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Biomedical subjects

F Waldhauser

Publications and source records attributed to F Waldhauser.

At least 55 records · Page 3Linked to original sources

Alterations in nocturnal serum melatonin levels in humans with growth and aging.

The available data on potential alterations in serum melatonin (MLT) levels during a human lifetime are fragmentary and inconsistent. We, therefore, measured day- and nighttime serum MLT concentrations in 367 subjects (210 males and 157 females), aged 3 days to 90 yr. Blood samples were collected between 0730 and 1000 h and between 2300 and 0100 h. Serum MLT levels were measured by RIA. The mean nighttime serum MLT concentration was low during the first 6 months of life, i.e. 27.3 +/- 5.4 (+/- SE) pg/mL (0.12 +/- 0.02 nmol/L). It then increased to a peak value at 1-3 yr of age [329.5 +/- 42.0 pg/mL; (1.43 +/- 0.18 nmol/L)], and it was considerably lower [62.5 +/- 9.0 pg/mL; (0.27 +/- 0.04 nmol/L)] in individuals aged 15-20 yr. During the following decades serum MLT declined moderately until old age (70-90 yr of age), i.e. 29.2 +/- 6.1 pg/mL (0.13 +/- 0.03 nmol/L). This biphasic MLT decline follows 2 exponential functions with different slopes (from age 1-20 yr: r = -0.56; P less than 0.001; y = 278.7 X e -0.09x; from age 20-90 yr: r = -0.44; P less than 0.001; y = 84.8 X e -0.017x). The decrease in nocturnal serum MLT in children and adolescents (1-20 yr) correlated with the increase in body weight (r = -0.54; P less than 0.001) and body surface area (r = -0.71; P less than 0.001). At a later age (20-90 yr) there was no correlation among these variables. Daytime serum MLT levels were low and no age-related alterations were found. This study revealed major age-related alterations in nocturnal serum MLT levels. The negative correlation between serum MLT and body weight in childhood and adolescence is evidence that expansion of body size is responsible for the huge MLT decrease during that period. The moderate decline at older ages must derive from other factors.

Adolescent↗

[Age-related changes in stimulation and secretory rhythm of serum gonadotropins in children with Ullrich-Turner syndrome].

In 22 girls with Ullrich-Turner-Syndrome (UTS) aged 1.3 to 17.6 years basal and LHRH-stimulated gonadotropin (Gn)-concentrations as well as spontaneous variations of Gn-secretions were measured in order to recognize age dependent changes. Basal Gn-concentrations were elevated in the 1-year old girl, showed normal values in patients whose bone age was less than 11 years and were elevated again in the group with a bone age greater than 11 years. Stimulated LH and FSH concentrations were significantly elevated in all age-groups when compared with the values of age-matched controls. Minimal and maximal Gn-concentrations during spontaneous secretion were low in patients with a bone age less than 11 years, whereas a distinct elevation could be noted in the 1-year old child and in the elder group when compared with age-matched controls. According to these findings the typical age-dependent change of Gn-secretory dynamics could also be demonstrated in children with UTS albeit on an elevated level. A bone age of 11 to 11.5 years, when serum concentrations of Gn rise in healthy girls followed by onset of puberty seems to be the biological indicator for changes of the hypothalamo-hypopituitary level also in girls with Ullrich-Turner-Syndrome.

Adolescent↗

A pharmacological dose of melatonin increases PRL levels in males without altering those of GH, LH, FSH, TSH, testosterone or cortisol.

Since reports on the influence of melatonin (aMT) on the human endocrine system are scant and inconsistent, the effect of an acute, pharmacological dose of aMT on various hormone levels in healthy males was examined in 3 different experiments. Experiment I: 80 or 240 mg of crystalline aMT were administered per os to 8 volunteers. Before, during and after this treatment, serum levels of aMT, PRL, LH, FSH and testosterone were examined. Although aMT increased at least 1,500-fold over basal levels, only PRL was significantly and consistently elevated after aMT treatment, whereas serum levels of the other hormones were not altered. Experiment II: in 2 subjects, the pulsatile secretion pattern of LH was monitored for 6 h before and 6 h after aMT administration (240 mg p.o.). Neither the amplitude nor the frequency of LH pulses was influenced by the pineal hormone. Experiment III: in 14 volunteers, serum PRL, GH, TSH and cortisol concentrations were examined, once after oral administration of 240 mg aMT and once after placebo. Serum PRL levels were significantly higher after aMT than after placebo; GH showed a slight but not significant trend towards elevation after aMT, whereas other hormones were not altered. An acute pharmacological dose of aMT causes isolated elevation of serum PRL levels and may slightly increase GH. Hormones of the pituitary gonadal axis as well as TSH and cortisol are not altered by aMT.

Adult↗

Serum melatonin levels: a new neurodiagnostic tool in pineal region tumors?

The pineal hormone melatonin (MLT) is secreted in a circadian rhythm with high serum levels during nighttime and low serum levels during daytime. Several authors have reported an altered secretion pattern of MLT in patients with pineal tumors and have proposed that MLT may be used as a tumor marker. In nine patients, a pineal region tumor was diagnosed by computer-assisted tomography. Before and after surgical removal of the tumor, several day- and nighttime serum samples were collected and MLT concentrations were estimated by radioimmunoassay. Before operation, five patients presented a normal circadian pattern of MLT secretion. In the remaining four subjects, MLT levels were undetectable or at the limit of detection, with no signs of a circadian secretion pattern. Eight patients were reexamined after tumor resection, when all but one had undetectable or very low MLT levels. The remaining subject, with a pineomesencephalic pilocytic astrocytoma, dislocating but not involving the pineal gland, presented a normal circadian secretion pattern of MLT after operation; in this case, tumor resection was possible without damaging the pineal gland. Thus, before operation, MLT deficiency rather than exaggerated serum levels may be used as a marker for pineal tumors that destroy the pineal gland. After tumor resection, serum MLT may serve to demonstrate complete pinealectomy.

Adolescent↗

[Basal gonadotropin level and gonadotropin response to stimulation in patients with anorexia nervosa].

Serum gonadotropin (GN) levels were examined before and after stimulation with luteinizing-hormone-releasing-hormone (LHRH) (100 micrograms/m2 body surface) in 25 female patients with anorexia nervosa (AN) and in 19 healthy young women. 12 patients were reexamined after clinical improvement. Basal GN levels and the luteinizing hormone (LH) response to stimulation were significantly lower in patients than in controls, whereas the response of follicle-stimulating hormone (FSH) to LHRH was normal. The GN response in patients was weight dependent, displaying an inverse correlation to the weight loss. After clinical improvement the GN response was significantly higher than in the acute stage of the disease. The data demonstrate that the activity of the hypothalamic-hypophyseal-gonadal (H-H-G) axis, evaluated on the basis of the GN response to LHRH, depends on the body weight of the patient. Hence, the alteration in activity of the H-H-G axis seems to be a consequence, and not the cause of AN.

Adolescent↗

[Increased prolactin concentration and thyrotropic insufficiency in patients with growth hormone deficiency].

An increase in TSH secretion in patients with growth hormone deficiency (GHD) indicates hypothalamic thyrotropic dysfunction. A simultaneous increase in prolactin (PRL) response to TRH is often observed in these patients. In order to find out whether these patients need additional thyroxine treatment, we investigated thyrotropic function in 15 patients with GHD and increased PRL secretion. 3 groups of patients emerged: 1. Four patients were clinically hypothyroid (T42.9 +/- 1.3 micrograms/dl); 2. Four patients developed low T4 levels during growth hormone therapy (T43.5 +/- 0.1 micrograms/dl), although their T4 levels were normal before growth hormone treatment was initiated (T45.7 +/- 0.5 micrograms/dl). 3. Seven patients had T4 levels in the lower normal range (7.0 +/- 0.8 micrograms/dl). The growth velocity of these patients was monitored when thyroxine treatment was given in addition to hGH. Thyroxine administration resulted in suppression of TSH secretion in all patients while PRL concentrations remained elevated. Growth velocity was improved with additional T4 therapy in groups 2 and 3 without undue acceleration of bone age. All patients with GHD and elevated PRL levels should be carefully monitored for thyrotropic dysfunction.

Body Height↗

Serum melatonin is not affected by glucocorticoid replacement in congenital adrenal hyperplasia.

Recently a hypothesis has been proposed suggesting a negative feedback in the regulation of cortisol (F) and melatonin (Mel). To study a possible influence of F on Mel regulation we examined 13 children with congenital adrenal hyperplasia (CAH) on two occasions: once 3 days after cessation of F substitution (group 1; n = 13) and once during treatment with dexamethasone (1 mg/m2/day) and fludrocortisone (0.1 mg/m2/day) (group 2; n = 11) 11 children matched by sex and age served as controls (group 3). While serum 17 OH-progesterone levels, an indicator for the activation of the hypothalamo-pituitary-adrenal axis in CAH, were significantly (P less than 0.001) elevated in untreated patients (group 1), serum Mel levels were not different among the 3 groups nor was the diurnal secretion pattern of Mel affected. Nocturnal serum Mel concentrations, however, correlated with the age of the subjects (r = 0.55, P less than 0.001 at 23.00 h), displaying high values in early childhood that declined with progressing age. The presented data do not support the view of a classical feedback mechanism in the regulation of Mel and F in humans. However, it confirms the description of a tremendous fall of nocturnal Mel concentrations during childhood.

17-alpha-Hydroxyprogesterone↗

Glycated plasma proteins in normal and diabetic mothers and their offsprings.

Glycated plasma proteins (GPP) and glycated hemoglobin (G Hb) has been evaluated in 134 non-diabetics (ND), 299 women with potential abnormality of glucose tolerance (pot.AGT), 75 with impaired glucose tolerance (IGT) and 34 insulin dependent diabetics (IDDM) during pregnancy or postpartum including 94 cord blood determinations. Mean HbA1c levels were significantly elevated in IDDM (6.6 +/- 1.3% M +/- SD) compared to ND (5.1 +/- 0.7%; P less than 0.01), but were similar for the other groups studied. Mean GPP were increased for the IDDM (0.58 +/- 0.29 nmol 5- HMF/mg protein; M +/- SD) and the IGT-group (0.53 +/- 0.22) over ND (0.3 +/- 0.13; P less than 0.01) and the Pot.AGT group (0.37 +/- 0.14; P less than 0.01). 6% of the ND, 15% of the Pot AGT-, 52% of the IGT- and 62% of the IDDM group were found to have GPP values exceeding the 97% confidential limit of the ND. However, the large overlap of individual values from patients with different degrees of glucose intolerance with the normal range of pregnancy precludes the use of GPP as a screening parameter for IGT during pregnancy. A 30-35% reduction of fetal hemoglobin- and plasma protein glycosylation relative to maternal values was observed.

Blood Proteins↗

Changes in melatonin secretion with age and pubescence.

At the turn of the century, reports on a coincidence of pineal tumors and precocious puberty in man initiated a host of animal experiments. Results of these experiments ultimately revealed a modulating effect on sexual maturation and on gonadal activity in several species, brought about by the pineal hormone melatonin (aMT) and particularly its circadian secretion pattern. In addition, it renewed interest in a possible interaction of the pineal and human sexual function. The introduction of specific and precise aMT assays provided exact evaluation of the circadian aMT secretion pattern in adults. Despite considerable efforts, however, a precise characterisation of this pattern has not yet been achieved in children. In a first step we examined single day- and nighttime serum samples from 280 subjects of all ages. aMT levels were low during early infancy, increased to their highest values around 1 to 3 years and dropped progressively by 75 percent until young adulthood, when they remained fairly stable. Thus, the pattern of aMT levels is the reverse of that of gonadotropin levels or gonadal activity in humans. Whether there is a causal relationship between the activity of the pineal gland and the hypothalamo-pituitary-gonadal axis in humans or whether the described negative correlation in the activity of both glands is purely coincidental remains to be clarified.

Adolescent↗

[Spinal lipoma with a dural closure defect as a cause of neurogenic bladder and chronic renal failure].

It is reported on a 6-year-old boy, in whom 3 years after the appearance of a neurogenic disturbance of the urinary bladder a lipoma in the spinal canal of the inferior thoracic region was diagnosed myelographically. The operative removal of the growing and displacing fatty tissue which by a (congenital?) dural gap continued in epidural direction indeed resulted in a far-reaching regression of the paresis of the lower extremities, not, however, in an improvement of the urological picture of the disease. The renal insufficiency caused by the hydronephrosis was no more reversible, which emphasizes the importance of the early diagnosis of this relatively infrequent malformation.

Child↗

Possible behavioral consequences of light-induced changes in melatonin availability.

Melatonin is a hormone secreted at night, in the dark, by the human pineal organ. This nocturnal release of melatonin, in humans and other species, is rapidly suppressed by exposure to sufficiently bright light. In humans, the function, if any, of this circadian pattern of melatonin release has not been determined. In fact, no function has been definitively attributed to the hormone melatonin in humans. In one study, conducted in our laboratory, pharmacologic doses of oral melatonin (240 mg over two hours) were administered to volunteers, and various behavioral parameters were assessed. Melatonin had substantial, but brief, sedative-like effects on mood and performance. Thus it appears that a mechanism exists, whereby light, of sufficient intensity to affect melatonin release in humans, can affect behavior. It can be hypothesized that sufficiently bright light, acting by way of the suppression of melatonin release, can acutely increase alertness or act as a zeitgeber (synchronizer of circadian cycles). The light intensity necessary to suppress melatonin secretion in humans is well above typical indoor lighting conditions, but well below normal outdoor daytime levels of illumination. Therefore, the hypothesis that light may affect behavior or circadian patterns of sleep and waking, if found to be true, could have considerable impact on the design of interior lighting.

Double-Blind Method↗

[Anorexia-nervosa--psychopathologic findings in relation to body weight and neuroendocrinologic changes].

The present study was conducted to investigate the relationship of psychopathological, behavioral and neuroendocrinological variables to weight profiles in patients with anorexia nervosa. The subjects were 67 patients with anorexia nervosa (61 females, 6 males). Eighteen (27%) were found to have a diffuse organic brain syndrome. Symptoms of hysterical and depressive neurosis predominated among the female subjects and those of obsessive-compulsive neurosis among the male subjects. Obsessive-compulsive and depressive traits were seen more frequently in the subjects with organic brain syndrome (14 of 18) than in the other subjects. One third of the female subjects showed resistance during therapy. Neuroendocrinological investigations (LHRH and TRH tests) were carried out on 27 of the female subjects. The stimulation values for the hormones LH, FSH, TSH and prolactin showed a significant dependence on weight. The symptomatology found in the subjects with organic brain syndrome largely parallels that of the psycho-organic hunger syndrome described by Baeyer. Correlations were found between weight loss and both blood chemistry findings and changes in psychosocial behavior.

Adolescent↗

Effects of melatonin on human mood and performance.

The function of melatonin, a hormone secreted by the pineal gland primarily at night, has not been definitively established in humans. To determine if pharmacologic doses of melatonin had any behavioral effects it was administered acutely to 14 healthy men. Their mood, performance, memory and visual sensitivity were assessed. Plasma melatonin concentration was assayed as well. Melatonin significantly decreased self-reported alertness and increased sleepiness as measured by the Profile of Mood States and the Stanford Sleepiness Scale self-report mood questionnaires. The effects were brief. Melatonin also affected performance, slowing choice-reaction time but concurrently decreasing errors of commission. Sustained fine motor performance was not impaired after melatonin administration nor were the tests of memory and visual sensitivity that were administered. It is concluded that melatonin, administered orally in pharmacological quantities, has significant but short acting sedative-like properties.

Adolescent↗

Fall in nocturnal serum melatonin during prepuberty and pubescence.

Morning (7:30 AM to 10:00 AM) and nighttime (11:00 PM to 1:00 AM) serum melatonin concentrations were measured in 89 children, adolescents, and young adults. Morning levels (generally 0-20 pg/ml) did not change with sexual maturation or with age. Nighttime levels decreased significantly both with sexual maturation and with age. Nighttime serum melatonin fell from 195 +/- 24 pg/ml (mean +/- SEM) in prepubertal children younger than 7 years of age, to 119 +/- 23 pg/ml in prepubertal children aged 7 years or older, to 49 +/- 4 pg/ml in young adults (puberty stage V). Similarly, nocturnal serum melatonin levels fell from 210 +/- 35 pg/ml in the youngest age group (ages 1-5) to 133 +/- 17 in children aged 5-11 years and to 46 +/- 4 in young adults. Nocturnal plasma concentrations of luteinising hormone measured at various stages of puberty tended to vary inversely with those of melatonin (r = -0.35). Past difficulties in demonstrating a relation between gonadal maturation and human pineal function may have reflected the use of insufficiently sensitive or specific melatonin assays, or serum sampling only during daytime, or the initiation of sample collection when subjects were already too old.

Adolescent↗

[Effect of intranasal administration of an LH-RH analog on basal gonadotropin concentrations and stimulation in patients with hypogonadotropic hypogonadism].

The effect of intranasal administration of the LHRH analogue D-Leu-6-des Gly-10 NH2EA on gonadotropin (Gn) stimulation was studied in 8 juvenile patients with ascertained hypogonadotropic hypogonadism, due to multiple pituitary deficiencies (MPD) in 5 cases and the Prader-Willi syndrome (PWS) in the remaining 3 patients. A bolus LHRH test was performed before and after a treatment period lasting between 2 and 5 weeks. In 2 MPD patients there was a transient rise in basal LH concentrations and a slight improvement in the second LHRH test; hence a hypothalamic lesion is assumed. In the other MPD patients there was no change in Gn stimulation. The sex steroid levels remained low. Gn stimulation was improved in all 3 patients with PWS after LHRH administration and in one 19-year-old boy the onset of puberty was probably induced by this therapy. However, after continuous administration of the analogue the initially increased Gn levels decreased again. In view of this inhibiting action on Gn levels the LHRH analogue does not appear suitable for the long-term treatment of hypogonadotropic hypogonadism.

Administration, Intranasal↗

Bioavailability of oral melatonin in humans.

We administered crystalline melatonin (80 mg) in gelatin capsules to 5 young male volunteers and measured serum and urinary melatonin levels at intervals. Changes in serum melatonin levels were best described by a biexponential equation with an absorption constant (ka) of 1.72 h-1 (half-life = 0.40 h) and an elimination constant (ke1) of 0.87 h-1 (half-life = 0.80 h). Peak serum melatonin levels, ranging from 350 to 10,000 times those occurring physiologically at nighttime, were observed 60-150 min after its administration, remaining stable for approximately 1.5 h. The fraction of ingested melatonin that was absorbed, estimated from the area under the curve describing serum melatonin concentrations as a function of time after melatonin administration (the concentration-time curve), varied by 25-fold among subjects. 3 additional volunteers received three melatonin-containing capsules (80 mg each) at 60-min intervals. This regimen extended the duration of elevated serum melatonin levels to 4-6 h. Melatonin excretion closely paralleled serum melatonin levels until 9 h after the hormone's administration, after which urinary levels tended to be higher than those predicted from serum levels. However, the area under the concentration-time curve for serum melatonin correlated well (r = 0.96) with the cumulative melatonin excretion during the initial 15 h after melatonin's administration, indicating that either approach can be used to estimate the absorption of orally administered melatonin.

Administration, Oral↗