Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple endocrine neoplasia type 2 (MEN-2) is an inherited multiglandular disease with age-related penetrance and variable expression. The prognosis of MEN-2 is linked to the carcinological evolution of medullary thyroid cancer (MTC), which depends mainly on the stage of discovery, and to the incidents related to pheochromocytomas. The emphasizes the need for early diagnosis and management of MEN-2. Since 1993, mutations evidenced on the protooncogene RET have allowed subjects at risk to be identified, thus leading to a three-step management of these patients. (1) For all the potentially affected members of a MEN-2 family, screening by molecular genetics of the ret gene enables one to identify the subjects at risk who bear the mutation. When no mutation is observed, a linkage analysis study may be proposed. (2) In the subjects at risk, early screening for the various types of endocrine lesions may then start in childhood and be performed using specific biological markers of MTC, pheochromocytoma and primary hyperparathyroidism, and particularly, basal and pentagastrin-stimulated calcitonin measurement, which is known to be the most sensitive marker for the monitoring of MTC. (3) This step of biological investigations enables the earliest possible treatment of any endocrine lesion detected before it is expressed clinically, thus improving the prognosis of MEN-2. When genetic screening cannot be performed, only annual clinical and biological monitoring remain available in all members of a family affected with MEN-2.
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PMID:Multiple endocrine neoplasia type 2: management of patients and subjects at risk. French Study Group on Calcitonin-Secreting Tumors (GETC). 916 55

The second type of multiple endocrine neoplasia syndromes can be described as rare syndromes, heritable in autosomal dominant manner and linking medullary thyroid carcinoma to different tumors of endocrine organ system and endocrinopathies. This syndrome is divided into multiple endocrine neoplasia syndrome type 2A (MEN 2A), characterized with combination of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism; type 2B (MEN 2B), characterized with combination of medullary thyroid carcinoma, pheochromocytoma, marfanoid habitus and ganglioneuromatosis, and familial medullary thyroid carcinoma syndrome, characterized with the only indication, which is hereditary medullary thyroid carcinoma. Though type 2 multiple endocrine neoplasia syndrome has been known since 1961, yet, the cause of the syndrome, which is germline mutations of c-ret protooncogene, was detected just a decade ago and syndrome pathogenesis with its characterized endocrine neoplasia carcinogenesis machinery were detected. Implementation of progressive genetic researches in clinical practice enabled precise diagnosis of multiple endocrine neoplasia syndrome and its subtypes not only for ill patients but also for healthy syndrome inheritors, e.g. relatives of the sick. Stated genotype link to phenotype helps to prognosticate possible combinations of endocrine neoplasia and endocrinopathies, and to choose purposeful patient observation. Genetic screening of the inheritors of multiple endocrine neoplasia type 2 syndrome enabled purposeful researches and observations of patients with a huge risk of uprising endocrine neoplasia, it also enabled application of effective prophylaxis methods, avoidance or early diagnostic of malignant tumors and life prognosis improvement for patients with malignant tumors while practicing well-timed treatment adaptation. This literature review contains the newest data on multiple endocrine neoplasia syndrome type 2 and its pathogenesis, diagnostics, patient observation, endocrine cancer prophylaxis and methods of treatment, which are characteristic for syndrome and which are being chosen according to biochemical endocrine neoplasia symptoms and genetic diagnosis.
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PMID:[Multiple endocrine neoplasia syndromes. Type 2]. 1586 1

Multiple endocrine neoplasia (MEN) type 2A, or Sipple syndrome, is a rare autosomal dominantly inherited syndrome, which is characterized as combination of medullary thyroid carcinoma, pheochromocytoma, primary hyperparathyroidism, sometimes with rarer inherited disorders like Hirschsprung disease and cutaneous lichen amyloidosis. Syndrome is caused by germinative mutations in c-ret protooncogene, which are typical for different MEN 2 syndromes. We report a clinical case of MEN 2A. A 43-year-old female patient was operated on for pheochromocytoma 7 years after diagnosis and treatment of spread medullary thyroid carcinoma. This is the most common combination of MEN 2A tumors. Diagnosis was based upon clinical data, tumors combinations and analysis of inherited endocrine pathology in first-line relatives. This syndrome has already been diagnosed in Lithuania, but in the last decade after determining the genetic basis of MEN 2 and applying modern genetic examinations in clinical praxis, the strategy of diagnostics and prophylaxis of this syndrome has changed and survival prognosis for patients with this syndrome has improved. Conception of pathogenesis and clinical features of MEN 2A syndrome, genetic selection of inheritors of this syndrome is one more step in early cancer diagnosis, which allows to use cancer prevention measures in time, to apply effective treatment and improve patients' prognosis. Reporting this clinical case of MEN 2A we aimed to pay attention of general practitioners to this rare, but in Lithuania diagnosed too, syndrome and its clinic, diagnostic, and treatment features.
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PMID:[Multiple endocrine neoplasia type 2A]. 1660 64

Among adrenal incidentalomas, pheochromocytomas are rare. Malignant pheochromocytoma is even less common, and it typically presents with classic hormonal symptoms, such as palpitations, labile blood pressures, and headaches. Bony metastasis usually occurs late in disease, but we report an unusual case of incapacitating bony pain as the initial presentation of malignant pheochromocytoma. Our patient is a 70-year-old woman with neurofibromatosis type 1 and a history of primary hyperparathyroidism, who tested negative for the ret mutation. She came to medical attention with chest pain and palpitations and was incidentally found to have an adrenal mass. Serum and urine testing was consistent with pheochromocytoma. Her blood pressure was easily controlled as she awaited elective adrenalectomy; however, she quickly developed severe, diffuse bony pain. She represented with hypercalcemia, spontaneous fractures, and incapacitating pain that required such high doses of pain medications that she had to be intubated. Further imaging and bone marrow biopsy confirmed metastatic neuroendocrine tumor. She received one round of chemotherapy with no change in her bony pain, which was her primary complaint. Unfortunately, her treatment options were limited by the heavy sedation required for comfort, and in the end, it was her bony pain rather than hormonal symptoms that made her disease untreatable.
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PMID:Malignant pheochromocytoma presenting as incapacitating bony pain. 2267 44

One of the components of trethe classical form of MEN2 syndromes is primary hyperparathyroidism (PHP). It occurs in 20-30% of the typical MEN2A syndrome. The prevalence is more rare in gene carriers as these frequently have familial MTC only. PHP is diagnosed more frequently in association with the exon 11, codon 634 mutation of the ret gene-so there is phenotype/genotype correlation. The clinical manifestations of PHP in MEN2 are usually mild and the peak age of diagnosis after the 3rd decade. The treatment is surgical excision of the enlarged gland(s). Although there can be multigland disease in the parathyroids, it is frequently the case that both hyperplasia and adenoma may coexist, or even a single adenoma may be found during the investigation and finally during the operation. Patients with MEN2 syndromes should be screened for PHP with serum calcium measurements. The intensity of the screening should be higher in those carrying the ret mutations most frequently associated with this manifestation.
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PMID:Primary Hyperparathyroidism in MEN2 Syndromes. 2649 89