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Biomedical subjects

Joseph L Shaker

Publications and source records attributed to Joseph L Shaker.

6 recordsLinked to original sources
PubMed2006

Tumoral calcinosis presenting with eyelid calcifications due to novel missense mutations in the glycosyl transferase domain of the GALNT3 gene.

CONTEXT: Familial tumoral calcinosis (TC) is a rare autosomal recessive disorder characterized by metastatic calcifications, often periarticular. Biochemical findings include hyperphosphatemia, high 1,25-dihydroxyvitamin D levels, and elevated tubular maximum for phosphate reabsorption per deciliter of glomerular filtrate (TmP/GFR). TC is caused by biallelic mutations of the genes encoding either fibroblast growth factor 23 (FGF23) or uridine diphosphate-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc transferase 3 or GALNT3). OBJECTIVE: The objective was to identify mutations in FGF23 or GALNT3 responsible for a mild TC phenotype by DNA sequencing and to determine serum FGF23 levels by ELISA. PATIENTS OR OTHER PARTICIPANTS: The subject was a 25-yr-old Caucasian woman with eyelid calcifications and biochemical features of TC. RESULTS: Eyelid biopsy revealed superficial dermis calcifications. There was no history of metastatic calcifications, mineral homeostasis abnormalities, or renal dysfunction. Biochemistry revealed normal levels of calcium, creatinine, PTH, and 25-hydroxyvitamin D, with elevated phosphorous, TmP/GFR, and high normal 1,25-dihydroxyvitamin D levels. Intact FGF23 was undetectable (< 3 pg/ml), whereas C-terminal FGF23 was elevated (698.2 RU/ml). Mutation detection revealed compound heterozygosity for two novel mutations in the glycosyl transferase domain of the GALNT3 gene. CONCLUSION: Previously reported GALNT3 mutations in TC have been null mutations. This study shows that missense mutations affecting the glycosyl transferase domain of GalNAc transferase 3 also cause TC. Elevated C-terminal FGF23 fragments with undetectable intact FGF23 suggest that the mutant enzyme lacks the ability to glycosylate FGF23 and that glycosylation by GalNAc transferase 3 is necessary for secretion of functional full-length FGF23.

Adult↗
PubMed2006

Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25-dihydryxyvitamin-D concentration, myopathy, and osteomalacia. Fibroblast growth factor 23 (FGF23) is a phosphaturic protein overexpressed in tumors that cause TIO and is, at least partly, responsible for the manifestations of TIO. OBJECTIVE: The objective of this study was to determine the sensitivity of FGF23 measurements in TIO. DESIGN: FGF23 concentrations were measured on stored samples with three ELISAs. SETTING: This study was conducted at subspecialty referral centers. PATIENTS: Twenty-two patients with suspected TIO, 13 with confirmed tumors, were studied. INTERVENTIONS: There were no interventions in this study. MAIN OUTCOME MEASURE: FGF23 concentration was the main outcome measure of this study. RESULTS: Elevated FGF23 concentrations were detected using the Immunotopics C-terminal assay in 16 of 22 TIO patients (for a sensitivity of 73%), the Immunotopics Intact assay in five of 22 patients (sensitivity, 23%), and the Kainos Intact assay in 19 of 22 patients (sensitivity, 86%). In the 13 patients with confirmed tumors, the sensitivity was higher with all assays: 92% for the Immunotopics C-terminal assay, 38% for the Immunotopics Intact assay, and 100% for the Kainos assay. CONCLUSION: The Kainos Intact assay was the most sensitive, followed by the Immunotopics C-terminal assay. The findings of normal FGF23 concentrations in some patients with TIO may indicate that FGF 23 is not responsible for the hypophosphatemia in these patients or that FGF23 secretion by some tumors is partially responsive to serum phosphate. Normal FGF23 concentrations should be interpreted in relation to the serum phosphate and 1,25-dihydryxyvitamin-D concentrations.

Adolescent↗
PubMed2005

Osteoporosis associated with excess glucocorticoids.

Excess glucocorticoids, whether endogenous or exogenous, can cause osteoporosis and fractures. Even low doses of oral glucocorticoids and mild endogenous hypercortisolism may be associated with bone loss. Patients treated with glucocorticoids, however, often are not evaluated and treated for this problem. Patients on chronic glucocorticoids or initiating these drugs should have their bone density measured and appropriate laboratory studies. They should be treated with adequate calcium and vitamin D, and antiresorptive therapy (particularly bisphosphonates) should be considered.

Glucocorticoids↗
PubMed2004

Artifactual reduction in bone density as a result of technetium-99m MDP for bone scanning: report of two cases.

We present two patients in whom marked changes in dual-energy X-ray absorptiometry (DXA)-measured bone mineral density were found to be the result of prior administration of technetium-99m methylene diphosphonate (MDP) for bone scanning. In patient 1, an artifactual 50% decrease in lumbar spine and 19% decrease in left total hip bone density over a 14-mo period was the result of technetium-99m injection 3 h before the second bone density measurement. In patient 2, a dramatic increase in bone density at 6 mo was the result of artifactual reduction in bone density on the baseline study as a result of technetium-99m injection 2 h earlier. Clinicians and technologists should be aware that technetium-99m used for bone scanning could cause artifactual reduction in DXA-measured bone mineral density.

Absorptiometry, Photon↗
PubMedDate not supplied

Evolution of a pheochromocytoma.

OBJECTIVE: To present a case that demonstrates the evolution of a pheochromocytoma over a several-year period and to emphasize the importance of a thorough work-up for pheochromocytoma in patients with neurofibromatosis type 1 (NF1) and hypertension. METHODS: We review the long-term clinical, biochemical, and imaging findings in a man with a complex medical history of hypertension, NF1, and cardiomyopathy. RESULTS: A 44-year-old man, with a well-documented history of headaches, hypertension, and NF1, was referred for evaluation of a right adrenal enlargement. He had developed cardiomyopathy and undergone an evaluation for cardiac transplantation. Initial computed tomography revealed subtle asymmetry in the upper right adrenal gland. Biochemical studies for pheochromocytoma yielded equivocal findings, with a 1.5-fold elevation in the urinary norepinephrine and near-normal urinary metanephrine level. Because 131I-metaiodobenzylguanidine imaging showed no tracer uptake in the area of the right adrenal gland, the patient was thought not to have a pheochromocytoma. The patient eventually underwent cardiac transplantation and did well. On reassessment 3 1/2 years later, he was found to have a larger right adrenal mass. The second endocrine evaluation demonstrated substantial elevation in the urinary metanephrine level, and the patient underwent laparoscopic right adrenalectomy to remove the tumor (3.5 by 3.0 by 2.5 cm), which proved to be a pheochromocytoma. CONCLUSION: This case shows that a pheochromocytoma can be difficult to diagnose and can evolve to become a large, biochemically active tumor. It is imperative that patients with an adrenal tumor undergo periodic reevaluation to ensure that the tumor remains stable in size. If the tumor enlarges, further biochemical testing is warranted.

3-Iodobenzylguanidine↗