PARATHYROID ADENOMA PRESENTING AS MULTIPLE BROWN TUMORS AND SEVERE ASYMPTOMATIC HYPERCALCEMIA

Abstract

Introduction

Primary hyperparathyroidism may have several presentations, varying from an incidental asymptomatic biochemical finding to gastrointestinal, psychiatric, renal and bone manifestations. Brown tumors are rare non-neoplastic lesions because of abnormal bone metabolism. Herein, we describe a patient who presented with lytic bony lesions and severe asymptomatic hypercalcemia due to parathyroid adenoma.

Case presentation

A 38-year-old male presented with multiple painful bony lesions over upper and lower limbs. Radiographs of long bones showed multiple lytic lesions with cortical thinning. Investigations revealed hypercalcemia and hyperparathyroidism. A radionuclide scan showed parathyroid adenoma. The patient was treated for hypercalcemia and a parathyroidectomy was performed.

Conclusions

In a patient presenting with multiple bony swellings and asymptomatic hypercalcemia, hyperparathyroidism should be suspected. Parathyroid adenoma is a treatable cause of primary hyperparathyroidism.

INTRODUCTION

Hyperparathyroidism is the third most common endocrine disorder after diabetes mellitus and thyroid dysfunction (1). The clinical signs and symptoms are mainly due to abnormalities in calcium, phosphate, and bone metabolism. Increased PTH level results in hypercalcemia and hypophosphatemia. Symptoms include renal stones, generalized weakness, neuromuscular or psychiatric disorders, gastrointestinal and cardiovascular manifestations. Bone manifestations of hyperparathyroidism typically present as a silent preferential cortical site bone loss with decreased bone mineral density and osteoporosis, while osteitis fibrosa cystica or brown tumor is a rare manifestation (2).

We report an unusual case wherein the patient presented with multiple bony swellings and asymptomatic hypercalcemia and was found to have hyperparathyroidism secondary to parathyroid adenoma. The associated radiological abnormalities have also been discussed.

CASE REPORT

A 38-year-old male patient attended the outpatient department with complaints of multiple bony swellings over both hands, legs and back. The swelling initially appeared over the right thigh and then on other parts of the body over the course of one year. He had pain in his limbs while walking. He also had asthenia and weight loss. He had developed renal stones 5-6 years back. He had not undergone any evaluation for it, neither was his serum calcium estimated. He took some indigenous herbal medicines for it and his pain was relieved. On admission, he was afebrile with normal vital parameters. He had tenderness to pressure over tibia, fibula on either side and pelvis. He had painful swellings over both forearms and back (Fig. 1). Radiographs of forearms and legs revealed expansile, lytic, centric, soap bubbly appearing lesions with cortical thinning over bilateral ulnar shafts, 5^th metacarpal of both hands, bilateral femoral shafts and shaft of the right fibula (Fig. 1). There were multiple tiny punctate radiolucent lesions in the skull and iliac crest, typically described as pepper pot appearance.

Figure 1.

Shows multiple swellings; Brown tumors (marked by black arrows) over the left forearm, right forearm and back.

Blood tests showed hypercalcemia (serum calcium – 14.6 mg /dL, normal range 8.4 – 10.2 mg/dL), hypophosphatemia (1.91 mg/dL, normal range 2.5 - 4.5 mg/L) and predominantly alkaline phosphatase elevation (884 IU/L, normal range, 90-120 IU/L). Blood urea and serum creatinine were within normal limits. Serum vitamin D levels were reduced (12.79 ng/ml, normal range >30 ng/mL). Urine calcium excretion was increased to 350 mg/24 h (normal range, 100 - 300 mg/24 h) (Table 1).

Table 1.

Summary of biochemical investigations on admission

Total calcium (at presentation)	14.8 mg/dL	8.4 – 10.2 mg/dL
Phosphate	1.9 mg/dL	2.5 – 4.5 mg/dL
Alkaline Phosphatase	884 IU/L	40-105 IU/L
PTH (before surgery)	1853 pg/mL	18-88 pg/mL
Vit D level	12.79 ng/mL	> 30 ng/mL

Subsequently, serum parathyroid hormone levels were found to be elevated to 1853 pg/mL (normal range 18.5 – 88 pg/mL). Serum calcitonin was not measured as thyroid was normal. USG abdomen was performed which showed a few tiny (largest measuring 7.8 mm) non-obstructive calculi in the left kidney. USG neck revealed 2.1 x 1.1 cm in size hypoechoic lesion inferior to left thyroid lobe likely to be parathyroid adenoma. The thyroid was normal with no other nodules. Further Tc-99M Sestamibi scanning confirmed the diagnosis of parathyroid adenoma inferolateral to the lower pole of the thyroid lobe (Fig. 3).

Figure 3.

Thyroid scan done with TC 99-M Sestamibi shows homogeneous tracer uptake by the gland with persistent abnormal tracer uptake close to inferior pole of left thyroid gland (black arrow).

Figure 2.

A. Shows multiple, well defined diaphyseal lytic lesions involving distal shaft of the right tibia and fibula and proximal and midshaft of the left tibia (white arrows); B. Shows expansile, lytic, soap bubbly appearing lesion with cortical thinning over the distal shaft of right ulna (white arrows).

Initially, hypercalcemia was medically managed with hydration and bisphosphonate therapy. Injection Zoledronate 4 mg was administered. Later, surgical removal of the tumor was performed. The other parathyroid glands were normal and were left behind. Intraoperative biopsy confirmed the diagnosis of parathyroid adenoma. Patient had an uneventful post-operative course. Usually post surgically patients develop severe hypocalcemia due to hungry bone syndrome but our patient did not develop it as his remaining three parathyroid glands were left behind. The patient came for follow up after 1 week of surgery. His serum phosphorus – 3.9 mg/dL, serum calcium – 9.0 mg/dL and serum PTH levels – 25 pg/ml were within normal limits. However, after a month, he developed pathological fracture of right lower limb at the site of osteolytic lesions. There was no history of fall or direct trauma. It was probably due to indirect stress on already weakened bone. Only cast was given, and fractures healed spontaneously over next 3 months. Brown tumours regressed significantly over next 6 months. The patient is under continuous follow up with us and all his parameters are normal.

DISCUSSION

Brown tumors are rare focal giant cell lesions that arise as a direct effect of parathyroid hormone on bone tissue in some patients with hyperparathyroidism. Brown tumors develop secondary to both primary and secondary hyperparathyroidism and have been reported to occur in 4.5 % of patients with primary hyperparathyroidism and 1.5 to 1.7 % of those with secondary disease (3).

Persistent high parathyroid hormone levels cause increased osteoclastic bone resorption leading to local destruction primarily in the cortical bone and the occurrence of osteoclastomas also called brown tumors. However, bone resorption is more common than brown tumor development in hyperparathyroid states. Typically, subperiosteal bone resorption occurs in the middle phalanges of the second and third digits as well as at the phalanges tuft. Resorption of lamina dura is another characteristic feature. Subchondral resorption is less common (4). In our case, similar findings of acro-osteolysis predominantly on radial sides at the mid shafts of distal and middle phalanges in both hands was observed. The most common sites of involvement are ribs, clavicles, pelvic bones, and mandible. Our patient had brown tumors over the thighs, legs, arms, forearms and back.

Our patient exhibited some clue to hypercalcemia in the form of renal calculi and should have been investigated. But he took indigenous medicine and became symptom-free. There was no history of paresthesias, headaches, recent fractures, constipation, polyuria/polydipsia, symptoms usually associated with hypercalcemia. Most patients with hypercalcemia are asymptomatic and are identified as a part of routine investigations (5). Asymptomatic hypercalcemia can lead to a delay in the diagnosis of hyperparathyroidism. In our case patient manifested with renal calculi 5 years back but was not investigated for hypercalcemia. Turan et al. retrospectively analyzed 119 patients of parathyroidectomy to study the risk factors for hypercalcemic crisis. Higher values of intact serum PTH, serum calcium, alkaline phosphatase, creatinine and increased hyperfunctional parathyroid gland size were identified as important risk factors for development of hypercalcemic crisis. They also did not find any specific relationship between symptoms of hypercalcemia and calcium value (6).

V. Pandzie Jaksic et al. reported parathyroid incidentalomas causing silent hyperparathyroidism and hypercalcemia in 41 patients. The majority of PHPT patients were detected by incidental laboratory findings of hypercalcemia (47.6%) or during the osteoporosis work-up (22.6%). Urolithiasis was the cause of PHPT detection in only 6.5%. Parathyroidectomy was performed to prevent progression of disease which is likely to occur in 5 years with grave consequenses (7). Parathyroidectomy may reduce the oxidative stress but it’s effect on mortality and morbidity is still not established (8).

Our patient had a large size hypersecreting parathyroid adenoma which was detected on ultrasonography of neck. Many a times small adenomas go undetected. Serum calcium and parathormone levels have a direct correlation with positivity on imaging. Anderson et al. in their study observed that patients with calcium over 2.80 mmol/L and PTH >125 pg/mL are more likely to have positive and concordant imaging (9).

Management of this condition is directed at reducing the circulating parathyroid hormone level. Medical management is an option but maybe insufficient in most cases. Our patient underwent parathyroidectomy, which is the treatment of choice. Parathyroidectomy is well recognized to cause the resolution of lytic lesions without resorting to local surgical intervention. A study aimed to evaluate the management of bony lesions after parathyroidectomy had been performed. In a series of 22 patients with primary hyperparathyroidism with confirmed brown tumors, 21 patients had their serum calcium normalized. Furthermore, all the tumors exhibited spontaneous regression; 18 cases regressed completely with a mean period of 10 months. Two cases regressed completely after 2 years and the last 2 were lost to follow-up (10). Regression of brown tumor is yet to occur in our case. Unfortunately, he developed fracture of right lower limb at the site of brown tumor. This emphasizes the importance of early recognition, diagnosis, and treatment of parathyroid adenoma.

In conclusion, a high index of suspicion of brown tumors should be kept when bony tumors are associated with hypercalcemia. Further evaluation for a hypersecreting parathyroid adenoma, which is surgically treatable should be done in patients presenting with brown tumors.

Conflict of interest

The authors declare that they have no conflict of interest.