ARTÍCULO CLÍNICO

 

Hyperparathyroidism-jaw tumour syndrome

Síndrome de hiperparatiroidismo por tumor maxilar

 

 

L. Barroso¹, J. Pedro Marcelino², L. Jiménez Romero¹, I. Amado², A. Ferreira², C. Alberto Ribeiro³

¹ Médico Residente
² Cirujano Oral y Maxilofacial
³ Jefe de Servicio
Servicio de Cirugía Oral y Maxilofacial. Hospitais da Universidade de Coimbra (HUC), Portugal

Correspondence

 

 

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ABSTRACT

Hyperparathyroidism frequently has bone effects. In one subset of patients, these effects involve mainly facial bones (hyperparathyroidism-jaw tumour syndrome).
The authors describe an affected family from central Portugal and discuss the features of this still poorly known disease, which can present initially as a facial tumour.

Key words: Hyperparathyroidism; Jaw tumours; Ossifying fibromas; HPT-JT syndrome.

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RESUMEN

El hiperparatiroidismo tiene con frecuencia manifestaciones óseas, de predomínio facial en algunos pacientes.
Los autores describen las manifestaciones en una família de la región central de Portugal, como punto de partida para una revisión de los conocimientos sobre esta entidade clínica todavía poco divulgada y que puede tener como primera manifestación la presentación de tumores faciales.

Palabras clave: Hiperparatiroidismo; Tumores faciales; Fibromas osificantes; Síndrome HPT-TM.

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Introduction

Primary hyperparathyroidism, with an incidence reaching 1:1000, is the third most frequent endocrine disease after diabetes mellitus and hyperthyroidism. ¹ Most cases are sporadic and only about 10% are familial.² Primary hyperparathyroidism includes mainly multiple endocrine neoplasm (MEN) syndromes type 1 or 2, as well as hyperparathyroidism associated with jaw tumours – hyperparathyroidism-jaw tumour syndrome (HPT-JT). A few cases of isolated familial hyperparathyroidism have been published but, for the most part, they seem to be minor cases of the other syndromes, with incomplete phenotypes, probably corresponding to slightly different mutations of the same gene.^3,4

 

Material and method

In our hospital, several members of a kindred (Fig. 1) with HPT-JT have been evaluated and treated. This kindred has been described in endocrinological journals,⁵ but we are presenting it to the oral and maxillofacial surgery community to highlight the facial manifestations.

Case 1

In 1993, a 73-year-old man was admitted to one of our Internal Medicine ward with the provisional diagnosis of bone metastasis of an unknown primary tumour. He had lost 15 kg in 18 months and had anorexia, constipation, pain over the left thigh and elevated blood levels of calcium, bilirubin, and acid and alkaline phosphatase. The bone scan (Fig. 2) showed multiple areas of elevated uptake and hypertrophic osteoarthropathy, suggesting metastatic disease.

The patient’s personal history was irrelevant, apart from surgery on a maxillary tumour at the age of 18 years (1938). The histological diagnosis of this tumour was not available.

During admission, elevated levels of urinary calcium and blood parathormone were found. Cervical ultrasonography showed an enlarged right inferior parathyroid gland.

The patient underwent right hemithyroidectomy, along with extirpation of the enlarged parathyroid and the other ipsilateral gland; blood calcium levels normalized immediately. Histopathological examination demonstrated an infiltrating carcinoma of the lower parathyroid and hyperplasia of the upper parathyroid.

Two years later, the bone pain and constipation reappeared, along with elevated blood calcium and parathormone levels. He had surgery again, undergoing left hemithyroidectomy, parathyroidectomy and thymectomy. The blood calcium normalized and the patient died two years later from unrelated causes.

Case 2

In 1987, a 43-year-old male patient, the older son of patient 1, was admitted to our Oral and Maxillofacial Surgery department with a very large tumour on the left mandible (Fig. 3).

This mass had appeared 11 years earlier, when he lived in another part of the country, and was diagnosed in the local hospital as an ossifying fibroma. Elevated blood calcium and parathormone levels were detected at the same time and he underwent resection of a parathyroid adenoma.

Meanwhile, the mandibular mass kept on growing and the patient submitted to curettage and radiation therapy several times.

When first seen in our department, the patient had a voluminous mass on the left mandible with areas of osteoradionecrosis and infection, and two smaller masses on the left maxilla and right mandible (Figs. 4 and 5). At the same time, he had painful left amaurosis caused by radiation therapy and initial renal failure.

He had left eye enucleation and left hemimandibulectomy; reconstruction was not performed because of the local infection. The excised tumour (13 x 18 cm) was an ossifying fibroma (Fig. 6).

Five years later, he underwent right hemimandibulectomy and reconstruction with 2 rib grafts (Fig. 7); the histopathological diagnosis of the right tumour was the same. The patient died 3 years later of renal failure complications, although he had been on haemodialysis since 1990.

Case 3

When he was 40 years old (1987), this patient suffered pain in his right hand and middle third of his left calf. He was examined in the Orthopaedics Department of our hospital and was found to have cystic lesions at these locations as well as in a rib and the right mandibular ramus (Fig. 8).

The patient had been aware of the mandibular lesion since he was 23 years old, when a biopsy showed that it was benign. As it had barely grown since then, he had not sought treatment.

Three years earlier, he had a pathologic fracture of the patella, which was treated in another hospital.

The cystic lesion on the right hand was diagnosed by biopsy as an osteoclastoma. Given the multiple lesions, he was believed to suffer from pluriostotic fibrous dysplasia. The following year, he had another pathological fracture of the left femur (Fig. 9) and several episodes of haematuria. During the evaluation of the haematuria, elevated blood calcium and parathormone levels and cortical renal cysts were found.

In 1989, he underwent right hemithyroidectomy and extirpation of a right lower parathyroid adenoma.

Since then, his blood calcium and parathormone levels have remained normal, his mandibular tumour has not grown and the patient does not wish to have it removed.

Case 4

This patient, the daughter of patient 2, was evaluated in our department in 1995, at the age of 21 years. She presented with a tumour on the fourth quadrant (Fig. 10) that was well demarcated, extended to the basilar border and looked almost like a cyst, but with slight trabeculation.

Knowing her family history of hyperparathyroidism and jaw tumours, she was referred to the endocrinology department for evaluation.

She was found to have elevated blood calcium and parathormone levels and advanced fibrous cystic osteitis (Fig. 11). Her parathyroid adenoma was removed, followed later by segmental right hemimandibulectomy and reconstruction with a cadaveric allograft (Fig. 12). The tumour was an ossifying fibroma.

Case 5

This patient, the daughter of patient 3, underwent biochemical and radiological screening when she was 14 years old. She was found to have hypocalcaemia, hyperparathyroidism, two tumours of the jaws (second and fourth quadrants) and several renal cysts.

Lower right parathyroidectomy was performed for a parathyroid adenoma. Blood calcium levels were normal for one year, after which they again started increasing. She underwent surgery again (left upper and lower parathyroidectomy, and removal of half of the right upper parathyroid for an adenoma in the left upper gland).

The jaw lesions kept on growing and several months later she had the two ossifying fibromas removed.

Subsequently, she had another episode of hyperparathyroidism and another operation to remove the adenoma on the remaining gland. There is no sign of relapse or new jaw tumours.

 

Discussion

In 1958, Jackson⁶ described a family with hereditary hyperparathyroidism, in most cases also with jaw tumours, after the observations of other authors defined this syndrome⁷ and differentiated it from MEN-1 and MEN-2.⁸

HPT-JT is an autosomal dominant hereditary disease mapped to chromosome 1 (1q25-q31)⁹ that causes parathyroid tumours, ossifying jaw fibroma, several renal lesions (cysts, Wilms’ tumour, hamartoma, cortical adenoma, papillary cell carcinoma), and other tumours (pancreatic adenocarcinoma, testicular tumour, Hürthle cell tumour of the thyroid, adenomyomatous polyps of the uterus).^10-12,18

The most frequent manifestations (parathyroid adenomas and ossifying fibromas) appear at younger ages than in sporadic cases, which are more frequent in middle age¹² and after the third decade,¹³ respectively.

Hyperparathyroidism is the result of the tumours, not parathyroid gland hyperplasia, as in MEN syndromes. In HPT-JT, adenomas are frequently cystic and the incidence of carcinoma is 5%, much higher than the incidence of this cancer in the general population (1:5,000,000).^11,14,15 It is not uncommon for a patient to develop several adenomas after the extirpation of one,⁸ as occurred with patients 1 and 5.

Ossifying fibromas are present in about half of the patients and their behaviour is independent from blood calcium levels.^8,9 They are well delimited and initially radiolucent, but become progressively calcified. They can displace or, rarely, destroy the dental roots. Radiologically, they might appear similar to fibrous dysplasia, but this disorder has undefined borders and does not destroy the dental roots. Histologically, they are composed of woven bone in a fibrocellular stroma, with areas of lamellar bone and, sometimes, cementum. In contrast, lamellar bone and cementum do not develop in fibrous dysplasia.

In patients with hyperparathyroidism, ossifying fibromas might coexist with fibrous cystic osteitis lesions, which are mostly radiolucent and multifocal, and consist histologically of fibrosis, bone marrow haemorrhage and numerous giant cells. These lesions, also known as brown tumours, are hard to distinguish histologically from giant-cell tumours and granulomas, aneurysmal bone cysts and even fibrous dysplasia (as occurred with patient 3), although giant cells are much less numerous in fibrous dysplasia. Hyperparathyroidism should be ruled out when one of the above findings is made in a biopsy, especially if lesions are multiple.

In this kindred, jaw tumours seemed to have a higher penetrance than the usual 50%, as 5 of 7 patients with the abnormal gene had jaw fibromas. These tumours appeared at the typical age (14 to 32 years) and showed variable clinical behaviour: no relapse in patients 1, 4 and 5 (for 58, 7 and 3 years), very slow growth for over 30 years in patient 3, and persistent, multifocal growth in patient 2.

Hyperparathyroidism manifested itself in several ways: by simulating bone metastases (patient 1), causing nephrolithiasis and pathologic fractures (patient 3), clinically silence with extensive bone lesions (patient 4), or as only a biochemical abnormality (patient 5). In every case except patient 1, patients were much younger than the average patient with sporadic hyperparathyroidism.

This is a rare disorder that can present initially with a jaw tumour. Oral and maxillofacial surgeons should be aware of its existence in order to rule out hyperparathyroidism in patients with ossifying fibroma, as many surgeons already do in cases of giant-cell granulomas and tumours or multiple fibrous dysplasia foci.

In the patients affected, hyperparathyroidism must be treated, and other organs, including the maxillofacial area, must be screened as ossifying fibromas can reappear even after the normalization of blood calcium levels. Families should be offered genetic counselling.

 

 

Correspondence:
Leonor Barroso
Serviço de Cirurgia Maxilo-Facial
Hospitais da Universidade de Coimbra
3000-075 Coimbra, Portugal
Email: leonorbarroso@netcabo.pt

Recibido: 24.11.05
Aceptado: 16.06.08

 

 

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