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Albright hereditary osteodystrophy (AHO) is a syndrome caused by inactivating mutations in the GNAS (guanine nucleotide-binding protein, alpha-stimulating) gene. Patients with AHO have short stature, obesity, brachydactyly and subcutaneous calcifications. AHO can be associated with pseudohypoparathyroidism type IA (PHP-IA) with upregulation of parathyroid hormone, whereas in pseudo-pseudohypoparathyroidism (PPHP), an endocrinopathy is not present. We report the case of a 5-month-old male infant who presented with slowly progressive linear atrophic skin lesions. The histological findings showed evidence of dermal hypoplasia. The child's father had PHP-IA. Four months after presentation, the infant developed calcifications within the pre-existent atrophic lesions. No alterations in calcium metabolism were noted. Analysis of the GNAS gene identified a short duplication leading to a frameshift mutation. We conclude that linear atrophic skin lesions may be an early sign of imminent cutaneous calcifications in AHO., (© The Author(s). CED © 2012 British Association of Dermatologists.)

Hyperparathyroidism is a rare finding in children. It is a typical sign of vitamin D-deficiency caused by different reasons. It may also be due to calcium wasting syndromes, and it can rarely be induced by adenomas of the parathyroid glands and in parathormone receptor mutations (pseudohyperparathyroidism). A 12-year old Gambian girl living in Hamburg, Germany, was developing abdominal and joint pain. Serum analysis revealed low serum-calcium, significantly elevated parathormone and decreased vitamin D. Immigrant rickets was assumed. Because of abdominal pain and iron deficiency, lambliasis was ruled out. Celiac disease was demonstrated by gliadin and endomysium antibodies as well as by intestinal mucosa biopsy. Despite of a gluten-free diet the joint pains persisted. They were declared by rheumatologists to be caused by a chronic juvenile arthritis (sister disease of celiac disease). However, there were no positive inflammation signals and no clear elevated rheuma-immunology. Follow up: Gluten-free diet and additional treatment with calcium and active vitamin D did not stop increasing parathormone levels, did not stop abdominal and joint pain, and did not stop increment of positive celiac disease antibodies. Assuming compliance problems the patient was then treated with vitamin D injections, which caused decreasing parathormone levels and vanishing joint pain. Celiac disease can cause intestinal rickets with elevated parathomone levels mimicking chronic juvenile arthritis, if gluten-free diet is not strictly performed by compliance problems.

Conventional assays for determination of growth hormone (GH) in serum measure immunoreactive molecules of a blood sample. The immunofunctional assay (IFA), on the other hand, is able to determine biologically active molecules. In our study, we evaluated GH determination in children with IFA to compare these data with clinical reliable data of conventional assay systems, since there is only insufficient data concerning the clinical use of IFA in children. The comparison of GH determinations by IFA and two immunoradiometric assays showed different results for the same serum sample. Peak and trough concentration levels determined by these three different assays were always measured at the same time, but absolute GH concentration levels varied. Statistic analysis verified a linear regression of our data and allowed a conversion of data measured by IFA to predict values of the other assays used and vice versa. The traditional cut-off level for the diagnosis of GH deficiency of 10 ng/ml was based originally on results of polyclonal radioimmunoassays. This internationally applied cut-off level has been converted based on the regression analysis for prediction of this study and we found the 95% confidence interval on the mean measurements by IFA to be between 3.11 and 3.28 ng/ml., (Copyright 2007 S. Karger AG, Basel.)

To delineate the development of melatonin (MLT) production during childhood, we measured the excretion of MLT and 6-hydroxymelatonin sulfate (MLTS) in the urine of children (n = 134) from the 26th week of gestation until the age of 20 years. MLTS excretion showed a diphasic pattern with declining values in preterm babies with lowest values around term. After birth, the values remained low for the first 6 months of life. The highest values were reached between 4 and 7 years of age with a smooth but steady decline thereafter. A night-day difference was not detectable before the age of 6 months; the greatest night-day variations occurred at the time of the highest MLTS excretions. The MLT values showed an identical pattern but with amounts 1,000 times smaller; the ratio of MLTS to MLT increased from 40:1 in preterm babies to 900:1 in prepubertal children. In summary, the MLT/MLTS excretion exhibits the highest activity with respect to total secretory capacities as well as night-day differences at the time of gonadal quiescence during childhood. The strong inverse correlation of MLT and MLTS excretion with the hypothalamic-pituitary-gonadal activity points to a causal relationship between pineal gland activity and pubertal development.

Cushing's disease resulting from intrasellar corticotropin-releasing hormone (CRH)-secreting gangliocytomas is very rare, and only two such cases have been reported in the literature to date. The authors present a third case in which an adrenocorticotropic hormone-secreting pituitary adenoma was found in addition to a gangliocytoma in a 10-year-old girl with clinical and endocrinological symptoms of Cushing's disease. Computed tomographic and magnetic resonance imaging scans showed a suprasellar and parasellar tumor. A green-colored, heterogeneous tumor and a small adenoma were removed transsphenoidally. Histological examination revealed a large gangliocytoma immunoreactive for CRH and a small, mucoid cell pituitary adenoma immunoreactive for ACTH. This is the first case of such a tumor causing Cushing's disease in a child. It might exemplify induction of an ACTH-secreting pituitary adenoma by means of chronic overstimulation of CRH.

Genetic counselling of the parents is prerequisite before prenatal diagnosis and prenatal therapy of CAH. Today, chorionic villous biopsy with DNA probe is the method of choice to identify homozygous CAH-fetuses. The aim of prenatal therapy is to prevent intrauterine virilization of the external genitalia in affected female fetuses. Therefore, dexamethasone (3 x 0.5 mg/d p.o.) is given to the mother immediately when pregnancy is confirmed, before prenatal diagnosis and karyotyping is possible. After the result of prenatal diagnosis, treatment is continued until term only when the fetus is affected and female. Prenatal diagnosis and effective treatment of female CAH fetuses greatly reduces the need for corrective surgery and thus helps to alleviate anxieties of prospective parents and therefore encourages further pregnancies. However, prenatal treatment of CAH to date still is an experimental therapy [corrected].

In an attempt to improve detection of heterozygote carriers of the gene for congenital adrenal hyperplasia (21-hydroxylase deficiency; CAH) 64 families with at least 1 affected member (72 homozygotes and 191 clinically healthy subjects) were studied by HLA genotyping and by the single-dose corticotropin stimulation test. Plasma samples were drawn immediately before corticotropin and 60 min after its injection, and they were analysed simultaneously for eight adrenal steroids by radioimmunoassay after extraction and automated gel chromatography. Heterozygosity was defined as the presence of one HLA haplotype in common with the affected relative. Of the various basal and corticotropin-stimulated steroid levels and their ratios, the ratio of 17-hydroxyprogesterone to 11-deoxycorticosterone after corticotropin had the greatest power to discriminate between heterozygotes and normal relatives; that ratio was significantly higher in the heterozygotes (n = 116) than in the normal relatives (n = 75) and there was no overlap between the groups (range 12.2-214 vs 1.2-11.9). Thus, it is possible to detect all CAH heterozygotes without examining the index case by means of specific steroid analysis.

36 tall girls aged 10.3 to 15.5 years were treated with ethinylestradiol (0.5 mg/day) and norethisterone (15 mg/day). To date treatment for seventeen girls has been completed. Before treatment their bone age ranged from 11.0 to 13.5 years and mean height prediction was 185.19 cm (181.40-193.00 cm). After about two years of treatment their final height averaged 178.96 cm (171.60-183.50 cm). Predicted height was reduced by an average of 6.23 cm. The reduction in final height was significantly greater when therapy was started before a bone age of 12 years. Thirteen girls, re-examined after discontinuation of therapy, all had regular menstrual bleeding within six months. There were no serious or irreversible side effects during the period of observation.

In 3 groups of 8 children and adolescents each with Prader-Willi-Labhart's Syndrome (PW-S), obese patients matched for body weight (control I), and normal weight subjects matched for pubertal stage (control II) plasma concentrations of melatonin, cortisol, growth hormone (hGH), insulin, gonadal hormones, and gonadotropins were measured every 1 to 4 hours in 24-hour-profiles. All hormones were determined by radioimmunoassay. The specific melatonin antibody was raised in rabbits. Criteria of the melatonin assay were as follows: detection limit for plasma concentrations of 13 pg/ml, intraassay and interassay variations: 8.4 and 11.2%, respectively. PW-S-patients showed cortisol fluctuations within normal limits. hGH was lower than 5 micrograms/l even during sleep, insulin ranged between 5 and 170 mU/l, and no excessively high glucose levels were found. Estradiol and testosterone were low for age and for pubertal development in all patients except in two girls. Basal LH and FSH levels were in the low normal range and showed sluggish response to LHRH. Plasma melatonin was low during the day, increased at mid-night and peaked at 3 a.m. Melatonin levels in PW-S were not significantly different from those in both control groups. We concluded that the impairment of gonadotropin secretion in patients with PW-S is not due to elevated levels of plasma melatonin.

Following ACTH-stimulation, in 40 patients plasma corticoid levels (CPB-technique) were determined every 15 min for three hours to demonstrate the period of maximal increase. There was no significant difference in the increase of plasma cortisol following intravenous or intramuscular injection of ACTH (beta1-23). Peak values were reached at 60 min (65.2 +/- 3.2 mug/100 ml). This is considered to be the right moment for blood sampling when using a short ACTH-test.

Epilepsy in early childhood has been treated successfully with ACTH. However, side effects were significant due to the stimulation of the adrenal cortex by high doses of ACTH over a long time. It has been suggested, that ACTH does not influence the seizures via the adrenal cortex. Therefore we administered an ACTH fragment (ACTH 4-10) which does not influence the adrenal cortex. Seven children aged between 8 months and 13 1/2 years were treated at least for 3 weeks with doses from 15 mg twice daily to 12 x 30 mg/day. Adrenal stimulation did not occur as proven by normal circadian plasma cortisol levels. However, the EEG regularly repeated, did not show improvements. The frequency of seizure was not reduced. It is concluded that this ACTH fragment (ACTH 4-10) does neither influence the adrenal cortex nor the EEG nor the frequency of seizures in early childhood epilepsy.

Twenty six females suffering from congenital adrenal hyperplasia due to 21-hydroxylase-deficiency with and without salt wasting were evaluated to determine their growth patterns with special regard to their pubertal growth spurt. 17 patients have been substituted with hydrocortisone 20-25 mg/m2 and if necessary with 9 alpha-fluoro-cortisol 0.025-0.15 mg (group 1), 9 patients have got an additional cyproterone-acetate-therapy during their pubertal development (group 2). Group 1: A pubertal growth spurt was found in 14 females (82.4%) with a peak height velocity of 6.2 +/- 1.6 (SD) cm/yr. At the beginning of puberty the early treated girls showed a progressing retardation of bone age. Therefore the peak height velocity based on advancing bone age was elevated up to 8.7 +/- 1.4 (SD) cm/yr bone age (p = 0.01). Salt wasting (n = 10) did not seem to influence the pubertal growth velocity and the pubertal growth spurt (p = 0.1, p greater than 0.1), but the growth until cessation which was found to be markedly decreased (p less than 0.1). Group 2: Cyproterone-acetate suppressed symptoms of puberty but did not extinguish growth spurt. During 6.3 +/- 1.3 (SD) yrs of treatment bone age advanced only 4.2 +/- 0.7 (SD) yrs. However, in this period height increased by 20.8 +/- 6.4 (SD) cm which corresponds to a mean height velocity of 3.3 +/- 0.8 (SD) cm/yr, and 4.9 +/- 0.8 (SD) cm/yr bone age. Furthermore at puberty peak height velocity results in 4.5 +/- 0.7 (SD) cm/yr and in 10.4 +/- 4.6 (SD) cm/yr bone age.(ABSTRACT TRUNCATED AT 250 WORDS)

16 girls with precocious puberty have been studied. Following low dosage cyproterone acetate (CA) therapy (mean daily dosage 65 mg/m2BSA) a beneficial effect on growth and skeletal maturation was observed. During high dosage therapy (150 mg/m2 per day) endocrinological studies were performed in 10 of these patients. There was no significant difference in HGH levels (insulin- and arginine-test), T3 and TSH values (TRH-test) between patients and controls, T4 concentration was significantly increased. Basal prolactin levels and prolactin response to TRH was definitely elevated. Oral glucose load and arginine infusion resulted in a significantly enhanced insulin release. There was a significant reduction in basal LH levels and an increase in FSH response to LH-RH. Basal and diurnal plasma cortisol values were markedly reduced and the cortisol release due to corticotrophin injection, lysinevasopressin (LVP) injection and insulin-hypoglycemia as well. A definite increase in basal ACTH levels was observed, during LVP- and insulin-hypoglycemia test ACTH concentrations were within or significantly above normal range. In our patients a primary adrenocortical insufficiency due to CA treatment was evident.

After 5 years of cyclic vomiting an 8 year old boy was presented with coma and hyponatremia. ACTH and renin plasma concentrations were elevated, cortisol concentrations did not rise after ACTH-stimulation. Behavioural abnormalities including secondary enuresis and dysarthria drew attention to the possibility of an association of adrenal insufficiency with leucodystrophy. NMR tomography of the brain showed symmetrical demyelinated areas in the parieto-occipital regions. Very long chain fatty acids were elevated. The mother showed discrete neurological symptoms and elevated long chain fatty acids. Cyclic vomiting might suggest adrenoleukodystrophy.

A 6 year 11 month old girl had pseudoprecocious puberty caused by multiple ovarian follicular cysts. In contrast to previously reported patients, oestrogen levels in blood and urine were not elevated though gonadotropins were suppressed. Despite the lack of measurable oestrogen elevation the child developed distinct oestrogenic effects. After removal of large bilateral ovarian cysts endocrine aberrations normalized and precocity regressed.

We report an 18-month-old girl with Cushing's disease caused by a large adenoma of the pituitary gland. Tumour size and extension were determined by X-ray, CT-scan and angiographic studies. The endocrinological findings were typical for this disease: elevated plasma levels of ACTH, cortisol, 17-Hydroxyprogesterone (17-OHP) and testosterone, elevated urinary excretion of 17-Ketosteroids (17-KS) and 17-Hydroxycorticoids (17-OHCS). Dexamethasone failed to suppress ACTH and cortisol plasma levels. TRH induced only a minimal TSH increase. Following LH-RH injection gonadotropin levels rose to pubertal values. The hGH response to insulin-induced hypoglycaemia was subnormal. After resection of the tumour the infant died because of non-treatable arrhythmia. Histological findings showed a non-differentiated adenoma with extension into the subarachnoid space and into nerve tissues. In vitro lysine-vasopressin (LVP) and arginine-vasopressin (AVP) exhibited only weak stimulatory effects on the ACTH secretion of the tumour cells.

In the present study the effects of artificial magnetic fields on pineal serotonin-N-acetyltransferase (NAT) activity and melatonin content in male Sprague-Dawley rats were investigated to study the secretory activity of the pineal gland. Experimental inversion of the horizontal component of the natural magnetic field, performed at night-time, led to a significant decrease of both parameters investigated. During day-time, this effect was less conspicuous. During night-time, inversion of the horizontal component is followed by a reduced pineal secretory activity for about 2 h. After 24 h exposure to the inverted horizontal component, return to the natural condition was followed by a renewed clear depression of pineal NAT activity and melatonin content, indicating that the main stimulus is not the inverted magnetic field itself but rather its change. Changing the inclination of the local magnetic field from 63 degrees to 58 degrees, 68 degrees or 78 degrees, respectively also decreased the secretory activity of the rat pineal gland.

8 children with different petit mal epilepsies were systematically treated with ACTH and dexamethasone. CCT examinations were performed before, during and after treatment. In all children severe cerebral changes. enlargement of ventricles and subarachnoid space developed during the initial phase of treatment with Depot-ACTH. Similar changes, but to a less severe degree, could be demonstrated during the phase of dexamethasone therapy thereafter. In all patients cerebral changes disappeared after hormonal treatment had ended. At this point many children had a developmental spurt, developmental relapses could not be observed. It is suggested that these reversible changes seen on CCT scans represent a form of morphological plasticity of brain structures. These results bear certain consequences as to the therapy of cerebral edema.

In patients with undescended testes the demonstration of the pampiniform plexus (i.e. venous network surrounding the testis) by selective retrograde contrast filling of the internal spermatic vein gives exact information about the existence and localization of the gonadal tissue. Especially with small hypoplastic testes and/or an intraabdominal position of the gonad the results of this technique are superior to those of ultrasound and computed tomography. The venographic information often helps to reduce the extent of the surgical exploration, most of all in those cases in which after an ineffective first procedure a second operation is planned. Venography can be done on an outpatient basis in children from an age of about 6 years upwards without general anesthesia and serious complications. Personal experiences with the spermatic venography in 11 patients (age: 7-32 years) with 18 undescended testes are demonstrated. Comparing the roentgenologic and surgical findings in 7 patients with 12 explored veins the results corresponded completely in 75%. In the remaining cases roentgenologic demonstration of one of the testicular veins with its pampinifom plexus suggested important information about the localization of the contralateral testis, surgically confirmed later.

Management of craniopharyngiomas is still controversial. 28 children with this tumor were studied. GH deficiency was present in 22 patients following surgery, 10 of these GH-lacking patients had normal or accelerated growth (usually associated with rapid weight gain) postoperatively. Somatomedin levels were normal in three of six normally growing patients. After craniotomy their basal and TRH-stimulated prolactin levels were in the normal range, but their insulin secretion was markedly increased. Postoperatively there was a significant correlation between peak insulin levels following arginine infusion and growth velocity in all patients. Complete tumor removal could be performed in 28% of our patients. Altogether 36% of all patients had at least one tumor recurrence. Recent literature with the addition of our series showed tumor recurrence in 22% of patients with "total" tumor excision and in 72% of patients with partial tumor removal. Radiotherapy seems to be capable of destroying craniopharyngioma tissue. The recurrence rate was only 26% in patients with subtotal excision plus radiotherapy. Unless radical tumor removal can be attempted with safety, subtotal tumor removal plus radiotherapy appears to be the treatment of choice for craniopharyngioma.

Convulsions in early childhood were treated successfully in a long term and high dosage regime with depot corticotrophin (80-120 IU/die) and dexamethasone (0.3 mg/kg/die). Depot-beta1-23corticotrophin stimulated, dexamethasone suppressed plasma cortisol levels, which, accordingly, ceased to show circadian rhythms. If dexamethasone was given alternately (every second day) and in a reduced dose (0.1 mg/kg) plasma cortisol levels increased, and if dosage was reduced again to 0.05 mg/kg cortisol levels showed circadian rhythms comparable to those before therapy. There was no disturbance of the hypothalamic--pituitary--adrenal system at the end of therapy. Considering experimental results in animals corticotrophin peptides and dexamethasone molecules might have a direct effect on the brain as far as cerebral convulsions are concerned. Because of serious side effects of steroids during treatment it seems to be worth while to try corticotrophin fragments, which had similar effects on the brain as beta1-24corticotrophin in animals, but without stimulating the adrenals.

A 2 1/2 year old girl with virilization and advanced bone age was found to have a leftsided adrenocortical adenoma. The secretion of mainly androgens besides estrogens was not suppressible with dexamethasone. Plasma cortisol levels were not elevated but did not show any circadian rhythm. The tumor was localized by retroperitoneal instillation of gas, intravenous urography and tomography. After complete removal of the tumor the originally strongly elevated excretion of 17-ketosteroids sank back to normal, the acceleration of skeletal development slowed down. The right adrenal cortex was not atrophic, 2 1/2 years after the operation the child is well and without evidence of recurrent disease. Differential diagnosis as well as ultrastructor and histology of the tumor are discussed with reference to the literature.

According to more recent knowledge L-thyroxine alone is recommended for thyroid hormone replacement therapy, no longer the combination of L-thyroxine and triiodothyronin, since L-thyroxine is converted to triiodothyronine in the periphery of the body. Additional application of triiodothyronine causes unphysiological elevations of blood levels of triiodothyronine. When changing from the combined thyroid hormone therapy to treatment with L-thyroxine alone it is enough in most cases to replace the previous amount of L-thyroxine only; previous recommendations for the dosage of thyroid hormone were rather high. Average requirements of adults for L-thyroxine are around 170 mug per day. Children need about 90--100 mug per m2 body surface per day. -- When hypothyroidism is suspected in newborns or infants no protracted diagnostic procedures are justified with respect to brain development and its requirement of thyroid hormone during this period of life. Replacement therapy should be started within 1--2 days. The exact diagnosis can be established later, for instance during the third day of life when a temporary interuption of treatment for diagnostic purposes has no longer such negative effect on normal brain development. As long as physiological doses of L-thyroxine are used no side effects are to be expected for patients who later turn out to be euthyroid. -- Following exclusion of hyperthyroidism goitres in children and adolescents equally need thyroid hormone replacement therapy to reduce the size or prevent further enlargement or even the development of nodules within the gland. The dosage for this is about half to three quarters of the full replacement dose. The nature of thyroid nodules should be investigated, even surgically, since malignancies can develop in children and juveniles as well as in adults.