Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relatives of 25 index patients with primary parathyroid hyperplasia were tested for hypercalcemia. At least 13 of these patients had one or more first degree relatives with hypercalcemia. Two familial syndromes each with autosomal dominant transmission were recognized. Two index patients were part of large kindreds categorized as having familial hypocalciuric hypercalcemia (FHH). Manifestations of multiple endocrine neoplasia type I were present in the kindreds of at least four other index patients (FMEN I). In seven other kindreds there were too few affected members to allow definitive classification. Differences between manifestations of FHH and FMEN I were described. Among offspring of affected persons in kindreds with FHH, as distinct from FMEN I, the prevalence of hypercalcemia approached the theoretic maximum of 50 per cent during the first two decades. In FHH, nephrolithiasis and peptic disease were unusual; moderate hypercalcemia occurred without hypercalciuria; and subtotal parathyroidectomy did not abolish hypercalcemia. Concentrations of peptide hormones other than parathyroid hormone (PTH) were normal in those with FHH; in FMEN I high concentrations of glucagon in plasma were found in five of six patients tested, and high concentrations of gastrin were found in three of 12 patients. Hypergastrinemia generally accompanied obvious peptic disease. Distinction of the two conditions is important since patients with FHH may not benefit from subtotal parathyroidectomy, but they generally have a better clinical prognosis than do patients with FMEN I.
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PMID:Family studies in patients with primary parathyroid hyperplasia. 87 Nov 27

AN UPCOMING PUBLIC HEALTH PROBLEM: There has been a considerable focus on osteoporosis in men recently. Bone mass is high in men who have larger bones than women. The frequency of fractures is also higher due to post-trauma lesions. Femoral neck fractures have also increased over the last few years although the F/M ratio remains about 2.8. Overall, there is a trend towards an increased incidence of masculine osteoporosis (and vertebral fractures) due to population aging. FAVORING FACTORS IN MEN: The most important factors are hypoandrogenism, hypoestrogenism (pre or post-puberty), the alcohol-smoking association, malnutrition, lack of sun exposure and chronic liver disease. Other causes of osteoporosis (hyperthyroidism, Cushing's disease, hemochromatosis, gastrectomy, inflammatory rheumatic disease, tubulopathy, hypercalciuria and iatrogenic causes) should also be taken into consideration. PRETHERAPY WORK-UP: All the different possible etiologies should be investigated. Therapeutic protocols should provide hormone replacement when required, withdrawal of causal drugs, better nutrition and reduced alcohol and tobacco use.
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PMID:[Male osteoporosis]. 981 8

Development of sporadic parathyroid tumors is accompanied by loss of heterozygosity (LOH) on several chromosomes like 1p, 1q, 6q, 11q, and 15q. Here, we investigate a unique variant of familial hypercalcemia, unrelated to multiple endocrine neoplasia and hyperparathyroidism-jaw tumor syndromes, with hypercalcemia due to a point mutation in the intracellular part of the calcium receptor (CaR) gene. The hypercalcemia and hypercalciuria of the family is accompanied by age-related growth of the parathyroid glands and transition from diffuse to nodular parathyroid hyperplasia. Genome-wide screening for allelic loss was performed on nine enlarged parathyroid glands (weighing 40-680 mg) from eight parathyroidectomized members of the family (aged 22-66 yr). Using 139 fluorescent- or (32)P-labeled microsatellite markers, informative results were obtained on all examined chromosome arms and 1p, 1q, 6q, 11q, and 15q were investigated more closely. All parathyroid glands displayed allelic loss on at least one chromosomal arm (range 1-7). Most of the common loci for allelic loss corresponded to findings in sporadic parathyroid tumors, but the unique variant of familial hypercalcemia also exhibited frequent LOH on 12q (67%) and 7q (44%). LOH could not be detected at 3q, where the CaR gene is located, and additional somatic mutations in exons 2-7 of the CaR gene was not found by sequencing. The point mutation resulting in alteration of the intracellular portion of CaR seems to cause sensitivity to secondary genetic hits, with increased frequency of allelic loss (P < 0.01, r(2) = 0.66) and weight of parathyroid tumors with age in this family.
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PMID:Loss of heterozygosity in parathyroid glands of familial hypercalcemia with hypercalciuria and point mutation in calcium receptor. 1216 40

Primary hyperparathyroidism (PHPT) generally affects older adults, yet it also occurs in a small number of children, adolescents, and young adults. The early presentation of PHPT in children and adolescents suggests that these parathyroid tumors may differ in pathobiology from more typical tumors that occur in older adults. We performed a retrospective analysis of cases of PHPT treated surgically at the Johns Hopkins Children's Center between 1984 and 2001. Patients were ascertained by review of surgical pathology records, which confirmed the diagnosis of PHPT, and clinical and biochemical characteristics were extracted from medical records. We retrieved data on 16 of 17 patients; these patients (9 male, 7 female) were aged 10.5-20 years (16.3 +/- 2.9 years, median 16.8 years) at the time of diagnosis. Five patients had known metabolic risk factors for development of hyperparathyroidism, whereas 11 patients had spontaneous PHPT. The preoperative serum calcium level was markedly elevated (2.98 +/- 0.25 mM) in all 13 patients with normal renal function. Nearly all (77%) of these patients were found to have at least one symptom or sign of PHPT, most commonly hypercalciuria (83%) or nephrolithiasis (54%). Of these patients, 11 (85%) had single adenomas (mean weight, 597 mg; median, 600 mg; range, 170-1550 mg) while 2 had multiple gland disease, including 1 patient with multiple endocrine neoplasia type 2 (MEN2). In all cases, surgery was curative. These data suggest that PHPT in children is a more severe disease than in older adults, which may reflect a bias of ascertainment or a difference in fundamental parathyroid pathobiology.
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PMID:Primary hyperparathyroidism in children and adolescents: the Johns Hopkins Children's Center experience 1984-2001. 1241 77

We report the case of an 11-year-old child with delayed development who developed signs of exercise-induced pain in the lower limb muscles after an acute attack of appendicitis. He had difficulty standing up from the sitting position and ascending and descending stairs. The physical examination revealed increased reflex activity in the lower limbs. Initially, blood tests, MRI and EMG were normal. Serum phosphorus and calcium were not assayed. Eight months later, the boy's condition worsened (myopathy gait, hyperlordosis) leading to the possible diagnosis of muscle disease. After muscle biopsy, blood tests revealed hypercalcemia at 3.5 mmol/l (normal 2.2-2.6), hypercalciuria, and hypophosporemia. The diagnosis of primary hyperparathyroidism was confirmed by the abnormal level of parathormone initially (19 ng/ml) and later (156 ng/ml) with hypercalcemia. Medical treatment failed and surgery was performed to remove three and a half parathyroid glands. After removal, blood tests returned to normal in six days and the physical examination in three years. The diagnosis of principal cell hyperplasia was retained at the pathology examination. We found no evidence of hypercalcemia or other endocrinopathy such as multiple endocrine neoplasia (MEN 1 or 2a). Study of the menine gene did not reveal any mutation. Muscle dysfunction suggest possible abnormal phosphocalcium regulation. A normal parathormone level with hypercalcemia reveals inappropriate synthesis and secretion.
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PMID:[Primary hyperparathyroidism revealed by pseudomyopathia]. 1595 13

Some neoplastic polyendocrine syndromes may affect the kidney. These include multiple endocrine neoplasia type 1 and 2 (MEN 1, MEN 2) as well as mixed syndromes characterized by endocrine and non-endocrine diseases. Kidney involvement may be related to secondary systemic hypertension or diabetes mellitus, direct hormonal effects, and benign or malignant kidney tumors or kidney malformations (very rare). Neoplastic polyendocrine syndromes are rare and it is important that the endocrinologist knows the possible renal complications or associated diseases for correct screening, and that the nephrologist is aware of the need for endocrinological assessment in young hypertensive patients who are resistant to therapy, hypertensive patients with adrenal lesions, and patients with hypercalciuria or renal calculi, especially at a young age.
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PMID:[Neoplastic polyendocrine syndromes and the kidney]. 2092 4

A 24-year-old female patient with parathyroid carcinoma, the rarest endocrine malignancy, had two pregnancies. In the first pregnancy, she had severe nausea and fatigue. Hypercalcemia and hyperparathyroidism were diagnosed in the postpartum period. Hyperemesis gravidarum masked a diagnosis of hypercalcemia. Neck ultrasound and Tc-99m sestamibi found an enlarged lower right parathyroid gland. The gland was surgically removed, and an initial pathology report described atypical adenoma. Shortly afterward, she became pregnant again. During the second pregnancy, her calcium level was frequently controlled but was always in the normal range. Normocalcemia is explained by the specific physiology of pregnancy accompanied by hemodilution, hypoalbuminemia and maternal hypercalciuria (mediated by increased glomerular filtration). During lactation, calcium levels rose, and a new neck ultrasound showed a solitary mass in the area of prior surgery and an enlarged pretracheal lymph node. Fine needle aspiration of the solitary mass and node showed parathyroid carcinoma cells. The tumor mass was resected en bloc with the contiguous tissues and surrounding lymph nodes (pathology report; parathyroid carcinoma with metastases). Over the next five years, four consecutive surgeries were performed to remove malignant parathyroid tissue, lymph nodes and local metastases. Following the surgical procedures, no hypocalcemia was observed. More serious hypercalcemia recurred; the calcium level was difficult to control with a combination of pamidronate, cinacalcet and loop diuretic. No elements of multiple endocrine neoplasia were present.
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PMID:Parathyroid carcinoma in pregnancy. 2486 16