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G Faglia

Publications and source records attributed to G Faglia.

At least 19 recordsLinked to original sources
PubMed1992

The silent corticotropinoma: is clinical diagnosis possible?

Up to now, the diagnosis of silent corticotroph cell pituitary adenomas has been made only on histopathological basis. In this paper we describe 6 women affected with pituitary adenomas, without evident clinical features of hypercortisolism, in whom retrospective data suggested the possibility of clinically diagnosing silent corticotropinomas in vivo. In all patients basal ACTH and cortisol levels were normal, and the low-dose dexamethasone test constantly suppressed serum cortisol and urinary 17-hydroxycorticosteroid levels. The CRH and/or lysine-vasopressin tests, performed in five patients, always induced exaggerated ACTH/cortisol rises. In three cases the response to the opiate agonist loperamide was assessed and no inhibition of ACTH/cortisol levels was found. All patients underwent pituitary surgery. In five cases evidence of corticotropinoma was obtained by immunohistochemistry or immunofluorescence studies; moreover, in one adenoma ACTH was secreted into the culture medium, and in another one CRH and arginine-vasopressin induced a marked intracellular [Ca++] rise. Electron microscopy study of the adenoma, removed from three patients, showed the presence of adenomatous corticotroph cells. Finally, in another woman no hormonal abnormalities were initially observed and she was operated for a "nonfunctioning" pituitary adenoma, but four years later an overt Cushing's disease appeared, suggesting that a silent corticotropinoma subsequently became functional, although the formation of a different adenoma cannot be excluded. In conclusion, the occurrence of ACTH/cortisol hyperresponsiveness to CRH and/or lysine-vasopressin and the lack of suppression of ACTH/cortisol secretion to opioid agonists in patients with apparently "nonfunctioning" pituitary tumors might allow the in vivo recognition of silent corticotropinomas.

17-Hydroxycorticosteroids↗
PubMed1992

Value of serum dehydroepiandrosterone sulfate assay in the evaluation of pituitary-adrenal insufficiency after pituitary adenomectomy.

The value of dehydroepiandrosterone sulfate (DHEA-S), a specific marker of adrenal androgen production, in the assessment of clinical states of hypercortisolism and hypocortisolism has been suggested. Since the way to simply test for ACTH reserve in patients (pts) with pituitary tumors after adenomectomy is not standardized, in this study serum DHEA-S concentration was measured in order to establish whether its determination might be a sensitive index of ACTH deficiency. Serum DHEA-S concentration was evaluated in 29 pts with hypothalamic-pituitary tumors (16 females, 13 males, aged 20-70 yr), 14 of whom had GH-secreting adenomas, 13 nonfunctioning adenomas, 1 prolactinoma and 1 craniopharyngioma. Serum DHEA-S and cortisol (F) levels were determined both before and every day for 8 days after pituitary adenomectomy. Before surgery in all pts mean DHEA-S and F basal values were 3.57 +/- 0.42 mumol/L and 391.8 +/- 29.0 nmol/L, respectively. Eight out of 29 pts showed reduced DHEA-S levels (0.85 +/- 0.19 mumol/L), which remained lower than normal in the postsurgical period; on the contrary, F levels were reduced in only 2 and 3 cases before and after surgery, respectively. In 3 other pts DHEA-S levels were normal before surgery and then were low in the postoperative period, while serum cortisol remained normal in all cases. In most of these patients, the finding of impaired responses to hypothalamic-pituitary-adrenal tests, together with a reduced corticosteroid urinary excretion, confirmed the existence of a secondary hypoadrenalism and the necessity for an adequate replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1992

Potential indications for octreotide in endocrinology.

Treatment with Sandostatin is established in acromegaly, thyroid-stimulating hormone (TSH)-producing pituitary, and endocrine-active gastroenteropancreatic tumors. Potential indications include ectopic hormone syndromes, medullary thyroid carcinomas, pituitary resistance to thyroid hormones, tall stature children, diabetes mellitus and diabetic complications, polycystic ovary syndrome, and Graves' ophthalmopathy. Particularly in the ectopic growth hormone-releasing hormone (GHRH) syndrome, Sandostatin is unequivocally effective and, in the ectopic corticotropin syndrome selected cases can be treated successfully with Sandostatin, leading to marked clinical improvement. In many of the above situations, only subgroups show a response to Sandostatin, which may be identified by scintigraphy with labeled Sandostatin. This pertains also to Graves' ophthalmopathy, for which Sandostatin may be particularly promising and where positive and negative Sandostatin scans have been demonstrated. However, for all these potential indications, larger, well-studied series are needed, before definitive conclusions can be drawn.

Acromegaly↗
PubMed1992

Pituitary resistance to thyroid hormones.

Pituitary thyroid hormone resistance (PRTH) refers to a particular form of thyroid hormone refractoriness that is accompanied by peripheral hyperthyroidism, as only the TSH-secreting pituitary cells appear to be resistant to the effects of thyroid hormones. The presence of PRTH is suspected and diagnosed on the basis of the finding of high free thyroid hormone levels along with unsuppressed TSH, clinical signs and symptoms of hyperthyroidism and values of at least one of the parameters evaluating peripheral thyroid hormone action in the hyperthyroid range. However, most patients with PRTH present with clinical signs and symptoms of thyroid dysfunction, particularly goiter and tachycardia, overlapping those recorded in patients with generalized thyroid hormone resistance (GRTH), i.e. refractoriness to thyroid hormones at both pituitary and peripheral tissue level. Moreover, most of them display normal values of other parameters evaluating the peripheral effects of thyroid hormones and bear mutations in the gene encoding for T3 nuclear receptors similar to those found in patients with GRTH. These findings are questioning the existence of PRTH as a separate clinical entity and support the view that the various forms of thyroid hormone resistance may be part of a spectrum of disease with variable expression in different issues.

Adolescent↗
PubMed1992

[Therapeutic use of somatostatin analogues in endocrinology].

The recent availability of the long-acting somatostatin analogue, octreotide, has allowed its therapeutical use in a wide variety of human diseases, including some digestive, neoplastic and autoimmune disorders. This review focuses on the treatment of some endocrine disorders with octreotide. Evidence is accumulating that octreotide treatment is effective in improving the cure rate of pituitary surgery in acromegaly by shrinking the tumour size, and in lowering GH and IGF-I levels in the vaste majority of patients. Octreotide is also effective in ameliorating TSH-induced hyperthyroidism in patients with TSH-secreting adenomas. Moreover, octreotide has proved useful in the management of endocrine tumours of the gastroenteropancreatic tract (vipomas, glucagonomas, gastrinomas, insulinomas, and carcinoids) by reducing hormone levels and in some instances the size of the primary and/or metastatic lesions. Besides the above well-established indications there are some other potential indications (non-secreting pituitary tumours, medullary thyroid carcinoma, ectopic Cushing's syndrome, diabete mellitus, Graves' ophthalmopathy, tall children and polycystic ovary syndrome) that still await further investigation. Side-effects of octreotide, particularly the formation of gallstones, should be carefully monitored.

Acromegaly↗
PubMed1992

Ectopic acromegaly.

Ectopic acromegaly is a rare syndrome (less than 1% of acromegalic patients) caused by ectopic growth hormone-releasing hormone (GHRH) or growth hormone (GH)-producing tumors. Its recognition is clinically important because acromegaly may be a symptom of an aggressive tumor, and different therapeutic approaches are required. Most cases are caused by either extra- or intracranial GHRH-producing tumors, whereas in rare instances the underlying disease is an ectopic GH-secreting tumor. The routine evaluation of circulating GHRH in all acromegalic patients may allow its early recognition, because plasma levels greater than 0.3 ng/mL are virtually diagnostic of a GHRH-producing tumor (frequently a bronchial or pancreatic carcinoid), whereas suppressed levels may suggest an ectopic GH-producing tumor. In addition to classic imaging techniques, whole body scintiscan with labeled octreotide may help in the localization of ectopic tumors. Surgical removal of the ectopic tumor is the therapy of choice, but it is not always feasible because patients often present with widespread metastases. Patients with GHRH-induced acromegaly benefit from the administration of the long-acting somatostatin analog, octreotide, which reduces GH, IGF-I, and GHRH, and may shrink the ectopic tumor, its metastases, and the secondary pituitary enlargement.

Acromegaly↗
PubMed1991

Patterns of gastrin secretion in patients with nonfunctioning pituitary adenomas.

The presence of gastrin in pituitary tissue as well as gastrin hypersecretion by some pituitary adenomas have been documented using different methodological approaches. In the present study, serum gastrin levels were measured in 93 patients with nonfunctioning pituitary adenoma, i.e. a condition lacking a reliable marker of the disease. Elevated gastrin levels (85-2, 180 ng/l; normal range: 15-80 ng/l) were found in 14/93 patients (15%), the highest values being observed in one patient with MEN I syndrome. In all but MEN I hypergastrinemic patient, a severe gastric hypochlorhydria (Basal Acid Output: 0.04 +/- 0.1 mmol H+/h) unresponsive to pentagastrin (Maximum Acid Output: 0.1 +/- 0.2 mmol H+/h) was seen. Secretin injection caused gastrin to increase in the patient with MEN I and in another hypergastrinemic patient. Antiparietal cells autoantibodies were positive in 3/11 patients. No changes in gastrin concentrations were found after administration of several agents usually employed in the evaluation of pituitary function, except a significant gastrin reduction after octreotide injection. In two hypergastrinemic patients who underwent pituitary adenomectomy, the high gastrin levels did not change after surgery. Finally, gastrin was undetectable in the culture media of 15 pituitary adenomas surgically removed from both normo- and hypergastrinemic patients and immunocytological studies of tumor cells did not show any gastrin staining. In conclusion, although in patients with pituitary adenomas serum gastrin evaluation is indicated in order to document the presence of a MEN I syndrome, the present data show that high gastrin levels cannot be taken as a specific marker of nonfunctioning pituitary adenomas unless the peripheral origin of hypergastrinemia is excluded.

Adenoma↗
PubMed1991

Thyrotropin alpha- and beta-subunit responses to thyrotropin-releasing hormone and domperidone in normal subjects and in patients with microprolactinomas.

Microprolactinoma is a particular pathological situation characterized by the presence of increased hypothalamic dopaminergic tone reactive to tumoral hyperprolactinemia. Since dopamine (DA) is a physiological regulating factor of the secretion of thyroid-stimulating hormone (TSH), we investigated the responses of serum TSH (holo-TSH) and its subunits (alpha-subunit: alpha-sub, and TSH-beta) to thyrotropin-releasing hormone (TRH) and domperidone (DOM; an antidopaminergic drug acting outside the blood-brain barrier) in 36 euthyroid subjects (20 controls and 16 patients with microprolactinoma) in order to evaluate the possible in vivo effects of DA excess on TSH subunit secretion. No significant difference in serum TSH increase after TRH (200 micrograms i.v.) was observed between patients with microprolactinoma and controls (TSH net incremental area under the curve, nAUC: 146 +/- 9, mean +/- SE, and 143 +/- 7.7 micrograms/l/60 min, respectively), while serum alpha-sub and TSH-beta responses were markedly reduced in patients with microprolactinoma as compared to those found in normals (alpha-sub nAUC: 3.0 +/- 0.5 vs. 19.8 +/- 2.2 micrograms/l/60 min, p less than 0.001; TSH-beta nAUC: 5.0 +/- 0.8 vs. 9.5 +/- 0.9 micrograms/l/60 min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Maternal thyroid function in early and late pregnancy.

Thyroid function was investigated during and after pregnancy in 12 healthy euthyroid women. During pregnancy, serum total T4 (TT4) levels were significantly elevated and nearly stable, while thyroxine-binding globulin (TBG) levels progressively increased till the 7th month. A slight elevation, though not significant, of free T4 (fT4) was recorded in early pregnancy. In the following months, fT4, free T3 (fT3) and the T4/TBG ratio progressively diminished, reaching a plateau at the 7th month. Serum TSH levels, measured by an ultrasensitive immunofluorometric assay, were comparable to postpartum values during the first trimester and showed a moderate upward trend with the progression of pregnancy. The evaluation of 24-hour TSH profiles was performed in 5 women during the first trimester of pregnancy. In all women, the circadian rhythm of TSH was present with a normal nocturnal surge, though anticipated in 1 case. In summary (1) during the first trimester of pregnancy, the increased thyroid activity does not seem to be only sustained by pituitary TSH which remains unmodified; the negative correlation between TSH and hCG levels might suggest that hCG also stimulates the gland to increase thyroid hormone output, and the presence of a normal TSH circadian rhythm indicates that the central mechanism of neuroregulation of the pituitary-thyroid axis is preserved in early pregnancy, and (2) in late pregnancy, a marked decrease in free thyroid hormone fractions is accompanied by serum TSH levels still in the normal range, indicating a modification of thyroid homeostasis which might recognize various etiological factors.

Adult↗
PubMed1991

In vivo detection of somatostatin receptors in patients with functionless pituitary adenomas by means of a radioiodinated analog of somatostatin ([123I]SDZ 204-090).

The recent availability of a Tyr3-substituted octreotide (SDZ 204-090) for radioiodination has allowed somatostatin (SRIH) receptor binding to be studied in vivo, and receptor-positive tumors of different origins to be visualized with a gamma-camera. This prompted us to investigate whether this compound could be used for external imaging of functionless pituitary adenomas displaying SRIH receptors. Eight patients with functionless pituitary adenomas, three patients with acromegaly, and three with macroprolactinoma were injected iv with 123I-labeled Tyr3-octreotide and then scanned with a gamma-camera. Positive scans were obtained in the three acromegalics and in two of the eight patients with functionless pituitary tumors. The patients with macroprolactinoma had negative scans. The diagnosis of functionless pituitary adenomas was confirmed by light and electron microscopic examination as well as immunocytochemical studies. In vitro binding of [125I]Tyr11-SRIH to cell membranes was evaluated in four functionless and three GH-secreting adenomas removed from seven of the patients. All of the GH-secreting as well as one of the four functionless adenomas had high affinity SRIH-binding sites, without differences in number or affinity, whereas SRIH-binding sites were not detected in the others. Positive scans were observed only in patients bearing tumors with high affinity SRIH-binding sites. In conclusion, [123I]Tyr3-octreotide appears to be a promising tool for singling out, in vivo, patients with functionless pituitary tumors displaying SRIH receptors who might potentially benefit from octreotide treatment.

Adenoma↗
PubMed1991

Hypothalamic peptides modulate cytosolic free Ca2+ levels and adenylyl cyclase activity in human nonfunctioning pituitary adenomas.

The effects of hypothalamic peptides (TRH, GnRH, arginine vasopressin, vasoactive intestinal peptide, GHRH, CRH, and SRIH) on cytosolic free calcium concentrations ([Ca2+]i) and adenylyl cyclase (AC) activity were evaluated in 12 nonfunctioning pituitary adenomas. TRH, GnRH, and arginine vasopressin induced a marked [Ca2+]i rise in 10/12, 4/12, and 2/5 tumors, respectively. The transients induced by these peptides were due to both Ca2+ mobilization from the intracellular stores and Ca2+ influx from the extracellular medium. AC activity was evaluated in 10 adenomas; 1 microM vasoactive intestinal peptide induced a 2- to 6-fold stimulation of the enzyme activity in all tumors, while neither GHRH nor CRH were effective. Moreover, in 5/10 tumors 1 microM SRIH reduced both AC activity and [Ca2+]i, while in 2/10 the peptide caused a significant rise in [Ca2+]i despite the AC inhibition and in 3/10 SRIH did not modify either AC activity or [Ca2+]i. This study indicates that in nonfunctioning pituitary adenomas a wide spectrum of hypothalamic peptides modulate [Ca2+]i and AC activity. Moreover, the presence of biologically active receptors may offer a possible target for therapeutic intervention.

Adenoma↗
PubMed1991

Size heterogeneity of circulating growth hormone in acromegaly. "Big-big" GH forms are associated with inappropriately low IGF-I levels.

UNLABELLED: Circulating GH consists of several molecular size species with different biological activity. A reduced sensitivity of some monoclonal antibodies towards high-molecular weight GH variants has been reported. The aim of the present work was to evaluate the molecular size species of circulating GH using Sephadex G-100 gel filtration chromatography in acromegalic patients and in normal subjects employing both RIA and an immunoradiometric assay for all GH determinations. In 6 normal subjects, studied under GHRH stimulation, little GH was 69.8 +/- 6% (mean +/- SD), big GH (44 kD) 26.4 +/- 6% and big-big GH (greater than 80 kD) 2.8 +/- 4%, in IRMA, with a good correspondence with RIA results (70.8 +/- 8, 27.0 +/- 4, and 3.2 +/- 2%, respectively). In 13 untreated acromegalic patients, studied in basal conditions, the little form constituted 76.2 +/- 7%, the big form 18.3 +/- 4%, which is significantly lower than in normals (p less than 0.05), and the big-big form 5.5 +/- 7%. Similar results were obtained with RIA. A clear elevation of big-big GH (21% for both in IRMA, and 15.7 and 27.8% in RIA) was found in 2 patients with IGF-I levels lower than expected on the basis of mean GH concentrations. The study was extended to an additional acromegalic patient, previously operated and irradiated on, characterized by discrepant serum GH levels in RIA (4.6 micrograms/l), and in IRMA (1.4 micrograms/l), and by normal IGF-I levels. Serum GH showed a lack of parallelism to standard GH in RIA, but not in IRMA. RIA immunoreactivity was almost completely composed (92%) of a high molecular weight GH form (greater than 90 kD), not recognized by IRMA. All IRMA immunoreactivity eluted with a Kav corresponding to 19-50 kD. IN CONCLUSION: a. the three main molecular size isomers of serum GH are similarly recognized by IRMA and RIA methods in normal subjects. b. in acromegaly, both quantitative and qualitative modifications of the GH chromatographic profile may be present. In particular, increased amounts of big-big forms, whether or not recognized by monoclonal antibodies, have been observed. Their lower bioactivity, suggested by the normal or lower than expected IGF-I levels, can account for the discrepancy between serum GH levels and the clinical picture or IGF-I levels sometimes observed in acromegaly.

Acromegaly↗
PubMed1991

Zinc and bromocriptine long-term administration in patients with prolactinomas: effects on prolactin and thymulin circulating levels.

Several studies have demonstrated zinc (Zn), prolactin (PRL) and thymulin (Zn-FTS) interplay: Zn inhibits, in a dose related manner, PRL release from lactotropes in vitro and stimulates thymulin synthesis in vivo both in humans and in animals. PRL receptors are present on thymic epithelial cells (TEC); PRL stimulates TEC trophism and activity. Little is known about the influence of PRL on Zn metabolism, though in prolactinomas we found reduced Zn and thymulin circulating levels. For this reason, we evaluated PRL, Zn, bioactive thymulin (Zn-FTS) and total thymulin (T-FTS: Zn-bound plus Zn-unbound form) serum levels in 58 patients with prolactinomas (PRL: 253 +/- 263 micrograms/L), Zn (82 +/- 23 micrograms/dl), Zn-FTS (2.2 +/- 0.20 log2(-1] and T-FTS (3.7 +/- 0.25 log2(-1] were significantly lower (p less than .01) than those found in age matched controls. Zn-unbound bioinactive thymulin form (FTS) levels were in the normal range. Bromocriptine administration (Brc) (2.5-5 mg p.o., b.i.d. for 9 months) to 20 patients with microprolactinomas lowered serum PRL levels (10.5 +/- 6.2 micrograms/L) and significantly increased (p less than .01) Zn (118.6 +/- 14.7 micrograms/dl), Zn-FTS (3.96 +/- 0.7 log2(-1)) and T-FTS (4.66 +/- 0.7 log2(1)) circulating levels. ZnSO4 administration (400 mg p.o. daily for 3 months) to 6 patients with microprolactinomas, significantly increased (p less than .01) Zn (136 +/- 18 micrograms/dl), Zn-FTS (4.5 +/- 0.5 log2(-1)) and T-FTS (5.6 +/- 0.9 log2(-1)) levels, while caused only a slight decrease in serum PRL concentrations (from 95 +/- 8 to 75 +/- 9 micrograms/L; p: NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗