Hypoglycemia in Children Referred to a Tertiary Care Pediatric Endocrine Clinic: Age-Dependent Etiological Variations.

INTRODUCTION: Diagnosing hypoglycemia in infants and children presents significant challenges. Our objective was to elucidate the diagnoses and clinical features of children with hypoglycemia referred to a pediatric endocrine tertiary clinic. METHODS: Retrospective study of 154 children (0-18 years old) presenting with hypoglycemia, during 1992-2018. RESULTS: The cohort was divided by clinical diagnosis into six groups: ketotic hypoglycemia (n=45, 29.2%), congenital hyperinsulinemic hypoglycemia (n=35, 22.7%), transient hyperinsulinemic hypoglycemia (n=28, 18.2%), metabolic disorder (n=14, 9.1%), systemic disease/syndrome (n=15, 9.7%), and hormone deficiencies (n=8, 5.2%). Two patients had insulinoma and in 7 (4.5%) no diagnosis was elucidated. At diagnosis, 58 (37.7%) were <1 month old, 23 (14.9%) aged 1-12 months, 58 (37.7%) aged 1-6 years, and 15 (9.7%) aged 6-18 years. Hypoglycemia etiology varied among neonates, infants, and children. In eight patients hypoglycemia was asymptomatic. Of 47 patients who completed a diagnostic fast, 31 became hypoglycemic, yet a significant added value for diagnosis was only found in 14 (29.8%) patients. CONCLUSIONS: Hypoglycemia etiology in children is heterogeneous and varies by age. Any hypoglycemia measured in a child should be seriously evaluated as 7% are asymptomatic. Work-up should be tailored based on age, and clinical, biochemical, and imaging findings. Despite extensive work-up, in a significant number of patients the mechanism underlying pediatric hypoglycemia remains an enigma. This emphasizes the unmet needs and challenges in studying pediatric hypoglycemia.

The second to fourth digit ratio in patients with congenital IGF-1 Deficiency.

The relationship between the length of the second and fourth ring finger (2D:4D ratio) is a sexually dimorphic trait, higher in females than in males. It is established during early prenatal development under the influence of sex hormones, as demonstrated in numerous studies both in humans and in mice. The current study involves patients with congenital GH/IGF-1 deficiency, a population not yet investigated. The 2D:4D ratio was measured from hand x-rays and compared with normal hand x-rays taken from the Greulich & Pyle Atlas. The analyses of our results revealed that patients with congenital GH/IGF-1 deficiency show an identical 2D:4D ratio for both sexes, but a higher (more feminine) ratio than the normal population. These findings may be explained by a higher estrogen effect resulting from the absence of a functional GH-IGF-1 axis prenatally.

Health and Lifestyle of Adult Patients with Congenital Isolated Growth Hormone Deficiency Treated in Childhood.

BACKGROUND: Treatment of patients with childhood growth hormone deficiency is usually terminated at the end of puberty. Follow-up into adult age is rare, even more so in patients with congenital isolated growth hormone deficiency (cIGHD). OBJECTIVES: To assess the clinical and social characteristics of adults with cIGHD who received growth hormone (hGH) treatment in childhood. METHODS: Thirty-nine patients (23 men, 16 women) diagnosed in our clinic with cIGHD at 7 ± 4.2 years, and treated with hGH during childhood for 2-18 years, were followed into adulthood (mean age 30.7 ± 13.3 years). Ascertained detailed data were found for 32 patients. RESULTS: Mean ± SD height for males was 160.2 ± 10.6 cm and for females 146.4 ± 5.4 cm. All patients achieved full sexual development and 14 were married. After cessation of GH treatment and with advanced age all exhibited a progressive increase in adiposity to the degree of obesity. Twelve patients suffered from hyperlipidemia, 4 developed diabetes mellitus, and 5 have cardiovascular diseases. One patient died in an accident. None developed cancer. Of the 39 patients, 22 have an education level of high school or higher, and 2 are in special institutions. Most are employed in manual labor. CONCLUSIONS: Patients with congenital IGHD who do not receive early and regular replacement treatment are prone to lag in achieving normal height and suffer from educational and vocational handicaps.

The relationship between serum levels of prolactin and growth hormone in the early postnatal period.

BackgroundIn the neonatal period, the pituitary hormones including prolactin (PRL) and human growth hormone (hGH) are secreted in high amounts due to immature feedback mechanisms. As both hormones are secreted in part by the same somatomammotrophic cells, we investigated their relationship in newborns with respect to sex, gestational week, method of delivery, and anthropometric data.MethodsThe serum levels of PRL and hGH were measured in blood drawn from 225 newborns. The newborn data were extracted from medical records.ResultsA positive correlation was found between log-transformations of PRL and hGH (r=0.17; P=0.01; n=225), with a stronger correlation in newborns whose blood samples were taken more than 2 days after birth (r=0.42; P<0.001; n=130). Log-transformations of the PRL/hGH ratio demonstrated a positive correlation with the gestational week (r=0.39; P<0.001; n=200). Multiple regression analysis showed that 15% of the variance in the logarithm of this ratio is attributed to the gestational week.ConclusionIn newborns, serum PRL and hGH levels show a positive correlation that can be explained by common regulatory factors or a drift phenomenon. A higher gestational week is associated with a higher PRL/hGH ratio. Further studies are needed to look for possible confounders and to determine the PRL-hGH relationship in different conditions.

Growth, development, puberty and adult height of patients with congenital multiple pituitary hormone deficiencies.

OBJECTIVE: Congenital MPHD is a rare condition caused by mutations in pituitary transcription factors genes: PROP1, POU1F1 (PIT1), HESX1, LHX3, LHX4. DESIGN: We evaluated in a retrospective study the effects on growth and development in 29 patients with congenital MPHD (cMPHD), during hGH replacement therapy alone and combined with sex hormones. Twenty nine patients with cMPHD were included and diagnosed, treated and followed in our clinic from diagnosis to adult age. Measurements on growth and development were taken by the same medical team. RESULTS: Mean birth weight of 21/29 neonates was 3126 ± 536 g. Mean birth length of 7/29 neonates was 48.7 ± 2 cm. Neuromotor development was normal or slightly delayed. Mean age at referral was 9.5 ± 7 years (m), 6.7 ± 3.5 years (f) (p=0.17). Height (SDS) before treatment was -2.8 ± 1.0 (m), -2.8 ± 1.0 (f) (p=0.99). Mean age at initiation of hGH treatment was 9.9 ± 6.7 years (m), 10.3 ± 4.2 years (f) (p=0.85). Mean age at initiation of sex hormone treatment was 17.0 ± 3.5 years (m), 17.1 ± 2.3 years (f) (p=0.88). Penile and testicular sizes were below normal before and after treatment. Head circumference (SD) was -1.9 ± 0.9 before and -0.6 ± 1.8 at end of treatment (p<0.001). Adult height (SDS) reached -1.1 ± 0.6 (p<0.001) for both males and females. CONCLUSION: Despite the multiple pituitary hormone deficiencies including hGH, children with congenital MPHD present with a better auxological development than children with congenital IGHD or congenital IGF-1 deficiency. These findings may be due to irregular and incomplete hormone deficiencies increasing with progressive age and late initiation of puberty.

Triglyceride levels and risk of type 2 diabetes mellitus: a longitudinal large study.

The relationship between triglyceridemia and diabetes mellitus remains unclear. This study evaluated the risk of diabetes and impaired fasting glucose associated with a wide range of triglyceride levels. A longitudinal retrospective study was carried out employing data from a screening center between the years 2000 and 2012. Inclusion criteria were absence of diabetes at baseline and attendance at the center at least twice over a 5-year period. Participants were divided by fasting blood glucose level (normal/impaired) at the first visit. A total of 5085 participants were eligible for the study. Of the 4164 normoglycemic participants at baseline, 40 (0.96%) had diabetes and 998 (24%) had impaired fasting glucose by the end of the study. On stepwise logistic regression analysis, every 10 mg/dL increase in triglyceride level significantly increased the risk of diabetes by 4% and of impaired fasting glucose by 2% (p<0.001). This association held true even when rising triglyceride levels remained within the accepted normal range (<150 mg/dL, p<0.001). Sustained increments in serum triglyceride level, even within the accepted normal range, are an independent risk factor for diabetes mellitus and impaired fasting glucose in normoglycemic participants.

Genetic Mutations, Birth Lengths, Weights and Head Circumferences of Children with IGF-I Receptor Defects. Comparison with other Congenital Defects in the GH/IGF-I axis.

BACKGROUND: In recent years more and more genetic defects along the GHRH-GH-IGF-I axis have been reported. Mutations of the IGF-I receptor (R) are a rare abnormality of whom only the heterozygote progenies survive. OBJECTIVES: To summarize, from the literature, data on birth length, weight and head circumference of neonates with IGF-I-R mutations, and to correlate the data with that of other types of mutations in the GH/IGF-I axis. SUBJECTS: Sixty seven neonates from 24 published articles were included and forty seven different mutations of the IGF-I (R) located on chromosome 15 have been identified. RESULTS: Mean (±SD) birth length (BL), available for 26, (10 M, 16F) neonates with a gestational age of 34-41weeks, was 44.2±4cm; one was premature (30cm at 31 weeks). There was a significant correlation between birth length and gestational age (GA) r=0.71 (p>.001). Mean birth weight (BW) of 41 neonates (18M, 23F) was 2388±743gr. Two premature neonates weighed 650gr and 950gr respectively. The BW correlated significantly with gestational age, (males: r=0.68; p=0.007, females: r=0.49; p=0.024). The BMI of 25 neonates ranged from 6 to 13. In 22 records marked microcephaly was ascertained or stated. Nine of 16 mothers were short (133 -148cm), m±SD = 150.5±7.3cm.

Growth, development, puberty and adult height before and during treatment in children with congenital isolated growth hormone deficiency.

OBJECTIVE: To describe the growth, development and puberty in children with congenital IGHD before and during hGH treatment. SUBJECTS: Patients with cIGHD treated by hGH between the years 1958-1992. SETTING: All patients were diagnosed, treated and followed in our clinic. PARTICIPANTS: Data were found in 37/41 patients (21 m, 16 f). 34 had hGH-1A deletions, 7 GHRH-R mutations. Patients, referred after age 25, were excluded. RESULTS: The birth length of 10/37 neonates was 48.29±2.26 (44-50) cm. Birth weight of 28/37 neonates was 3380±370 g (m), 3230±409 g (f). Neuromotor milestones were variable. Age at referral was 5.7±4.2 y (m) and 5.6±3.8 y (f). Initiation of hGH treatment (35µg/kg/d) was 7.5±4.8, (0.8-15.08) y (m) and 6.8±4.36 (0.8-16.5) y (f). Height SDS increased from -4.3 to -1.8 (m) and from -4.5 to -2.6 (f). Head circumference increased from -2.6 to -1.3 (m) and from -2.7 to -2.3 (f). BMI increased from 15.8 to 20.6 (m) and from 15.5 to 20.4 (f). There was a negative correlation between age of hGH initiation and change in height SDS (r=-0.66; ρ<0.01), same for bone age (r=-0.69; ρ<0.01). Upper/lower body ratio decreased from 2.5±2.1 (m±SD) to 1.08±0.1 (ρ<0.0005). Puberty was delayed in boys, less so in girls. Mean age of 1st ejaculation (14 m) was 17.6±2.2 y and of menarche (14 f. was 13.7±1.2 y. In both genders there was a positive correlation between age at start of hGH and age at onset of puberty (r=0.57; ρ<0.01). All reached full sexual development but the penile and testicular sizes were below normal. There was a positive correlation between length of hGH treatment and final testicular volume (r=0.597, ρ=0.05) and a negative correlation between the age at initiation of hGH treatment and final testicular volume(r=-0.523, ρ=0.018). All were obese and hGH treatment increased the adiposity progressively (r=0.418, ρ=0.013). CONCLUSION: Early diagnosis and treatment of cIGHD enables normal or near normal growth, development and puberty.

Biphasic response of subscapular skinfold thickness to hGH or IGF-1 administration to patients with congenital IGHD, congenital MPHD and Laron syndrome.

OBJECTIVE: To evaluate changes in adiposity in congenital GH/IGF-1 deficient children during hGH or IGF-1 treatment. SUBJECTS AND METHODS: 27 children with congenital isolated growth hormone deficiency (cIGHD) treated with hGH for 2.5-€“15.2 years (mean 10.0 ± 3.4), 18 children with congenital multiple pituitary hormone deficiency (cMPHD), treated with hGH for 2.3-€“17.9 years (mean 6.1 ± 4.3), and 14 children with Laron syndrome (LS) treated with IGF-1 for 1.2-12 years (mean 5.5 ± 3.7) were studied. Changes in the degree of adiposity were evaluated by subscapular skinfold thickness (SSFT), before, during and up to 2 years after treatment. All the children had various degrees of obesity. RESULTS: During the pretreatment period, cIGHD patients showed little changes in SSFT (P = 0.45), cMPHD and LS patients showed an increase in SSFT (P = 0.01, P = 0.06 respectively). During the initial 0.6-1.1 years of hGH/IGF-1 treatment, the SSFT decreased in all 3 groups (P < 0.001), while during subsequent years a significant increase in SSFT (P < 0.001) was observed, in all types of patients, notably in females. Only the cIGHD patients demonstrated a significant correlation between the degree of SSFT decrease and height SDS gain (R = -ˆ’0.56, P = 0.002) in the first period of treatment. CONCLUSIONS: Short term replacement therapy of 0.6-€“1.1 years with either hGH or IGF-1, induced a reduction in subscapular subcutaneous fat whereas prolongation of therapy led to an increase in the subcutaneous fat.

Bedside neuropathy disability score compared to quantitative sensory testing for measurement of diabetic neuropathy in children, adolescents, and young adults with type 1 diabetes.

BACKGROUND: While regular yearly screening for diabetic retinopathy and nephropathy is well established in patients with diabetes mellitus, there are no standardized diagnostic tests for diabetic peripheral neuropathy (DPN). In the present study, we compared the bedside neuropathy disability score (NDS) with quantitative sensory testing (QST) for screening for DPN in youth with type 1 diabetes mellitus. METHODS: One hundred sixty-six patients aged 10 to 34 years (median 21 years) were evaluated for DPN by the NDS and QST. Quantitative sensory testing was also done in 43 healthy, age-matched controls. Diabetic peripheral neuropathy grade by both methods was correlated with disease-related variables. RESULTS: On QST, the diabetic group had significantly higher mean scores for vibration (P<.001) and warm sensation (P<.01) than controls, and lower scores for cold sensation (P<.05); however, there was a great degree of overlap. The NDS significantly correlated with the vibration threshold, but not with the warm and cold thresholds. The NDS significantly correlated with age at testing, diabetes duration, and long-term and current HbA1c levels (P<.001), and with the presence of microalbuminuria and diabetic retinopathy (P<.001). Analysis of the QST variables yielded significant correlations of vibration and warm sensation with age at testing (P<.001, P<.05, respectively) and of vibration with diabetes duration (P<.001) and retinopathy (P=.05); none of the quantitative tests correlated with glycemic control. CONCLUSIONS: The stronger association of the NDS with glycemic control and other microvascular complications compared to the perception thresholds, and its shorter time of performance and lack of costly equipment, may make the NDS the preferred method for measuring DPN in this population.

Foot length before and during insulin-like growth factor-I treatment of children with laron syndrome compared to human growth hormone treatment of children with isolated growth hormone deficiency.

OBJECTIVE: To compare foot length deficits between patients with Laron syndrome (LS) (primary growth hormone [GH] insensitivity) and congenital isolated GH deficiency (IGHD) and their response to replacement therapy with insulin-like growth factor-I (IGF-I) and hGH, respectively. DESIGN: Data for the study were collected from the records of nine children with LS (3 M, 6 F) 7.8 +/- 4.8 years old (mean +/- SD), and nine children with IGHD (3 M, 6 F), 3.8 +/- 3.3 years old. Fifteen non-treated adult patients with LS were also included in the study. METHODS: Measurements of foot length were recorded without treatment and monitored during 9 years of treatment in the children and in the untreated adult patients. For statistical analysis the non-parametric Mann-Whitney U test was used. RESULTS: With almost similar basal values in growth deficit and pre-treatment growth velocities, the achievements towards norms after 9 years of treatment were greater in the patients with IGHD than in the patients with LS: foot length reached -1.4 +/- 0.8 vs. -3.3 +/- 1.0 SDS (mean +/- SD), and body height -2.2 +/- 1.0 vs. -3.9 +/- 0.5 SDS. The difference between the two groups could be due to the initiation of replacement therapy in the patients with IGHD at a younger age. Adult foot size of untreated patients with LS is small but less retarded than the height deficit. CONCLUSIONS: Both IGF-I and hGH are potent growth stimulating hormones of linear growth and acrae as exemplified by foot growth.

Body composition in untreated adult patients with Laron syndrome (primary GH insensitivity).

OBJECTIVE: To quantify body adiposity and its distribution in untreated adult patients with Laron syndrome (LS; primary GH insensitivity) caused by molecular defects of the GH receptor gene or postreceptor pathways and characterized by dwarfism, obesity, insulin resistance and hyperlipidaemia. PATIENTS: Eleven LS patients (seven females and four males) aged 28-53 years were studied. Seven healthy males and six healthy females served as controls. MEASUREMENTS: Body composition of the total body trunk, upper and lower extremities was determined using dual-energy X-ray absorptiometry (DEXA). Statistical analysis using an analysis of variance (anova) and Mann-Whitney nonparametric methods was performed separately in males and females. RESULTS: Percentage body fat in the LS patients was much higher (P < 0.01) than that in the control population and the female LS patients were significantly more obese (59% total body fat) than the male patients (39% total body fat) (P < 0.002). It was also evident that in these types of patients with markedly increased body fat and decreased muscle and bone mass, body mass index (BMI) does not accurately reflect the body composition. CONCLUSIONS: Lifelong congenital IGF-I deficiency leads to extreme adiposity.

Insulinlike growth factor I affects ocular development: a study of untreated and treated patients with Laron syndrome.

OBJECTIVE: To evaluate the ocular dimensions in patients with primary growth hormone receptor insensitivity (Laron syndrome [LS]) and to study the effect of supplemental insulinlike growth factor I (IGF-I) on ocular growth. DESIGN: Retrospective case series. PARTICIPANTS: Twelve patients with LS, 8 untreated (LS group) and 4 treated (LS-T group) with supplemental IGF-I, and 30 healthy controls. METHODS: Ocular dimensions and refraction were measured, and a full ophthalmologic examination was performed. MAIN OUTCOME MEASURES: Differences in the average ocular dimension data among IGF-I-treated patients, untreated ones, and controls. RESULTS: The average axial length of eyes in the LS group was 21.94 mm (standard deviation [SD], 0.81). Corresponding values for the LS-T and control group eyes were 22.53 mm (SD, 1.74) and 23.20 mm (SD, 1.35) respectively. The average anterior chamber depth of eyes in the LS group was 2.55 mm (SD, 0.26). Corresponding values for eyes in the LS-T and control groups were 3.48 mm (SD, 0.09) and 3.84 mm (SD, 0.16) respectively. The average lens thickness of eyes in the LS group was 4.56 mm (SD, 0.36). Corresponding values for the LS-T and control groups were 3.77 mm (SD, 0.23) and 3.51 mm (SD, 0.25), respectively. The average corneal curvature of eyes in the LS group was 46.9 diopters (D) (SD, 2.32). Corresponding values for the LS-T and control groups were 47.6 D (SD, 2.83) and 44.4 D (SD, 1.5), respectively. CONCLUSIONS: Insulinlike growth factor I seems to be an important regulator of ocular growth as documented in patients with primary growth hormone insensitivity. The mechanism of this observation should be investigated further.

Glycemic patterns detected by continuous subcutaneous glucose sensing in children and adolescents with type 1 diabetes mellitus treated by multiple daily injections vs continuous subcutaneous insulin infusion.

OBJECTIVE: To compare glycemic patterns by mode of therapy in children with type 1 diabetes mellitus using the Continuous Glucose Monitoring System (CGMS). DESIGN: Open randomized crossover comparing 3(1/2) months of multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII). SETTING: Tertiary care, university-affiliated medical center. Patients Twenty-three children and adolescents with type 1 diabetes mellitus. INTERVENTIONS: The CGMS was applied for 72 hours after 1 month and at the end of each study arm. MAIN OUTCOME MEASURES: Hemoglobin A(1c) levels and glucose level profiles were compared between the 2 study arms and the 2 sensor applications for each arm. RESULTS: The arms were similar for mean (SD) hemoglobin A(1c) levels (CSII, 8.0% [0.8%]; and MDI, 8.2% [0.8%]) and glucose levels. Areas under the curve were significantly larger during MDI for nocturnal and 24-hour hypoglycemia (P =.01 and.04, respectively) and for postprandial hypoglycemia and hyperglycemia (P =.03 and.05, respectively). The rate of hyperglycemia increased during CSII (P =.03), but 24-hour duration and area under the curve for hyperglycemia were similar. Compared with the first CGMS reading in each arm, the second had a longer mean duration of postprandial within-target glucose levels (P =.04), tendency for lower rate of diurnal hypoglycemic events (P =.1), shorter duration of nocturnal hypoglycemia (P =.05), and smaller 24-hour area under the curve for hypoglycemia (P =.04). CONCLUSIONS: Intensive treatment with CSII seemed to be associated with slightly better prebreakfast, postprandial, and within-target glucose profiles than MDI, as well as a smaller area under the curve for hypoglycemia. Lower hypoglycemia-related variables in the second sensor reading in each arm indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia.

Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens in children with type 1 diabetes: a randomized open crossover trial.

OBJECTIVE: To compare the efficacy and feasibility of continuous subcutaneous insulin infusion (CSII) with multiple daily insulin injections (MDI) in children with type 1 diabetes. METHODS: The study sample included 23 children (10 males) aged 9.4 to 13.9 years with type 1 diabetes. An open randomized crossover design was used to compare 3.5 months of CSII to 3.5 months of MDI therapy for the following variables: diabetic control, incidence of adverse events, daily insulin requirement, body mass index standard deviation scores, treatment satisfaction, and quality of life. RESULTS: The changes in HbA(1c) and fructoseamine values were similar in the 2 arms over time. At the end of the study, mean HbA(1c) level measured 8.05 +/- 0.78%. There were no differences between the treatment modes in frequency of symptomatic hypoglycemic or hyperglycemic events. There was 1 event of severe hypoglycemia during pump therapy and 3 during MDI, yielding a rate of 0.26 events per patient-year. There were no episodes of diabetic ketoacidosis. Body mass index standard deviation scores decreased during CSII and increased during MDI, as did mean insulin dose. Patients expressed a higher treatment satisfaction from CSII than MDI, although there was no difference in quality of life between the 2 modes. CONCLUSIONS: Intensive insulin therapy by either insulin pump or MDI is safe in children and young adolescents with type 1 diabetes, with similar diabetes control and a very low rate of adverse events. We suggest that both modes be available to the diabetic team to better tailor therapy.

Effects of insulin-like growth factor-I deficiency and replacement therapy on the hematopoietic system in patients with Laron syndrome (primary growth hormone insensitivity).

BACKGROUND: Primary insulin-like growth factor-I (IGF-I) deficiencies, such as in Laron syndrome (LS), are a unique model in man to study the consequences resulting from defects in growth hormone (GH) signal transmission. OBJECTIVE: To assess retrospectively the effect of IGF-I deficiency and its therapy on the various cells of the hematopoietic system as reflected by peripheral blood counts. PATIENTS AND METHODS: Two groups of patients were studied. The first group consisted of 11 untreated patients with LS, seven males and four females, who were followed from childhood into adult age. Average age at the time of data analysis was 45.4 +/- 9.6 years. The second group included ten children with LS, six males and four females, who received IGF-I replacement therapy for an average period of 6 years, ranging in age from 0.9-11 years. The mean age at initiation of therapy was 6.9 +/- 4.28 years. Only the seven children treated for 5 years or more were included in the analysis. Data on blood counts were collected from the patients' charts. Blood samples were drawn at baseline, weekly during the first month, once a month during the first year, and once every 3 months thereafter. Statistical analysis of the change over time was performed using repeated measures ANOVA. RESULTS: Children with LS had red cell indices in the lower normal range and an elevated monocyte count. A statistically significant rise in red blood cell (RBC) indices was seen in children during IGF-I therapy: RBC rose from 4.66 x 10(6)/ml to 4.93 x 10(6)/ml (p = 0.011); hemoglobin from 11.55 g/dl to 13.01 g/dl (p < 0.001); hematocrit from 34.94% to 38.52% (p = 0.007), and mean corpuscular volume from 72.27 fl to 79.93 fl (p < 0.001). The platelet count diminished significantly during IGF-I therapy from 316 x 10(3)/ml to 219 x 10(3)/ml (p = 0.02), and the monocyte count from 0.74 x 10(3)/ml to 0.49 x 10(3)/ml (p < 0.001). CONCLUSIONS: The present investigation, the first of its kind in this syndrome, confirms that IGF-I has a strong stimulatory effect on erythropoiesis. In addition, IGF-I therapy had a reducing effect on monocytes and platelets, an effect not previously described. The mechanism by which IGF-I mediates these effects needs further elucidation.

Decreased cortisol secretion in nonclassical 21-hydroxylase deficiency before and during glucocorticoid therapy.

OBJECTIVE: The cortisol response in patients with nonclassical 21-hydroxylase deficiency (NC21OHD) was assessed before and during hydrocortisone therapy and the findings were related to genotype. DESIGN: Comparative study. METHODS: The study sample comprised 41 patients (10 males) with NC21OHD, divided into two groups according to the genetic analysis of the CYP21 gene: Group A carried two mild mutations (n = 29), and Group B were compound heterozygotes for one mild and one severe mutation (n = 12). The 250 microg short ACTH test was performed at diagnosis. To evaluate the degree of treatment-induced suppression of adrenal function, 31 patients also underwent the 1 microg/1.73 m2 ACTH test during hydrocortisone therapy. Basal and stimulated cortisol levels and the increment in cortisol response were compared between Groups A and B and between the whole patient sample and healthy controls (32 subjects for the 250 microg test and 29 for the 1 microg/1.73 m2 test). RESULTS: The basal, stimulated, and incremental cortisol levels were similar in Groups A and B; therefore, all the patients were considered together. At diagnosis, the basal cortisol levels were similar in the patients and controls, but the stimulated and incremental cortisol levels were significantly lower in the patients (p <0.001 for both). During hydrocortisone therapy, the patients had slightly higher basal cortisol levels than the controls (p = 0.04), but significantly lower stimulated and incremental cortisol levels (p <0.001 for both). CONCLUSIONS: Cortisol levels in NC21OHD are similar in patients carrying two mild mutations and in compound heterozygotes for one mild and one severe mutation. Stimulated and incremental cortisol levels in response to the short ACTH test might be decreased not only during but also before hydrocortisone therapy. Therefore, coverage with a stress dose of hydrocortisone during serious intercurrent illness or surgery is recommended in patients with NC21OHD, especially those previously treated with corticosteroids.