Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage

It is commonly accepted that at least in girls puberty starts when a minimum level of body mass or a certain amount of body fat are present. However the precise signal by which adipose stores inform the hypothalamus of the degree of energetic reserves is unknown. Leptin is a hormone produced by the adipocytes to regulate food intake and energy expenditure at the hypothalamic level. To understand whether leptin is the adipose tissue signal that allows puberty, 789 normal children of both sexes, age 5-15 yr, were transversally studied. Leptin levels, as well as gonadal and gonadotropins, levels, were analyzed in addition to the determination of auxological parameters. In an age-related analysis, leptin levels in girls rose from 5-15 yr (from 4.3 +/- 0.4 to 8.5 +/- 0.9 micrograms/L) in parallel with body weight. Boys always had lower leptin levels than girls (3.3 +/- 0.3 micrograms/L at 5 yr), but they rose in parallel with weight until 10 yr (5.3 +/- 0.7 micrograms/L), when a striking decrease was observed until 15 yr (3.0 +/- 0.3 micrograms/L). In girls, leptin was the first hormone to rise followed by FSH and later by LH and estradiol. A similar pattern occurred in boys, despite the fact that leptin dropped after 10 yr when testosterone rises. Divided into three pubertal stages, i.e. P1 = prepuberty, P2 = early puberty, and P3 = overt puberty, in girls the four hormones rose progressively from P1 to P3, but from P2 to P3 the present increment was greater for LH and estradiol. In boys, leptin decreased from P1 to P3, whereas FSH, LH, and testosterone rose. The age-related changes were not caused by adiposity variations, because data did not change when subtracting values of children over 97% of standard deviation score of body mass index. In conclusion: 1) leptin appears to increase in both boys and girls before the appearance of other reproductive hormones related to puberty; 2) leptin levels in boys are always lower than in girls, although they increase with age until the age 10 yr; 3) leptin in boys declines about the time testosterone increases. Leptin may well be a permissive factor for the initiation of pubertal events.     

Temporal relationship between basal body temperature nadir and luteinizing hormone surge in normal women

Basal body temperature (BBT) as a predictor of ovulation was assessed by examining the temporal relationship between the BBT shift and the luteinizing hormone (LH) surge in individual cycles of 27 normal women. For 22 of the subjects, the LH surge occurred on the same day or within one day of the BBT nadir. For the remaining five subjects, the surge fell within 2 days after or 3 days before the nadir. Despite the BBT nadir's close temporal association with the LH surge, daily examination of BBT for the purpose of predicting the day of ovulation during a given cycle is unsatisfactory. By 48 hours following the nadir, when one could usually be certain that temperature elevation had occurred, all subjects had already exhibited the LH surge.     

Circadian rhythm of plasma leptin levels in upper and lower body obese women: influence of body fat distribution and weight loss

Plasma leptin concentrations were measured every 20 min for 24 h in eight normal weight women and in eight upper body and eight lower body obese women matched for body mass index. The circadian rhythm of leptin, which could mathematically be described by a cosine, was characterized by an acrophase just after midnight in all subjects. The amplitude of a cosine fit as well as the average 24-h leptin concentration were increased by 280% and 420%, respectively, in obese compared to normal weight women. All characteristics of leptin concentration profiles were similar in upper body and lower body obese women, except for a significantly higher amplitude in the lower body obese group. Visceral and sc body fat depots were measured using magnetic resonance imaging in all three groups. Average 24-h leptin concentrations were strongly correlated with sc fat (r = 0.84), whereas visceral fat was not an independent predictor of the plasma leptin level. A loss of 50% of the overweight was associated with a 55% decrease in the average 24-h leptin concentrations in obese women (95% confidence interval, 12.3, 26.6), whereas the characteristics of the circadian rhythm of leptin remained unchanged. Finally, it was observed that a fasting plasma leptin concentration is not an acceptable indicator of the average leptin concentration over 24 h.     

Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity

Cloning and sequencing of the circular, single-stranded DNA of one isolate of psittacine beak and feather disease virus (BFDV) demonstrate a genome composed of a circular molecule of 1993 nucleotide bases. An analysis of the assembled replicative form demonstrated seven open reading frames (ORFs) (three in the virion strand and four in the complementary strand), potentially encoding seven viral proteins of >8.7 kDa. High amino acid sequence similarity was demonstrated between a potential 33.3-kDa protein product of ORF1 of BFDV and the replicase-associated protein of porcine circovirus (PCV), subterranean clover stunt virus, and faba bean necrotic yellows virus. However, significant similarity in nucleotide or amino acid sequences was not present between BFDV and chicken anaemia virus. A potential stem-loop structure similar to that found in PCV and plant circoviruses was present in the putative encapsidated strand of the BFDV genome. At the top of this structure, a nonanucleotide motif (TAGTATTAC) similar to that of PCV, plant circoviruses, and geminiviruses also was recognised. Comparison of the deduced amino acid sequences of ORF2 of BFDV and PCV demonstrated 29.1% identity, and in both viruses, ORF2 is located on the complementary strand, beginning close to or within the hairpin stem. Our findings provide further evidence of a close relationship among BFDV, PCV, and plant circoviruses but not chicken anaemia virus.     

Circadian and ultradian variation in pancreatic secretion of meal-fed pigs after weaning

We studied the time structure of pancreatic secretion in two experiments involving seven 6- to 7-wk-old intact male pigs, surgically fitted with a jugular vein catheter for blood sampling, pancreatic catheter, and a duodenal T-cannula for chronic pancreatic juice sampling for 72 h at 30- to 60-min intervals. Pigs were kept in metabolic cages in a regimen of 12 h of light alternating with 12 h of darkness and were fed at 0800, 1500, and 2200 daily a standard diet based on barley, soybean meal, and fish meal. Beginning 4 d after surgical recovery, three 24-h collections of pancreatic juice and blood sampling were begun either at 0700 or 0800 every 2nd d for 5 d. Pancreatic secretion exhibited a pattern characterized by distinct meal-related secretions of the first phase (postprandial), containing large amounts of protein and enzymes (trypsin and chymotrypsin), and by non-food-stimulated secretions of the second phase with less protein and enzymes. During the dark span, the first phase was practically absent; the response of the pancreatic secretion to the 2200 meal was not very pronounced. Apart from the anticipated circadian rhythm demonstrable by single cosinor analysis on a group basis, a prominent 8-h component was almost invariably statistically significant. Moreover, an approximately 3.43-h component was also prominent. These data indicate that pancreatic secretions are circadian periodic and that their response to a standard meal is also circadian-stage dependent. The circadian components may have been free-running because the pigs were adjusting themselves to the changing phase and that resulted in the period being different from exactly 24 h.     

Effects of body temperature on ventilatory response to hypoxia and breathing pattern in man

The ventilatory response to hypoxia (PAO2 55 and 45 Torr) at each of four levels of PACO2 was studied in five healthy subjects before and after a rise in rectal temperature of 1.4 degrees C had been induced by means of a heated flying suit. At a given level of chemical drive both ventilation and mean inspiratory flow increased after heating, frequency relatively more than tidal volume. In isoventilation comparisons mean inspiratory flow was identical in normo- and hyperthermia, whereas the durations of inspiration (TI) and expiration (TE) were proportionately shortened. It is suggested that a rise in temperature shortens TI by affecting a central "clock" and that TE changes are secondary to changes in end-inspiratory volume. The euoxic CO2 response in hyperthermia was suggestive of multiplication between CO2 and temperature. Hypoxic sensitivity was significantly increased, indicating a temperature effect on the arterial chemoreceptors. The breathing pattern was in either temperature condition identical in euoxia and in hypoxia.     

Anemia and neutropenia due to copper deficiency in enteral nutrition

Although thrombomodulin (TM) in circulating blood is regarded as an indicator of vascular endothelial disorders, blood TM levels are also known to be affected by renal dysfunction. We measured plasma TM levels in primary glomerular disease (PGD) and lupus glomerulonephritis (GN) with the EIA method, and assessed the extent to which renal dysfunction and endothelial disorders contribute to plasma TM levels in these diseases. The plasma TM/serum creatinine (TM/Cr) ratio was significantly higher in lupus GN patients than in PGD patients or normal controls. A significant positive correlation was found between plasma TM and serum Cr levels in both PGD and lupus GN patients, but the slope (A) of the regression line (TM = A.Cr+B) in lupus GN patients was significantly steeper than in PGD patients. We conclude that plasma TM levels are greatly influenced by renal dysfunction, but that not only renal dysfunction but endothelial disorders may be an important determinant of increased plasma TM levels in diseases such as lupus GN.     

Circadian and ultradian rhythms of drinking behavior of albino rats maintained in constant darkness

The objective of the present study was to investigate the circadian and the ultradian rhythms of drinking behavior in Wistar rats maintained under conditions of constant darkness. Six mature male rats (weighing 270-350 g) were exposed to light-dark 12:12-h cycles (LD 12:12, light on at 12:00 h) for 35 days and then switched to constant darkness (DD) conditions for at least 2 weeks. Drinking behavior was monitored continuously with a standard drinkometer circuit and the data was stored in 5-min bins. A modification of Enright's periodogram technique was used to evaluate the free-running drinking behavior circadian rhythm. Ultradian rhythms in drinking behavior were estimated by the Fast Fourier Transform (FFT) technique. Two of the animals (rats 4 and 6) showed no statistically significant circadian or ultradian rhythms and the other four showed free-running drinking circadian rhythm behavior shorter than 24 h (ranging from 23.333 to 23.967 h). Ultradian rhythms of drinking behavior of 12- and 8-h periods were detected in 4 (rats 1, 2, 3 and 5) and 2 (rats 1 and 5) animals, respectively. The relation of the compound structure of the circadian and ultradian rhythms is discussed demonstrating that drinking behavior is a good marker for studies of physiology of temporal organization.     

Circadian and homeostatic influences on sleep in the squirrel monkey: sleep after sleep deprivation

A series of sleep deprivation (SD) experiments were performed to examine the relative influence of circadian and homeostatic factors on the timing of sleep in squirrel monkeys free-running in constant illumination. All SDs started at the beginning of subjective night and lasted 0, 1/4, 1/2, 1, 1 1/4, or 1 1/2 circadian cycles. These six lengths represented three pairs: (0.1), (1/4, 1 1/4), (1/2, 1 1/2). Within each pair, SD ended at the same circadian phase but differed by one circadian cycle in duration. Both before and after SD, consolidated sleep (CS) episodes occurred predominantly during subjective night, even after long SDs ending at the beginning of subjective day. CS duration was strongly influenced by circadian phase but had no overall correlation with prior wake duration. Sleep loss incurred during SDs longer than 1/4 cycle was only partially recovered over the next two circadian cycles, though total sleep duration was closer to baseline levels after the second circadian cycle after SD. There was a trend toward a positive correlation between prior wake duration and the amount of NREM and delta activity measures during subjective day. Delta activity was not increased in the first 2 hours of CS after the SD. Relatively high levels of delta activity occurred immediately after the SD ended and again at the time of baseline CS onset. These data indicate that the amount of sleep and delta activity after SD in squirrel monkeys is weakly dependent on prior wake duration. Circadian factors appear to dominate homeostatic processes in determining the timing, duration and content of sleep in these diurnal primates.     

Circadian and seasonal variation of the body temperature of sheep in a tropical environment

To determine whether racial differences exist in psychosocial variables among patients with non-insulin-dependent diabetes mellitus (NIDDM), the authors administered a series of questionnaires to 211 Black and White patients of the Wake Forest Family Medicine ambulatory care unit and the Reynolds Health Center, a community health center. In general, Blacks in the study population had higher levels of external locus of control, higher levels of stress, and lower levels of family functioning compared with Whites. These differences may account partially for the disparity of diabetes control and the consequences of diabetes among Blacks. Health professionals may benefit from understanding and addressing these psychosocial variables and may be more successful in implementing intervention programs in this population by tailoring programs to the psychosocial orientation of their population.     

Circadian patterns of locomotor activity and body temperature in blind mole-rats, Spalax ehrenbergi

A wide variety of organisms exhibit circadian rhythms, regulated by internal clocks that are entrained primarily by the alternating cycle of light and darkness. There have been few studies of circadian rhythms in fossorial species that inhabit a microenvironment where day-night variations in most environmental parameters are minimized and where exposure to light occurs only infrequently. In this study, daily patterns of locomotor activity and body temperature (Tb) were examined in adult blind mole-rats (Spalax ehrenbergi). These fossorial rodents lack external eyes but possess rudimentary ocular structures that are embedded in the Harderian glands and covered by skin and fur. Most individual mole-rats exhibited circadian rhythms of locomotor activity, but some animals were arrhythmic. Individuals that did exhibit robust rhythms of locomotor activity also showed rhythms of Tb. In most cases, Tb was highest during the phase of intense locomotor activity. Locomotor activity rhythms could be entrained to light:dark cycles, and several mole-rats exhibited entrainment to non-24-h light cycles (T-cycles) with period lengths ranging from T = 23 h to T = 25 h. Some individuals also showed entrainment to daily cycles of ambient temperature. There was considerable interindividual variation in the daily patterns of locomotor activity among mole-rats in virtually all the conditions of environmental lighting and temperature employed in this study. Thus, whereas it appears likely that photic cues have a significant role in the entrainment of circadian rhythms in mole-rats, the amount of variability in rhythm patterns among individuals appears to be much greater than for most species that have been studied.     

Decreased leptin levels in normal weight women with hypothalamic amenorrhea: the effects of body composition and nutritional intake

Leptin is a protein encoded by the ob gene and expressed in adipocytes. A sensitive marker of nutritional status, leptin is known to correlate with fat mass and to respond to changes in caloric intake. Leptin may also be an important mediator of reproductive function, as suggested by the effects of leptin infusions to restore ovulatory function in an animal model of starvation. We hypothesized that leptin levels are decreased in women with hypothalamic amenorrhea and that leptin may be a sensitive marker of overall nutritional status in this population. We, therefore, measured leptin levels and caloric intake in 21 women with hypothalamic amenorrhea (HA) and 30 age-, weight-, and body fat-matched eumenorrheic controls. Age (24 +/- 5 vs. 24 +/- 3 yr), body mass index (20.6 +/- 1.3 vs. 21.1 +/- 1.5 kg/m2), percent ideal body weight (94.9 +/- 5% vs. 96.3 +/- 6.3%), and fat mass (14.2 +/- 3.6 vs. 15.5 +/- 2.9 kg, determined by dual energy x-ray absortiometry) did not differ between the groups. Leptin levels were significantly lower in the HA subjects compared with those in the controls (7.1 +/- 3.0 vs. 10.6 +/- 4.9 micrograms/L; P = 0.005). Total caloric intake (1768 +/- 335 vs. 2215 +/- 571 cal/day; P = 0.003), fat intake (333 +/- 144 vs. 639 +/- 261 cal/day; P < 0.0001), and insulin levels (5.6 +/- 1.2 vs. 7.4 +/- 3.2 microU/mL; P = 0.015) were lower in the women with HA than in the eumenorrheic controls. The difference in leptin levels remained significant after controlling for insulin (P = 0.023). These data are the first to demonstrate hypoleptinemia, independent of fat mass, in women with HA. The hypoleptinemia may reflect inadequate calorie intake, fat intake, and/or other subclinical nutritional disturbances in women with HA. The mechanism and reproductive consequences of low leptin in this large population of women remain unknown.     

Serum leptin is increased in growth hormone-deficient adults: relationship to body composition and effects of placebo-controlled growth hormone therapy for 1 year

The gene product from the ob gene, leptin, has recently been characterized in humans. The circulating level of leptin is related to body mass index (BMI) and more closely to estimates of total body fat, whereas visceral fat has been reported to be of minor importance. However, it is unknown if leptin is directly regulated by hormones that influence substrate metabolism and body composition. We studied leptin in adult growth hormone (GH)-deficient (GHD) patients substituted with GH treatment for 12 months in a parallel double-blind, placebo-controlled study. Twenty-seven GHD adults aged 44.9 +/- 1.9 years underwent anthropometric measurements for determination of regional and total body fat (BMI, waist to hip ratio [WHR], computed tomographic [CT] scan, dual-energy x-ray absorptiometry [DEXA] scan, and bioimpedance analysis [BIA]) before and after 12 months of placebo-controlled GH substitution (2 IU/m2) in a parallel design. The same measurements were performed in 42 healthy adults aged 39.1 +/- 1.7 years. The logarithm of serum leptin levels correlated positively with abdominal subcutaneous fat and total body fat (BIA and DEXA) in untreated GHD patients and healthy subjects. Fasting insulin did not correlate with leptin levels in either of the groups. After 12 months of GH administration, the body composition of GHD patients was significantly changed with respect to a marked decrease in body fat. The relations of leptin to the estimates of body fat were maintained, and leptin was furthermore related to BMI and fasting insulin. In multiple linear regression analyses, additional estimates of visceral adiposity (intraabdominal fat and maximal anterior-posterior diameter determined by CT scan) were significant determinants of leptin in the healthy subjects. The increase in fasting insulin levels during GH substitution correlated negatively with the reduction in leptin levels (r = -.823, P = .003). At baseline, leptin levels were increased in the patients compared with controls in both sexes (women, 21.8 +/- 3.3 v 11.3 +/- 1.4 ng/mL, P = .002; men, 8.1 +/- 1.2 v 4.7 +/- 0.7 ng/mL, P = .008). Leptin levels were similar in GHD patients treated for 12 months compared with healthy controls for both women and men (women, 15.9 +/- 2.3 and 11.3 +/- 1.4 ng/mL, P = .163; men, 7.1 +/- 2.8 and 4.7 +/- 0.7 ng/mL, P = .759). In healthy adults and in GHD patients, leptin levels were significantly higher in women than in men (11.3 +/- 1.4 v 4.7 +/- 0.7 ng/mL, P < .001; 21.8 +/- 3.3 v 8.1 +/- 1.2 ng/mL, P < .001). Gender remained a significant determinant of leptin levels in several models of multiple linear regression analysis also including age, estradiol levels, insulin, and estimates of body fat. We conclude that leptin is increased but not differently regulated in GHD patients compared with normal subjects, and that leptin levels are closely related to estimates of body fat. This relationship is maintained during a decrease in body fat due to GH substitution.     

Absence of tonic electromyographic activity during sleep in normal and spastic nonmimetic skeletal muscles in man

An electromyographic study of nonmimetic skeletal muscles was carried out in 8 normal adults and 4 patients with spastic hemiparesis during all stages of sleep for a total of 21 nights. All normal subjects showed absence of tonic electromyographic activity in all nonmimetic skeletal muscles in all stages of sleep. Also, during quiet, relaxed wakefulness, tonic muscle discharges disappeared in the normal subjects. Three patients with upper motor neuron spasticity demonstrated results during sleep similar to those obtained in the normal subjects. In the fourth patient, tonic muscle discharges persisted into stage 2 non-REM sleep, disappeared within 30 to 240 seconds following the onset of stage 2 sleep, and were absent during stages 3 and 4 sleep and REM sleep.     

Circadian variations in the occurrence of cardiac arrests: initial and repeat episodes

The purpose of this study was to predict diameters of lesions induced by laser-induced thermotherapy (LITT) of benign prostatic hyperplasia (BPH) from MRI signal/tissue temperature correlations during on-line monitoring with a temperature-sensitive fast low-angle shot (FLASH) sequence. Twenty LITT procedures with Nd:YAG (1,064 nm) and diode (830 nm) lasers were monitored on line with a T1-weighted FLASH sequence at 1.5 Tesla. Interstitial prostate temperature (T) was measured on line in 10 LITT procedures and laser energy deposition in 12. Slopes of linear regression curves for signal intensity (SI) over T were applied to determine SI at 60 degrees C to estimate diameters of intraprostatic LITT lesions. Diameters of unperfused LITT lesion cores in contrast-enhanced T1-weighted images served as gold standards. Linear regression curves with an average slope of -.54% SI/degrees C were obtained in 17 LITT procedures. Correlation coefficients were r = .92-.95 for SI/T and SI/energy deposition. Baseline variation of SI at body temperature was +/-3.9%, corresponding to +/-7 degrees C. Prediction of size (13 lesions) from on-line FLASH imaging was correct in 10 of 13, whereas 3 lesions were overestimated. Prediction of LITT lesion diameters from on-line MRI monitoring is possible with a temperature-sensitive FLASH sequence in the prostate. Accuracy may suffice to assign target regions of interest to tissue locations to be protected from coagulation.     

An improved approach to delivery of enteral nutrition in the intensive care unit

Using immunohistochemistry, vasoactive intestinal peptide (VIP) was visualized in taste bud cells of the carp, Cyprinus carpio, and the European catfish, Silurus glanis, by means of light and electron microscopy. Intracellular membrane systems, presumably smooth endoplasmic reticulum, of light (sensory) cells, but not of dark (supporting) cells and basal cells, were densely labelled with antibody. In the frog (four species: Rana temporaria, R. ridibunda, R. arvalis, R. pipiens), taste bud cells did not label. However, the dense basal nerve fibre plexus, some subepithelial ganglionic cells, but no ascending intragemmal fibres, were immunoreactive. In fish, the results support evidence that VIP is involved in the modulation of taste transduction at the level of receptor cells. In the frog, an indirect, possibly vasodilatatory effect on taste perception may be considered.     

Daytime melatonin administration in elderly good and poor sleepers: effects on core body temperature and sleep latency

Melatonin has been shown to have hypnotic and hypothermic effects in young adults and has been proposed as treatment for insomnia. However, the hypnotic and thermoregulatory effects of melatonin remain to be simultaneously investigated for aged good and poor sleepers. The aim of this study was to explore the short-term effects of exogenous oral daytime melatonin on core body temperature, sleep latency, and subjective vigor and affect in aged women. Twelve sleep maintenance insomniacs and 10 good sleeping postmenopausal female subjects [mean (SD) age = 65.2 (7.4) years] participated in a double-blind, crossover study in which they received a capsule containing either melatonin (5 mg) or a placebo at 1400 hours. Continuous core body temperature and hourly multiple sleep latency tests (MSLT) were collected from 1100-2030 hours. Self-reported estimates of global vigor (sleepiness) and affect were collected prior to each MSLT using visual analog scales. Comparison of good and poor sleepers failed to reveal any significant differences in core body temperature, sleep latency, or subjective vigor and affect. However, for both groups combined, melatonin administration [absolute postadministration mean (SEM) = 36.9 (0.05) degrees C] significantly lowered core body temperature compared with placebo [37.1 (0.05) degrees C]. Similarly, melatonin administration significantly reduced latency to stage 1 (SOL1) and stage 2 (SOL2) [absolute postadministration mean SOL1 = 20.1 (1.7) and SOL2 = 20.7 (1.6) minutes] compared with placebo [SOL1 = 24.3 (1.2) and SOL2 = 25.2 (1.1) minutes]. Treatment had no significant effect on either vigor or affect. Overall, our results suggest that although short-term exogenous oral daytime melatonin has significant hypothermic and hypnotic effects in aged women, the size of the effects is modest.     

Insulin-like growth factor-I in growth hormone-deficient adults: relationship to population-based normal values, body composition and insulin tolerance test

BACKGROUND: Although an insulin tolerance test (ITT) is the most commonly used method for detecting growth hormone (GH) deficiency (GHD) in adults, measurements of serum insulin-like growth factor-I (IGF-I) may also be of value. OBJECTIVE: To validate the use of serum IGF-I concentration in the diagnosis of GHD in adults. DESIGN: A cross-sectional study. PATIENTS: One hundred and four patients, 60 men and 44 women, with known pituitary disease and verified GHD based on ITT. MEASUREMENTS: Serum IGF-I was determined by radioimmunoassay after acid-ethanol extraction. Body composition was estimated with total body potassium combined with total body water assessments. RESULTS: According to age- and sex-adjusted population-based references values, 51 patients had serum IGF-I concentrations below -2 SD of the predicted values and 53 had concentrations within 2 SD. Fifty-seven per cent of the patients aged 41 years (25th percentile) or below and 39% of the patients aged 57 years (75th percentile) or above had serum IGF-I concentrations below -2 SD. Women had lower mean IGF-I SD scores than men (P < 0.01). Serum IGF-I was correlated with peak GH response during ITT (r = 0.40; P < 0.001), age (r = -0.27; P < 0.01), duration of hypopituitarism (r = -0.52; P < 0.001), number of pituitary hormonal deficiencies (r = -0.35; P < 0.001), body cell mass (r = 0.30; P < 0.01) and serum insulin (r = 0.21; P < 0.05). The peak GH response during ITT correlated with spontaneous GH secretion, duration (P = -0.48; P < 0.001) and number of deficiencies (r = -0.50; P 0.001). CONCLUSION: The measurement of serum IGF-I concentrations is not suitable as a single diagnostic test for growth hormone deficiency in adults. Even as a screening test, its use appears to be limited, especially in elderly subjects. The serum level of IGF-I was influenced by several factors in addition to GH, such as age, gender, anthropodometry and serum insulin level. The peak GH response during the insulin tolerance test appears to be influenced to a lesser degree by these factors.