Jordan W. Finkelstein

Studies with human growth hormone (HGH): An attempt to correlate metabolic response during short-term administration with linear growth during prolonged therapy

Abstract All fifteen patients (twelve hypopituitary dwarfs, one primordial dwarf and two patients with gonadal dysgenesis) studied exhibited one or another metabolic response to human growth hormone (HGH) during initial short-term studies. Decreased urinary nitrogen, increased urinary calcium and increased urinary hydroxyproline: creatinine ratio were observed in all patients so studied. All twelve hypopituitary dwarfs showed a significant fall in serum urea nitrogen. The magnitude of the various responses to HGH varied in individual patients. No effect of the short-term administration of HGH could be used to predict the response in linear growth to prolonged therapy with the possible exception of minimal nitrogen retention ( The data presented here suggest that the administration of HGH, 5 mg. daily for six days, will correct reactive hypoglycemia but that a longer period of treatment is necessary for correction of sensitivity to exogenous insulin. No increase in growth rate was observed in the primordial dwarf treated for six months with Wilhelmi HGH, (W HGH), 2 mg. daily for the first fourteen days of each twenty-eight day cycle. Two patients with gonadal dysgenesis treated in a similar manner with 5 mg. of HGH daily showed accelerated linear growth. All preparations of HGH used were metabolically active, including two preparations from pituitaries from embalmed bodies. All three of the preparations of HGH, including one from pituitaries from embalmed bodies, used for prolonged treatment were capable of stimulating growth rate. A comparison of the potency of the various preparations is not possible due to the limited use of any HGH other than that extracted by Wilhelmi. During initial metabolic studies the administration of HGH was equally effective when the total dosage was given in one dose daily or in divided doses. No unequivocal evidence for contamination of the HGH with TSH, ACTH or gonadotropins was obtained. Ten of twelve hypopituitary dwarfs showed accelerated growth when given 2 mg. of HGH daily for the first fourteen of each twenty-eight days. One patient failed to respond at this dosage level but showed comparable response to a dose of 5 mg. HGH. Patients receiving more than one eight-month course of injections of HGH, using the same dosage and preparation, exhibited diminished growth response during succeeding courses. This waning effectiveness occurred in one patient despite increases in the dose.

Psychological stress, ego defenses, and cortisol production in children hospitalized for elective surgery.

&NA; This study was designed to investigate the relationship between the effectiveness of coping mechanisms and physiological indicators of distress in children faced with the experience of hospitalization and surgery. Twenty‐five children between the ages of 7 and 11 were studied in the out‐patient department, 2 weeks before surgery, and again during their hospital stay. Effectiveness of defenses and defense style was measured by a clinical interview and by the Rorschach test. Cortisol production rates were measured by the analysis of 24‐hour urine collections at home and again in the hospital. Ward adjustment was also rated by a ward questionnaire. The results indicated no relationship between defense effectiveness and cortisol production rates in the out‐patient department and an inverse relationship between cortisol production and defense effectiveness under the stress of hospitalization. Defense style was found to correlate with coping under stress. Four different groups of children emerged, suggesting four different types of reaction to the hospital experience.

The relationship between aggressive behavior and puberty in normal adolescents: a longitudinal study.

PURPOSE To assess changes in aggressive behaviors as related to progression from early to late puberty in normal adolescents. METHODS Subjects were normal English schoolchildren. An observational cohort design was employed. Pubertal status was measured by Tanner staging. Self-reports of verbal aggression against adults, physical aggression against peers, aggressive impulses and aggressive inhibitory responses, were collected at three points in time. Analyses were performed for the entire group of 106 subjects in 1983, 77 subjects in 1985 and 70 subjects in 1987. Statistical methods included analysis of variance, regression and correlation and cluster formation. RESULTS There were decreases in all aggression variables except in aggressive impulses over this time period. When analyzed by gender, boys were initially more aggressive than girls, but by late puberty all gender differences in self-reported aggressive behaviors had disappeared. When only those subjects who were evaluated at all three data collection times were grouped by similar responses on both aggression and physical variables, three clusters of boys and girls were identified. Clusters contained varying proportions of boys and girls. Cluster one (48.5% of the entire sample) was a low aggression group. Cluster two (30.3%) was a high aggression group, and cluster three (21.2%) was an intermediate aggression group. These clusters seemed to have relatively stable aggression characteristics over time. CONCLUSIONS These data suggest that groups of boys and girls who report similar aggression characteristics and have similar growth and pubertal characteristics can be identified. Neither gender alone, nor pubertal status alone, nor by inference, hormones alone is sufficient to explain the complex set of behaviors which are involved in aggression.

The effect of sex hormone replacement therapy on behavior problems and moods in adolescents with delayed puberty

OBJECTIVE The objective of this clinical study was to determine the effects of sex steroids on behavior and mood in adolescents with hypogonadism. STUDY DESIGN The experimental design consisted of a randomized, double-blind, placebo-controlled, crossover trial lasting for 21 months. The study group consisted of 39 boys and 16 girls recruited from a pediatric endocrine clinic for delayed puberty. Depo-testosterone (to boys) or conjugated estrogens (to girls) was administered in 3-month blocks, alternating with placebo, at 3 dose levels approximating early, middle, and late pubertal amounts. The Child Behavior Checklist, Youth Self Report, Differential Emotion Scale, and Daily Mood Diary were administered after each placebo and treatment period to ascertain the effect of sex steroids on self- and parent-reported behavior problems and moods. RESULTS The data demonstrated only one significant treatment effect, namely, an increase in withdrawn behavior problems during administration of low-dose estrogen in girls. There were no consistent sex differences. CONCLUSION These results demonstrate that administered testosterone or estrogen has minimal effects on behavior problems or mood in adolescents.

Twenty-four-hour Cortisol Profiles Demonstrate Exaggerated Nocturnal Rise in Diabetic Children

Plasma cortisol was measured every 20 min for 24 h in 12 normal and 8 insulin-dependent, nonketotic, diabetic children treated with one daily injection of insulin. Plasma glucose was also measured every 20 min in the diabetic children. The diurnal pattern of cortisol secretion was identical. The mean 24- h plasma cortisol was similar in both groups, but significantly elevated in the diabetic children between 0200 and 0920 h. Peak cortisol levels were higher in the diabetic than in the normal children. No correlation was found between average plasma glucose and average plasma cortisol, or between the nocturnal change in plasma glucose and average nocturnal plasma cortisol in the diabetic subjects. These studies demonstrate an exaggeration of the normal nocturnal rise in plasma cortisol in diabetic children not related to the levels of plasma glucose.

The effect of developmental changes in adolescence on drug disposition

Biological and behavioral change occurs throughout the lifespan. The nature and rapidity of change during adolescence is striking. The effects of rapid growth, sexual maturation, and psychological reorganization on pharmacodynamics and pharmacokinetics must be considered during studies on teenagers. It is important to consider the large amount of variability in the timing of normal developmental events. The concept of developmental rather than chronological age should be considered. Measurement of organismic and behavioral variables includes whole organism measures such as body height, weight, surface area, body mass index, self-concept, sexual identity/role, and many other behavioral measures. Pubertal development may be assessed by sexual maturity ratings. Bone age may be a particularly useful estimate of developmental status. Biochemical measures include gonadotropin, sex steroids, other hormonal or hormone receptor values.

Diversity of pubertal testosterone changes in boys with constitutional delay in growth and/or adolescence.

In a group of 22 boys with constitutional delay in growth and/or adolescence, intermittent testosterone enanthate treatment was employed in a randomized clinical trial at multiple doses ranging from 25-100 mg every two weeks for three month periods extending over 15-21 months. Twelve of the patients displayed a prompt increase in endogenous testosterone levels during the study period, reaching levels in the adult male range (> 250 ng/dl). The remaining 10 boys showed sluggish changes in endogenous testosterone during the investigation, ranging from 35-177 ng/dl. The bone ages and testicular sizes of the two groups at study initiation did not differ though urine LH was significantly less at study entry in the slowly maturing group. The data reveal a great diversity in the pace and pattern of endogenous testosterone changes in the study population. The results also suggest that exogenous sex steroid treatment of such patients does not speed up the central nervous system processes controlling the onset and progression of puberty. Boys with delayed puberty should be followed until endogenous testosterone levels reach the adult male range in order to rule out mild gonadotropin deficits.

The syndrome of congenital adrenal unresponsiveness to ACTH in 5 patients

Because of the demonstration of human growth hormone-like activity by prolactin in the treatment of hypopituitary dwarfs (McGarry and Beck: Lancet 2: 915, 1962) we have been interested in comparing the effects of prolactin and growth hormone upon the chemistry of the connective tissue. The skins of large numbers of rats which had received either hormone were sequentially extracted in the cold with 0.15M NaC1, 0.5M NaC1, and 0.5M citrate buffer to remove quantitatively the ground substance, salt, and acid extractable collagens, respectively. The results indicate that while growth hormone was without profound effect upon the dermal chemistry of rats, prolactin administration resulted in an increase in the dermal concentration of the citrate extractable collagen (250 per cent) and marked losses of ground substance (40 per cent) , salt extractable collagen (50 per cent) , and insoluble collagen (28 per cent) from the skin. The apparent mechanism of the catabolic effect of prolactin upon dermal collagen was found to consist of three steps: (1) the release of a cytoplasmic protease into the extraeellular compartment of the skin, (2) the proteolytie activation of the collagenase-ogen found in this compar tment by the protease, and (3) the enzymatic digestion of insoluble collagen into two components, one diffusable, the other extractable in citrate buffer. This released protease also digested enzymatically the proteins of the ground substance thereby permitt ing acid mucopolysaccharides to drain away from the tissue. Thus, all the dermal chemical alterations with prolactin administration may be explained as a consequence of the release of a protease from the cells.

Dysregulation of the Hypothalamic-Pituitary-Adrenal Axis in Short Children With and Without Growth Hormone Deficiency

The effects of L-dopamine (LD) administration and insulin-induced hypoglycemia in adrenocorticotropin (ACTH) and cortisol secretion were studied in 14 short boys. LD caused moderate changes in both hormones. The four boys with isolated, idiopathic growth hormone (GH) deficiency (IGD) demonstrated a greater cortisol increase in response to hypoglycemia than the 10 boys with normal GH secretion. In at least some short children with IGD, abnormal regulation of the hypothalamic-pituitary-adrenal axis may be present.

Estrogen or Testosterone Increases Facial and Body Attractiveness in Hypogonadal Adolescents 13

Estrogen or Testosterone Increases Facial and Body Attractiveness in Hypogonadal Adolescents 13