Carlos Cervantes

Body composition in hypopituitary dwarfs before and during human growth hormone therapy

The clinical characteristics and body composition of eight hypopituitary dwarfs (10.2-21.6 yr) were analyzed before and after 6 and 12 mo of growth hormone therapy. 2 IU 3 times/wk. Before treatment, growth rate was 1.8 +/- 0.7 cm/yr, height age was 2.0-12.8 yr less, and bone age 2.0-11.1 yr less than chronologic age. Total body water (TBW), lean body mass (LBM), extracellular water (ECW), and intracellular water (ICW) were below normal for chronologic age, but normal for height. Muscle mass (MM) was below normal for age and height. During HGH therapy, growth rate was 7.1 +/- 1.6 cm/yr in the first 6 mo and 7.8 +/- 1.4 cm/yr during the next 6 mo; the ratio of change in height age to change in chronologic age was greater than or equal to 1.0 in all patients and the ratio of change in bone age to change in height age was 1.2 in one patient and less than or equal to 1.0 in the others. TBW, LBM, ECW, and ICW increased according to height increments; however, MM increased at a faster rate than expected from the height gains. Also, a relative or absolute loss of total body fat was recorded during the first 6 mo of therapy. It is suggested (1) that among the body composition parameters studied, muscle mass is the tissue most closely reflecting the lack of HGH and also its therapeutic benefits and (2) evaluation of body composition in hypopituitary dwarfs in response to HGH therapy shows striking changes not reflected by the determination of stature or weight alone.

Plasma gonadotropins and gonadal steroids in children treated with cyclophosphamide.

Twelve boys (4.7 to 15.4 years) and five girls (4.3 to 14.1 years) treated with cyclophosphamide, 50 to 100 mg/day for periods of two to 12 months were studied. Plasma follicle-stimulating hormone, luteinizing hormone, Δ 4 -androstenedione, testosterone, 17β-estradiol, 17-hydroxyprogesterone, and progesterone were determined by radioimmunoassay in four to six samples from each patient. At time of the study, cyclophosphamide had not been given for 1.0 to 5.3 years. Results were compared to age-matched healthy boys and girls. Four boys treated when prepubertal had a normal hormonal profile. Three out of seven boys treated during stage II of puberty had elevated FSH and LH levels, low Δ 4 -androstenedione levels, but normal plasma testosterone (0.9 to 2.7 years after therapy). Follow-up studies in two of these three boys (4.0 and 6.1 years, respectively, after therapy) disclosed azzospermia in one and severe oligospermia in the other; each had elevated plasma FSH concentrations. In the remaining four boys of this group with previously normal hormonal profiles, follow-up studies in three of them (4.0 to 7.9 years after cyclophosphamide therapy) disclosed normal sperm counts and plasma FSH in one boy and mild oligospermia with normal plasma concentration in two. No evidence of primary ovarian failure was detected in any of the girls. It is suggested that caution should be maintained not only in the total dose and duration of cyclophosphamide therapy, but also in the degree of pubertal development at time of initial therapy.

Immunoreactive insulin and growth hormone responses in patients with Prader-Willi syndrome

Six children with Prader-Willi syndrome were studied in order to assess their plasma immunoreactive insulin and growth hormone levels in responses to oral glucose, protein-glucose meal, and intravenous l -arginine. Their responses were almost identical to those observed in children with long-standing obesity: marked hyperinsulinemia, blunted growth hormone responses, normal plasma glucose levels, and high fasting levels of free fatty acids. The plasma decrements in free fatty acids during administration of the different stimuli were, in general, similar to those of normal or obese children. It is suggested that the described hormonal changes are related to the obesity of children with Prader-Willi syndrome and by no means represent a characteristic hormonal profile of the syndrome, per se.

Propranolol effect on plasma glucose, free fatty acid, insulin, and growth hormone in Graves' disease.

A 3-hr glucose tolerance test was performed in 12 thyrotoxic patients before and after propranolol treatment for 30 days (120 mg/day). Plasma glucose, free fatty acid, insulin, and growth hormone levels were determined on each test and compared to each other and against nine clinically healthy volunteers. In eight thyrotoxic patients (subgroup A) an improvement in carbohydrate tolerance was observed after propranolol treatment, along with a fall in the previously elevated fasting FFA; no change in plasma insulin levels was observed. Plasma growth hormone levels were higher than normal both before and after propranolol; however, a 46% glucose-induced suppression was seen in both instances. In the other four patients (subgroup B) (who had had a marked and rapid weight loss) a deterioration of the previously normal glucosnificant changes in insulin levels. Elevated fasting plasma free fatty acids remained so despite propranolol treatment. Plasma growth hormone was higher than normal before and after propranolol; a late suppression (at 120 min) and no suppression at all were seen, respectively. After propranolol treatment, subgroup B had higher plasma free fatty acid than subgroup A in the fasting state and at 30 and 180 min. It is proposed that the improvement or deterioration in carbohydrate tolerance after propranolol treatment might be related to whether or not a satisfactory propranolol-induced lipolytic blockade is achieved, leading to a decrease in plasma free fatty acid levels, improved insulin sensitivity, and better peripheral glucose utilization. Therefore, a uniform dose of propranolol will not always be sufficient to obtain adequate lipolytic blockade, particularly if the thyrotoxic patient has had a marked and rapid weight loss.

Accumulation of Ethinylestradiol in Blood and Endometrium of Women Taking Oral Contraceptives: The Sequential Therapy *

A radioimmunoassay to quantitate ethinylestradiol (EE-2) in both plasma and endometrium is described. In 29 women under sequential oral contraceptive therapy (chlormadinone acetate, 2 mg, plus mestranol, 80 microgram) for 6 to 84 months, a single blood sample and a single endometrial sample were simultaneously obtained on different days of the pseudomenstrual cycle. In 24 women under 40 years of age the mean plasma EE-2 concentrations were similar during the first (989 +/- 94 pg/ml) and the second half of the cycle (1053 +/- 186 pg/ml) (P greater than 0.05). A similar finding was observed with regard to mean endometrial EE-2 concentrations (3.55 +/- 2.1 and 5.89 +/- 1.7 microgram/gm of wet tissue, respectively). On the other hand, five women over 40 years of age had plasma EE-2 concentrations similar to those of the previous group, but the mean endometrial EE-2 concentrations was 0.9 +/- 0.6 microgram/gm of wet tissue (P less than 0.05). Although plasma follicle-stimulating hormone and luteinizing hormone did not show midcycle peak values, complete suppression of both gonadotropins was not observed. These results show that endometrium has a great ability to concentrate EE-2, and this ability seems to be greater in women below age 40 than above. Whether or not this observation might be related to the known higher incidence of endometrial cancer in women less than 40 years old who have been under chronic sequential oral contraceptive therapy cannot be disclosed from this limited number of determinations.

Effect of Paramethasone Acetate on Women with Secondary Amenorrhea: A Preliminary Report

Twelve women of normal weight (ages 17 to 36 years) with scanty menstrual bleeding were studied. They had no signs of virilization, gynecologic or endocrine pathology, or past history of hormonal treatment. Five women (group 1) experienced withdrawal bleeding after a 3-day course of chlormadinone acetate (2 mg/day) and the other seven did not (group 2). Daily venous blood samples were obtained 10 to 15 days afterward for 5 consecutive days of no treatment (control period) and during the next 5 days while the women received paramethasone acetate (PA), 2 mg/day (treatment period). In each plasma sample the concentrations of 17beta-estradiol (E2) and luteinizing hormone (LH; LER-907) were determined. The mean plasma E2 levels in group 1 were 35 +/- 8 and 86 +/- 10 pg/ml during the control and treatment periods, respectively (P less than 0.001), and the mean plasma LH levels were 28 +/- 6 and 94 +/- 34 ng/ml, respectively (P less than 0.001). No significant changes in plasma E2 and LH levels were observed in group 2 in either period. During the control period, the plasma E2 level in group 2 (14 +/- 2 pg/ml) was lower than that in group 1 (P less than 0.01); however, plasma LH levels were similar in both groups. The administration of PA for 5 months induced monthly ovulation in group 1 but not in group 2. These data suggest that the best results are obtained in women with optimal pretreatment levels of plasma E2.

Paramethasone Acetate (PA): Corticosteroid potency vs hypothalamic pituitary-gonadal axis☆

Because paramethasone acetate (PA) suppresses basal and midcycle LH surge and blocks estrogen synthesis in the female, its possible effect upon testicular physiology was evaluated in 13 healthy men by measuring the circulating levels of FSH, LH, prolactin (PRL), testosterone (T), dihydrotestosterone (DHT), androstenedione (A), estradiol (E2) and cortisol (C) every 4 h throughout the day, before (control) and after PA (6 mg/d/7 d). The total concentrations of each hormone, as well as the PA-induced suppressibility (measured as percent decrease in the mean 24 h plasma level) were analyzed. PA suppressed neither the basal nor circadian rhythm of T and had no effect on LH, FSH or PRL output. DHT, A, E2 were significantly reduced and the basal concentrations and circadian variations of C were abolished. PA showed a dual control on the pituitary gonadal axis and while causing a maximal suppressed adrenocortical activity it had no interference in testosterone synthesis.

Changes in haemoglobin and haematocrit values in children aged 6 to 13 1/2 years in Mexico City.

Levels of haemoglobin (Hb), haematocrit (Ht) and mean corpuscular haemoglobin concentration (MCHC) were determined in 523 boys and 350 girls, clinically healthy, ages 6-0 to 13-5 years, middle socio-economic class living in Mexico City. In girls no significant differences according to age were observed in Hb or MCHC; however, Ht was significantly greater at 10-5 than at 10-0 years, without subsequent modifications. In boys, Hb and Ht had a first increase between 10-5 and 11-0 years and a second rise from 12-5 years on: MCHC remained unchanged. Boys were six to twelve months behind girls in regard to Ht increase; however, Ht increased when boys and girls reached similar mean weights (34 kg), heights (138 cm) and surface areas (1-15 m2); concomitantly, they had progressed to stage 2 of sexual development. Clear sex differences began to appear at age 11-5 when boys had higher Hb and Ht values than girls. These data suggest that Hb and Ht changes in these children are not related to chronological age but can be better interpreted if compared to weight, height, surface area or stage of sexual development.