Search PubMed⌕ Search

Biomedical subjects

G Faglia

Publications and source records attributed to G Faglia.

At least 145 records · Page 8Linked to original sources
PubMed1987

Loperamide modifies but does not block the corticotropin-releasing hormone-induced ACTH response in patients with Addison's disease.

The effect of loperamide - a peripheral opiate agonist - on plasma ACTH response to Corticotropin-releasing Hormone (CRH) has been investigated in 6 patients with Addison's disease. After placebo administration CRH induced a marked ACTH increase. After loperamide administration ACTH levels fell to a nadir of 135 +/- 76 pg/ml, and then CRH was still able to induce an ACTH increase; the pattern of ACTH response to CRH was slightly delayed. There was a significant difference between the two ACTH curves after CRH only in the early phase of the response. These data suggest that the inhibitory role of loperamide on ACTH secretion is exerted at supra-pituitary level, although a pituitary site of action can not be excluded.

Addison Disease↗
PubMed1986

Evidence for an inhibition of thyroid hormone effects during chronic treatment with amiodarone.

The effects of chronic amiodarone treatment on several thyroid and cardiac function parameters were studied in 50 euthyroid patients with refractory ventricular arrhythmias, divided in responders and nonresponders according to their sensitivity to the antiarrhythmic action of the drug. No differences in the severity of cardiac disease and blood amiodarone concentrations were found in the two groups. Amiodarone induced a significant inhibition of peripheral T4 monodeiodination, more pronounced in responders compared to nonresponders. On the contrary, only in responsive patients, elevated basal and TRH-stimulated TSH levels were observed (despite serum T3 levels were not different from those in nonresponders) and the indirect indices of cardiac performance, particularly the systolic time intervals, fell in a range usually observed in the hypothyroid states. These findings suggest that amiodarone, besides the well-known inhibition of T4 to T3 conversion, also induces a partial resistance to the thyroid hormones, which is probably involved in the therapeutical effectiveness of the drug.

Adolescent↗
PubMed1986

Loperamide, an opiate analogue, inhibits plasma ACTH levels in patients with Addison's disease.

The effects of loperamide, an opiate analogue of the piperidine class on pituitary hormone secretion were evaluated in eight patients with Addison's disease. In all patients loperamide administration (16 mg orally) induced a marked fall in plasma ACTH levels (P less than 0.01), without affecting GH, PRL and LH levels. Plasma ACTH concentration fell significantly from 854 +/- 167 pg/ml (mean +/- SEM) to 460 +/- 123 pg/ml at 60 min (P less than 0.01). The inhibition persisted throughout the whole test period, the nadir being reached at 300 min. Low dose naloxone infusion 180 min after loperamide administration caused plasma ACTH to rise from 181 +/- 61 pg/ml to 539 +/- 99 pg/ml (P less than 0.01). The present data suggest that the opiate analogue loperamide is a potent inhibitor of ACTH secretion in patients with Addison's disease, which may be acting on mu receptors, since its effect is blocked by low doses of naloxone.

Addison Disease↗
PubMed1986

Effect of thyrotropin-releasing hormone on growth hormone release in normal subjects pretreated with human pancreatic growth hormone-releasing factor 1-44 pulsatile administration.

Growth hormone (GH) increase after thyrotropin-releasing hormone (TRH) has been documented in many pathological conditions. In order to evaluate whether exposure to growth hormone-releasing factor (GRF) might contribute to this effect in normal subjects, we studied GH responses to placebo, TRH, GRF and GRF plus TRH either in basal condition or after GRF administration. Ten subjects received placebo, TRH, GRF and GRF plus TRH on four separate occasions. GRF induced a clear rise in plasma GH, statistically different from those obtained after placebo or TRH (p less than 0.01). TRH was completely ineffective in both stimulating GH release and amplifying the secretory GH response to GRF. Twenty subjects, subdivided in four groups, received 3 consecutive intravenous GRF boli at two-hour intervals. Two hours later they were given a fourth stimulus: 5 had another 25 micrograms GRF i.v., 5 had 200 micrograms TRH i.v., 5 were tested with simultaneous 25 micrograms GRF and 200 micrograms TRH i.v. injection, and 5 with 1 ml saline. GH secretory responses were quantitated by determining the net incremental area under the curve (nAUC) over 60 min after the administration of each stimulus. The pattern of GH secretion after 1-3 GRF boli was not statistically different among the four groups. Plasma GH nAUC was higher after the first GRF injection than after the following ones (p less than 0.01). The administration of a fourth GRF bolus also caused a GH increase which was significantly smaller than that after the first one (p less than 0.01), but greater than that after placebo (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Endocrine, biochemical, and morphological studies of a pituitary adenoma secreting growth hormone, thyrotropin (TSH), and alpha-subunit: evidence for secretion of TSH with increased bioactivity.

A 40-yr-old man who had acromegaly and hyperthyroidism due to a GH/TSH-secreting pituitary adenoma is described. Serum free T4 was 2.8 ng/dl, free T3 was 1.1 ng/dl, and TSH was 1.2-1.5 microU/ml; the latter was measured in an immunoradiometric assay with a sensitivity of 0.07 microU/ml. Serum TSH was immunologically identical to standard TSH and did not decrease during a T3 suppression test. Serum free alpha-subunit and the molar alpha-subunit to TSH ratio were high (6.1 ng/ml and 31.2, respectively). TRH administration induced significant increases in both GH (+129%) and alpha-subunit (+156%) levels. Conversely, dopamine infusion resulted in a decrease in serum GH (-66%) and alpha-subunit (-43%) levels, and subsequent administration of the dopamine antagonist sulpiride induced significant increases in both GH and alpha-subunit (+393% and +106%, respectively). Similarly, somatostatin infusion inhibited GH (-43%) and alpha-subunit (-61%) secretion. Serum TSH levels were not affected by TRH, dopamine, or somatostatin. The biological to immunological activity ratio of serum TSH purified by immunoaffinity chromatography and measured in an adenylate cyclase assay was significantly increased compared to that in serum from hypothyroid or euthyroid subjects [biological to immunological activity ratio, 6.9 +/- 0.2 (+/- SD) vs. 4.4 +/- 1.1; P less than 0.001]. In gel chromatography, the apparent mol wt of the patient's TSH was smaller than that of the controls. After adenomectomy, all of the altered parameters of pituitary function became normal. Double gold particle immunostaining of the adenomatous tissue showed that all of the cells contained secretory granules positive for GH and alpha-subunit, while very few cells were positive for TSH beta as well as GH and alpha-subunit. These data indicate that in this patient serum TSH had an apparent mol wt smaller than that of normal TSH and an increased biological activity which, along with the autonomous TSH secretion, account for hyperthyroidism in the presence of low normal TSH levels; alpha-subunit originated from the same adenomatous cells that secreted GH but not TSH, thus explaining the in vivo observation that alpha-subunit responses to several agents were dissociated from TSH responses and parallel to GH responses; and TSH and GH were colocalized in a minority of the neoplastic cells.

Adenoma↗
PubMed1985

Decreased receptor binding of biologically inactive thyrotropin in central hypothyroidism. Effect of treatment with thyrotropin-releasing hormone.

Previous studies have suggested that certain cases of idiopathic central hypothyroidism of hypothalamic origin may result from the secretion of biologically inactive thyrotropin. To investigate this possibility and to define the mechanism of defective hormone action, we measured the adenylate cyclase-stimulating bioactivity (B) and receptor-binding (R) activity of purified immunoreactive serum thyrotropin (I) from seven patients with hypothalamic hypothyroidism. We found a strikingly decreased R/I ratio (less than 0.15) in patients as compared with controls (0.6 to 2.7) and a similarly decreased B/I ratio (less than 0.2 vs 2.8 to 5.6). After acute injection of thyrotropin-releasing hormone (TRH, 200 micrograms intravenously), the R/I ratio increased in two of three patients, but the B/I ratio became normal in only one. After administration of TRH for 20 to 30 days, an increase in immunoreactive serum thyrotropin was observed in all patients. Moreover, both ratios returned to normal in all but one patient, who had apparent desensitization. The increase in the amount and bioactivity of secreted thyrotropin after long-term TRH therapy resulted in enhanced secretion of serum thyroid hormones in all patients studied. We conclude that in certain cases of hypothalamic hypothyroidism, secreted thyrotropin lacks biologic activity because of impaired binding to its receptor; TRH treatment can correct both defects. These data suggest that TRH regulates not only the secretion of thyrotropin but also its specific molecular and conformational features required for hormone action.

Adult↗
PubMed1985

In vitro studies on TSH secretion and adenylate cyclase activity in a human TSH-secreting pituitary adenoma. Effects of somatostatin and dopamine.

We have studied the in vitro TSH secretion and the adenylate cyclase (AC) activity of a human pituitary adenoma surgically removed from a hyperthyroid patient showing high serum TSH levels. The tumor appeared almost homogeneously constituted by cells positive for an anti-TSH-beta antiserum and showing the ultrastructural characteristics of the adenomatous thyrotrophs. Adenoma fragments released in vitro a large amount of TSH (148.4 microU/mg prot/30 min), alpha-subunit (35.5 ng/mg prot/30 min) and TSH-beta (10.1 ng/mg prot/30 min). The effects of somatostatin (GHRIH) and dopamine (DA) on the hormone release have been tested in vitro. Both agents markedly inhibited the release of intact TSH and TSH-beta whereas the release of alpha-subunit was less affected. The two agents were effective at concentrations higher than 10(-8)M. The ability of GHRIH and DA in modulating the AC activity was investigated in membrane fraction preparations. GHRIH inhibited AC at concentrations higher than 10(-7)M. The maximal inhibition was 32% at 10(-5)M. Conversely, DA slightly stimulated AC activity. This effects was not mimicked by the dopaminergic ergot CH 29-717, which was completely ineffective on the enzyme. These results suggest that: 1) in this TSH-secreting pituitary adenoma a normal secretory response to the inhibiting agents (GHRIH and DA) is present; 2) different mechanisms of transduction of the GHRIH and DA signals (cAMP dependent and cAMP independent) could be operating in this tumor.

Adenoma↗
PubMed1985

Persistence of a circadian rhythmicity of glucocorticoid secretion in a patient with Cushing's syndrome: study before and after unilateral adrenalectomy.

A 47-year-old woman affected by Cushing's syndrome due to an adrenal adenoma is described. An altered but rhythmometrically apparent cortisol secretory rhythm was detected using the single-cosinor computation. In fact serum cortisol levels and urinary excretion of 17-OHCS were elevated in the PM hours, particularly between 14:00-18.00 h and 18:00-22:00 h, and normal between 02:00-10:00 h. The patient was cured by unilateral adrenalectomy and one year later the circadian rhythm of corticosteroids secretion was investigated again. A normal rhythm of cortisol secretion and of 17-OHCS urinary excretion was found. Though it may be hypothesized that factors intrinsic to the tumoral adrenal cells were responsible for the rhythmic, but phase-shifted, hormonal release, the cause of the persistent and abnormal cortisol secretory rhythm is unknown.

17-Hydroxycorticosteroids↗
PubMed1985

Human pancreatic growth hormone-releasing factor (hpGRF-44) in acromegaly before and after adenomectomy. Modifications induced by somatostatin (GHRIH) infusion.

The influence of human pancreatic growth hormone-releasing factor (hpGRF-44) on GH secretion was investigated in 15 patients with active acromegaly. Following the administration of hpGRF-44 (1 microgram/kg, iv) mean (+/- SE) serum GH level increased from 22.4 +/- 6.3 ng/ml to 42.9 +/- 8.2. ng/ml (peak, p less than 0.01). The pattern and the magnitude of the GH rises were widely variable and it was possible to identify three types of responses: in fact in 2 cases a very large serum GH rise, eight folds over baseline, was observed, in 7 patients a clear GH stimulation, two-three fold over baseline was noticed and in 6 patients no significant GH modifications were seen. No correlation was found between the response to hpGRF-44 and the existence of abnormal GH responses to dopamine infusion, TRH and dopamine-sulpiride test. In 5 acromegalic patients hpGRF-44 was injected again after transsphenoidal adenomectomy. The magnitude of serum GH response decreased in one hyperresponsive patient, increased in 2 previously unresponsive cases and did not change in the remaining cases. In 6 GH responsive patients hpGRF-44 was injected at 120 min during a 4 hour infusion of somatostatin (GHRIH, 3.33 micrograms/min). GHRIH infusion significantly suppressed GH levels in all the patients and blunted the hpGRF-44 stimulated GH increase. The different patterns of GH response to hpGRF-44 in acromegalic patients suggest a different sensitivity of the adenomatous somatotrophs and a possible contribution by normal GH-secreting cells to hpGRF-44 induced GH response.

Acromegaly↗
PubMed1985

Bromocriptine treatment of microprolactinomas: evidence of stable prolactin decrease after drug withdrawal.

Thirty-six women with PRL-secreting pituitary microadenomas [mean PRL, 114 +/- 12.5 (+/- SE) ng/ml] were treated with bromocriptine (BRC; 2.5-10 mg/day) for 12 months. During BRC treatment, serum PRL decreased in all patients. After termination of treatment, mean serum PRL levels, evaluated at 15, 30, and 45 days, were significantly decreased (-41.6%, -43.0%, and -40.2%, respectively) compared to pretreatment values. The patients were arbitrarily divided into 3 groups: 12 responders, in whom the PRL persistent posttreatment decrease was greater than 50%, 8 hyporesponders, in whom the PRL decrease was between 30% and 50%, and 16 nonresponders with absent or negligible PRL decrease. Four patients had normal PRL levels and clinical remission for 14-30 months after BRC withdrawal. In 18 women, BRC treatment was repeated for another 12 months. After termination of treatment, 11 patients were responders, 1 was a hyporesponder, and 6 were nonresponders. Four of these 18 patients still had normal PRL levels 8-28 months after drug discontinuation. The responses of PRL to TRH and domperidone were compared before and after termination of treatment at 30 and 45 days, respectively. Both mean peak values of PRL and absolute increases after TRH treatment were similar before and after BRC administration; however, a PRL response to TRH was present in 15% of 26 patients before treatment and in 42% after treatment. The mean peak values after domperidone were similar before and after BRC treatment, but the absolute increase over the basal value was much higher after BRC; PRL response to domperidone was present in 16% of 19 patients before BRC treatment and in 74% after BRC. These data suggest that BRC is effective in the treatment of some microprolactinomas; BRC effectiveness improves after prolonged periods of administration. The variations in PRL responses to TRH and domperidone suggest profound modification of PRL secretion after BRC treatment.

Adenoma↗
PubMed1985

Glycoprotein hormone alpha-subunit response to growth hormone (GH)-releasing hormone in patients with active acromegaly. Evidence for alpha-subunit and GH coexistence in the same tumoral cell.

Basal serum concentrations of glycoprotein hormone alpha-subunit and its response to GH-releasing hormone (GHRH) were studied in 22 acromegalic patients and in normal subjects. Four out of 22 patients had a basal alpha-subunit concentration (1.2-3.5 ng/ml) clearly above the upper limit of the normal range. GHRH injection (1 microgram/kg body weight, bolus dose iv) produced a clear alpha-subunit response [mean % increase: 120 +/- 37 (SD)] in the 4 patients with elevated basal alpha-subunit levels. No increase in serum glycoprotein hormones (TSH, LH, and FSH) occurred. Selective adenomectomy in 2 patients resulted in normalization of both serum GH and alpha-subunit levels, as well as disappearance of the abnormal alpha-subunit response to GHRH. In in vitro studies, only these 2 adenomas secreted alpha-subunit in large amounts (534 and 388 ng/mg protein . 30 min) and was it further stimulated by GHRH (% increase: 83 and 126). Morphological studies done with protein A-gold particle immunotechnique demonstrated that in these adenomas the great majority of the cells contained secretory granules positive for both GH and alpha-subunit. We conclude that: 1) alpha-subunit hypersecretion is present in some acromegalic patients (about 20%), 2) GHRH stimulates alpha-subunit release both in vivo and in vitro only in patients with elevated basal alpha-subunit levels, and 3) in these patients alpha-subunit derives from a common adenomatous cell secreting both alpha-subunit and GH molecules.

Acromegaly↗
PubMed1985

Serum gonadotrophin pulsatile secretion in men with Prl-secreting and non-secreting pituitary tumours.

In order to investigate the possible influence of prolactin (Prl) at the hypothalamic level, serum LH and FSH pulsatility was studied in 16 male patients with prolactinomas, normally LH responders to GnRH (group A): 8 of them were untreated (group A1) and 8 had undergone previous unsuccessful pituitary treatments (group A2). In 7 patients the study was repeated when serum Prl was normalized by bromocriptine treatment (group B). For comparison the secretory pattern of LH and FSH was studied in 6 male patients with non-secreting pituitary tumours (group C). All parameters of LH pulsatile secretion (i.e. arithmetic mean of the single concentration, coefficient of variation from the mean value, frequency of peaks, amplitude of pulses expressed as either absolute or per cent value) were significantly lower in patients of groups A1, A2 and C than in normal subjects and no difference was found between the three groups. Furthermore the 7 patients with prolactinomas studied both before and after bromocriptine-induced Prl normalization showed no difference in all the parameters of LH pulsatility in both conditions. No significant abnormalities of FSH secretory pattern were found in the patients of groups A1, A2, B and C in comparison to normal subjects. In all groups of patients mean serum testosterone basal levels were significantly lower than in normals, while the mean oestradiol-17 beta basal concentration was normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1984

Evaluation of free thyroxine methods in the presence of iodothyronine-binding autoantibodies.

Circulating iodothyronine-binding autoantibodies interfere with total T4 and T3 RIAs, giving falsely high or falsely low values depending on the assay separation method used. Direct serum free T4 (FT4) measurement should compensate for such abnormal binding if the method is free of artefact. We assessed 5 different FT4 methods in 12 patients with immunoglobulin binding of iodothyronines, with limited assessment of a sixth method in 2 subjects. Thyroid status was assessed clinically and by measurement of TSH and its response to TRH. T4 methods which use analog tracers, i.e. Amerlex, and Clinical Assays One-step FT4, gave spuriously high values in almost all hypothyroid and some euthyroid patients, due to immunoglobulin binding of the tracers used in these techniques. The kinetic indirect method (Corning Immunophase FT4) gave inappropriately high values in 4 of 6 hypothyroid patients. FT4 by equilibrium dialysis or by adsorption chromatography and RIA, accurately assessed thyroid status. These findings suggest that FT4 methods are valid in patients with circulating iodothyronine-binding immunoglobulins only if the free hormone fraction is physically separated from serum binding proteins before the assay procedure.

Adult↗
PubMed1983

Effects of sodium-valproate administration on plasma ACTH levels in patients with ACTH hypersecretion.

The effects of the acute administration of sodium-valproate (400 mg po) on plasma ACTH levels were studied in 4 patients with Cushing's disease, 1 with Nelson's syndrome and in 3 with Addison's disease. No significant reduction of corticotropin concentration was observed, as compared to saline infusion. These data do not favor the hypothesis of an inhibitory role of sodium-valproate on ACTH secretion in such patients.

Addison Disease↗
PubMed1983

Circulating antitriiodothyronine autoantibodies in two euthyroid patients: apparent lack of interference in total T3 radioimmunoassay based on second antibody or solid phase separation techniques.

Two clinically euthyroid patients were noted to have low total T3 levels as assessed by RIA using either dextran-charcoal (DC) or polyethylene glycol (PEG) for separation of bound from unbound T3, in spite of normal free T3, total and free T4 and basal and TRH-stimulated TSH concentrations. The presence of circulating substances binding T3 was suggested by high nonspecific binding in total T3 RIA system using either DC or PEG separation. The presence of anti-T3 autoantibodies was then suspected and confirmed by the presence of [125]-T3 bound to patients' gammaglobulins, precipitated with rabbit anti-human immunoglobulins. Serum T3 concentration determined by extracting T3 from patients' sera with methanol was 166 and 226 ng/dl. Similar or even lower values were unexpectedly obtained in RIA systems with solid phase or second antibody (anti-rabbit) separation and with competitive protein binding assay. To face this paradoxical finding, simulated experiments were carried out by incubating T3- and T4-free sera added with various amounts of stable T3 and T4 in the presence of goat anti-T3 or anti-T4 serum. These samples were then radioimmunoassayed. The DC separation caused a consistent underestimation of the actual T3 and T4 concentration. The second antibody separation caused a T3 and T4 overestimation for actual levels below 200 ng/dl and 10 micrograms/dl, respectively, while at the higher T3 or T4 concentrations, an overlap or, even, an underestimation of actual T3 or T4 levels were found. These data provide evidence that, with second antibody or solid phase separation methods, there could be an apparent lack of interfering effect of endogenously occurring antibodies.

Adult↗