Recurrent acute pancreatitis and primary hyperparathyroidism in patients presenting to the emergency department: Diagnostic challenges

Abstract

We read the article by Karim MM et al discusses the presentation of primary hyperparathyroidism as recurrent acute pancreatitis, a rare clinical condition in pediatric patients presenting to the emergency department. As emergency medicine clinicians, we frequently encounter diverse and complex cases, and such rare conditions pose significant challenges in the diagnostic process. This article will discuss the management and diagnostic approach of such cases encountered in the emergency department.

Key Words: Pancreatitis; Recurrent pancreatitis; Primary hyperparathyroidism; Hypercalcemia; Emergency medicine; Pediatric pancreatitis; Parathyroid adenoma; Abdominal pain; Multidisciplinary approach; Imaging techniques

Core Tip: Recurrent cases of acute pancreatitis can present a diagnostic challenge in the emergency department and are rarely caused by underlying endocrine disorders such as primary hyperparathyroidism (PHPT). PHPT can lead to hypercalcemia, increasing the risk of pancreatitis, which may present with less pronounced symptoms, especially in children. Emergency medicine clinicians should adopt a careful clinical assessment and multidisciplinary approach to differentiate rare etiologies, especially in cases of atypical pancreatitis. This case highlights that PHPT may be missed in pediatrics and suggests using high clinical suspicion and advanced imaging techniques to make the correct diagnosis.

INTRODUCTION

Abdominal pain is a common symptom among patients presenting to emergency departments, with acute pancreatitis being one of the most common causes[1]. While acute pancreatitis is usually associated with gallstones or alcohol consumption, in pediatrics, the etiology is more diverse and includes rare causes[2]. One of these rare causes is primary hyperparathyroidism (PHPT), which may increase the risk of pancreatitis through hypercalcemia[3]. PHPT develops due to adenomas of the parathyroid glands and is characterized by hypercalcemia. Hypercalcemia may contribute to the development of pancreatitis by increasing enzyme activation in pancreatic cells[4]. The clinical presentation of PHPT, especially in children, is often atypical and ambiguous, which can complicate the diagnostic process[5,6]. The unexpected presentation of PHPT, such as recurrent acute pancreatitis, increases the diagnostic challenges of this condition[6]. This delay can cause the patient to unnecessarily experience recurrent episodes of pancreatitis and develop potentially serious complications[5]. In a recent article by Karim MM et al[7], a patient who presented to the emergency department with recurrent pancreatitis was diagnosed with PHPT. This demonstrates the importance of maintaining a high level of clinical suspicion and a multidisciplinary approach in difficult cases. With appropriate laboratory tests and advanced imaging methods, PHPT can be diagnosed early, and possible complications can be prevented with appropriate treatments. Therefore, this article will focus on epidemiology, risk factors, pathogenesis, clinical presentation, diagnostic methods, and therapy to increase awareness about PHPT and help clinicians diagnose it.

EPIDEMIOLOGY AND RISK FACTORS

Abdominal pain is one of the most common causes of emergency department visits, accounting for approximately 7% of all adult cases in emergency settings worldwide[8]. The etiology of abdominal pain in adults ranges from benign conditions such as gastrointestinal disorders to life-threatening emergencies such as acute pancreatitis, appendicitis, or gastrointestinal perforation[9]. In pediatrics, abdominal pain also accounts for a significant proportion of emergency department visits and is estimated to account for approximately 5%-10% of all cases[10]. In pediatrics, common causes of abdominal pain include infantile colic, constipation, gastroenteritis, systemic viral infections, infections outside the gastrointestinal tract (such as streptococcal pharyngitis, urinary tract infections, and lower lobe pneumonia), and mesenteric lymphadenitis[11]. Approximately 1.89% of children and adults who apply to the emergency department with complaints of abdominal pain are diagnosed with pancreatitis[12].

Acute pancreatitis is a significant cause of morbidity worldwide, with an annual incidence ranging from 30 cases to 40 cases per 100000 adults, depending on geographic and demographic factors[13]. Acute pancreatitis mortality is around 1%-5%, varying depending on the severity of the disease, etiology, and complications[14]. In adults, the leading causes of acute pancreatitis include gallstones, which account for 30%-50% of cases, and chronic alcohol abuse[15]. While less common than in adults, acute pancreatitis in children has been increasingly recognized, with an incidence of approximately 3 cases to 13 cases per 100000 children annually[16]. While common causes of pancreatitis in pediatrics include trauma, infections, and hereditary diseases, rare conditions such as PHPT are often overlooked. However, it should be kept in mind that PHPT may lead to acute pancreatitis due to hypercalcemia, and this condition may rarely be seen in children[17]. Hypercalcemia disrupts the secretory functions of the pancreas by causing calcium deposition in the pancreatic ducts, leading to enzyme activation within the pancreas. This process can trigger the development of pancreatitis. If left untreated, PHPT often results in recurrent episodes of pancreatitis, making early diagnosis and appropriate treatment crucial[7].

PHPT is a relatively common endocrine disorder, with an estimated prevalence of 1-7 per 1000 adults[18]. The most common cause of high serum calcium levels is PHPT, which occurs in approximately 30 cases per 100000[4]. Epidemiological data suggest that PHPT-related hypercalcemia is a rare but important cause of acute pancreatitis in adults, contributing to approximately 3%-13% of cases[19]. PHPT is rare in children and often presents with atypical symptoms, creating diagnostic challenges for emergency clinicians[20]. When such cases are encountered in the emergency department, it is crucial to consider PHPT as an underlying cause of hypercalcemia, particularly in patients with recurrent episodes of pancreatitis. The study by Karim MM et al[7] highlights the challenges in diagnosing PHPT when the patient initially presents with normal parathyroid hormone levels, emphasizing the importance of clinical suspicion, especially in cases of recurrent attacks.

PATHOGENESIS

The pathogenesis of PHPT is associated with hypercalcemia, usually caused by a parathyroid adenoma. Hypercalcemia can increase the autoactivation of trypsinogen in pancreatic acinar cells, which can lead to pancreatic auto-damage[21]. In addition, calcium deposits can obstruct the pancreatic ducts, blocking the flow of pancreatic secretions and increasing inflammation[22]. Elevated serum calcium levels may be a diagnostic clue in patients presenting with symptoms of pancreatitis in the emergency department. Many studies have shown that the association between pancreatitis and PHPT is due to hypercalcemia. However, it is crucial not to rule out PHPT when calcium levels are normal or slightly elevated[3,4,22-27].

While PHPT is typically associated with hypercalcemia, it can also manifest in normocalcemic patients, which adds complexity to the diagnostic process. In cases of normocalcemia, the mechanism behind pancreatitis is not entirely understood; however, it is hypothesized that the elevated serum parathyroid hormone may affect pancreatic enzyme activation despite normal calcium levels[28,29]. This highlights the importance of considering PHPT as a potential underlying cause in patients with recurrent pancreatitis, even when calcium levels are normal. The case reported by Karim MM et al[7] underscores the significance of recognizing this atypical presentation of PHPT to ensure accurate diagnosis and appropriate management.

CLINICAL PRESENTATION

PHPT is an endocrine disorder characterized by hypercalcemia, usually asymptomatic, resulting from overactivity of the parathyroid glands. PHPT has a broad spectrum of clinical manifestations and often follows a silent clinical course[30]. However, in some cases, specific symptoms and complications due to hypercalcemia may occur[31]. Acute pancreatitis is a rare but essential presentation of PHPT in emergency departments. This is associated with the effects of hypercalcemia on the pancreas[4]. The clinical presentation of PHPT can be summarized by the classic “skeletal, renal, gastrointestinal, and neuropsychiatric” symptoms. Skeletal symptoms may manifest as loss of bone mineral density, such as osteopenia and osteoporosis, while renal symptoms may include nephrolithiasis (kidney stones) and polyuria. Gastrointestinal symptoms include loss of appetite, nausea, vomiting, and abdominal pain. Neuropsychiatric symptoms may include fatigue, depression, cognitive impairment, and distraction[32]. In general, these symptoms are non-specific and can be seen in many patients in the emergency department. Therefore, it should be kept in mind that the most critical factor in the diagnosis is suspicion.

Early and accurate diagnosis of PHPT is essential in patients presenting to the emergency department. Hypercalcemia-induced pancreatitis usually occurs due to increased calcium levels triggering enzyme activation in pancreatic cells. High serum calcium levels can cause autoactivation of trypsinogen in pancreatic acinar cells, leading to pancreatic tissue damage. Therefore, evaluating serum calcium levels is essential in the early detection of PHPT, mainly before recurrent pancreatitis develops[4]. Since the clinical presentation of PHPT is usually non-specific, the diagnosis may be delayed in many cases. Physical examination findings are often vague and limited to signs characteristic of pancreatitis, such as abdominal distension and tenderness. In such cases, it is crucial to maintain a high index of suspicion for PHPT[5].

Emergency department clinicians should act with a high clinical suspicion to differentiate rare endocrine disorders such as PHPT, especially in cases of recurrent pancreatitis in pediatric patients. A multidisciplinary approach and advanced imaging techniques can improve diagnostic accuracy and allow for rapid initiation of appropriate treatment[33].

DIAGNOSTIC TOOLS

The diagnostic process begins with a thorough clinical evaluation of patients presenting to the emergency department with suspected acute pancreatitis. Classic symptoms include sudden, severe upper abdominal pain radiating to the back, often accompanied by nausea and vomiting. A detailed medical history is essential, focusing on risk factors such as alcohol use, gallstone disease, and metabolic disorders. Laboratory tests are pivotal, with serum lipase being the preferred marker due to its high sensitivity and specificity. A threefold elevation in serum lipase levels above the upper limit of normal is typically diagnostic. Elevated amylase levels may also be present but are less specific. Additional tests, such as alanine aminotransferase for biliary etiology and CRP for inflammation severity, can further inform the diagnosis[34-36].

Imaging studies are crucial for confirming the diagnosis and identifying complications. Abdominal ultrasonography is often the first choice to assess for gallstones and biliary tract disease. Contrast-enhanced computed tomography is the gold standard if the diagnosis is uncertain or complications like necrosis are suspected. magnetic resonance imaging and magnetic resonance cholangiopancreatography are practical alternatives, particularly when detailed imaging of the pancreatic ducts and biliary system is required. The diagnosis of acute pancreatitis is confirmed when two of the following three criteria are met: Characteristic abdominal pain, serum lipase or amylase levels at least three times the upper limit of normal, and imaging findings consistent with pancreatitis[34-36].

While PHPT is a rare cause of acute pancreatitis, particularly in the emergency setting, it remains an important differential diagnosis due to the potential for recurrent episodes if left untreated. However, it is essential to note that PHPT is not typically among the first diagnoses considered in cases of acute pancreatitis in the emergency department, and routine assessment for PHPT, including neck ultrasonography, is not common practice in this setting. For patients with recurrent or unexplained pancreatitis, a broader diagnostic approach should be taken, which may include advanced imaging techniques to explore less common etiologies. Neck ultrasonography is a widely used non-invasive method for detecting parathyroid adenomas and can be an effective diagnostic tool if PHPT is suspected. Additionally, nuclear medicine methods, such as scintigraphy, can be utilized to assess the functional activity of the parathyroid glands, further aiding in the diagnosis[37,38].

In a case report by Karim MM et al[7], the patient’s serum parathyroid hormone levels were within the normal range before the diagnosis of parathyroid adenoma. Still, advanced imaging modalities allowed the correct diagnosis to be made. This case highlights the importance of a multidisciplinary approach in diagnosing PHPT and a careful evaluation process in the emergency department. In the diagnosis and treatment process of PHPT, especially in complex cases encountered in the emergency department, a careful clinical assessment and multidisciplinary approach are of great importance. Emergency medicine clinicians should carefully evaluate serum calcium levels and parathyroid hormone levels, considering the rare etiologies seen in pediatric patients. Even in cases where parathyroid hormone levels are within the normal range, advanced imaging techniques, especially neck ultrasonography, and scintigraphy, should be used to confirm the diagnosis of PHPT and to make the necessary planning for surgical intervention. In this process, the collaboration of specialists from different disciplines, such as endocrinologists, pediatric gastroenterologists, radiologists, and surgeons, increases diagnostic accuracy and enables the creation of optimal treatment plans. In addition, the involvement of supportive healthcare personnel, such as nutritionists and pediatric nurses, is critical for long-term patient management and quality of life. This multidisciplinary approach can improve patient outcomes by preventing unnecessary delays in diagnosing and treating PHPT.

TREATMENT

The treatment of PHPT usually involves surgical removal of the parathyroid adenoma. In patients diagnosed with PHPT in the emergency department, it is essential to control hypercalcemia symptoms and plan appropriate treatment. Surgical intervention is usually an effective method for controlling the symptoms of hypercalcemia and preventing complications[39]. The primary treatment for PHPT patients is surgical treatment. In a case report by Karim MM et al[7], following the surgical removal of a parathyroid adenoma, the patient’s serum calcium levels normalized, and the episodes of pancreatitis ceased. After surgical intervention, the patient’s serum calcium levels should be monitored, and it should be confirmed that the symptoms of hypercalcemia are under control. Keeping calcium levels under control is also critical to prevent long-term complications. In this context, it is recommended that patients be informed about diet and lifestyle changes after surgical intervention and supportive therapies should be applied when necessary.

CONCLUSION

Cases encountered in the emergency department are often complex and diverse. As emergency medicine clinicians, we must deal with common and rare conditions. The case presented by Karim MM et al[7] demonstrates that PHPT, a rare condition in pediatrics, can present as recurrent pancreatitis. This case highlights the diagnostic challenges of PHPT and the difficulties encountered in clinical management and provides a valuable contribution compared to similar cases in the literature. Difficulties in the diagnosis of PHPT are often related to the fact that parathyroid hormone levels are initially within the normal range and symptoms are atypical. In the literature, such conditions leading to delayed diagnosis of PHPT have been frequently reported[40]. Therefore, it is recommended to use advanced diagnostic tools and a multidisciplinary approach in case of clinical suspicion in the emergency department setting.

The pediatric patient presented with recurrent episodes of pancreatitis and was eventually diagnosed with parathyroid adenoma. The etiology of the pancreatitis was not clear before the diagnosis was made, but advanced imaging techniques allowed the correct diagnosis to be made. This case demonstrates that PHPT may be associated with pancreatitis, albeit rarely, in pediatrics and emphasizes the need for careful clinical evaluation during the diagnostic process. PHPT should be considered in the differential diagnosis when encountering cases of recurrent pancreatitis in the emergency department setting. PHPT poses a diagnostic challenge for clinicians due to its rarity. However, it should be remembered that it may present with atypical symptoms, especially in pediatric patients. The study by Karim MM et al[7] provides essential information to healthcare professionals on the early diagnosis and management of such rare cases. It contributes to raising awareness in the literature.