Misdiagnosis of macroamylasemia in pregnancy as pancreatitis

Introduction

Hyperamylasemia is characterized by excess serum amylase above the normal levels of 0-137 U/L and is one of the indications of pancreatitis [1]. However, a benign cause of elevated serum amylase is macroamylasemia caused by macroamylase in the blood. The present report concerns failure to carry out urinary amylase measurement in a pregnant woman with abdominal pain and elevated serum amylase but normal lipase, resulting in misdiagnosis of probable macroamylasemia as pancreatitis and unnecessarily aggressive management. The case emphasizes the need to consider macroamylasemia in all cases of elevated serum amylase.

Case

The patient was a nulligravid woman on her first pregnancy, a result of in vitro fertilization. She presented in her 32^nd week plus 3 days of gestation with regular contractions and antepartum vaginal bleeding, without cervical dilation or effacement. Ultrasonographic examination confirmed a complete placenta previa with placental mass overlying the internal cervical os (previously known). The patient had no other medical or surgical illness, and her family history was noncontributory.

The patient was administered ritodrine HCl intravenously to inhibit myometrial contractions, starting with 0.05 mg/min doses and increased by 0.05 mg every 10 min up to 0.15 mg/min doses. Oral nifedipine was also given in 20 mg initial doses, repeated every 6 h and then followed by 60 mg every 12 h for 48 h. The patient also received two doses of betamethasone to promote lung maturity.

On the day following hospitalization, the patient complained of right upper-quadrant and epigastric pain, which had first manifested at 26 weeks but had not been the subject of examination or laboratory tests. Pain was not associated with nausea and vomiting and was characterised as radiating from the back, fluctuant, unrelated to eating and causing awakening from night sleep. There was no history of urinary symptoms or constipation. Vital signs were stable, and the patient was afebrile.

Laboratory findings indicated white blood cell (WBC) count 15.1×10⁹/L, hemoglobin 9.8 g/dL, hematocrit 29.6% and platelets 232 k/μL. Serum chemistry values indicated sodium 137.6 mmol/L, potassium 3.58 mmol/L, chloride 106.3 mmol/L, CO₂ 27 mmol/L, blood urea nitrogen 7.0 mg/dL, creatinine 0.52 mg/dL, glucose 84 mg/dL, aspartate aminotransferase −17 IU/L, alanine transaminase −20 IU/L, alkaline phosphatase 70.2 IU/L, total bilirubin 0.56 mg/dL, prothrombin time 12-s, partial thromboplastin time −27.6 s and international normalized ratio (INR) 0.99. Elevated amylase of 861 U/L was noted but lipase was within normal range (32 U/L). Urinalysis indicated specific gravity 1.005, WBC 2–4 and many epithelial cells; remaining urinalysis results were unremarkable. C-reactive protein reactive levels were within normal limits. Urinary amylase measurement was not available in the hospital and was not performed elsewhere due to concerns of expense to the patient.

Abdominal ultrasound demonstrated minimal biliary sludge in the bladder. The gallbladder wall did not appear thickened, and no pericholecystic fluid was observed, nor was fluid identified in Morison’s pouch.

As serum amylase levels were not in keeping with the patient’s condition, a gastroenterology consult was sought. The patient was diagnosed with suspected acute pancreatitis and responded to conservative management and bowel rest. Intravenous hydration was started, via intracath (no. 16 1.75 mm/45 mm), changed daily, causing trauma for vessels and patient. Oral intake was stopped. A repeat serum amylase was carried out, and it was confirmed that levels remained elevated (1259 IU/L). This finding, along with normal lipase levels, suggested that in fact the patient had macroamylasemia rather than pancreatitis.

Fetal growth and well-being was closely monitored. The pregnancy progressed uneventfully and fetal growth was adequate. The patient was delivered of a healthy female infant weighing 2590 g with Apgars of 9 and 10 at 36 weeks’ gestation, by caesarean section for placenta previa. Perinatal outcomes for mother and infant were favorable. Mother and baby were discharged 2 days later. At a 6-week postnatal appointment, mother and baby were well, with no problems reported.

Discussion

Every case of high serum amylase levels is not due to acute pancreatitis; other reasons for hyperamialsemia should be considered before aggressive management is commenced. Macroamylasemia is a benign cause of hyperamylasemia resulting from the presence of immunoglobulin-bound amylase [2]. This macromolecule is too large to be filtered by the renal glomeruli and remains in the serum, resulting in high serum amylase levels but normal or decreased urinary amylase [3]. Macroamylasemia should be considered in any case of high serum amylase levels in the absence of clear clinical signs of pancreatitis or inflammation of salivary glands and differential diagnosis carried out. Differential diagnosis of macroamylasemia versus pancreatitis can be assisted by measurement of serum lipase, which is typically elevated in pancreatitis but normal in macroamylasemia, as in this case [4]. Measurement of urinal amylase, typically elevated in pancreatitis but normal or decreased in macroamylasemia, should be the main indicator for differentially diagnosing acute pancreatitis versus macroamylasemia. Analysis of serum amylase isoenzyme patterns is another useful indicator. Differential diagnosis in this case would have prevented unnecessary and expensive treatment for pancreatitis and spared stress to the patient caused by the pancreatitis misdiagnosis.

Macroamylasemia is usually without symptoms but can be accompanied by abdominal pain and should always be considered in cases of elevated serum amylase. One reported case in pregnancy concerned a 31-year-old G2P1, who complained of recurring right-sided abdominal pain. She also had elevated serum amylase and had previously been treated for acute cholecystitis and gallstone pancreatitis [5]. Nothing suggestive of acute cholecystitis or gallstone pancreatitis was found and the authors concluded that in such cases, urinary amylase and serum amylase isoenzymes should be evaluated. An example of misdiagnosis of pancreatitis on the basis of elevated serum amylase was the case of a 4-year-old girl with abdominal pain who was treated for pancreatitis, before macroamylasemia was confirmed by electrophoretic analysis of serum amylase isoenzyme patterns [6].

One possible reason for the elevated serum amylase in the case reported here was transient ritodrine-induced hyperamylasemia, which has been associated with tocolytic treatment of pregnant women with ritodrine HCl for preterm labor [7]. However, reported results are conflicting, for example, another more recent study on umbilical cord blood of pre-term infants suggested that ritrodine HCl treatment left serum amylase largely unchanged [8].