Use of percutaneous estrogen gel for induction of puberty in girls with Turner syndrome.

The aim of pubertal induction by estrogen in hypogonadic girls is to achieve physical and psychological development similar to that in natural puberty. We investigated the use of percutaneous estradiol gel for induction of puberty in girls with Turner syndrome (TS).Twenty-three girls with TS and hypogonadism were included in the study. The initial percutaneous dose of 0.1 mg ended as 1.5 mg in the fifth year. The efficacy of the treatment was monitored by measuring height, weight, skeletal age, pubertal status, and serum hormone levels and gynecological ultrasonographic examinations throughout the study. Mean serum estradiol concentrations increased from 22.2 pmol/liter at baseline to 162.2 pmol/liter, and mean FSH levels decreased from 77.4 IU/liter at baseline to 19.2 IU/liter after 5 yr. There were no significant differences between GH users and nonusers with regard to height sd score, weight sd score, bone age acceleration, or adult height. The development of secondary sexual characteristics and uterine growth progressed gradually during the study. All girls reached at least stage B4P4. With percutaneous estradiol gel, the development of secondary sexual characteristics and uterine growth proceeded gradually, mimicking natural puberty. Estradiol gel was safe, easy to use, and well accepted by the subjects and provides an excellent way to individualize pubertal induction.

Growth and adrenal androgen status at 7 years in very low birth weight survivors with and without bronchopulmonary dysplasia.

AIMS: To evaluate whether 7 year old VLBW (very low birth weight, <1500 g) survivors with and without bronchopulmonary dysplasia (BPD) evince similar growth status and higher adrenal androgen (AA) levels than term controls, and whether AA levels are higher in VLBW children born small for gestational age (SGA) than in non-SGA cases. METHODS: Assessment of height standard deviation score (SDs), body mass index (BMI), and serum androstenedione and dehydroepiandrostenedione sulphate levels in 31 VLBW children with BPD, 33 without BPD (no-BPD group), and 33 term controls. RESULTS: Lower median (range) height SDs was found in BPD (-1.0 (-3.4 to 1.4) SD) and no-BPD (-0.9 (-2.9 to 2.2) SD) children than in term controls (0.3 (-1.5 to 1.9) SD). Low BMI (below 10th centile) was more common in both the BPD (18 (58%)) and no-BPD (16 (49%)) children compared to term cases (3 (9%)). The median (range) androstenedione levels tended to be higher in the BPD (0.8 (0 to 2.8) nmol/l) and no-BPD (0.8 (0 to 2.3) nmol/l) groups than in term controls (0.6 (0 to 1.8)). Higher median (range) dehydroepiandrostenedione sulphate levels were detected in the no-BPD compared to the term group (0.9 (0 to 4.1) v 0.3 (0 to 2.3) micro mol/l). VLBW children born SGA had higher AA levels compared to non-SGA cases. CONCLUSIONS: At 7 years of age, VLBW children are shorter and tend to have higher AA levels than term controls, but VLBW children with and without BPD do not differ from each other in growth or AA status. Those born SGA have higher AA levels compared to non-SGA cases. The consequences of these findings to final height and to later metabolic and vascular health remain to be determined.

Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1.

ATP-sensitive potassium channels play a major role in linking metabolic signals to the exocytosis of insulin in the pancreatic beta cell. These channels consist of two types of protein subunit: the sulfonylurea receptor SUR1 and the inward rectifying potassium channel Kir6.2. Mutations in the genes encoding these proteins are the most common cause of congenital hyperinsulinism (CHI). Since 1973, we have followed up 38 pediatric CHI patients in Finland. We reported previously that a loss-of-function mutation in SUR1 (V187D) is responsible for CHI of the most severe cases. We have now identified a missense mutation, E1506K, within the second nucleotide binding fold of SUR1, found heterozygous in seven related patients with CHI and in their mothers. All patients have a mild form of CHI that usually can be managed by long-term diazoxide treatment. This clinical finding is in agreement with the results of heterologous coexpression studies of recombinant Kir6.2 and SUR1 carrying the E1506K mutation. Mutant K(ATP) channels were insensitive to metabolic inhibition, but a partial response to diazoxide was retained. Five of the six mothers, two of whom suffered from hypoglycemia in infancy, have developed gestational or permanent diabetes. Linkage and haplotype analysis supported a dominant pattern of inheritance in a large pedigree. In conclusion, we describe the first dominantly inherited SUR1 mutation that causes CHI in early life and predisposes to later insulin deficiency.

Vulvar symptoms in paediatric and adolescent patients.

Vulvovaginal symptoms in children and young adolescents are not yet very well understood, nor is the actual incidence known. This study evaluates the character and possible infectious aetiology of vulvar symptoms of females aged up to 16 y. The signs, symptoms and bacteriological findings of 68 consecutive cases were studied. The study was conducted in the University Hospital of Tampere at a special gynaecological consultation clinic for children and adolescents. Sixty-eight patients were included in the study: 48 girls (71%) were prepubertal, at Tanner stage M1P1, 26 patients were 2-4-y-old and 15 were 5-7-y-old. The duration of symptoms was known for 46 patients: 41% had had symptoms for >1 mo and 20% for >6 mo. Forty-eight patients had abnormal clinical findings on examination and 16 (33%) of them had an infectious aetiology. Streptococcus pyogenes infection was identified in 11 (16%) patients, all of whom had symptoms. Candida was identified in 6 (9%) patients. No infectious aetiology was found among 26 patients who had symptoms and abnormal clinical findings. Vulvovaginal symptoms during childhood are more common among younger children (<7 y). In 67% of patients no infectious aetiology could be found. Samples for microbiological culture should be taken from symptomatic patients and symptomatic areas. Cultures of Candida and bacteria are necessary but usually sufficient. If a microbiological aetiology is established, treatment can be assigned accordingly. Patients with vulvar symptoms and findings but with an unclear aetiology need support and advice on proper hygiene and can intermittently use mild corticosteroids locally.

Surgery for ovarian masses during childhood and adolescence: a report of 79 cases.

STUDY OBJECTIVE: Abdominal pain is a common symptom in female children and adolescents that may be caused by appendicitis, other gastrointestinal or urological conditions, or gynecological problems. This study evaluates retrospectively the preoperative work-up and the operative treatment of ovarian masses in young girls at our institution. SETTINGS: The medical records of all female patients aged 17 years or less operated on for an ovarian mass in 1971-1995 at the Tampere University Hospital were reviewed. RESULTS: Seventy-nine patients were identified. In the 1970's preoperative sonography was done on only 15% of the patients. In the 1990's the figure was 65%. Thirty-seven (47%) of all operations were emergency procedures; of these, 41% were performed by a gynecologist. Seven of the tumors were malignant. Thirty-four patients had a benign neoplasm and 26 had functional ovarian cysts. Eight patients were operated on for an adnexal torsion and four patients had other adnexal conditions. Unilateral salpingo-oophorectomy was performed on 20 patients, unilateral oophorectomy on 12 patients, and ovarian resection on 27 patients. An occasional appendectomy was performed on 37 patients. CONCLUSIONS: Surgery for benign neoplasms and functional lesions seems to be too extensive. This is likely to be due to inadequate preoperative work-up and to the fact that many of the operations were performed on an emergency basis and by non-gynecologists. A gynecological examination with sonography should be included in the diagnostic work-up of a young girl's abdominal complaints. With a proper preoperative work-up adequate treatment, which often consists of expectation, can be chosen for the patient and subsequent problems related to fertility and abdominal complaints can be avoided.

Growth of prepubertal children with juvenile chronic arthritis.

The height and height velocity standard deviation scores (HSDS and HVSDS) of 64 prepubertal children with mild to moderate chronic arthritis were calculated at the time of diagnosis and then annually during treatment and follow-up of 4 y. Preceding the diagnosis, children with chronic arthritis were as a group slightly taller than their healthy peers. During the year before the diagnosis they had grown faster than their peers. During the first year of treatment their growth velocity decreased (change in the mean HVSDS from +0.63 to -0.52), but during further follow-up it returned to the pretreatment level (the mean HVSDS being +0.53 four years after the diagnosis). The growth was influenced more by polyarticular than by pauciarticular disease. The cumulative total dose of glucocorticosteroids did not have statistically significant influence on growth. In conclusion, growth retardation in prepubertal children with chronic arthritis was seen following the diagnosis and initiation of treatment, more so in polyarticular disease. During further follow-up, growth velocity increased. This reflected the growth promoting effect of inflammatory process control.

Experiences of special gynaecological services for children and adolescents: a descriptive study.

Gynaecological examination of girls during childhood is undertaken somewhat infrequently. These genital examinations should not be taboo or a frightening experience for the girl, for her parents or for the physician. Studies of children suspected of sexual abuse have paid attention to the wide variety of gynaecological conditions already present in childhood. In 1988 we founded a special gynaecological outpatient clinic for girls under 16 y of age at a university hospital to develop the special knowledge and skills needed in children's gynaecology. In this gynaecological clinic for children and adolescents we were able to gain and offer expert knowledge of the problems of this age group. In this special clinic for children, gynaecological examination by special techniques and sonography led to a diagnosis in 71% of the patients without any instrumentation. Children and adolescent girls in need of special gynaecological care should be recognized specifically. Particular attention should be paid to the gynaecological care of victims of child sexual abuse and mentally or physically handicapped girls. In good co-operation with the girl, a gynaecological examination can become a positive experience during the development of female identity.

Normal growth of prepubertal nephrotic children during long-term treatment with repeated courses of prednisone.

The growth of 21 prepubertal children with steroid-dependent frequently relapsing nephrotic syndrome was studied before and during treatment with repeated courses of oral prednisone for 4 y. The height and height velocity standard deviation scores (HSDS and HVSDS) of the nephrotic children were -0.11 and -0.06, respectively, at the onset of the disease and -0.12 and +0.05, +0.14 and +1.02, +0.21 and +0.78 and +0.17 and +0.66, respectively, thereafter yearly during the treatment. The mean yearly cumulative dose of prednisone was 6300, 3459, 2677 and 2081 mg/body area (m2) at the first, second, third and fourth year, respectively. The nephrotic children grew normally for their age before onset of the disease and growth remained normal despite prednisone treatment.

Growth of prepubertal children with inflammatory bowel disease.

BACKGROUND: Growth retardation has been reported in children with chronic inflammatory bowel disease, especially in those with Crohn's disease. Most of these studies concern adolescent patients. METHODS: The growth of 47 prepubertal children (20 boys and 27 girls, mean age at diagnosis 7 years) with inflammatory bowel disease was studied at Tampere University Hospital, Department of Paediatrics. The mean height and height velocity standard deviation scores were calculated at diagnosis and, after that, yearly. The cumulative doses of oral and rectal prednisone per year were calculated. The severity of the disease was scored. The statistical analysis was carried out using the analysis of variance for repeated measurements. RESULTS: During the year preceding the diagnosis, children with inflammatory bowel disease had grown more slowly than their healthy peers. At diagnosis, they were slightly shorter as a group than are healthy children. During treatment and follow-up the mean height velocity of children with inflammatory bowel disease increased (change in the mean height velocity standard deviation scores from -0.84 to +1.08), normalizing the mean heights of these children compared with those of their healthy peers (change in the mean height standard deviation scores from -0.32 to +0.05). In the analysis of covariance, the poorest growth was seen in children with Crohn's disease, scored as severe, and the best growth in children with mild ulcerative colitis. No difference was seen in groups with or without prednisone treatment. CONCLUSIONS: Growth retardation is an important sign of chronic inflammatory bowel disease in prepubertal as well as adolescent children. During treatment, increasing growth velocity brings these children as a group to normal heights for age and sex.

Growth hormone therapy with three dosage regimens in children with idiopathic short stature. European Study Group Participating Investigators.

OBJECTIVE: In children with idiopathic short stature (ISS) we studied the growth-promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in three dose regimens and evaluated whether increasing the dosage after the first year could prevent a decline in height velocity (HV). DESIGN: Included were 223 patients who were treated with subcutaneous administrations of rhGH 6 days per week. They were randomized to three groups: 3 IU/m2 body surface/day, 4.5 IU/m2/day, and 3 IU/m2/day during the first year and 4.5 IU/m2/day thereafter, corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively. Growth was compared with a standard of 229 untreated children with ISS [ISS standard]. RESULTS: During the first year of treatment HV almost doubled and was higher with 4.5 IU/m2 than with 3 IU/m2. In the second year HV no longer differed among the groups, but increasing the dosage slowed the rate of the fall of HV. During 4 years of therapy the height SD score for age increased by a mean (SD) of 2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7). After 4 years the results of the group with 4.5 IU/m2 were slightly better than those of the other groups. When dropouts were included in the analysis (assuming a stable height SD score after discontinuation of rhGH therapy), height gain was still significant. CONCLUSIONS: During 4 years of rhGH therapy, growth and final height prognosis improved, slightly more with 4.5 IU/m2 than with 3 IU/m2 or 3 to 4.5 IU/m2. However, bone age advanced on average 4.8 years during this period; therefore, any effect on final height will probably be modest.

Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids.

Reports on the influence of inhaled glucocorticoids on growth have been controversial. We studied the growth of prepubertal asthmatic children prior to and during glucocorticoid therapy. We collected retrospectively the notes of 201 asthmatic children aged 1-11 years receiving inhaled beclomethasone dipropionate or budesonide. We calculated their height and height velocity standard deviation scores (HSDS and HVSDS, respectively) before the treatment and up to 5 years during the treatment and compared those with the growth of healthy peers. The dose of the medication was calculated and the severity of asthma was assessed. The asthmatic children grew similarly to their healthy peers before treatment with inhaled glucocorticoids: the mean HSDS was +0.02 and the mean HVSDS +0.01 for boys and -0.16 and +0.13 for girls, respectively. Growth retardation took place soon after the start of the treatment, the most profound decrease in the growth velocity (the change in the mean HVSDS from +0.05 to -0.88) occurring during the first year of treatment. The growth-retarding effect of inhaled glucocorticoids was not dose dependent. In the covariance analysis the increasing severity of asthma had a significant interaction with repeated measurements, showing more growth retardation along with more severe asthma, especially during long-term treatment. Asthma per se does not impair growth, but inhaled glucocorticoids may do so. Careful monitoring of the growth of all asthmatic children receiving inhaled glucocorticoids is necessary because the growth-retarding effect of the medication is not dose dependent. Individual sensitivity might explain the differences seen in the growth patterns of children receiving inhaled glucocorticoids.

Craniofacial features in patients with deficient and excessive growth hormone.

We studied the role of growth hormone (GH) in craniofacial growth by analyzing the craniofacial structures in patients with either deficient or excessive GH. The cephalogrammes of 21 patients with isolated or combined GH deficiency and of two patients with GH excess were compared with cephalogrammes of age and sex matched controls, and the patients with deficient GH also with height and sex matched controls. In cephalometric measurements, skeletal anatomy was followed as closely as possible. All patients had a Class I or an end-to-end dental occlusion. Head circumference was normal in all patients. Facial widths were significantly smaller in patients with deficient GH but at the level of + 2 SDs in the two with GH excess when compared to Finnish norms. In patients with deficient GH, facial heights were significantly smaller than in age matched controls, but of the same order with height controls for anterior facial height. Posterior facial height was smaller even in this comparison. In patients with GH excess, facial heights were much larger and at the levels of +3 and +6 SD. Clivus was shorter in patients with deficient GH and longer (+ 1.9 and +3 SD) in the two with GH excess. All angulations of the sphenoidal plane deviated from those of the controls in the group with GH deficiency. The cranial base angle (CL-SPhen) was smaller than in controls while it was normal in patients with GH excess. We are inclined to interpret the craniofacial structure of those with deficient GH as being unique to the condition rather than merely negative allometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of conventional dose growth hormone therapy for two years on height velocity and height prognosis in girls with Turner syndrome.

The aims of this national multicentre study in Finland were to evaluate whether the height velocity of patients with Turner syndrome would increase with the conventional human growth hormone (GH) therapy regimen normally given to GH-deficient children and whether girls with Turner syndrome actually show GH neurosecretory dysfunction. Finally, the study should show whether GH therapy improves height prognosis and, eventually, final height. Twenty-five girls with Turner syndrome, aged 7.5-14.4 years, entered the study. Their ability to secrete GH was determined and, surprisingly, several would have been classified as having GH deficiency. All girls received GH, 0.1 IU/kg/day (maximum dose 4 IU/day) s.c., and once over 12.5 years old, they also received oestradiol valerate and fluoxymesterone. They showed a convincing increase in height velocity, and rapid growth continued during the second year of therapy. The effect of GH therapy on final height is still unknown. The therapy was remarkably free of side-effects.

Oestrogen treatment of tall girls: effect decreases with age.

Fifty-nine tall girls were treated with oestrogen to reduce final height, starting at the ages of 9.1 to 16.2 years. We assessed the result of this treatment by comparison with matched controls. The epiphyseal bone age at the start of therapy, the final height, the Bayley-Pinneau (BP) and Roche-Wainer-Thissen (RWT) predictions of final height, and the errors in both predictions were evaluated. The matched pairs were divided into three groups according to bone age at the start of treatment; I less than 10.5 (n = 16), II 10.5-12.0 (n = 22) and III greater than 12.0 years (n = 21). The mean (SD) intrapair reduction of height for these groups was 9.7 (4.0) cm, 4.3 (4.3) cm and 3.5 (3.2) cm, respectively, according to BP predictions and 6.3 (4.3) cm, 3.4 (3.0) cm and 1.2 (3.3) cm according to RWT predictions. No method of predicting height is accurate for tall girls and simultaneous predictions may differ greatly. Close agreement between the BP and RWT predictions does not indicate greater accuracy. The earlier therapy is started, the greater is the effect. Young girls need psychosocial support with therapy.

Turner syndrome: effect of hormone therapies on height velocity and adult height.

76 patients with Turner syndrome received estrogen alone, androgen and estrogen started simultaneously or, after preceding androgen therapy, estrogen with or without androgen. Six patients had spontaneous pubertal development and received no estrogen. Two patients received human growth hormone with androgen during greater than 2.0 years. Height velocity increased during all therapies to mean SD scores of 7.6 during androgen-estrogen started simultaneously, 4.6 during androgen alone, 4.2 during androgen-estrogen after preceding androgen, 2.7 during estrogen alone, and 0.6 during estrogen after preceding androgen. Adult height was measured in all cases, it was 145.5 +/- 5.7 (mean +/- SD) for the whole series without significant differences between the groups. It correlated strongly with midparent height, and was greater for patients with the 45,X karyotype than for the others combined.

Ultrasound imaging in diffuse thyroid disorders of children.

The diagnosis of diffuse thyroid disorders in children is based mainly on hormone and antibody determinations and a cytologic sample taken by aspiration biopsy. The cytologic sample is not always obtainable in small children or when the thyroid gland is not enlarged. Thyroid antibodies lead to diagnosis only in a proportion of cases. Gamma imaging is not recommended in children because of the radiation risk. The aim of this study was to demonstrate that ultrasound imaging can detect diffuse thyroid disorders in children. Ultrasound images were abnormal in 92% of all subjects; they were abnormal in 97% of cases with thyroiditis and in most cases ultrasound was diagnostic. With antibody determinations, only 60% of the cases of thyroiditis could be diagnosed. Ultrasound imaging--a risk-free method--should be included in the diagnostic investigation of thyroid disorders.

Ultrasonography in congenital hypothyreosis.

To our knowledge, ultrasonography has not so far been used as an additional source of information in the early screening for congenital hypothyreosis. This study demonstrated, firstly, that the normal neonatal thyroid gland could always be recognized by ultrasonography and, secondly, that in congenital hypothyreosis absence of thyroid tissue from the normal site could be detected by ultrasonography, whereas ectopic tissue in the tongue could not readily be identified. The findings may be useful in the diagnosis of congenital hypothyreosis.