Growth response to growth hormone (GH) treatment in children with GH deficiency (GHD) and those with idiopathic short stature (ISS) based on their pretreatment insulin-like growth factor 1 (IGFI) levels and at diagnosis and IGFI increment on treatment.

OBJECTIVES: Some idiopathic short stature (ISS) patients may have varying degrees of insulin-like growth factor 1 (IGFI) deficiency. Others with growth hormone deficiency (GHD) (peak GH < 7 ng/dL after provocation) have normal IGFI levels. Do children with ISS or those with GHD with variable pretreatment IGFI standard deviation score (IGFISDS) have different IGFI and growth responses to recombinant human growth hormone (rhGH) therapy? METHODS: We studied the effect of GH therapy (0.035-0.06 mg/kg/day) on linear growth and weight gain per day (WGPD) in children with ISS (n=13) and those with GHD (n=10) who have low pretreatment IGFISDS (IGF SDS < -1.5) and compared them with age-matched prepubertal children with ISS (n=10) and GHD (n=17) who had normal pretreatment IGFISDS. An untreated group of children with ISS (n=12) served as a control group. RESULTS: At presentation, the height standard deviation score (HtSDS) of children with ISS who had low pretreatment IGFISDS was significantly lower compared to the normal IGFI group. The age, body mass index (BMI), BMISDS, peak GH response to clonidine provocation and bone age did not differ between the two study groups. After 1 year of treatment with rhGH (0.035-0.06 mg/kg/day) IGFISDS increased significantly in both groups (p<0.05). Both had significantly increased HtSDS (catch-up growth). The increase in the HtSDS and WGPD were significantly greater in the lower pretreatment IGFISDS group. The IGFSDS, BMISDS, HtSDS and difference between HtSDS and mid-parental HtSDS were significantly greater in the rhGH treated groups vs. the not treated group. In the GHD groups (normal and low IGFISDS), after 1 year of GH therapy (0.03-0.05 mg/kg/day), the HtSDS increased significantly in both, (p<0.01). The WGPD and increment in BMI were significantly greater in children who had low pretreatment IGFISDS. There was a significant increase in the IGFSDS in the two treated groups (p<0.05), however, the WGPD was greater in the pretreatment low IGFISDS. CONCLUSIONS: IGFI deficiency represents a low anabolic state. Correction of IGFI level (through rhGH and/or improved nutrition) in short children (ISS and GHD) was associated with increased linear growth and WGPD denoting significant effect on bone growth and muscle protein accretion.

Defective Cortisol Secretion in Response to Spontaneous Hypoglycemia but Normal Cortisol Response to ACTH stimulation in neonates with Hyperinsulinemic Hypoglycemia (HH).

INTRODUCTION: Hyperinsulinemic Hypoglycaemia (HH) is the most common cause of recurrent and persistent hypoglycemia in the neonatal period. Cortisol and GH play an important role as a counterregulatory hormone during hypoglycemia. Both antagonize the peripheral effects of insulin and directly influences glucose metabolism Patients and Methods: We studied cortisol and GH secretion in newborn infants with HH during spontaneous hypoglycemia. In addition, their basal ACTH level and cortisol response to a standard dose ACTH was performed. RESULTS: Nine newborns with HH were studied during the first 2 weeks of life. During HH, their mean glucose concentration was 1.42 ± 0.7 mmol/L, mean beta hydroxybutyrate level was 0.08 ± 0.04 mmol/L, and mean serum insulin level was 17.78 ± 9.7 µU/mL. Their cortisol and GH levels at the time of spontaneous hypoglycemia were 94.7 ± 83.1 nmol/L and 82.4 ± 29 m IU/L respectively. They had relatively low level of ACTH (range: 14 :72 pg/ml, mean: 39.4 ± 20 pg/mL) during hypoglycemia. All infants had GH concentration > 20 mIU/L at the time of hypoglycemia. All infants underwent ACTH test. Their basal serum cortisol levels did not differ compared to cortisol levels during hypoglycemia, and all had a normal peak cortisol response (> 500 nmol/L) in response to i.v. ACTH stimulation test. CONCLUSION: Infants with HH have low cortisol response to spontaneous hypoglycemia with normal response to exogenous standard-dose ACTH. Checking hypothalamic-pituitary axis (HPA) axis later in infancy using low dose ACTH may be useful to diagnose persistent HPA abnormalities in these infants. All HH infants had appropriate elevation of GH during hypoglycemia.

Postnatal growth of Infants with neonatal diabetes: insulin pump (CSII) versus Multiple Daily Injection (MDI) therapy.

BACKGROUND: Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life. Their diabetes is associated with partial or complete insulin deficiency with variable degree of intrauterine growth retardation. Insulin therapy corrects the hyperglycemia and results in improvement of growth. However, no studies have reported the longitudinal growth of these infants (head circumference, length and weight gain) after starting insulin therapy. PATIENTS AND METHODS: We assessed the growth parameters weight (Wt), Length (L) and head circumference (HC) in 9 infants with PNDM, during the first 2 years of their postnatal life. Five infants were on insulin pump therapy (CSII) and 4 were on multiple doses of insulin injection (MDI) therapy. RESULTS: On insulin therapy for 20±4 months catch-up growth occurred in the majority of infants. L-SDS increased from -1.45 to -0.65 , HC-SDS from -2.3 to - 0.51 and Wt-SDS increased from -1.94 to - 0.7 at the end of the 20±4 months of age, after starting insulin therapy. Two out of 9 infants had a L-SDS <-2 , in 4 Wt-SDS was <-2 and in 1 the HC-SDS was <-2 at  at 20±4 months of postnatal growth.  The level of HbA1c was lower in infants on CSII compared to those on MDI (9.6±1%) compared to those on MDI (10.2±2%). However, growth parameters improved significantly in both groups (CSII and MDI) with no significant difference among them. CONCLUSIONS: Infants with PNDM with positive anti-GAD and antiTPO were diagnosed later and their intra-uterine and postnatal growth differed compared to those with negative antibodies. The majority of infants with PNDM exhibited significant catch up growth within the first two years of life irrespective of the etiology of diabetes. HbA1c appeared to be better in infants with PNDM on CSII therapy when compared to those on MDI therapy.