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Biomedical subjects

M L Vance

Publications and source records attributed to M L Vance.

At least 73 records · Page 4Linked to original sources
PubMed1988

Transdermal testosterone treatment of hypogonadal men.

Hypogonadism, either primary or secondary, results in diminished libido and/or impotence. Conventional treatment consists of periodic intramuscular injections (usually bimonthly) of a depot testosterone preparation or daily oral ingestion of methyl testosterone. These conventional treatments may be associated with side effects, such as gynecomastia, liver function abnormalities and edema. A new method of administering testosterone is by daily application of a transdermal therapeutic system. We studied the efficacy and safety of the transdermal therapeutic system in 4 hypogonadal men. Three patients were treated for 12 weeks and 1 for 7 weeks, and they were evaluated weekly. Of 4 patients 3 had improvement in erectile and/or sexual function. Mean plasma testosterone levels increased significantly compared to pre-treatment values during 7 of 12 treatment weeks. There were no adverse effects of the transdermal therapeutic system as indicated by serial physical examinations, daily reports, blood chemistry studies, liver function tests, urinalysis and hematological profiles. This preliminary report of transdermal testosterone delivery indicates that it may provide an effective alternative method of gonadal steroid replacement.

Administration, Cutaneous↗
PubMed1988

Contemporary tools for the analysis of episodic growth hormone secretion and clearance in vivo.

The evaluation of episodic GH release is made difficult by the apparently random nature of GH secretory bursts, the frequent occurrence of minimally detectable plasma GH concentrations, the relatively rapid plasma disappearance rate of endogenous GH, and the large number of metabolic and environmental cues that alter GH dynamics. Nonetheless, the development of objective, statistically based, and reproducible computerized algorithms to quantify episodic GH release has offered new insights into the pathophysiological regulation of GH secretion in health and disease. Moreover, the recent formulation of algebraically explicit biophysical models of GH secretion and clearance has made possible a complete quantitative description of GH secretory and clearance dynamics over a full 24 hours of observation. Such analytical tools allow investigators to enumerate with statistically bounded confidence limits the number, amplitude, durations, and temporal locations of all significant underlying secretory bursts and simultaneously calculate the half-life of endogenous GH disappearance from all GH concentrations and their variances considered together. Accordingly, in conjunction with contemporary refinements in GH assay techniques, such novel approaches to dissecting the temporal structure of GH secretion and clearance in vivo should result in significantly enhanced understanding of GH dynamics in health and disease.

Child↗
PubMed1987

Role of dopamine in the regulation of growth hormone secretion: dopamine and bromocriptine augment growth hormone (GH)-releasing hormone-stimulated GH secretion in normal man.

The role of the dopaminergic system and its interaction with GH-releasing hormone (GHRH) in the regulation of GH secretion was investigated in normal men in two complementary studies. The men were given continuous iv infusions of 0.15 M saline (5 h), dopamine (4 micrograms/kg X min; 1 h), GHRH (2 ng/kg X min; 2 h), and GHRH (2 ng/kg X min; 2 h) plus dopamine (4 micrograms/kg X min; 1 h) on four separate occasions, and serum GH responses were measured. In a second study, on separate days, placebo or bromocriptine (2.5 mg/dose) was administered, and GH and PRL responses to a single iv GHRH dose were measured. A continuous infusion of dopamine and GHRH on separate days stimulated GH secretion in all subjects. The mean integrated GH secretion was 13.2 +/- 3.1 (+/- SEM) ng/mL X h during the dopamine infusion and 14.7 +/- 4.6 during GHRH, compared with 1.7 +/- 0.4 during the saline infusion. The combination of GHRH and dopamine resulted in the greatest stimulation of GH secretion (29.8 +/- 5.7 ng/ml X h; P less than 0.05 vs. 3 other study days). The oral dopamine agonist bromocriptine also augmented GHRH-stimulated GH secretion. Integrated GH secretion after a single iv injection of GHRH following two doses of bromocriptine was 160 +/- 29.5 ng/ml X h compared with 81.3 +/- 22.2 after placebo (P = 0.04). We suggest that these findings are compatible with the hypothesis that dopamine inhibits hypothalamic somatostatin secretion, which then allows for a greater stimulatory effect of GHRH.

Adult↗
PubMed1987

Reversibility of gastric dysmotility in cortisol deficiency.

This case documents scintigraphically that gastric dysmotility associated with hypoadrenalism secondary to hypothalamic-pituitary dysfunction was reversed when the adrenal insufficiency was treated. The patient reported upon received almost immediate relief of symptoms after corticosteroid replacement therapy and improvement of gastric motility, as demonstrated by both liquid and solid phase 99mTc-labeled studies. This experience suggests that glucocorticoids are important permissive hormones for normal gastrointestinal motor function and may have a role in the pathophysiology of gastrointestinal tract disease.

Adrenal Insufficiency↗
PubMed1987

Medical treatment of idiopathic infertility.

We conclude that, although many therapies have been advocated, no regimen has proved to be consistently effective in the treatment of idiopathic male infertility. Couples in which the husband is identified as having idiopathic infertility should be advised of the inconsistent and often low conception rates obtained with medical therapy. This should be weighed against the possibility of greater success with in vitro fertilization and the likelihood of success with artificial insemination by donor. Matson and colleagues performed in vitro fertilization on 75 couples in which the husband was oligospermic. When the husband was moderately (5.1 to 11.9 million motile sperm per milliliter) or severely (less than or equal to 5 million motile sperm per milliliter) oligospermic, fertilization rates were 56 and 30 per cent, respectively. This is in comparison to a fertilization rate of 72 per cent in normospermic couples. Following embryo transfer, pregnancy rates were similar in all groups. In vitro fertilization, although expensive and often not covered by insurance policies, may yield results in 1 month. Pharmacologic treatment of the male, which is less expensive, requires several months before improvement might be expected. The decision as to which course to recommend should be made after careful consultation with the couple. If empiric therapy is decided upon, the choice of an agent is somewhat arbitrary. Reasonable initial choices for the oligospermic patient are tamoxifen (or clomiphene citrate) or HCG (HCG may also be used in the patient with idiopathic asthenospermia). Testosterone rebound, with its risk of permanent azoospermia, is not an acceptable initial therapy. Similarly, the results of studies of testolactone, GnRH, pentoxifylline, and kallikrein either demonstrate low pregnancy rates or are too preliminary to recommend at this time. Regardless of the choice of therapy, it should be administered for at least 3 months to include the length of one spermatogenic cycle. The performance of randomized, double-blind, placebo-controlled, cross-over studies of present and future treatments will allow more definite conclusions to be drawn.

Chorionic Gonadotropin↗
PubMed1987

Prolactinomas.

Prolactin-secreting pituitary tumors are not rare. The diagnosis of a patient with hyperprolactinemia and possible tumor should be carried out in an orderly fashion by first excluding secondary causes. If the patient has pathologic hyperprolactinemia, assessment of pituitary anatomy with a high resolution CT scan (or MRI) should be done. In patients who have a macroadenoma, quantitative visual field examination should be a part of the ophthalmologic examination. The choice of therapy is dependent on the clinical findings, the risks of therapy, and patient preference. Currently, the most effective therapy for a patient with a macroadenoma is medical therapy with a dopamine agonist, but this must be given chronically. Regardless of the therapy selected, these patients must be followed regularly. Once fertility is established, there is usually no contraindication to pregnancy in women who wish to become pregnant.

Diagnosis, Differential↗
PubMed1986

The effect of intravenous, subcutaneous, and intranasal GH-RH analog, [Nle27]GHRH(1-29)-NH2, on growth hormone secretion in normal men: dose-response relationships.

A 29 amino acid analog of growth hormone releasing hormone (GH-RH)-40 was given intravenously, subcutaneously, and intranasally to normal men to determine its effectiveness in stimulating growth hormone (GH) release. The GH-RH analog, [Nle27]GH-RH(1-29)-NH2, is an amidated 29 amino acid peptide that has one amino acid substitution at position 27. This peptide stimulates GH secretion when given by the intravenous, subcutaneous, and intranasal routes without adverse effect. The degree of GH stimulation was variable among subjects and the greatest amount of stimulation occurred with the highest doses. GH stimulation occurred in a dose-responsive manner after all three routes of administration. A tenfold higher subcutaneous dose was required to stimulate a comparable amount of GH secretion as compared with intravenous administration, and a thirtyfold higher intranasal than intravenous dose was required to stimulate approximately one fifth the amount of GH release. For comparison, one dose of GH-RH-40, 1 microgram/kg, was administered intravenously. GH secretion after 1 microgram/kg GH-RH-40 and 1 microgram/kg Nle27 GH-RH was comparable between the two groups of subjects. Stimulation of GH secretion by Nle27 GH-RH occurred within 5 minutes of intravenous and within 10 minutes of subcutaneous and intranasal administration; peak GH levels were observed within 30 minutes. GH levels declined and returned to near baseline levels 2 hours after administration of the analog.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1986

Clinical studies with GHRH in man.

GHRH was isolated from two GHRH-secreting pancreatic tumors which resulted in clinical acromegaly. Over 98% of acromegalic patients have a pituitary adenoma; however, acromegaly may occasionally result from ectopic or eutopic GHRH secretion. Administration of GHRH to normal adults stimulates growth hormone (GH) secretion; it may also stimulate GH release in some adults with GH deficiency in childhood and in a majority of GH-deficient children. Continuous infusion of GHRH to normal men stimulates GH secretion which augments naturally occurring GH pulses. GHRH is effective when administered subcutaneously and intranasally, but requires 30- and 300-fold higher doses, respectively. Intermittent subcutaneous GHRH therapy promotes acceleration of linear growth in GH-deficient children and appears promising as a treatment for these children.

Acromegaly↗
PubMed1986

Dual effects of growth hormone (GH)-releasing hormone infusion in normal men: somatotroph desensitization and increase in releasable GH.

Continuous infusion of human GH-releasing hormone (GHRH) stimulates GH secretion in normal subjects, but a single supramaximal iv dose of GHRH thereafter elicits a diminished serum GH response compared to that after a saline infusion; the response to the single dose challenge is inversely related to the dose of GHRH previously infused. To determine if this attenuated GH response is a result of depletion of available GH or desensitization of the somatotroph, a 6-h infusion of saline or GHRH (10 ng/kg . min) was administered to 10 normal men, and an iv bolus dose of either GHRH (3.3 micrograms/kg) or regular insulin (0.15 U/kg) was given after 5.5 h of infusion. On both days of GHRH infusion, there was significant stimulation of GH secretion compared to that after saline infusion. The GH response to the supramaximal dose of GHRH was greater after saline infusion than after GHRH infusion, and the GH response to insulin-induced hypoglycemia was significantly greater after GHRH infusion compared with the responses on the other 3 study days. The greatest GH secretion occurred during GHRH infusion followed by insulin administration; therefore, pituitary reserve was not decreased by prior exposure to GHRH. These studies suggest that somatotrophs become partially refractory to GHRH stimulation over time, but remain responsive to an alternate stimulus of GH secretion. We suggest that the hypoglycemia-induced GH response occurs via a reduction in hypothalamic somatostatin secretion, and the attenuated GH response to the supramaximal GHRH dose after GHRH infusion probably represents either partial desensitization or down-regulation of the GHRH receptor.

Adult↗
PubMed1986

Growth hormone releasing factor and somatomedin C production: extrahypothalamic localization and possible functional significance.

Growth hormone-releasing factor (GRF) is found in the highest concentration (albeit lower compared to other hypothalamic regulatory hormones) in the hypothalamus. There is mounting evidence that GRF-like immunoreactivity is found in other sites in the CNS and in the periphery. The role of GRF, other than to stimulate growth hormone secretion by the somatotroph, is unknown. In addition generation of IGF-1 in response to GRF appears to be dependent on an intact pituitary.

Animals↗
PubMed1985

Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion.

Growth hormone (GH) secretory patterns were studied in a patient with ectopic growth hormone releasing factor (GRF) secretion and in normal men given continuous infusions of human growth hormone releasing factor (1-40)-OH (hGRF-40). In the patient with ectopic GRF secretion, GH secretion was pulsatile despite continuously elevated immunoreactive GRF levels. To determine if pulsatile GH secretion is maintained in normal subjects, we administered to six healthy young men vehicle or hGRF-40, 2 ng/kg per min, for 24 h and gave a supramaximal intravenous bolus dose of hGRF-40, 3.3 micrograms/kg, after 23.5 h of infusion. hGRF-40 infusion resulted in greater GH secretion than did vehicle infusion and pulsatile GH secretion was maintained throughout hGRF-40 infusion. During the 23.5 h of vehicle infusion, total GH secretion (microgram; mean +/- SEM) was 634 +/- 151 compared with 1,576 +/- 284 during hGRF-40 infusion (P = 0.042). The GH response to the intravenous bolus of hGRF-40 was greater after vehicle infusion than after hGRF-40 infusion; 877 +/- 170 and 386 +/- 125 micrograms of GH was secreted after the bolus on vehicle and hGRF-40 days, respectively (P = 0.015). The total amount of GH secreted during the 25.5 h of the two study days was not different; 1,504 +/- 260 and 1,952 +/- 383 micrograms were secreted during vehicle and hGRF-40 days, respectively (P = 0.36). Not only was pulsatile GH secretion maintained during hGRF-40 infusion, but there was augmentation of naturally occurring GH pulses, which is in contrast to the effect of gonadotropin-releasing hormone on gonadotropin secretion. We suggest that GH pulses are a result of GRF secretion that is associated with a diminution or withdrawal of somatostatin secretion.

Acromegaly↗
PubMed1985

Effects of growth hormone-releasing factor on growth hormone secretion in acromegaly.

Twenty-nine patients with acromegaly (8 untreated and 21 previously treated in various ways) and 16 normal men were given iv bolus doses of human pancreatic tumor GH-releasing factor (hpGRF-40). Twenty-five of the 29 patients responded to hpGRF-40 with elevations of plasma GH. The magnitude of the responses varied widely. Responses of untreated patients were generally similar to those of the normal subjects. Previously treated patients had a significantly lower response than normal individuals [change in GH, 7.5 +/- 1.8 vs. 42.0 +/- 11.0 ng/ml (mean +/- SEM); P less than 0.01], and 4 patients who had received radiation therapy failed to respond to hpGRF-40. There was no significant correlation between the magnitude of the response and patients' age, sex, baseline GH levels, GH responsiveness of TRH, or GH suppression after oral glucose administration. Patients studied both pre- and postoperatively were responsive to hpGRF-40 at all times tested, but the magnitude of the response decreased after successful surgical removal of the adenoma. Thus, most patients with treated or untreated acromegaly respond to hpGRF-40, but their responses do not clearly distinguish them from normal subjects. GH-releasing hormone testing is unlikely to replace other endocrine tests available for the diagnosis and evaluation of acromegaly.

Acromegaly↗
PubMed1985

Evidence for a limited growth hormone (GH)-releasing hormone (GHRH)-releasable quantity of GH: effects of 6-hour infusions of GHRH on GH secretion in normal man.

Human GH-releasing hormone [hGHRH-40 (GHRH)] stimulates GH release in a dose-dependent fashion when administered as single iv bolus doses or as continuous 90-min infusions. However, there has been variability in the GH responses, and it appears that there are waxing and waning effects of GHRH. To address whether these are a result of the dose of GHRH, time, or intermittent changes in sensitivity of the somatotrophs, we administered 6-h infusions of vehicle and different doses of GHRH to six normal men. In addition, an iv bolus injection of GHRH was given after 5.5 h of infusion to evaluate residual GH secretory capacity. The subjects were given infusions of either vehicle or GHRH (1, 3.3, and 10 ng/kg X min), followed by an iv bolus injection of 3.3 micrograms/kg on four separate occasions. GHRH infusions stimulated GH secretion compared to basal secretion. The changes from basal GH secretion (mean +/- SEM) were 2.0 +/- 1.6, 4.6 +/- 1.5, 12.7 +/- 5.1, and 8.2 +/- 1.8 ng/ml X h during the vehicle and GHRH (1, 3.3, and 10 ng/kg X min) infusions, respectively. The changes from basal GH secretion for 2 h after the iv bolus dose (after 5.5 h of infusion) were 33.3 +/- 8.7, 22.4 +/- 3.8, 14.0 +/- 3.6, and 10.5 +/- 2.0 ng/ml X h on the vehicle and GHRH (1, 3.3, and 10 ng/kg X min) infusion days, respectively. The magnitude of the GH response was inversely related to the GHRH infusion dose. The total amount of GH released during the 7.5-h study periods was not different among the vehicle and 3 GHRH infusion days. Thus, it appears that a finite amount of GH is released by GHRH. There was variability in the degree of responsiveness to the continuous infusions of GHRH. Surges of GH release occurred during the GHRH infusions, which may be attributed to intermittent secretion of a GH inhibitor, such a somatostatin.

Adult↗
PubMed1985

Follicle-stimulating hormone- and alpha-subunit-secreting pituitary tumor treated with bromocriptine.

Glycoprotein-secreting pituitary tumors are uncommon. With increased awareness that pituitary tumors may secrete FSH, LH, TSH, and the alpha-subunit, either as a sole product or in any combination, these tumors are more likely to be recognized. The standard therapy is surgical resection and, possibly, postoperative radiotherapy for residual tumor mass or persistent hormonal secretion. We report a patient with a FSH- and alpha-subunit-secreting tumor who refused surgery and was treated with the dopamine agonist bromocriptine as primary therapy. Bromocriptine treatment resulted in reduction of serum FSH and alpha-subunit levels to normal, improvement of visual field defects, and improvement in hypogonadism despite lack of demonstrable change in tumor size, as assessed by computed tomographic scan. Chromatographic analysis of the serum revealed distinct peaks corresponding to those of labeled FSH and alpha-subunit. The clinical and biochemical responses in this patient suggest that some glycoprotein-secreting tumors may be responsive to dopamine agonist therapy.

Adenoma↗
PubMed1985

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↗