Biomedical subjects

M G Magotti

Publications and source records attributed to M G Magotti.

11 recordsLinked to original sources

PubMed2003

Serum total prostate-specific antigen assay in women with Cushing's disease or alcohol-dependent pseudo-Cushing's State.

BACKGROUND: The distinction between Cushing's disease (Cushing's syndrome dependent on adrenocorticotropic hormone (ACTH)-secreting tumors of pituitary origin) and pseudo-Cushing's states (Cushingoid features and hypercortisolism sometimes present in alcoholic, depressed or obese subjects) can present a diagnostic challenge in clinical endocrinology. Recently, the availability of a highly sensitive immunofluorometric assay for the measurement of total prostate-specific antigen (PSA) provided the possibility to measure serum PSA levels in women. Interestingly, PSA gene expression and protein production has been found to be upregulated by steroid hormones, such as androgens, glucocorticoids, mineral corticoids and progestins. In fact, serum total PSA concentrations appear to be higher in female patients with Cushing's disease than in normal women. We wondered whether a similar phenomenon also occurs in pseudo-Cushing's state. METHODS: In order to answer this question, we compared the serum total PSA levels measured in 10 female subjects with alcohol-dependent pseudo-Cushing's state with those observed in 8 female patients with Cushing's disease and in 15 age-matched healthy women. Serum testosterone, ACTH and cortisol, and 24-hour urinary cortisol levels were measured; cortisol suppression after dexamethasone was also tested in all subjects. RESULTS: The basal serum levels of ACTH and cortisol were significantly lower in normal subjects than in patients with Cushing's disease or pseudo-Cushing's state; these latter groups showed similar basal hormonal values. Dexamethasone administration was unable to suppress serum cortisol levels in 5 subjects with Cushing's disease and 6 subjects with pseudo-Cushing's state. Serum testosterone values in the group with Cushing's disease were higher than in the other groups. No differences were observed between pseudo-Cushing's and normal subjects. Serum total PSA levels were significantly higher in women with Cushing's disease than in subjects with pseudo-Cushing's state and normal controls; these latter groups showed similar PSA values. When serum total PSA and testosterone levels were considered together, a significant positive correlation was observed in the group with Cushing's disease, but not in the other groups. CONCLUSIONS: These data indicate that the steroid milieu responsible for the elevation in serum PSA in women with Cushing's disease is not present in subjects with alcohol-dependent pseudo-Cushing's state, suggesting the possible use of PSA as a marker of differentiation between these pathological conditions in women.

Adult↗

PubMed2003

Effect of oxytocin on nitric oxide activity controlling gonadotropin secretion in humans.

BACKGROUND: Previously described inhibitory effects of the nitric oxide synthase (NOS) inhibitor L-NAME on luteinizing hormone-releasing hormone (LH-RH)-induced LH and follicle stimulating hormone (FSH) secretion in humans suggested modulation by nitric oxide (NO) of the gonadotropin-releasing action of LH-RH. DESIGN: In order to establish whether oxytocin (OT) participates in this regulatory mechanism, 10 normal men were treated with LH-RH (100 micro g as an i.v. bolus) given alone or in the presence of L-NAME (40 micro g kg-1 injected plus 50 micro g kg-1 infused i.v. for 60 min), OT (2 IU injected plus 4 IU infused i.v. for 60 min) or a combination of both drugs. RESULTS: The administration of OT was unable to change the gonadotropin responses to LH-RH. In contrast, L-NAME significantly reduced both FSH and LH increments induced by LH-RH. When L-NAME was given in the presence of OT, the LH and FSH responses to LH-RH were similar to those observed after the administration of LH-RH alone. CONCLUSION: These data suggest antagonistic actions of OT and L-NAME in the control of NOS activity in regulation of gonadotropin secretion induced by LH-RH.

Adult↗

PubMed1999

Are thyroid function tests too frequently and inappropriately requested?

In spite of data supporting the use of the serum thyrotropin (TSH) concentration as the best test to detect abnormal thyroid function, measurement of circulating thyroid hormones with or without a serum TSH continues to be frequently requested to evaluate thyroid function. We have analyzed how combinations of thyroid function tests were ordered by referring physicians and the results of the tests in order to offer some suggestions as to how to use thyroid function tests in a cost effective manner. During 1995, 19,181 inpatient and outpatient requests (45,865 different tests) for thyroid function tests were received by the laboratory of a 1600 bed University Hospital in Parma, Italy. The following tests were carried out: T4, free T4, T3, free T3 and TSH. Serum TSH values below and above the normal range were considered to reflect abnormal thyroid function i.e. hyperthyroidism, or hypothyroidism including subclinical disease independent of the results of the other tests. Combinations of ordered tests and the percent of the total for each combination were: TSH+T4+T3 (56%), TSH+FT4+FT3 (14%), TSH (12%), TSH+FT4 (9%), TSH+T4 (1%), TSH+T4+T3+FT4+FT3 (5%), others (3%). The T4+T3+TSH panel (10,780 requests) had normal serum TSH values in 80.6% and the FT4+ FT3+TSH panel (2,590 requests) had normal TSH values in 73.2%. Elevated serum TSH concentrations were observed more frequently in hospitalized than in ambulatory patients (9.7% vs 7.4% p<0.001). T3 (elevated serum T3, normal T4 and low TSH concentrations) and T4 (elevated serum T4, normal T3 and low TSH concentrations) toxicosis were observed in 8.1% and 9.4%, respectively, of the requested test (NS). FT3 and FT4 toxicosis, defined as for T3 and T4 toxicosis, were observed in 7.5% and 4.9%, respectively (NS). The low T3 and low FT3 syndrome in hospitalized patients was present in 1.6% and 2.3% of the requests, respectively (NS). The low T4+low T3 and low FT4+low FT3 syndrome was present in only 0.3% and 0.2%, respectively, of the requests. Our study shows that a) in hospitalized patients thyroid function tests were requested in 20% of the patients and only one in 14 of these patients at the highest could have abnormal thyroid function, as indicated by abnormal TSH value b) FT4 (or T4) is as useful as FT3 (or T3) in the diagnosis of hyperthyroidism, c) in hospitalized patients the low T3 syndrome was far less common than that reported in the literature, probably due to the lower severity of illness, d) panels which include T3 and FT3 are not justified, and e) serum TSH alone is the most appropriate initial thyroid function test.

Cost-Benefit Analysis↗

PubMed1999

Recombinant interferon alpha (rIFN-alpha) does not potentiate the effect of iodine excess on the development of thyroid abnormalities in patients with HCV chronic active hepatitis.

OBJECTIVE: To determine whether the administration of pharmacological quantities of iodine during interferon-alpha (rIFN-alpha) treatment of chronic viral hepatitis B and C (HCV) would exacerbate the potential adverse effects of rIFN alpha on thyroid function. DESIGN: Thyroid function tests were carried out in 48 euthyroid patients before and during rIFN-alpha therapy of HCV. Twenty-one of these patients were also treated with 10 drops saturated solution of potassium iodine (SSKI, approximately 350 mg iodine daily). Eight patients with HCV but not treated with rIFN-alpha received 10 drops SSKI. PATIENTS: All patients were enthyroid prior to rIFN-alpha therapy for HCV or iodine and thyroid function tests were similar in the three groups. MEASUREMENTS: Serum free T4, free T3, and TSH concentrations were measured prior to and at 30 and 60 days of rIFN-alpha therapy in the three groups of patients. The serum TSH response to TRH was assessed before rIFN-alpha therapy and on day 60. Thyroid peroxidase antibodies were measured before and during therapy. RESULTS: During the 2-month study period, similar small but significant decreases in serum FT4 and FT3 and compensatory small significant increases in TSH concentrations were observed in the patients treated with rIFN-alpha + iodine and iodine alone but not in the patients receiving rIFN-alpha alone. Abnormal thyroid function tests were observed more frequently in patients receiving rIFN-alpha + iodine and iodine alone compared to those receiving rIFN-alpha alone. CONCLUSIONS: Excess iodine administered to patients treated with rIFN-alpha induced small changes in thyroid function similar to those observed in patients treated with iodine alone. Thus, rIFN-alpha and iodine do not appear to be synergistic in the development of abnormal thyroid function tests over a 2-month treatment period.

Adult↗

PubMed1998

5-HT3 serotonergic receptor mediation of hypoglycemia-induced arginine-vasopressin but not oxytocin secretion in normal men.

The present study was undertaken in order to establish the possible involvement of 5-HT3 serotonergic receptors in the control of basal and/or hypoglycemia-stimulated arginine vasopressin (AVP) and/or oxytocin (OT) secretion. For this purpose, 12 normal men were injected intravenously with a bolus of 4 mg ondansetron, a specific 5-HT3 receptor antagonist, under basal conditions (n = 6) or 30 min before insulin (0.15 IU/kg body weight) administration (n = 6) (insulin tolerance test (ITT)). Control experiments with normal saline instead of ondansetron treatment were performed. Furthermore, on a different occasion, the same subjects were tested in identical experimental conditions with 8 mg ondansetron. Our results showed that the hypoglycemic response to insulin was similar during the ITT and ondansetron plus ITT. Inhibition of 5-HT3 serotonergic receptors with ondansetron (4 or 8 mg) did not modify the basal secretion of AVP and OT and the OT response to insulin-induced hypoglycemia. In contrast, the administration of 4 or 8 mg ondansetron significantly reduced in a similar manner hypoglycemia-induced AVP rise. Mean peak level at 45 min after insulin injection was 2.25 times higher than baseline in the control ITT and 1.5 times higher than basal value in the ondansetron (4 or 8 mg) plus ITT. These data demonstrate that 5-HT3 serotonergic receptors at least partially mediate the AVP response to hypoglycemia, without modifying the simultaneous OT response. On the other hand, 5-HT3 receptors do not appear to be involved in the control of basal posterior pituitary hormone secretions.

Adult↗

PubMed1998

Arginine vasopressin and oxytocin responses to angiotensin II are mediated by AT1 receptor subtype in normal men.

This study was performed to determine whether the stimulatory effect of plasma angiotensin II (ANG II) on arginine vasopressin (AVP) and oxytocin (OT) secretion in humans is mediated by AT1 subtype receptors. For this purpose, the effects of the AT1 receptor antagonist losartan (50 mg orally) or a placebo on the AVP and OT responses to ANG II (intravenous infusion for 60 minutes of successively increasing doses of 4, 8, and 16 ng/kg min; each dose for 20 minutes) administration were evaluated in seven normal men. In additional experiments, the same subjects were tested with losartan (50 mg orally) alone or placebo alone. Neither losartan nor placebo given alone modified the basal levels of AVP and OT. ANG II infusion induced significant increments in both serum AVP and OT levels (mean peaks were 1.55 and 1.41 times higher than baseline, respectively). Both hormonal responses to ANG II were completely abolished by pretreatment with losartan. These data provide evidence of AT1 receptor involvement in mediation of the ANG II-stimulating effect on AVP and OT secretion.

Adult↗

PubMed1997

Age-related decrease in the opioid control of LH secretion during reproductive years in normal women.

UNLABELLED: Our previous studies showed that naloxone is unable to stimulate LH secretion in elderly men, suggesting a loss in the endogenous opioid inhibitory control of LH in senescence. METHODS: In the present study, we examined whether increasing age during the reproductive period in women is associated with alterations in the LH-releasing effect of naloxone. Studies were performed in younger (age 20-28 years, n = 8) and older (age 40-48 years, n = 8) subjects with normal menstrual cycles and normal gonadal steroid levels to avoid the interference of premenopause or menopause on gonadotropin secretion. The LH response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 h) was tested not only in normal conditions, but also after chronic dopaminergic stimulation with bromocriptine (5 mg/day for 7 days), because this treatment has been found able to restore normal LH responses to naloxone in elderly men. All tests were performed on the 22nd day of normal menstrual cycles. RESULTS: Naloxone induced a 100% increase in plasma LH levels in the younger group. In contrast, naloxone enhanced only by 50% LH secretion in the older subjects. When experiments were repeated after bromocriptine treatment, the effect of naloxone did not change in the younger subjects, whereas it was significantly higher in the older group. In the presence of bromocriptine, naloxone-induced LH increment in the older group was indistinguishable from that observed in the younger group. These data suggest that during the reproductive period, increasing age is associated with an impairment in the endogenous opioid control of LH secretion. In addition, age-related dopaminergic alterations independent of circulating gonadal steroid levels appear to underlie the defective endogenous opioid control of LH secretion in normally cycling women.

Adult↗

PubMed1996

Different effects of the serotonergic agonists buspirone and sumatriptan on the posterior pituitary hormonal responses to hypoglycemia in humans.

The responses of serum oxytocin (OT) and vasopressin (AVP) to the serotonergic HT1A agonist buspirone (15 mg p.o.) or the HTD1 agonist sumatriptan (6 mg injected subcutaneously) were evaluated in 7 normal men either in basal conditions or during an insulin (0.15 iu/kg as an i.v. bolus) tolerance test (ITT). Neither buspirone nor sumatriptan administration modified the basal secretion of AVP and OT. Stimulation of 5HT-1D receptors with sumatriptan was unable to change neither AVP nor OT response to insulin-induced hypoglycemia. On the other hand, the pretreatment with the 5HT1A agonist buspirone significantly enhanced the OT response during hypoglycemia, without modifying the AVP rise. The results of this study suggest that serotonergic 5HT1A receptors may interact with hypoglycemia in the stimulation of OT, but not AVP secretion.

Adult↗

PubMed1996

Effects of intravenously infused pituitary adenylate cyclase-activating polypeptide on adenohypophyseal Hormone secretion in normal men.

The possible stimulatory effects of an intravenous infusion of increasing amounts of pituitary adenylate cyclase-activating polypeptide (PACAP) on anterior pituitary hormone secretions were evaluated in humans. Successively increasing doses of PACAP-38 (2, 4 and 8 pmol.kg-1.min-1; each dose for 20 min) were infused i.v. in 7 normal male subjects. On a different occasion, the same subjects were tested with vasoactive intestinal peptide (VIP; 4 pmol.kg-1.min-1 for 60 min). Circulating GH, ACTH, PRL, TSH and gonadotropin concentrations were measured before PACAP infusion and every 20 min, just before increasing the infusion dose of PACAP. Blood samples were taken before and every 15 min after the beginning of VIP administration. Serum levels of GH, TSH and gonadotropins did not change during PACAP or VIP infusion. Circulating ACTH and PRL concentrations were not modified by the infusion of the lowest dose of PACAP, whereas they were significantly increased in a dose-response fashion when higher amounts of PACAP were given. PRL, but not ACTH levels were significantly increased by VIP infusion. These data show for the first time in humans that ACTH and PRL secretions from the anterior pituitary gland are stimulated by the systemic administration of PACAP. In addition, since VIP stimulated only PRL secretion, PACAP-induced ACTH release appears to be mediated by specific receptors.

Adult↗

PubMed1996

Inhibition by somatostatin of the growth hormone, but not corticotropin response to angiotensin II in normal men.

The effect of an i.v. infusion of somatostatin (SRIH) (4.1 micrograms/min/180 min) on angiotensin II (ANG II infusion for 60 min of successively increasing doses of 4, 8 and 16 ng/kg/min; each dose for 20 min)-stimulated growth hormone (GH) and corticotropin (ACTH) release was studied in 7 normal men. In addition, 7 additional normal subjects were tested with ANG II alone (as described above), GH-RH (0.1 microgram/kg body weight as an i.v. bolus) alone or the combination of GH-RH and ANG II. The ACTH response to ANG II was not modified by SRIH infusion; in contrast, the GH response to ANG II was significantly reduced by the concomitant treatment with SRIH. On the other hand, the administration of GH-RH together with ANG II produced peak GH levels comparable to the sum of the individual responses to ANG II and GH-RH, given alone. These findings provide evidence that the stimulatory effect of ANG II on GH, but not ACTH secretion, is under the inhibitory control of somatostatin, suggesting an interaction between ANG II and SRIH in regulation of GH secretion.

Adrenocorticotropic Hormone↗

PubMed1995

Mediation by nitric oxide of LH-RH-stimulated gonadotropin secretions in human subjects.

In order to establish whether nitric-oxide (NO) participates in the regulation of gonadotropin secretion in humans, seven normal men were treated with a placebo (normal saline) or the NO synthase inhibitor L-NAME, given at doses (40 micrograms/kg injected plus 50 micrograms/kg infused i.v.) previously found to be unable to change blood pressure. Experiments were carried out either in basal conditions or during stimulation of gonadotropin secretion with an intravenous injection of 100 micrograms LH-RH. The administration of L-NAME was unable to change the basal secretion of FSH and LH. In contrast, L-NAME significantly reduced both FSH and LH increments induced by LH-RH. These data fail to provide evidence of NO involvement in regulation of basal gonadotropin secretion. In contrast, the inhibitory effect of L-NAME on LH-RH-induced LH and FSH secretion suggests the modulation by NO of the gonadotropin releasing action of LH-RH.

Adult↗