Giant Parathyroid Adenoma-Associated Fracture, Not All Lytic Bone Lesions are Cancer: A Case-Based Review

Abstract

Introduction. Due to the early diagnosis of primary hyperparathyroidism the musculoskeletal manifestations of this disease are becoming less frequent. When this disease manifests secondary to a giant adenoma, it presents with more aggressive symptoms and can have important repercussions such as the hungry bone syndrome after parathyroidectomy. There are few reported cases of hyperparathyroidism secondary to a giant adenoma in the literature, as the presence of a brown tumor is often misinterpreted as a metastatic lesion from an unknown primary tumor. Methods. We describe a case and performed a literature review to identify all case reports. A literature search was carried out on PubMed/MEDLINE and EMBASE bibliographic databases. All available studies from May 2009 to May 2021 were included. Data were tabulated, and outcomes were cumulatively analyzed. Results. Twenty-four cases of primary hyperparathyroidism due to giant adenoma have been described; the majority were women, with a mean age of 52 years. They presented with heterogeneous symptoms such as palpable nodules (45%), bone pain (33%), brown tumor (12.5%), asymptomatic (12.5%), metabolic profile with a mean calcemia of 13.8 mg/dL, PTH 1109 ng/L, and mean tumor weight of 47.24 g. Conclusion. Primary hyperparathyroidism due to giant adenoma increases the risk of developing potentially serious postoperative complications such as hungry bone syndrome. This implies the need of implementing preventive measures comprising administration of intravenous zoledronic acid and early supplementation of oral calcium to prevent complications after resection.

Forestalling Hungry Bone Syndrome after Parathyroidectomy in Patients with Primary and Renal Hyperparathyroidism

“…The authors reviewed data on 2 medical databases concerning giant PT adenomas starting with 2009, since first report was introduced, until 2021 and found 24 studies; HBS rate was reported in 25% of the cases with RHPT (USA), and in 4-87% of the participants diagnosed with PHPT. HBS was found to be correlated with larger tumors (such as giant PT adenomas), a PTH value above 1000 pg/mL, serum AP concentration of 3 times above normal upper limit, an increased number of osteoclasts at bone biopsy, the co-presence of skeleton complications such as brown tumors, and osteititis fibrosa cystica [7]. A similar case of a giant PT adenoma (of 5.6 cm largest diameter, and a weight of 28.7 g) was admitted for high calcium (of 13.7 mg/dL) and PTH (of 1240 pg/mL); the 66-year-old female associated a 4-week episode of HBS starting from the first day after PTx [51].…”

“…Giant PT adenomas (of more than 2-3 g) display a higher rate of bone complications in terms of brown tumors and osteitis fibrosa cystica which themselves are prone to post-PTX HBS, noting that usually the size of PT tumor associates with the levels of serum PTH [50]. Alvarez-Payares et al [7] added a new such case, a 55-year-old female with a giant PT adenoma (of 5 cm, and a weight of 16 g) who was post-operatory re-admitted for HBS (the symptoms started 72 h after surgery and the patient remained hospitalized for one month, also associating an aggravation of chondrocalcinosis and an acute episode of pulmonary embolism). The authors reviewed data on 2 medical databases concerning giant PT adenomas starting with 2009, since first report was introduced, until 2021 and found 24 studies; HBS rate was reported in 25% of the cases with RHPT (USA), and in 4-87% of the participants diagnosed with PHPT.…”

“…Hypocalcemia (usually below the value of 8.2-8.4 mg/dL), a typically severe and even life-threatening unless prompt intervention, arises within the third (varying between the first/second and the fourth-seventh) post-operatory day and it usually progresses through a 3-day period of time up to 30 days, requiring intravenous calcium replacement. Associated hypophosphatemia, hypomagnesiemia, and, exceptionally, hyperkaliemia (in patients undergoing chronic dialysis) are identified [3,[7][8][9]. This severe, but transitory, event is followed by mild or asymptomatic hypocalcemia requiring oral calcium and vitamin D substitution, particularly calcitriol, which may take a few months up to a year in order to register the restauration of normal mineral metabolism without the help of any medication [3,10,11].…”

“…Pre-operatory assessments that might be a clue for further developing HBS after PTx vary; the most common are extremely high serum PTH and bone formation marker alkaline phosphatase (AP), noting that HBS involves an increased osteoblastic activity in association with a normal or low osteoclastic activity. Correction of hypercalcemia and starting calcium replacement from the first day of PTx might improve the outcome of HBS [7,14,15].…”

“…The pre-operatory use of anti-resorptives such as bisphosphonates (for example, pamidronate or zoledronic acid) in PHPT is controversial to associate benefits for HBS, but some authors reported it [16][17][18][19]. Moreover, PT and bone imaging assessments before surgery in addition to histological information through bone biopsy for associated pathological skeletal masses and through post-PTx examination of PTs might suggest other contributors to HBS such as: giant PT or atypical tumors (typically larger than 2 cm diame-ter), PT carcinoma, respectively, the presence of brown skeletal tumors, and osteitis fibrosis cystica [7,14,20,21].…”