Diabetes due to recurrent pancreatitis secondary to hypercalcemia due to primary hyperparathyroidism.

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.

INTRODUCTION

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.

CASE REPORT

A 21-year-old woman, presented with acute onset of abdominal pain over epigastric region radiating towards back with vomiting.

On admission

The patient was overweight with a body mass index (BMI) of 24.8 kg/m2. 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.

Table 1

Laboratory analysis

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. 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].

Table 2

Laboratory analysis

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].

Figure 1

USG showing hypoechoic mass suggestive of parathyroid adenoma

Abdominal contrast-enhanced computed tomography (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].

Figure 2

Magnetic Resonance Cholangiopancreatography showing chronic pancreatitis

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:

PHPT presenting as acute pancreatitis

PHPT presenting as acute recurrent pancreatitis with no evidence of chronic pancreatitis

PHPT presenting as chronic pancreatitis with or without pancreatic calcification

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]

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.[578] 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.[57] 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.