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Biomedical subjects

G Faglia

Publications and source records attributed to G Faglia.

At least 163 records · Page 9Linked to original sources
PubMed1983

Excess of beta-subunit of thyrotropin (TSH) in patients with idiopathic central hypothyroidism due to the secretion of TSH with reduced biological activity.

alpha-Subunit and beta-subunit of TSH were measured in the sera of five patients with idiopathic central hypothyroidism due to the secretion of biologically inactive TSH, in seven normal controls matched for bone age and sex, and in five subjects with mild primary thyroid failure before and after TRH (200 micrograms, iv) stimulation. Basal serum alpha-subunit concentration in patients did not differ from that in normal controls (mean +/- SD, 0.40 +/- 0.20 vs. 0.38 +/- 0.28 ng/ml; P, NS), whereas TSH and TSH-beta were significantly higher in patients (TSH, 1.51 +/- 0.74 vs. 0.59 +/- 0.53 ng/ml, P less than 0.025; TSH-beta, 0.56 +/- 0.18 vs. 0.10 +/- 0.02 ng/ml, P less than 0.001). The concentration of TSH-beta was also significantly higher in patients with central hypothyroidism than in subjects with mild primary thyroid failure (0.56 +/- 0.18 vs. 0.24 +/- 0.08 ng/ml; P less than 0.01), although serum TSH levels did not differ in the two groups (1.51 +/- 0.74 vs. 2.16 +/- 0.52 ng/ml; P, NS). alpha-Subunit was significantly higher in primary hypothyroid subjects (1.50 +/- 0.87, P less than 0.05 compared with patients with central hypothyroidism). After TRH, alpha-subunit, TSH, and TSH-beta net increases (peak) were significantly higher in patients with central hypothyroidism than in normal controls (alpha-subunit: 0.95 +/- 0.5 vs. 0.47 +/- 0.19 ng/ml, P less than 0.05; TSH: 7.1 +/- 3.1 vs. 2.9 +/- 1.8 ng/ml, P less than 0.005; TSH-beta: 0.89 +/- 0.35 vs. 0.22 +/- 0.18 ng/ml, P less than 0.005), whereas they did not significantly differ from those recorded in hypothyroid controls. The beta/alpha ratio, which was 1.67 +/- 0.86 in patients and 0.35 +/- 0.18 in normal controls (P less than 0.005), slightly decreased after TRH to 1.24 +/- 0.78 in patients, but remained unchanged in normal controls (0.39 +/- 0.1). After TRH the alpha-subunit peak occurred at 20 min both in patients and in controls, whereas TSH and TSH-beta peaked at 60 min in patients and at 20 min in controls. One patient was given oral TRH (40 mg/day for 4 weeks). The beta/alpha ratio fell from 1.85 to 0.13. Interestingly, serum thyroid hormones, which did not increase after iv TRH and after the first doses of oral TRH, showed a definite increase. Sera from two patients were filtered on Sephadex G-100: in one of them TSH-beta eluted in the same position as labeled reference standard, whereas in the other one radioimmunoassayable TSH-beta eluted near the void volume. The above data indicate that in patients with idiopathic central hypothyroidism due to biologically inactive TSH there is an excess of circulating TSH-beta and suggest that TRH is implicated in the secretion of TSH of full biological potency.

Adult↗
PubMed1983

Clinical use of pre- and postsurgical evaluation of abnormal GH responses in acromegaly.

The criteria by which acromegalic patients are considered "cured" after surgical therapy are still controversial. Since the abnormal growth hormone (GH) increase after the administration of some agents has been demonstrated to be characteristic of the tumoral somatotrophs, its disappearance after surgery may be taken as an index of the complete removal of the tumor. Serum GH increases after thyrotropin-releasing hormone (TRH, 200 micrograms intravenously), gonadotropin-releasing hormone (Gn-RH, 100 micrograms intravenously), and sulpiride (100 mg intramuscularly) injected during dopamine infusion (DA-Slp test), were evaluated in 68 acromegalic patients before and after transnasosphenoidal adenomectomy, and every 12 to 18 months during a follow-up period of 6 months to 11 years (average 42 months). Forty-two patients had abnormal responses to at least one test before surgery: 32 out of 68 (47%) to TRH, six out of 40 (15%) to Gn-RH, and 20 out of 28 (71%) to the DA-Slp test. Of 18 patients who underwent all three tests, 78% had abnormal responses to at least one of them. Twenty-three patients became unresponsive after surgery, and none of them had a recurrence or became abnormally responsive again during the follow-up period. Three out of six patients with postoperative serum GH levels between 5.1 and 10 ng/ml and three out of six patients with postoperative serum GH levels between 2.1 and 5 ng/ml remained abnormally responsive: one of them relapsed 1 year after the operation. The abnormal responses were lost in all 11 patients whose postoperative serum GH levels were below 2 ng/ml, and abnormal responses were maintained in all the patients in whom surgery was considered unsuccessful because postoperative serum GH levels were higher than 10 ng/ml. The TRH, Gn-RH, and DA-Slp tests should thus be considered useful tools in verifying the total removal of an adenoma. The reappearance of active acromegaly in the patient with low postoperative GH levels, who was still responsive to TRH, should be regarded as a reactivation and not a true recurrence of the disease.

Acromegaly↗
PubMed1982

Pituitary function before and after transsphenoidal adenomectomy in patients with Cushing's disease.

Over the past 4 years 11 patients with Cushing's disease have been operated on by a transsphenoidal microsurgical technique. All patients had small intrahypophyseal adenomas found at operation. Eight of the 11 patients had a remission of the disease on the basis of clinical evaluation and hormonal studies. The endocrinological results revealed a transient state of hypocorticism in all successfully treated patients. Within 6-8 months after operation recovery of hypothalamic-pituitary-adrenal function and other tropin function took place. These findings, together with the absence of recurrence up to now, further confirm the efficacy of transsphenoidal surgery in the management of patients with Cushing's disease.

Adolescent↗
PubMed1982

Metergoline in the management of hyperprolactinemic amenorrhea and anovulation.

84 patients with elevated serum PRL levels, ranging from 25 to 253 ng/ml, were treated with an antiserotonin agent, metergoline, at the dose of 12 mg/day for 90 days. The clinical complaint was of amenorrhea in 70 cases (plus galactorrhea in 44 cases) and of anovulation in 14 cases (plus galactorrhea in 6 cases). Hyperprolactinemia was due to a pituitary adenoma in 18 cases; in 53 cases it was of unknown origin, while in 7 cases it followed treatment with neuroleptics or with oral contraceptives and in 6 cases it followed a puerperium. In patients with amenorrhea, metergoline induced the appearance of menses in 61 cases (94%), and of ovulation in 46 cases (82%). In 13 of the 14 patients with anovulation, ovulation was restored. Galactorrhea disappeared in 40 out of 50 patients. Metergoline normalized serum PRL levels (less than 20 ng/ml) in 46 cases and significantly reduced serum PRL levels in all but 3 of the remaining patients. In spite of suggested nonhormonal contraceptive measures, 14 patients became pregnant; 2 had abortions and the remaining 12 patients completed by vaginal delivery, uneventful pregnancies. These results indicate metergoline as a safe and effective drug in the management of hyperprolactinemic amenorrhea and anovulation. 49 patients were followed for 2 additional months, receiving no treatment (24 cases) or metergoline at a reduced daily dosage (8 mg/day, 25 cases). Within 60 days, 60% of the first group had relapse of the clinical condition and a rebound elevation of serum PRL levels while only 20% of the second group experienced relapse of amenorrhea and rebound elevation of serum PRL levels (p less than 0.01).

Amenorrhea↗
PubMed1982

Effect of bromocriptine and metergoline in the treatment of hyperprolactinaemic states.

The effects of bromocriptine or metergoline treatment were evaluated in 80 hyperprolactinaemic patients (62 women and 18 men). The patients were subdivided into 4 groups: group A) 16 women with idiopathic hyperprolactinaemia; group B) 19 women with untreated Prl-secreting microadenomas; group C) 27 women with unsuccessfully operated prolactinomas; group D) 18 men with unsuccessfully treated macroprolactinomas. Sixty-eight patients were given bromocriptine (2.5-20 mg/day) for 3-58 months and 33 patients were given metergoline (4-16 mg/day) for 3-19 months. Bromocriptine and metergoline were equally effective in the treatment of functional hyperprolactinaemia and of untreated microadenomas, while bromocriptine showed a more potent Prl-lowering effect than metergoline in patients with higher Prl levels and large prolactinomas; both drugs restored the gonadal function to a similar extent, though metergoline was effective in some cases, even in the absence of full Prl suppression. Bromocriptine seems to exert an antitumoral effect, as documented by CT scan in some patients with macroadenomas, but the precise role of both drugs with respect to dose, length of treatment and effectiveness after withdrawal needs to be evaluated further.

Adenoma↗
PubMed1981

Mineralocorticoid hypertension due to a nasal spray containing 9 alpha-fluoroprednisolone.

The finding of hypokalemia and of low plasma renin activity (PRA) in a hypertensive patient suggests a diagnosis of primary hypermineralocorticoidism. Medications containing compounds with mineralocorticoid-like activity (licorice, carbenexolone) may also cause the same syndrome. Recently, we carried out detailed studies on 10 patients with severe hypertension and hypokalemic alkalosis, suppressed PRA and low aldosterone levels. Plasma levels of cortisol and ACTH were suppressed in most of the cases. Measurement of deoxycorticosterone and corticosterone (and in some patient of 18-hydroxydeoxycorticosterone and 18-hydroxycorticosterone) was not significantly higher than normal. Therapeutic trials of dexamethasone and aminoglutethimide were ineffective. In contrast, spironolactone and amiloride treatment resulted in substantial but incomplete amelioration of both hypertension and hypokalemia. All of the patients share a common history of chronic rhinitis and habitual use of large doses of nasal spray containing 9 alpha-fluoroprednisolone and vasoconstrictor agents. Withdrawal resulted in a complete remission of hypokalemia in one to two weeks in all patients. The hypertension and depressed levels of PRA, aldosterone and cortisol took longer to return to normal, varying from case to case; in all but one patient, the values returned to normal within two months. This report reveals another cause of factitious mineralocorticoid excess which may be considered in the differential diagnosis of hypokalemic hypertensive syndromes.

Administration, Intranasal↗
PubMed1980

Evaluation of two inhibitory tests (nomifensine and L-dopa + carbidopa) for the diagnosis of hyperprolactinaemic states.

It has been reported that administration of nomifensine (Nom) or of L-dopa + carbidopa (L-dopa + Carb) potentiates central dopaminergic tonus, resulting in decreased prolactin (PRL) secretion. It has been proposed that these drugs would help to discriminate patients with PRL-secreting pituitary tumours from those with so-called 'functional' hyperprolactinaemia. In this study, oral Nom (200 mg) was given to forty-three hyperprolactinaemic patients and L-dopa + Carb (50 mg Carb every 6 h for four doses followed by L-dopa 100 mg and Carb 35 mg) to thirty of them and both treatment to ten normal subjects. The hyperprolactinaemic patients were divided into four clinical groups. Group A, twenty patients with proven PRL-secreting pituitary tumours; Group B, thirteen women with elevated PRL levels (less than 100 ng/ml) without any radiological evidence of a pituitary tumour (hyperprolactinaemia of unknown aetiology or 'functional' hyperprolactinaemia); Group C, four women with polycystic ovarian disease and mildly elevated serum PRL; Group D, six patients with various other disorders associated with hyperprolactinaemia. PRL levels decreased in the normal controls below the basal values by 61.3% +/- 6.2 (SEM) after Nom and 77.6% +/- 4.2 after L-dopa + Carb. Decreases in serum PRL of at least 50% (in three consecutive determinations) were found in group A in 20% of patients after Nom and in 25% after L-dopa + Carb; in group B in 15% and 40% of cases; in most of the hyperprolactinaemic women in group C; and some in group D. In conclusion, these two treatments did not discriminate between tumorous and non-tumorous cases of PRL hypersecretion.

Adenoma↗
PubMed1979

Effects of serotonin antagonists in sexually impotent men.

Thirty-one men affected with sexual impotence were studied. Since sexual function in the male seems to be controlled by both dopaminergic stimulatory and serotoninergic inhibitory mechanisms, the patients were treated with serotonin antagonists. In basal conditions mean serum LH, FSH, PRL and testosterone did not significantly differ from those found in normal subjects; no significant variations, except for PRL reduction, were observed after treatment. Both methysergide, in association with bromocriptine or mesterolone, and metergoline, either alone or in association with mesterolone, were ineffective in significantly improving sexual activity.

Adult↗
PubMed1979

Thyrotropin secretion in patients with central hypothyroidism: evidence for reduced biological activity of immunoreactive thyrotropin.

TSH concentration was measured in plasma before and after TRH administration (200 micrograms, iv) in 89 patients with documented hypothyroidism consequent to various hypothalamic-pituitary disorders. Basal plasma TSH was less than 1.0 microI/ml in 34.8%, between 1.0-3.6 microU/ml in 40.5% and slightly elevated (3.7-9.7 microU/ml) in 24.7% of the cases. The plasma TSH response to TRH was absent in 13.5%, impaired in 16.8%, normal in 47.2%, and exaggerated in 22.5% of the cases, with delayed and/or prolonged pattern of response in 65% of the cases. The dilution curves of several plasmas drawn before and after TRH were parallel to those obtained with TSH standard preparation. After gel filtration, the elution pattern of TRH-stimulated plasmas from 4 patients did not show any major difference from that of pooled plasmas from normal subjects given TRH or from that of patients with primary hypothyroidism. Plasma TSH values determined by cytochemical bioassay on both basal and TRH-stimulated samples of 5 patients were markedly lower than those obtained by RIA. The serum T3 response to TRH was absent or low in 40 out of 53 patients in whom it was evaluated. The administration of T3 (100 micrograms/day for 3 days) or dexamethasone (3 mg/day for 5 days) respectively suppressed or reduced both basal and TRH-induced plasma TSH levels. Two patients became hypothyroid shortly after pituitary surgery in spite of basal and TRH-induced plasma TSH levels similar to or higher than those before surgery. Though thyroid atrophy due to chronic understimulation could explain the low T3 response to TRH in secondary hypothyroidism, it is difficult to reconcile thyroid understimulation with normal or increased plasma TSH unless the immunoreactive material has low biological activity. Present data suggest that several patients with hypothyroidism consequent to hypothalamic-pituitary diseases secrete a material which is immunologically similar to pituitary standard TSH and responds to stimulatory and suppressive agents in a manner similar to normal TSH but has low or absent biological activity. Thus, hypothyroidism due to insufficient TSH stimulation can be termed central hypothyroidism and can be due 1) to pituitary insufficiency (secondary hypothyroidism), 2) to a hypothalamic defect (tertiary hypothyroidism), or 3) to the secretion of biologically inactive TSH.

Biological Assay↗
PubMed1978

Evaluation of the results of trans-sphenoidal surgery in acromegaly by assessment of the growth hormone response to thyrotrophin-releasing hormone.

Eighteen acromegalic patients GH-responsive to TRH were reinvestigated following trans-sphenoidal surgery and radiotherapy. Basal serum GH decreased below 10 microgram/1 in thirteen cases; nine of them became GH-unresponsive to TRH 1 month after operation, and another one following conventional pituitary irradiation. Four of these ten patients also showed a normal GH response to L-Dopa after treatment, and five responded normally to insulin-induced hypoglycaemia; two patients had a normal GH secretory pattern after both these stimuli. No recurrences were observed over a follow-up period of 15-80 months among the ten patients who became GH-unresponsive to TRH following operation, while one of the three subjects still responsive to TRH in spite of normalized basal serum GH concentration relapsed 10 months after surgery. Three patients with normalized TRH test following operation were repeatedly reinvestigated over a 3-6 years period and always found unresponsive. The present study shows that the 'paradoxical' GH responses to TRH and L-Dopa frequently disappear after surgery, that complete normalization of GH secretory pattern may rarely be attained, and that the disappearance of GH response to TRH probably indicates satisfactory treatment of acromegaly. These data suggest that the 'paradoxical' GH responses frequently found in acromegaly are dependent on the adenoma per se and not on hypothalamic dysfunction.

Acromegaly↗