Unusual pathological fracture of the clavicle revealing primary hyperparathyroidism: a case report

A 50-year-old Moroccan man presented to our orthopedic department after tripping on a step and falling onto his left side. He had a 4-year history of type 2 diabetes and hypertension. His medication included furosemide, captopril, and metformin. He had a tobacco smoking history of 30 pack years, but he had quit smoking approximately 5 years ago.

A review of his social and environmental history did not indicate exposure to any other known toxins or carcinogens. He denied any family history of cancer. He is a police officer and he lives with his wife and two children.

A physical examination revealed a blood pressure at 135/80 mmHg, a normal pulse rate, and no fever; he had no symptoms except for the left clavicular pain.

Radiographs showed a lytic lesion in his left clavicle and an asymptomatic lytic lesion in the left humeral head. A computed tomography (CT) scan was performed and objectified multiple osteolytic lesions on the whole skeleton (Fig. 1).

A neoplastic origin was first suspected; our patient was then referred to our nuclear medicine department with suspected bone metastases.

A whole-body bone scintigraphy with technetium-99m (^99mTc)-methylene diphosphonate (MDP) was particularly interesting insofar as it was able to orient the diagnosis to a metabolic bone disease. It demonstrated diffusely increased uptake in both axial and appendicular skeleton, absent urinary activity, and prominent calvarian and periarticular uptake, with a focal accumulation of radiotracer on the left clavicle (Fig. 2).

His complete blood count hemoglobin level was 15 g/dl, white cell count at 8900, and platelet count at 170,000; his transaminases and his serum electrolytes were normal. Hepatitis A serology, hepatitis B serology, hepatitis C serology, and human immunodeficiency virus (HIV) serology were also negative.

Laboratory studies also revealed an elevated serum calcium level of 3.8 mmol/l (corrected range, 2.15 to 2.60) and a circulating level of PTH of 1905 pg/ml (normal range, 14 to 72), his creatinine level was within normal limits. The diagnosis of PHPT was then confirmed.

Considering possible hyperparathyroidism caused by a parathyroid nodule, a cervical ultrasound was done and identified an adenoma in the right inferior parathyroid gland; this was confirmed by a parathyroid scintigraphy with ^99mTc-methoxyisobutylisonitrile (MIBI) using washout method, which showed a focal increased uptake in inferior right parathyroid gland (Figs. 3 and 4).

A parathyroidectomy was performed and a large parathyroid tumor was removed and confirmed to be a benign parathyroid adenoma on histological examination.

After surgery, our patient’s PTH level returned to normal but he developed hypocalcemia, requiring doses of orally administered calcium. He was alive and showed no symptoms during a 6-month follow-up period.

Before undergoing the bone scintigraphy, our patient was suspected to have bone metastases. Fortunately, the bone scan demonstrated an aspect of metabolic disease; his serum calcium and PTH levels led to the correction of the diagnosis to PHPT.

This case highlights that pathological fracture is not always synonymous with cancer, several differential diagnoses must be taken into consideration, among them PHPT.

PHPT is a relatively common endocrine disorder, with prevalence estimates of one to seven cases per 1000 adults. It is believed to be the most common cause of hypercalcemia, predominantly affecting elderly populations and women two to three times as often as men. The incidence of PHPT has been difficult to assess, available estimates vary widely from 0.4 to 21.6 cases per 100,000 person-years [3].

In most patients with PHPT (80 to 85%), the disease develops due to a parathyroid adenoma, in 15 to 20% due to parathyroid gland hyperplasia, and in < 0.5% due to parathyroid carcinoma [4].

Many cases of PHPT are diagnosed in the early stages of the disease process, before the development of classical clinical findings of prolonged disease such as nephrolithiasis, brown tumors or osteitis fibrosa cystica, bone cysts, or pathologic fracture. Early diagnosis has resulted in a significant decline in what were once the common morbidities of the disease [5].

The incidence of pathological fractures in PHPT is relatively rare accounting for around 10% in two large series [6]. However, PHPT revealed by pathological fracture, as in our case, is very uncommon.

Morgan et al. reported a case of subtrochanteric fracture of the femur through an area of lytic bone with hypercalcemia which was felt to be a metastatic pathological fracture [7], the same presentation was found in the case reported by Khaoula et al. [2]. Rachha also reported three cases which involved the long bones [1].

A literature review of other reported cases using the PubMed database revealed that our case is the first presentation of PHPT revealed by clavicle fracture.

A cancerous origin is suspected before a pathological fracture with multiple lytic bone lesions; this was the situation in our patient, who underwent skeletal scintigraphy to look for bone metastases. However, fortunately, the bone scan showed a feature of metabolic bone disease. With metabolic bone disease there is a generalized increased uptake throughout the skeleton and markedly reduced soft tissue background activity. The kidneys appear faint or there may be absence of the normal renal activity, giving the “super scan” because of the predominance of the bone images [8]. PHPT is one of the main etiologies of this feature on bone scintigraphy. Other skeletal anomalies secondary to hyperparathyroidism are also possible and are detailed in Table 1 [9‐12].

Once the diagnosis of PHPT is confirmed by increased serum PTH level, parathyroid localization studies such as neck ultrasound scan and ^99mTc-MIBI scintigraphy are used to confirm the location of the diseased gland rather than for establishing the diagnosis of PHPT preoperatively.

Initially, ^99mTc-MIBI is concentrated in the thyroid gland and abnormal parathyroid tissue and then differentially clears from these organs in a time-dependent manner; washout of the thyroid gland is more rapid than from the abnormal parathyroid tissue that allows dual-phase ^99mTc-MIBI scintigraphy to detect the hyperfunctioning parathyroid tissue [5].

Parathyroidectomy is the treatment of choice in PHPT. In the last 10 to 15 years, surgery for PHPT has moved from the wide bilateral neck exploration to minimally invasive approaches, such as the minimally invasive radio-guided parathyroidectomy [13].

This case illustrates a rare presentation of a parathyroid adenoma revealed by clavicle fracture, and highlights the importance of explorations using nuclear medicine. When a patient presents with unexplained osteolytic lesions, although metastatic malignancies should be ruled out first, other differential diagnoses such as metabolic bone disease including hyperparathyroidism should be kept in mind as well, in order to reach an accurate diagnosis.