Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel &lt;i&gt;CDC73&lt;/i&gt; mutation

Shibata, Yusuke; Yamazaki, Masanori; Takei, Masahiro; Uchino, Shigehiko; Sakurai, Akihiro; Komatsu, Mitsuhisa

doi:10.1507/endocrj.ej15-0057

Cited by 14 publications

(11 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inactivating CDC73 mutation is a major driver of parathyroid carcinoma; in contrast, such mutations are extremely rare in sporadic parathyroid adenomas (Howell et al 2003, Cetani et al 2004, Krebs et al 2005, Bradley et al 2006, Guarnieri et al 2012a. When found, they were typically associated with uncommon histologic and/or clinical features, such as cystic appearance (Carpten et al 2002, Domingues et al 2012, large gland weight (Sulaiman et al 2012a), young age at presentation (Starker et al 2012a,b), or recurrence (Cetani et al 2007, Shibata et al 2015, and are often found in the germline.…”

Section: Other Genesmentioning

confidence: 99%

Molecular genetic insights into sporadic primary hyperparathyroidism

Brewer

Costa-Guda

Arnold

2019

Endocrine-Related Cancer

View full text Add to dashboard Cite

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by dysregulation of parathyroid hormone release. The large majority of PHPT cases are attributable to sporadic, single-gland parathyroid adenoma, in which MEN1 and CCND1/cyclin D1 are the most well-established drivers of tumorigenesis. Sporadic parathyroid carcinoma, which appears to mostly arise through molecular pathways distinct from those causing benign parathyroid tumors, is rare and is most frequently driven by mutational inactivation of the CDC73 (HRPT2) tumor suppressor gene. Targeted investigation of suspected tumor driver genes, as well as unbiased whole-genome or exome sequencing of small cohorts, have revealed additional novel candidate tumor genes in sporadic parathyroid neoplasia, generally at modest or low mutational frequencies consistent with marked molecular genetic heterogeneity from tumor to tumor. The ability of these additional candidates to participate in the pathogenic process of driving parathyroid tumorigenesis in vivo largely remains to be demonstrated experimentally. This review will summarize the molecular genetic abnormalities identified to date in sporadic PHPT and discuss the strength of evidence for their proposed roles in parathyroid tumor formation.

show abstract

Section: Other Genesmentioning

confidence: 99%

Molecular genetic insights into sporadic primary hyperparathyroidism

Brewer

Costa-Guda

Arnold

2019

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Precise incidence and prevalence data for this disorder are unknown . Approximately 70–80% of patients develop symptomatic hyperparathyroidism by the age of 40 years, with males affected slightly more commonly than females . Jaw tumours occur in up to 12.5% of CDC73 gene carriers.…”

Section: Hyperparathyroidism‐jaw Tumour Syndrome (Hpt‐jt)mentioning

confidence: 99%

Heritable forms of primary hyperparathyroidism: a current perspective

DeLellis

Mangray

2017

Histopathology

View full text Add to dashboard Cite

Primary hyperparathyroidism (PHPT) is one of the most common of all endocrine disorders encountered by the practising histopathologist. The vast majority of lesions are sporadic in nature, approximately 85% of which are parathyroid adenomas, while hyperplasia and carcinoma account for 10-15% and fewer than 1%, of cases, respectively. Heritable forms of PHPT are much less common and present challenges both to clinicians and pathologists, particularly when they are the presenting feature of an endocrine syndrome. In such instances, pathologists play a key role in alerting physicians to the possibility of an underlying heritable endocrine syndrome and the potential for extra-endocrine manifestations. Therefore, a working knowledge of these disorders is essential for providing guidance to treating physicians. The aim of this update is to review the clinicopathological features, genetic bases and current management for patients with PHPT associated with multiple endocrine neoplasia (MEN) types 1, 2A and 4 and hyperparathyroidism-jaw tumour (HPT-JT) syndrome in the context of the 2017 World Health Organization (WHO) Classification of Tumours of the Endocrine Organs. Additionally, familial isolated hyperparathyroidism, familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidism are discussed.

show abstract

“…CDC73 mutation analysis should be performed in cases of early-onset, recurrent, pHPT with polyglandular parathyroid involvement and pHPT presenting with severe hypercalcaemia, even if there is no positive family history. 7 Other rare forms of genetic hyperparathyroidism, including hyperparathyroidism-jaw tumour syndrome (also CDC73), gain of function mutation of GCM2 and MEN (multiple endocrine neoplasia) types 1 (menin mutation), 2 (RET) and 4 (CDNK1B) had been described.…”

Section: Discussionmentioning

confidence: 99%

Treatment of extreme hypercalcaemia: the role of haemodialysis

et al. 2018

View full text Add to dashboard Cite

A patient with extremely high calcium level of 23.9 mg/dL (5.97 mmol/L) was admitted to our department unconscious with pathological ECG recording, demonstrating shortening of QT interval. The patient was treated by fluid resuscitation, bisphosphonates, salmon calcitonin and steroids. Haemodialysis with low calcium bath had been promptly provided with improvement of consciousness and calcium level. ECG changes disappeared. Subsequent investigations revealed hyperparathyroidism and a large parathyroid adenoma was then surgically removed. Extreme and rapid calcium elevation (parathyroid crisis) is rarely seen in primary hyperparathyroidism and usually is distinctive for malignancy. In the context of acute kidney injury and refractory hypercalcaemia with life-threatening complications (coma, ECG changes with impending danger of arrhythmia), haemodialysis may effectively decrease calcium levels. It should be pointed out that dialysis is an efficient method of treatment of refractory hypercalcaemia, parathyroid crisis, but it is rarely used due to its invasive nature.

show abstract

Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel <i>CDC73</i> mutation

Cited by 14 publications

References 20 publications

Molecular genetic insights into sporadic primary hyperparathyroidism

Molecular genetic insights into sporadic primary hyperparathyroidism

Heritable forms of primary hyperparathyroidism: a current perspective

Treatment of extreme hypercalcaemia: the role of haemodialysis

Contact Info

Product

Resources

About