Primary Hyperparathyroidism as a Rare Cause of Unexplained Recurrent Abdominal Pain: Case Presentation and Literature Review

Abdominal pain is a common symptom in surgical practice. Around 11%-45% of pediatric population present with abdominal pain. In 29%-87.5% of pediatric population diagnosed with primary hyperparathyroidism (PHPT), abdominal pain and other gastrointestinal (GI) symptoms were the presenting complaint. Hyperparathyroidism is a condition characterized by increased parathyroid hormone (PTH) secretion. It usually presents with nonspecific symptoms of fatigue, poor appetite, weight loss, abdominal pain, nausea, emesis, and bone pain. We present a case of a 13-year-old girl who experienced a recurrent abdominal pain associated with nausea and vomiting, which was diagnosed eight months later when her laboratory investigation revealed high amylase, calcium, and PTH, which raised a suspicion of pancreatitis secondary to hyperparathyroidism. Imaging studies showed retrosternal lesion within the thymus gland, most likely a thymic parathyroid adenoma. The patient's symptoms resolved following thoracoscopic thymectomy, which was performed in another center. To assess the relationship between GI symptoms and PHPT, we reviewed 13 articles published between 2007 and 2020 in the English literature which reported 331 cases of primary PHPT and found that GI symptoms are the fourth most common presentation in patients with PHPT. In those patients, the reported incidence of GI symptoms including abdominal pain was 18.67%. Out of the 331 cases included, only one case mimicked our case as abdominal pain was the main presenting symptom. Unexplained recurrent abdominal pain should raise the suspicion for rare causes. Hyperparathyroidism should be included in the differential diagnosis of recurrent abdominal pain.


Introduction
Recurrent abdominal pain is not an uncommon symptom in children and is frequently described as nonspecific [1]. However, 8-30% of pediatric patients presenting with abdominal pain can originate from organic conditions [1]. In one study by Belcher et al., gastrointestinal (GI) symptoms including abdominal pain, nausea, and constipation were the main complaints in 29%-87.5% of the pediatric population diagnosed with hyperparathyroidism [2]. Another study by Abboud et al. demonstrated that vague abdominal pain comprises 29% of symptomatic pediatric patients with hyperparathyroidism [3].
Hyperparathyroidism is a condition characterized by increased parathyroid hormone (PTH) secretion. Patients with hyperparathyroidism usually present with nonspecific symptoms of fatigue, poor appetite, weight loss, abdominal pain, nausea, emesis, and bone pain [4]. Serum calcium and serum PTH level are essential to establish the diagnosis. Technetium (99mTc) sestamibi scan is performed to locate the hyperfunctioning gland [5]. Ectopic parathyroid adenoma was located in 22% of all cases of children and usually close to the thymus [4]. Additionally, multiple endocrine neoplasia type 1 syndrome (MEN1) was identified in 23% of children with hyperparathyroidism, whereas only 2.6% had multiple endocrine neoplasia type 2 syndrome (MEN2) [6]. Surgical treatment by parathyroidectomy is required for definitive treatment [7].

Case Presentation
We report the case of a 13-year-old girl who was medically and surgically free with an eight months history of vague recurrent attacks of abdominal pain, nausea, vomiting, and migratory joint pain. During her several visits to medical centers, the physical examination was unremarkable, but at her last presentation to a higher medical center her laboratory investigation revealed elevated amylase and lipase indicating pancreatitis. At this stage, the patient was transferred to our center for further investigations. Further laboratory investigation showed high PTH (339.4 pg/mL; normal range: 22-88 pg/mL), total calcium (3.02 mmol/L; normal range: 2.2-2.7 mmol/L), adjusted calcium (2.83 mmol/L; normal range: 2.10-2.55 mmol/L), and total 25-OH vitamin D (35.2 nmol/L; optimal: >75 nmol/L). With this high PTH and calcium level, diagnosis of primary hyperparathyroidism (PHPT) was established. CT scan was performed, which showed a lesion in the anterior mediastinum, as seen in Figure 1. To localize the hyperfunctioning gland, sestamibi scan was performed, as seen in Figure 2. Genetic testing ruled out MEN1 and MEN2. The patient then underwent laparoscopic thymectomy in a different center, and the family reported that the symptoms had resolved.

Discussion
In order to assess the relationship between GI symptoms and PHPT, we reviewed 13 articles published between 2007 and 2020 in the English literature, which reported 331 cases of primary PHPT, and found that GI symptoms are the fourth most common presentation in patients with PHPT. There were no reports in the English literature discussing PHPT as a primary cause of recurrent vague abdominal pain. Search terms included "primary hyperparathyroidism", "children", "pediatrics", "adolescents", "adenoma", "ectopic", and "hyperplasia". Ages range from 0 to 19 years. Retrospective review studies, literature reviews, and case reports were included. Parathyroid adenoma, symptoms, and management were the main focus, whereas other parathyroid pathologies such as hyperplasia and carcinoma were excluded. We ended up yielding a total of 35 articles. After excluding the articles that did not meet the criteria, we used 13 articles, as seen in Table 1, with a number of 331 patients. Eleven of these articles reported the site of adenoma. In those patient, the reported incidence of GI symptoms including abdominal pain were 18.67%.   Table 2 illustrates that GI symptoms including abdominal pain were the fourth most common presenting symptom of hyperparathyroidism in pediatrics and adolescent. Patients also presented with other symptoms, as shown in Table 2.  The diversity of nonspecific symptoms such as inability to concentrate, headaches, bone pain, deformity, fractures, fatigue, growth retardation, and abdominal pain makes the diagnosis challenging to physicians [2]. Since these symptoms are common in pediatric and adolescent age groups, the diagnosis is considered challenging. Furthermore, 91% of symptomatic pediatrics and adolescents have had severe complications such as nephrolithiasis, nephrocalcinosis, pancreatitis, bone and joint deformities, and fractures [2]. Since unexplained recurrent abdominal pain could be the only presenting symptom, hyperparathyroidism should be included in the differential diagnosis.

Conclusions
Unexplained recurrent abdominal pain should raise the suspicion for rare causes. Hyperparathyroidism should be included in the differential diagnosis of recurrent abdominal pain. Diagnosis of PHPT is almost delayed in all children with atypical symptoms. For that reason, we presented this case to draw attention to the diagnosis of PHPT with recurrent abdominal pain as the main symptom in order to prevent further complications.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. King Abdullah International Medical Research Center issued approval nrj213/044/02. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.