Chronic hypomagnesemia and hypokalemia due to renal wasting in siblings

A 13 year old girl with carpopedal spasm is presented. Investigation values showed hypomagnesemia and hypokalemia. Her younger brother and sister demonstrated the same biochemical abnormalities without any symptoms. Their urinary excretion of magnesium and potassium were inappropriately high compared with their serum levels. Treatment with oral magnesium sulfate failed to correct the abnormalities, but serum levels of magnesium and potassium were just below the lower limits. This familial disease may represent congenital renal wasting of magnesium and potassium.     

Neonatal hypophosphatasia with elevated serum parathyroid hormone

Two cases of neonatal hypophosphatasia are described. In case 1, hypercalcemia developed at 21/2 months of age and continued until death at 101/2 months of age. Serum calcium levels decreased transiently in response to phosphate supplementation, prednisolone, and calcitonin. Significantly elevated levels of PTH were detected at 21/2 months of age. At autopsy, no parathyroid glands were found. In case 2, hypercalcemia was not detected in his course. Elevated level of serum PTH was recorded on the 17th day of life. A post-mortem examination revealed the presence of one normal parathyroid gland.     

Indices of intact serum parathyroid hormone and renal excretion of calcium,phosphate, and magnesium.

Up to date reference ranges were established for fasting renal excretion of calcium, phosphorus, and magnesium on 101 healthy children aged 2-15 years. A normal range for intact parathyroid hormone was also measured. The indices of calcium and magnesium excretion showed no correlation with age or sex so that a common range for all children could be established. The 97th centile values for urinary calcium:creatinine and magnesium:creatinine ratios were 0.69 mmol:mmol and 1.05 mmol:mmol respectively. The calculated tubular maximum for phosphate/litre of glomerular filtrate (TmPO4/GFR) showed no correlation with age with a geometric mean value of 1.67 mmol/l. The normal range for intact serum parathyroid hormone for the age group was 11-35 ng/l, which is lower than the adult normal range using the same assay. There was an inverse correlation between TmPO4/GFR and intact parathyroid hormone in this group of normal children.     

Reversible cardiomyopathy due to carnitine deficiency from renal tubular wasting

The clinical course of a 4-month-old male infant with a dilated cardiomyopathy secondary to renal tubular losses of carnitine is outlined. He was admitted to the hospital with severe congestive heart failure. An echocardiogram demonstrated normal anatomy. The left ventricular shortening fraction measured 10%. A comprehensive cardiomyopathy evaluation was initiated.The total plasma carnitine level was only 25 mol/ml, but the urine carnitine measured 434 nm/mg of creatinine. He was begun on orall-carnitine and weaned from mechanical ventilation and inotropic support 10 days later. Two years later he remains asymptomatic with normal left ventricular function.     

Circulating immunoreactive growth hormone releasing hormone concentrations and growth hormone response to growth hormone releasing hormone in short children

To study the role of peripheral immunoreactive growth hormone releasing hormone (ir-GHRH) concentrations and the GHRH test in the evaluation of growth hormone (GH) secretion in short stature, 46 children with a mean age of 9.4 years (range 1.6–16.3 years) and a mean relative height score of –3.2 SD (range –5.0–2.1 SD) were investigated. The children were divided into prepubertal (n=35) and pubertal (n=11) and the prepubertal children further into three groups based on their maximal GH responses to insulin-induced hypoglycaemia (IIH) and clonidine: (1) GH deficient subjects (maximal GH<10 g/l in both test); (2) discordant responders (maximal GH<10 g/l in one test and 10 g/l in the other); and (3) normal responders (maximal GH10 g/l in both test). Peripheral ir-GHRH concentrations were measured during the IIH test by radioimmunoassay after purification of plasma samples on Sep-pak cartridges. Among the prepubertal children 10 fell into group 1, 16 into group 2 and 9 into group 3. Children in group 1 were older, than those in group 3. There were no significant differences in relative heights and weights or absolute and relative growth velocities between the groups. Subjects in groups 1 and 2 had lower maximal GH responses to GHRH than those in group 3. There were no significant differences in the basal plasma ir-GHRH concentrations between the groups. Nine children (19.6%) had somatotrophs with a poor response to a single dose of exogenous GHRH (maximal GH<10 g/l). These subjects had increased basal plasma ir-GHRH concentrations. All of them had a decreased GH response to IIH and/or clonidine. Pubertal children had higher circulating ir-GHRH levels than the prepubertal subjects. There was an inverse correlation (r=–0.46;P<0.001) between the maximal GH response to GHRH and calendar age in the whole series. These observations suggest that: (1) a substantial proportion of short children have a heterogenous GH response to pharmacological stimuli necessitating complementary evaluation of their spontaneous GH secretion; (2) a poor response to exogenous GHRH is associated with increased ir-GHRH levels in the peripheral circulation; (3) all children with normal GH responses in pharmacological tests respond normally to GHRH and (4) the pituitary sensitivity to GHRH decreases with increasing age. Peripheral ir-GHRH concentrations do not differentiate between short children with growth hormone deficiency (GHD) and those with undefined short stature. The GHRH test is of limited value in the diagnosis of GHD, since a normal GH response does not exclude GHD, although a subnormal response appears to reflect dysfunctional GH secretion.     

Circulating immunoreactive parathyroid hormone levels in premature infants and the response to calcium therapy

Serum immunoreactive parathyroid hormone (iPTH), calcium, magnesium, and phosphorus levels were measured in 13 premature infants during the first 96 hours of life. Hypocalcemia at 12-24 hours of age was associated with a markedly elevated mean serum iPTH level. Six of the hypocalcemic infants received a continuous infusion of calcium while seven were not treated. In the untreated infants, the mean serum calcium remained in the hypocalcemic range while the serum iPTH progressively increased. By contrast, the mean serum calcium in the treated infants increased to 2.35 mmol/l at 96 hours of age and was accompanied by a decline in serum iPTH. At 72 and 96 hours, the mean serum iPTH was twofold greater in the untreated than in the treated infants. The results indicate that the parathyroid glands of premature infants respond to calcium signals and that a factor(s), other than parathyroid insufficiency, plays an etiologic role in the hypocalcemia of prematurity.     

Maternal-fetal relationships in the parathyroidectomized rat. Intestinal calcium transport, serum calcium, immunoreactive parathyroid hormone and calcitonin

We studied the role of the parathyroids in the adaptation of intestinal Ca transport that occurs during pregnancy, and whether maternal hypoparathyroidism causes fetal hyperparathyroidism. Serum Ca of pregnant parathyroidectomized (PTX) rats was significantly greater than nonpregnant, PTX animals. Intestinal active Ca transport was increased 2.1- and 2.2-fold by pregnancy in intact and PTX rats, respectively. Serum levels of immunoreactive parathyroid hormone (PTH) were nondetectable in PTX-pregnant rats. Fetuses from PTX rats appeared grossly normal. The serum PTH was not different in fetuses from PTX compared to fetuses from intact mothers and serum Ca, Mg, and P were normal. Thus, alleviation of maternal hypocalcemia during pregnancy in PTX rats may be due to an adaptive increase in intestinal Ca transport, which does not require the parathyroids. Fetuses from PTX mothers were euparathyroid and were protected from Ca deficiency during pregnancy.     

Circulating levels of biologically active and immunoreactive intact parathyroid hormone in human newborns

We evaluated circulating levels of biologically active and immunoreactive intact parathyroid hormone [iPTH-(1-84)] in 47 newborns at birth and eight hypocalcemic preterm infants during the first 10 d of life. Use of two sensitive detection systems, the cytochemical bioassay and an immunoradiometric assay specific for intact parathyroid hormone, enabled us to compare plasma concentrations of PTH-like bioactivity (bioPTH) and iPTH-(1-84). Mean umbilical venous plasma bioPTH was elevated in nondiabetic term and preterm newborns [22.5 +/- 3.1 (+/- SEM) and 15.8 +/- 2.5 ng-equiv/L, respectively] compared with normal adult subjects (9.8 +/- 2.6 ng-equiv/L; p less than 0.01). Umbilical bioPTH was suppressed in five term infants of diabetic mothers (2.6 +/- 0.4 ng-equiv/L). In contrast, iPTH-(1-84) was low in term and preterm nondiabetic infants' and term infants of diabetic mothers' umbilical samples (5.4 +/- 1.5, 4.3 +/- 1.5, and 2.4 +/- 1.0 ng/L, respectively). Umbilical venous bioPTH was highly correlated with the magnitude of the transplacental calcium gradient (r = 0.90; p less than 0.05). In eight preterm infants studied longitudinally, by 24-36 h of life, declining plasma total and ionized calcium (1.71 +/- 0.04 and 0.78 +/- 0.03 mmol/L, respectively) were accompanied by a significant rise in both bioPTH (41.2 +/- 6.3 ng-equiv/L) and iPTH-(1-84) (56.3 +/- 11.6 ng/L). These data indicate that the 3rd trimester fetoplacental circulation contains levels of bioPTH several-fold higher than those of immunoreactive intact hormone. We also conclude that even hypocalcemic preterm newborn infants can significantly elevate circulating levels of PTH.     

Hypercalcemia and elevated parathyroid hormone levels in association with nephroblastoma.

A three-month-old girl with nephroblastoma had at the same time a hypercalcemia and elevated parathyroid hormone levels. Both biochemical findings disappeared after surgical removal of the tumor.     

Persistent elevated serum levels of intact parathyroid hormone after reoperation for primary hyperparathyroidism and after pamidronate therapy

Primary hyperparathyroidism is a life-threatening rare disorder. It is seen as a result of neonatal primary hyperparathyroidism, familial hypocalciuric hypercalcemia, increased vitamin D levels and inactivation of calcium sensing receptor mutations. The clinical findings are hypotonia, bone demineralization, hypercalcemia and parathyroid hyperplasia. We present a six-month-old female patient, the first child of nonconsanguineous parents, who was referred for the investigation of failure to thrive, vomiting, constipation, fever, abdominal distention and hypotonia. Physical examination revealed weight under 3rd percentile, height 3rd-10th percentile, decreased subcutaneous fat, and distention of the abdomen. In neurological examination, hypotonia, motor-mental retardation, and active deep tendon reflexes were found. The biochemical values at the time of admission revealed primary hyperparathyroidism. Since hypercalcemia did not respond to calcitonin therapy and due to the mortality of hypercalcemia, parathyroidectomy was performed. Because hyperparathyroidism and hypercalcemia continued, angiography was done which revealed increased parathyroid hormone levels in the periphery of the innominate vein. Exploratory surgery followed, but hyperparathyroidism and hypercalcemia persisted after all of these procedures. Calcium-sensing receptor mutations and supernumerary gland were considered. Because hypercalcemia persisted, pamidronate therapy was initiated on a monthly basis.     

窒息新生儿甲状旁腺素变化及临床意义

甲状旁腺素（PTH）是调节钙代谢的重要激素,其自身的合成与释放又要受血钙水平的影响。除已知的新生儿窒息后常见合并低钙血症,缺氧缺血时钙离子内流引起细胞损伤外,近年来,对于调节血钙的内分泌激素已受到人们的关注。但对于甲状旁腺激素在窒息新生儿中的变化了解甚少。本文对正常出生及同期出生重度窒息的新生儿,出生后24h、72h、7d的血清PTH、血钙水平进行对照分析。     

Severe reversible renal failure due to naproxen-associated acute interstitial nephritis

Acute interstitial nephritis is uncommon in children and has very rarely been described with naproxen treatment. We report the occurrence of severe acute renal failure in a 10-year-old girl with juvenile rheumatoid arthritis after 1 month of naproxen therapy. Renal biopsy showed severe acute interstitial nephritis. The patient recovered completely after discontinuation of naproxen and administration of methylprednisolone. A review of the literature regarding non-steroidal anti-inflammatory drug-associated acute interstitial nephritis is provided. CONCLUSION: In an era of increasing popularity of non-steroidal anti-inflammatory drugs for use in children, paediatricians should be aware of the potential renal complications of this class of drugs.     

Plasma thyrocalcitonin and parathyroid hormone concentrations in early neonatal hypocalcaemia.

During the first week of life serum calcium, phosphorus, magnesium, immunoreactive thyrocalcitonin hormone, and parathyroid hormone concentrations were determined daily in 36 preterm and 29 small for gestational age, full term, healthy infants. Preterm babies with early neonatal hypocalcaemia had significantly higher concentrations of serum thyrocalcitonin hormone in the first four days of life than normocalcaemic preterm babies. Parathyroid hormone concentrations were similar in hypocalcaemic and normocalcaemic infants. In contrast, in the full term group no significant differences were detected in thyrocalcitonin hormone and parathyroid hormone patterns between hypocalcaemic and normocalcaemic subjects. This suggests two different pathogeneses for early hypocalcaemia in low birthweight infants. Hyperthyrocalcitoninaemia seems to be the main determining factor in preterm infants, while a non-hormonal pathogenesis should be considered in full term infants who are small for gestational age.