To define the earliest renal morphological changes in patients with type I diabetes, we studied renal function and morphometric analysis of renal biopsies in 59 patients with diabetes for 5-12 years and normal blood pressure, normal creatinine clearance (CCr), and negative dipstick urinary protein. Arteriolar hyalinization and intimal fibrous thickening were noted in 43%. Glomerular basement membrane thickness and fractional mesangial volume were increased in 51% and 56%, respectively. The pre-pubertal and post-pubertal years of diabetes were associated with similar degrees of renal structural changes, but during the pre-pubertal years normal urinary albumin excretion (UAE) was seen. Principal factor analysis of morphometric structural parameters yielded four clusters of variables: "glomerular size" correlated with patient age, CCr, and UAE; "peripheral capillary decrease" correlated with glycosylated hemoglobin, diastolic blood pressure, glomerular filtration rate, and UAE; "mesangial increase" correlated with UAE; and "interstitial scarring" correlated with diastolic blood pressure. This study provides unique documentation of renal structural abnormalities which precede clinically evident renal functional abnormalities and documents that these early structural abnormalities are present in the pre-pubertal years of diabetes as well as postpuberty, and are associated with each other in constellations that correspond to postulated mechanisms in diabetic nephropathy.

We have attempted to identify any characteristics which could be used to predict the development of cerebral edema in four children under 5 years of age with new onset insulin-dependent diabetes mellitus and diabetic ketoacidosis. We retrospectively analysed and compared the concentration of serum sodium (corrected for serum glucose value) and effective serum osmolality of these 4 children with values of 10 age-matched controls with new onset insulin-dependent diabetes mellitus who did not develop cerebral edema during treatment of diabetic ketoacidosis. The initial serum sodium values of the two groups were not statistically different. Patients who developed cerebral edema had lower initial serum glucose values and effective serum osmolality. During treatment, patients who developed cerebral edema had consistently lower mean serum sodium and osmolality than controls at each 4-h interval after the first 4 h of therapy. Serum sodium and osmolality declined progressively after the initiation of therapy in cerebral edema patients, while remaining stable in controls. These data suggest that children who develop cerebral edema during treatment for diabetic ketoacidosis initially may have a relatively normal serum osmolality and subsequently develop progressive hyponatremia and/or a trend of declining serum sodium before developing cerebral edema.

OBJECTIVE.Central

In girls with early clinical signs of precocious puberty and low serum concentrations of LH and oestradiol in random samples, the LH and oestradiol responses to leuprolide stimulation accurately predict pubertal progression.

BACKGROUND:Testosterone measurements that are accurate, reliable, and comparable across methodologies are crucial to improving public health. Current US Food and Drug Administration-cleared testosterone assays have important limitations. We sought to develop assay performance requirements on the basis of biological variation that allow physiologic changes to be distinguished from assay analytical errors.

We used the GnRH agonist (GnRHa) stimulation test (20 micrograms/kg leuprolide sc, followed by 24-h serial sampling) to investigate the relationship between gonadotropin and estradiol (E2) secretion in the early phase of female central precocious puberty (CPP). Girls with CPP and moderately increased (early pubertal) peak E2 concentrations after GnRHa stimulation (136 +/- 11 pmol/L; range, 92-176; group B; n = 7) were compared to girls with CPP and higher (midpubertal) peak E2 responses to GnRHa (mean +/- SE, 590 +/- 63 pmol/L; range, 235-1189; group C; n = 19) and to a group of subjects with no breast development and a prepubertal hypothalamic-pituitary-gonadal axis (peak E2 response to GnRHa, 39 +/- 7 pM/L; range, 18-62; group A; n = 6). Compared to group A subjects, patients in group B had similar (P > 0.2) peak GnRHa-stimulated LH concentrations (B, 4.8 +/- 1 IU/L; A, 2.3 +/- 0.5 IU/L) and peak nocturnal LH (B, 0.81 +/- 0.2; A, 0.25 +/- 0 IU/L), but higher peak GnRHa-stimulated FSH concentrations (B, 26 +/- 7; A, 11 +/- 2 IU/L; P < 0.05) and mean nocturnal FSH (B, 4.2 +/- 1; A, 1.1 +/- 0.3 IU/L; P < 0.05) concentrations. Compared to group B, group C patients had higher (P < 0.001) GnRHa-stimulated peak LH (67 +/- 19 IU/L) and higher (P < 0.05) peak nocturnal LH (9.7 +/- 2.9 IU/L) concentrations, but similar GnRHa-stimulated peak FSH (27 +/- 3 IU/L) and mean nocturnal FSH (3.8 +/- 0.5 IU/L) levels. Group C patients with a ratio of peak GnRHa-stimulated LH to FSH concentrations below or above 1, respectively, had similar peak E2 responses to GnRHa (516 +/- 80 vs. 644 +/- 92 pM/L; P > 0.1). Stepwise regression analysis indicated that the peak LH response to GnRHa (r = 0.76; P < 0.001), but none of the FSH secretory parameters (P > 0.10), affected the E2 response to GnRHa. These data suggest that girls with CPP in the early phase of activation of the hypothalamic-pituitary-gonadal axis are capable of clinically relevant E2 production, which may occur in the face of low LH secretion and low LH/FSH ratios and cannot be explained solely on the basis of increased FSH secretion. Thus, endocrine or paracrine factors other than gonadotropins may be important in amplifying E2 secretion in the early phase of CPP.

We used the GnRH agonist (GnRHa) stimulation test (20 micrograms/kg leuprolide sc, followed by 24-h serial sampling) to investigate the relationship between gonadotropin and estradiol (E2) secretion in the early phase of female central precocious puberty (CPP). Girls with CPP and moderately increased (early pubertal) peak E2 concentrations after GnRHa stimulation (136 +/- 11 pmol/L; range, 92-176; group B; n = 7) were compared to girls with CPP and higher (midpubertal) peak E2 responses to GnRHa (mean +/- SE, 590 +/- 63 pmol/L; range, 235-1189; group C; n = 19) and to a group of subjects with no breast development and a prepubertal hypothalamic-pituitary-gonadal axis (peak E2 response to GnRHa, 39 +/- 7 pM/L; range, 18-62; group A; n = 6). Compared to group A subjects, patients in group B had similar (P > 0.2) peak GnRHa-stimulated LH concentrations (B, 4.8 +/- 1 IU/L; A, 2.3 +/- 0.5 IU/L) and peak nocturnal LH (B, 0.81 +/- 0.2; A, 0.25 +/- 0 IU/L), but higher peak GnRHa-stimulated FSH concentrations (B, 26 +/- 7; A, 11 +/- 2 IU/L; P < 0.05) and mean nocturnal FSH (B, 4.2 +/- 1; A, 1.1 +/- 0.3 IU/L; P < 0.05) concentrations. Compared to group B, group C patients had higher (P < 0.001) GnRHa-stimulated peak LH (67 +/- 19 IU/L) and higher (P < 0.05) peak nocturnal LH (9.7 +/- 2.9 IU/L) concentrations, but similar GnRHa-stimulated peak FSH (27 +/- 3 IU/L) and mean nocturnal FSH (3.8 +/- 0.5 IU/L) levels. Group C patients with a ratio of peak GnRHa-stimulated LH to FSH concentrations below or above 1, respectively, had similar peak E2 responses to GnRHa (516 +/- 80 vs. 644 +/- 92 pM/L; P > 0.1). Stepwise regression analysis indicated that the peak LH response to GnRHa (r = 0.76; P < 0.001), but none of the FSH secretory parameters (P > 0.10), affected the E2 response to GnRHa. These data suggest that girls with CPP in the early phase of activation of the hypothalamic-pituitary-gonadal axis are capable of clinically relevant E2 production, which may occur in the face of low LH secretion and low LH/FSH ratios and cannot be explained solely on the basis of increased FSH secretion. Thus, endocrine or paracrine factors other than gonadotropins may be important in amplifying E2 secretion in the early phase of CPP.

Childhood cases of myxedema coma are extremely rare. We report a case of a 5-year-old girl transferred to a tertiary care pediatric emergency department with hypoxemia and altered mental status and diagnosed with severe hypothyroidism and myxedema coma in the setting of acute influenza infection. Although it is rare, myxedema coma must remain in the differential diagnosis for altered mental status and organ dysfunction in the pediatric population.