Adherence to growth hormone therapy: results of a multicenter study.

OBJECTIVE: To evaluate the adherence to growth hormone (GH) therapy and identify the influencing factors and outcomes in children. METHODS: A total of 217 GH-naïve patients in 6 pediatric endocrinology clinics were enrolled in the study. Structured questionnaires were filled out and patients were evaluated at the initiation and 3rd, 6th, and 12th months of therapy. Patients were categorized into 4 adherence segments based on percentage of doses omitted at each evaluation period, classified as excellent if 0%, good if 5%, fair if 5 to 10%, and poor if > 10%. RESULTS: There was a decrement in adherence to GH therapy during the study period (P = .006). Patients who showed excellent and good adherence to therapy had better growth velocity and growth velocity standard deviation scores (SDSs) (P = .014 and P = .015, respectively). A negative correlation between growth velocity SDS and number of missed injections was also observed (r = -.412; P = .007). A positive correlation between delta insulin-like growth factor-1 (IGF-1) SDS and growth velocity was demonstrated (r = .239; P = .042). IGF-1 levels were significantly higher in patients who showed excellent and good adherence to therapy (P = .01). Adherence was better in boys than in girls (P = .035), but adherence rates were not associated with age, cause of GH treatment, socioeconomic status, person who administered the injections, type of injection device, or GH product. CONCLUSION: Poor adherence to GH therapy was common in our group of patients and was one of the factors underlying suboptimal growth during therapy. Before considering other problems that can affect growth, clinicians should confirm good adherence to therapy.

Refractive errors and strabismus in children with laurence-moon-biedl syndrome.

PURPOSE: To describe the ocular and refractive findings in patients with Laurence-Moon-Biedl syndrome. METHODS: Seventeen patients with Laurence-Moon-Biedl syndrome were evaluated retrospectively. All children underwent complete ophthalmologic examination. RESULTS: Of the patients evaluated, 88.2% had an ocular or refractive finding, 58.8% had myopia (degenerative in three cases), 52.9% had astigmatism, 11.7% had an-isometropia, 17.6% had strabismus, 11.7% had retinitis pigmentosa, 5.9% had keratoconus, 5.9% had optic atrophy, and 5.9% had nystagmus. CONCLUSION: Early and regular ophthalmologic assessment is required to prevent visual loss as a result of amblyogenic factors in children with Laurence-Moon-Biedl syndrome.

Variables related to behavioral and emotional problems and gender typed behaviors in female patients with congenital adrenal hyperplasia.

We investigated the effects of type of congenital adrenal hyperplasia (CAH), treatment, endocrinological, surgical, and socio-demographic factors as well as patients' body perception on the gender-typed play and behavioral and emotional problems in female children with CAH. The sample included 28 females with CAH (mean age: 12.6 years). We compared patients with CAH to 28 age-matched patients with type 1 diabetes mellitus and 28 healthy controls. Patients with CAH had significantly higher externalization and total problems scores and were less interested in typically female behaviors. The behavioral and emotional problems in patients with CAH were associated with patient satisfaction with the appearance of their genitalia, the surgeons' assessment of the success of the surgical procedures, and mean testosterone level. Our results showed the severity of the behavioral and emotional problems was associated with severity of androgenization, patients' perception of their genitalia and the surgical outcome.

Characterization of GH-1 mutations in children with isolated growth hormone deficiency in the Turkish population.

Isolated growth hormone deficiency (IGHD) is defined as a medical condition associated with growth failure due to insufficient production of growth hormone (GH) or lack of growth hormone action. It occurs with an incidence of between 1/4,000 and 1/10,000 live births. Most cases are sporadic and idiopathic but 5-30% of growth hormone deficiency (GHD) has genetic etiology. Mutations in the GH encoding gene (GH-1) have been detected in patients with IGHD. The purpose of this study was to characterize mutations of the GH-1 gene in children with IGHD in the Turkish population. We found four missense mutations (E33G, N47D, T-24A and A13S), one nonsense mutation (W-7X), one insertion and two deletions in nine patients out of seventy-five patients with IGHD. The missense mutation A13S, GAAA insertion at intron 1 (+178A), and the deletions of +83C in intron 1 and deltaF166 in exon 5 are novel mutations.

Final height of patients with classical congenital adrenal hyperplasia.

The management of children with congenital adrenal hyperplasia (CAH) remains a challenge, especially with regard to their growth potential. We aimed to determine the correlation of the final height of Turkish children with classical CAH to their genetic height potential and to determine the effect of hydrocortisone replacement therapy on the final height. A total of 24 CAH (16 simple virilizing and 8 salt-wasting form) were included in this retrospective longitudinal study. The final height (FH), final height standard deviation score (FHSDS), target height (TH), target height standard deviation score (THSDS), corrected height for target height (CHSDS), weight, and body mass index (BMI) were calculated for all patients. We evaluated the adult height taking into consideration the correlation with the genetic height potential and the country standards. The average follow-up time was 14.2 +/- 3.1 years and the average daily hydrocortisone dose was 19.7 +/- 2.9 mg/m2. The mean FH and FHSDS were 152.2 +/- 7.2 cm and -1.0 +/- 1.1 SD, respectively, in females and 163.1 +/- 6.6 cm and -1.2 +/- 1.0 SD, respectively, in males. The CHSDS was found to be -0.73 +/- 0.9 SD. FH was below the TH in 79.1% of our cases. In 20.8% of our patients, FH was less than the third percentile for the standard height for our country. Interestingly, the FH showed no correlation with the dosage of hydrocortisone. Thirteen of our cases (54.2%) reaching FH were obese/overweight. A positive correlation was detected between hydrocortisone treatment and the BMI. The observations that 79.1% of our classical CAH cases receiving an average daily hydrocortisone dose of 19.7 +/- 2.9 mg/m2 ended up with an adult height below the TH and that 54.2% of the cases were overweight/obese lead us to believe that we should be using the lowest possible dose for treatment.

Management of central diabetes insipidus with oral desmopressin in a patient with ectrodactyly and cleft lip/palate (ECP) syndrome.

We present a female infant with facial abnormalities such as bilateral cleft lip and palate, ectrodactyly and central diabetes insipidus. She had a history of recurrent hypernatremic attacks and she was treated successfully with oral desmopressin. As an alternative to the nasal route, long-term management was achieved using oral route and she had a favorable growth and development during infancy.

The effect of growth hormone treatment on bone mineral density in prepubertal girls with Turner syndrome: a multicentre prospective clinical trial.

BACKGROUND: Patients with Turner syndrome (TS) are treated with GH to increase adult height. Although it is well established that GH promotes longitudinal bone growth, the effects of GH treatment on bone density are less clear. OBJECTIVE: To determine how GH treatment affects trabecular bone mineral density (BMD) in girls with TS at prepubertal ages in a prospective multicentre study. PATIENTS AND METHOD: Twenty-two patients with TS in the prepubertal period with a mean age of 9.8 +/- 2.5 (range 3.6-12.8) years were included in the study. All girls with TS underwent measurement of areal BMD using dual-energy X-ray absorptiometry (DXA) to obtain pretreatment anteroposterior (AP) lumbar spine values at L1-L4. Patients received GH (Genotropin) subcutaneously for 1 year at a dose of 0.05 mg/kg/day. Height and weight were measured at 3-monthly intervals. The AP lumbar spine areal BMD was remeasured using the same technique after 1 year of treatment. Lumbar spine BMD Z-scores and volumetric BMD (vBMD) Z-scores were calculated using national standards. RESULTS: The height SDS of our cases showed a significant increase with GH therapy. The pretreatment lumbar spine (L1-L4) BMD Z-score was -1.2 +/- 1.2 SD and the vBMD Z-score was -0.8 +/- 1.6 SD. There were no significant changes in these values after 1 year of GH treatment. Prepubertal TS girls more than 11 years of age had lower vBMD Z-scores (-1.7 +/- 1.7 SD) than the girls aged less than 11 (-0.1 +/- 1.0 SD) (P < 0.05) at the onset of therapy. No significant changes were observed in these values after 1 year of GH therapy. CONCLUSIONS: Osteopaenia becomes apparent in prepubertal TS patients as they reach pubertal age. BMD evaluation may be necessary in these prepubertal TS girls at diagnosis. Short-term GH therapy in these TS patients does not have a significant effect on bone density when measured at a site with a predominance of trabecular bone.

A very rare cause of virilization in childhood: ovarian Leydig cell tumor.

Virilization in childhood results from an adrenal and/or ovarian disorder. These children usually present with hyperandrogenism: acne, deepening voice, abnormal hair growth, cliteromegaly. Ovarian Leydig cell tumor is a very rare cause of hyperandrogenism in childhood. They are usually benign and surgical treatment is usually curative if the tumor is limited to the ovaries. We present the youngest case of ovarian Leydig cell tumor reported in the literature who presented with hyperandrogenism that was satisfactorily resolved after resective surgery. Rare causes of virilization should be investigated with special attention paid to tumoral disease in the differential diagnosis.

Effects of growth hormone on growth, insulin resistance and related hormones (ghrelin, leptin and adiponectin) in Turner syndrome.

BACKGROUND: Concomitant evaluation of the metabolic and growth-promoting effects of growth hormone (GH) therapy in Turner syndrome (TS) may be used in the prediction of the growth response to GH therapy. AIM: To evaluate the metabolic effects of GH therapy in TS and correlation with the short-term growth response. PATIENTS: 24 prepubertal children with TS, aged 9.4 +/- 2.6 years were followed for auxology and IGF-I, IGFBP-3, leptin, ghrelin, adiponectin, lipids and OGTT results in a prospective multicenter study. INTERVENTION: GH (Genotropin) in a dose of 50 microg/kg/day for 1 year. RESULTS: Height standard deviation score (SDS) increased from -3.9 +/- 1.5 to -3.5 +/- 1.4 (p = 0.000) on therapy. BMI did not change. IGF-I SDS increased from -2.3 +/- 0.4 to -1.6 +/- 1.1 at 3 and 6 months (p = 0.001) and decreased thereafter. Serum leptin decreased significantly from 2.3 +/- 3.9 to 1.7 +/- 5.3 ng/ml (p = 0.022) at 3 months and increased afterwards. Serum ghrelin decreased from 1.2 +/- 0.8 to 0.9 +/- 0.4 ng/ml (p = 0.005) with no change in adiponectin. Basal and stimulated insulin levels also increased significantly. Delta height SDS over 1 year showed a significant correlation with Delta IGF-I(0-3 months) (r = 0.450, p = 0.027). CONCLUSION: IGF-I may be considered as a marker of growth response in TS at short term. Leptin shows a decrease at short term but does not have a correlation with growth response. The decrease in ghrelin in face of unchanged weight seems to be associated with increase in IGF-I and insulin levels. The unchanged adiponectin levels in spite of an increase in insulin levels indicates that adiponectin is mainly affected by weight, not insulin.

Relationship between intraocular pressure and obesity in children.

PURPOSE: To establish the relationship between intraocular pressure (IOP) and obesity in children. METHODS: Seventy-two obese children (body mass index in the 95th percentile or greater) were compared with 72 age-matched and sex-matched controls (body mass index <95th percentile). Both groups underwent Goldmann applanation tonometry (3 times), blood pressure measurement (3 times), and Hertel exophthalmometry. Paired and unpaired t tests and the Cochran-Mantel-Haenzel statistics were used for statistical analysis. RESULTS: The mean IOP between the obese children and controls were significantly different (P<0.0001), even after adjusting for systolic and diastolic blood pressure (P<0.001). Diurnal variation of IOP was higher in obese children (P<0.001). Obese children had higher Hertel values (P<0.001). Sex did not significantly effect IOP in either group (P>0.05). CONCLUSIONS: In addition to its indirect effect on IOP via blood pressure change, obesity is also an independent risk factor for increased IOP.

Disorders of gonadal development: a broad clinical, cytogenetic and histopathologic spectrum.

The most complicated group of sexual differentiation disorders is that of gonadal development. Disorders of gonadal development form a wide clinical, cytogenetic and histopathological spectrum. There are still some unsolved difficulties of diagnosis, development of malignancy and the sex rearing of these patients. We reviewed 23 cases of gonadal developmental disorders among 169 patients with ambiguous genitalia or delayed puberty. Among 169 patients, 87 patients were 46,XY disorders of sex development (DSD), 59 patients were 46,XX DSD without disorders of gonadal development and the remaining 23 patients had disorders of gonadal development. Nine of these 23 patients were diagnosed as 46,XY gonadal dysgenesis, 7 patients had ovotesticular DSD, 5 patients had 45,X/46,XY mixed gonadal dysgenesis. Fourteen patients with disorders of gonadal development had genital ambiguity, 5 patients had a female genital phenotype with a palpable gonad and/or delayed puberty. Four patients had the male genital phenotype. Disorder of gonadal development is a very important clinical problem with different aspects of diagnosis, treatment, rearing sex and prophylaxis. Each patient should be evaluated individually employing a multidiciplinary approach.

Experience with long-term glucocorticoid treatment in congenital adrenal hyperplasia: growth pattern compared with genetic height potential.

OBJECTIVE: Long-term replacement treatment with high doses of steroids in congenital adrenal hyperplasia (CAH) is known to have a negative influence on growth. We evaluated the effects of long-term steroid treatment in patients with classical CAH on height development in relation to genetic height potential. PATIENTS AND METHODS: Twenty-three patients with CAH (16 females, 7 males, mean age: 9.8 +/- 3.5 years) were included in this longitudinal study. The effect of steroid treatment on growth was determined by monitoring patients for 8.61 +/- 3.46 years (2-17 years) while they were treated with hydrocortisone at a mean dosage of 17.64 +/- 3.60 mg/m2/day. The height standard deviation scores (Ht-SDS), target Ht-SDS, and corrected Ht-SDS for target height was calculated for all patients. Predicted adult height according to bone age was calculated and it was determined whether height was developing according to the genetic height potential. In addition, patients were grouped as 'tight control' or 'poor control' according to their mean serum 17OH-progesterone or ACTH levels while on treatment. We evaluated whether height development was different for the tight and poor control groups. RESULTS: The mean chronological age of our patients at the time of the study was 9.89 +/- 3.53 years, Ht-SDS -0.77 +/- 1.57, target height (TH) 161.03 +/- 6.54 cm, TH-SDS -0.60 +/- 0.90, predicted height (PH) 157.2 +/- 11.16 cm, PH-SDS -1.1 +/- 1.69, and corrected Ht-SDS -0.75 +/- 1.14. There was no significant difference between the actual Ht-SDS and TH-SDS of our patients (p >0.05) but the corrected Ht-SDS was less than zero. Only 28.5% of our patients had normal height according to their genetic potential while 71.5% were shorter than their genetic height potential. While the Ht-SDS and corrected Ht-SDS were similar in the tight and poor metabolic control groups, the predicted height was significantly greater in the tight control group. CONCLUSION: We demonstrated that a hydrocortisone dose of 17.64 +/- 3.60 mg/m2/day in classical CAH had a negative influence on height development for genetic height potential in 8.5 years of follow-up and that it is necessary to use the lowest possible steroid dosage by individualizing the dose.

Niikawa-Kuroki (Kabuki) syndrome with congenital sensorineural deafness: evidence for a wide spectrum of inner ear abnormalities.

Hearing loss, mainly due to recurrent otitis media, has been reported in approximately 40% of individuals with Niikawa-Kuroki (Kabuki) syndrome (NKS). Sensorineural hearing loss leading to congenital or prelingual deafness has been described rarely. We have identified two unrelated individuals with Niikawa-Kuroki syndrome among 535 probands who have severe to profound sensorineural deafness. Bilateral absence of the cochlea with dilated dysplastic vestibule and unilateral enlarged vestibule were demonstrated in these two individuals. In conclusion, Niikawa-Kuroki syndrome should be kept in mind when evaluating an individual with congenital deafness and a wide spectrum of inner ear abnormalities occurs in this syndrome.

Evaluation of low-dose hCG treatment for cryptorchidism.

The aim of this study was to evaluate the efficiency of low-dose hCG (human chorionic gonadotropin) (500 IU/week for 3 weeks) in the treatment of cryptorchidism and in the assessment of Leydig cell functions. We include 35 male patients who had been diagnosed with cryptorchidism by the pediatric endocrinology specialist in the study. Twenty-one cases (Group I) received 500 IU/week of hCG while 14 patients (Group II) received 1500 IU/m2 three times a week, both for three weeks. The percentage of testis descent was calculated for both groups for the right and left testes. Leydig cell functions were evaluated by the pre- and post-treatment measurement of plasma testosterone level in all cases. A delta testosterone greater than 100 was considered to be a sufficient response. Among our patients, 77% had unilateral and 23% bilateral cryptorchidism. Unilateral cryptorchidism was detected in 80.9% of Group I patients and 71.4% of Group II patients. The pre-treatment percentages for Group I of right- and left-sided cryptorchidism were 81% and 38.1%, respectively, which decreased to 23.8% and 9.5% after treatment. The pre-treatment percentages for Group II of right- and left-sided cryptorchidism were 57.1% and 71.4%, respectively, which decreased to 14.3% and 35.7% after treatment. The success rate of hCG treatment, as defined by the testis descending into the scrotum, was 66.7% for Group I and 57.1% for Group II (p > 0.05). There was no significant difference between the two groups when Leydig cell functions were assessed. In conclusion, it is possible to use low-dose hCG for the treatment of cryptorchidism and the assessment of Leydig cell functions.

Propylthiouracil-induced hypersensitivity syndrome.

Propylthiouracil (PTU) is usually the first choice for the treatment of hyperthyroidism, but it has serious side effects such as hepatitis, cholestatic jaundice, splenomegaly and lupus-like syndrome, in addition to mild and common side effects like granulocytopenia, pruritus, urticaria and maculopapular or papular eruption. Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis is another serious side effect. A 14-year-old female receiving PTU treatment for hyperthyroidism was referred to our clinic with fever, cough and dyspnea. The PTU dosage was first decreased but pericardial, dermal and joint involvement ascribed to PTU developed later and the drug was discontinued. ANCA-positive vasculitis due to PTU was considered when tests revealed an ANCA-positive state. We suggest that severe multisystemic vasculitis due to PTU should be considered during PTU usage.

5 alpha steroid reductase deficiency in Turkey.

5 alpha steroid reductase 2 (5 alpha SR2) deficiency is an autosomal recessive enzyme defect causing male pseudohermaphroditism (MPH) because of an abnormally low peripheral conversion of testosterone to dihydrotestosterone (DHT), which is required for the normal differentiation of external male genitalia. The present report describes the distribution of 5 alpha steroid reductase gene mutations in the Turkish population in the light of published reports from different centers. Eight Turkish patients from unrelated Turkish families and a large pedigree of one of these patients are also discussed. These patients were followed up at Ankara University Department of Pediatric Endocrinology. The presence of Leu 55 Gln mutation in six patients out of 8 indicates the increased prevalence of this mutation in the Turkish population with different presentations. One patient out of six (patient FG) had a large pedigree of Leu 55 Gln mutation in exon 1. The pedigree of this family with marital consanguinity was very remarkable and extraordinary. A further 85 members of this family were analyzed for exon 1 Leu 55 Gln 5 alpha SR2 gene mutations. Forty two out of the 85 subjects (49.41% ) had this alteration in gene mutation. Thirty-one of them were heterozygous (18 genetic male, 13 genetic female) and 11 of them were homozygous (8 genetic male, 3 asymptomatic female carriers) for this mutation. A trinucleotid deletion at straddling codons 156 and 157 is responsible for a methionize residue at position 157 (delta Met 157) of 5 alpha SR type 2 gene which was first described in our patient NA. Two additional Turkish patients were reported by different investigators with this rare mutation and this also suggests an increased prevalence of this mutation in the Turkish population. In conclusion Leu 55 Gln mutation in exon 1 seems to be a hot spot in Turkish patients. Hence 5 alpha SR2 gene mutation analysis especially Leu 55 Gln mutation in exon 1 and delta Met 157 in exon 3, must be evaluated in Turkish patients with male pseudohermaphroditism according to our results and other Turkish patients reported by different investigators. It is important that homozygous asymptomatic female carriers be taken into consideration in this clinical entity especially in closed populations because of the risk of carrying the disease to their offspring.

Evaluation of therapeutics management patterns and glycemic control of pediatric type 1 diabetes mellitus patients in Turkey: A nationwide cross-sectional study.

AIMS: To evaluate the management strategies, glycemic control and complications of pediatric type 1 diabetes mellitus (T1DM) patients in Turkey. METHODS: Study included 498 patients with T1DM between the ages 1-18. Data provided from patients' hospital files were recorded on standard case report forms by applicant clinicians within the 3months of data collection period between October 2012 and July 2013. RESULTS: Mean age of patients was 11.3±3.8years. Mean duration of DM was determined as 3.7±3.1years. Majority of patients (85.5%) used basal/bolus injection (BBI), and 6.5% used continuous subcutaneous insulin infusion pump. Assessment of glycemic control based on HbA1c levels showed that 29.1% of patients had an HbA1c value <7.5% (58mmol/mol), 16.1% had a value between 7.5% (58mmol/mol) and 8% (64mmol/mol), 19.1% had a value between 8.1% (64mmol/mol) and 9%(75mmol/mol) and 35.7% a value >9%(75mmol/mol). Hypoglycemia was reported in 145 (29.1%) patients and the number of severe hypoglycemic attacks in the last 3months was 1.0±2.4. Taking into consideration the carbohydrate count and insulin correction dose and parents with high socioeconomic status was related to have better glycemic control. The most common comorbidities were Hashimoto's thyroiditis/hypothyroidism (6.2%) followed by celiac disease (3.8%), epilepsy(1.2%), and asthma(1.0%). CONCLUSIONS: BBI insulin therapy is widely used among pediatric T1DM patients in Turkey. However, despite improvements in treatment facilities and diabetic care, glycemic control is not at a satisfactory level. Therefore, new and comprehensive initiatives require for pediatric T1DM patients with poor glycemic control. Promoting use of carbohydrate count and insulin correction doses may improve the glycemic control of pediatric T1DM in Turkey.

Molecular analysis of PROP1, POU1F1, LHX3, and HESX1 in Turkish patients with combined pituitary hormone deficiency: a multicenter study.

To investigate the specific mutations in PROP1, POU1F1, LHX3, and HESX1 genes in patients with combined pituitary hormone deficiency (CPHD) in Turkey. Seventy-six patients with CPHD were included in this study. Based on clinical, hormonal, and neuro-radiological data, relevant transcription factor genes were evaluated by Sanger sequencing and multiplex ligation-dependent probe amplification. Total frequency of mutations was 30.9 % in patients with CPHD. Frequency was significantly higher in familial patients (p = 0.001). Three different types of mutations in PROP1 gene (complete gene deletion, c.301-302delAG, a novel mutation; IVS1+2T>G) were found in 12 unrelated patients (21.8 %). Mutations in PROP1 gene were markedly higher in familial than in sporadic cases (58.8 vs. 5.3 %, p < 0.001). Homozygous complete gene deletion was the most common mutation in PROP1 gene (8/12) and was identified in six familial patients. Four different homozygous mutations [p.Q4X, novel mutations; exons 1-2 deletion, p.V153F, p.I244S] were detected in POU1F1 gene. Central precocious puberty was firstly observed in a sporadic-male patient with homozygous POU1F1 (p.I244S) mutation. A homozygous mutation in HESX1 gene (p.R160H) was detected in one patient. This study is the first to investigate specific mutations in CPHD patients in Turkey. Complete deletion in PROP1 gene was the most common mutation encountered in patients with CPHD. We believe that the results of this study will contribute to the establishment of genetic screening strategies in Turkey, as well as to the studies on phenotype-genotype correlations and early diagnosis of CPHD patients.

The risk of functional ovarian hyperandrogenism and polycystic ovary syndrome in patients with hyperandrogenism.

To describe the presence of dysregulations in steroid biosynthesis and the risk of functional ovarian hyperandrogenism (FOH) and polycystic ovary syndrome (PCOS)-like development in children with hyperandrogenism, 28 girls were studied. Adrenal steroidogenic profile was defined by basal and ACTH-stimulated levels of 17OHP, cortisol, DHEAS and androstenedione, and delta precursor/delta product ratios. Ovarian hyperandrogenism was defined by 17OHP response to LHRH stimulation, and pelvic ultrasonography (US) was performed to evaluate ovarian morphology. Basal and ACTH-stimulated hormonal results revealed non-classical 21-hydroxylase deficiency-like status in one patient (3.6%), and 21-hydroxylase deficiency heterozygote carrier-like state in four patients (14.3%), while the other 23 patients (82.1%) had functional adrenal hyperandrogenism (FAH). Among these patients with FAH, 47.83% had FOH; when these patients were evaluated by pelvic US, 30.4% had morphological changes which were not concordant with their age. We suggest that even mild forms of hyperandrogenism must be considered seriously and dysregulations of the steroidogenic pathway and ovarian abnormalities must be evaluated carefully to determine the risk of FOH/PCOS.

Lower lid retraction: a valuable finding in juvenile Graves' orbitopathy.

PURPOSE: To evaluate the findings of juvenile Graves' orbitopathy. SUBJECTS AND METHODS: Retrospective evaluation of our patients with Graves' disease who are younger than 16 years. RESULTS: Seventeen patients younger than 16 years were identified among 138 patients who were being treated for hyperthyroidism and goiter. Eleven (64.7%) of them had lid findings, orbital findings, or both and constituted 8.8% of the total of 125 such patients. Ophthalmic signs were common and were among the presenting signs in children with Graves' disease. Orbitopathy was mild and was more frequent in girls. Lower lid retraction and lag (ie, hesitation of the lower lids to follow upgaze) appeared to be constant and early findings. CONCLUSION: Ophthalmologists and pediatricians should be aware of and look for lid signs in children presenting with related complaints and a history suggesting hyperthyroidism, goiter, or both.