Impact of the parathyroidectomy on quality of life in multiple endocrine neoplasia type 1.
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ABSTRACT: Background
Potential influences of the parathyroidectomy (PTx) on quality of life (QoL) in multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) are unknown.Method
Short Form 36 Health Survey Questionnaire was prospectively applied in 30 HPT/MEN1 patients submitted to PTx (20, subtotal; 10, total with autograft), before, 6 and 12 months (mo.) after surgery. Parameters analyzed included QoL, age, HPT-related symptoms, general pain, comorbidities, biochemical/hormonal response, PTx type and parathyroid volume.Results
Asymptomatic patients were younger (30 vs 38 years; p=0.04) and presented higher QoL scores (physical component score, PCS, 92.5 vs 61.2 p=0.0051; mental component score, MCS, 82.0 vs 56.0, p=0.04) than symptomatic ones. In both groups, QoL remained stable one year after PTx, independently of number of comorbidities. Preoperative general pain was negatively correlated with PCS (r =-0.60, p=0.0004) and MCS (r=-0.57, p=0.0009). Also, moderate/intense pain was progressively (6/12mo.) more frequent in cases developing hypoparathyroidism. The PTx type and hypoparathyroidism did not affect the QoL at 12mo. although remnant parathyroid tissue volume did have a positive correlation (p=0.0490; r=0.3625) to PCS 12mo. after surgery. Patients with 1-2 comorbidities had as pre-PTx PCS (p=0.0015) as 12mo. post-PTx PCS (p=0.0031) and MCS (p=0.0365) better than patients with 3-4 comorbidities.Conclusion
A variable QoL profile was underscored in HPT/MEN1 reflecting multiple factors associated to this complex disorder as comorbidities, advanced age at PTx and presence of preoperative symptoms or of general pain perception. Our data encourage the early indication of PTx in HPT/MEN1 by providing known metabolic benefits to target-organs and avoiding potential negative impact on QoL.
SUBMITTER: Brescia MDG
PROVIDER: S-EPMC9254320 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended.
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Project description:Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors of the parathyroids, pancreatic islets, and anterior pituitary. The MEN1 gene, on chromosome 11q13, has recently been cloned, and mutations have been identified. We have characterized such MEN1 mutations, assessed the reliability of SSCP analysis for the detection of these mutations, and estimated the age-related penetrance for MEN1. Sixty-three unrelated MEN1 kindreds (195 affected and 396 unaffected members) were investigated for mutations in the 2,790-bp coding region and splice sites, by SSCP and DNA sequence analysis. We identified 47 mutations (12 nonsense mutations, 21 deletions, 7 insertions, 1 donor splice-site mutation, and 6 missense mutations), that were scattered throughout the coding region, together with six polymorphisms that had heterozygosity frequencies of 2%-44%. More than 10% of the mutations arose de novo, and four mutation hot spots accounted for >25% of the mutations. SSCP was found to be a sensitive and specific mutational screening method that detected >85% of the mutations. Two hundred and one MEN1 mutant-gene carriers (155 affected and 46 unaffected) were identified, and these helped to define the age-related penetrance of MEN1 as 7%, 52%, 87%, 98%, 99%, and 100% at 10, 20, 30, 40, 50, and 60 years of age, respectively. These results provide the basis for a molecular-genetic screening approach that will supplement the clinical evaluation and genetic counseling of members of MEN1 families.
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Project description:BackgroundMultiple endocrine neoplasia (MEN) type 1 syndrome is an uncommon inherited disorder characterized by the occurrence of tumors involving two or more endocrine glands. These tumors include pheochromocytoma, adrenal cortical and neuroendocrine tumors including (bronchopulmonary, thymic, gastric), lipomas, angiofibromas, collagenomas, and meningiomas. MEN-4 is very rare and has been characterized by the occurrence of parathyroid and anterior pituitary tumors in association with tumors of the adrenals, kidneys, and reproductive organs.SummaryWe report the case of a 40-year-old male without significant family history of endocrine disease who was found to have primary hyperparathyroidism, a pituitary tumor causing acromegaly, thyroid cancer, renal cell carcinoma, and pancreatic cysts. We posit that this represents a new version of MEN-4. While renal tumors (angiomyolipoma) have been reported as part of the MEN-4 phenotype, to our knowledge, this is the first case reported of the association of MEN-1 and/or MEN-4 phenotype with this unique constellation of tumors, including renal cell carcinoma. Interestingly, this patient tested negative (DNA sequencing/deletion) for MEN-1 (menin), MEN-4 (CDKN1B) and VHL genes.Key messageThus, while this case has clinical characteristics consistent with either MEN-1 or MEN-4, it may represent a unique genetic variant.
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