Increased Bone Age Research Articles

Combined assisted bone age assessment and adult height prediction methods in Chinese girls with early puberty: analysis of three artificial intelligence systems

BackgroundThe applicability and accuracy of artificial intelligence (AI)-assisted bone age assessment and adult height prediction methods in girls with early puberty are unknown.ObjectiveTo analyze the performance of AI-assisted bone age assessment methods by comparing the corresponding methods for predicted adult height with actual adult height.Materials and methodsThis retrospective review included 726 girls with early puberty, 87 of whom had reached adult height at last follow-up. Bone age was evaluated using the Greulich–Pyle (GP), Tanner–Whitehouse (TW3–RUS) and China 05 RUS–CHN (RUS-CHN) methods. Predicted adult height was calculated using the China 05 (CH05), TW3 and Bayley–Pinneau (BP) methods.ResultsWe analyzed 1,663 left-hand radiographs, including 155 from girls who had reached adult height. In the 6–8- and 9–11-years age groups, bone age differences were smaller than those in the 12–14-years group; however, the differences between predicted adult height and actual adult height were larger than those in the 12–14-years group. TW3 overestimated adult height by 0.4±2.8 cm, while CH05 and BP significantly underestimated adult height by 2.9±3.6 cm and 1.3±3.8 cm, respectively. TW3 yielded the highest proportion of predicted adult height within ±5 cm of actual adult height (92.9%), with the highest correlation between predicted and actual adult heights.ConclusionThe differences in measured bone ages increased with increasing bone age. However, the corresponding method for predicting adult height was more accurate when the bone age was older. TW3 might be more suitable than CH05 and BP for predicting adult height in girls with early puberty. Methods for predicting adult height should be optimized for populations of the same ethnicity and disease.

Poster 262: Correlation of Tanner Stage and Hypermobility with Meniscal and Articular Cartilage Injury in the Pluto Cohort

Objectives:To determine whether the relationship between hypermobility and meniscal and/or articular cartilage injury varies by stage of pubertal development. Patients with hypermobility will have a lower risk of meniscal and articular cartilage injury than patients with normal laxity.Methods:At 10 geographically diverse institutions in the United States, consecutive skeletally immature patients diagnosed with complete ACL tears between January 2016 and April 2020 were enrolled. Beighton score was collected at the preoperative physical exam; bone age was determined from a hand/wrist radiograph; and the presence of meniscal tears and articular cartilage injuries was collected from the surgical assessment. Tanner stage was documented at time of surgery. Univariable and multivariable logistic regression analysis was used to assess the effect of Tanner stage and Beighton score on the likelihood of cartilage injury and meniscal tear.Results:Seven hundred forty-seven skeletally immature patients with complete ACL tears were analyzed with an average age at surgery of 12.3 years; the cohort was 62% male.Eighty-five patients had documented cartilage injuries for an event rate of 11.4%. Bivariate analysis found that those with cartilage injuries had a slightly higher bone age (13.9 versus 13.1 years; p=0.001) and a higher Tanner stage (p=0.009). For each additional Tanner stage, the odds of cartilage injury increased by approximately 1.6 (p<0.001). No association was detected between hypermobility and the likelihood of a cartilage injury.Four hundred twenty-three patients had documented meniscal tears for an event rate of 56.6%. Bivariate analysis found that those with meniscal tears were slightly older (12.6 versus 12.0 years; p<0.001), had a slightly higher bone age (13.5 versus 12.8 years; p<0.001) and a higher Tanner stage (p=0.002). For each additional Tanner stage, the odds of a meniscal tear increased by approximately 1.3 times (p<0.001). No association was detected between hypermobility and the likelihood of a meniscal tear.Conclusions:There is a high rate of concomitant articular cartilage and meniscal injuries in skeletally immature patients who sustain ACL tears. The risk of concurrent injury is associated with increasing bone age and Tanner score. There was no association between these concurrent injuries and hypermobility.Figure 1.Distribution of Tanner stage by cartilage injury groups.Figure 2.Distribution of Tanner stage by meniscal tear groups.

Correlation of Tanner Stage and Hypermobility with Meniscal and Articular Cartilage Injury in the Pluto Cohort

Background:ACL injuries in adults are frequently accompanied by meniscal and articular cartilage damage. However, little is known regarding the correlation of Tanner stage and hypermobility in ACL-deficient skeletally immature patients and the risk of these associated injuries.Hypothesis/Purpose:The relationship between hypermobility and meniscal and/or articular cartilage injury varies by stage of pubertal development. Patients with hypermobility will have a lower risk of meniscal and articular cartilage injury than patients with normal laxity.Methods:At 10 geographically diverse institutions in the United States, consecutive skeletally immature patients diagnosed with complete ACL tears between January 2016 and April 2020 were enrolled. Beighton score was collected at the preoperative physical exam; bone age was determined from a hand/wrist radiograph; and the presence of meniscal tears and articular cartilage injuries was collected from the surgical assessment. Tanner stage was documented at time of surgery. Univariable and multivariable logistic regression analysis was used to assess the effect of Tanner stage and Beighton score on the likelihood of cartilage injury and meniscal tear.Results:Seven hundred forty-seven skeletally immature patients with complete ACL tears were analyzed with an average age at surgery of 12.3 years; the cohort was 62% male. Eighty-five patients had documented cartilage injuries for an event rate of 11.4%. Bivariate analysis found that those with cartilage injuries had a slightly higher bone age (13.9 versus 13.1 years; p=0.001) and a higher Tanner stage (p=0.009). For each additional Tanner stage, the odds of cartilage injury increased by approximately 1.6 (p<0.001). No association was detected between hypermobility and the likelihood of a cartilage injury. Four hundred twenty-three patients had documented meniscal tears for an event rate of 56.6%. Bivariate analysis found that those with meniscal tears were slightly older (12.6 versus 12.0 years; p<0.001), had a slightly higher bone age (13.5 versus 12.8 years; p<0.001) and a higher Tanner stage (p=0.002). For each additional Tanner stage, the odds of a meniscal tear increased by approximately 1.3 times (p<0.001). No association was detected between hypermobility and the likelihood of a meniscal tear.Conclusion:There is a high rate of concomitant articular cartilage and meniscal injuries in skeletally immature patients who sustain ACL tears. The risk of concurrent injury is associated with increasing bone age and Tanner score. There was no association between these concurrent injuries and hypermobility.Figure 1.Distribution of Tanner stage by cartilage injury groups.Figure 2.Distribution of Tanner stage by meniscal tear groups.

Causes of Precocious Puberty in Children Referred to an Endocrine Clinic in Qazvin City, Iran From 2006 to 2018

Background: Puberty is an essential milestone in a person’s life. Studies show that precocious puberty is more common in girls than in boys. Objectives: The aim of this study was to survey the causes of precocious puberty in children referred to the endocrine clinic in Qazvin city, Iran, from 2006 to 2018. Methods: This case-series study was performed from March 2006 to June 2018 on patients referred to the endocrine clinic of Qazvin University of Medical Sciences, Qazvin City, Iran, for precocious puberty. To diagnose premature puberty and find its causes, we surveyed sex steroids levels, thyroid function, and, if necessary, performed GnRH test. The patients’ height and weight were measured, and their BMIs (Body Mass Index) were calculated. Uterine ultrasound was performed for all girls. Additionally, brain MRI was performed for all boys and girls under age 6 with precocious puberty. X-ray of the left hand was performed to assess skeletal growth acceleration. Based on the type of puberty, the patients were divided into three groups: Central Precocious Puberty (CPP), Peripheral Precocious Puberty (PPP), and normal variant of puberty. The study data were collected from patients› electronic files and analyzed using SPSS 23. Results: Out of 724 cases, 642 (88.70%) were girls. The mean age of all children was 7.07 (95%CI: 6.99-7.15) years. About 70.5% of cases had CPP, 5% PPP, and 24.5% normal variant of puberty. Cases of Idiopathic Precocious Puberty (IPP), PPP, Neurogenic Central Precocious Puberty (NCPP), and premature pubarche were significantly higher in girls than boys (P&lt;0.001). None of the boys had NCPP. Most girls had normal BMI, but boys were more obese. Mean bone age and bone age/age ratio were higher in girls with NCPP (P&lt;0.001). Conclusions: In our study, most girls and boys had idiopathic precocious puberty, and none of the boys had brain lesions. About half of the cases were overweight or obese, indicating the role of obesity in increasing bone age and the onset of puberty.

Neurodevelopment and Genetic Evaluation of Sotos Syndrome Cases with a Novel Mutation: a Single-Center Experience.

Sotos syndrome is a non-progressive neurological disease with overgrowing, increased bone age, and developmental retardation. The aim of this study is to evaluate the prenatal, natal, and postnatal clinical findings of patients with Sotos syndrome. Sixteen patients suspected to have Sotos syndrome with clinical findings were examined retrospectively, ranging in ages between 3 and 23. In our file screening, we screened the FISH results of all 16 patients, but not all patients had NSD1 gene analysis results. We collected NSD1 gene analysis results, if there were any. The parameters that we investigated for these patients are birth weight, birth length, Apgar score at the 5th minute, dysmorphological face appearance, bone age, seizure, learning disability, feeding difficulties, surgical operation, and other accompanying abnormalities (brain MRI, abnormal echocardiographic findings, chronic otitis media, etc.). The anamnesis, clinical examination findings, and genetic reports of the patients were examined. For this, the hospital registration system was used. Breech presentation, Apgar score in the 5th minute of between 4 and 7, atrial septal defect at echocardiography, and consanguineous marriage rate were detected to be increased in individuals with Sotos syndrome compared to the normal population. When compared to the general population, delayed psychomotor development was determined. Macrocephaly, increased bone age, chronic otitis media frequency, and hernia operation frequency were determined to see if all patients were consistent with the literature. As a result of NSD1 gene sequencing analyses (NSD1 gene analysis was performed in 6 patients and a mutation was detected in 3 of them), three were found to have NSD1 gene mutation (one of them was novel). A novel deletion-type mutation that was not previously reported in the literature in the 19th exon of the NSD1 gene was determined. Xiphoidal protrusion was detected on this patient that had the novel mutation, and this situation has not been reported in the literature previously. If a patient has rapid growth, difficulty in learning, macrocephaly, speech delay, and timid personality, Sotos syndrome can be considered at the pre-diagnosis stage.

Ridge regression neural network for pediatric bone age assessment

Bone age is an important measure for assessing the skeletal and biological maturity of children. Delayed or increased bone age is a serious concern for pediatricians, and needs to be accurately assessed in a bid to determine whether bone maturity is occurring at a rate consistent with chronological age. In this paper, we introduce a unified deep learning framework for bone age assessment using instance segmentation and ridge regression. The proposed approach consists of two integrated stages. In the first stage, we employ an image annotation and segmentation model to annotate and segment the hand from the radiographic image, followed by background removal. In the second stage, we design a regression neural network architecture composed of a pre-trained convolutional neural network for learning salient features from the segmented pediatric hand radiographs and a ridge regression output layer for predicting the bone age. Experimental evaluation on a dataset of hand radiographs demonstrates the competitive performance of our approach in comparison with existing deep learning based methods for bone age assessment.

Relationship between final adult height and birth weight after gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty.

PurposeThe clinical significance of birth weight relative to gestational age in girls with central precocious puberty is unclear. This study sought to compare clinical parameters such as final adult height (FAH) and menarche onset after treatment with gonadotropin-releasing hormone agonist (GnRHa) on birth weight in girls with central precocious puberty treated.MethodsThis retrospective study reviewed data of 69 girls with precocious puberty who had reached their FAH in a long-term trial of GnRHa treatment between January 2007 and December 2017. The subjects were divided into small for gestational age (SGA) (n=19) and appropriate for gestational age (AGA) (n=50) groups.ResultsWhen starting GnRHa treatment, bone age was 10.9±0.9 and 10.3±0.8 years in the SGA and AGA groups, respectively (P<0.05). The predicted adult height (PAH) (established according to the Bayley-Pinneau average table) and advanced PAH (established according to the Bayley-Pinneau advanced table) were 151.5±4.8 cm and 155.8±4.9 cm in the SGA group, respectively, and 153.4±5.3 cm and 159.0±6.0 cm in the AGA group. After treatment, no significant difference in bone age was found between the groups. The time to menarche after treatment was 12.5±7.6 and 21.1±12.3 months in the SGA and AGA groups, respectively (P<0.05). FAH in the SGA and AGA groups was 161.0±4.7 cm and 161.6±5.0 cm, respectively, without a significant difference.ConclusionsSGA girls with precocious puberty have increased bone age and earlier menarche relative to AGA girls. However, no difference in FAH after treatment was found between these groups.

MON-241 Relationship between Final Height and Birth Weight after Gonadotropin-Releasing Hormone Agonist Treatment in Girls with Central Precocious Puberty

Objectives: Small for gestational age (SGA) children may present an earlier onset of pubertal development, advanced bone maturation and reduced final height. The aim of this study was to compare the clinical parameters such as final adult height (FAH) and menarche with birth weight in girls with idiopathic precocious puberty (PP) treated with gonadotropin releasing hormone agonist (GnRHa). Subjects and methods: We retrospectively reviewed the medical records of 69 girls with PP who have reached FAH in a long-term trial of GnRHa treatment. The subjects were divided into SGA group and appropriated for gestational age (AGA) group. Anthropometric and endocrine parameters were obtained at diagnosis, at 6 months, and at cessation of GnRHa treatment. We investigated chronological age (CA), bone age (BA), BA / CA ratio, height and height SDS, predicted adult height (PAH-calculated with average table of BP method), PAH SDS, PAHa (calculated with advanced table of BP method), basal and stimulated gonadotropin levels, duration of treatment, duration of menarche, and FAH after treatment. The statistical significances of the clinical parameters between the two groups were compared. Results: The BA at the time of diagnosis was higher in SGA than in AGA (p <0.05). In the SGA, PAH SDS and PAHa were lower than those of AGA (p <0.05), but there was no significant difference in FAH between two groups. The FAH after GnRHa treatment was higher than PAH at diagnosis between SGA and AGA groups (p <0.05) . Body mass index was higher at the end of treatment in SGA group than in AGA (p <0.05). In addition, it was confirmed that the menarche was fast after treatment in SGA than in AGA (p <0.05). Target height, height SDS at diagnosis, PAH at diagnosis, and height SDS at end of treatment were found to be factors affecting FAH (p <0.05) . Conclusion: SGA girls with PP have increased bone age and rapid menarche than those of AGA group. But FAH after GnRHa treatment was not difference between the SGA and AGA groups. GnRHa treatment in SGA with PP may be helpful in improving FAH, and further large - scale studies will be needed in the future.

Children with premature pubarche: is an alterated neonatal 17-Ohp screening test a predictive factor?

BackgroundNeonatal screening for 21 hydroxylase deficiency is designed to detect classical form of congenital adrenal hyperplasia (CAH). It is still unclear whether newborns who result false positives at neonatal screening might later develop signs of androgen excess. The aim of this study is to verify whether a slightly elevated 17-OHP at newborn screening is a predictive factor for premature pubarche.MethodsWe evaluated all infants born between 2001 and 2014 with premature pubarche. In case of increased bone age, they were submitted to functional tests to find out the cause of their symptoms. Their 17-OHP values at newborn screening for CAH were reconsidered.ResultsWe identified 330 patients (269 females, 61 males) with premature pubarche. All these children had a normal 17-OHP at newborn screening with the exception of a child, born preterm and not affected by CAH.ConclusionsAn elevated 17-OHP at newborn screening is not a predictive factor for premature pubarche. A likely cause of increased 17-OHP level at screening is an immaturity of adrenal gland or a neonatal stress. Therefore a strict follow up of these neonates during childhood is not necessary.

G112(P) Early Pubertal Changes in Neurodisabled Children – an Under Diagnosed Issue?

AimEvaluation of pubertal changes is an easily missed component in the assessment of the complex neurodisabled child .There is limited literature available in the UK regarding pubertal changes in these...

Complex malformation (Ruggieri–Happle) phenotype with “cutis tricolor” in a 10-year-old girl

The term cutis tricolor describes the combination of congenital hyper- and hypo-pigmented skin lesions in close proximity to each other in a background of normal complexion. It is currently regarded as a twin-spotting phenomenon and today is clear that not all cases of cutis tricolor represent one single entity. This phenomenon has been reported so far: (a) as an isolated skin manifestation; (b) as a part of a complex malformation syndrome (Ruggieri–Happle syndrome – RHS); (c) as a distinct phenotype [cutis tricolor parvimaculata]; (d) in association with other (e.g., vascular) skin disturbances. We report a novel case of cutis tricolor in a 10-year-old girl who had dysmorphic facial features [alike those seen in cases with syndromic (RHS) cutis tricolor], overall overgrowth [weight, length, and head circumference were >90th percentile; there was increased bone age], mild cognitive delay (current IQ=55), behavioural disturbances, febrile seizures and (later) partial complex epilepsy (currently under good control), and skeletal defects [i.e., posterior scalloping of the lumbar vertebrae]. We discuss the main similarities and differences between the various phenotypes in the spectrum of cutis tricolor and with other conditions sharing features with the present case.

Puberdade precoce central como única manifestação de cisto aracnoide supraselar

OBJETIVO: Os cistos aracnoides são achados raros. Em 10% dos casos, sua localização é supraselar e ocorrem quase exclusivamente em crianças. Em geral, apresentam manifestações neurológicas e visuais, sendo incomum a puberdade precoce central como sinal clínico de sua presença. DESCRIÇÃO DO CASO: Menina avaliada aos dois anos e sete meses por telarca iniciada com um ano e oito meses e pubarca e axilarca com dois anos, com aumento da velocidade de crescimento (13cm/ano) e da idade óssea (sete anos e um mês). Ao exame, apresentou peso de 22,6kg (Z+4,0), estatura de 106cm (Z+3,5) e Tanner de M3P2. Exames realizados: teste de estímulo com GnRH (LH basal 8,3 UI/L, pico aos 30 minutos 94,3 UI/L; FSH basal=10,1 UI/L, pico aos 30 minutos 29,5 UI/L), ressonância nuclear magnética de crânio com cisto aracnoide supraselar e demais testes de função hipofisária normais. Foi iniciado tratamento com análogo de GnRH. Atualmente, aos quatro anos e três meses com estadio puberal M3P2, velocidade de crescimento e desenvolvimento neuropsicomotor normais para a idade. COMENTÁRIOS: A puberdade precoce central pode ser manifestação única de um cisto aracnoide, sendo essenciais o diagnóstico e o tratamento precoces, além de seguimento prolongado, uma vez que outras disfunções hipofisárias podem ocorrer tardiamente.

TREATMENT OF GROWTH FAILURE IN CHILDREN AFTER RENAL TRANSPLANTATION1

Growth failure continues to be a problem in the management of children with renal failure. Children have improved growth after successful renal transplantation, but seldom have "catch-up" growth, or normal adult height. In this study we report the findings of an open label pilot study to determine the safety and efficacy of the use of recombinant human growth hormone (rhGH) in children with growth failure after successful renal transplantation. Eleven children completing at least 1 year of treatment had a mean age of 11.5 years (+/- 3.3) and mean bone age of 8.4 years (+/- 2.4), and were significantly growth-retarded (mean standard deviation score of -3.18 [+1.1]). After receiving rhGH (0.05 mg/kg) subcutaneously each day the height velocity increased from 5.2 cm/year to 8.4 cm/year (P = 0.003), and the standard deviation score improved from -3.18 to -2.23 (P = 0.004). Treatment was associated with advancement in Tanner stage from 1 to 2.8 (P = 0.004), increased bone age from 8.4 years to 10.9 years (P = 0.0002), and although it was not at the point of statistical significance, moderate decrease in creatinine clearance from 75 ml/1.73m2/min to 60 ml/1.73m2/min (P = 0.1). The advancement in Tanner stage and bone age was not out of proportion to the advancement in height age. These data suggest that children with functioning renal allografts have improved growth with supraphysiologic doses of rhGH.

Evaluation of gonadotropin responses to synthetic gonadotropin-releasing hormone in girls with idiopathic hypopituitarism

We hypothesized that prepubertal girls with gonadotropin deficiency would produce less follicle-stimulating hormone (FSH) in response to synthetic gonadotropin-releasing hormone (GnRH) than would gonadotropin-sufficient children. To test this hypothesis, we performed 103 GnRH tests serially in 21 children who had idiopathic hypopituitarism with growth hormone deficiency. We tried to predict whether puberty would occur in the 17 girls with bone ages of 8 years or less. Of these 17 girls, 4 failed to have spontaneous secondary sexual characteristics by age 16 1/2 years, and 12 had spontaneous complete pubertal development. One girl had incomplete pubertal maturation with partial gonadotropin deficiency; her results were combined with those of the girls who had no spontaneous pubertal development. With increasing bone age, the girls with complete pubertal development had a decrease in the increment of FSH released in response to GnRH, although basal gonadotropin concentrations did not change. For GnRH tests performed at bone ages of 8 years or less, basal luteinizing hormone (LH) values did not differ between girls with complete puberty and those with absent or incomplete puberty. However, basal FSH and the incremental response of LH and FSH to GnRH were greater in those with complete puberty. Only two girls with prepubertal bone ages at the time of testing, who subsequently had complete puberty, had incremental FSH responses to GnRH that were less than 5 IU/L. Individual incremental LH responses to GnRH did not discriminate well between groups. None of the girls with adrenocorticotropic hormone deficiency, either originally or subsequently, had spontaneous puberty, but 4 of 12 girls with thyrotropin deficiency, either originally or subsequently, had complete puberty. We conclude that a significant increase in GnRH-stimulated FSH suggests that spontaneous pubertal development will occur in girls with idiopathic hypopituitarism. However, a low FSH response to GnRH may not be diagnostic of gonadotropin deficiency.

Experimental determination of “the law of bone remodeling” and effect of rat parathyroid hormone (1–34) infusion on derived parameters

The dependence of bone remodeling probability on bone age was investigated by fitting a previously described mathematical model to data describing the decline of radioactivity in the femurs of growing rats prelabeled with [3H]tetracycline. The remodeling probability declined with increasing bone age, but because the data were obtained at the whole bone level, several explanations for this finding are possible, and the results cannot be extrapolated beyond the duration of the experiment. A simpler exponential model that assumes remodeling probability is constant can be used to calculate bone resorption rate within a limited time period. A significantly increased bone resorption rate in PTH-infused rats could readily be demonstrated using the exponential model. A more sophisticated statistical analysis was required to discriminate between control and PTH-infused rats using the more complex model in which resorption rate was not constant.

Congenital Adrenal Hyperplasia

The incidence of congenital adrenal hyperplasia in Saudi Arabia and the frequency of the carrier rate are not well known. Both figures should be high, considering the commonness of first-degree consanguinity in this part of the world. We present 25 cases of congenital adrenal hyperplasia, most of them due to a defect of the 21 hydroxylase enzyme, diagnosed and followed over three years at Suleimania Children's Hospital in Riyadh. There were ten boys and 15 girls exhibiting all degrees of masculinization, mostly Grade III (53%) and Grade IV and V (13.3% each). The degree of masculinization of the external genitalia in the girls (46XX) was sufficiently pronounced in seven patients to lead to sex identity errors at birth. This aggravated the psychological reactions in the families, particularly before the surgical correction. The frequency of neonatal deaths in the patients' families related to a similar disorder was high (12%). The mean age at onset of the salt-losing crises in affected infants was 9 days in females and 25 days in males and this was the most common clinical presentation of the disorder (80%). Systemic neonatal screening and intrauterine diagnosis in at risk families must be done to provide hormonal intervention and thus prevent the formation of ambiguous genitalia and avoid the resulting plastic surgery that must be performed in female patients.

The Use of Parenteral Testosterone Therapy in Genital Reconstructive Surgery

Previously, testosterone cream has been used for penile enlargement before genital surgery. The results not only were inconsistent but the absorption was variable. Therefore, we elected to study the use of parenteral testosterone as an adjunct before reconstructive surgery.In 44 patients with hypospadias (36), epispadias (5) or urethral fistulas (3) 2mg. per kg. testosterone enanthate were given intramuscularly 5 and 2 weeks before reconstructive surgery. Testosterone caused a mean increase in penile length of 2.7cm. and in circumference of 2.3cm. as well as local vascularity in all patients. In addition to surgical results the potential side effects of testosterone treatment were monitored 3 months to 1 year postoperatively. Basal testosterone levels were obtained in patients before and during therapy, and postoperatively. In addition, side effects, such as increased bone age and excessive pubic hair, were not a problem.The use of preoperative testosterone significantly contributed to the successful reconstruction of these patients, particularly those with a paucity of penile skin and those who had undergone previous repairs. Temporary penile stimulation by testosterone enanthate allows for an earlier penile operation as well as provides negligible side effects.

Precocious Pseudopuberty and Ovarian Follicular Cysts-Reply

<i>In Reply</i>.—We would like to reassure Drs Stanhope and Brook that our two patients had more than just premature thelarche; they had precocious pseudopuberty. It would be wrong to suggest that every girl with premature thelarche should be operated on if small cysts were present in the ovaries. In our two patients, the diagnosis of precocious pseudopuberty was based on their ages, on elevated serum estrogen levels, and on clinical findings of estrogen excess, eg, increased nipple and areolar pigmentation, increased bone age, and morning sickness. In our second patient, the morning nausea was so severe that it interfered for almost two months with our patient's school attendance. Both sets of parents were extremely (justifiably) anxious about the rapidly progressive breast enlargement of their little girls. Precocious pseudopuberty is rare, and these two children were highly selected. Our pediatric endocrine clinic serves as the tertiary referral center for a population of

Transient impairment or delay of urinary trihydroxypregnanone (THS) response to metyrapone in boys with delayed adolescence and in patients with isolated growth hormone deficiency.

Twenty three boys with delayed adolescence (age 15.7 +/- 2.0, bone age 12.4 +/- 2.1 years) were studied. Their cortisol response to insulin was normal. After oral metyrapone (500 mg/m2 by mouth) one to three consecutive 12 h urine samples were collected for analysis of THS. Thirty seven tests with 37 first, 21 second, and 11 third samples were carried out. The results could be divided into two main groups: 25 tests (group A) were subnormal in the first sample, 12 of them with a very weak (40 +/- 8 micrograms/m2/12 h) and 13 with an insufficient (191 +/- 16 micrograms/m2/12 h) THS response. Values in the second and third sample were higher, indicating a delayed response. In 12 tests (group B), the results were normal (1016 +/- 143 micrograms/M2/12 h) in the first and lower in the second and third samples. In three patients with repeated tests, there was improvement with increasing bone age. The THS-responses to metyrapone did not correlate with those of growth hormone, gonadotrophins, and TSH to stimuli. It is concluded that the THS-response to a single dose of metyrapone may be temporarily insufficient or delayed in delayed adolescence. We interpret this finding as showing transiently reduced or slow hypothalamic responsiveness.

Plasma somatomedin-C as a screening test for growth hormone deficiency in children and adolescents.

Random plasma somatomedin-C (SM-C) levels were measured in 143 children and adolescents with growth at or below the 5th percentile. 124 patients had short stature due to constitutional delay or genetic predisposition and 19 patients were growth hormone deficient (GHD). When analyzed according to bone age, mean somatomedin-C levels rose gradually with increasing bone age in non-GHD patients, while there was no change with increasing bone age in GHD patients. All patients with SM-C levels less than 0.05 U/ml underwent growth hormone testing to rule out GHD. This criterion resulted in 52% accuracy in identifying non-GHD patients and 100% accuracy in identifying GHD patients. Comparison of the SM-C test with the exercise GH screening test demonstrated the advantage of greater convenience for the SM-C test, and comparable cost effectiveness despite a lower specificity associated with the SM-C test. SM-C levels were not predictive of peak growth hormone response nor could they be used to differentiate constitutional delay of growth and maturation from genetic short stature.