Linear skin atrophy preceding calcinosis cutis in pseudo-pseudohypoparathyroidism.

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.

Hyperparathyroidism due to auto-immunological malabsorption in an African girl.

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.

Growth hormone (GH) determinations by RIA and IFA during GH stimulation tests in children with short stature.

Growth hormone deficiency (GHD) as a syndrome comprises multiple pathogenetically distinct entities caused by disorders of secretion or peripherial action of growth hormone (GH). Confirmation of the diagnosis of GH deficiency in children is based on provocative testing for human growth hormone (hGH). Immunofunctional assay (IFA) allows quantitation of only biological active GH forms in circulation. The aim of this study was to compare the results of GH determinations by radioimmunoassay (RIA) and IFA, and to establish cut-off-levels for IFA in insulin tolerance test (ITT). We have investigated 32 children (30 males and 2 females) with short stature. All patients underwent insulin tolerance test (ITT), GH was measured in duplicate by radioimmunoassay (RIA, Seria) and IFA (DSL). Children with peak GH concentration below 10 ng/ml in ITT (by RIA) underwent arginin tolerance test (ATT, arginin 0,5 g/kg). The correlation between the results of growth hormone determination by radioimmunoassay and immunofunctional assay was excellent and cut-off-level in stimulatory test was established for the immunofunctional assay.

Hip fractures in Finland--a comparison of patient characteristics and outcomes in six hospitals.

BACKGROUND AND AIMS: To compare six Finnish hospitals for the quality of treatment of hip fractures and to obtain information for the development of care. MATERIAL AND METHODS: Data of 1179 consecutive hip fracture patients (about 200 patients per hospital) was collected prospectively, using similar standardized forms and focusing on background factors and the four-month functional outcome. RESULTS: There were significant differences between the hospitals in patient characteristics (age, place of residence, walking ability, use of walking aids, morbidity and type of fracture) and in the unadjusted outcome variables at four months' follow-up (place of residence, mobility, use of walking aids and pain in injured hip). After adjustment for baseline characteristics, there was a significant difference in the post-fracture walking ability between the centres but no significant differences in post-fracture place of residence. Unadjusted mortality did not vary between the centres, but adjustment resulted in significant differences. The most marked difference in surgical methods between the hospitals was seen in the use of either sliding hip screw or Gamma Nail for trochanteric fractures, but this difference was not reflected in the results of multivariate analysis. CONCLUSIONS: We found minor differences in mobility and mortality between the participating hospitals, and these might serve them as a stimulus for improving their standard of good practice. Continuous quality improvement by repeating the audit cycle is recommended in order to reach and then improve the prevalent standards in the care of hip fracture patients. Confounding factors should be adjusted when comparing the medical centres treating hip fractures, and the evaluation of the results should be multidimensional.

Factors related to occurrence of hip fracture during a fall on the hip.

Recently, it has been shown that hip fractures can be effectively prevented by use of hip protectors. To determine who would gain most benefit from use of hip protectors, we conducted a study with the aim to clarify factors that contribute to the occurrence of fracture in individuals who fall on their hip. Hip fracture patients were compared with individuals who had fallen on their hip without sustaining a fracture. The study group consisted of 123 consecutive hip fracture patients aged 70 years or over (mean age 82 years, female 82 years and male 80 years). The control group comprised 132 individuals (mean age 81 years, female 81 years and male 80 years) obtained from a prospective study on falls, who had experienced a fall that caused a visible soft tissue injury (bruise or wound) at the hip or gluteal region without sustaining a fracture. Patients were questioned about associated diseases, medications, place of residence, walking ability, need for locomotor aids and some activities in daily living (ADL). Patients who sustained a hip fracture were more likely to be women, living in long-term institutional care, using neuroleptics, dependent in ADL and had more history of previous stroke with hemiparesis, more Parkinsonism and lower body mass indexes (BMI) than those who did not sustain a fracture on fall on the hip. According to a logistical regression model, institutional residence, low BMI and history of stroke with hemiplegic status differed between fracture cases and controls. Institutional residence, low BMI and history of hemiplegic stroke discriminate hip fracture patients from fallers who sustain a soft tissue injury on the hip region. In clinical practice, patients who have these characteristics would be potential candidates to use hip protectors and other preventive measures.

Mortality and quality of life after trochanteric hip fracture.

The objective was to evaluate the survival and some aspects of the quality of life of patients with trochanteric hip fracture after long-term follow-up in comparison with the age- and sex-matched controls without fracture. Two hundred consecutive patients (mean age at fracture 77 y) with trochanteric hip fractures were compared with the age- and sex-matched controls representing an average population from the same area. After a mean 7 y follow-up period a questionnaire concerning their place of residence, ambulation, causes leading to impairment, need for locomotor aids and management of activities in daily living (ADL) functions was sent to the surviving patients and controls. Mortality increased gradually being 4.5 percent above the control level one month after the fracture, 6.0 percent above at three months, 3.5 percent above at one year, 4.5 percent above at two years, 6.5 percent above at five years and 9.0 percent above at six years. Thirty (48%) of the surviving 62 patients and 83 (90%) of the 92 surviving controls were living in their own homes and 2 (3%) and 4 (4%) in service apartments respectively. Seventeen (27%) of patients alive were institutionalized in a chronic care hospital unit and 13 (21%) in an old people's home as compared with 2 (2%) and 3 (3%) of the controls respectively. Twenty-two (35%) of the patients and 73 (79%) of the controls were able to move about independently. The patients were significantly worse at ADL-management, required more home help and had fewer social contacts and outdoor hobbies than the controls. In conclusion surgically-treated trochanteric hip fractures markedly increase mortality rate, reduce independence and impair walking ability and ADL-functions, and thus seriously affect the health-related quality of life of the patients. This fact should be considered in the planning of the healthcare of elderly people.

Effect of age on some blood variables relating to bone metabolism in women.

BACKGROUND: The available laboratory parameters reflecting bone metabolism are not adequate for reliable diagnosis of osteoporosis. They display a marked biological variation and are inaccurate in individual cases. Therefore precise knowledge of these variations, as upon aging in healthy people is important. AIMS: The purpose was to examine the age- and weight-related variation of some blood constituents relating to mineral metabolism and commonly used in hospital laboratories in healthy women aged over 40, and to estimate their mutual correlations and normal values in different age groups. METHODS: The study series consisted of 238 healthy Caucasian women without any diseases related to bone metabolism and aged 40-86 years, who were divided into the following age categories: 40-45, 50-55, 60-65, 70-75 and over 80 years. RESULTS: Markers of bone formation, alkaline phosphatase (AP) and osteocalcin, and marker of bone resorption, tartrate resistant acid phosphatase (TrAcP), as well as parathyroid hormone, phosphorus and creatinine increased with age, whereas 25-hydroxyvitamin D and oestradiol decreased. All these parameters except calcium showed a significant age relation. Only the relation of weight versus osteocalcin and weight versus TrAcP remained significant when the effect of age was included in the multiple regression analysis or the partial correlation coefficients were examined. There was a significant correlation between serum osteocalcin and serum AP. Serum TrAcP had a significant positive correlation with serum osteocalcin and serum AP. Percentage fat mass correlated significantly with AP and TrAcP. CONCLUSION: Our observations may be useful when these markers of bone metabolism having inadequate sensitivity and specificity, are used as a battery in the diagnosis of osteoporosis and other metabolic bone diseases and in the assessment of normality in population studies.

[Investigations on the concentration and emission of ammonia and nitrous oxide in various deep litter keeping systems for fattening pigs and in slatted floor keeping]. / Untersuchungen zu Konzentration und Emission von Ammoniak und Lachgas bei verschiedenen Tiefstreuhaltungssystemen für Mastschweine und bei Vollspaltenbodenhaltung.

Concentration of ammonia and nitrous oxide was measured in an air conditioned pig site with two chambers during six rounds (app. 650 measuring days) with different deep litter and a slatted floor keeping system for fattening pigs. Emissions and gaseous nitrogen losses were calculated. With exception of a system with mixing twice a week deep litter keeping leads to decrease of NH3 concentration (up to 26%), partly also of NH3 emission, but to higher N2O emissions compared to liquid manure system. With exception of ENVIROZYME deep litter keeping all other deep litter systems cause higher gaseous nitrogen losses compared to slatted floor keeping.

Melatonin and 6-hydroxymelatonin sulfate excretion is inversely correlated with gonadal development in children.

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.

Decreasing melatonin and 6-hydroxymelatonin sulfate excretion with advancing gestational age in preterm and term newborn male infants.

We investigated the ontogeny of melatonin synthesis during fetal maturation by measuring the melatonin (MLT) and 6-hydroxymelatonin sulfate (MLTS) excretion in the urine of male infants aged 2-7 days and gestational age 26-42 weeks. We found a negative correlation between advancing gestational age and the MLT and MLTS excretion expressed as total 24-h amount, ratio of 24-h amount to creatinine and ratio of 24-h amount to body surface area. The ratio of MLT to MLTS was found to be about ten times higher in the study group than in prepubertal children, which might reflect the immaturity of hepatic sulfation capacities. The total amount of excreted MLT and MLTS was only one-tenth the prepubertal values. No day/night differences in MLT and MLTS excretion could be detected. We conclude that the fetal pineal gland is capable of a limited melatonin synthesis from the 26th week of gestation onwards, with decreasing values reaching its nadir around term. This indicates that the amount of fetal MLT excretion is not determined by synthesizing capacities of the pineal gland but by the development of neural connections to the pineal gland.

[Determination of concentration and emission of gases relevant to animal and environmental hygiene in different systems for fattening of pigs with the aid of multigas monitoring]. / Zur Bestimmung von Konzentration und Emission tier- und umwelthygienisch relevanter Gase bei verschiedenen Schweinehaltungssystemen mit Hilfe des Multigas-monitoring.

Multigasmonitoring is a method to measure continuously gases relevant from the view point of animal and environmental hygiene with high sampling rate and to calculate emission. The methodical procedure has been described by example from different deep litter systems with additives and slatted floor system with liquid manure storage for fattening pigs. It has been shown that the emission of ammonia from an obviously good working deep litter system can be lowered by approximately 30% in comparison with slatted floor. The mean concentration of nitrous oxide in deep litter system with additives was approximately 2 ppm, whereas in the liquid manure system the N2O concentration was less than the outdoor value.

Intravenous adenosine as first-line prehospital management of narrow-complex tachycardias by EMS personnel without direct physician control.

This study was conducted to evaluate the safety and efficacy of intravenous adenosine therapy for prehospital treatment of narrow-complex tachycardias with a presumptive field diagnosis of paroxysmal supraventricular tachycardia (PSVT) by paramedics without direct physician control. A ten-month prospective case series was designed in an urban EMS system that has paramedics operating under standing orders before physician radio contact. All patients with PSVT field diagnosis were included. Diagnosis of PSVT was made by regular, narrow-complex tachycardia with a heart rate greater than 160 beats/min by field ECG. Interpretation was performed solely by paramedics; ECG transmission was not available. In hemodynamically stable patients, vagal maneuvers were followed by intravenous placement and administration of adenosine was recommended by the manufacturer. If three adenosine boluses failed to convert the arrhythmia, patients were monitored and transported, with electrical cardioversion available. Data collection included demographic, history, medications, vital signs, and EGG tracings. Of 14 included patients, 31 were correctly diagnosed with PSVT (75.6%), with mean ventricular rate of 205 beats/min (SD 7 beats/min); one had sinus tachycardia; nine had atrial fibrillation (AF) (22%). Of the 31 cases correctly diagnosed as PSVT, 28 converted to sinus rhythm after adenosine (90.3%). Of those converted, 16 required a single dose (57.1%), nine required one additional dose (32.1%), and three required two additional doses (10.8%). None reverted to PSVT after adenosine conversion during the study period (conversion to arrival at emergency department). No significant difference in length of asystolic pause or in outcome was detected between the true PSVT cases and the AF cases receiving adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

No effect of ethinylestradiol treatment on melatonin secretion in healthy pubertal girls.

The present study investigated the impact of high estrogen doses on melatonin blood concentrations in healthy young girls. Melatonin secretion was investigated in 7 girls (chronological age 13.2 +/- 0.2 years; bone age 12.8 +/- 0.2 years) before and during treatment with ethinylestradiol (EE2, daily dose 0.5 mg/d orally) aimed at the reduction of final prospective height in familial tall stature. Melatonin, LH, FSH, E2 and EE2 were measured by radioimmunoassay. In all subjects, LH and FSH were completely suppressed, but melatonin secretion, day/night plasma values as well as the area under the curve (AUC) remained unchanged under pharmacological administration of ethinylestradiol. We therefore conclude that melatonin secretion is not affected by pharmacological doses of the synthetic estrogen derivative ethinylestradiol in healthy young girls. The decrease of melatonin blood concentrations during puberty is not caused by increasing concentrations of estrogens but must be due to some other process.

Cushing's disease in a child caused by a corticotropin-releasing hormone-secreting intrasellar gangliocytoma associated with an adrenocorticotropic hormone-secreting pituitary adenoma.

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.

[Prenatal diagnosis and therapy of adrenogenital syndrome with 21-hydroxylase deficiency]. / Pränatale Diagnostik und Therapie des Adrenogenitalen Syndroms (AGS) mit 21-Hydroxylase-Defekt.

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].

Improved test to identify heterozygotes for congenital adrenal hyperplasia without index case examination.

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.

Congenital adrenal hyperplasia. I: Gender-related behavior and attitudes in female patients and sisters.

Thirty-five female patients with congenital adrenal hyperplasia (CAH) were compared to a group of 16 healthy sisters in regard to gender-related behavioral patterns, present attitudes, and plans for the future. A semi-structured interview with the subjects, ages 11 to 41 yr, and their mothers concentrated on four to five age stages. Results of retrospective data from single items as well as from several related composite scales ("interests and behavior," "appearance," "overall scores") revealed significant group differences: Both in mother-assessment and self-assessment, CAH patients showed a "more masculine" orientation than their sisters, but this was far from consistent across all age stages, especially for single items. Unexpectedly, the gender-behavior differences between CAH patients and sisters did not hold for certain items and scales of "social behavior" (e.g., assertiveness, dominance, acceptance in peer groups) and, in contrast to some of the existing literature, also not for "high-energy expenditure." With regard to expectations for the future, CAH patients had less of a "wish to have their own children" and a higher preference for "having a career versus staying at home." Age, socioeconomic status, intelligence, and presence or absence of a sister as possibly intervening psychosocial/demographic factors could not explain the group differences in behavior. Degree of genital masculinization (Prader stages) or "onset and quality" of therapy as measures of pre- and postnatal androgenization, respectively, could also not account for the degree of the "more masculine" orientation in the CAH group. Nevertheless, the overall results are compatible with earlier findings on the masculinizing effects of prenatal androgens on behavior in humans and point to a time period after sexual differentiation of the genitalia and before birth as the most likely one for the effects of prenatal hormones on behavioral masculinization in humans.

Congenital adrenal hyperplasia. II: Gender-related behavior and attitudes in female salt-wasting and simple-virilizing patients.

The salt-wasting (SW) and simple-virilizing (SV) forms of congenital adrenal hyperplasia (CAH) are characterized by distinct prenatal hormonal milieus. To test whether these hormonal milieus differentially influence the development of a "more masculine" behavioral pattern in female CAH patients (Dittmann et al., 1990), SW patients (N = 13) were compared both to SV patients (N = 20) and healthy sisters of both groups (N = 16). The data are based on semi-structured interviews in which subjects (11-41 yr) and mothers were asked about aspects of "Gender-related interests and behavior," "Level of activity," "Social behavior," (reflecting e.g., assertiveness, dominance, and acceptance by peer groups) and "Appearance"; these areas of interest were represented by composite scales. On most scales, and by both mother-assessment and self-assessment, SW patients differed significantly from both SV patients and sisters in having a "more masculine" orientation. SW patients also showed a higher "Level of activity." These SW group results probably account for much of the CAH/sister differences reported in the companion article (Dittmann et al., 1990). In contrast, SV patients differed from the sister sample on only a few scales. There were no significant differences between SV and SW subjects in the degree of virilization of the external genitalia (indicating no group difference in prenatal androgenization). SW patients were treated "earlier" and "better" after birth (indicating less postnatal androgenization). However, these medical conditions, as well as several psychosocial/demographic variables, could not explain the group behavioral differences. These results do not support a primarily psychosocial explanation of behavioral development in CAH patients, especially those with the SW condition; they rather suggest differential organizational effects of two different hormonal environments (SV vs. SW) during critical periods of prenatal CNS development.

Precocious pseudopuberty associated with multiple ovarian follicular cysts and low plasma oestradiol concentrations.

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.