Brief Communication
Diabetes due to recurrent pancreatitis secondary to hypercalcemia due to primary hyperparathyroidism Sumit Kumar Chakrabarti, Dibakar Biswas, Sandeep Chaudhury, Rajesh Jain, Manoj Kataria, Sujoy Ghosh Department of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India
A B S T R A C T Acute pancreatitis due to hypercalcemia associated with hyperparathyroidism (HPT) is not very common. We herein report a case of a 21-year-old woman, who presented with acute pancreatitis. She had a past history of recurrent nephrolithiasis. Subsequent evaluation revealed hypercalcemia (serum calcium: 12.6 mg/dL); low phosphate (2.9 mg/dL) with elevated parathyroid hormone (PTH, 156.7 pg/mL) and HbA1c (6.9%). Diagnosis of primary HPT (PHPT) was made. Recurrent pancreatitis due to hypercalcemia may have resulted in diabetes mellitus. Key words: Diabetes, diabetes mellitus, hypercalcemia, hyperparathyroidism, pancreatitis, primary hyperparathyroidism
INTRODUCTION
CASE REPORT
Episodes of acute pancreatitis can be recurrent, if the underlying factor remains uncorrected. Alcohol, autoimmune diseases, injury, and drugs are identified causes for recurrent pancreatitis.[1] Primary hyperparathyroidism (PHPT) is a rare cause for pancreatitis. PHPT is associated with high parathyroid hormone (PTH) levels, which usually leads to hypercalcemia and hypophosphatemia. Patients may present with recurrent nephrolithiasis, or be asymptomatic, detected on routine biochemical screening.[2] PHPT patients are also associated with altered carbohydrate metabolism characterized by insulin resistance, hyperinsulinemia, and glucose intolerance and even frank diabetes. However, the corelation between the two remains controversial and has been explained only based on few case reports.[3] We present a patient with recurrent episodes of pancreatitis primarily due to hypercalcemia of PHPT and eventually leading to diabetes mellitus.
A 21-year-old woman, presented with acute onset of abdominal pain over epigastric region radiating towards back with vomiting.
Access this article online Quick Response Code: Website: www.ijem.in DOI: 10.4103/2230-8210.119575
On admission
The patient was overweight with a body mass index (BMI) of 24.8 kg/m 2. General physical examination was noncontributory apart from a nodule in the lower pole of right lobe of thyroid gland. No acanthosis nigricans and hirsutism were seen. Her menstrual history was normal. Systemic examinations revealed mild hepatomegaly. However, serum amylase and lipase were high [Table 1]. Abdominal ultrasonography revealed features suggestive of acute pancreatitis along with left renal calculus. There was no evidence of gall stones. The patient was diagnosed with acute pancreatitis and managed conservatively. Past history
The patient’s past history shows repeated episodes of abdominal pain over last 3 years, which required hospitalization. There was recurrent history of pain in the flanks and on two occasions she had passed stones while passing urine. Straight X-ray of kidney, ureter, and bladder region showed the presence of renal stones in both the kidneys. There was no history of polyuria and polydipsia.
Corresponding Author: Dr. Sumit Kumar Chakrabarti, Department of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata - 700 020, West Bengal, India. E-mail: [email protected]
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Indian Journal of Endocrinology and Metabolism / 2013 / Vol 17 / Supplement 1
Chakrabarti, et al.: Pancreatitis due to hypercalcemia associated with PHPT
She had a history of constipation. She however did not have any behavioral or mood disorders. The patient was then diagnosed with recurrent pancreatitis and nephrolithiasis. Course in hospital
During the course of pancreatitis she never had any hypocalcemia. On repeated occasion her serum calcium was around 10 mg/dL. Her serum albumin was within normal range. She was detected to have diabetes mellitus with HbA1c 6.9% and was put on insulin. Lipid profile, liver function, renal function, and thyroid function tests were normal. Prothrombin time was 11.6 s (control 11.5 s) with international normalized ratio (INR) 1.01. Routine urine analysis was also normal. CT scan did not reveal any growth. Further investigation of laboratory parameters, such as serum calcium, albumin, and PTH was abnormal [Table 2]. Thyroid ultrasonography showed small, well defined, oval shaped hypoechoic structure just inferior to the lower pole of right lobe of thyroid gland suggestive of parathyroid adenoma or small lymph node [Figure 1]. Abdominal contrast-enhanced computed tomography Table 1: Laboratory analysis Parameters
Results
Normal levels
Serum amylase Serum lipase
970 U/L 2195 U/L
30-110 U/L 23-300 U/L
Table 2: Laboratory analysis Parameters Serum calcium Serum phosphorus Serum albumin Serum uric acid iPTH Serum 25 OH vitamin D
Results
Normal levels
12.6 mg/dL 2.9 mg/dL 4.5 g/dL 4.3 mg/dL 156.7 pg/mL 9.4 ng/mL
8.5-10.3 mg/dL 2.5-4.5 mg/dL 3.5-5 g/dL 2.5-7.5 mg/dL 15-65 pg/mL 10-55 ng/mL
(CECT) showed features suggestive of mild acute pancreatitis with left renal calculus. Magnetic resonance cholangiopancreatography showed chronic pancreatitis with no evidence of biliary obstruction or choledocholithiasis [Figure 2]. Diagnosis
Patient was diagnosed with PHPT causing hypercalcemia which resulted in nephrolithiasis and recurrent pancreatitis further leading to pancreatic diabetes.
DISCUSSION PHPT is an endocrine disorder, characterized by excessive secretion of PTH. Increased PTH leads to hypercalcemia and hypophosphatemia. [4] PHPT symptoms include polyuria, depression, nephrolithiasis, peptic ulcer, and pancreatitis.[5] Hypercalcemia due to HPT is not a very common cause for acute pancreatitis, usually seen between 1.5 and 7% in the different series.[4] Presentation of pancreatic disease in PHPT can be classified in four classes: 1. PHPT presenting as acute pancreatitis 2. PHPT presenting as acute recurrent pancreatitis with no evidence of chronic pancreatitis 3. PHPT presenting as chronic pancreatitis with or without pancreatic calcification 4. PHPT complicated by acute pancreatitis in the postoperative period. Literature review on case series suggested, PHPT patients presenting with acute pancreatitis are more common (44%) than those with chronic pancreatitis. But, no evidence has been reported for patients who developed acute pancreatitis in the postoperative state.[6]
iPTH: Intact parathyroid hormone
Figure 1: USG showing hypoechoic mass suggestive of parathyroid adenoma
Figure 2: Magnetic Resonance Cholangiopancreatography showing chronic pancreatitis
Indian Journal of Endocrinology and Metabolism / 2013 / Vol 17 / Supplement 1
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Chakrabarti, et al.: Pancreatitis due to hypercalcemia associated with PHPT
Several pathophysiological approaches are suggested to explain the relationship between pancreatitis and hypercalcemia. Few researchers have reported that patients with hypercalcemia secondary to HPT have low pancreatic secretion but normal enzyme activity. In such cases, pancreatitis may result due to damage of parenchymal cell and pancreatic duct caused by activation of intrapancreatic trypsinogen to trypsin due to high calcium concentration in pancreatic juice.[5,7,8] Few theories also suggest the mutations of genes such as serine protease inhibitor Kazal type 1 (SPINK1) or cystic fibrosis transmembrane conductance regulator (CFTR) may also be involved.[4] Pancreatitis is usually diagnosed before identifying HPT. Hypercalcemia during pancreatitis can be an indication for HPT, whereas hypocalcemia can occur during an attack of pancreatitis.[5,7] Patients with chronic pancreatitis due to PHPT also have significant incidence of renal colic, nephrolithiasis, and nephrocalcinosis.[6] In our case, there was no clear etiology for pancreatitis except hypercalcemia. So any patient with pancreatitis should be investigated for hypercalcemia to avoid missing the diagnosis of HPT.
S214
REFERENCES 1. 2.
3.
4.
5.
6. 7. 8.
Lara LF, Levy MJ. Idiopathic recurrent acute pancreatitis. Med Gen Med 2004;6:10. Misgar RA, Mathew V, Pandit K, Chowdhury S. Primary hyperparathyroidism presenting as recurrent acute pancreatitis: A case report and review of literature. Indian J Endocrinol Metab 2011;15:54-6. Reddy PA, Harinarayan CV, Suresh V, Jena A, Reddy MK, Kalawat TC, et al. Can diabetes associated with hyperparathyroidism be an additional indication for parathyroidectomy? A case report. Int J Endocrinol Metab 2009;3:208-11. Egea Valenzuela J, Belchi Segura E, Sanchez Torres A, Carballo Alvarez F. Acute pancreatitis associated with hypercalcemia. A report of two cases. Rev Esp Enferm Dig 2009;101:65-9. Nikolaidis LA, Leon MN, Paslidis NJ. Acute pancreatitis as the first manifestation of hyperparathyroidism in an otherwise asymptomatic patient. J Ark Med Soc 1995;92:273-5. Kumar R. A case of chronic pancreatitis due to hyper parathyroidism. Apollo Med 2010;7:54-7. Smith MD, Pawlak M, Pantanowitz DP, Botha RJ. Hyperparathyroidism and chronic pancreatitis. S Afr J Surg 1999;37:12-4. Kelly TR. Relationship of hyperparathyroidism to pancreatitis. Arch Surg 1968;97:267-74.
Cite this article as: Chakrabarti SK, Biswas D, Chaudhury S, Jain R, Kataria M, Ghosh S. Diabetes due to recurrent pancreatitis secondary to hypercalcem! ia due to primary hyperparathyroidism. Indian J Endocr Metab 2013;17:S212-4. Source of Support: Nil, Conflict of Interest: None declared.
Indian Journal of Endocrinology and Metabolism / 2013 / Vol 17 / Supplement 1
Copyright of Indian Journal of Endocrinology & Metabolism is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Diabetes due to recurrent pancreatitis secondary to hypercalcemia due to primary hyperparathyroidism Sumit Kumar Chakrabarti, Dibakar Biswas, Sandeep Chaudhury, Rajesh Jain, Manoj Kataria, Sujoy Ghosh Department of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India
A B S T R A C T Acute pancreatitis due to hypercalcemia associated with hyperparathyroidism (HPT) is not very common. We herein report a case of a 21-year-old woman, who presented with acute pancreatitis. She had a past history of recurrent nephrolithiasis. Subsequent evaluation revealed hypercalcemia (serum calcium: 12.6 mg/dL); low phosphate (2.9 mg/dL) with elevated parathyroid hormone (PTH, 156.7 pg/mL) and HbA1c (6.9%). Diagnosis of primary HPT (PHPT) was made. Recurrent pancreatitis due to hypercalcemia may have resulted in diabetes mellitus. Key words: Diabetes, diabetes mellitus, hypercalcemia, hyperparathyroidism, pancreatitis, primary hyperparathyroidism
INTRODUCTION
CASE REPORT
Episodes of acute pancreatitis can be recurrent, if the underlying factor remains uncorrected. Alcohol, autoimmune diseases, injury, and drugs are identified causes for recurrent pancreatitis.[1] Primary hyperparathyroidism (PHPT) is a rare cause for pancreatitis. PHPT is associated with high parathyroid hormone (PTH) levels, which usually leads to hypercalcemia and hypophosphatemia. Patients may present with recurrent nephrolithiasis, or be asymptomatic, detected on routine biochemical screening.[2] PHPT patients are also associated with altered carbohydrate metabolism characterized by insulin resistance, hyperinsulinemia, and glucose intolerance and even frank diabetes. However, the corelation between the two remains controversial and has been explained only based on few case reports.[3] We present a patient with recurrent episodes of pancreatitis primarily due to hypercalcemia of PHPT and eventually leading to diabetes mellitus.
A 21-year-old woman, presented with acute onset of abdominal pain over epigastric region radiating towards back with vomiting.
Access this article online Quick Response Code: Website: www.ijem.in DOI: 10.4103/2230-8210.119575
On admission
The patient was overweight with a body mass index (BMI) of 24.8 kg/m 2. General physical examination was noncontributory apart from a nodule in the lower pole of right lobe of thyroid gland. No acanthosis nigricans and hirsutism were seen. Her menstrual history was normal. Systemic examinations revealed mild hepatomegaly. However, serum amylase and lipase were high [Table 1]. Abdominal ultrasonography revealed features suggestive of acute pancreatitis along with left renal calculus. There was no evidence of gall stones. The patient was diagnosed with acute pancreatitis and managed conservatively. Past history
The patient’s past history shows repeated episodes of abdominal pain over last 3 years, which required hospitalization. There was recurrent history of pain in the flanks and on two occasions she had passed stones while passing urine. Straight X-ray of kidney, ureter, and bladder region showed the presence of renal stones in both the kidneys. There was no history of polyuria and polydipsia.
Corresponding Author: Dr. Sumit Kumar Chakrabarti, Department of Endocrinology and Metabolism, Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata - 700 020, West Bengal, India. E-mail: [email protected]
S212
Indian Journal of Endocrinology and Metabolism / 2013 / Vol 17 / Supplement 1
Chakrabarti, et al.: Pancreatitis due to hypercalcemia associated with PHPT
She had a history of constipation. She however did not have any behavioral or mood disorders. The patient was then diagnosed with recurrent pancreatitis and nephrolithiasis. Course in hospital
During the course of pancreatitis she never had any hypocalcemia. On repeated occasion her serum calcium was around 10 mg/dL. Her serum albumin was within normal range. She was detected to have diabetes mellitus with HbA1c 6.9% and was put on insulin. Lipid profile, liver function, renal function, and thyroid function tests were normal. Prothrombin time was 11.6 s (control 11.5 s) with international normalized ratio (INR) 1.01. Routine urine analysis was also normal. CT scan did not reveal any growth. Further investigation of laboratory parameters, such as serum calcium, albumin, and PTH was abnormal [Table 2]. Thyroid ultrasonography showed small, well defined, oval shaped hypoechoic structure just inferior to the lower pole of right lobe of thyroid gland suggestive of parathyroid adenoma or small lymph node [Figure 1]. Abdominal contrast-enhanced computed tomography Table 1: Laboratory analysis Parameters
Results
Normal levels
Serum amylase Serum lipase
970 U/L 2195 U/L
30-110 U/L 23-300 U/L
Table 2: Laboratory analysis Parameters Serum calcium Serum phosphorus Serum albumin Serum uric acid iPTH Serum 25 OH vitamin D
Results
Normal levels
12.6 mg/dL 2.9 mg/dL 4.5 g/dL 4.3 mg/dL 156.7 pg/mL 9.4 ng/mL
8.5-10.3 mg/dL 2.5-4.5 mg/dL 3.5-5 g/dL 2.5-7.5 mg/dL 15-65 pg/mL 10-55 ng/mL
(CECT) showed features suggestive of mild acute pancreatitis with left renal calculus. Magnetic resonance cholangiopancreatography showed chronic pancreatitis with no evidence of biliary obstruction or choledocholithiasis [Figure 2]. Diagnosis
Patient was diagnosed with PHPT causing hypercalcemia which resulted in nephrolithiasis and recurrent pancreatitis further leading to pancreatic diabetes.
DISCUSSION PHPT is an endocrine disorder, characterized by excessive secretion of PTH. Increased PTH leads to hypercalcemia and hypophosphatemia. [4] PHPT symptoms include polyuria, depression, nephrolithiasis, peptic ulcer, and pancreatitis.[5] Hypercalcemia due to HPT is not a very common cause for acute pancreatitis, usually seen between 1.5 and 7% in the different series.[4] Presentation of pancreatic disease in PHPT can be classified in four classes: 1. PHPT presenting as acute pancreatitis 2. PHPT presenting as acute recurrent pancreatitis with no evidence of chronic pancreatitis 3. PHPT presenting as chronic pancreatitis with or without pancreatic calcification 4. PHPT complicated by acute pancreatitis in the postoperative period. Literature review on case series suggested, PHPT patients presenting with acute pancreatitis are more common (44%) than those with chronic pancreatitis. But, no evidence has been reported for patients who developed acute pancreatitis in the postoperative state.[6]
iPTH: Intact parathyroid hormone
Figure 1: USG showing hypoechoic mass suggestive of parathyroid adenoma
Figure 2: Magnetic Resonance Cholangiopancreatography showing chronic pancreatitis
Indian Journal of Endocrinology and Metabolism / 2013 / Vol 17 / Supplement 1
S213
Chakrabarti, et al.: Pancreatitis due to hypercalcemia associated with PHPT
Several pathophysiological approaches are suggested to explain the relationship between pancreatitis and hypercalcemia. Few researchers have reported that patients with hypercalcemia secondary to HPT have low pancreatic secretion but normal enzyme activity. In such cases, pancreatitis may result due to damage of parenchymal cell and pancreatic duct caused by activation of intrapancreatic trypsinogen to trypsin due to high calcium concentration in pancreatic juice.[5,7,8] Few theories also suggest the mutations of genes such as serine protease inhibitor Kazal type 1 (SPINK1) or cystic fibrosis transmembrane conductance regulator (CFTR) may also be involved.[4] Pancreatitis is usually diagnosed before identifying HPT. Hypercalcemia during pancreatitis can be an indication for HPT, whereas hypocalcemia can occur during an attack of pancreatitis.[5,7] Patients with chronic pancreatitis due to PHPT also have significant incidence of renal colic, nephrolithiasis, and nephrocalcinosis.[6] In our case, there was no clear etiology for pancreatitis except hypercalcemia. So any patient with pancreatitis should be investigated for hypercalcemia to avoid missing the diagnosis of HPT.
S214
REFERENCES 1. 2.
3.
4.
5.
6. 7. 8.
Lara LF, Levy MJ. Idiopathic recurrent acute pancreatitis. Med Gen Med 2004;6:10. Misgar RA, Mathew V, Pandit K, Chowdhury S. Primary hyperparathyroidism presenting as recurrent acute pancreatitis: A case report and review of literature. Indian J Endocrinol Metab 2011;15:54-6. Reddy PA, Harinarayan CV, Suresh V, Jena A, Reddy MK, Kalawat TC, et al. Can diabetes associated with hyperparathyroidism be an additional indication for parathyroidectomy? A case report. Int J Endocrinol Metab 2009;3:208-11. Egea Valenzuela J, Belchi Segura E, Sanchez Torres A, Carballo Alvarez F. Acute pancreatitis associated with hypercalcemia. A report of two cases. Rev Esp Enferm Dig 2009;101:65-9. Nikolaidis LA, Leon MN, Paslidis NJ. Acute pancreatitis as the first manifestation of hyperparathyroidism in an otherwise asymptomatic patient. J Ark Med Soc 1995;92:273-5. Kumar R. A case of chronic pancreatitis due to hyper parathyroidism. Apollo Med 2010;7:54-7. Smith MD, Pawlak M, Pantanowitz DP, Botha RJ. Hyperparathyroidism and chronic pancreatitis. S Afr J Surg 1999;37:12-4. Kelly TR. Relationship of hyperparathyroidism to pancreatitis. Arch Surg 1968;97:267-74.
Cite this article as: Chakrabarti SK, Biswas D, Chaudhury S, Jain R, Kataria M, Ghosh S. Diabetes due to recurrent pancreatitis secondary to hypercalcem! ia due to primary hyperparathyroidism. Indian J Endocr Metab 2013;17:S212-4. Source of Support: Nil, Conflict of Interest: None declared.
Indian Journal of Endocrinology and Metabolism / 2013 / Vol 17 / Supplement 1
Copyright of Indian Journal of Endocrinology & Metabolism is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
