Systemic Amyloidosis Associated with Primary HyperparathyroidismKamNewman,MojtabaAkhtari,SalimShackour,AjitKesaniStFrancisHospital Evanston Learning Objectives1- Recognizing the association of systemic amyloidosis and primary hyperparathyroidism (PHPT) 2- Understanding possible common pathophysiologic pathways between primary plasma cell dyscrasias and PHPT

DepartmentofMedicine,StFrancisHospital,Evanston,IL

Case HistoryAn 84-y-o female presented with confusion. Past medical history included systemic amyloidosis, HTN and DVT. Drug history included Tramadol. Positive clinical signs were obtundation and macroglossia. Blood tests showed HB 11.5 g/dl, Hct 33.5%, MCV 83 fl, WBC 9.4 k/mm3, Neut 73.6%, BUN 42 mg/dl, Cr 0.9 mg/dl, Ca 12.6 mg/dl, PO4 1.8 mg/dl, Mg 1.4 mg/dl, Alb 2.6 g/dl, Ionized Ca 1.77 mmol/l, 24-hr urine protein 1234.1 mg, PTH 125.3 pg/ml, 1-25 dihydroxy Vit. D 22 pg/ml and 25-hydroxy Vit. D 35 ng/ml. Two months earlier she presented with Rt hip pain and femoral neck pathologic fracture. An x-ray showed a lucency in neck of Rt femur. MRI of Rt hip showed a 4.6 x 2.6 cm relatively well-defined lesion in Rt femoral neck, which was suggestive of pathological fracture. A skeletal survey did not show any other lytic bone lesions. SPEP showed low albumin, elevated 2 globulin and a monoclonal spike. Serum immunofixation showed Kappa light chain. Urine electrophoresis revealed Kappa light chain, too. Patient had an arthroplasty. Rt femoral head biopsy showed a large area of amorphous eosinophilic material, positive for Congo red, occupied bone marrow. Polarized light examination showed green birefringence. Immunohistochemical staining was negative for Kappa, Lambda light chains and CD138. A chest CT showed 5-cm soft tissue mass in left axilla, which was positive for Congo red. Amyloid protein did not lose affinity for Congo red after pretreatment with potassium permanganate. Sample was strongly positive for Kappa, which corresponded to protein electrophoresis results. CT of abdomen did not show hepatomegaly. Patient's hypercalcemia was treated with intravenous fluid, Pamidronate infusion and nasal Calcitonin, which responded to treatment. Her BUN and Cr became normal and mental status returned to its base line.

DiscussionThis patient presented with anunusual association of systemic amyloidosis and PHPT. Diagnosis of systemic amyloidosis was based on the presence of Kappa light chain inBonetumorsofthemidfemoral diaphysisinapatientwithprimary hyperparathyroidismThyroidandparathyroidglands

serum and urine. Biopsies from bone and left axilla showed amyloid. Diagnosis of PHPT was based on laboratory tests, which showed increased PTH, hypercalcemia, hypomagnesemia and hypophosphatemia. Association between MGUS or multiple myeloma and PHPT has bee previously reported. However, to our knowledge this is the first case report of systemic amyloidosis and PTHP. It is not clear if there is a direct link between those conditions. Bertrand and coworkers

SummaryPrimary hyperparathryroidism (PHPT) is the number one cause of hypercalcemia in the non-hospitalized patient, with malignancy predominating in hospitalized patients. A cause for primary hyperparathyroidism can be identified in only a small number of patients, such as irradiation or the rare genetic abnormalities in the multiple endocrine neoplasia (MEN). Primary hyperparathyroidism can be divided pathologically into adenoma, glandular hyperplasia, and carcinoma. Adenomas clearly are the most prevalent entity representing 80-85% of cases. Hyperplasia is the second most common diagnosis constituting 15% of cases. Carcinoma represents less than 1% of cases. The major areas of debate surrounding primary hyperparathyroidism include the issues of differentiating an adenoma from hyperplasia and the question whether asymptomatic hyperparathyroidism truly exists. The male to female ratio is 1:2, and incidence increases with age. Amyloidosis is a group of diseases that result from the extra cellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins, many of which circulate as a constituents of plasma. The most frequent types of amyloidosis seen on the internal medicine services and tertiary referral centers are the AL (primary) and AA (secondary) types. AL amyloid is due to deposition of protein derived from immunoglobulin light chain fragments.

. Immuneperoxidasestainofabonemarrowbiopsyfroma

found MGUS in 10% of patients with PHPT, compared with 3% of controls. There is evidence that parathyroid hormone can stimulate osteoblasts to produce interleukin-6, which has an important role in survival and growth of plasma cells in Multiple myeloma, and inhibits induction of Apoptosis during chemotherapy. Also,it has been shown that patients with PHPT have increased levels of IL-6. In conclusion, coexistence of plasma cell dyscrasias and PHPT should be suspected in patients known to have either condition alone, and serum protein electrophoresis should be performed routinely in all patients with PHTP.

patientwithprimary(AL)amyloidosis

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Brown tumors of the pelvis in a patient with primary hyperparathyroidism

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