Case e Report Left Parathyr roid Aden noma Hyp perparathy yroidism Panc creatitis: A Rare Case e Report I Induced Necrotisin ng Hariprasath Jagachandra an Affilia ated MD to o MGR Me edical Unive ersity, FCC CP to Amerrican Colleg ge of Ches st Physicians (Con nsultant In nternal Me edicine and d Diabetolo ogy, Apollo o Hospitals s, Tondiarpet), Che ennai, India. Email: drrhariprasath [email protected] m . Inter rnational Journal J of Clinical Ca ases and I Investigatio ons. Volum me 6 (Issu ue 2),15 5 :19 , 1st January J 20 015. Absttract We report r a ca ase of a female patien nt with sev vere acute necrotizing pancreatitis chara acterized by y hypercalce emia induced by intra tthyroidal parathyroid ad denoma. Th he patie ent was initially diagnos sed to have e acute panccreatitis and d treated co onservatively for the t same. Following the t identific cation of le eft parathy yroid adeno oma throug gh SPEC CT, the pattient underrwent hemithyroidecto omy and p parathyroide ectomy. Th he patie ent graduallly improved d. The ass sociation be etween parrathyroid ad denoma an nd acute e necrotizin ng pancreattitis was un nknown, al though few w hypothese es were pu ut forwa ard. Surgica al resection of the paratthyroid aden noma was tthe ultimate e therapy an nd may prevent the e recurrence e of pancrea atitis. words: hypercalcemia, pancreatitis parathyroid d adenoma Keyw Intro oduction Acute e Necrotizing pancreatitis is associiated with a higher rate e of mortality. The mos st comm mon reason ns were alcohol and biliary b stone es. It may occur once e or may b be recurrrent, which h can range e in severitty from mi ld to severre and life threatening g. Mana agement strrategy range es from brie ef hospitalizzation to inttensive care e monitoring g. According to the grading of acute no on-alcoholicc pancreatittis, decreas sed levels o of calciu um has been shown to have assoc ciated with a acute pancrreatitis1. Butt an increas se in the levels of calcium an nd its relationship with h severe pa ancreatitis is s one of th he hints for hyperp parathyroidis sm. Severe acute panccreatitis pro ogresses in two phases s. Relea ase of inflam mmatory me ediators tak kes in the firrst phase off 14 days an nd this resu ult in sy ystemic inflammatory response. 2, 3 During g the second phase of infection n, pancreatic necro osis takes place and that resultts in sepsiss related co omplications s. ction of pan ncreatic nec crosis occurs in 40% to 70% off patients w which is th he Infec 15 significant risk factor of death from Necrotizing pancreatitis.4 Acute pancreatitis may occur as an isolated attack or may be recurrent. It has a variety of causes and can range in severity from mild to severe and life threatening. Some patients may require brief hospitalization, to intensive care monitoring. Abdominal pain, typically epigastric; serum amylase or lipase 3 times the upper limit of normal; and characteristic findings of acute pancreatitis on contrast-enhanced computed tomography (CECT) were the criteria for the diagnosis of acute pancreatitis. Clinical history and laboratory results provide the accurate results in most of the cases and no imaging is required. A CECT in the initial 3–4 days of acute pancreatitis might underestimate or miss the amount of necrosis.5 In general, a CECT is advised if a patient does not improve after the first week of treatment to evaluate the extent of local complications.5 In clinical practice, however, it is not uncommon for patients to undergo CT earlier than 1 week, especially in case of early complications. Case Report 60 year old female, diabetic, normotensive patients got admitted with the symptoms of fever, abdominal pain, vomiting, dark color urine and pale stools for the past one week. Investigations revealed plasma glucose 373mg/dL, serum amylase 375U/L, Serum lipase 400U/L, total bilurubin 8.9mg/dl and serum bilurubin 6.0mg/dl. The patient had anaemia, high serum bilirubin with hypercalcemia, raised renal parameters, and altered liver function. Her serum calcium level was 14.1mg/dL. She was conservatively treated for pancreatitis. Patient USG abdomen report showed as acute edematous pancreatitis while CT scan abdomen revealed acutenecrotic pancreatitis with bilateral renal calculi. Since D-dimer was highly elevated, CT pulmonary angiogram done, showed no evidence of pulmonary thromboembolism. Serum CRP (52mg/dL), C 19-9 (54.2U/mL), calcium (10.5mg/dL) and serum (PTH 102pg/mL) were elevated. An endoscopy was done which revealed pangastritis/extraneous impression at medial wall D2. Nuclear isoptope study of the thyroid done revealed functioning left parathyroid adenoma and advised surgery. ECHO cardiogram showed normal LV function. Then the patient underwent hemithyroidectomy and parathyroidectomy by an endocrine surgeon. Patient was discharged post surgery after her blood investigations and biopsy revealed normal. Discussion Pancreatitis association with parathyroid hormone was first revealed by martin and Canseco in 1947. After that series of case reports were published. A retrospective study6 performed in 1980 denied this association saying that it was only due to bias in patient selection or just chance. Serra and colleagues7 had countered this statement by present 10 new cases of hypercalcaemic hyperparathyroidism associated with different types of pancreatitis. Presenting their own 10 cases in support they have stressed that pancreatitis is more likely to develop in patients who exhibit moderate to severe hypercalcemia. The prevalence of acute pancreatitis in patients with PHPT is very uncommon and it is estimated between 1.5% and 7%.8 In accordance to the epidemiological studies, it is not possible to derive a causal relationship between hyperparathyroidism and acute necrotizing pancreatitis but when both occurs concomitantly, pancreatitis could be severe and the extent of hypercalcemia seems to play a crucial role in this association. Proposed 16 pathophysiological links are: 1. Calcium deposition in the pancreatic duct may cause pancreatic duct obstruction.9 2. Hypercalcemia induced activation of trypsinogen causing autodigestion of the pancreas.10 3. Genetic variants in SPINK 1 (serine protease inhibitor Kazal type 1) and CFTR (cystic fibrosis transmembrane conductance regulator) genes in combination with hypercalcemia increase the risk of developing acute pancreatitis in patients with PHPT. 11 Most commonly decreased calcium levels were associated with acute pancreatitis and it becomes rare to find hypercalcemia with acute necrotizing pancreatitis. When elevated calcium levels coexist with acute pancreatitis, it should alert the treating physician to evaluate for malignancy. Early testing of serum calcium levels in the patients presents with acute severe pancreatitis would help in ruling out the presence of hyperparathyroid adenoma. It is also important to consider the possibility of an ectopic localization of a parathyroid adenoma as a cause of acute pancreatitis. Left parathyroid adenoma in the present case was diagnosed using Tc-99m SPECT CT in which scintigraphic features suggestive of functioning parathyroid lesion at the inferior aspect of lower pole of left lobe of thyroid. Surgical resection and histological examination of the tumor remains the ultimate therapy and may prevent the recurrence of pancreatitis. References: 1. Ranson JH. Etiological and prognostic factors in human acute pancreatitis: a review. Am J Gastroenterol 1982; 77: 633-638. 2. Norman J. The role of cytokines in the pathogenesis of acute pancreatitis. Am J Surg 1998; 175(1):76–83. 3. Gloor B, Reber HA. Effects of cytokines, and other inflammatory mediators on human acute pancreatitis. J Int Care Med 1998; 13(6):305–312. 4. Beger HG, Rau B, Mayer J, Pralle U. Natural course of acute pancreatitis.World J Surg 1997; 21(2):130 –135. 5. Spanier BW, Nio Y, van der Hulst RW, et al. Practice and yield of early CT scan in acute pancreatitis: a Dutch observational multicenter study. Pancreatology 2010;10:222–228. 6. Bess MA, Edis AJ, von Heerden JA. Hyperparathyroidism and pancreatitis. Chance or a causal association? JAMA 1980; 243: 246-7. 7. Sitges-Serra A, Alonso M, de Lecea C, Gores PF, Sutherland DE. Pancreatitis and hyperparathyroidism. Br J Surg 1988 Feb; 75 (2): 158-60. 8. Egea Valenzuela J, Belchí Segura E, Sánchez Torres A, Carballo Alvarez F. Acute pancreatitis associated with hypercalcemia. A report of two cases. Rev Esp Enferm Dig 2009; 101: 65-69. 9. Ward JB, Petersen OH, Jenkins SA, Sutton R. Is an elevated concentration of acinar cytosolic free ionised calcium the trigger for acute pancreatitis? Lancet 1995; 346: 1016-1019. 10. Mithöfer K, Fernández-del Castillo C, Frick TW, Lewandrowski KB, Rattner DW, Warshaw AL. Acute hypercalcemia causes acute pancreatitis and ectopic trypsinogen activation in the rat. Gastroenterology 1995; 109: 239-246. 11. Felderbauer P, Karakas E, Fendrich V, Bulut K, Horn T, Lebert R, Holland-Letz T, Schmitz F, Bartsch D, Schmidt WE. Pancreatitis risk in primary hyperparathyroidism: relation to mutations in the SPINK1 trypsin inhibitor (N34S) and the cystic fibrosis gene. Am J Gastroenterol 2008; 103: 368-374 17 Figures Figurre 1 18 Figure 2 19