1/7. PHEX expression in parathyroid gland and parathyroid hormone dysregulation in X-linked hypophosphatemia.X-linked hypophosphatemia (XLH), a renal phosphate (Pi) wasting disorder with defective bone mineralization, is caused by mutations in the PHEX gene (a Pi-regulating gene with homology to endopeptidases on the x chromosome). parathyroid hormone (PTH) status in XLH has been controversial, with the prevailing belief that hyperparathyroidism develops in response to Pi therapy. We report a 5-year-old girl with XLH (patient 1) who had significant hyperparathyroidism at presentation, prior to initiation of therapy. We examined her response to a single oral Pi dose, in combination with calcitriol, and demonstrated a rise in serum concentration of intact PTH, which peaked at 4 h and paralleled the rise in serum Pi concentration. We also present two other patients whose parathyroid glands were analyzed for PHEX mRNA expression following parathyroidectomy. Patient 2 had autonomous hyperparathyroidism associated with chronic renal insufficiency, and patient 3, with XLH, developed autonomous hyperparathyroidism after 8 years of therapy with Pi and calcitriol. Following parathyroidectomy, patient 3 exhibited an increase in both serum Pi concentration and renal Pi reabsorption. The abundance of PHEX mRNA, relative to beta-actin mRNA, in parathyroid glands from patients 2 and 3 was several-fold greater than that in human fetal calvaria, as estimated by ribonuclease protection assay. In summary, we have shown that hyperparathyroidism can be a primary manifestation of XLH and that PHEX is abundantly expressed in the parathyroid gland. Given that PHEX has homology to endopeptidases, we propose that PHEX may have a role in the normal regulation of PTH.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
2/7. Familial isolated parathyroid adenoma in a consanguineous family.The 23-year-old Caucasian male propositus presented with symptomatic hypercalcemia, hypophosphatemia and normocalciuria for 2 months. His 29-year-old brother had undergone an operation for recurrent parathyroid adenoma at age 26 and 28. No other member of the family was affected. His father and mother were second-degree relatives. Laboratory studies showed primary hyperparathyroidism (pHPT), while the remaining endocrine studies and genetic testing for multiple endocrine neoplasia 1 and 2A were normal. technetium-cardiolite scintigraphy and ultrasound scans revealed a parathyroid mass at the left lower neck. Apart from bilateral hearing loss due to gentamicin treatment as a pre-term child, the patient was in of good health. Signs or symptoms of other endocrinopathies were absent. The patient was referred for parathyroidectomy with subsequent autotransplantation of the remaining glands into his sternocleidomastoid muscle. Histological examination revealed an adenoma with oncocytic differentiation, similar to that seen in his brother. The disease may follow a recessive mode of inheritance or may be due to a dominant germ-cell mutation in one of the parents. The presented case may ultimately help in elucidating the molecular genetic basis of this rare form of pHPT.- - - - - - - - - - ranking = 0.14285714285714keywords = gland (Clic here for more details about this article) |
3/7. Asymptomatic hypercalcemia due to an ectopic parathyroid adenoma in an 8-year-old boy.The diagnosis of primary hyperparathyroidism in children is often delayed and is usually based on symptoms of hypercalcemia rather than abnormal laboratory values alone. We report the case of an 8-year-old boy with hypercalcemia, hypophosphatemia and mildly, but inadequately elevated intact parathyroid hormone (iPTH) who presented without any symptoms of hyperparathyroidism. Although imaging studies were misleading and four normal parathyroid glands were found intraoperatively, exploration of the thymus revealed an ectopic parathyroid adenoma. After removal of the ectopic gland, a rapid iPTH immunoassay proved immediate normalization of iPTH. This is the first report of sporadic isolated primary hyperparathyroidism diagnosed in an asymptomatic child on the basis of hypercalcemia and hypophosphatemia.- - - - - - - - - - ranking = 0.28571428571429keywords = gland (Clic here for more details about this article) |
4/7. Somatic mutations of the MEN1 gene and microsatellite instability in a case of tertiary hyperparathyroidism occurring during high phosphate therapy for acquired, hypophosphatemic osteomalacia.Somatic mutations of the MEN type 1 (MEN1) gene were recently shown to be responsible for tumorigenesis in 13-26% of sporadic, nonfamilial primary hyperparathyroidism. However, it is unknown whether these mutations are also involved in tumorigenesis of parathyroid glands occurring during high phosphate therapy for hypophosphatemic rickets or osteomalacia. A male patient with adult-onset, hypophosphatemic osteomalacia had been treated with 1alpha-OHD3 and oral phosphate for 13 yr when tertiary hyperparathyroidism developed. After total resection of four enlarged parathyroid glands and autotransplantation of a hyperplastic gland, the patient has continued to do well for the last 2 yr. sequence analysis of the coding exons of MEN1 gene revealed a 36-bp deletion with a 2-bp insertion (exon 2) in the right upper parathyroid gland accompanied with loss of heterozygosity at 11q13 locus and a heterozygous mutation of 2-bp deletion (AG) in exon 10 in the right lower gland, in which microsatellite instability was also found. No MEN1 gene mutation was detected in the other two hyperplastic parathyroid glands or in the peripheral blood. These findings indicate that MEN1 gene mutations contributed to tumorigenesis of the right upper parathyroid gland in this case of phosphate-induced tertiary hyperparathyroidism. Very recently a bone tumor was found in the right femoral neck, and the tumor (chondroblastoma) was resected.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
5/7. Evaluation of the parathyroid function in six patients with hypophosphatemic osteomalacia, including a case of tertiary hyperparathyroidism developing during combined oral phosphate and vitamin d therapy.AIM: To describe a case of tertiary hyperparathyroidism after long-term phosphate and vitamin d therapy and the retrospective evaluation of parathyroid function in 6 patients with hypophosphatemic osteomalaica. methods: We evaluated the parathyroid function by measuring iPTH before and during treatment and divided the patients into normal and elevated serum iPTH groups. RESULTS: In the normal serum iPTH group, the 4 patients were all males, whereas the 2 patients in the elevated serum iPTH group were females. Clinical characteristics and biochemical results showed no differences between the two groups. One of the women with an elevated iPTH level (224 pg/ml) had a normal serum calcium level and no evidence of increasing parathyroid uptake by (99m)Tc-MIBI scan 52 months after treatment. The other woman also had an elevated iPTH level (483 pg/ml) and a normal serum calcium level 56 months after treatment. However, in this latter case both her iPTH (1,447 pg/ml) and serum calcium (11.3 mg/dl) levels were elevated 113 months after treatment, when a (99m)Tc-MIBI scan showed increased uptake in all four parathyroid glands during early and delayed phases of the scan. parathyroidectomy was performed after the diagnosis of tertiary hyperparathyroidism was made, and the histological findings showed adenomatous hyperplasia. CONCLUSIONS: Our findings indicate that even with vitamin d therapy, long-term phosphate therapy may lead to the development of secondary or tertiary hyperparathyroidism in hypophosphatemic osteomalacia and, therefore, suggest that it is important to carefully monitor the parathyroid function during therapy in those with hypophosphatemic osteomalacia.- - - - - - - - - - ranking = 0.14285714285714keywords = gland (Clic here for more details about this article) |
6/7. kinetics of the circulating levels of bone alkaline phosphatase in a case of hungry bone disease following total parathyroidectomy.We present the case of a 55-year-old patient who underwent total parathyroidectomy for severe hyperparathyroidism unresponsive to medical therapy, 4 years after having started hemodialysis treatment. It was decided to perform total parathyroidectomy because at macroscopic evaluation the parathyroid glands appeared completely compromised. After surgery, the patient developed hungry bone disease, characterized by severe hypocalcemia and hypophosphatemia. After parathyroidectomy, serial measurements were made for the long-term monitoring of the calcemia, phosphatemia and the serum levels of intact parathormone and bone alkaline phosphatase, a marker of bone turnover that mainly expresses bone formation. There was initially a slight decrease in the circulating levels of bone alkaline phosphatase as the calcemia dropped dramatically, then a new increase that anticipated the subsequent calcemia increase and finally, 6 months later, a decrease to very low values. We believe that the calcemia and blood bone alkaline phosphatase could be useful for the laboratory monitoring of the hungry bone state, providing information which may be useful to avoid excessive calcium administration and the dangerous consequences such as soft-tissue calcification.- - - - - - - - - - ranking = 0.14285714285714keywords = gland (Clic here for more details about this article) |
7/7. Secondary hyperparathyroidism as a palpable intrathyroid parathyroid gland in a patient with hypophosphatemic osteomalacia.Secondary hyperparathyroidism is sometimes seen in patients with hypophosphatemic osteomalacia after long-term oral phosphate therapy. parathyroidectomy is sometimes needed for the correction of hypercalcemia in these patients, and is rarely performed in patients without hypercalcemia. A 46-year-old female patient had hypophosphatemic osteomalacia with unknown cause and secondary hyperparathyroidism. A palpable neck mass developed after long-term oral phosphate therapy. An intrathyroid parathyroid gland was confirmed through partial thyroidectomy and parathyroidectomy. Renal phosphate wasting decreased strongly, and serum parathyroid hormone was in the normal range after the operation. A correction of secondary hyperparathyroidism may partially overcome hyperphosphaturia in some patients with hypophosphatemic rickets.- - - - - - - - - - ranking = 0.71428571428571keywords = gland (Clic here for more details about this article) |