerden JA.Hyperparathyroidism and pancreatitis. Chance or acausal association? JAMA 1980; 243: 246-7.

2. . Sitges-Serra A, Alonso M, de Lecea C, Gores PF,Sutherland DE. Pancreatitis andhyperparathyroidism. Br J Surg 1988 Feb; 75 (2):158-60.

3. Carnaille, B.; Oudar, c. Pattou, F.; Combemale, F.Rocha, ].; Proye, C. Pancreatitis and primary

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hyperparathyroidism forty cases. Aust N Z J Surg1998 Feb; 68 (2): 117-19.

4. Reeve ST, Delbridge LW. Pancreatitis followingparathyroid surgery. Ann. Surg. 1982; 195: 158-62

5. Shepherd, J J. Hyperparathyroidism presenting aspancreatitis or complicated by postoperativepancreatitis. Aust N Z J Surg 1996 Feb; 66 (2): 85-7