Familial Hyperparathyroidism Due to A Germline Mutation of the Cdc73 Gene: Implications for Management and Age-Appropriate Testing of Relatives At Risk

Pichardo-Lowden, Ariana; Manni, Andrea; Saunders, Brian; Baker, Maria

doi:10.4158/ep10337.ra

Cited by 37 publications

(29 citation statements)

References 29 publications

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“…The youngest reported case of PHPT in a family diagnosed with HPT-JT syndrome is in a 7 year old child. Therefore, we recommend genetic screening within affected families at 5 years of age (16). For those found to be asymptomatic carriers, current recommendations include lifelong serum testing for biochemical evidence of PHPT every 6 to 12 months, with panoramic dental imaging and renal ultrasound at least every 5 years after identification of germline mutation.…”

Section: Discussionmentioning

confidence: 99%

Hyperparathyroidism-jaw tumor syndrome: Results of operative management

Mehta

Patel

Rosenberg

et al. 2014

Surgery

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Background Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant disease secondary to germline inactivating mutations of the tumor suppressor gene HRPT2/CDC73. The aim of the present study is to determine the optimal surgical approach to parathyroid disease in patients with HPT-JT. Method A retrospective analysis of clinical and genetic features, parathyroid operative outcomes, and disease outcomes in seven unrelated HPT-JT families. Results Seven families had five distinct germline HRPT2/CDC73 mutations. Sixteen affected family members (median age of 30.7 years) were diagnosed with primary hyperparathyroidism. Fifteen of the 16 patients underwent preoperative tumor localization studies and uncomplicated bilateral neck exploration at initial operation - all were in biochemical remission at most recent follow up. 31% of patients had multiglandular involvement. 37.5% of patients developed parathyroid carcinoma (median overall survival 8.9 years; median follow-up 7.4 years). Long-term follow-up showed 20% of patients had recurrent primary hyperparathyroidism. Conclusions Given the high risk of malignancy and multiglandular involvement in our cohort, we recommend bilateral neck exploration and en-bloc resection of parathyroid tumors suspicious for cancer and life-long postoperative follow-up.

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Section: Discussionmentioning

confidence: 99%

Hyperparathyroidism-jaw tumor syndrome: Results of operative management

Mehta

Patel

Rosenberg

et al. 2014

Surgery

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“…The prevalence of pHPT increases with age, and whilst the onset is typically in early adulthood, the earliest reported age is 7 years [58]; the earliest parathyroid carcinoma has been found at the age of 20. However, the onset may be delayed until the sixth decade, and some older healthy mutation carriers have been reported.…”

Section: Clinical Featuresmentioning

confidence: 99%

“…pHPT in HPT-JT is usually caused by a single benign parathyroid adenoma, which is often cystic or has atypical histologic features [60]. In contrast to other variants of familial disease, parathyroid carcinoma may be found in 21.6 % of cases (Table 4) [47,48,50,53,54,[56][57][58]. Multiglandular involvement occurs rarely at initial surgery (20 % of cases); a second parathyroid tumour may occur metachronously in the years to decades after the appearance of the first tumour (23.9 % of cases) ( Table 4).…”

Section: Clinical Featuresmentioning

confidence: 99%

Hereditary hyperparathyroidism—a consensus report of the European Society of Endocrine Surgeons (ESES)

Iacobone

Carnaille

Palazzo

et al. 2015

Langenbecks Arch Surg

110

126

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Hereditary hyperparathyroidism typically presents at an earlier age than the sporadic variants. Gene penetrance and expressivity varies. Parathyroid multiple gland involvement is common, but in some variants, it may occur metachronously often with long disease-free intervals, simulating a single-gland involvement. Bilateral neck exploration with subtotal parathyroidectomy or total parathyroidectomy + autotransplantation should be performed, especially in MEN 1, in order to decrease the persistent and recurrent hyperparathyroidism rates; in some variants (MEN 2A, HPT-JT), limited parathyroidectomy can achieve long-term normocalcemia. In FHH, surgery is contraindicated; in NSHPT, urgent total parathyroidectomy is required. In FIHPT, MEN 4 and ADMH, a tailored case-specific approach is recommended.

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“…Proper screening for HPT-JT associated tumors is recommended to start at age five to ten in asymptomatic patients with germline CDC73 gene mutation found through genetic testing (Jackson MA 2015; Pichardo-Lowden, et al 2011). Screening includes biochemical testing every 6–12 months, and panoramic dental imaging and renal ultrasound every 5 years (Jackson MA 2015).…”

Section: Parathyroid Cancer In the Hyperparathyroidism-jaw Tumor Syndmentioning

confidence: 99%

“…Due to the high recurrence rate of hyperparathyroidism (about 20%) in HPT-JT patients, some experts recommend en bloc resection of parathyroid tumors with bilateral neck exploration (Mehta et al 2014). Other authors recommend ipsilateral thyroidectomy and complete central neck dissection for malignant tumors (Pichardo-Lowden et al 2011), or use of radiological evidence of multiglandular involvement to guide subtotal parathyroidectomy and/or bilateral neck exploration (Haciyanli, et al 2011; Pichardo-Lowden et al 2011). For initial surgery, we would recommend en bloc resection for a lesion highly suspicious for parathyroid carcinoma, with strong consideration for bilateral neck exploration guided by radiological findings for other candidate lesions.…”

Section: Parathyroid Cancer In the Hyperparathyroidism-jaw Tumor Syndmentioning

confidence: 99%

Endocrine neoplasms in familial syndromes of hyperparathyroidism

Li¹,

Simonds²

2016

Endocrine-Related Cancer

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Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2 to 5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and non-endocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome, thymic, bronchial and enteropancreatic neuroendocrine tumors in MEN1, and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared to their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential.

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Familial Hyperparathyroidism Due to A Germline Mutation of the Cdc73 Gene: Implications for Management and Age-Appropriate Testing of Relatives At Risk

Cited by 37 publications

References 29 publications

Hyperparathyroidism-jaw tumor syndrome: Results of operative management

Hyperparathyroidism-jaw tumor syndrome: Results of operative management

Hereditary hyperparathyroidism—a consensus report of the European Society of Endocrine Surgeons (ESES)

Endocrine neoplasms in familial syndromes of hyperparathyroidism

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