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)

Endocrine tumors of thyroid, adrenal and parathyroid glands may be due to germline and inheritable mutations in 5-30% of patients. Medullary Thyroid Carcinoma, Pheochromocytoma, Paraganglioma, and Familial Primary Hyperparathyroidism are the most frequent entity. Hereditary endocrine tumors usually have a suggestive familial history; they occur earlier than sporadic variants, are multifocal, and have increased recurrence rates. They may be present as isolated variant or associated to other neoplasms in a syndromic setting. Genetic diagnosis should be preferably available before surgery because specific and targeted operative management are needed to achieve the best chance of cure. This review was aimed to discuss the surgical approaches for some of the most frequent hereditary endocrine tumors of thyroid, adrenal and parathyroid glands, focusing on medullary thyroid carcinoma, Pheochromocytoma, Paraganglioma and hereditary primary hyperparathyroidism (pHPT). Hereditary Medullary Thyroid Carcinoma is caused by RET mutations, and may be associated to Pheochromocytomas in MEN 2 setting. Total thyroidectomy and at least central neck nodal dissection is required. The availability of genetic screening allows prophylactic or early surgery in asymptomatic patients, with subsequent definitive cure. Hereditary Pheochromocytomas may be present in several syndromes (MEN 2, VHL, NF1, Paraganglioma/Pheochromocytoma syndrome); it may involve both adrenals; in these cases, a cortical sparing adrenalectomy should be performed to avoid permanent hypocorticosurrenalism. Hereditary Primary Hyperparathyroidism may frequently occur associated to MEN 1, MEN 2A, MEN 4, Hyperparathyroidism-Jaw Tumor Syndrome; it may involve all the parathyroid glands, requiring subtotal parathyroidectomy or total parathyroidectomy plus autotransplantation. In some cases, a selective parathyroidectomy might be performed.
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PMID:Surgical approaches in hereditary endocrine tumors. 2845 35

Changes in sensitivity to insulin occur in the course of a number of endocrine disorders. Most of the hormones through their antagonistic action to insulin lead to increased hepatic glucose output and its decreased utilisation in peripheral tissues. Carbohydrate disorders observed in endocrine diseases result from the phenomenon of insulin resistance, and in some cases also a reduction in insulin secretion is present. Abnormalities of glucose metabolism are observed in acromegaly, but also in growth hormone deficiency, hypercortisolism in the course of Cushing's syndrome, hyper- or hypothyroidism, primary hyperparathyroidism, aldosteronism, pheochromocytoma, congenital hypertrophy of the adrenal glands, polycystic ovaries syndrome, hypogonadism, or other hormonally active neuroendocrine tumours. They are of a secondary nature in relation to impaired hormonal balance. Hyperglycaemia is therefore often reversible, and the most effective method of treatment of impaired insulin sensitivity is successful therapy of specific endocrinopathies. Insulin sensitisers, also with a good effect, are used. Most experiences to date can be attributed to metformin therapy. Attempts have been made at treatment with other agents that are also effective in reducing insulin resistance as incretins or glitazones. In the presented paper, the authors reviewed endocrine diseases in which there is a clinically significant change in insulin sensitivity. Moreover, methods of therapy of concomitant disturbed glucose metabolism were presented.
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PMID:Insulin resistance in endocrine disorders - treatment options. 2866 Sep 91

Genetic association studies hinge on definite clinical case definitions of the disease of interest. This is why more penetrant mutations were overrepresented in early multiple endocrine neoplasia type 2 (MEN2) studies, whereas less penetrant mutations went underrepresented. Enrichment of genetic association studies with advanced disease may produce a flawed understanding of disease evolution, precipitating far-reaching surgical strategies like bilateral total adrenalectomy and 4-gland parathyroidectomy in MEN2. The insight into the natural course of the disease gleaned over the past 25 years caused a paradigm shift in MEN2: from the removal of target organs at the expense of greater operative morbidity to close biochemical surveillance and targeted resection of adrenal tumors and hyperplastic parathyroid glands. The lead time provided by early identification of asymptomatic MEN2 carriers under biochemical surveillance delimits a 'window of opportunity', within which (i) pre-emptive total thyroidectomy alone is adequate, circumventing morbidity attendant to central node dissection; (ii) subtotal 'tissue-sparing' adrenalectomy is sufficient, trading the risk of steroid dependency for the risk of a second pheochromocytoma in the adrenal remnant and (iii) parathyroidectomy is limited to enlarged glands, trading the risk of postoperative hypoparathyroidism for the risk of leaving behind hyperactive parathyroid glands. Future research should delineate further the mutation-specific, age-dependent penetrance of pheochromocytoma and primary hyperparathyroidism to refine the risk-oriented approach to MEN2. The sweeping changes in the management of MEN2 since the new millenium hold the hope that death and major morbidity from this uncommon disease can be eliminated in our lifetime.
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PMID:Advances in risk-oriented surgery for multiple endocrine neoplasia type 2. 2888 84

Six syndromes of familial hyperparathyroidism are compared: 1) Familial hypocalciuric hypercalcemia (FHH) expresses primary hyperparathyroidism (PHPT) beginning at birth with lifelong hypercalcemia. There is nonsuppressed PTH secretion from outwardly normal parathyroid glands. It reflects germline heterozygous mutation in CASR, GNA11, or AP2S1. 2) Neonatal severe primary hyperparathyroidism is severest of the six syndromes. It requires urgent total parathyroidectomy in infancy. It usually reflects biallelic inactivation of the CASR. 3) Multiple endocrine neoplasia type 1 (MEN1) is most frequently expressed as PHPT with asymmetric enlargement of 3-4 parathyroids. Benign or malignant tumors may occur among 30 other tissues. It is predisposed by germline inactivation of MEN1 or rarely by inactivation of a cyclin dependent kinase inhibitor, and then termed MEN4. 4) Multiple endocrine neoplasia type 2A from RET activating mutation rarely presents as familial hyperparathyroidism, because medullary thyroid cancer and pheochromocytoma are more prominent. 5) Hyperparathyroidism-jaw tumor syndrome (HPT-JT) has frequent PHPT and benign jaw tumors. Twenty percent develop parathyroid cancer. It is predisposed by inactivating mutation in CDC73. 6) Familial isolated hyperparathyroidism causes multiple parathyroid tumors. It can be an incomplete expression of FHH, MEN1, HPT-JT or even of relatives without a shared driver mutation. However, in 20% of families it reflects GCM2 activating mutation. Five of the PHPT syndromes reflect overgrowth of parathyroid tissue; in contrast, familial hypocalciuric hypercalcemia reflects dysregulation of PTH secretion with little or no parathyroid overgrowth. These differences underlie major differences in clinical expression.
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PMID:Familial Hyperparathyroidism - Disorders of Growth and Secretion in Hormone-Secretory Tissue. 2987 37

Pheochromocytomas are neuroendocrine tumors that can arise sporadically or be inherited as a familial disease, and they may occur in isolation or as part of a multitumor syndrome. Familial disease typically presents in younger patients with a higher risk of multifocality. Recently, the tumor suppressor MYC-associated factor X (MAX) gene has been implicated as a cause of familial isolated pheochromocytoma and paraganglioma. We describe a patient with a pituitary prolactinoma and bilateral pheochromocytomas who tested positive for a germline MAX mutation. Interestingly, the patient also had mild primary hyperparathyroidism that resolved upon resection of the pheochromocytomas despite the absence of parathyroid hormone staining in the tumors. To our knowledge, this case is the first report of prolactinoma in a patient with a MAX mutation, which suggests the possibility of germline MAX mutations also contributing to the development of prolactinomas.
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PMID:Case Report of a Prolactinoma in a Patient With a Novel MAX Mutation and Bilateral Pheochromocytomas. 2926 63

A 12-year old dog with a 9-year history of primary adrenal insufficiency was referred to the service for hyporexia, muscle weakness, polyuria and polydipsia. Ultrasound examination showed an unresectable mass in the left adrenal gland, with local vascular invasion, which prompted the euthanasia of the animal. Additionally, necropsy revealed a nodular lesion in the right adrenal gland and enlargement of one of the four parathyroid glands. Parathyroid hormone levels were elevated, but ionized and total calcium levels were normal. Histopathology supported the diagnosis of parathyroid chief cell adenoma and bilateral pheochromocytoma. Immunohistochemical staining was positive for synaptophysin, and negative for Melan-A and calretinin, which confirmed the diagnosis of pheochromocytoma. This case highlights an unusual presentation of multiple endocrine neoplasias within the context of primary adrenal insufficiency and normocalcemic primary hyperparathyroidism.
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PMID:Addison disease and normocalcemic primary hyperparathyroidism in a dog with multiple endocrine neoplasia. 2929 92

We 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.
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PMID:Concurrent primary hyperparathyroidism and pheochromocytoma in a Chinese lady with neurofibromatosis type 1. 2962 9

Multiple endocrine neoplasia type 1 is a rare genetic syndrome, characterized by the co-occurrence, in the same individual or in related individuals of the same family, of hyperparathyroidism, duodenopancraetic neuroendocrine tumors, pituitary adenomas, adrenocortical tumors, and neuroendocrine tumors (carcinoids) in the thymus, the bronchi, or the stomach. Multiple endocrine neoplastic type 2 is a rare genetic syndrome, characterized by the familial occurrence of medullary thyroid carcinoma either isolated or associated with pheochromocytoma, primary hyperparathyroidism, or typical features (Marfanoid habitus, mucosal neuromas). Subjects with clinical MEN1 and those who carry a mutation in the MEN1 gene should be offered biochemical and imaging screening in order to detect tumors and evaluate their progression over time. Children with mutation in the RET gene should have prophylactic total thyroidectomy according to the category of aggressiveness of the detected mutation whereas those with clinical MEN2 should be operated on upon diagnosis. In MEN1 patients, special attention should be paid to evaluate the progression duodenopancraetic neuroendocrine tumors because of their malignant potential. Also, thymic neuroendocrine tumors should be detected as soon as possible because they represent the most lethal tumor. In MEN2, calcitonin and carcinoembryonic antigen (CEA) serve as excellent tumor markers for medullary thyroid carcinoma. Their preoperative levels are correlated with tumor size and predict postoperative cure. Moreover, calcitonin or CEA doubling time has important prognostic value. In both MEN syndromes, multidisciplinary approaches are very important in the care of affected patients. Moreover, those patients should be comprehensively informed and enabled to participate in the decision-making procedure. In addition to multidisciplinary approaches, every effort should be made to follow the recommendations and guidelines issued by national (the French Group of Endocrine Tumors) and international groups.
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PMID:Update on multiple endocrine neoplasia Type 1 and 2. 2990 63

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant hereditary cancer syndrome caused by missense gain-of-function mutations in the RET proto-oncogene on chromosome 10. Specific RET mutations can predispose toward a particular phenotype and clinical course, with strong genotype-phenotype correlations. MEN2 is highly penetrant in medullary thyroid carcinoma (MTC), and it can be associated with bilateral pheochromocytoma and primary hyperparathyroidism. Two different clinical variants of MEN2 are known: MEN2A, which includes the familial subtype, and MEN2B. Treatment includes early thyroidectomy. Recommendations on the timing and extent of surgery are based on the RET mutation risk categories (moderate-, high-, or highest-risk) regarding the age of MTC onset. Early identification of patients with hereditary MTC has improved treatment outcomes. Previously, MTC was diagnosed based on clinical tumors; in contrast, with genetic screening, MTC can be diagnosed at preclinical disease states. This approach has resulted in a high cure rate and a much better prognosis for MTC. However, classification into one of the three RET mutation risk groups for predicting aggressiveness and prognosis has had limited impact. Increasing evidence has shown that patients with RET mutations in different risk classifications exhibit a broad spectrum of MTC aggressiveness during follow-up, with no relevant difference in survival. The specific germline activating mutation of the RET proto-oncogene appears to be the first determinant of the age of MTC onset, but, presumably, different regulatory events determine long-term tumor behavior.
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PMID:Update on Multiple Endocrine Neoplasia Type 2: Focus on Medullary Thyroid Carcinoma. 3008 48

Individuals with a familial predisposition to the development of parathyroid tumors constitute a small minority of all patients with primary hyperparathyroidism (PHPT). These familial syndromes exhibit Mendelian inheritance patterns and the main causative genes in most families have been identified. They include multiple endocrine neoplasia (MEN; types 1, 2A, and 4), hyperparathyroidism-jaw tumor (HPT-JT) syndrome, familial isolated hyperparathyroidism, familial hypocalciuric hypercalcemia (FHH), and neonatal severe PHPT. Each MEN type is associated with the various combinations of specific tumors. MEN1 is characterized by the occurrence of parathyroid, enteropancreatic, and pituitary tumors; MEN2A is characterized by medullary thyroid carcinoma and pheochromocytoma, and MEN4 is characterized by a pathological spectrum similar to that of MEN1 in association with tumors of the adrenal, kidney, and reproductive organs. HPT-JT is characterized by PHPT, ossifying fibromas of maxillary bones, kidney disease, and uterine neoplasias. The prompt diagnosis of these diseases is of great importance for planning appropriate surveillance of the mutant carriers and correct surgical management. The search for mutation is also useful for the identification of the family members who do not carry the mutation and can avoid unnecessary biochemical and instrumental evaluations. Surgery remains the treatment of choice in all familial forms except FHH.
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PMID:Familial and Hereditary Forms of Primary Hyperparathyroidism. 3064 19


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