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)

Acromegaly is uncommon in kindreds with multiple endocrine neoplasia type 1 (MEN1), whereas primary hyperparathyroidism (PHP) has the highest penetrance of any endocrinopathy. We report an unusual MEN1 kindred with frequent expression of pituitary tumors and a low penetrance of PHP. Four members were found to have disease: PHP in generation I, acromegaly (2 cases) in generation II, and hyperprolactinemia associated with a pituitary tumor in generation III. There was no evidence for PHP in 1 patient with acromegaly (age 60 yr), the patient with hyperprolactinemia and the pituitary tumor (age 22 yr), and 1 asymptomatic obligate carrier (age 50 yr). Screening of 26 members revealed the possible diagnosis of PHP in 1 family member in generation II and possible early acromegaly in 2 members of generation III with elevated serum concentrations of insulin-like growth factor I and insulin-like growth factor-binding protein-3 but normal patterns of pulsatile GH release. Although the predisposing genetic defect in typical MEN1 families has previously been mapped to chromosome location 11q13 without evidence of heterogeneity among the 87 families analyzed, linkage of disease in this family to the MEN1 region is unlikely based on haplotype analysis. Localization of the gene(s) responsible for disease in such atypical families may aid in the understanding of the pathogenesis of MEN1. In addition, further study of the earliest changes in patterns of pulsatile GH release in familial acromegaly may allow more insight into the pathogenesis and natural history of this disease.
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PMID:A kindred with a variant of multiple endocrine neoplasia type 1 demonstrating frequent expression of pituitary tumors but not linked to the multiple endocrine neoplasia type 1 locus at chromosome region 11q13. 902 41

The continuous treatment with parathyroid hormone (PTH) or endogenous PTH excess by primary hyperparathyroidism cause enhanced bone resorption and subsequent decreased bone volume. However, the intermittent treatment with PTH is expected as a drug for osteoporosis for its stimulation of bone formation and marked increase in bone volume. The mechanism of different PTH actions due to the administration method still remains unclear. Several reports suggested the hypothesis about the role of insulin-like growth factor-1, anti-apoptotic effects through Runx2 or Smad3 and the differences of its effects on bone resorption. The investigation about the mechanism of bone formation by PTH intermittent treatment would lead to the development of bone-forming reagent in the future.
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PMID:[Parathyroid and bone. Effects of parathyroid hormone on bone resorption and formation: differences between intermittent and continuous treatment]. 1805 58

We report a case of a female, born in 1952, diagnosed with a rare Multiple Endocrine Neoplasia type 1 (MEN1) gene variant of uncertain clinical significance (p.Val167Ala) presenting with acromegaly, late-onset primary hyperparathyroidism (PHP) and bilateral adrenal tumors. The diagnosis of acromegaly due to pituitary macroadenoma was confirmed at the age of 45. After a non-radical transsphenoidal resection of the pituitary tumor, with histopathological confirmation of adenoma chromophobe, treatment with long-acting somatostatin analogue was introduced, resulting in successfully normalized both insulin-like growth factor and growth hormone values. Mild hypercalcemia was discovered for the first time during endocrinological follow-up at the age of 56, with elevated parathyroid hormone level and increased urine excretion of calcium. 99mTc-MIBI single-photon emission computed tomography/computed tomography showed no typical focal accumulation of the tracer, only an increased uptake in the topography of the upper right parathyroid. The radiological image of the hypothalamic-pituitary area remained stable since medical treatment implementation: pituitary magnetic resonance imaging showed the remnants of the pituitary gland, less than 1 mm in diameter, at the bottom of the sella turcica and two hypointense masses enhancing heterogeneously after contrast administration: 11x8x13 mm in the right lateral part of the turkish saddle and a similar 7x4x5 mm lesion on the left, in direct proximity to cavernous sinuses. Low density 25x16x21 mm tumor in the right adrenal gland and a similar 13 mm focal lesion in the left adrenal were confirmed in abdominal computed tomography. Endocrinological evaluation detected no abnormal hormonal function of the adrenal tumors. Sanger sequencing confirmed the MEN1 variant p.Val167Ala - a missense variant registered in NCBI dbSNP under the accession number rs748648909. In NCBI ClinVar, it was summarized to be of uncertain clinical significance (RCV000632131.2). So far, this variant has not been described in HGMD and UMD-MEN1 databases. Multiple neuroendocrine neoplasia type 1 is a rare genetic disorder with an autosomal dominant inheritance. 1336 MEN1 gene sequence abnormalities were described in only 10 years following the identification of the gene. The phenotype-genotype correlation among MEN1 patients in terms of tumor localization, age of onset and clinical aggressiveness has not been established yet. Further follow-up of the patient and cascade screening of her family members should be carried out to determine the clinical significance of the variant p.Val167Ala.
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PMID:Acromegaly and late-onset primary hyperparathyroidism in a female with a rare MEN1 gene variant of yet undetermined clinical significance (p.Val167Ala). 3312 95