Images in clinical densitometry.
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Journal Article↗
Biomedical subjects
J L Borges
Publications and source records attributed to J L Borges.
Congenital dislocation of the hip in boys.
Fifty-five boys with seventy-eight congenitally dislocated hips were treated between 1965 and 1990. The patients were divided into three groups according to the initial treatment. Group I included thirty hips (twenty-two boys) that had been treated initially with a Pavlik harness. Two hips (7 per cent) had a successful outcome, and twenty-eight (93 per cent) needed additional methods of treatment. Group II included forty-two hips (twenty-nine boys) that had been treated initially with closed reduction and immobilization in a hip-spica cast. After the closed reduction, twenty-nine hips (69 per cent) were considered stable, although fifteen (52 per cent) of them needed a secondary procedure because of residual subluxation or persistent acetabular dysplasia. Thirteen hips (31 per cent) were considered unstable after the closed reduction and subsequently had an open reduction. Group III included six hips (four boys) that had been treated initially with open reduction. Two of these hips redislocated after the open reduction, and they were reduced with an additional open reduction. A pelvic osteotomy was later performed to treat persistent acetabular dysplasia in these two hips. Two hips that had been treated with an open reduction and concomitant pelvic and femoral procedures did not need additional treatment. This study demonstrates that boys who have congenital dislocation of the hip do not always respond well to treatment and constitute a high-risk group.
Casts, Surgical↗
Cerebral toxoplasmosis after renal transplantation. Case report and review.
Infection caused by Toxoplasma gondii is a frequent event in Portugal. When this occurs in immunocompetent individuals, it is rarely a matter of concern; the contrary occurs with immunosuppressed patients or in pregnancy. Transplant patients are treated with immunosuppressive drugs which mainly disturb their mechanisms of cellular immunity, and that opens the way to infections by opportunistic intracellular microorganisms. We recently treated a renal transplant patient who suffered from cerebral toxoplasmosis, and this provided an opportunity for a review of the other 20 patients reported in medical literature to date.
Adult↗
Restaging of colorectal cancer based on the identification of lymph node micrometastases through immunoperoxidase staining of CEA and cytokeratins.
The present study was performed to identify tumor cells in lymph nodes from colorectal adenocarcinomas considered free of disease by the classic hematoxylin-eosin stain, based on the detection of the carcinoembryonic antigen (CEA) and cytokeratins in neoplastic epithelial cells. For this purpose, 603 lymph nodes from 46 lesions were stained by the peroxidase-antiperoxidase technique. Tumor cells were detected in 22 nodes from 12 patients, mainly in the subcapsular sinuses, permitting a restaging of these patients into two groups: those now considered to have metastatic disease and those free of metastases. However, the 5-year follow-up showed no statistical differences in survival between the two groups.
Adenocarcinoma↗
Actions of calcium ions and a calcium-influx blocker on basal and TRH- and GnRH-stimulated hormone release in patients with pituitary adenomas.
We investigated the influence of calcium ions on the secretion of anterior pituitary hormones basally and in response to exogenous hypothalamic releasing factors in 6 men with pituitary tumors. To this end, concentrations of LH, FSH, TSH, growth hormone and prolactin were measured in blood collected at 10-min intervals basally and during a continuous infusion of combined TRH (2 micrograms/min) and GnRH (1 microgram/min). Study sessions were randomized to iv saline, calcium, or diltiazem infusions or oral diltiazem administration. Our results indicate that in contrast to responses in normal men, iv calcium injections do not suppress circulating prolactin concentrations in patients with prolactin-secreting pituitary tumors. Moreover, neither oral diltiazem administration for one week nor acute iv diltiazem infusion suppressed the hyperprolactinemia of tumor patients. However, there were significant effects of drug and calcium treatments on serum concentrations of FSH, GH and testosterone, but not LH or TSH. Moreover, during GnRH-TRH stimulation, there were significant differences in LH, TSH, and testosterone responses in tumor patients compared to normal men. In summary, iv calcium infusion was associated with invariant basal release of anterior pituitary tumoral hormones in patients with pituitary adenomas. However, there were significant differences in the GnRH/TRH-stimulated release of certain anterior pituitary hormones in tumor patients compared to normal men in response to iv calcium and the calcium-channel antagonist, diltiazem.
Adenoma↗
Physiological and clinical studies of GRF and GH.
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Acromegaly↗
Human pancreatic tumor GH-releasing factor.
Within the past year, three similar peptides with specific growth hormone (GH) releasing effects have been extracted from human tissue, identified, and synthesized. Human pancreatic tumor GH releasing factor (I-40)-OH (hpGRF-40) was the sole hpGRF isolated from the pancreatic tumor of a patient in Charlottesville and was the predominant peptide isolated from the pancreatic tumor of a patient in Lyon. The Lyon tumor also contained hpGRF(1-37)-OH and hpGRF(1-44)-NH2. Both immunological and biochemical data suggest that hpGRF-40 and hpGRF-44 are present in the human hypothalamus and may be the human GH releasing hormone(s) (GHRH). In cultures of rat pituitary cells, hpGRF stimulates GH but affects neither basal and dopamine-inhibited prolactin release nor basal and gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. hpGRF stimulates cyclic AMP production within seconds, an effect which is blocked by somatostatin. In contrast, while hpGRF stimulates phosphatidylinositol turnover in the pituitary, the effect is not inhibited by somatostatin. In the human, hpGRF-40 (1 microgram/kg) given intravenously (i.v.) stimulates GH release within 5 minutes. hpGRF-40 does not elevate serum prolactin levels, thyrotropin (TSH), LH, or corticotropin (measured indirectly through plasma cortisol), or blood glucose or plasma concentrations of insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, or somatostatin. When graded doses of hpGRF (0.1-10 micrograms/kg) are given i.v., no differences are noted in the maximal levels of serum GH achieved.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
Divergent influences of the structurally dissimilar calcium entry blockers, diltiazem and verapamil, on thyrotropin- and gonadotropin-releasing hormone-stimulated anterior pituitary hormone secretion in man.
We have tested the influence of a new calcium ion channel antagonist, diltiazem, on hypothalamic releasing hormone-stimulated secretion of LH and other anterior pituitary hormones in man. To this end, six normal men received a continuous infusion of GnRH (1 microgram/min) and TRH (2 micrograms/min) for 3 h under three different experimental conditions: 1) saline (control) infusion; 2) iv diltiazem (0.3 mg/kg bolus dose, and 0.002 mg/kg . min) infusion for 4 h beginning 1 h before releasing hormone injection; and 3) oral diltiazem (60 mg, every 6 h) administration for 1 week before pituitary stimulation. Blood was sampled at 10-min intervals for the subsequent immunoassay of LH, FSH, TSH, PRL, and GH concentrations and at hourly intervals for the assay of plasma diltiazem concentrations by high performance liquid chromatography. Despite sustained plasma diltiazem concentrations of 80-120 ng/ml during either iv or oral drug administration, the GnRH/TRH-stimulated release of LH, FSH, TSH, and PRL or the basal secretion of GH did not differ significantly from that during saline infusion. In contrast, when these subjects underwent the same infusion schedule using a structurally dissimilar calcium influx blocker, verapamil (5-mg bolus dose and 15 mg/h, continuous infusion), there was significant suppression of the delayed component of GnRH/TRH-stimulated LH release, with simultaneous enhancement of PRL secretion. We conclude that exogenously stimulated anterior pituitary hormone secretion in man exhibits differential susceptibility to the structurally discrete calcium entry blockers diltiazem and verapamil. Moreover, the differential influence of these two calcium ion channel antagonists on gonadotropes is distinct from that described in cardiac and smooth muscle cells.
Administration, Oral↗
Effects of intravenous, subcutaneous, and intranasal administration of growth hormone (GH)-releasing hormone-40 on serum GH concentrations in normal men.
In addition to stimulating GH release in normal subjects, GH-releasing hormone-40 (GHRH-40) stimulates GH secretion in some adults and children with GH deficiency. Recognizing that GHRH-40 may have potential as a therapeutic agent for the treatment of GH deficiency, we examined the effects of iv, sc, and intranasal (in) GHRH-40 administration on GH secretion and measured the plasma levels of immunoreactive GHRH achieved after the administration of the peptide via these different routes. Normal men were given vehicle or GHRH-40 iv (0.003, 0.01, 0.03, and 0.1 micrograms/kg; n = 10), sc (1, 3.3, and 10 micrograms/kg; n = 8), or in (3, 10, 30, and 100 micrograms/kg; n = 5). No subject had any symptoms after administration of vehicle or GHRH-40. During the 2-h period after iv administration of GHRH-40, the maximal increment in serum GH levels above basal (nanograms per ml; mean +/- SD) after the 0.1 micrograms/kg dose was 15.5 +/- 10.4 compared to 2.4 +/- 4.1 after vehicle (P = 0.0017). During the 3-h period after sc administration, when compared to the maximal increment in serum GH above basal after vehicle alone (10.2 +/- 12.9), the maximal increments above basal in serum GH were increased after both the 3.3 micrograms/kg (26.2 +/- 23.1; P = 0.022) and 10 micrograms/kg (63.6 +/- 53.5; P = 0.0003) doses. During the 3-h period after in administration, when compared to the maximal increment in serum GH above basal after vehicle alone (2.8 +/- 6.4), the maximal increments above basal in GH were higher after both the 30 micrograms/kg (18.5 +/- 10.4; P = 0.0053) and 100 micrograms/kg (21.7 +/- 8.1; P = 0.0028) doses. In addition, significant dose-response relationships were documented between the maximal increments above basal in serum GH and GHRH-40 administered by all routes. The mean (+/- SEM) peak plasma level of IR-GHRH (nanograms per ml) achieved after administration of 10 micrograms/kg GHRH-40, iv, as reported previously (66.6 +/- 17.6), was approximately 60- and 500-fold higher than the mean levels in the current study after administration of the same dose sc (1.11 +/- 0.39) or in (0.14 +/- 0.02), respectively. In summary, although GHRH-40 stimulates GH release when administered iv, sc, or in, significantly higher doses were required using the sc and in routes to achieve responses comparable to those obtained with iv administration.
Administration, Intranasal↗
Mesulergine, a new dopamine agonist: effects on anterior pituitary function and kinetics.
We investigated the effects of single doses of mesulergine on basal and thyrotropin-releasing hormone (TRH)-stimulated serum levels of several anterior pituitary hormones in healthy men and defined its kinetics. We also compared the effects on serum prolactin (PRL) levels of three doses (0.1, 0.35, and 0.5 mg) of mesulergine to those in response to 2.5 mg bromocriptine. Secretory rates of PRL before the first dose of TRH were not affected by any dose of mesulergine or bromocriptine. TRH-stimulated PRL secretion was not altered by 0.1 mg mesulergine but was blunted by both the 0.35- and 0.5-mg doses at 10 A.M. and 1 P.M. Bromocriptine inhibited TRH-stimulated PRL secretion at 10 A.M. and 8 P.M. When analyzed as the 8 A.M. to 8 P.M. and the 8 P.M. to 9 A.M. (day 2) intervals, PRL secretion was not changed by 0.1 or 0.35 mg mesulergine but was suppressed during both periods by the 0.5-mg dose. A dose-response relationship was evident, however, between mesulergine and PRL secretion during both the 8 A.M. to 8 P.M. (R2 = 0.27) and the 8 P.M. to 9 A.M. (day 2; R2 = 0.18) intervals. Bromocriptine lowered PRL secretion during both intervals. Secretory rates of growth hormone during these intervals were not affected by 0.1 mg or 0.35 mg mesulergine but were increased during both intervals by the 0.5-mg dose. Neither the secretory rates of thyrotropin in response to TRH nor those of cortisol, luteinizing hormone, or follicle-stimulating hormone were changed by 0.1 or 0.35 mg mesulergine.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
The self-priming effect of gonadotropin-releasing hormone on luteinizing hormone release: observations using rat anterior pituitary fragments and dispersed cells continuously perifused in parallel.
To study in vitro the self-priming effect of GnRH on LH release, rat anterior pituitaries were prepared either as fragments or dispersed cells and continuously perifused in parallel chambers. The experimental groups consisted of rats killed at 0800 h on diestrus day 1, diestrus day 2, proestrus or estrus, or at 1400 h on proestrus. To insure truly independent observations, each experimental preparation was tested on three occasions. After basal LH release had stabilized, the tissue preparations were exposed to 10 nM GnRH as two 30-min challenges separated by 1 h. LH secretory rates (nanograms per min/pituitary for fragments; nanograms per min/10(7) cells for dispersed cells) were calculated 1) for basal release (during the 20-min period immediately preceding each GnRH challenge), 2) in response to GnRH, and 3) as the sum of basal and GnRH-stimulated release. Comparison of the two preparations revealed that basal and GnRH-stimulated LH release by pituitary fragments was more variable than LH release by dispersed cells. In addition, while dispersed cells responded promptly to the addition/withdrawal of stimuli, fragments did so more gradually. With respect to GnRH self-priming, the second mean secretory rate for basal LH release by fragments (range, 28.8-46.5) was significantly (0.1 greater than P greater than 0.01) higher than the first rate (range, 14.4-22.0) on diestrus day 1, diestrus day 2, proestrus at 0800 h, and estrus. With dispersed cells, the first and second basal rates were similar to each other on diestrus day 1 and estrus, but on diestrus day 2 and on proestrus at 0800 and 1400 h, the second basal rate (range, 36.8-93) was significantly (P less than 0.001) higher than the first range (range, 17.7-31.7). When fragments received GnRH, the second mean secretory rate (range, 35.2-64.2) was significantly (0.1 greater than P greater than 0.03) higher than the first rate (range, 13.4-34.1) on diestrus day 2 and proestrus at 0800 h. With dispersed cells, the mean secretory rate in response to the second GnRH challenge was higher only on diestrus day 2 (37.0 +/- 4.1 vs. 60.3 +/- 3.8; P less than 0.05). When considered as the total of basal plus GnRH-stimulated LH release, the second secretory rate by fragments (range, 54.5 - 110.8) was significantly (0.1 greater than P greater than 0.02) higher than the first rate (range, 27.9 - 51.4) on diestrus day 1, diestrus day 2, and proestrus at 0800 h.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Human pancreatic tumor growth hormone-releasing factor: dose-response relationships in normal man.
Human pancreatic GRF (hpGRF-40; 1 microgram/kg, iv) selectively stimulates GH release in normal men (9). We now report the effects of graded doses of hpGRF-40 on GH release in 12 normal men. Mean peak increments in serum GH after vehicle and the various doses of hpGRF-40 were 1.13, 11.40, 14.60, 17.01, 14.45, and 15.60 ng/ml after vehicle and 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40 (iv bolus), respectively. Peak values were observed 30-60 min after hpGRF-40 treatment. There was considerable variability of responsiveness among individual subjects, and no dose-response relationship between the doses and maximal GH values was found. However, the higher doses of 3.3 and 10.0 micrograms/kg resulted in a more prolonged and biphasic pattern of GH release. A side effect of facial flushing of less than 5-min duration occurred in 4 or 6 subjects who received 3.3 micrograms/kg and in all 5 who received 10 micrograms/kg of hpGRF-40. No changes in serum glucose, LH, TSH, PRL, plasma cortisol, or 8 enteropancreatic hormones occurred after hpGRF-40 treatment. There were small increases in serum somatomedin C levels 24 h after the administration of various doses of hpGRF-40 in 11 of 13 studies. Plasma immunoreactive GRF levels measured 5 min after injection were 0.09, 2.0, 4.9, 23.9, and 66.6 ng/ml after 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40, respectively. Serum GH responses after insulin-induced hypoglycemia were compared to GH responses after hpGRF-40. Comparable peak GH stimulation occurred with both provocative tests. Mean +/- SEM peak GH was 20.2 +/- 1.0 ng/ml after insulin and 20.9 +/- 3.2 after hpGRF-40 treatment. hpGRF-40 selectively stimulates GH release in normal men over a dose range of 0.1-10 micrograms/kg and is an effective probe to investigate the dynamics of GH release.
Adult↗
Follicle-stimulating hormone-secreting pituitary tumor with concomitant elevation of serum alpha-subunit levels.
Hypersecretion of FSH and alpha-subunit was documented in a man with a pituitary adenoma that was previously diagnosed on clinical grounds as nonfunctioning who had been treated by transsphenoidal surgery and postoperative irradiation. Postoperatively, the patient had high serum FSH levels and normal serum, LH levels. Ten years after the surgery, immunostaining of the tumor revealed the presence of beta FSH, beta LH, and beta TSH in the cytoplasm of scattered adenoma cells, although not always in the same cells. LH levels were elevated during the middle portion of the 12 yr that this patient was followed. However, as LH immunoreactivity was shown (in specimens recently drawn) to be largely due to cross-reactivity in the alpha-subunit RIA, the high LH values may represent high alpha-subunit levels. The elevated FSH levels and alpha-subunit concentrations did not rise after GnRH administration. Thus, during the course of 12 yr, this patient's tumor hypersecreted FSH and alpha-subunit and possibly LH. The evolution of these events may represent the natural history of the tumor or the effects of the therapeutic modalities used. We conclude that adult men with pituitary tumors and complaints of hypogonadism should be evaluated for a FSH-secreting tumor.
Adenoma↗
Stimulation of growth hormone (GH) and somatomedin C in idiopathic GH-deficient subjects by intermittent pulsatile administration of synthetic human pancreatic tumor GH-releasing factor.
After initial challenges with vehicle alone and then 10 micrograms/kg human pancreatic tumor GH-releasing factor (hpGRF)-40, six adult subjects who had presented in childhood with idiopathic GH deficiency were given 0.33 micrograms/kg hpGRF-40, iv, every 3 h for 5 days. Serum GH levels were monitored daily for 90 min after the 0800 h doses of 0.33 micrograms/kg hpGRF-40, and serum somatomedin C was measured at 0800 and 2000 h. In addition, plasma levels of cholesterol, high density lipoprotein cholesterol, and triglycerides were measured daily at 0800 h. Three hours after the last 0.33 micrograms/kg dose, all subjects were rechallenged with 10 micrograms/kg hpGRF-40. In response to the initial 10 micrograms/kg challenge with hpGRF-40, and although serum GH levels rose in two of six subjects, the mean maximum GH level achieved was no different from that after treatment with vehicle alone. Within 12 h after initiation of the intermittent administration of hpGRF-40, mean +/- SEM serum somatomedin C had risen by 0.1 +/- 0.05 U/ml, and at the end of the 5-day period, had increased from 0.24 +/- 0.07 to 0.78 +/- 0.32 U/ml. In response to the second challenge with 10 micrograms/kg hpGRF-40, serum GH levels rose in three of the four subjects who initially failed to respond or had a less than 1 ng/ml GH response. The increase in serum GH was greater in one of the two subjects who had responded to the first dose. In addition, unlike the first dose, the mean maximal serum GH level achieved in response to the second 10 micrograms/kg dose of hpGRF-40 was higher than that in response to vehicle (P = 0.031). Although there was no statistically significant change during the 5-day period, in plasma cholesterol, high density lipoprotein cholesterol, or triglycerides, the latter exhibited a trend toward increased levels. Our preliminary data show that 5 days of intermittent hpGRF-40 administration augment GH secretion in some adults with GH deficiency, suggesting that somatotropes are present in idiopathic GH deficiency and may be primed by hpGRF-40. The rise in serum somatomedin C to normal levels after multiple injections of hpGRF-40 is encouraging, since circulating levels of somatomedin C may be more important than the increase in immunoreactive GH levels as an index of response for induction of linear growth. The demonstration of biological effects of hpGRF-40 in all six subjects without any serious adverse effects suggests that hpGRF-40 has promise in the treatment of GH deficiency.
Adult↗
Divergent influences of calcium ions on releasing factor-stimulated anterior pituitary hormone secretion in normal man.
To investigate the influence of calcium ions on the secretion of anterior pituitary hormones in response to stimulation by exogenous hypothalmic releasing factors in man, we measured serum concentrations of pituitary hormones serially during a continuous infusion of combined TRH (2 micrograms/min) and GnRH (1 microgram/min), with concomitant iv saline or calcium administration. Compared to saline, calcium administration was associated with a significant increase in GnRH-TRH-stimulated LH and FSH release and a corresponding rise in serum testosterone concentrations. The effect of calcium ions on gonadotropin secretion was specific, because releasing factor-stimulated secretion of TSH and PRL was suppressed by hypercalcemia. Serum concentrations of GH were not significantly altered under these conditions. In summary, the present results provide the first in vivo evidence that acute infusion of calcium ions augments GnRH-TRH-stimulated secretion of LH and FSH, with an accompanying increase in serum testosterone levels. In contrast, hypercalcemia did not alter serum GH concentrations, and it suppressed GnRH-TRH-stimulated release of PRL and TSH. We conclude that calcium ions can selectively influence releasing factor-stimulated secretion of certain anterior pituitary hormones in man.
Adult↗
Effects of human pancreatic growth hormone-releasing factor-40 on serum growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, and somatomedin-C concentrations in normal women throughout the menstrual cycle.
Human pancreatic tumor GH-releasing factor-40 (hpGRF-40) selectively stimulates GH secretion in normal men and in some adults with GH deficiency. To study its effects in women, we administered hpGRF-40 (3.33 micrograms/kg) or an equivalent volume of vehicle as an iv bolus at 0900 h to 10 normal women during the early follicular, late follicular, and midluteal phases of the menstrual cycle. Serum concentrations of GH, PRL, LH, and FSH were measured at intervals between 0800-1100 h. Serum somatomedin-C concentrations were measured before and 24 h after the administration of vehicle of hpGRF-40. Within 1-3 min after the injection of hpGRF-40 all women described warmth localized to the head and neck and exhibited facial flushing. No changes in pulse rate or blood pressure were noted. When expressed as change from baseline and compared to control values, peak levels of serum GH (nanograms per ml; mean +/- SEM) were higher after hpGRF-40 treatment during the early follicular (5.4 +/- 3.2 vs. 34.9 +/- 8.3; control vs. test day; P = 0.011), late follicular (5.6 +/- 1.5 vs. 25.2 +/- 6.8; P = 0.014), and luteal (0.8 +/- 1.0 vs. 32.7 +/- 12.8; P = 0.033) phases of the menstrual cycle. Similarly, integrated serum GH levels (nanograms per ml/h) were higher after hpGRF-40 administration during the early follicular (0.72 vs. 16.1; P = 0.011), late follicular (0.83 vs. 9.9; P = 0.037), and luteal (-1.54 vs. 17.0; P = 0.036) phases of the cycle. When the increases in serum GH after hpGRF-40 treatment were compared among the phases of the menstrual cycle, however, no differences were found. Serum somatomedin-C values 24 h after hpGRF-40 treatment were higher than those 24 h after vehicle at all stages of the menstrual cycle. hpGRF-40 did not stimulate the release of PRL, LH, or FSH. We conclude that hpGRF-40 stimulates the release of GH, but that in response to the dose used, hpGRF-40-stimulated GH release does not vary during the menstrual cycle.
Adult↗
Effects of human pancreatic tumour growth hormone releasing factor on growth hormone and somatomedin C levels in patients with idiopathic growth hormone deficiency.
Human pancreatic tumour growth hormone releasing factor (hpGRF-40) 10 micrograms/kg was administered intravenously to 6 normal young men and 12 adult patients who had presented in childhood with growth hormone (GH) deficiency (7 patients had isolated GH deficiency, 4 had multiple anterior pituitary hormone deficiencies, and 1 had Hand-Schüller-Christian [HSC] disease). hpGRF-40 administration increased serum GH concentrations in all normal subjects and in 3 of 7 patients with isolated GH deficiency and in the 1 with HSC disease; however, the mean serum GH concentration in the patients who responded was less than that of the normal subjects. Somatomedin C concentrations were increased 24 h after a single dose of hpGRF-40 in 8 of 10 patients with GH deficiency. All subjects experienced flushing in response to hpGRF-40. A patient with isolated GH deficiency received 0.33 micrograms/kg hpGRF-40 every 3 h for 5 days. Despite the modest increase in GH in response to a subsequent dose of 10 micrograms/kg hpGRF-40, serum somatomedin C levels increased within 12 h from 0.06 to 0.1 U/ml and peaked at 0.36 U/ml at 72 h; in addition the patient with HSC disease, treated with hpGRF-40 daily for 5 days, demonstrated an increase in somatomedin C from 0.4 to 0.58 U/ml. The increase after hpGRF-40 in serum GH levels in this patient and the similar or greater responses in 3 of 7 patients suggest that at least some of these patients may have hypothalamic GH-releasing-hormone deficiency. hpGRF-40 may be useful in distinguishing pituitary disease from hypothalamic disease. After hpGRF-40 administration serum somatomedin C levels may increase without a change in serum immunoreactive GH concentrations. Further studies are needed to determine whether hpGRF-40 is useful in promoting linear growth in children with GH deficiency.
Adult↗
Human pancreatic growth-hormone-releasing factor selectively stimulates growth-hormone secretion in man.
A growth-hormone-releasing factor has been characterised and sequenced from a pancreatic tumour removed from a patient with acromegaly. It is a 40-residue linear peptide. Synthetic human pancreatic growth-hormone-releasing factor (hpGRF-40), 1 microgram/kg bodyweight, was administered as an intravenous bolus to six healthy men. hpGRF-40 selectively stimulated growth-hormone secretion. Serum growth-hormone concentrations were increased within 5 min, reaching a peak between 30 and 60 min (20 . 4 +/- 6 . 5 ng/ml compared with 2 . 1 +/- 0 . 1 ng/ml after placebo). Serum levels of prolactin, thyrotropin, luteinising hormone, and corticotropin (measured indirectly through plasma cortisol) were not increased after administration of hpGRF-40. Similarly, the concentrations of blood glucose, plasma insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, and somatostatin were unaffected by hpGRF-40. There were no changes in blood pressure, pulse rate, or body temperature, and no side-effects were noted. The characteristics of this peptide fulfil many of the criteria required of the hypophysiotropic growth-hormone-releasing hormone. hpGRF holds promise for a new approach to the diagnosis and treatment of various disorders of growth-hormone secretion.
Acromegaly↗