Systemic Amyloidosis Associated with Primary Hyperparathyroidism
Kam Newman, Mojtaba Akhtari, Salim Shackour, Ajit Kesani 
St Francis Hospital
       Evanston
Learning Objectives
1- Recognizing the association of systemic
amyloidosis and primary
hyperparathyroidism (PHPT)
2- Understanding possible common
pathophysiologic pathways between primary
plasma cell dyscrasias and PHPT
Summary
Primary 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.    PHTP.
Department of Medicine, St Francis Hospital, Evanston, IL 
Case History
An 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
á2 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.
Brown tumors of the pelvis in a patient with
primary hyperparathyroidism
Thyroid and parathyroid glands
Bone tumors of the midfemoral  axilla showed amyloid. Diagnosis of PHPT was
diaphysis in a patient with primary 
hyperparathyroidism
. Immuneperoxidase stain of a bone marrow biopsy from a  found MGUS in 10% of patients with PHPT,
patient with primary (AL) amyloidosis 
References
1. Merlini,
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amyloidosis by abdominal fat pad aspiration. Analysis of four years'
experience. Am J Med 1987; 82:412
4. Dember, LM. Emerging treatment approaches for the systemic
amyloidoses. Kidney Int 2005; 68:1377
5. Silverberg, SJ, Bilezikian, JP. Evaluation and management of primary
hyperparathyroidism. J Clin Endocrinol Metab 1996; 81:2036
6. Tordjman, KM, Greenman, Y, Osher, E, et al. Characterization of
normocalcemic primary hyperparathyroidism. Am J Med 2004; 117:861
7. Silverberg, SH, Shane, E, De La Cruz, L, et al. Skeletal disease in
primary hyperparathyroidism. J Bone Miner Res 1989; 4:283
Discussion
This patient presented with anunusual association
of systemic amyloidosis and PHPT. Diagnosis of
systemic amyloidosis was
based on the presence of Kappa light chain in
serum and urine. Biopsies from bone and left
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
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