|Year : 2021 | Volume
| Issue : 1 | Page : 54-57
A rare case of pulmonary tuberculosis-associated hypercalcaemia and pancreatitis
CV Harinarayan1, Kini Dinesh2, Sachin Kumar3, HJ Vijay4, Anisha Tandon4, E Shanthi Sree5
1 Institute of Endocrinology, Diabetes, Thyroid and Osteoporosis Disorders, Sarka World Hospitals, Bengaluru, Karnataka; Department of Medicine and Endocrinology, Saveetha Institute of Medical and Technical Sciences University, Saveetha Medical College, Chennai, Tamil Nadu, India
2 Institute of Digestive and Hepatobiliary Sciences, Institute of Hepatobiliary Sciences, Sakra World Hospital, Bangalore, Karnataka, India
3 Department of Pulmonology and Critical Care, Sarka World Hospitals, Bengaluru, Karnataka, India
4 Department of Radiology, Sarka World Hospitals, Bengaluru, Karnataka, India
5 Institute of Endocrinology, Diabetes, Thyroid and Osteoporosis Disorders, Sarka World Hospitals, Bengaluru, Karnataka, India
|Date of Submission||05-Sep-2020|
|Date of Decision||30-Sep-2020|
|Date of Acceptance||26-Nov-2020|
|Date of Web Publication||4-Mar-2021|
C V Harinarayan
Director, Institute of Endocrinology, Diabetes, Thyroid and Osteoporosis Disorders, Sakra World Hospitals, SY No 52/2 and 53/3, Deverabeesanahalli (Opp. Intel, Outer Ring Road), VarathurHobili, Marathahalli, Bengaluru 560 103, Karnataka
Source of Support: None, Conflict of Interest: None
Hypercalcaemia is commonly seen in the context of parathyroid dysfunction and malignancy. When severe, it can precipitate a life-threatening sequel. The diagnostic evaluation of hypercalcaemia is contributed by several competing aetiologies, multiple co-existing conditions and confounded by polypharmacy. A 60-year-old female was rushed to emergency with severe pain in the abdomen. Her serum calcium level was 3.92 mmol/l. Pancreatitis was confirmed by biochemical and radiological investigations. She was subsequently diagnosed to have smear-positive pulmonary tuberculosis (TB). She was successfully managed with intravenous fluids, diuresis and bisphosphonates and showed good response to anti-TB treatment. This case emphasizes considering pulmonary TB in the list of differential diagnosis for hypercalcaemia.
Keywords: Acute, hypercalcaemia, pancreatitis, pulmonary, tuberculosis
|How to cite this article:|
Harinarayan C V, Dinesh K, Kumar S, Vijay H J, Tandon A, Sree E S. A rare case of pulmonary tuberculosis-associated hypercalcaemia and pancreatitis. J Clin Sci Res 2021;10:54-7
|How to cite this URL:|
Harinarayan C V, Dinesh K, Kumar S, Vijay H J, Tandon A, Sree E S. A rare case of pulmonary tuberculosis-associated hypercalcaemia and pancreatitis. J Clin Sci Res [serial online] 2021 [cited 2021 Apr 12];10:54-7. Available from: https://www.jcsr.co.in/text.asp?2021/10/1/54/310769
| Introduction|| |
Pancreatitis is a life threatening clinical condition that is often seen in Medical Emergency. Hypercalcemia causing pancreatitis is known and is often due to Parathyroid adenoma. Other non-parathyroid causes of Hypercalcemia a granulomatous diseases, hematological and non-hematological malignancies. Sarcoidosis is the commonest cause of hypercalcemia due to granulomatous disorders. Tuberculosis (TB) is widely prevalent in India and its varied manifestations are well known. However this granulomatous disease leading to hypercalcemia and related pancreatitis is seldom reported. Here we present a case of pulmonary tuberculosis associated hypercalcemia and pancreatitis.
| Case Report|| |
A 60-year female presented to the emergency department with severe diffuse non-radiating abdominal pain with vomiting. She had significant weight loss (13–14 kg in 3–4 months), intermittent constipation, and loss of appetite and was diabetic and hypertensive on medications, with no history of fever or gastrointestinal (GI) bleed or allergies. On examination, she was afebrile with stable vitals, no pallor, icterus, cyanosis, clubbing, lymphadenopathy and oedema. Cardiovascular, respiratory and neurological examinations were normal, with no organomegaly. Laboratory investigations were random blood sugar 9.77 mmol/L, creatinine – 147.92 umol/L, sodium and potassium 125.5 and 4.14 mEq/L, respectively, normal bilirubin, serum albumin 2.9 g/dL, aspartate aminotransferase/alanine aminotransferase 60/45 IU/L (normal 15–41/14–54), serum alkaline phosphatase (SAP) 688 IU/L (normal 32–91), gamma-glutamyl transferase (GGT) 920 IU/L (normal 7–50), amylase/lipase 1060/2249 U/L (normal amylase/lipase 28–100/20–50), calcium (corrected) 3.92 mmol/L (normal 4.67), phosphorus 0.68 mmol/L, parathyroid hormone (PTH) 13.7 pg/mL (normal 12-88), 25-hydroxy vitamin D (25OHD) 56.4 ng/mL (normal 30-100) and elevated 1,25-dihydroxy vitamin D [1,25 (OH) 2D3] levels. A month ago, she was found to have 25OHD levels of 15.95 ng/mL and she was treated by a physician with cholecalciferol 60,000 IU weekly for 4 weeks. Serum electrophoresis did not reveal myeloma band. Other laboratory investigations were as follows: Serum kappa/lambda chains ratio 1.56 (normal 0.26–1.65), beta-2 microglobulin 10,111 ng/mL (normal 607–2295), angiotensin-converting enzyme (ACE) levels 36.2 IU/mL (normal 12–68), carcinoembryonic antigen 2.38 ng/mL (normal 0–3), cancer antigen 125 – 51 U/mL (normal 0–35), thyroid-stimulating hormone 1.66 μg/mL (normal 0.4–4.2), triglycerides 122 mg/dL, fasting blood sugar 141.1 mg/dL, glycosylated haemoglobin 6.8%; serum sodium and potassium normal. Peripheral blood smear did not reveal immature cells. Bilateral lung fields showed nodular lesions on chest radiograph, which were metabolically active on positron-emission tomography-computed tomography (PET-CT) [Figure 1], as well as metabolically active parenchymal thickening of the left breast extending to retro-areolar region [Figure 1]d. Bulky metabolically active pancreas suggesting pancreatitis was noted on PET-CT [Figure 1]e and [Figure 1]f. Fine-needle aspiration biopsy of breast lesion was negative for malignancy. CT guided biopsy of lung nodule [Figure 1]c revealed necrotising inflammation; Ziehl–Neelsen stain showed clumps of acid-fast bacilli.
|Figure 1: Chest radiograph showing multiple nodules (arrows) (a); PET-CT showing multiple fluorodeoxyglucose-avid nodules (arrow) (b); CT--guided biopsy of the left upper lobe lung nodule (arrow) (c) confirmed the diagnosis of TB. PET-CT showing fluorodeoxyglucose-avid lesion in the left breast (arrow) (d); CT showing bulky pancreas (arrow) (e). PET-CT showing fluorodeoxyglucose-avid pancreas (arrow) (f)|
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Hypercalcaemia was managed by intravenous fluids with diuresis and bisphosphonates. The serum calcium levels became normal [Figure 2]. Serum sodium and potassium-138.9 and 3.37 mmol/L on 3rd day after admission. Serum amylase and lipase were 79 and U/L respectively whereas serum creatinine was 1.11 mg/dL on 14th day after admission. SAP (IU/L) levels were 467 (5th day), 505 (14th day), 245 (3rd month) and 147 (5th month). GGT levels were 479 IU/L 2 weeks after admission. ACE levels on 21st day and 6 months later were 47.8 and 33.7 U/L, respectively. Anti-TB therapy was started. Serum transaminases and SAP normalised and the patient started gaining weight. A diagnosis of TB-associated hypercalcaemia and pancreatitis was made. Pancreatitis resolved with normocalcaemia. Postulated pathophysiology of pancreatitis in patients with TB is shown in [Figure 3].
|Figure 3: Pathophysiology of pancreatitis in patients with TB. PET-CT = Positron-emission tomography-computed tomography; CT = Computed tomography; TB = Tuberculosis|
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| Discussion|| |
A clinical diagnosis of non-PTH-related hypercalcaemia was made. Common causes for PTH-independent hypercalceamia are malignancies (solid tumours haematological malignancies), granulomatous diseases and endocrinopathies as hyperthyroidism, adrenal insufficiency, acromegaly and other rare causes.
Classical symptoms and signs of hypercalcaemia, namely stones, bones, abdominal moans and psychic overtones are not found in all patients. Our patient had GI symptoms (abdominal moans) such as severe abdominal pain, diffuse non-radiating with an episode of vomiting, significant weight loss 13–14 kg, associated with intermittent constipation and loss of appetite. Further biochemical and radiological evaluation revealed hypercalcaemia with normal PTH and pancreatitis. Hypercalcaemia can be because of bone resorption, increased intestinal absorption of calcium and increased reabsorption at level of renal tubules. Stable hypercalcaemia can turn into increased calcium levels. This can be due to severe infection and underlying conditions leading to clinical deterioration. This high calcium level leads to vicious cycle of preventing the reabsorption of water directly on the tubules leading to dehydration and pre-renal azotemia, with hydration serum creatinine being normalised. On achieving normocalcaemia, pancreatic enzymes normalised [Figure 3]. The rise in the GGT and SAP is due to oedema of the pancreatic head abutting the hepatobiliary structures.
Hypercalcaemia is often seen in primary hyperparathyroidism (PHPT), granulomatous disease and malignancy. However, among granulomatous disease, it is more frequent in sarcoidosis than other aetiologies, such as, TB and fungal infections. The prevalence of hypercalcaemia in patients with TB varies from 2.3% to 10%–48% across studies. It is supposed to be dependent on dietary calcium intake and Vitamin D status of an individual. In the past, hypercalcaemia secondary to TB was attributed to administration of cod liver oil, supplementation of Vitamin D for lupus vulgaris. Several other theories for hypercalcaemia in TB include alteration in metabolism of Vitamin D, impairment in degradation of PGE which further stimulate bone resorption secondary to increased osteoclast activating factor by chronic leucocyte activation in TB or isoniazid-induced. Autopsy findings of the patient with miliary TB and pancreatitis showed formation of multiple small microabscess affecting acinar tissue. Chronic calcific pancreatitis is commonly seen in patients with diabetes and TB. Literature supporting TB leading to hypercalcaemia and pancreatitis is sparse. However, granulomas leading to hypercalcaemia is well known. There are also other mechanisms where hypercalcaemia is a part of TB. This leads to calcium deposition in the ductal system of the pancreas causing obstruction and pancreatitis.
Vitamin D and calcium intake is known to be a plausible explanation for this variability. Drugs like rifampicin and isoniazid can reduce the substrate concentration (25OHD) and reduce the degree of hypercalcaemia. Rifampicin induces enzymes to degrade 25OHD, and isoniazid inhibits 1,25(OH) 2D3 synthesis [Figure 3].
There are not many reports of hypercalcaemia leading onto pancreatitis in patients with TB., In a recent case report, the authors reported symptomatic hypercalcaemia, acute pancreatitis and acute renal cortical necrosis in a patient with ileal TB. In the other recent case report, hypercalcaemia and acute pancreatitis were documented in a patient with acute promyelocytic leukaemia and pulmonary TB, during all-trans-retinoic acid treatment.
The present case highlights the probable mechanism of pancreatitis in a patient with TB.
The most common cause of hypercalcaemia-related pancreatitis is PHPT (PTH dependant). The causes of PTH-independent hypercalcaemia are malignancies (solid tumours and haematological malignancies) and granulomatous disorders (sarcoidosis and TB). The most common causes are multiple myeloma, lymphomas and solid tumours in order of occurrence. Hypercalcaemia in the background of severe and rapid weight loss associated with anorexia, nausea and vomiting granulomatous disorders should be considered. Hypercalcaemia is more common in sarcoidosis. For evaluation of hypercalcaemia, serum calcium has to be interpreted along with serum albumin, creatinine, SAP, PTH and 25(OH) D levels.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]