Parathyroid Carcinoma Causing Mild Hyperparathyroidism in Neurofibromatosis Type 1: A Case Report and Systematic Review

Author(s): Vincenzo Triggiani*, Marco Castellana, Paolo Basile, Giuseppina Renzulli, Vito Angelo Giagulli.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 19 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Neurofibromatosis type 1 is an autosomal dominant disorder characterized by an increased incidence of tumors, including endocrine ones. Primary hyperparathyroidism can be rarely caused by a parathyroid carcinoma; these patients are generally characterized by severe symptoms, large neck lesions and high levels of PTH and calcium. We report a case of hyperparathyroidism due to parathyroid carcinoma in a patient affected by neurofibromatosis type 1. A systematic review of the literature was also conducted.

Patient Findings: A 56-year-old woman was referred for a 13 mm-nodular lesion of the neck incidentally discovered on ultrasound examination and mild hyperparathyroidism. A 99mTctetrofosmin/ pertechnetate subtraction scintigraphy was negative for parathyroid disease. Given the absence of suspicious ultrasound finding, a fine-needle aspiration cytology was performed with iPTH determination in the aspirate, confirming the parathyroid origin of the lesion. The patient underwent left inferior parathyroidectomy with intraoperative monitoring of iPTH and became normocalcemic. On histopathological examination, parathyroid carcinoma presenting at the resection margin was diagnosed, thus a surgery revision was requested.

Conclusion: Even if literature does not support a syndromic association between neurofibromatosis type 1 and primary hyperparathyroidism, the benefit of precociously diagnosing and treating this condition may outweigh costs associated with screening. This case report moreover demonstrates that sometimes clinical, laboratory and imaging aspects suspicious for cancer may be missing. A prompt referral to a high-volume center is crucial for the management of those cases of incidental histopathological diagnosis.

Keywords: Parathyroid carcinoma, neurofibromatosis type 1, primary hyperparathyroidism, systematic review, case report, autosomal dominant.

[1]
Gutmann, D.H.; Ferner, R.E.; Listernick, R.H.; Korf, B.R.; Wolters, P.L.; Johnson, K.J. Neurofibromatosis type 1. Nat. Rev. Dis. Primers, 2017, 3, 17004.
[2]
Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch. Neurol., 1988, 45(5), 575-578.
[3]
Uusitalo, E.; Rantanen, M.; Kallionpää, R.A.; Pöyhönen, M.; Leppävirta, J.; Ylä-Outinen, H.; Riccardi, V.M.; Pukkala, E.; Pitkäniemi, J.; Peltonen, S.; Peltonen, J. Distinctive cancer associations in patients with neurofibromatosis type 1. J. Clin. Oncol., 2016, 34(17), 1978-1986.
[4]
Walker, L.; Thompson, D.; Easton, D.; Ponder, B.; Ponder, M.; Frayling, I.; Baralle, D. A prospective study of neurofibromatosis type 1 cancer incidence in the UK. Br. J. Cancer, 2006, 95(2), 233-238.
[5]
Goswamy, J.; Lei, M.; Simo, R. Parathyroid carcinoma. Curr. Opin. Otolaryngol. Head Neck Surg., 2016, 24(2), 155-162.
[6]
Walker, M.D.; Silverberg, S.J. Primary hyperparathyroidism. Nat. Rev. Endocrinol., 2018, 14(2), 115-125.
[7]
Abdel-Wanis, M.E.; Kawahara, N.; Tomita, K. The association of neurofibromatosis 1 and spinal deformity with primary hyperparathyroidism and osteomalacia: Might melatonin have a role? J. Orthop. Sci., 2001, 6(2), 193-198.
[8]
Altinova, A.E.; Toruner, F.; Cimen, A.R.; Karakoc, A.; Atasever, T.; Yetkin, I.; Ayvaz, G.; Cakir, N.; Arslan, M. The association of neurofibromatosis, bilateral pheochromocytoma and primary hyperparathyroidism. Exp. Clin. Endocrinol. Diabetes, 2007, 115(7), 468-470.
[9]
Al-Wahhabi, B. Parathyroid adenoma and bilateral pheochromocytoma in a patient with neurofibromatosis. Ann. Saudi Med., 2005, 25(3), 255-257.
[10]
Bahadir, C.; Gürleyik, G.; Ocak, E. Neurofibromatosis type 1 and primary hyperparathyroidism with spinal deformity and osteoporosis. Acta Chir. Belg., 2009, 109(1), 123-125.
[11]
Behera, K.K.; Nanaiah, A.; Gupta, A.; Rajaratnam, S. Neurofibromatosis type 1, pheochromocytoma with primary hyperparathyroidism: A rare association. Indian J. Endocrinol. Metab., 2013, 17(2), 349-351.
[12]
Bretagne, J.F.; Le Pogamp, P.; Lancien, G.; Gastard, J. Ulcerative hemorrhagic colitis, hyperparathyroidism and Recklinghausen’s disease. Gastroenterol. Clin. Biol., 1980, 4(6-7), 497-498.
[13]
Buderi, S.I.; Saleh, H.Z.; Theologou, T.; Shackcloth, M. Endobronchial ultrasound-guided biopsy to diagnose large posterior mediastinal parathyroid adenoma prior to video-assisted thoracoscopic resection. BMJ Case Rep., 2014, 2014, pii: bcr2013200131.
[14]
Caniggia, A.; Gennari, C.; Guideri, R.; Cesari, L. Comparison between the results of radiocalcium studies and histological findings in a case of primary hyperparathyroidism (osteitis fibrosa cystica generalisata of von Recklinghausen) before and after removal of parathyroid adenoma. J. Clin. Endocrinol. Metab., 1966, 26(8), 867-874.
[15]
Chakrabarti, S.; Murugesan, A.; Arida, E.J. The association of neurofibromatosis and hyperparathyroidism. Am. J. Surg., 1979, 137(3), 417-420.
[16]
Cinamon, U.; Avinoach, I.; Harell, M. Neurofibromatosis type 1, hyperparathyroidism, and osteosarcoma: interplay? Eur. Arch. Otorhinolaryngol., 2002, 259(10), 540-542.
[17]
Daly, D.; Kaye, M.; Estrada, R.L. Neurofibromatosis and hyperparathyroidism--A new syndrome? Can. Med. Assoc. J., 1970, 103(3), 258-259.
[18]
Demirjian, A.N.; Grossman, J.M.; Chan, J.L.; Parangi, S. Parathyroid carcinoma and neurofibromatosis. Surgery, 2008, 144(5), 827-829.
[19]
Dieter, R.A., Jr; O’Brien, T.; Carpenter, R. Giant mediastinal parathyroid adenoma with hypercalcemia. Int. Surg., 2002, 87(4), 217-220.
[20]
Doerffel, E.; Kirsh, R.; Mangakis, N.; Vollmar, R. Directed radioiodine diagnosis in detection of a parathyroid gland adenoma in generalized osteitis fibrosa (von Recklinghausen). Radiobiol. Radiother., 1961, 2, 337-344.
[21]
Duquenne, M.; Klein, M.; Duriez, T.; Hadjadj, S.; Weryha, G.; Leclère, J. Hyperparathyroidism in a patient with neurofibromatosis associated with Steinert’s disease. Ann. Med. Interne (Paris), 1994, 145(7), 505-507.
[22]
Favere, A.M.; Tsukumo, D.M.; Matos, P.S.; Santos, S.L.; Lalli, C.A. Association between atypical parathyroid adenoma and neurofibromatosis. Arch. Endocrinol. Metab., 2015, 59(5), 460-466.
[23]
Gkaliagkousi, E.; Erlic, Z.; Petidis, K.; Semertzidis, P.; Doumas, M.; Zamboulis, C.; Neumann, H.P.; Douma, S. Neurofibromatosis type 1: should we screen for other genetic syndromes? A case report of co-existence with multiple endocrine neoplasia 2A. Eur. J. Clin. Invest., 2009, 39(9), 828-832.
[24]
Godlewski, G.; Sawan, S.; Targhetta, P.; Pignodel, C.; Marty-Double, C.; Gaujoux, A.F. A malignant schwannoma of the jejunum associated with multiple neurofibromas and a primary adenoma of the parathyroid. Ann. Gastroenterol. Hepatol., 1989, 25(1), 13-17.
[25]
Hoppe, L.B.; Collicott, P.E.; Stivrins, T.J. von Recklinghausen’s neurofibromatosis and primary hyperparathyroidism: a case report and literature review. Nebr. Med. J., 1986, 71(12), 435-437.
[26]
Kodama, H.; Iihara, M.; Okamoto, T.; Obara, T. Water-clear cell parathyroid adenoma causing primary hyperparathyroidism in a patient with neurofibromatosis type 1: Report of a case. Surg. Today, 2007, 37(10), 884-887.
[27]
Moiton, M.P.; Bijou, F.; Vargas, F.; Valentino, R.; Gruson, D.; Hilbert, G.; Bénissan, G.; Cardinaud, J.P. Association of type 1 neurofibromatosis and primary hyperparathyroidism. Presse Med., 2002, 31(34), 1604-1605.
[28]
Popescu, E.; Popa, C.; Mogoş, V.; Niculescu, D.; Dănilă, V.; Balan, M.; Moisii, L.; Laba, E. Brown tumors of upper and lower jaws in Recklinghausen neurofibromatosis. A case report. Rev. Med. Chir. Soc. Med. Nat. Iasi, 2007, 111(1), 238-243.
[29]
Røkke, O.; Due, J.; Dale, K. Osteitis fibrosa cystica von Recklinghausen. Tidsskr. Nor. Laegeforen., 1990, 110(8), 960-961.
[30]
Rosenberg, N.L.; Diliberti, J.H.; Andrews, A.M.; Buist, N.R. Myotonic dystrophy and hyperparathyroidism: Association with neurofibromatosis and multiple endocrine adenomatosis type 2A. J. Neurol. Neurosurg. Psychiatry, 1988, 51(12), 1578-1580.
[31]
Spektorova, Z.G.; Baider, A.A. Remote results in Recklinghausen’s disease following excision of a tumor of the parathyroid gland. Khirurgiia, 1950, 6, 61-64.
[32]
Troitskaia, V.D. Treatment of Recklinghausen’s disease by removing parathyroid adenoma. Probl. Endokrinol. Gormonoter., 1964, 10, 59-62.
[33]
Vogelzang, P.J.; Oates, E.; Bankoff, M.S. Parathyroid adenoma associated with neurofibromatosis: correlative scintigraphic and magnetic resonance imaging. Clin. Nucl. Med., 1989, 14(3), 168-170.
[34]
Weinstein, R.S.; Harris, R.L. Hypercalcemic hyperparathyroidism and hypophosphatemic osteomalacia complicating neurofibromatosis. Calcif. Tissue Int., 1990, 46(6), 361-366.
[35]
Yamamoto, Y.; Kodama, K.; Yokoyama, S.; Takeda, M.; Michishita, S. A pleural solitary fibrous tumor, multiple gastrointestinal stromal tumors, moyamoya disease, and hyperparathyroidism in a patient associated with NF1. Case Rep. Surg., 2015, 2015, 375416.
[36]
Zöller, M.E.; Rembeck, B.; Odén, A.; Samuelsson, M.; Angervall, L. Malignant and benign tumors in patients with neurofibromatosis type 1 in a defined Swedish population. Cancer, 1997, 79(11), 2125-2131.
[37]
Vickaryous, M.K.; Hall, B.K. Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest. Biol. Rev. Camb. Philos. Soc., 2006, 81(3), 425-455.
[38]
Cetani, F.; Pardi, E.; Marcocci, C. Update on parathyroid carcinoma. J. Endocrinol. Invest., 2016, 39(6), 595-606.
[39]
Devcic, Z.; Jeffrey, R.B.; Kamaya, A.; Desser, T.S. The elusive parathyroid adenoma: Techniques for detection. Ultrasound Q., 2013, 29(3), 179-187.
[40]
Solorzano, C.C.; Carneiro-Pla, D. Minimizing cost and maximizing success in the preoperative localization strategy for primary hyperparathyroidism. Surg. Clin. North Am., 2014, 94(3), 587-605.
[41]
Triggiani, V.; Resta, F.; Giagulli, V.A.; Iovino, M.; Licchelli, B.; De Pergola, G.; Tafaro, A.; Benigno, M.; Sabbà, C.; Guastamacchia, E. Parathyroid hormone determination in ultrasound-guided fine needle aspirates allows the differentiation between thyroid and parathyroid lesions: Our experience and review of the literature. Endocr. Metab. Immune Disord. Drug Targets, 2013, 13(4), 351-358.
[42]
Ortuzar, R.; Atria, P.; Mena, I. Clinical aspects of 20 cases of fibrous dysplasia of the bones, von Recklinghausen’s neurofibromatosis, osteomalacia, osteoporosis and hyperparathyroidism. Rev. Med. Chil., 1956, 84(8), 417-429.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 3
Year: 2019
Page: [382 - 388]
Pages: 7
DOI: 10.2174/1871530318666180910123316
Price: $58

Article Metrics

PDF: 27
HTML: 3