Journal of Mucosal Immunology Research
Open Access

Familial hyperparathyroidism, Parathyroid cancer.

Introduction

Parathyroid carcinoma (PCA), a very rare endocrine neoplasm first described by de Quervain in 1904, occurs either sporadically or as a part of a genetic syndrome [1]. It accounts for less than 1% cases of sporadic primary hyperparathyroidism in the world with a higher incidence of 5 % in Japan and Italy. It affects men and women equally frequency during the fourth or fifth decade of life [2]. Parathyroid carcinomas are generally hormonally active, presented by very high serum levels of intakt PTH (iPTH) and serum calcium levels but 10% of them are non-functional [3,4]. Patients with parathyroid carcinoma usually present with a severe form of hyperparathyroidism during the diagnosis including bone disease, renal failure, neurologic manifestations and gastrointestinal complaints, compared to the relatively asymptomatic presentation of benign parathyroid disease [5,6]. PHPT is observed in 80-90% of patients with the HPT-JT syndrome, parathyroid cancer is seen in 10-15%, and ossifying fibromas of the maxilla or mandible is seen in approximately 30%; furthermore, some patients have renal or uterine abnormalities [7]. We report a case of parathyroid carcinoma that developed 6 years after the first operation in a patient with familial hyperparathyroidism (Figure 1).

Figure 1: 99mTc-sestamibi parathyroid scan

Case Presentation

A 59-year-old male with a history of subtotal parathyroidectomy for parathyroid adenoma and nephrolithiasis admitted to the hospital with fatigue and resistant pain in the back and legs for a few months. He has a familial hyperparathyroidism history of his two sons. Both two sons of this patient developed parathyroid adenomas and jaw tumors. His boy was detected bilateral mandibula tumors with hyperparatiroidism. So this may be familial. Initial evaluation was notable for serum calcium concentration to 15,1 mg/dl (Reference range: 8,6-10,2 mg/dl), serum creatinine to 2.3 mg/dl (Reference range: 0,7-1,2 mg/dl) and parathyroid hormon level 420 pg/ml (Reference range: 15-65 pg/ml).

Neck ultrasound reported to show a 10x5 mm probable parathyroid lesion intimately related to the anterior pole of the left lobe of thyroid.

Computerized tomography (CT) scan of the neck viewed a 1.8x1.5 cm sized nodule located inferoposterior to the left thyroid lobe (Figure 2).

Figure 2: Histological appearance of surgical material

Microscopically:

• A-In section stroma, parathyroid parenchymal cells and several fibrous bands are observed.

• B- In section fibrous bands and parathyroid cells are observed.

• C- In section oncocytic cells with eosinophilic cytoplasm and small ovoid round nucleus and chief cells with hypercromatic nucleus and wide pale cytoplasmic are observed.

• D- In section fibrovascular stroma and cells with paled eosinophilic cytoplasm and large hypercromatic nucleus and clear nucleolus are followed. Postoperatively, patient’s calcium levels started to decrease. PTH and serum calcium values had returned normal levels 25 pg/ml and 8,7mg/dl respectively.

Discussion

Primary hyperparathyroidism (PHPT) is a general endocrine disease affecting up to 2% of individuals over the age of 55 years [8]. It is caused by solitary benign adenoma in 80–85%, hyperplasia in 10–15%, and parathyroid carcinoma in less than 1%. In up to 10% of cases PHPT is part of a familial syndrome like multiple endocrine neoplasia (MEN) types 1 or 2, hyperparathyroidism-jaw tumor syndrome (HPT-JT), familial isolated hyperparathyroidism (FIHP) or familial benign hypocalciuric hypercalcemia [9]. Our patient was investigated for MEN (pituitary, pancreas, stromal tumor) but no pathology was detected. A case of his boy whose bilateral brown tumors in the jaws spontaneously and totally improved after subtotal parathyroidectomy and endocrinological therapy who was closely followed up for 4 years even though the lesions were associated with impacted third molars [10]. Clinical findings of parathyroid malignancy include neck tumor, high serum parathormon values and associated hypercalcemia, and common fibrous osteitis [11, 12]. In addition, a report also states that findings such as depth/width ratio (D/W) ≥1 in the ultrasound image and a tumor growing into the thyroid gland could be useful evidences indicating malignancy [13]. From a genetic focus of view, the parathyroid carcinoma can consist of as a solitary finding in the isolated familial hyperparathyroidism or as a part of multiple endocrine neoplasia type I (MEN-1) [14]. Other genetic changes have been also found: the mutations of men1 gene (kr 11q13), loss of heterozygosity (LOH) in locus for retinoblastoma and overexpression of cyclin D1 [15]. Our patient has relatives parathyroidectomy due to parathyroid adenoma. Some patients had radiation therapy of the neck region in their medical history [16]. Our patient had no head and neck radioation story. The systemic oncological therapy of parathyroid carcinoma is not yet available. Some authors assume that radiotherapy could be useful against recurrent growth of the tumor. The post-operative follow of serum calcium value is significant. When taking operation decision, the value of intact parathormone as an initial parameter should be identified. Patients with parathyroid malignancy are repeatedly reoperated due to relapse. Persistent or relapsing disorder occurs in 50% of cases. When metastases are occuring, they are producing hormones and thus the aim is to remove metastatic focus in order to decrease the high parathormone serum levels. The surgical excision of local as well as distant metastatic lesions is the most effective process [17]. Significantly , with every reoperation, the frequency of perioperative complications increases (60%); the occurrence of recurrent laryngeal nerve paresis arrives up to 38 % [18].FIHP is an autosomal-dominant disease characterized by the absence of a nonparathyroid clinical appearance of common syndromic PHPT [19].

The cause of death of patients is mostly by uncontrolled hypercalcaemia, which leads to renal failure, heart dysrhythmias or pancreatitis [20]. Survivals rates vary from 90% at 5 years to 67% at 10 years in patients who undergo complete en bloc tumor resection. Lymph node metastases dur the diagnosis, distant metastases and non-functioning carcinomasing are a few negative prognostic factors.

Conclusion

In conclusıon patients with familial hyperparathyroidism should be followed closely and should be alert for the development of parathyroid cancer.

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