somatomedin-C Levels Research Articles

Relationship between Clinical and Endocrinological Features following Transsphenoidal Surgery for Acromegaly

Fourteen patients with acromegaly who had undergone transsphenoidal surgery were followed for 1 to 7 years (average, 4.3 years). Pre- and postoperative growth hormone (GH) levels, changes in the GH response to thyrotropin releasing hormone (TRH) tolerance testing, and the correlation between clinical improvement and postoperative GH and somatomedin-C levels were studied. Clinical improvement was assessed by scoring of the pre and postoperative symptoms. A significant correlation was found between the postoperative GH and somatomedin-C levels (p<0.01). All patients with postoperative somatomedin-C levels of less than 2 IU/ml, including one of the three patients whose postoperative GH levels were between 5 and 10 ng/ml, showed clinical improvement. Normal responses to TRH testing were rare and were poorly correlated with clinical improvement. These results suggest that somatomedin-C is more useful than GH in predicting clinical improvement following surgery for acromegaly.

Polycystic ovarian disease: endocrinological parameters with specific reference to growth hormone and somatomedin-C.

Thirty-three women (22-38 years old) with polycystic ovarian disease (PCOD) were included in this study. The criteria for diagnosis were: an LH/FSH ratio greater than 2.0; polycystic ovaries, diagnosed by means of palpation and ultrasound; androgenism and menstrual cycle abnormalities. Using endocrine parameters, we attempted to define distinct forms of PCOD. The patients were placed in three groups according to serum levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17 alpha OHP) and the estrone/androstendione (E1/delta 4A) ratio. Patients in group I (n = 18) had an elevated T level (greater than 1.0 ng/ml) and a 17 alpha OHP level under 4.0 ng/ml. This type of POCD was called the "androgen" type. Patients in group II (n = 7) had normal T- and 17 alpha OHP levels under 4.0 ng/ml and an elevated (E1/delta 4A) ratio. This type of PCOD was called the "estrogen" type. Group III (n = 8) comprised patients with 17 alpha OHP levels over 4.0 ng/ml. This type of PCOD was called the "adrenocortical" type. In two patients of this group, a modified ACTH test revealed late-onset congenital hyperplasia. The endocrine parameters of the patients with PCOD were compared with those of 17 adult without signs of PCOD. Statistical evaluation was done by variance analysis. Women with acromegaly often show signs of androgenism as well as menstrual cycle abnormalities. This may indicate an association between the growth factors human growth hormone (HGH) and somatomedin-C (Sm-C) and the biosynthese and metabolism of steroid hormone. Recent experiments have demonstrated such associations. Our study showed an association between the HGH and Sm-C levels and abnormal steroid hormone concentrations in women with androgen type PCOD (group I). These patients had a significantly decreased HGH level, a significantly decreased HGH/Sm-C ratio, and an increased average Sm-C level. These data suggest that elevated Sm-C levels can, by a negative-feedback mechanism, inhibit pituitary HGH production. We discuss the possible mechanisms causing elevation of plasma Sm-C, HGH, steroid hormones, excessive food intake, and possibly prolactin seem responsible for the clinical manifestation of increased Sm-C production in adolescence and for its level in the fertile years of patients.

EVALUATION OF GROWTH HORMONE (GH) SECRETION IN SHORT CHILDREN: SLEEP SECRETION AND STIMULATION TESTS

GH sleep secretion (SS) and GH response to pharmacologic stimuli (PS) were compared in 215 short children (-3.2 ± 0.9 SD), aged from 2 to 18 years (147 boys, 68 girls), 123 at pubertal stage P1 and 92 P2. Somatomedin C (SmC), DHA sulfate (DHAS), testosterone (T) or estradiol (E2) were measured. SS and PS were slightly correlated at both stages P1 (r = 0.4; p<0.01) and P2 (r = 0.31; p<0.01), SS being higher at P2 than at PI. SS is related to growth velocity at P1. At P2, SS is positively correlated to T in boys and negatively to E2 in girls. SmC is correlated to SS and PS at P1 and P2, and is higher at P2. It is not significantly correlated to sex steroids. SS and PS are discrepant in 67 cases : either normal SS and low PS in 37 or the contrary in 30, and moreover SmC level did not rise at P2 in these patients. Some of the patients with such discrepancies enhanced their growth velocity under hGH treatment. It is concluded : 1/ Early pubertal increase of SS preceeds that of PS. It is controlled by sex steroids. 2/ SmC is related to SS and puberty, but there may be other regulation factors than sex steroids. 3/ SS/PS discrepancy was observed in 30 % of cases in this study. 4/ In these cases, SmC does not rise at P2 and hGH treatment may improve the growth velocity.

Plasma growth hormone half-life after selective removal of adenoma in acromegalics determines the outcome of surgery.

We measured plasma GH levels during transsphenoidal surgery in eight patients with acromegaly. After removal of the adenoma GH levels fell monoexponentially in six subjects while they were still under general anaesthesia, but no decrease was noted for two other subjects. Normal postoperative GH and Somatomedin-C levels were found for those patients who exhibited a reduction in GH during surgery. During follow-up studies one patient with a normal GH level exhibited a paradoxical reaction to TRH, attributed to tumour remnants. The plasma half-life found for five patients was 18-33 min; for another cured subject it was longer, i.e. 58 min. The major fraction of the circulating GH, as determined by gel-chromatography, was mol. wt 22,000; this applied for six subjects, while the patient with the long plasma half-life appeared to have a mol. wt 33,000 variant. From this study we conclude that a clear drop in the plasma GH level after removal of the adenoma predicts a favourable outcome of surgery; however, if some tumour remnants are left behind, paradoxical reactions may occur despite normal basal GH levels.

Changes in growth and serum growth hormone and plasma somatomedin-C levels during suppression of gonadal sex steroid secretion in girls with central precocious puberty.

Suppression of gonadal sex steroid secretion in children with central precocious puberty (CPP) by LHRH analogs affords an opportunity to study sex steroid modulation of GH and somatomedin-C (Sm-C) secretion and to examine the role of GH and Sm-C in pubertal and prepubertal statural growth. Nocturnal serum GH and plasma Sm-C levels were measured in 10 preadrenarchal girls [mean age, 3.0 +/- 0.6] ( +/- SEM) yr with CPP before and during 2 yr of LHRH analog-induced gonadal suppression. Their mean height velocity, initially 4.6 +/- 0.6 ( +/- SEM) SD above the mean for chronological age, decreased to -0.1 +/- 0.4 SD during 12-24 months of ovarian suppression (P less than 0.00005). The mean peak nocturnal plasma GH level was 22.5 +/- 5.4 ( +/- SEM) micrograms/L during puberty, and it decreased to 10.2 +/- 2.1 micrograms/L after 3 months of suppression of gonadarche. This decrease persisted throughout the 2 yr of gonadal suppression (P less than 0.05). The reduction in GH secretion was accompanied by a decrease in mean plasma Sm-C levels from 3.5 +/- 0.7 to 1.5 +/- 0.2 U/mL after 3 months of suppression of gonadal sex steroids, which persisted during 2 yr of gonadal suppression (P less than 0.01). Suppression of ovarian function in girls with CPP results in decreased height velocity. This slowing of growth occurs in association with decreased nocturnal serum GH and plasma Sm-C levels, suggesting that acceleration of growth during puberty is partially mediated by sex steroid-induced augmentation of GH secretion.

Somatomedin-C and growth in children with precocious puberty: a study of the effect of the level of growth hormone secretion.

This study was undertaken to investigate the role of GH secretion in the pubertal increase in plasma somatomedin-C (Sm-C) concentrations and its relation to growth in children with true precocious puberty (PP) and normal or deficient GH secretion. We studied 37 children (9 boys and 28 girls), divided into 3 groups according to their pubertal stages and their peak stimulated plasma GH concentration. Group I (n = 20) contained patients with PP and normal GH secretion. In group II (n = 8), PP was accompanied by GH deficiency. Group III (n = 9) patients were GH deficient and prepubertal. The mean plasma Sm-C (RIA) levels in groups I and II were 2.01 +/- 0.17 (+/- SEM) and 0.59 +/- 0.21 U/mL, respectively (P less than 0.001), and it was 0.09 +/- 0.01 U/mL in group III (P less than 0.001 compared to group II). The higher mean plasma Sm-C level in group II compared to that in group III could be related to a significantly higher GH response to arginine-insulin stimulation (P less than 0.02), although this value was in the hypopituitary range. The mean growth rate in group II (6.8 +/- 0.9 cm/yr) was also much higher than the rate in group III (1.9 +/- 0.5 cm/yr; P less than 0.001) and only slightly lower than that in group I (90 +/- 0.8 cm/yr; P less than 0.05). These data indicate that plasma Sm-C values are closely correlated with even small changes in GH secretion. The observed growth rates could, in general, be linked to plasma GH and Sm-C levels, as modulated by sex steroids, in these patients with precocious puberty.

Growth hormone (GH) response to GH-releasing hormone in depression.

To explore the GHRH-GH-somatomedin axis integrity in major depressive disorder, 11 drug-free patients and normal subjects matched for age, sex, ovarian status, and body weight received 1 microgram/kg synthetic human GHRH-44 amide as an iv bolus dose. Compared to the normal subjects, the depressed patients had reduced mean basal serum GH levels [2.2 +/- 0.5 (+/- SE) vs. 1.1 +/- 0.2 ng/mL (micrograms/L); P less than 0.05] and a significant attenuation of the net GH response to GHRH [1346 +/- 499 vs. 217 +/- 46 ng.min/mL (micrograms.min/L); P less than 0.01]. The blunted GH responses occurred in the face of significantly increased plasma somatomedin C (Sm-C) levels [1.1 +/- 0.2 vs. 0.6 +/- 0.1 U/mL; P less than 0.05]. The magnitude of GH responses to GHRH did not differ between men and women and was not significantly correlated with age, body weight, baseline serum GH levels, or plasma Sm-C levels in either individual groups or both groups combined. The increased plasma Sm-C levels in the depressed patients could have resulted from diurnal hypersecretion of GH, and the diminished GH responses to GHRH may reflect normal Sm-C-mediated feedback at the level of the pituitary. The presumed GH hypersecretion may be due to decreased hypothalamic somatostatin release and/or hyperactivity of GHRH-containing neurons. Thus, the pathological process resulting in abnormal GH secretory patterns associated with depression may occur primarily at a suprapituitary site.

GH binding to liver in young and old female rats: relation to somatomedin-C secretion.

Age-related changes in binding of 125I-bovine GH to liver membrane fractions were measured in female Long-Evans rats 2, 6, 12 and 20 months of age. Specific GH binding did not change between 2 and 6 months of age but increased significantly at 12 and 20 months of age. Scatchard analysis showed that the plots were curvilinear and consisted of high- and low-affinity binding sites. The age-related increases in binding sites were mainly due to an increase in number of low-affinity binding sites. Serum somatomedin-C (SM-C) levels in 20-month-old rats were about half those in the 6-month-old rats. Twice daily injections of ovine GH (2 mg/kg body wt) for 7 days depressed liver GH binding and increased serum SM-C levels in 19-month-old female rats, but had no effect on GH binding in 2-month-old female rats. These results suggest that the increase in liver GH binding sites and the decrease in SM-C secretion are associated with our previously reported decrease in GH secretion in old female rats.

Investigation of the criteria for assessing the outcome of treatment in acromegaly.

The outcome of treatment in acromegaly is usually assessed by measuring plasma concentrations of growth hormone (GH)--either basal spontaneous levels or during hyperglycaemia. There is no consensus on how cure should be defined. Many studies have considered basal plasma growth hormone concentrations below 20 mU/l (10 ng/ml) as proof of cure, although some recent studies have applied lower values. At present a limit of 10 mU/l (5 ng/ml) seems to be accepted as evidence of cure. We have studied 28 acromegalic patients after transsphenoidal adenomectomy. Plasma GH concentrations (basal and during hyperglycaemia) as well as plasma somatomedin C (SMC) concentrations were measured and compared to the clinical symptoms. There was a close correlation between plasma GH and SMC concentrations (except when plasma GH levels were low) and between the clinical assessment and SMC concentrations. Very low plasma GH levels (less than 1 mU/l or 0.5 ng/ml) were associated with normal SMC values and clinical cure, high GH levels (greater than 10 mU/l or 5 ng/ml) with elevated SMC levels and persisting acromegaly. Moderately elevated plasma GH concentrations (1.9-9.6 mU/l) did not allow any conclusions on the outcome of treatment as assessed from SMC determinations and clinical evaluation. It is concluded that the usual criteria for cure in acromegaly may not be sufficiently strict.

SMS 201-995 induces a continuous decline in circulating growth hormone and somatomedin-C levels during therapy of acromegalic patients for over two years.

Ten acromegalic patients, four previously untreated, were studied before and at regular intervals during treatment with the long-acting somatostatin analog SMS 201-995 (200-300 micrograms daily for 2 or 3 sc injections for 16-108 weeks). All patients had rapid clinical improvement, with disappearance of excessive perspiration, paresthesias, and headache within the first 6 weeks of therapy. The mean 24-h serum GH concentrations fell from 44.0 +/- 7.8 (+/-SE) micrograms/L before to 5.9 +/- 1.0 microgram/L at the end of therapy. The GH levels from 2-6 h after the acute administration of 50 micrograms SMS 201-995 before the start of therapy correlated significantly with the mean 24-h GH concentrations after 16-108 weeks of treatment (P less than 0.05). The initially increased serum somatomedin-C (Sm-C) levels normalized in 5 of these 10 patients; the mean values were 7.3 +/- 0.9 U/mL before and 2.9 +/- 0.7 U/mL at the end of therapy. The Sm-C and mean GH levels continuously decreased during long term therapy; the concentrations after 1.5-2 yr of therapy were significantly lower than those after 6-12 months of therapy (P less than 0.01 and P less than 0.01, respectively). A slight decrease in the size of the pituitary tumor was noted by computed tomography in three of six patients. Transient clinically detectable steatorrhea occurred in two patients. Postprandial hyperglycemia occurred during therapy in eight patients, while in two patients with type 2 diabetes mellitus carbohydrate tolerance improved in one and deteriorated in the other. SMS 201-995 is a highly effective medical treatment for acromegaly. Clinically improvement occurs rapidly, and the inhibition of serum GH and Sm-C levels persisted even after more than 1 yr of therapy. No important subjective side-effects were noted. SMS 201-995 is an excellent drug in patients in whom acromegaly persists after surgery and for interim treatment to shorten the period of clinical activity after irradiation.

Relationship between growth hormone and somatomedin-C levels in untreated acromegaly, after surgery and radiotherapy and during medical therapy with sandostatin (SMS 201-995).

Several conflicting reports have been published with regard to the relationships between circulating growth hormone (GH), Somatomedin-C (SM-C) levels and clinical activity during different stages of therapy of acromegaly. We did not find a significant correlation between (fasting, post-prandial and mean 24-h) plasma GH and SM-C concentrations in twenty-two untreated acromegalic patients. There was a statistical significant correlation, however, if only the GH levels below 100 micrograms 1(-1) were considered (n = 18 patients, P less than 0.01). The distribution of molecular forms of GH ('little', 'big' and 'big-big') did not differ between the four patients with GH levels above 100 micrograms 1(-1) and in four patients with levels between 40 micrograms 1(-1) and 80 micrograms 1(-1). Therefore, it is suggested that GH levels of 80-100 micrograms 1(-1) maximally activate Somatomedin-C production in man and that further increases in GH in general will not result in a further increase in SM-C generation. There was a significant correlation between GH and SM-C levels in forty-nine acromegalic patients after surgery and/or radiotherapy (P less than 0.001). In twenty-three of thirty-one patients with elevated SM-C levels the disease was subjectively still active, while this was the case in none of the patients with normal SM-C levels. In eight patients the disease was considered not to be clinically active any more, despite slightly increased SM-C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

REDUCED GROWTH HORMONE RESPONSE TO GROWTH HORMONE‐RELEASING HORMONE IN CHILDREN WITH SIMPLE OBESITY: EVIDENCE FOR SOMATOMEDIN‐C MEDIATED INHIBITION

We have evaluated the plasma GH response to a single injection of 1 microgram/kg of GH-releasing hormone (GHRH)-40 in 15 obese children and 15 age-matched control children. Most of the obese children showed a subnormal plasma GH response to GHRH and the mean plasma GH integrated area (IC-GH) following stimulation was significantly smaller in obese than control children. Plasma somatomedin-C (SM-C) levels were significantly higher in obese than control children, and were negatively correlated with the peak plasma GH levels (r = -0.616, P less than 0.01) and the IC-GH (r = -0.554, P less than 0.02) after GHRH. Non-esterified fatty acids (NEFA) and fasting plasma insulin levels were also elevated in obese children, but did not correlate with the extent of plasma GH response to GHRH. These data confirm previous observations on the refractoriness of obese children to release GH after GHRH, and imply that it may be due to the feedback inhibition operated by the elevated plasma levels of SM-C.

Results of 1-Year Growth Hormone (GH)-Releasing Hormone-(1-44) Treatment on Growth, Somatomedin-C, and 24-Hour GH Secretion in Six Children with Partial GH Deficiency

Six children with short stature and partial GH deficiency in response to two pharmacological tests received GHRH for 12 months (10 micrograms/kg X day, sc) each evening. Twenty-four-hour GH secretion was studied before and after 3 and 12 months of treatment, and GHRH tests (2 micrograms/kg, iv) were done before and after 6 months of treatment. Plasma somatomedin-C was measured before and after 1.5, 3, 6, 9, and 12 months of treatment. Statural growth was measured at 3-month intervals. Mean growth velocity increased from 4.2 to 8.6 cm/yr, with a good result in five children and no response in the other. The growth response was substantial during the first 3 months. It was maintained during the following 6 months, and then decreased during the last 3 months. The peak plasma GH level in response to GHRH increased from 34.5 +/- 14.2 (+/-SD) ng/mL before treatment to 47.8 +/- 3.4 ng/mL after 6 months of treatment. Twenty-four-hour GH secretion increased in all parameters at 3 months (maximum peak, area under the curve, integrated concentration, and number of peaks) and at 12 months (with the exception of the maximum peak). Nycthemeral secretory profiles became normal, with reappearance of secretory pulses in two children, slight increases in three children, and no change in one child. Plasma somatomedin-C levels rose from 0.8 +/- 0.3 U/mL before treatment to 2.0 +/- 1.0 U/mL at 3 months, then decreased to 1.3 +/- 0.6 U/mL at 12 months. These results indicate that GHRH administered by sc injection for a 1-yr period stimulated growth and GH secretion. However, a decrease in activity was noted during the last 3 months of treatment. Tests for anti-GHRH antibodies were positive in the only child who did not respond to treatment.

Growth in Turner's syndrome: long term treatment with low dose ethinyl estradiol.

The growth response to 100 ng/kg BW X day ethinyl estradiol (2-4 micrograms/day) given for 18 months was studied in a group of nine patients with Turner's syndrome, aged 8.6-13.3 yr. All patients were prepubertal and had elevated gonadotropin levels. Growth velocity increased from 3.09 +/- 1.05 (+/-SD) to 7.09 +/- 1.47 cm/yr in the first 6 months, 6.08 +/- 1.78 cm/yr in the second 6 months, and 4.03 +/- 1.65 cm/yr in the third 6 months. Bone age increased a mean of 0.82 +/- 0.34, 0.89 +/- 0.79, and 0.74 +/- 0.59 yr, respectively, in the three 6-month periods. Predicted height prognosis did not change after any period. All patients had pubertal changes, limited in most to slight breast development. Mean diurnal spontaneous GH secretion did not change during treatment. Plasma somatomedin-C levels were low before treatment, and ethinyl estradiol did not significantly increase somatomedin-C values. Our data confirm the ability of a low dose of ethinyl estradiol to increase growth velocity in girls with Turner's syndrome, although the effect diminished with time, and the excess bone age advancement precluded improvement of predicted height.

A longitudinal study of the relationship of plasma somatomedin-C concentration to the pubertal growth spurt.

Cross-sectional studies from our institutions (Wyler Children's Hospital, Chicago, and Children's Hospital of Philadelphia) and others have shown that plasma somatomedin-C (Sm-C) concentrations rise during puberty. To determine the relationship between rising plasma Sm-C levels and the growth spurt at puberty, we undertook a longitudinal study of 11- to 18-year-old children. Twelve male and eight female subjects were followed up on a yearly basis for two to seven years (mean, 4.4 years). Height velocity, plasma Sm-C concentrations, and stage of sexual development were determined during each visit. All patients progressed normally in puberty during the study. The plasma Sm-C level rose during early puberty in each child and reached a maximal level of at least 2 U/mL In midpuberty, approximately one year after the attainment of peak height velocity. Maximal plasma concentrations of Sm-C were similar in male (3.5 +/- 0.71, mean +/- SEM) and female (3.5 +/- 1.46) subjects. Plasma Sm-C levels subsequently decreased slowly but remained above normal adult values for as long as four years after peak height velocity was reached. Plasma Sm-C concentrations increased steadily with increasing height velocity until peak height velocity was attained with a mean rise of approximately 0.5 U for each centimeter per year increase in height velocity. Since Sm-C levels remained elevated while height velocity decreased, there was no significant correlation between Sm-C levels and height velocity throughout puberty. These results suggest that caution is required in interpreting Sm-C concentrations during puberty; while normal pubertal levels may be in the acromegalic range for adults, a plasma Sm-C level of less than 1 U/mL in early puberty or less than 1.5 U/mL during middle to late puberty must be considered subnormal.

Effect of growth hormone on growth and glucose tolerance of normal rats.

To determine the effect of growth hormone (GH) administration on growth rate, ultimate size, and glucose tolerance of intact rats, we administered ovine GH to male Sprague-Dawley weanling rats for six weeks. Growth hormone, in a dose sufficient to double the growth rate and increase sixfold the somatomedin C (SM-C) levels of hypophysectomized rats, failed to increase the rate of growth or size of visceral organs of intact rats. Their SM-C levels increased only 10%. Following glucose administration, the mean blood glucose levels were higher at every time point measured in those treated with GH compared with the intact control animals. We conclude that, although there was no difference in somatic or visceral growth, the dose of exogenous GH administered increased SM-C levels and decreased glucose tolerance in the intact rats. While a larger GH dose might increase the final body size of non-GH-deficient animals, impaired glucose tolerance could be a significant side effect.

Serum Factor Responsible for Thymidine Uptake by Lymphocytes Is Independent of Somatomedin-C

ABSTRACT Lymphocytes have specific receptors for somatomedin-C (Sm-C) and GH. To test whether these cells are sensitive to the growth-promoting properties of these growth factors, we studied serum (with low or normal Sm-C and GH levels) from children having various statural disorders by means of the lymphocyte proliferation assay. Peripheral lymphocytes from each subject were cultured in media containing either autologous serum (AS) or normal pooled human serum (HS). The mitogenic response (MR) was assessed by determining the amount of tritiated thymidine incorporated into cellular DNA. The MR was studied both in phytohemagglutinin-stimulated and in unstimulated lymphocytes. MR was expressed as thymidine uptake (CPM) in the presence of AS divided by CPM in the presence of HS. The MR in serum from (1) 27 control subjects was 1.01 ± 0.03 (SEM); (2) 14 children with short stature and normal serum GH-RIA and Sm-C levels was 0.98 ± 0.04; and (3) 12 children with GH deficiency showed two widely different responses. In four patients (subgroup 1), the MR was 0.05 ± 0.02 and in eight (subgroup 2) the MR was 1.11 ± 0.06. Eleven patients were studied after GH therapy (three from subgroup 1), and the MR was 1.12 ± 0.03. Neither Sm-C levels nor linear growth rate correlated well with the growth-promoting property of the serum when tested on lymphocytes. In seven additional patients with GHD, the MR when studied at varying concentrations of serum (0.1–5.0%), showed results identical to subgroup 2. Addition of purified Sm-C to cultures did not enhance the MR of serum from GHD patients prior to GH therapy. GH-dependent factors other than Sm-C may have a role in in vitro lymphocyte proliferation; in its current form, however, this bioassay is not sensitive enough to be useful in the diagnosis of children with GH deficiency.

FAILURE OF CLONIDINE TO IMPROVE THE GROWTH HORMONE RESPONSE TO L-DOPA ADMINISTRATION

We have previously shown that oral administration of clonidine (C) during one year period increases plasma somatomedin C (SM-C) levels, growth velocity and growth hormone (GH) response to C in prepubertal short children. We have now studied the effect of chronic administration of C on SM-C level and GH response to L-Dopa (DA) administration in three short children (aged 13.8 ± 1.8 yrs) with blunted GH response to DA administration but normal GH response to insulin-induced hypoglycemia and C. C was administered orally in a single dose (0.15 mg/m2/body surface area) daily at night during a 3-month period. The GH response to DA (250 mg) administration was determined before and one week after the treatment with C was terminated. Our results suggest that the increase in SM-C levels seen after long term administration is not mediated by Dopaminergic pathway.

Pituitary-hypothalamic response in adolescents with growth failure due to fear of obesity.

Nine patients (4F, 5M) aged 12-17 years with "fear of obesity" were studied with a sequential stimulation test utilizing insulin, LRH, TRH, and L-dopa. The comparative groups were nine female with classic anorexia nervosa, five males with undifferentiated nutritional dwarfing, and nine children (1F, 8M) with constitutional growth delay. The serum TSH, glucose, cortisol, somatotropin, prolactin, LH, and FSH were sampled periodically over 2 hours. Basal T3, T4, transferrin, and Somatomedin-C levels were also obtained. The "fear of obesity" patients did not have any pituitary function changes that were unique. These patients, as well as the comparison groups, revealed a delayed TSH response in proportion to the weight deficit which, when expressed as an integrated response, correlated well to the weight deficit for height (P less than 0.001) and to the ability to recover from hypoglycemia (p less than 0.001). The Somatomedin-C level was low and correlated to the T3 level (p less than 0.05) and not correlated to the elevated Somatotropin levels. The pituitary response to combined stimulation in patients with fear of obesity was determined to be a component of the spectrum starting at normal and proceeding to the extreme undernutrition of anorexia nervosa. Pituitary responsiveness, therefore, changes not as a function of the etiology of the malnutrition, but simply as a function of its severity.

Chronic sex steroid exposure increases mean plasma growth hormone concentration and pulse amplitude in men with isolated hypogonadotropic hypogonadism.

Sex steroid administration can increase the GH response to provocative stimuli, but the relationship of sex steroids to spontaneous GH secretion is still controversial. We sought to characterize the effect of sex steroids on the plasma GH concentration by examining the 24-h pattern of episodic GH secretion in nine previously untreated adult men with isolated hypogonadotropic hypogonadism before and during long term testosterone, gonadotropin, or pulsatile GnRH treatment. After chronic sex steroid exposure, the mean 24-h plasma GH level, mean GH pulse amplitude, and mean area under the curve of pulses were significantly increased compared to pretreatment values [3.2 +/- 1.8 ( +/- SD) vs. 1.8 +/- 1.2 ng/mL (P less than 0.01); 11.4 +/- 7.2 vs. 5.5 +/- 4.4 ng/mL (P less than 0.05); and 720 +/- 547 vs. 316 +/- 371 ng/mL X 20 min (P less than 0.05), respectively], while mean 24-h pre- and posttreatment GH pulse frequencies were indistinguishable (5.7 +/- 2.1 posttreatment vs. 5.0 +/- 3.2 pretreatment; P = NS). The mean posttreatment plasma somatomedin-C level also rose significantly during treatment (1.89 +/- 0.65 vs. 1.28 +/- 0.48 U/mL; P less than 0.01). We conclude that the increase in the mean plasma GH level during chronic sex steroid exposure is due mainly to augmentation of GH pulse amplitude, and that sex steroids probably increase spontaneous GH secretion.