Endocrinol Metab.  2010 Dec;25(4):374-377. 10.3803/EnM.2010.25.4.374.

A Case of Familial Isolated Primary Hyperparathyroidism with a Novel Gene Mutation

• Kim SW
• Lee SJ
• Kim HS
• Kim JY
• Jung ED
• Jung DS

• KMID: 1497766
• DOI: http://doi.org/10.3803/EnM.2010.25.4.374

Abstract

Familial isolated primary hyperparathyroidism (FIHP) is an autosomal dominant disorder that is characterized by an early stage of either multiple endocrine neoplasia type 1 (MEN1) or hyperparathyroidism-jaw tumor (HPT-JT) syndrome. We report here on a case of a 42-years old woman who was diagnosed with papillary thyroid cancer and primary hyperparathyroidism. Her younger brother also had primary hyperparathyroidism. On the genetic analysis, they were both proven to have a novel frameshift mutation in the MEN1 gene (exon 10).

Keyword

Hyperparathyroidism-jaw tumor syndrome; MEN1; Primary hyperparathyroidism

MeSH Terms

Female
Frameshift Mutation
Humans
Hyperparathyroidism, Primary
Multiple Endocrine Neoplasia Type 1
Siblings
Thyroid Neoplasms

Figure

• 

  Fig. 1 Thyroid ultrasonography demonstrates 0.5 cm sized hypoechoic nodule in left thyroid gland (A), preoperative 99mTc-tetrofosmin parathyroid scan shows no significant radioactivity lesion at neck area (B).

• 

  Fig. 2 High power light microscopic finding shows parathyroid hyperplasia (H&E stain, × 200).

• 

  Fig. 3 Postoperative 99mTc-tetrofosmin parathyroid scan shows focal faint uptake (arrow) at superior mediastinal area (A), and postoperative chest-enhance CT scan shows 1.2 cm sized-well enhancing nodule (arrow) in superior mediastinum (B).

• 

  Fig. 4 Sequencing of exon 10 shows P551R (del C) and subsequently frameshift mutation.

Reference

1. Adami S, Marcocci C, Gatti D. Epidemiology of primary hyperparathyroidism in Europe. J Bone Miner Res. 2002. 17:N18–N23.

2. Khan A, Bilezikian J. Primary hyperparathyroidism: pathophysiology and impact on bone. CMAJ. 2000. 163:184–187.

3. Pannett AA, Kennedy AM, Turner JJ, Forbes SA, Cavaco BM, Bassett JH, Cianferotti L, Harding B, Shine B, Flinter F, Maidment CG, Trembath R, Thakker RV. Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism. Clin Endocrinol (Oxf). 2003. 58:639–646.

4. Simonds WF, James-Newton LA, Agarwal SK, Yang B, Skarulis MC, Hendy GN, Marx SJ. Familial isolated hyperparathyroidism: clinical and genetic characteristics of 36 kindreds. Medicine (Baltimore). 2002. 81:1–26.

5. Pannett AA, Thakker RV. Multiple endocrine neoplasia type 1. Endocr Relat Cancer. 1999. 6:449–473.

6. Powell AC, Libutti SK. Multiple endocrine neoplasia type 1: clinical manifestations and management. Cancer Treat Res. 2010. 153:287–302.

7. Bilezikian JP, Brandi ML, Rubin M, Silverberg SJ. Primary hyperparathyroidism: new concepts in clinical, densitometric and biochemical features. J Intern Med. 2005. 257:6–17.

8. Carling T. Multiple endocrine neoplasia syndrome: genetic basis for clinical management. Curr Opin Oncol. 2005. 17:7–12.

9. Thakker RV. Multiple endocrine neoplasia type 1. Endocrinol Metab Clin North Am. 2000. 29:541–567.

10. Raue F, Frank-Raue K. Multiple endocrine neoplasia type 2: 2007 update. Horm Res. 2007. 68:101–104.

11. Teh BT, Farnebo F, Kristoffersson U, Sundelin B, Cardinal J, Axelson R, Yap A, Epstein M, Heath H 3rd, Cameron D, Larsson C. Autosomal dominant primary hyperparathyroidism and jaw tumor syndrome associated with renal hamartomas and cystic kidney disease: linkage to 1q21-q32 and loss of the wild type allele in renal hamartomas. J Clin Endocrinol Metab. 1996. 81:4204–4211.

12. Tsukada T, Yamaguchi K, Kameya T. The MEN1 gene and associated diseases: an update. Endocr Pathol. 2001. 12:259–273.

13. Williamson C, Cavaco BM, Jauch A, Dixon PH, Forbes S, Harding B, Holtgreve-Grez H, Schoell B, Pereira MC, Font AP, Loureiro MM, Sobrinho LG, Santos MA, Thakker RV. Mapping the gene causing hereditary primary hyperparathyroidism in a Portuguese kindred to chromosome 1q22-q31. J Bone Miner Res. 1999. 14:230–239.

14. Hannan FM, Nesbit MA, Christie PT, Fratter C, Dudley NE, Sadler GP, Thakker RV. Familial isolated primary hyperparathyroidism caused by mutations of the MEN1 gene. Nat Clin Pract Endocrinol Metab. 2008. 4:53–58.

15. Dedivitis RA, Guimarães AV, Pontes GB. Multiple ectopic parathyroid adenomas. Sao Paulo Med J. 2004. 122:32–34.

16. Miura D. Ectopic parathyroid tumor in the sternohyoid muscles: supernumerary gland in a patient with MEN type 1. J Bone Miner Res. 2005. 20:1478–1479.