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

Abstract

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).

A pheochromocytoma in a patient with neurofibromatosis type 1: A case report

“…The prevalence of Pheo in patients with NF1 is more important in patients with hypertension in general population, 1.0%-5.7% versus 0.2-0.6% and even higher rates are in those with NF1 and hypertension at 20%-50% [1,[9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Two prospective studies showed higher prevalence of Pheo in which patients with NF1 were screened for Pheo (7.7% [3] and 14.6% [22]).…”

“…NF1 patients should undergo screening for this affections especially when associated with catecholamine-symptoms or hypertension [25]. The mean age at the moment of diagnosis was reported between the age of fourty and fifty in some studies [19,20].…”

“…Currently, studies did not establish a genetic-clinical association between NF1 and Pheo due to the variability of the expression of this disease, the large size of the gene, the lack of hot spots and the high rate of de novo mutations [19,25]. But some studies reported that loss of heterozygosity was observed in Pheo associated with NF1 and it seems to be that Pheo is considered as a true component of NF1 [26].…”

Neurofibromatosis Type 1 With Cherubism-like Phenotype, Multiple Osteolytic Bone Lesions of Lower Extremities, and Alagille-syndrome: Case Report With Literature Survey

“…Later, patients were diagnosed with metaphyseal bone lesions (defects/NOF) who also had developed neurofibromas (104) and fulfilled the current diagnostic criteria of NF1 (40,106). The clinical diagnosis of the skeletal findings as lesions associated with NF1 requires the exclusion of endocrine disorders (52,46,47,112). Meanwhile, the simultaneous occurrence of CGCG of the jaw and NOF of the long bones in cases with NF1 has been described in detail [40, 53 (in the latter case, jaw lesion was initially diagnosed as GCT)].…”

Vandetanib in a Child Affected by Neurofibromatosis Type 1 and Medullary Thyroid Carcinoma with Both <i>NF1</i> and Homozygous <i>RET</i> Proto-oncogen Germ-line Mutations

“…An increased frequency of various endocrine pathologies, such as central precocious puberty, short stature, diencephalic syndrome, growth hormone deficiency or growth hormone hypersecretion has been reported in children. In addition, pheochromocytoma, parathyroid carcinoma, parathyroid adenoma, somatostatin producing neuroendocrine tumor, duodenal carcinoid tumor producing somatostatin, thyroid papillary carcinoma with pheochromocytoma have been described in patients with NF1 ( 1 , 2 , 3 ).…”