Recurrent acute pancreatitis as an initial presentation of primary hyperparathyroidism in juvenile patient

Abstract

Acute pancreatitis recurrence should always alert clinicians to primary hyperparathyroidism, especially in younger patients and those with a hereditary condition. When parathyroid abnormalities are adequately recognized and addressed, more recurrent attacks of acute pancreatitis are unlikely to occur.

Key Words: Acute pancreatitis; Parathyroid hormone; Primary hyperparathyroidism; Ultrasound; Scintigraphy; Dual-energy X-ray absorptiometry

Core Tip: Primary hyperparathyroidism is a very uncommon cause of acute pancreatitis. Medical management may go unreported due to primary hyperparathyroidism’s gradual progression and, on occasion, normal parathyroid hormone levels despite hypercalcemia. The diagnosis and treatment of juvenile acute pancreatitis, particularly in its recurrent form, require a comprehensive work-up. Clinicians need to be aware that recurrent juvenile pancreatitis may be caused by primary hyperparathyroidism.

TO THE EDITOR

In gastroenterology, acute pancreatitis is one of the most frequent diagnoses at admission[1]. It is defined as a predominantly sterile pancreatic inflammation caused by aberrant enzyme activation. It produces an inflammatory response with a broad range of histological findings, from moderate edema to severe gland necrosis[1,2]. Regardless of the etiology, recurrent acute pancreatitis is characterized by two or more episodes of acute pancreatitis, with a symptom-free interval in between and no evidence of chronic pancreatitis[3]. Gallstones and ethanol consumption account for 70% of the cases of acute pancreatitis. Smoking, drug use (glucocorticoids, azathioprine, acetaminophen, furosemide, thiazides, lithium, carbamazepine, valproic acid, etc.), trauma, medical procedures (endoscopic retrograde cholangiopancreatography), infections (mumps), vascular diseases (polyarteritis nodosa, anti-neutrophil cytoplasmic antibody vasculitis), metabolic abnormalities (hypercalcemia, hypertriglyceridemia), and autoimmunity are other less frequent causes[1-3].

CASE REPORT ANALYSIS AND REVIEW OF THE LITERATURE

In this case report, the authors highlight how a juvenile patient’s acute pancreatitis was caused by undiagnosed primary hyperparathyroidism (PHPT)[4]. Despite hypercalcemia, the initial laboratory analysis revealed normal parathyroid hormone (PTH) levels, thus delaying the accurate diagnosis. Another episode of severe pancreatitis necessitated more extensive diagnostic tests and procedures, and a parathyroid adenoma was discovered during neck ultrasonography (US) and parathyroid scintigraphy. No additional pancreatitis attacks were observed following the successful surgical removal of the parathyroid adenoma[4]. The most common cause of PHPT is a single parathyroid adenoma, but additional causes include parathyroid malignancy and parathyroid hyperplasia, sometimes as the component of multiple endocrine neoplasia syndromes (MEN 1, MEN 2A). Persistent hypercalcemia results from unregulated PTH synthesis, which increases renal reabsorption of calcium and mobilizes calcium from the bone[5].

According to a study by Rashmi et al[6], the prevalence of acute pancreatitis in PHPT is 9.8%. Individuals who have both acute pancreatitis and PHPT tend to be younger and male[7]. Hypercalcemia is the primary cause of recurrent pancreatitis in PHPT patients. In addition to enhancing the formation of pancreatic calculi and ductal obstruction, it also promotes the conversion of trypsinogen to trypsin (the pancreatic autodigestion enzyme). This results in acute pancreatitis or recurrent episodes of chronic pancreatitis, particularly in individuals who are genetically predisposed[7-12]. Typically, the diagnosis of PHPT is mostly neglected before the occurrence of two or more pancreatitis episodes[1,3,11]. In one case report, acute pancreatitis occurred four times in 15 months in a 32-year-old male[12]. The association between PHPT and pancreatitis does not correlate just with acute but also subacute and chronic calcifying pancreatitis[13,14]. Another trick in the presented case was normal levels of serum PTH associated with hypercalcemia. Normohormonal PHPT incidence is a notable factor, ranging from 3% to 10.5%. This term refers to patients exhibiting normal PTH levels alongside hypercalcemia. These individuals are typically younger and present greater challenges in recognition and management[15].

PHPT is diagnosed by measuring serum calcium and PTH levels. In most patients with PHPT, both levels are elevated. Occasionally, an individual may present with normal or mildly elevated serum PTH levels alongside hypercalcemia. An elevated or normal PTH level suggests PHPT, as serum PTH is expected to be low in increased calcium levels. Individuals with familial hypocalciuric hypercalcemia exhibit this appearance, which results from a rare heterozygous mutation in the gene encoding the calcium-sensing receptor, leading to a lifelong elevation in serum calcium levels. Alterations in PTH levels frequently coincide with vitamin D deficiency; however, hypercalcemia is rare. Accurate diagnosis of PHPT involves measuring serum PTH, calcium, and 25-hydroxyvitamin D levels, along with urine calcium and creatinine excretion. Additionally, calculating the calcium/creatinine excretion ratio and conducting genetic panel testing for familial hypocalciuric hypercalcemia are essential components of the diagnostic process[16-18].

Parathyroid US serves as the principal imaging technique for assessing parathyroid disease. It has a sensitivity of 85% (95% confidence interval: 75.7%-91.2%) and a positive predictive value (PPV) of 95.2% (95% confidence interval: 87.5%-98.4%) to locate parathyroid adenomas 1.7 cm ± 0.9 cm in maximum diameter (69.4% in smaller glands), showing a significant correlation with maximum diameter and volume of the excised adenoma. The integration of technetium-99 methoxy-isobutyl-isonitrile scintigraphy with neck US exhibited enhanced diagnostic efficacy, achieving a sensitivity of 96.8% and a predictive value of 95.8%[19]. Additionally, the patients with PHPT undergo assessment for end-organ damage and complications through multiple diagnostic methods. Bone density is assessed by dual-energy X-ray absorptiometry. Serum creatinine is measured to evaluate kidney function, while 24-hour urine calcium excretion is assessed to determine kidney stone risk in patients with PHPT. Abdominal X-rays and US, or computed tomography, are utilized to identify silent kidney stones[16,17,19].

CONCLUSION

This case study shows the need to precisely determine the cause of a disease to prevent recurrences. In a young male patient presenting with recurrent pancreatitis, lacking a history of alcoholism or smoking, and with negative gallstone radiology, PHPT should be considered as a potential causative factor. A comprehensive investigation is warranted, even in the presence of hypercalcemia and normal serum PTH levels. Effective PHPT management can prevent pancreatic disease recurrence.