Association between atypical parathyroid adenoma and neurofibromatosis

Favere, Aline Mesquita Ferreira de; Tsukumo, Daniela Miti Lemos; Matos, Patrícia Francisca de; Santos, Sergio L.M.; Lalli, Cristina Alba

doi:10.1590/2359-3997000000092

Cited by 16 publications

(9 citation statements)

References 23 publications

(26 reference statements)

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“…Mutations of NF1 are linked to neurofibromatosis type 1 (NF1), a tumor syndrome associated with malignant peripheral nerve sheath tumors, central nervous system tumors, and breast cancers [23]. PC has previously been observed in a single patient with NF1 [24], and a few other case reports suggest some association of NF1 and parathyroid adenoma [25][26][27]. This series further links NF1 mutation to PC, which could be verified with further studies.…”

Section: Discussionsupporting

confidence: 70%

Genomic Profiling of Parathyroid Carcinoma Reveals Genomic Alterations Suggesting Benefit from Therapy

Kang

Pettinga²,

Schubert

et al. 2018

The Oncologist

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Background Parathyroid carcinoma (PC) is a rare endocrine malignancy that can cause life‐threatening hypercalcemia. We queried whether comprehensive genomic profiling (CGP) of PC might identify genomic alterations (GAs), which would suggest benefit from rationally matched therapeutics. Methods We performed hybrid‐capture‐based CGP to identify GAs and tumor mutational burden (TMB) in tumors from patients with this malignancy. Results There were 85 total GAs in 16 cases (5.3 GAs per case), and the median TMB was 1.7 mutations per megabase (m/Mb), with three cases having >20 m/Mb (18.7%). The genes most frequently harboring GA were CDC73 (38%), TP53 (38%), and MEN1 (31%). All MEN1‐mutated cases also had loss of heterozygosity at that locus, but in contrast all CDC73‐mutated cases retained heterozygosity. GAs suggesting potential benefit from matched targeted therapy were identified in 11 patients (69%) and most frequently found in PTEN (25%), NF1 (12.5%), KDR (12.5%), PIK3CA (12.5%), and TSC2 (12.5%). A patient whose tumor harbored KDR T668 K and who was treated with cabozantinib experienced a > 50% drop in parathyroid hormone level and radiographic partial response of 5.4 months with duration limited by toxicity. Conclusion CGP identified GAs in PC that suggest benefit from targeted therapy, as supported by an index case of response to a matched tyrosine kinase inhibitor. Moreover, the unexpectedly high frequency of high TMB (>20 m/Mb) suggests a subset of PC may benefit from immune checkpoint inhibitors. Implications for Practice Parathyroid carcinoma (PC) is a rare endocrine malignancy that can cause life‐threatening hypercalcemia. However, its molecular characteristics remain unclear, with few systemic therapeutic options available for this tumor. Hybrid‐capture‐based comprehensive genomic profiling of 16 primary cancers demonstrated presence of potentially actionable genomic alterations, including PTEN, NF1, KDR, PIK3CA, and TSC2, and a subset of hypermutated cancers with more than 20 mutations per megabase, the latter of which could benefit from immune checkpoint inhibitor therapy. A case benefiting from rationally matched targeted therapy for activating KDR mutation is also presented. These findings should be further investigated for their therapeutic potential.

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Section: Discussionsupporting

confidence: 70%

Genomic Profiling of Parathyroid Carcinoma Reveals Genomic Alterations Suggesting Benefit from Therapy

Kang

Pettinga²,

Schubert

et al. 2018

The Oncologist

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“…Given the absence of calcium malabsorption, it could be a primary hyperparathyroidism. Indeed, the association of hyperparathyroidism with parathyroid adenoma and neurofibromatosis is known [8] .…”

Section: Discussionmentioning

confidence: 99%

A Rare Case of Hypophosphataemic Osteomalacia in von Recklinghausen Neurofibromatosis

Yasmine

Boussaid

Ajlani

et al. 2021

European Journal of Case Reports in Internal Medicine

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Background: Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a one of the more common hereditary autosomal disorders. However, osteomalacia in neurofibromatosis type 1 is very rare tumour-induced osteomalacia; fibroblast growth factor-23 is usually implicated. Patients and methods: We report the case of a patient with a history of von Recklinghausen neurofibromatosis who presented with hypophosphataemic osteomalacia. Results: The patient was treated with high-dose calcitriol and oral phosphate with clinical improvement. Conclusion: Even though it is a rare entity, we must consider the diagnosis of hypophosphataemic osteomalacia in patients with neurofibromatosis in order to deliver appropriate treatment.

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“…By contrast, the association between PHPT and NF-1 is less clear. Since 1970s, there have been approximately 20 cases of PHPT in NF-1 reported in the literature ( 5 , 8 , 19 , 20 , 21 , 22 ). The mean age of presentation was around 45 years while osteoporosis was a common feature.…”

Section: Discussionmentioning

confidence: 99%

“…have reported thyroid C-cell hyperplasia and abnormal calcitonin response to pentagastric stimulation in 7 out of 17 patients with NF-1, suggesting a link of NF-1 to thyroid C-cell pathology ( 31 ). It has been suggested that NF-1 in association with PHPT and PPGL may be a variant of MEN-2 ( 20 ). Despite the above observations, more systemic studies are required to establish whether there exists true relationship between NF-1 and MEN-2.…”

Section: Discussionmentioning

confidence: 99%

Concurrent primary hyperparathyroidism and pheochromocytoma in a Chinese lady with neurofibromatosis type 1

Wong

Fok

Tam

2018

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryWe report a case of elderly Chinese lady with neurofibromatosis type-1 presenting with longstanding palpitation, paroxysmal hypertension and osteoporosis. Biochemical testing showed mild hypercalcaemia with non-suppressed parathyroid hormone level suggestive of primary hyperparathyroidism, and mildly elevated urinary fractionated normetanephrine and plasma-free normetanephrine pointing to a catecholamine-secreting pheochromocytoma/paraganglioma. Further scintigraphic investigation revealed evidence of a solitary parathyroid adenoma causing primary hyperparathyroidism and a left pheochromocytoma. Resection of the parathyroid adenoma and pheochromocytoma resulted in normalization of biochemical abnormalities and hypertension. The rare concurrence of primary hyperparathyroidism and pheochromocytoma in neurofibromatosis type-1 is discussed.Learning points:All NF-1 patients who have symptoms suggestive of a pheochromocytoma/paraganglioma (PPGL), even remotely, should undergo biochemical testing.The initial biochemical tests of choice for PPGL in NF-1 are either plasma-free metanephrines or urinary fractionated metanephrines. Any elevations of metanephrines should be carefully evaluated for the presence of PPGLs in NF-1 patients.Primary hyperparathyroidism (PHPT) is described in subjects with NF-1. Due to the lack of epidemiological and functional studies, their association is yet to be substantiated. Meanwhile, PHPT may further exacerbate the metabolic bone defect in these patients and should be treated when present according to published guidelines.Coexistence of PPGL and PHPT can occur in subjects with NF-1, mimicking multiple endocrine neoplasia type 2 (MEN2).

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Association between atypical parathyroid adenoma and neurofibromatosis

Cited by 16 publications

References 23 publications

Genomic Profiling of Parathyroid Carcinoma Reveals Genomic Alterations Suggesting Benefit from Therapy

Genomic Profiling of Parathyroid Carcinoma Reveals Genomic Alterations Suggesting Benefit from Therapy

A Rare Case of Hypophosphataemic Osteomalacia in von Recklinghausen Neurofibromatosis

Concurrent primary hyperparathyroidism and pheochromocytoma in a Chinese lady with neurofibromatosis type 1

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