Abstract:
Osteitis fibrosa cystica or brown tumor is a rare skeletal manifestation
of hyperparathyroidism. Awareness of this condition is imperative to
making a correct diagnosis. We present a case with multiple pathological
fractures who had undergone extensive workup for malignancy before
reaching the definitive diagnosis of primary hyperparathyroidism.
KEYWORDS
brown tumor, hyperparathyroidism, osteitis fibrosa cystica
INTRODUCTION
Primary hyperparathyroidism is an endocrine disorder arising due to
excessive production of parathyroid hormone, which if uncontrolled,
results in deranged calcium homeostasis. Chronic exposure to parathyroid
hormone leads to increased bone turnover that culminates into
generalized osteopenia or multiple osteolytic bone lesions namely
osteitis fibrosa
cystica.1This pathological process makes bone susceptible to fracture even with
minor
trauma.2In most instances, the clinical diagnosis of this condition is
challenging and radiographic findings can be counterproductive as they
often mimic features of primary bone neoplasm or metastatic bone
disease.3,4As a consequence, the duration of illness can be quite protracted before
arriving at an accurate diagnosis adding to the physical, mental, and
financial burden on the patient. In this instance, we present a case of
40 years male who had multiple pathological fractures initially thought
to be due to multiple myeloma but later turned out to be the skeletal
manifestation of primary hyperparathyroidism.
CASE REPORT
40 yrs male presented to our center, who was bedridden due to
unremitting pain in the hip, arm, and buttock region for 7 months. He
has had multiple hospital visits with a myriad of diagnostic
investigations. He had a history of fractures sustained over the left
shoulder after a fall injury from standing height 5 months back for
which he was referred to the higher center for the pathological
fracture. Initial review of records revealed an osteolytic lesion in the
left clavicle, left humerus and femur on plain radiographs (Figure 1),
and blood parameters showed calcium 11.8mg/dL (8.5 - 11.0 mg/dL),
alkaline phosphatase (ALP) 2258 U/L (98 - 279 U/L), erythrocyte
sedimentation rate (ESR) 40mm/hr (0-20 mm/hr ), serum creatinine 1.2
mg/dL (0.9 - 1.4 mg/dL), serum urea 30mg/dL (10 - 50mg/dL), hemoglobin
11.2gm% (12 -16), total leukocyte count 9,190 cells/cumm (4000 -
11,000) and plenty of red blood cells in urinalysis. Ultrasonography of
abdomen/pelvis reported bilateral nephrolithiasis and cholelithiasis.
Contrast-enhanced computed tomography (CECT) and Magnetic resonance
imaging (MRI) of the pelvis and hip reported multiple expansile lytic
lesions in the pelvis and bilateral femurs (Figure 2). Meanwhile, he had
a history of left subtrochanteric femur fracture 3 months back followed
by a right proximal third femur fracture two weeks later after
sustaining a fall injury from standing height. The patient was then
referred to the cancer center, where further workup with bone marrow
biopsy and urine electrophoresis was inconclusive for multiple myeloma
and tumor markers were within the normal limits.
The patient then visited to the Department of Endocrinology of our
center one month back and further blood investigations were performed in
the line of hyperparathyroidism: calcium 15.9 mg/dL (8 - 11), phosphorus
2.8 mg/dL (2.5 - 5), serum parathyroid hormone (PTH) 1959.4 pg/mL (11.1
- 79.5), vitamin D 31.88 ng/mL (30 - 80), hemoglobin 9.3 gm/dL (12 -
16), platelet 161,000 cells/cumm (150,000 - 400,000), creatinine 1.31
mg/dL (0.4 - 1.4). Iron studies showed ferritin 915.5 ng/mL (22-322),
iron 50 μg/dL (50 - 175) and total iron binding capacity (TIBC) 292
μg/dL (250 -450). The patient was admitted and was managed immediately
for hypercalcemia with intravenous fluid normal saline, intravenous
furosemide, and intravenous Zoledronate 5 mg under close monitoring
after which his calcium level reduced to 10.44 mg/dL on the next day.
Serum calcium and potassium were monitored daily over the subsequent
days. The patient underwent further diagnostic evaluation via Tc99m
sestamibi (Figure 3), and an ultrasound of the neck suggesting the
parathyroid lesion.
He underwent a partial parathyroidectomy after reviewing the case from
the Department of Otorhinolaryngology. His intraoperative PTH level
declined abruptly by 91% (173.8 pg/mL). Postoperatively, intravenous
antibiotics and intravenous calcium gluconate 10% bolus were given.
Subsequent histopathology was suggestive of parathyroid adenoma (Figure
4). On the second postoperative day, he developed an episode of
hypocalcemia along with “hungry bone syndrome” as the subsequent
investigation showed calcium 7.11 mg/dL (8 - 11) and PTH 5.5 pg/mL (18.5
- 88), albumin 2.57 gm/dL (3.4 - 5.5). He also complained of a tingling
sensation around his mouth and in both of his hands and feet. He was
then managed with an infusion of calcium gluconate at the rate of 100
mL/hr for 3 days along with a high dose of calcitriol 1 mcg/day and
calcium carbonate 1500 mg/day + vitamin D3 750 IU/day. The patient’s
symptoms gradually improved and were discharged with a reduced daily
dose of calcitriol, calcium carbonate + vitamin D3, and once monthly
dose of cholecalciferol 60,000 IU.
DISCUSSION
Osteitis fibrosa cystica or brown tumor is one of the severe
manifestations of prolonged hyperparathyroidism resulting from excess
osteoclast activity consisting of collections of osteoclasts intermixed
with fibrous tissue and cancellous bone. The brown coloration is due to
hemosiderin
deposition.2,4It appears as a well-defined expansile osteolytic lesion with osteopenia
on plain radiographs, and various bone erosion and cortical attenuation
on CT while MRI imaging show hypointense on T1-weighted images,
hypo-intense or hyperintense on T2-weighted
images.4,5Brown tumor is a non-neoplastic lesion with the reported incidence in
primary hyperparathyroidism of
3%.6Primary hyperparathyroidism manifests with a wide array of clinical
features that includes bone fracture, kidney stones, abdominal pain, and
psychiatric
disturbances.7And in most cases, the brown tumor eventually regresses following
normalization of the parathyroid
levels.8–10
The diagnosis of the brown tumor can be challenging and misleading in
various aspects. The differential diagnosis of brown tumor includes
metastasis, giant cell tumor, giant cell reparative granuloma,
aneurysmal bone cyst, multiple myeloma, and non-ossifying fibroma. The
multiple expansile osteolytic lesions on the radiograph can be
misleading to the primitive bone neoplasm and bone
metastasis.5It also becomes difficult to solely make a diagnosis on basis of a
histopathological point of view as a surgical bone biopsy can be
inconclusive.3,4Because these conditions resemble one another on imaging and
histopathology, the index case has primarily gone through extensive
workup for malignancy and developed multiple pathological fractures in
the meantime. In the differential diagnosis of osteolytic bone lesions,
it is essential to pay attention to calcium and phosphorous homeostasis.
Clinicians need to have a high suspicion of a brown tumor when their
abnormal level accompanies the raised parathyroid hormone
level.2The overactivity of the parathyroid gland can be triggered by hereditary
factors, parathyroid carcinoma, parathyroid adenoma, or renal
osteodystrophy. Of patients with primary hyperparathyroidism, 80-85%
account for parathyroid
adenoma.11Thus, the rise in parathyroid hormone concentration along with the
ultrasonography of the neck and Tc99m sestamibi facilitate the diagnosis
of parathyroid
adenoma.3
The definitive management of primary hyperparathyroidism is
parathyroidectomy and literature has reported intraoperative PTH
decrease by 50% or more which is in accordance with the index case.12,13When parathyroidectomy is performed, partial or even total regression of
the brown tumor has been reported in several
studies.11,14,15Unfortunately, we could not evaluate the eventual regression pattern of
the brown tumor after a successful parathyroidectomy.
This case report emphasizes brown tumors to be considered as the
differential diagnosis of multiple osteolytic lesions when abnormal
calcium and phosphorous accompany the high concentration of parathyroid
level. Thus, awareness regarding this condition can avoid unnecessary
investigations along with timely diagnosis and treatment.
AUTHOR
CONTRIBUTIONS
SS, SL, SS, SK, and SD wrote the manuscript. SS and SL reviewed and
edited the manuscript. All authors accepted the final version.
ACKNOWLEDGMENTS
We would like to thank Dr. Umesh Bartaula for providing us with the
histology pictures.
CONFLICT OF
INTEREST
None declared.
ETHICAL
APPROVAL
Written informed consent was obtained from the patients. Formal approval
was not necessary for a case report in our hospital setting.
CONSENT
Written informed consent was obtained from the patient in accordance
with the journal’s patient consent policy.
REFERENCES
1. Grey AB. The skeletal effects of primary hyperparathyroidism.
Baillieres Clin Endocrinol Metab. 1997 Apr;11(1):101–16.
2. Wasiak M, Popow M, Bogdańska M, Starzyńska-Kubicka A,
Ma\ldyk P, Wasilewski P. Treatment of pathological
fractures due to brown tumours in a patient with hyperparathyroidism and
lack of parafibromin expression – A case report. Trauma Case Rep.
2020;30(October):100367.
3. Vaishya R, Agarwal AK, Singh H, Vijay V. Multiple ‘Brown Tumors’
Masquerading as Metastatic Bone Disease. Cureus. 2015;7(12).
4. Lee JH, Chung SM, Kim HS. Osteitis fibrosa cystica mistaken for
malignant disease. Clin Exp Otorhinolaryngol. 2013;6(2):110–3.
5. Hu J, He S, Yang J, Ye C, Yang X, Xiao J. Management of brown tumor
of spine with primary hyperparathyroidism : A case report and
literature review. Med U S. 2019;98(14).
6. Fazaa A, Makhlouf Y, Miladi S, Sellami M, Ouenniche K, Souebni L, et
al. Hyperparathyroidism: Unusual location of brown tumors. Clin Case
Rep. 2022;10(2):1–5.
7. Silverberg SJ, Bilezikian JP. Chapter 66. Primary
Hyperparathyroidism. In: Primer on the Metabolic Bone Diseases and
Disorders of Mineral Metabolism. John Wiley & Sons, Ltd; 2008 [cited
2022 Aug 14]. p. 301–6.
8. Dagang DJT, Gutierrez JB, Sandoval MAS, Lantion-Ang FL. Multiple
brown tumours from parathyroid carcinoma. Case Rep. 2016 Jun
29;2016:bcr2016215961.
9. Panagopoulos A, Tatani I, Kourea HP, Kokkalis ZT, Panagopoulos K,
Megas P. Osteolytic lesions (brown tumors) of primary
hyperparathyroidism misdiagnosed as multifocal giant cell tumor of the
distal ulna and radius: a case report. J Med Case Reports. 2018 Jun
25;12(1):176.
10. Minisola S, Gianotti L, Bhadada S, Silverberg SJ. Classical
complications of primary hyperparathyroidism. Best Pract Res Clin
Endocrinol Metab. 2018 Dec;32(6):791–803.
11. Mantar F, Gunduz S, Gunduz UR. A reference finding rarely seen in
primary hyperparathyroidism: Brown tumor. Case Rep Med. 2012;2012:6–9.
12. Madkhali T, Alhefdhi A, Chen H, Elfenbein D. Primary
hyperparathyroidism. Turk J SurgeryUlusal Cerrahi Derg. 2016 Mar 1
[cited 2022 Aug 13];32(1):58–66.
13. Jain N, Reilly RF. Hungry bone syndrome. Curr Opin Nephrol
Hypertens. 2017 Jul;26(4):250–5.
14. Hadad Z, Tjelum L, Eiken P, Trolle W, Haupter I, Afzelius P.
Multiple brown tumors caused by primary hyperparathyroidism as a
differential diagnosis to multiple osteolytic bone metastases: A case
report. J Endocrinol Metab. 2020;10(3–4):94–100.
15. De Crea C, Traini E, Oragano L, Bellantone C, Raffaelli M, Lombardi
CP. Are brown tumours a forgotten disease in developed countries? Acta
Otorhinolaryngol Ital. 2012;32(6):410–5.