HPT is a clinical condition caused by an excessive production of PTH (3). This overstimulation of PTH can lead to pathological disorders, classified as PHPT, SHPT, or THPT (4).
PHPT is mainly associated with parathyroid adenomas (80% of cases), followed by parathyroid hyperplasia (10–15%), and parathyroid carcinoma (1%)(1). It may also involve hereditary disorders such as multiple endocrine neoplasia types 1, 2A, and 4, as well as hyperparathyroidism-jaw tumor syndrome(1, 4).
SHPT usually arises from chronic renal disease, resulting in decreased calcium levels and increased PTH secretion (5)
THPT is the rarest form of HPT, observed in about 2% of patients with renal failure. It commonly develops in the context of SHPT.(6)
It differs from SHPT as it persists or recurs despite addressing the underlying renal disease, often through renal transplantation(7). Additionally, it is characterized by elevated levels of both calcium and phosphorus.
In this case, THPT has been observed as a result of long-term dialysis ( since 2006). It is noteworthy that the patient presented with normal calcium levels, introducing a distinctive aspect to this observation.
The term "Brown tumor" (BT) describes a distinctive histological finding characterized by the presence of a dark brown tissue mass. Despite its name, BT do not stem from a cancerous process but rather are focal bony lesions that develop as a result of HPT or paraneoplastic syndrome(3, 8).
Early detection measures for HPT have led to decreased occurrences of BT. Incidence is around 4.5% in PHPT and even lower, ranging at 1.5–2% SHPT and THPT(9).
A literature review within the past decade identified 37 patients in 34 reports with jaw BT associated to HPT. (Detailed cases of brown tumors associated with hyperparathyroidism are provided in table 2)(see additional file 1)
Females were predominantly affected, accounting for 78,37% of cases where PHPT constituted the highest percentage at 54.05% followed by SHPT at 32.45%, and THPT representing the remaining 13.5%.
BT are usually central lesions in the jaws, with rare occurrences in a peripheral form. The mandible is commonly affected(3), as observed in this review where 28 out of 37 patients had central mandibular BT. This corresponds to this case’s observation of central mandibular location.
Radiographically, BT typically present as well-defined lytic lesions, sometimes showing intralesional trabeculations and cortical bone thinning(10). Signs of HPT may be expressed alongside other indicators such as the loss of the lamina dura and the classic “salt and pepper” appearance of the skull which were evident in this case. Furthermore, generalized bone loss and teeth mobility were observed. Thise can be explained by both the effect of PTH’s over secretion and the compromised oral hygiene and altered periodontal status of the patient.
Clinically and radiographically, BT can resemble other diseases, necessitating a thorough differential diagnosis. Histological analysis of BT typically reveals specific features shared with various oral conditions(3) (as seen in Table 1 ), making it essential to consider both clinical and radiological findings alongside the patient's medical history and blood tests to accurately differentiate from other giant cell lesions.
Table 1
Summary of BTs differential diagnosis
| Lesion | Age | Sex | Site | Clinical features | Radiological features | Histology | Serum Ca | Serum P |
| GCGs(3, 19) | < 30 | F | Jaw | Painless swelling of the jaw Extraoral asymmetric swelling Aggressive form-pain | Unilocular radiolucency with well-defined margins | Clusters of multinucleated giant cells embedded in a stroma of spindle-shaped mononuclear cells | N | N |
| PGCGs(3, 20–22) | < 30 | F | Jaw | Smooth, pedunculated tumorous proliferations with firm consistency and red color. Reactive lesions | | Ulcerations covered by Para keratinized thinned epithelium, interstitial hemorrhage and hemosiderin accumulations | N | N |
| Cherubism(23) Autosomal dominant condition | Childhood | F | Max and Mand | Slow, symmetrical expansion of the jaws, leading to tooth displacement, speech alteration | Multiloculated “soap-bubble” radiolucency. Thin cortical, replacement of the fibrous tissue by new bone leading to sclerosis | multinucleated osteoclast-like giant cells within vascular fibrous connective tissue stroma. Eosinophilic cuff-like perivascular deposits can also be seen | N | N |
| Aneurysmal bone cysts(23) | < 20 | M = F | Mand > Max Long bones | Painful enlargement | Unilocular or multilocular radiolucent with well-defined margins | Blood filled or empty sinusoidal spaces lined by macrophages and fibroblasts separated by fibrous septa containing scattered multinucleated osteoclastic giant cells | N | N |
| Simple bone cysts(23) | 20–30 | M = F | Mand | Asymptomatic, found incidentally during routine examination | Well-defined radiolucencies extending between the roots of associated teeth | Compressed connective tissue with myxomatous change and immature lace-like osteoid or spiky collagen deposits | N | N |
| GCG: giant cell granuloma; PGCG: peripheral giant cell granuloma |
For instance, in this case, the presence of chronic kidney disease led to consideration of a BT related to HPT, which was confirmed by subsequent blood tests indicating elevated serum parathyroid hormone and abnormal levels of calcium, phosphorus, and alkaline phosphatase.
Management of brown tumors in PHPT involves the removal of the offending parathyroid gland, with some advocating for intralesional steroid therapy(11–14). Surgical intervention is necessary for large lesions that persist beyond six months or cause functional or aesthetic alterations(15) .
For SHPT and THPT, addressing underlying chronic renal disease or vitamin D deficiency is key, with treatment options including hemodialysis, dietary phosphorus restrictions, calcimimetic binders, and vitamin D derivatives (16, 17). Parathyroidectomy becomes the preferred treatment in cases resistant to medical therapy (12).
Despite the use of calcimimetic agents, the patient's parathyroid hormone level remained high, raising questions about the indication of parathyroidectomy in normocalcemic THPT.
The decision-making criteria for parathyroidectomy in THPT lacks clear guidelines, particularly regarding the role of serum calcium levels versus PTH levels and what constitutes a successful operation(7, 18).
Most research findings indicate that persistent hypercalcemia is consistently considered a prerequisite for surgery, and normalizing PTH levels is not always necessary to define surgical success. Instead, achieving normocalcemia during follow-up serves as the main indicator(7). This contrasts with the criteria for success in primary hyperparathyroidism, where normalization of both PTH and serum calcium levels is required.
This case raises questions about performing parathyroidectomy in normocalcemic THPT, an area with limited research attention despite well-documented advantages of surgery in THPT cases. A study compared the effectiveness and safety of parathyroidectomy in normocalcemic THPT to hypercalcemic cases(18). It founds similar efficacy but a higher rate of permanent hypocalcemia. However, all patients were successfully managed with oral calcium and calcitriol with minimal morbidity(18).
In this case, the general surgeon performed parathyroidectomy despite the normal calcium level.
After the surgery, there was a 50% reduction in PTH ( from 4868.0 pg./ml to 1762,60 while maintaining normal calcium levels ( 92mg/l)
However, 3 months later, there was an increase in PTH level reaching 2250,4pg/ml. The calcium level was at 96mg/l (normal range: 86–100 mg/l )and phosphore level at 47mg/l (normal range: 27–45 mg/l). the patient was readdressed to endocrinologist. It was decided to increase the dosage of calcimimetic agents.
The BT lesion exhibited signs of regression, after 7 months, following the parathyroidectomy, underscoring the critical importance of effectively controlling the underlying disease.
The patient is still under control for both the oral lesion and the PTH and calcium levels.