Primary hyperparathyroidism associated with multiple myeloma: a case report

Primary hyperparathyroidism associated with multiple myeloma: a case report

Meryam Elbahi^1,&, Sana Rafi¹, Ghizlane Elmghari¹, Nawal Elansari¹

¹Department of Diabetology, Endocrinology, Nutrition and Metabolic Diseases, Errazi Hospital, University Hospital Center Mohammed VI, Marrakech, Morocco

^&Corresponding author
Meryam Elbahi, Department of Diabetology, Endocrinology, Nutrition and Metabolic Diseases, Errazi Hospital, University Hospital Center Mohammed VI, Marrakech, Morocco

Introduction    

Hypercalcemia is a common clinical problem, it occurs in 15% of hospitalized patients [1]. Multiple Myeloma (MM) and Primary Hyperparathyroidism (PHPT) are among the most common causes of hypercalcemia but concomitant diagnosis of the two pathologic processes in one patient has have been included in a few reports. In this article we have discussed a patient presenting with this extremely rare phenomenon and have reviewed the relevant scientific literature.

Patient and observation     

Forty-six year old woman was admitted for malignant hypercaelcemia of 166mg/l, review of symptoms during admission was significant for anorexia, weight loss, general asthenia and polyuropolydipsic syndrome. Vitals at the time of admission were blood pressure 140/58mmhg, pulse 100 BPM, respiratory rate 18 c/mn, Laboratory data indicated anemia, leucopenia, trombopenia, concentrations of immunoreactive parathyroid hormone (PTH) were elevated 379,1ng/l, phosphorus was low 27 mg/dl, vitamine D was normal 32,48 ng/ml(30-75), albumin was low 21,1 g/dl, total protein was hight 100 g/dl (66- 87), blood urea nitrogen 0,29 g/l (0,25-0,48), creatinine 7 mg/l (5-9), GFR=168 ml/mn. The dosage of urinary metoxyl derivatives was negative, calcitinine was normal 3.6 (<10). X-ray and MRI of the upper left limb showed a brown tumor appearance of proximal radius (Figure 1), Cervical Ultrasound coupled to neck computed tomographic (CT) scans disclosed a mass on the posteroinferior aspect of the right lobe of the thyroid gland, it measures 1,48 * 1,2 cm (Figure 2), the diagnosis was primary hyperparathyroidism. Multiple myeloma was also suspected given the pancytopenia on the cell blood count associated to hypercalcemia. X-ray of the skull and lumbar spine showed diffuse bone lytic lesions of various sizes (Figure 3). Serum immunoelectrophoresis revealed only Lambda monoclonal bow, urine immunoelectrophoresis indicated Bence Jones protein (L type) and bone marrow biopsy showed mildly hypercellular bone marrow with plasmacytosis (30%). Hypercalcemia was managed with intravenous hydration, bisphosphonates and furosemide. A parathyroidectomy was initially indicated as the first etiological treatment of the hypercalcemia. The postoperative course following parathyroidectomy was good and serum calcium and phosphorus showed normal values. Serum PTH rapidly fell to the normal level. The patient was referred in a second time to the department of oncology, for a specialized treatment of multiple myeloma.

Discussion     

Primary Hyperparathyroidism (PHPT) is more common in females, whereas the opposite is true for Multiple Myeloma (MM). Differences in incidence of the two diseases may explain female preponderance cases of concomitant MM and PHPT [2]. A recent review identified a total of 29 case reports describing the association of PHPT and MM, including the first case described by Drezner and Lebovitz in 1978 [3]. The mechanism of this association remains unclear. Given that the diagnosis of PHPT often precedes the diagnosis of MM it has been hypothesized that the high rate of PTH induces MM [4]. Pest et al. hypothesized that elevated PTH may mediate the induction of MM through the downstream biological effects of IL-6 [4]. This hypothesis was supported by the study performed by Pirih et al. who showed that PTH decreases apoptotic cell death of the hematopoietic stemcells via the IL-6 [5]. Arnulf et al. showed that the prevalence of monoclonal gammopathy is higher in patients with PHTP as compared to general population [6]. The above-mentioned pathogenic mechanism gives an insight to how PHPT and MM may be linked. Hypercalcemia in multiple myeloma can be explained by multiple mechanisms. First, plasma cells produce various cytokines, including TNF-α and IL-6, that activate osteoclasts and lead to calcium washout from bones to the bloodstream [7]. Second, some studies suggest that MM cells may secrete parathyroid hormone-related peptide similarly to other malignancies, such as squamous cell lung carcinoma [8]. Third, serum calcium may be falsely elevated because of a binding to immunoglobulin [9]. PHPT leads to hypercalcemia via direct bone resorption mediated by osteoclasts. Another important mechanism is through an increased calcium absorption in the duodenum and greater reabsorption in the kidneys. In the present case, primary hyperparathyroidism was initially diagnosed as the cause of hypercalcemia and multiple myeloma was suspected concomitantly to HPPT given the associated panctopenia on cell blood count (CBC). It is interesting that at only 1 month following parathyroidectomie hypercalcemia returned despite of a normal level of PTH. Parathyroidectomy, combination of radiotherapy and chemotherapy had been used for treatment of this coexistent condition with variable success. Rao et al. [10] suggested that parathyroidectomy in patients with coexistent PHPT and MM serves three folds; first, it removes confusion about etiology of hypercalcemia; second, it alters prognosis of myeloma; third, calcium can be used as a tumor marker in cases if there is a recurrence of tumor.

Conclusion     

Based on the present experience and the review of the literature hypercalcemia patients should be carefully examined. Diagnoses of primary hyperparathyroidism and multiple myeloma should be discussed in a systematic way and to perform a PTH assay and an immunofixation of serum proteins in the balance of one or the other of these two pathologies; their association is possible and not fortuitous, although their causal link has not yet been identified.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

All the authors have read and agreed to the final manuscript.

Figures     

Figure 1: brown tumor appearance of proximal right radius on MRI

Figure 2: neck computed tomographic (CT) showing a parathyroid adenoma

Figure 3: bone lytic lesion of the skull

References     

1. French S, Subauste J, Geraci S. Calcium abnormalities in hospitalized patients. Southern Medical Journal. 2012;105(4):231-237. PubMed | Google Scholar


2. Goto S, Yoshioka M, Nagai K, Abe A, Murakawa E, Yamazaki N et al. Primary hyperparathyroidism associated with multiple myeloma. Int Med. 1995;34(10):988-991. PubMed | Google Scholar


3. Hussain N, Khan M, Natarajan A, Mohammedabdul M, Mustafa U, Yedulla K et al. A case of multiple myeloma coexisting with primary hyperparathyroidism and review of the literature. Case Rep Oncol Med. 2013;2013:420565. PubMed | Google Scholar


4. Pest EP, McQuaker G, Hunter JA, Moffat D, Stanley AJ. Primary hyperparathyroidsm, amyloid andmultiplemyeloma: an unusual association. Scottish Medical Journal. 2005;50(1):32-34. PubMed | Google Scholar


5. Pirih FQ, Michalski MN, Cho SW, Koh AJ, Berry JE, Ghaname E et al. Parathyroid hormone mediates hematopoietic cell expansion through interleukin-6. PLoS One. 2010;5(10):e13657. PubMed | Google Scholar


6. Arnulf B, Bengoufa D, Sarfati E, Toubert ME, Meignin V, Brouet JC et al. Prevalence of monoclonal gammopathy in patients with primary hyperparathyroidism: a prospective study. Archives of Internal Medicine. 2002;162(4):464-467. PubMed | Google Scholar


7. Mundy GR, Yoneda T, Guise TA. Hypercalcemia in hematologic malignancies and in solid tumors associated with extensive localized bone destruction. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 1999;4:208-211.


8. Tsujimura H, Nagamura F, Iseki T, Kanazawa S, Saisho H. Significance of parathyroid hormone-related protein as a factor stimulating bone resorption and causing Hypercalcemia in myeloma. American Journal ofHematology. 1998;59(2):168-170. PubMed | Google Scholar


9. John R, Oleesky D, Issa B, Scanlon MF, Williams CP, Harrison CB et al. Pseudohypercalcaemia in two patients with IgM paraproteinaemia. Annals of Clinical Biochemistry. 1997;34(6):694-696. PubMed | Google Scholar


10. Rao DS, Antonelli R, Kane KR, Kuhn JE, Hetnal C. Primary hyperparathyroidism and monoclonal gammopathy. Henry Ford Hospital Medical Journal. 1991;39(1):41-44. PubMed | Google Scholar