Urinary 17α-hydroxyprogesterone in management of 21 -hydroxylase deficiency

Objectives: The study was designed to assess the reliability of measurement of 24-hour urinary 17α-hydroxyprogesterone (17-OHP) by radio-immunoassay (RIA) as an alternative biochemical assessment for monitoring the treatment of congenital adrenal hyperplasia (CAH) due to 21 -hydroxylase deficiency (21 -OHD) and to assess the need for sample purification by column chromatography to improve assay specificity.
Methodology: Morning serum 17-OHP was measured using RIA and 24-hour urinary pregnanetriol using gas chromatography. Twenty-four-hour urinary 17-OHP was measured in samples from 17 prepubertal patients with CAH due to 21 -OHD, and 20 normal prepubertal children as controls. In 24 urine samples, RIA of 17-OHP was performed with and without column chromatography.
Results: There was a good correlation between 24-hour urinary 17-OHP and 24-hour urinary pregnanetriol (r = 0.962, P <0.01) and between 24-hour urinary 17-OHP and morning serum 17-OHP ( r = 0.955, P <0.01). There was no significant difference in the RIA of the urine samples with and without purification by column chromatography.
Conclusions: The measurement of 24-hour urinary 17-OHP is a reliable alternative for the biochemical monitoring of 21-OHD, and RIA specificity is unaffected by omission of column chromatography.     

Correlation of blood-spot 17-hydroxyprogesterone daily profiles and urinary steroid profiles in congenital adrenal hyperplasia

OBJECTIVE: To compare the value of blood-spot 17-hydroxyprogesterone (17-OHP) daily profiles and urinary steroid excretion in untreated and treated patients with congenital adrenal hyperplasia (CAH). PATIENTS: Ten patients with CAH were investigated during steroid replacement therapy (Group 1), and 11 patients were investigated without treatment (Group 2). METHODS: Capillary blood samples were collected for measurement of blood-spot 17-OHP values by non-chromatographic radioimmunoassay. Steroid profiles of 24-h urine samples were analyzed by gas chromatography. RESULTS: There was a close correlation between the individual daily means of blood-spot 17-OHP measurements and the pregnanetriol/ tetrahydrocortisone ratio in both groups of patients (Group 2: r=0.839, p<0.001; Group 1: r=0.686, p<0.001). Almost the same correlation was found between the blood-spot 17-OHP value and the sum of three 17-hydroxyprogesterone metabolites/the sum of three cortisol/cortisone metabolites ratio (Group 2: r=0.918, p<0.001; Group 1: r=0.741, p<0.001). CONCLUSIONS: Blood-spot 17-OHP measurements and 24-h urinary steroid profile have the same impact in identification and monitoring therapy of children with CAH.     

Treatment of central precocious puberty with an intranasal analogue of GnRH (Buserelin)

One boy and 13 girls with central precocious puberty were treated for 1 year using Buserelin, a GnRH analogue, given intranasally (0.3 mg, four times a day). After 1, 3 and 12 months of therapy, the gonadotropin responses to GnRH were abolished in all the patients whereas mean basal serum concentrations of luteinizing hormone (LH) remained similar to those of pubertal controls. During Buserelin treatment, genital development in the boy and breast development in the girls showed no further progress or some regression. In the boy, serum testosterone levels returned to prepubertal values. In the girls, serum oestradiol levels were variable and, in four of them, vaginal smears showed the persistence of a slight oestrogenic effect during therapy. Pelvic ultrasonography did not show any significant variation in ovarian and uterine lengths. Among the 14 patients, 3 had some progression of pubic hair development, irrespective of serum dehydroepiandrosterone sulphate (DHEAS) levels. In eight patients previously treated with cyproterone, elevated prolactin levels were observed before and during the first month of Buserelin administration. During treatment, mean height velocity was markedly reduced from 11.6 to 6.1 cm/year and mean bone age velocity (±1 SD) was 0.85±0.38 year/year. After 1 year of treatment, the differences in predicted adult height ranged between −0.74 and +1.04 SDS (standard deviation score). These differences were inversely related (r=−0.72) to the prognosis of adult height calculated before treatment. We conclude that, in central precocious puberty, intranasal administration of Buserelin, 1.2 mg/day, may arrest sexual development and reduce height velocity and bone maturation. Improvement of adult height prognosis may occur, especially when it was markedly impaired before treatment.     

Management of congenital adrenal hyperplasia using serum dehydroepiandrosterone sulfate and 17-hydroxyprogesterone concentrations.

Simultaneous serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) and 17-hydroxyprogesterone (17-OHP) were compared with urinary 17-ketosteroid (17-KS) and pregnanetriol (PT) excretion during therapy in 18 prepubertal patients with the 21-hydroxylase deficiency form of congenital adrenal hyperplasia (CAH). Patients were classified into those in good, poor, or questionable control on the basis of clinical examination, skeletal age, and 17-KS and PT excretion. During therapy, use of serum steroid concentrations was found to be nearly as accurate in judging adequacy of control as use of urine steroid concentrations. Of 34 evaluations, a definite assessment of adequacy of control could be arrived at 25 times using urinary values and 22 times using both serum DHEA-S and 17-OHP concentrations. DHEA-S concentration responded sluggishly when treatment was not adequate, being greater than 100 microgram/dl only in patients significantly undertreated. It was never elevated in well-controlled patients. Mid-afternoon 17-OHP concentrations were less than 200 ng/dl in well-controlled patients but readily escaped suppression and could not be used to differentiate poor from borderline control or from temporary noncompliance. Therefore, an increases DHEA-S concentration indicated poor control and a suppressed 17-OHP concentration indicated good control. The combination of normal DHEA-S level with elevated 17-OHP level, however, did not permit exact evaluation of the degree of control. Of significance is that not all patients with CAH present with an elevated DHEA-S concentration, and only in those in whom an elevated level has been documented can DHEA-S level be used as an index of control during therapy.     

Compensatory maturational deceleration of growth or “catch-down growth” in patients with congenital adrenal hyperplasia after delayed initiation of therapy

The growth pattern is reported of 16 patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency in whom therapy was started after the age of 3 years.Treatment was initiated at a mean chronological age (CA) of 4.7 years (range 3.0–7.2) and at a mean bone age (BA) of 10.4 years (range 10.2–13.2). It consisted of hydrocortisone (mean dosage 26 mg/m²) or prednisone (8.7 mg/m²) in all, and of fluorohydrocortisone (0.05–0.1 mg daily) in five patients. At the last examination the mean duration of therapy was 5.2 years, the mean CA 10.0 years, and the mean BA 12.6 years. In 13 of the 16 patients a catch-down growth pattern was observed, which was characterised by a decrease in height (expressed, as SDS) for CA, a deceleration of bone maturation and increase of height (SDS) for BA, and an improvement in predicted height (Bayley-Pinneau).Abbreviations CAH Congenital adrenal hyperplasia - CA chronological age - BA Bone age - SDS Standard deviation score     

17-Hydroxyprogesteron im Speichel

Background

In patients with classic congenital adrenal hyperplasia (CAH) the estimation of morning 17-alpha-hydroxyprogesterone (17-OHP) in saliva was used for monitoring therapy.

Patients and methods

In 47?patients with well-controlled CAH and 5?patients in whom treatment failure was suspected 17-OHP was estimated every 3?months at outpatient clinics. The values were analyzed retrospectively according to the age of the patients.

Results

At the start of the observation period the age of the patients was 10.5?±?5.3?years and at the end 20.5?±?5.8?years; thus, the length of observation was 10.0?±?2.8?years. In every patient 30.3?±?10.0 values had been collected, resulting in a total number of 1,424 values which were analyzed. Desired median levels up to 0.6?nmol/l could be achieved in 21 of 47 patients. Reasons for higher values observed at all ages were problems with compliance, nonoptimal doses of corticosteroids, or treatment failure. In 24.5% of necessary alterations of dosage, 17-OHP levels proved to be a valuable tool in addition to the clinical investigation.

Conclusions

For monitoring purposes, salivary 17-OHP levels collected stressless at home are sufficient. It is possible to achieve results in the normal range. In patients with constant or repeatedly high levels it proved difficult or impossible to decide between poor compliance and treatment failure.     

Adult height in children with short stature and idiopathic delayed puberty after different management

By retrospectively collecting data from nine Italian centres of pediatric endocrinology, we assessed the different management and final outcome of children with short stature and idiopathic delayed puberty. Data were obtained in 77 patients (54 males, 23 females) diagnosed and followed-up in the various centres during the last 15 years. Inclusion criteria were short stature at initial observation and idiopathic delayed puberty diagnosed during follow-up. At first observation, age was 13.8 ± 1.0 years and height standard deviation score (SDS) was –2.6 ± 0.6 in males. In females age was 13.1 ± 0.9 years and height SDS –2.6 ± 0.4. Local diagnostic and therapeutic protocols included testing for growth-hormone deficiency (six centres) and treatment in case of deficiency or, in the remaining centres, testosterone or no treatment in males, and no treatment in females. At diagnosis, both in males and in females, the auxological features (height SDS, target height SDS and bone age delay) were similar in the patients treated with growth hormone, testosterone or not treated. Overall 32 patients received growth hormone (25 males, 7 females), 33 no treatment (17 males, 16 females) and 12 testosterone. There was no difference in the adult height of males and females in the different treatment groups. In males there were no differences between adult and target height SDSs (growth hormone-treated 0.31 ± 0.79, untreated 0.10 ± 0.82, testosterone-treated 0.05 ± 0.95), between adult and initial height SDSs (growth hormone-treated 1.70 ± 0.93, untreated 1.55 ± 0.92, testosterone-treated 1.53 ± 1.43) and percentage of subjects with adult height above target height. In females, there were no differences between adult and target height SDSs (growth hormone-treated –0.49 ± 1.13; untreated 0.10 ± 0.97) and between adult and initial height SDSs (growth hormone-treated 1.76 ± 0.92; untreated 1.77 ± 0.98), whereas a significantly higher percentage of patients remained below target height in the growth hormone-treated group (6/7, 85.7% vs 5/11, 31.3%) (P = 0.02). In conclusion, the diagnostic and therapeutic management of the patients with short stature and delayed puberty is different among Italian pediatric endocrinologists. Our data do not support the usefulness of growth-hormone therapy in improving adult height in subjects with short stature and delayed puberty, particularly in the female sex.     

Arm span, serum IGF-1 and IGFBP-3 levels as screening parameters for the diagnosis of growth hormone deficiency in patients with myelomeningocele – preliminary data

Short stature is a common problem in patients with myelomeningocele (MMC) and hydrocephalus. We evaluated auxological and laboratory parameters to differentiate short stature due to neurological defect from short stature additionally caused by growth hormone deficiency (GHD). In a group of 38 prepubertal patients with MMC and hydrocephalus aged 3.8–11.0 years, auxological parameters, including arm span and bone age, and serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured. Patients with normal supine length (n = 15) had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal (≥ 10th percentile) in 14/15 patients. Twenty-three MMC patients had short stature (height SDS < −2), 11/23 patients had reduced arm span (SDS < −2), and 12/23 had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal in 10/12 of short statured patients with normal arm span, but low (<10th percentile) in those patients with reduced arm span (IGF-1: 8/11 patients, P<0.05; IGFBP-3: 9/11 patients, P<0.005). In 7/11 short statured MMC patients with reduced arm span and low serum IGF-1 and IGFBP-3 levels, growth hormone secretion was investigated. All had a disturbed growth hormone secretion (GHD: n = 4; neurosecretory dysfunction: n = 3). Conclusion Arm span, serum IGF-1 and IGFBP-3 levels are estimated to be appropriate screening parameters for GHD in patients with MMC. Initiating growth hormone therapy should be considered not only according to endocrine findings but also with respect to neurological and orthopaedic anomalies. Received: 27 March 1997 / Accepted: revised form 18 September 1997     

Type I glycogen storage disease: favourable outcome on a strict management regimen avoiding increased lactate production during childhood and adolescence

Our objective was to evaluate the long-term effects of dietary therapy of tyep I glycogen storage disease which avoids increased lactate production during childhood and adolescence. In order to suppress hepatic glucose and increased lactate production consistently day and night, the treatment regimen included nocturnal intragastric feeding of glucose polymer during childhood and adolescence. The aim was to keep the blood glucose concentration in the “high normal range” (4.3–5.5 mmol/l) and the lactate concentration in urine in the normal range (<0.06 mol/mol creatinine). The amounts of dietary carbohydrate required decreased in an age-related manner from 11.9±1.3 mg/kg body weight per min by day and 6.9±0.9 mg/kg body weight per min by night at 1 year of age to 5.2±1.0 and 2.9±1.2 mg/kg body weight per min, respectively, at the age of 16 years. In 15 infants, therapy started at 5.8±3.2 months of age and induced catch up growth over 1–2 years by which time the mean height SDS increased from −1.02±0.91 to −0.19±1.07. In the well controlled patients, further growth continued within that range. From 12 years of age, mean height SDS was in line with the respective mean SDS of mid-parental target height. The plasma lipid concentrations were markedly reduced, but were not brought into the normal range. So far, no adolescent showed liver adenoma or renal damage. Four patients with poor metabolic control due to poor compliance with treatment (frequently subnormal plasma glucose concentrations, severe hypoglycaemia, and increased urinary lactate excretion) showed retardation of growth and bone maturation.Conclusion: avoiding increased lactate production by keeping the blood glucose concentration permanently in the “high normal range” seems to be crucial for growth according to the genetic potential. Published online: 22 August 2002     

Final height, gonadal function and bone mineral density of adolescent males with central precocious puberty after therapy with gonadotropin-releasing hormone analogues

Few data are available on the outcome of boys with central precocious puberty (CPP) treated with gonadotropin-releasing hormone (GnRH) analogues. We report on final height, endocrine and exocrine testicular function, and bone mineral density (BMD) in nine males (age 16.7 ± 1.5 years) treated with GnRH analogues from the age 6.0 ± 1.8 years for a mean period of 5.6 ± 2.4 years. The following parameters were evaluated: final height, serum gonadotropin and gonadal steroid levels, spermarche, semen analysis, area and volumetric BMD. Final height (−0.4 ± 1.1 SDS) was significantly higher than pre-treatment predicted adult height (−2.0 ± 1.2 SDS) and not significantly different than midparental height (−0.1 ± 0.8 SDS). Pubertal response of gonadotropins to GnRH test occurred within 1.5 years (mean 0.7 ± 0.4 years) and spermarche (n=7) from 0.7 to 3 years (1.8 ± 0.9 years) after the discontinuation of GnRH analogue therapy. No alteration in semen analysis was found (n=6, sperm count, 10⁶/ml: 52.0 ± 18.7; normal motility (%): 49.5 ± 18.7; atypical morphology (%): 44.5 ± 11.4). Area and volumetric BMD were not reduced (0.2 ± 1.0 SDS and −0.1 ± 0.9 SDS, respectively). Conclusion Long-term treatment with gonadotropin-releasing hormone analogues improves final height in boys with central precocious puberty. Post-therapy data demonstrating normal endocrine and exocrine testicular function support the safety of gonadotropin-releasing hormone analogues on reproductive function. Long-term pharmacological suppression of testicular function in childhood does not impair bone mineral density in late adolescence. Received: 4 May 1999 / Accepted: 30 November 1999     

Growth hormone therapy in Silver Russell Syndrome: 5 years experience of the Australian and New Zealand Growth database (OZGROW)

Data were analysed on 33 children (22 males) with Silver Russell syndrome treated with growth hormone for periods up to 5 years. Baseline data (medians) at commencement of growth hormone (GH) therapy were age 6.7 years, bone age delay 1.7 years, height standard deviation score (SDS)-3.2, weight SDS –3.1, and growth velocity 5.7 cm/ year. All were prepubertal. Median birth weight SDS for gestational age was –3.2. GH was commenced at 14 IU/m² per week and subsequently adjusted according to response. Growth velocity and growth velocity SDS for chronological age (CA) improved over baseline and gains in height SDS for CA were 1.0, 1.5 and 1.8 SD over 3, 4 and 5 years respectively (P < 0.001). No significant increase in height SDS for bone age was observed. Increased GH doses were required after the 1st year to maintain growth rates. Mean bone age advancement was 3.1 years after 3 years of treatment, and 6.0 years after 5 years treatment. Younger age was a predictor of the growth response over the 1st year. Predictors of response after 3 years were catch-up growth, low weight SDS at birth and low height SDS for CA. Age at onset of puberty was normal, but height at onset of puberty was lower than normal means. Conclusion We have demonstrated significant improvement in growth in Silver Russell syndrome after 3 years of GH therapy, however data on estimated mature height and final height are insufficient to conclude final outcomes. Further follow up is required to assess the long-term benefit. Received: 19 July 1995 Accepted: 4 March 1996     

Growth in childhood thyrotoxicosis

Childhood thyrotoxicosis is an uncommon condition. To investigate the effect of thyrotoxicosis on the growth of children and to detect possible influence of the disease on their final height, 105 Chinese children (90 girls; 15 boys) with thyrotoxicosis were studied longitudinally from diagnosis. At presentation their mean age was 11.57 years. Their height and weight measurements were converted to standard deviation scores (SDS) using normal height and weight-for-height reference standards for Chinese children established in Hong Kong. Their mean height SDS at diagnosis was +0.73. Bone age assessment at diagnosis was done in 48 girls and 8 boys and their mean ± S.D. bone development quotient was 1.16 ± 0.11. A total of 53 girls have reached adult height and their mean height was 161.3 cm, corresponding to a SDS of +0.63. Their final heights significantly exceeded their target heights. Conclusion This study demonstrates that children with thyrotoxicosis were tall for age and their bone ages were advanced at presentation. They continued to be tall for age after starting treatment and they achieved final heights exceeding their target height. Received: 4 January 1999 / Accepted in revised form: 23 March 1999     

Endocrinology and auxology of sibships with non-classical congenital adrenal hyperplasia.

The symptoms, auxological characteristics, and stimulated 17-hydroxyprogesterone (17-OHP) concentrations in a group of patients with non-classical 21-hydroxylase deficiency (NCCAH) were compared with those of their siblings. Ten index cases consisting of nine females and one male patient aged 3-33 years and 16 siblings were studied. In the sibling group five subjects were slightly virilised and of these, two females were found to have NCCAH according to their stimulated 17-OHP concentrations. The remaining nine siblings, who were not virilised, all had normal stimulated 17-OHP concentrations. Among the total NCCAH group (index cases and affected siblings) eight patients had the diagnosis made within two years of the onset of symptoms. In four patients diagnosis was delayed until adulthood. In seven patients investigated, bone age was significantly increased before treatment. The mean height and body mass index Z scores of the affected patients as a total group or when divided according to skeletal maturity were not significantly different from either the normal mean or from their unaffected siblings. Virilised siblings of patients with NCCAH should have stimulated 17-OHP levels measured to exclude the disease. Patients with NCCAH do not appear to be at risk of short adult stature despite increased bone age in childhood.     

Growth hormone secretion, puberty and adult height after cranial irradiation with 18 Gy for leukaemia

The dose of prophylactic cranial irradiation given to patients for acute lymphoblastic leukaemia has been decreased from 24 to 18 Gy, but the beneficial effect of this decrease on growth is controversial. This study compares the growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at 3.7 ± 0.3 (SE) years, and routinely evaluated 5.4 ± 0.4 years after irradiation to define the indications for GH treatment in these patients. Of these, 63% had a low GH peak (<10 μg/l) after one (22 cases) or two (17 cases) stimulation tests. The plasma concentrations of insulin-like growth factor I and its GH-dependent binding protein were normal for age in all but two cases. The height changes between irradiation and evaluation were correlated with the GH peaks (P < 0.03) and were concordant, except in patients with early puberty. This occurred in 16 patients including all 12 girls irradiated before 4 years of age. A significant (P < 0.03) reduction in height (SD) between irradiation and adult height occurred in untreated GH-deficient patients (−1 ± 0.3, n = 6), but not in GH-deficient patients given GH (−0.6 ± 0.3, n = 8) or in those with normal GH peak (−0.4 ± 0.3, n = 7). Conclusion In children irradiated for acute lymphoblastic leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height is smaller than after higher doses. We suggest that the indications for gonadotropin releasing hormone analogue therapy should be broad in patients with early or rapidly progressing puberty and those for GH therapy in those patients with a below average constitutional height before irradiation. Received: 17 November 1997 / Accepted: 9 February 1998     

Congenital adrenal hyperplasia: Renin and steroid values during treatment

Plasma renin activity (PRA), aldosterone (Aldo), 17-hydroxyprogesterone (17-OHP) and testosterone (T), together with urine sodium, pregnanetriol, 17-oxosteroids and the 11-oxygenation index (11-OH) were estimated in 23 patients (age 5.7–18 yrs.) with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency during glucocorticoid treatment.Elevated PRA levels (1400–17200 ng Al/l/hr) were found in 13 out of 15 patients with a history of salt loss. Three non-salt losers showed high PRA levels and in the remaining 5 the levels were in the upper normal range (540–900 ng Al/l/hr). Plasma Aldo levels were normal (25–620 pmol/l) in 18 patients and slightly elevated (690–2360 pmol/l) in 5. While these results indicate persistent impairment of sodium homeostasis in CAH patients, no significant correlations between log. PRA, log. Aldo and urinary sodium excretion were found.Mid-day 17-OHP levels ranged from 9 to 117 nmol/l and T from 0.3 to 18.0 nmol/l. Neither the 17-OHP nor the T results correlated well with the clinical assessment of therapeutic control. The results of the urinary steroid determinations showed better agreement with the clinical assessment of treatment and the 17-oxosteroid, pregnanetriol and 11-OH index results appeared to be better discriminants between good and poor control.Twelve of the patients with a history of early salt loss were reinvestigated after one month's treatment with oral 9-flurohydrocortisone (0.05 mg/day). PRA was reduced in 7 patients and 17-OHP fell in 10 patients. No consistent changes were found in Aldo, T, or urinary sodium and steroid excretion during this low-dose mineralocorticoid treatment.     

Changes with growth hormone treatment in growth hormone deficient children

A total of 54 previously untreated patients (15 girls, 39 boys) with poor growth due to idiopathic growth hormone deficiency (IGHD) were treated with human growth hormone (hGH), continuously up to 4 years. All of the patients had a peak hGH level which was below 10 ng/mL after at least two pharmacological tests and/or blunted physiologic hGH secretion, and their height was below ?2.5 s.d. for age and gender. After the 1st year of therapy, height velocity (HV) increased significantly when compared with baseline (from 3.18 ±0.76 cm/year to 9.17±1.03 cm/year; P <0.001), declined during the 2nd year and then remained significantly higher than pretreatment HV. When considering improvement in height expressed by height standard deviation score (SDS), during the therapy all of the patients showed a significant gain ± 1.72±1.09 (from ?4.11±0.61 to ?2.21±0.48). The height values were significantly higher than pretreatment, but remained below ?2 s.d. after 4 years of hGH therapy in our patients. Increased height velocity has been sustained, but height improvement after therapy was inversely correlated to height SDS for chronological age of patients at the start of therapy. In conclusion post-treatment height has been shown to be related to height deficit at the beginning of therapy. Therapy was well tolerated with no local or systemic adverse effects or acceleration of bone age.     

Effect of continuous glucose therapy with uncooked cornstarch on the long-term clinical course of type 1a glycogen storage disease

To evaluate the effects of uncooked cornstarch (UCS) on metabolic control, growth, and complications of pubertal and postpubertal, subjects with type 1 a glycogen storage disease, we studied 26 subjects (16 males), mean age 20.8±5.1 years, in whom continuous glucose therapy with cornstarch began at 6.8±4.3 years. At the time of this analysis, subjects had received cornstarch for 14.1±3.5 years. Metabolic control was determined with subjects receiving their usual home dietary regimens: 4.1±1.3 doses of UCS in the day (9.7±2.6 g/h) and 2.0±0.4 doses at night (11.7±2.2 g/h). Mean height standard deviation score (SDS) was −1.2±1.3, significantly less than the mean target height of −0.2±1.1 (P<0.01). Mean weight SDS was 0.5±1.9 and body mass index SDS was 0.7±1.0. Of all subjects, 50% had at least one focal hepatic lesion consistent with an adenoma. Urinary albumin excretion was increased (>20 μg/min) in 31% of subjects; two subjects had clinical albuminuria (>300 mg per 24 h), but none has progressed to chronic renal insufficiency. Of 26 subjects, 13 (50%) had anemia. All of the complications were associated with evidence of suboptimal metabolic control, whereas subjects with no evidence of any long-term complications had near normal blood lactate and total CO₂ concentrations.Conclusion: The achievement of optimal biochemical control of glycogen storage disease type 1a continues to be a challenge, but is attainable by meticulous adherence to an individualized dietary regimen based on the results of periodic metabolic evaluation and home blood glucose monitoring. Minimizing the metabolic abnormalities of the disease may decrease the risk of long-term complications. Published online: 31 July 2002     

The Role of Serum 17 Alpha-Hydroxy Progesterone in the Diagnosis of Virilizing Congenital Adrenal Hyperplasia

It has been shown by Strott et al. in 1969 that 17 α-hydroxy progesterone (17-OHP) was the main plasma steroid in patients with virilizing congenital adrenal hyperplasia (CAH) due to a deficiency in 21 hydroxylase. Estimation of this steroid in the plasma of children however was not readily performed until the adaptation of the technique of competitive protein binding (CPB). Barnes and Atherden (1972) showed that by using such a CPB assay, the determination of serum 17-OHP was of value in the diagnosis of CAH due to 21 hydroxylase deficiency. This paper reports the experience gained at the Royal Children's Hospital Melbourne using a CPB assay for 17-OHP in the diagnosis of patients with suspected CAH.     

The effect of colchicine on physical growth in children wıth familial mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive disease, characterized by recurrent, self-limited attacks of fever with serositis involving the peritoneum, pleura, and joints. There is very scarce information on physical growth of affected children. The aim of this study was to determine whether there is significant improvement in growth parameters in FMF patients after colchicine treatment. Patient files were retrospectively evaluated and patients that used colchicine for more than 1 year were included in the study. Demographic features, clinical findings before and after colchicine therapy, duration and dosage of therapy, weight, height, parentally adjusted height, and body mass index before and after colchicine therapy were noted and transformed into standard deviation scores (SDS). The study group consisted of 50 FMF (25 male and 25 female) patients. Median age at the time of diagnosis was 6.5 years. Median follow-up period was 3.6 (1–12.5) years. Mean height SDS increased from −0.19 ± 1.01 to 0.13 ± 0.99 (p = 0.026), and mean parentally adjusted height increased from −0.18 ± 1.23 to 0.13 ± 1.24 (p = 0.027), and both of them were found to be statistically significant. Mean body mass index SDS increased from −0.61 ± 1.32 to −0.32 ± 1.33, but this improvement was statistically insignificant (p = 0.18). In this study, we found that colchicine significantly improved height development in FMF patients.     

Failure of cortisone acetate therapy in 21-hydroxylase deficiency in early infancy

BACKGROUND: Pediatric endocrinologists initially treat congenital adrenal hyperplasia with either cortisone acetate (CA) or hydrocortisone (HC). Despite high doses of CA, we noted that 17-hydroxyprogesterone (17-OHP) and corticotropin were not fully suppressed in serum from neonates with 21-hydroxylase deficiency (21-OHD) until they were 40- to 80-days-old. In contrast, serum concentrations of 17-OHP were suppressed immediately by oral treatment with HC. METHODS: We sought to understand the reason for this discrepancy. Serum cortisol (F), cortisone (E), and 17-OHP were measured by radioimmunoassay or high-performance liquid chromatography in seven neonates with 21-OHD and in 118 normal subjects. From the time of diagnosis, CA was administered to four of the neonates with 21-OHD, while HC was given to the other three. RESULTS: In normal subjects serum E concentrations were greater than F during the first 2 months after birth, whereas F concentrations exceeded E after 2 months of age. Although infants receiving CA initially were given a high dose, serum F concentrations were extremely low, while 17-OHP concentrations were high until about 2 months of age. Then serum F exceeded E, and 17-OHP became fully suppressed even though infants received only a moderate dose of CA. In contrast, HC administration successfully normalized serum 17-OHP in the neonatal period. With temporary switching of neonates from HC to CA, serum F concentrations immediately decreased and 17-OHP concentrations increased. CONCLUSION: Conversion of E to F may be limited during early infancy, adversely affecting treatment with CA. Cortisone acetate may be inappropriate as a glucocorticoid replacement during early infancy in patients with 21-OHD.