Oral Manifestations of Secondary Hyperparathyroidism: A Case Report and Literature Review

Case report

A 52-year-old male reported to the University of British Columbia Nobel Biocare Oral Health Center (Vancouver, BC, Canada) for general dental care and maintenance. Medical history indicated that, at age 17, he was diagnosed with polycystic kidney disease and suffered from chronic renal insufficiency. At age 35, he received a cadaverous kidney transplant that failed to integrate, and within a year, both the transplanted and natural kidneys were removed. He has been receiving dialysis for the past 18 years.

Subsequent to nephrectomy, in order to manage high PTH levels, at age 42, he underwent partial parathyroidectomy. The patient indicated that, in discussion with his surgeon, he was informed that approximately 1% of original gland size was left behind.

Currently, the patient utilizes a home dialysis system five days a week. He does not consume alcohol or tobacco products. He has been placed on a low potassium diet and takes supplemental erythropoietin, vitamin D, and iron dextrin.

An intra-oral examination did not reveal any evidence of maxillary or mandibular expansion in the soft tissue. Teeth UR8, UL8, LL5, LL6, LL7, LL8, LR2, LR6 and LR8 were found to be missing. There was generalized Grade I mobility in the dentition except the lower premolars, which exhibited Grade II mobility. There were no complaints of halitosis, reduction of saliva, unspecific jaw pain, or teeth sensitivity on mastication.

Intra-oral and panoramic radiographs showed marked evidence of altered bone density (Figures 1 and 2). Bilaterally, well-circumscribed multilocular radiolucent lesions suggest potential brown tumour⁷ in the mandible (Figures 1b and 2). Diminished or complete absence of lamina dura was observed both in the anterior and posterior mandibular regions. There was evidence of trabeculation in the anterior mandible, but not in the posterior region that exhibited a ground glass appearance. The cortical border of the mandible and the mandibular canal were clear in the radiograph (Figure 2). There was, however, profound horizontal bone loss in the maxilla.

The biochemical profile of the patient revealed: calcium 2.41 mmol (Normal: 2.10–2.60 mmol), phosphate 0.8 mmol (Normal: 0.1–1.5 mmol), alkaline phosphate 57 U/L (Normal: 40–145 U/L), and PTH 40.1 pmol/L (Normal: <7.0 pmol/L). These data indicate elevated levels of parathyroid hormone, establishing the diagnosis of hyperparathyroidism. Further observations of the normal blood calcium, phosphate, and alkaline phosphatize levels suggest secondary hyperparathyroidism.⁷ Additionally, the patient's medical history of nephrectomy, as a result of renal failure from polycystic kidney disease, and continuation of long-term dialysis further corroborated the diagnosis of secondary hyperparathyroidism with ROD.

Discussion

Although the earliest evidence of primary hyperparathyroidism was identified in a 7000-year-old cadaver from an early Neolithic cemetery, the first clinical case of primary hyperparathyroidism was diagnosed by Felix Mandl in 1925. Later, the oral manifestations were described by Albright et al in 1934.^21,22 Subsequently, in 1948, osteolytic lesions were recognized in the mandible of a patient thought to have hyperparathyroidism secondary to kidney failure,²³ but it was not until 1963 that the first confirmed case of maxillofacial brown tumour was reported in a secondary hyperparathyroidism patient.²⁴

It was well recognized that dialysis may prolong the life of a CKD patient but an elongated period of high levels of PTH exacerbates secondary hyperparathyroidism. Subsequently, associated brown tumours may progress to localized bone pain or pathological fractures.²⁵ Ideally, clinicians could use radiographic oral manifestations to evaluate an associated severity of secondary hyperparathyroidism in a long-term dialysis patient. This is, however, not always straightforward because the oral manifestations of hyperparathyroidism vary considerably in different patients.

A review of English language literature of published cases of the previous 80 years (1934–2017), from 15 different countries, showed 544 cases of varying oral manifestations related to primary or secondary hyperparathyroidism (Table 1). Although initial studies were reported from USA, subsequent reports from 14 other countries indicate that hyperparathyroidism can occur across all ethnic groups (Table 1). Of 544 cases, 210 showed a loss or absence of lamina dura (male: 36, female: 49, unspecified: 125), 103 demonstrated a ground glass mandible (male: 15, female: 12, unspecified: 76), 76 showed the appearance of osteolytic lesions (male: 25, female: 4, unspecified: 47), 73 reported thinning of the cortical boundary of the mandible (male: 25, female: 40, unspecified: 8), and 64 documented a clinical brown tumour (male: 16, female: 23, unspecified: 25). The analysis suggests that, with increasing age, there appears to be a trend towards a higher frequency of oral manifestations in hyperparathyroidism cases. Females may be less prone to presenting with a ground glass mandible but more prone to presenting with a thinning of cortical boundary. Since the unspecified count, however, is substantial, any relationship between specific gender and oral manifestation, if any, remains unclear.

There was a total of 308 primary and 236 secondary hyperparathyroidism cases and, in both circumstances, the lamina dura loss appears to be the most common finding (46% and 32% of cases, respectively), while ground glass appears more frequently in secondary hyperparathyroidism (15% and 25% of cases, respectively). Radiolucent osteolytic lesions, brown tumour, and thinning of mandibular border seem to have similar prevalence in both types of hyperparathyroidism.

Loss of lamina dura has been heavily debated as a pathognomonic feature of hyperparathyroidism. Earlier studies by Silverman et al indicated that only 4 patients out of 55 primary hyperparathyroidism patients demonstrated changes in lamina dura.^16,17 In contrast, three separate studies of secondary hyperparathyroidism noted lamina dura loss in 17 of 38 (45%),²⁶ 5 of 9 (55%),²⁷ and 15 of 15 (100%).¹⁹ It is plausible that the stronger relationship between lamina dura loss and secondary hyperparathyroidism patients might be related to the duration of dialysis, reflecting changes in extensive osseous calcium-leeching from prolonged PTH exposure.²⁸ The average duration of dialysis reported in the aforementioned studies were 0.6,²⁶ 8.05²⁷ and 3.5¹⁹ years, respectively, and are associated with the high frequency of lamina dura loss.

Additionally, more recent single case reports with long-term dialysis patients (>5 years) appear to have a high frequency of lamina dura loss, ground glass appearance, presence of brown tumours, and thinning of the cortical boundaries of the mandibular border.^18,25,29 In the present case, the patient has undergone dialysis for 18 years and exhibits all radiographic traits, except for maxillofacial swelling of a brown tumour and thinning of the mandibular border. In spite of this, he still presents with clearly demarcated radiographic osteolytic lesions (Figures 1b and 2). These observations strengthen the notion that some oral manifestations may appear after long-standing disease.¹⁷

An invasive biopsy to verify the presence of brown tumour⁷ was not undertaken in the present case because there was no evidence of intra-oral swelling or other symptomatic complaints. Both classical oral surgery textbooks and current guidelines of putative brown tumour management emphasize directly addressing the hyperparathyroidism treatment rather than immediate brown tumour excision.^7,30,31,32

The patient recorded in the present study continues to demonstrate an elevated serum level of PTH, despite having the majority of its parathyroid hormone removed. One hypothesis is that there may have been an inadequate resection of PTH gland, a missed fifth PTH gland, or presence of an ectopic gland.³³ Alternatively, a study where the parathyroid glands were genetically ablated from mice demonstrated that experimental mice had detected PTH levels equivalent to wildtype control mice.³⁴ The auxiliary source of PTH was attributed to the thymus, suggesting an ectopic source of PTH release may become available despite parathyroid gland removal. Regardless, re-occurrence risk of secondary hyperparathyroidism increases with time in post-parathyroidectomy patients.³³

The patient described in the present study continues to attend the dental clinic at the University of British Columbia on a regular basis. During a one-year follow-up with the patient, there have not been any changes or concerns regarding oral manifestations, including focal bone pain or intra-oral enlargements in the maxilla or mandible.

Conclusion

This report presents a patient who exhibits oral manifestations commonly attributed to prolonged secondary hyperparathyroidism resulting from long duration dialysis. Findings showed lamina dura loss, ground glass mandible, and the presence of osteolytic lesions, but no evidence of clinical intra-oral maxillofacial enlargement. Further, although there was no concrete observed gender predilection, lamina dura loss may occur with increasing frequency in cases of prolonged dialysis and subsequent secondary hyperparathyroidism.