Why does hyperparathyroidism cause pancreatitis

Karakas, V. Fendrich, K. Bulut, T. Horn, R. Lebert, et al. Pancreatitis risk in primary hyperparathyroidism: relation to mutations in the SPINK1 trypsin inhibitor N34S and the cystic fibrosis gene.

Am J Gastroenterol, , pp. Rosendahl, H. Witt, R. Szmola, E. Bhatia, B. Landt, et al. Chymotrypsin C daldecrin variants that diminish activity or secretion are associated with chronic pancreatitis. Nat Genet, 40 , pp. Fendrich, R. Lebert, D. Bartsch, K. Exp Clin Endocrinol Diabetes, , pp.

Publication History. Subscribe to our newsletter. Print Send to a friend Export reference Mendeley Statistics. Article options. An interesting clue indicating the correlation between acute pancreatitis and primary hyperparathyroidism is fast and surprising clinical recovery of patients with pancreatitis and hyperparathyroidism after surgical removal of the parathyroid gland 5. However, due to the limited evidences, there is no verification on the exact pathogenesis of pancreatitis in primary hyperparathyroidism 4.

Hence, it is recommended that the determination of serum calcium in case of repeated acute pancreatitis might be useful for the early detection of occulted primary hyperparathyroidism. However, in cases with abnormal serum calcium level, a complete laboratory investigation on other endocrine and autoimmune disorder should be done.

At least, a thyroid assessment is recommended since the abnormal serum calcium level can also be the manifestation of thyroid disorder. In addition, since the condition of pancreatitis in primary hyperthyroidism can be chronic, the investigation of other complications such as diabetes mellitus is useful. Wiwanitkit, V. Iranian Journal of Pathology , 7 3 , Viroj Wiwanitkit. Iranian Journal of Pathology , 7, 3, , Patients characteristics are summarized in Table 1.

The secreting lesion was found in all cases by ultrasound or computed tomography. This was a parathyroid nodular lesion in 3 patients. In one case, the nodule was lateroesophageal right at the cervicothoracic hole whose character of hyperfunctional parathyroid was confirmed by MIBI-Tcm scintigraphy Figure 1. For the last patient, a parathyroid lesion or suspicious cervical or thoracic lesion has not been found at scanner and MRI.

But the abdominal CT scan showed a left adrenal lesion whose appearance might suggest an ectopic parathyroid lesion. However, she could not get a scintigraphy for confirmation. Thus, the etiology of hyperparathyroidism was adenoma with variable size in our five patients with parathyroid localization in 3 cases and ectopic in 2 cases.

Multiple endocrine neoplasia MEN was investigated in all patients with the dosage of calcitonin and urinary methoxyamines that were negative in all cases. Furthermore, two patients who had an AP on CP had bilateral renal lithiasis. Therapeutically, all patients initially received symptomatic management of the AP.

Only one patient received bisphosphonates awaiting surgery. An explorative cervicotomy was performed in three patients with resection of the parathyroid adenoma. The patient who is 74 years old did not have surgery due to significant comorbidities. The death was noted in one who had severe AP, following a superinfection of necrosis flows.

The outcome was favorable in 3 patients operated on, with normalization of PTH and serum calcium and no recurrence of the AP. The other one with CP and PHPT, who was not operated on, presented recurrent minor abdominal pain relieved by simple painkillers. The occurrence of pancreatitis secondary to PHPT is not so rare, with a prevalence of 3. Our hospital prevalence of 1. The discovery of a pancreatic disease increases by 33 the risk of having a PHPT [ 2 ], while the existence of PHPT would multiply by a factor of 10 to 30 the risk of pancreatitis [ 1 — 3 ].

Some authors, however, refute this increased risk of pancreatic disease with PHPT. Indeed, they found in the general population, a prevalence of pancreatitis lower or equivalent in patients with PHPT than in the control group [ 4 , 5 ].

Pancreatitis occurs at an advanced stage of parathyroid disease [ 1 ], which would explain the low prevalence of this association in the developed countries, PHPT being diagnosed earlier. The mean age at diagnosis is variable, but patients are older than those with only PHPT [ 2 , 6 ].

They are young adults in midlife in the cases described in India and Latin America [ 2 , 7 , 8 ], while patients were older 60—70 years in the United States and France [ 5 , 6 ]. Our series has the feature of having only women with an average age of 54 years. The occurrence mechanism of pancreatitis during PHPT remains controversial but may be related to hypercalcemia, only statistically significant factor associated [ 6 ].

Shah suggested that a high calcium level in more than 1. In the CP, this mechanism seems obvious ahead of calcium deposits in the absence of other causes. Hypercalcemia would act by several mechanisms: increased level of calcium in pancreatic juice at the origin of activation of trypsinogen to trypsin; activation of pancreatic enzymes through the lysosomal system and hydrolases; calcium precipitation and formation of protein plugs responsible for upstream pancreatitis.

A genetic risk factor has also been found. In our patients, hypercalcemia present in all cases despite pancreatitis seems to be the main mechanism. Thus, viewing these different mechanisms, the association of PHPT and pancreatitis can take many forms.

So, Jacob et al. The diagnosis of AP is classic in front of abdominal pain, with the dosage of pancreatic enzymes and imaging.

There may be varying severity of AP. In our patients AP was benign in 4 of 5 cases, unlike the series of Gupta et al. This AP may occur on normal pancreas or CP. In the meta-analysis of Bai et al. The PHPT was diagnosed in all of our patients in the course of etiological research of this pancreatitis and hypercalcemia. The diagnosis is made by the PTH dosage which was elevated in 4 of our patients. The localization of the secretory lesion was made by the anterior cervical ultrasound and CT scan.

This examination confirmed the hyperfunctional character of this parathyroid laterocervical nodule. Parathyroid lesion was in any case an adenoma in our series, as in Indian series [ 2 , 7 , 12 ].

It was ectopic in two cases out of 5. The discovery of PHPT imposes the research of other events related to hypercalcemia. Diagnosis is challenging because of non-specific symptoms and changes in maternal calcium homeostasis. Information about the optimal treatment strategy for the prevention of catastrophic consequences to the mother and foetus is limited.

Here, we describe a rare lethal case of severe acute necrotizing pancreatitis due to a parathyroid adenoma in a woman in her third trimester of pregnancy. PHPT-induced acute necrotizing pancreatitis was diagnosed on the basis of her serum calcium, parathyroid levels and imaging results.

Histological examination confirmed a right inferior parathyroid adenoma with a size of 2. Following the parathyroidectomy, the patient had eucalcaemia and presented normal parathyroid hormone PTH levels.

Although the foetus was normal, the patient died of multiple organ failure due to severe pancreatitis. PHPT-induced acute necrotizing pancreatitis is a rare clinical entity and life-threatening condition to both the mother and the foetus during pregnancy. Early diagnosis can be challenging and is crucial. Peer Review reports. Primary hyperparathyroidism PHPT , the most common cause of hypercalcaemia, predominates among postmenopausal women and has a female:male ratio of 3— [ 1 ].

PHPT is diagnosed on the basis of the persistent elevation of serum calcium levels with corresponding elevated or inappropriately normal PTH levels [ 3 ]. The manifestations of PHPT often vary due to hypercalcaemia itself and its effects on target organs.

Symptoms of PHPT include polyuria, osteopenia, depression, constipation, vomiting, and even potentially life-threatening hypercalcemia and pancreatitis [ 1 ]. PHPT during pregnancy occurs rarely and often goes undiagnosed due to a lack of symptoms, non-specific presentation and gestational physiological changes [ 4 ].

Worsening hypercalcaemia may cause acute pancreatitis during pregnancy or after delivery. Few cases of pancreatitis due to PHPT during pregnancy have been reported, and those that have been reported were generally mild oedematous pancreatitis.

Past medical and routine obstetric examinations were unremarkable. She denied a history of familial endocrine tumours and there was no history of alcohol abuse or smoking. Her vital signs were stable, and a physical examination revealed rebound tenderness in the epigastric area. The foetal heart rate was a reassuring beats per minute. Initial laboratory data showed the following: white blood cell count, Her liver function and triglyceride were normal.

An ultrasound examination revealed the patient had exudative pancreatitis with peripancreatic fluid as well as bilateral nephrolithiasis and biliary sludge without evidence of cholelithiasis. The patient was diagnosed with acute pancreatitis. Her pancreatitis was managed with fasting, intravenous fluids, analgesics, and empirical antibiotics; however, her clinical status and laboratory parameters did not improve. A caesarean delivery with spinal anaesthesia was performed the next day after the patient provided consent and discussed the procedure with a multidisciplinary team for high foetal risk.

Her symptoms of pancreatitis worsened, and an abdominal enhanced computed tomography CT scan revealed severe necrotizing pancreatitis Fig. The aetiology of pancreatitis showed that her initially ionized calcium levels were increasing, with a value of 1. Detailed relevant laboratory tests are shown in Table 1. The diagnosis of PHPT was confirmed. A single right inferior parathyroid adenoma 2. Histological examination revealed the chief-cell type of the parathyroid adenoma Fig.

However, the clinical situation of pancreatitis aggravated rapidly, and ultrasound revealed massive necrotizing tissue around the pancreas. The baby boy grew uneventfully during follow-up. Abdominal CT scan. It showed diffuse enlarged pancreas with indistinct boundaries and surrounding exudates a : non-contrast-enhanced image; b : arterial phase image; c : delayed phase image. Hematoxylin and eosin staining of the parathyroid adenoma. The adenoma was composed mainly of chief cells.