Effects of pump versus twice-daily injection delivery of synthetic parathyroid hormone 1-34 in children with severe congenital hypoparathyroidism.

OBJECTIVE: To compare the response with synthetic human parathyroid hormone (PTH) 1-34 delivered by twice-daily injection vs insulin pump in children with severe congenital hypoparathyroidism due to calcium receptor mutation or autoimmune polyglandular syndrome type 1. STUDY DESIGN: Children and young adults aged 7-20 years with congenital hypoparathyroidism (N = 12) were randomized to receive PTH 1-34, delivered either by twice-daily subcutaneous injection or insulin pump for 13 weeks, followed by crossover to the opposite delivery method. The principal outcome measures were serum and urine calcium levels. Secondary outcomes included serum and urine magnesium and phosphate levels and bone turnover markers. RESULTS: PTH 1-34 delivered via pump produced near normalization of mean serum calcium (2.02 ± 0.05 [pump] vs 1.88 ± 0.03 [injection] mmol/L, P < .05, normal 2.05-2.5 mmol/L), normalized mean urine calcium excretion (5.17 ± 1.10 [pump] vs 6.67 ± 0.76 mmol/24 h/1.73 m(2), P = .3), and significantly reduced markers of bone turnover (P < .02). Serum and urine calcium and magnesium showed a biphasic pattern during twice-daily injection vs minimal fluctuation during pump delivery. The PTH 1-34 dosage was markedly reduced during pump delivery (0.32 ± 0.04 vs 0.85 ± 0.11 µg/kg/d, P < .001), and magnesium supplements were also reduced (P < .001). CONCLUSION: Compared with twice-daily delivery, pump delivery of PTH 1-34 provides more physiologic calcium homeostasis and bone turnover in children with severe congenital hypoparathyroidism.

[Hypocalcemia and neonatal seizures: a rare case of congenital hypoparathyroidism]. / Hipocalcemia e crises neonatais: Um caso raro de hipoparatireoidismo congênito.

We report the case of a white male infant, 2 months-old, with tremor and hypertonia since 15th day of life transferred to our service and diagnosed as seizures. Investigation showed hypocalcaemia (4 mg/dl) and hypomagnesemia (1.6 mg/dL) and the infant's serum metabolic disturb was corrected by intravenous calcium gluconate and magnesium sulphate, but attempted to "wean" him from intravenous treatment led to a relapse of hypocalcemia. At this time hypoparathyroidism was suspected and the additional investigation confirmed this suspect ion. The neurologic examination revealed an irritable patient with marked extensor hypertonia and opisthotonos. Cranial CT and MRI scans were normal, but the EEG exam showed severe abnormalities. The infant was given the oral calcium gluconate, magnesium chloride and colecalciferol daily to maintain a normal calcium concentration, but the control was very difficult. The patient had an extend hospitalization of 6 months and death was due to repetitive infection. We discuss the clinical findings, imaging, EEG exam, differential diagnosis and treatment of this disorder.

Pseudohipoparatiroidismo Tipo I

El pseudohipoparatiroidismo es una entidad infrecuente y heterogénea causada por la pérdida heterocigótica de aproximadamente el 50 por ciento de la proteína Gs alfa, caracterizada por losvalores séricos de calcio bajos, grados de fosfatemia variable elevada y resistencia variable de la PTH, con hallazgos clínicos dismórficos y en algunos casos (tipo I) asociado a retardo mental. La alteración descrita es el resultado de la disfunción de la proteína Gs alfa miembro de la superfamilia de proteínas heterotriméricas transductoras de señales intracelulares estimuladoras de la adenil ciclasa intracelular. Se revisan dos casos con el tipo pseudohipo-hiperparatiroidismo y uno de tipo I.

Calcium and phosphate metabolism in children with idiopathic hypoparathyroidism or pseudohypoparathyroidism: effects of 1,25-dihydroxyvitamin D3.

Two children with congenital hypoparathyroidism and two children with pseudohypoparathyroidism were given maintenance doses of 15 to 45 ng/kg/day 1,25-dihydroxyvitamin D3 for a total of 255 months. The urinary calcium excretion showed an upward elevation after the first 2 years of treatment but was not significantly higher than that in 10 normal control subjects. The renal threshold for phosphate excretion stayed within the normal ranges compared with control values. Two hypercalcemic and two hypocalcemic episodes occurred during this period of treatment. Hypercalcemia was reversed within 1 week after withdrawal of 1,25-dihydroxyvitamin D3. Hypocalcemia was countered by increasing the dose of 1,25-dihydroxyvitamin D3. Renal functions were not adversely affected, as estimated by creatinine clearance and reciprocals of serum creatinine concentrations. The mean serum calcium concentration during 1,25-dihydroxyvitamin D3 treatment was significantly higher (P = 0.001) compared with that obtained during vitamin D2 treatment at a dose of 500 to 3000 IU/kg/day. These data provide additional support for the long-term use of 1,25-dihydroxyvitamin D3 in idiopathic hypoparathyroidism and pseudohypoparathyroidism.

Transient congenital hypoparathyroidism: possible association with anomalies of the pulmonary valve.

Transient congenital hypoparathyroidism was observed in four neonates who also had congenital cardiac defects. Severe hypocalcemia and hyperphosphatemia were noted at 2 or 3 weeks of age, but resolved by 2 to 4 months of age with minimal treatment (oral calcium alone). Parathyroid hormone, measured with a highly sensitive, homologous antiserum, was initially borderline detectable and became easily detectable as the hypocalcemia resolved. Immune function was normal in each patient. The congenital cardiac defects in each case involved the pulmonary valve. These patients might be regarded as having either a partial form of the DiGeorge syndrome or a separate syndrome in which congenital pulmonary valve lesions are linked to delayed maturation of parathyroid function by an as yet obscure mechanism.