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Biomedical subjects

G Faglia

Publications and source records attributed to G Faglia.

At least 55 records · Page 3Linked to original sources
PubMed1998

The one microgram adrenocorticotropin test in the assessment of hypothalamic-pituitary-adrenal function.

The possibility of assessing hypothalamic-pituitary-adrenal (HPA) function by the standard ACTH test (250 microg) has been widely discussed in the past years and compared with the role of the insulin tolerance test (ITT). Recently, it was shown that low doses of ACTH, such as 1 microg i.v., induce a maximal adrenal response and, by reducing the discrepancies compared with the ITT also allow one to detect mild forms of secondary hypoadrenalism. In the present study the 1 microg ACTH test was performed in patients with hypothalamic-pituitary disease in order to assess adrenal function, and the results have been compared with those obtained after the insulin test. Fifty-seven patients (31 men and 26 women, aged 19-73 years) with hypothalamic-pituitary diseases were studied: 51 patients were affected with pituitary tumor and 6 patients had hypothalamic disorders. All these patients and 18 healthy volunteers (7 men and 11 women, aged 19-46 years) received 1 microg i.v. ACTH injection. In addition, the ITT (0.1-0.15 U/kg body weight) was performed in all patients. In normal subjects mean cortisol levels significantly (P<0.001) increased from a baseline of 393+/-43 nmol/l to a peak of 770+/-41 nmol/l after 1 microg ACTH. In 44 patients with hypothalamic-pituitary disease 1 microg ACTH caused a cortisol rise similar to that of normal subjects (from 332+/-17 to 769+/-24 nmol/l; P<0.001), while an impaired response (from 124+/-23 to 312+/-46 nmol/l) was observed in 13 cases (23%), 7 of them with low morning cortisol levels (10-127 nmol/l) and 6 with basal values at the lower limit of normality. The cortisol response to ITT was compared with that obtained after the 1 microg ACTH test: 10 patients failed both challenges, 4 patients who passed the ACTH test failed the ITT, while 3 patients who failed the ACTH test passed the ITT. The 23 out of 57 patients (40%) who showed a cortisol peak greater than 750 nmol/l after 1 microg ACTH had a normal response to ITT. A positive correlation between cortisol peaks after ACTH and after insulin was also found (r = 0.68, P<0.001). Assuming a 100% accuracy of ITT, the low dose ACTH test yielded a 71% sensitivity and a 93% specificity. In conclusion, the low-dose ACTH test is a useful, safe and inexpensive tool for the initial assessment of HPA function in patients with hypothalamic-pituitary disease. In fact, the ITT is unnecessary when cortisol peaks are greater than 750 nmol/l after 1 microg ACTH and also when very low cortisol basal levels indicate an overt hypoadrenalism. Within these limits the ITT is mandatory and its important role in the recognition of secondary adrenal failure is further confirmed.

Adrenocorticotropic Hormone↗
PubMed1997

Immunodetection of glycoprotein hormone subunits in nonfunctioning and glycoprotein hormone-secreting pituitary adenomas.

While it is established that nonfunctioning pituitary adenomas (NFPA) produce a spectrum of glycoprotein hormones, the ability of glycoprotein hormone-secreting adenomas to synthesize hormones other than those in vivo hypersecreted has been poorly investigated so far. In this study the immunolocalization of the beta-subunits of LH, FSH, CG and TSH and the common alpha-subunit was investigated in 10 NFPA, 3 gonadotropin-secreting adenomas (Gn-omas, 1 LH-oma, 1 FSH-oma and 1 LH/FSH-oma) and 3 TSH-secreting adenomas (TSH-omas) using an immunohistochemical technique with specific antibodies to glycoprotein subunits. The percentage of positive cells was determined observing at least 5 photograph fields containing about 50 cells. Nine of the 10 NFPA were positive for FSH beta with a high percent of positive cells (> or =30%), 6 for LH beta and 5 for TSH beta with a lower number of labelled cells (from 5 to 30%). Of the 8 NFPA tested, 5 showed a marked positivity for CG beta. In Gn-omas, tumors were positive for the gonadotropin that was in vivo hypersecreted (10-60% positive cells) and negative for either TSH beta or CG beta. Similarly, in TSH-omas TSH beta was detected in a variable proportion of cells (10-30%) with no immunoreactivity for either LH beta or FSH beta or CG beta. This study indicates that the coexpression of FSH beta, LH beta, CG beta and TSH beta molecules is characteristic of NFPA since Gn-omas were negative for CG beta and TSH beta and TSH-omas were negative for FSH beta, LH beta and CG beta. Moreover, the biological events that make NFPA 'silent' glycoprotein hormone-secreting adenomas remain unclear since the positivity for gonadotropins and TSH showed by NFPA was similar to that observed in Gn-omas and TSH-omas, respectively.

Adenoma↗
PubMed1997

Granulomatous sarcoidotic lesion of hypothalamic-pituitary region associated with Rathke's cleft cyst.

The association of large pituitary mass, lack of clinical syndromes of pituitary hypersecretion, hypopituitarism and visual field defects suggests the diagnosis of nonfunctioning pituitary adenoma, but the same characteristics can be present in patients affected by other tumorous lesions, cysts, inflammatory processes or vascular disease. The management of these patients depends on a correct diagnosis. A 53-year-old woman was admitted for nausea, vomiting and severe hypotension. For three months she had complained of weakness, sleepness, skin-dryness and loss of weight. Imaging and endocrine evaluations revealed an intra and extrasellar mass causing hypopituitarism without diabetes insipidus. Histological examination of the tissue obtained at transsphenoidal surgery showed a Rathke's cleft cyst, surrounded by areas of noncaseous granulomatous tissue with scattered multinucleated giant cells of foreign body type, similar to a sarcoid lesion. Other systemic sarcoidosis localizations were absent. After two years of full well-being, the patient reported a sudden visual impairment, due to sarcoidosis involvment of the prechiasmatic tract of the optic nerve, that promptly improved with corticosteroid treatment. This report emphasizes the overlap of signs and symptoms between non functioning tumors and nontumoral masses of hypothalamic-pituitary region and underlines the fact that a correct diagnosis is feasible only on histopathological basis. Although, occasionally, the coexistence of Rathke'cyst with pituitary adenoma has been reported, to the best of our knowledge, this is the first report of the association between Rathke's cleft cyst and noncaseating granuloma tissue. Finally, the remission of neurolgical symptoms following corticosteroid therapy confirms this treatment as a valid medical approach and suggests its use in a short therapeutic trial when the diagnosis is doubtful.

Cysts↗
PubMed1997

Use of cabergoline in the long-term treatment of hyperprolactinemic and acromegalic patients.

Cabergoline (Cab), a very potent and long-lasting dopaminergic compound, was administered to 26 women with pituitary microprolactinoma [mean serum PRL levels: 124.8 +/- 11.3 micrograms/l (+/- SE), range 62-300 micrograms/l] and 3 patients with GH-secreting pituitary adenoma (2 with associated PRL hypersecretion) for 12 and 24 months, respectively. In microprolactinomas, a stable normoprolactinemia was achieved in 96.1% of cases: in 13 women (50%) with the lowest dose of the drug (0.5 mg/week), and in other 12 patients (46.1%) with increasing doses up to 3 mg/week. All the oligomenorrheic/amenorrheic women, except one, restored regular and ovulatory menses. Two patients became pregnant. Pituitary abnormalities at high resolution-CT (HR-CT) scan disappeared in 13 of 19 patients (68.4%) after 12 months of therapy and this feature persisted in 8/13 cases (61.5%) 12 months after drug withdrawal. During Cab discontinuation (range: 3-60 months), mean serum PRL levels remained significantly lower than the basal ones. Six of 25 women are still without therapy. In 2 patients, normoprolactinemia persisted up to 38 and 60 months, respectively. Cab treatment was re-instituted in 13 patients because of the recurrence of hyperprolactinemia. Five patients were lost at follow up. In all the acromegalic patients, Cab (1-3 mg/week) normalized serum GH, IGF-I and PRL levels. A clear improvement in clinical symptoms was observed in all patients, but neuroradiological improvement in only one. Cab therapy was very well tolerated, as only seven patients complained of mild and transient side-effects and none had to stop treatment. In conclusion, Cab is an effective, safe, and well tolerated dopaminergic compound for the treatment of hyperprolactinemic disorders and the control of the clinical and hormonal features of dopamine-sensitive acromegalic patients.

Acromegaly↗
PubMed1997

Effect of desmopressin on ACTH and cortisol secretion in states of ACTH excess.

OBJECTIVE: To assess the ability of desmopressin administration to stimulate ACTH/cortisol secretion in patients with Cushing's disease, either before or after surgery, and in patients with other states characterized by ACTH hypersecretion, and to compare the results with those obtained after CRH testing. DESIGN AND SUBJECTS: Plasma ACTH and serum cortisol levels were evaluated after the administration of desmopressin (10 micrograms i.v.), CRH (1 microgram/kg i.v.) and saline on different days in 17 patients with Cushing's disease, 1 with occult ectopic ACTH syndrome, 5 with Addison's disease, 3 who had been bilaterally adrenalectomized for Cushing's syndrome and 4 normal subjects. After pituitary adenomectomy desmopressin and CRH were administered again to 13 of the patients who had undergone pituitary surgery for their Cushing's disease. RESULTS: In 16 patients with Cushing's disease with microadenoma a positive ACTH/cortisol rise occurred in 11 patients after both desmopressin and CRH, 2 other patients were responsive only to desmopressin and 2 only to CRH, while in 1 patient equivocal responses to both tests were found. The persistence of a hormonal response to desmopressin after pituitary adenomectomy for Cushing's disease correlated with unsuccessful surgery, while, contrary to CRH, absent ACTH/cortisol rises were found in cured patients 1 and 12 months after operation. In 1 patient suspected for ectopic ACTH hypersecretion, desmopressin and CRH administration did not cause any ACTH/cortisol rise. Significant ACTH rises occurred after both desmopressin and CRH testing in patients with Addison's disease. All the 3 patients adrenalectomized for Cushing's syndrome showed a rise of ACTH levels after CRH, while a similar response after desmopressin occurred in only one of them. CONCLUSIONS: Desmopressin is able to stimulate ACTH and hence cortisol release in Cushing's disease. It may be a useful test in patients with doubtful responses to CRH test, in those exhibiting responses to CRH indistinguishable from those of normal subjects and in the postoperative follow-up of Cushing's disease. In some patients with abolished or reduced cortisol feed-back at hypothalamic-pituitary level the sensitivity of normal corticotrophs to desmopressin is enhanced.

ACTH Syndrome, Ectopic↗
PubMed1997

Multiple endocrine neoplasia type 1 in patients with recognized pituitary tumours of different types.

OBJECTIVE: We have investigated the prevalence of MEN 1 in patients with recognized pituitary adenomas. Since hyperparathyroidism is present in nearly 95-100% of patients with MEN 1 and frequently is the first condition to be identified, the study was limited to the identification of patients with hyperparathyroidism while the screening for gastroenteropancreatic (GEP) lesions was carried out in patients with both pituitary and parathyroid lesions. PATIENTS AND MEASUREMENTS: Serum total and ionized calcium, phosphate and intact PTH 1-84 (EASIA) were measured in 166 patients (68 with non-functioning pituitary adenoma, 42 with prolactinoma, 35 with GH-secreting adenoma, 17-with ACTH-screening adenoma, 1 with TSH-secreting adenoma, 1 with FSH-secreting adenoma and 2 with an only alpha-subunit secreting adenoma) referred to our clinic from 1990 to 1996. Plasma gastrin, somatostatin, pancreatic polypeptide and vasoactive intestinal peptide were measured by RIA in patients with hyperparathyroidism. RESULTS: Eight of 166 patients (4.8%) were found to have primary hyperparathyroidism and among these 2 also had a gastrinoma while there was no evidence of other GEP tumours. Considering the tumour type, 6 had prolactinoma (14.3%), 1 GH-secreting adenoma (2.8%) and 1 non-functioning adenoma (1.5%). In most patients the diagnosis of pituitary tumour was made several years before that of hyperparathyroidism (from 1 to 15 years) although 6 patients had previously suffered from urolithiasis and one had undergone gastric resections for recurrent peptic ulcers. One patient was identified as a MEN 1 gene carrier and 2 had relatives with signs and symptoms referable to parathyroid or GEP lesions. CONCLUSIONS: The study shows a prevalence of 4.8% of primary hyperparathyroidism in unselected patients with known pituitary tumours similar to that reported in a previous study. By contrast, the prevalence of MEN 1 in patients with prolactinoma was definitely high (14.3%). In most patients the diagnosis of pituitary tumours was made several years before that of hyperparathyroidism. Although the patients were believed to harbour a sporadic pituitary tumour, most of them had had signs and/or symptoms referable to one or both of the other organs involved in MEN 1, often concomitantly with those of pituitary tumours. These data indicate that the diagnosis of MEN 1 syndrome is missed in a substantial proportion of patients with prolactinomas and therefore the screening of these patients for the syndrome is strongly recommended.

Adenoma↗
PubMed1997

Clinical results of long-term slow-release lanreotide treatment of acromegaly.

Medical therapy is frequently needed to normalize growth hormone/insulin-like growth factor I secretion in acromegaly. The aim of this study was to determine the long-term effects of the slow-release (SR) somatostatin analogue lanreotide in 57 acromegalic patients. SR lanreotide (30 mg) was given every 14 days for 12 months. In 33% of patients, the drug dosage was raised to 60 mg and/or the time interval was shortened to 10 days. Two months of clinical evaluation followed drug discontinuation in 47 out of 48 (84%) patients who completed the 12-month period. A drug-related decrease in GH/IGF-I levels was observed. Basal GH/IGF-I levels were significantly (P < 0.001) reduced at 12 months, IGF-I was normalized in 35% of patients and GH levels were < 5 micrograms L-1 in 54%. There was a clinical improvement in patients complaining of joint pain, rachialgias, headache, digital paraesthesias and hyperhidrosis. Soft-tissue changes were documented by significant (P < 0.001) decreases in finger size. In 52 (91%) patients without overt diabetes, a slight but significant increase in integrated glycaemia (P < 0.001) was noted, while integrated insulin levels were reduced (P < 0.001). Of 33 (58%) patients with normal basal ultrasound examination of the gall bladder, three (9%) had developed asymptomatic gall stones or biliary sludge after 12 months. Adverse events were generally mild. They frequently (52%) occurred after the first SR lanreotide administration; only 28% were recurrent and 20% appeared for the first time during therapy. SR lanreotide is an effective treatment in most unselected acromegalic patients. Tolerance towards the drug is high. Subjective benefits seem to override the simple biochemical control of the disease. Glucose homeostasis more than the incidence of gall stones seems to require monitoring on therapy. SR lanreotide is clearly advantageous in improving patient compliance with medical treatment for acromegaly.

Acromegaly↗
PubMed1997

Adults with childhood-onset growth hormone deficiency: effects of growth hormone treatment on cardiac structure.

OBJECTIVES: To evaluate the effects of growth hormone deficiency (GHD) and of growth hormone (GH) therapy on cardiac structure in adults with childhood-onset GHD. SETTING: Out-patient clinic in the Italian Institute for Auxology, Milan. SUBJECTS: Eight adults with childhood-onset GHD and eight healthy controls, matched for sex, age, exercise and body mass index. INTERVENTIONS: Recombinant GH (Saizen Serono, Italy), administered in a conventional dose of 0.5 IU kg-1 week-1 for 6 months. MAIN OUTCOME MEASURES: Cardiac structure parameters, evaluated by two-dimensional, M-mode and Doppler echocardiograms, and stress test, by means of a modified Bruce protocol with a bicycle ergometer, were determined before and after 6 months GH therapy. RESULTS: Before treatment, mean (+/- SE) intraventricular septal thickness (IVST: 7.1 +/- 0.2 mm), LV posterior wall thickness (LVPT: 5.2 +/- 0.1 mm), LV mass (LVM: 94.6 +/- 5.0 g), LV mass index (LVM/body surface area, LVMI: 65.1 +/- 3.0 g m-2) and left ventricular end-diastolic diameter (LVED: 41.4 +/- 0.6 mm) of patients were significantly lower (P < 0.01) than in controls, whilst LV end-systolic diameter (LVES) of patients (25.5 +/- 0.7 mm) was similar to controls (27.5 +/- 0.7). GH treatment significantly (P < 0.01) increased LVPT (6.8 +/- 0.2 mm), LVM (111.6 +/- 4.6 g) and LVMI (80.5 +/- 3.5 g m-2); no significant changes were observed in LVED, LVES and IVST values. The stress test showed a significant improvement of cardiac performance, as demonstrated by the reduction of blood pressure x heart rate product at the same workload (basal: 32,722.5 +/- 897.4 vs. after: 25,574.6 +/- 439.7). CONCLUSIONS: GH plays a role in the maintenance of a normal cardiac structure in adulthood. The present study suggests that GH treatment might be able to improve the cardiac structure of patients with childhood-onset GHD.

Adult↗
PubMed1997

Contractile properties and fiber type distribution of quadriceps muscles in adults with childhood-onset growth hormone deficiency.

Adults with GH deficiency (GHD) report weakness and fatigability. The origin of such symptoms is still debated. This work aimed to clarify whether weakness and fatigability depend on impairment of skeletal muscle contractile capacity. Five males with childhood-onset GHD (age +/- SE, 29.6 +/- 1.9) and 13 age- and sex-matched controls were enrolled in the study. Quadriceps muscle cross-sectional area (CSA), strength, twitch characteristics, and fatigue index of voluntary and electrically evoked contractions were determined in vivo in all subjects. Fiber type distribution and CSA of identified types of skeletal fibers were determined on needle biopsy samples of the vastus lateralis muscle of all subjects. Fiber type distribution was assessed on the basis of myosin heavy chain (MHC) isoform composition determined by electrophoresis on polyacrylamide gels. Fiber CSA was determined on cross-cryosections of fiber bundles immunostained by monoclonal antibodies against MHC isoforms. Absolute values of strength and fiber CSA of quadriceps were significantly lower in patients affected by GHD than in controls. However, once strength and fiber CSA were normalized for quadriceps CSA and subject height, respectively, differences disappeared. No difference was found between GHD patients and controls for quadriceps muscle twitch characteristics, fatigue index, and fiber type distribution. The results reported here suggest that weakness and fatigability in childhood-onset GHD do not have a skeletal muscle origin.

Adult↗
PubMed1996

In vivo imaging of chromogranin A-positive endocrine tumours by three-step monoclonal antibody targeting.

The detection of chromogranins (Cg) by immunohistochemistry and serology represents a new in vitro diagnostic tool for endocrine tumours. We have recently reported on the feasibility of targeting chromogranin A (CgA) for in vivo detection of pituitary adenomas by immunoscintigraphy (ISG). The scintigraphic procedure, based on an anti-CgA monoclonal antibody and on the avidin-biotin three-step method (Cg-3S-ISG), was evaluated on a group of 29 consecutive patients with known or suspected endocrine tumours other than pituitary adenomas, i.e. medullary thyroid carcinoma, carcinoid, insulinoma and parathormone- or ACTH-producing tumours. Primary tumours (10) and recurrences (16) were visualised in 26 patients, whereas conventional imaging techniques (planar radiography, computerised tomography, magnetic resonance imaging and ultrasonography) failed to detect the tumour sites in ten of the same (Cg-3S-ISG-positive) patients. Therefore, these preliminary results indicate that Cg-3S-ISG, the first immunological method able to detect endocrine tumours in vivo, has a higher diagnostic accuracy than conventional imaging techniques (93.1% compared with 65.5%).

Antibodies, Monoclonal↗
PubMed1996

Effects of recombinant growth hormone (GH) treatment on bone mineral density and body composition in adults with childhood onset growth hormone deficiency.

Lumbar spine, whole proximal femur and total body bone mineral density (BMD, g/cm2) and the regional soft tissue composition were measured with dual energy X-ray absorptiometry (Hologic QDR 1000/W) in eight adults with childhood onset GHD, before and after 6 months of recombinant GH treatment (0.5 IU/kg/week). Data obtained from patients were compared with those recorded in an age and sex matched control group. Before treatment, lumbar (L2-L4) spine BMD (mean +/- SD: 0.811 +/- 0.159 g/cm2), whole proximal femur BMD (0.739 +/- 0.094 g/cm2) and total body BMD (0.946 +/- 0.087 g/cm2) of patients were significantly (p < 0.001, 0.01 and 0.001, respectively) lower than those recorded in an age- and sex-matched control group (1.077 +/- 0.155 g/cm2, 0.968 +/- 0.166 g/cm2 and 1.168 +/- 0.058 g/cm2, respectively), although three patients showed BMD values at the lower limit of the normal range. Mean lumbar spine BMD, whole proximal femur BMD and total body BMD did not significantly change alter 6 months' GH treatment (-1.4 +/- 3.7%, +2.7 +/- 3.7% and -1.1 +/- 5.0% vs basal values, respectively). On the other hand, trochanteric subregion showed a significant 4.8 +/- 5.3% increase (vs basal, p < 0.05), while other hip subregions did not show significant changes. GH therapy caused marked effects on body composition; in fact, a significant decrease (p < 0.01) of trunk fat (-25.2 +/- 15.0%) and a marked increase (p < 0.01) of limbs lean mass (+10.0 +/- 5.3%), resulting in a significant (p < 0.02) reduction (-16.5 +/- 13.5%) of the axial to peripheral fat ratio (APFR), were clearly evident after six months of therapy. In conclusion, our study shows that six months of GH treatment do not exert relevant effects on the BMD of adults with childhood onset GHD. On the contrary, the effects of GH therapy on body composition are more marked, being clearly appreciable after six months of treatment.

Adult↗
PubMed1996

GS protein mutations and pituitary tumors: functional correlates and possible therapeutic implications.

In more than one third of growth hormone (GH)-secreting pituitary adenomas, a point mutation in the gene for the alpha-chain of the G stimulatory protein (gsp oncogene) causes the constitutive activation of the membrane adenylyl cyclase (AC) resulting in uncontrolled cyclic adenosine monophosphate (cAMP) elevation and GH hypersecretion. Tumors expressing gsp are characterized by high membrane AC activity, elevated intracellular cAMP content, and high rates of GH release in culture medium. The AC activity is not further stimulated by GH-releasing hormone (GHRH) and other specific and non-specific agents, while it is lowered by somatostatin, as the G inhibitory protein (Gi) is normally working. Acromegalic patients bearing adenomas with the gsp mutation do not present with any obvious clinical or epidemiological distinctive features. However, they have smaller tumors in relation to their circulating GH levels, suggesting that the gsp oncogene maintains a high rate of secretory activity in vivo. Most of these patients show paradoxical GH increases to thyrotropin-releasing hormone (TRH), but none to gonadotropin-releasing hormone (GnRH) or an oral glucose tolerance test (OGTT). As with the in vitro data, these patients are not very sensitive to GHRH administration, but are sensitive to the inhibitory action of somatostatin. In our experience, only three of six patients with non-gsp-mutated tumors had lowered serum GH levels during the administration of octreotide (100 micrograms thrice daily for 4 years), while all of six patients with gsp-mutated tumors had serum GH levels suppressed by octreotide treatment. Such a good GH suppressibility by somatostatin makes patients with gsp-mutated tumors the best candidates for medical treatment with somatostatin analogs.

Acromegaly↗
PubMed1996

Growth, growth hormone and cognitive functions.

The interactions among short stature, growth hormone (GH) and cognitive functions have been extensively studied so far. However, although it seems well established that short stature is associated with cognitive problems, little effort has been made to point out the presence of specific psychological effects related to the different forms of short stature. In 'short normal' children, the presence of a scholastic underachievement seems to suggest that short stature 'itself' might predispose these patients to some of their psychosocial difficulties. The higher incidence of academic failure, in presence of a normal intellectual functioning, has been attributed to environmental and psychosocial factors, including over-protective parents and low self-esteem resulting from the impact of short stature. These problems appear to be common also to other forms of short stature (such as Turner's syndrome) where, however, they are frequently associated with other specific deficits. The in vivo model which might allow, at least in part, better understanding of GH (per se)-dependent effects is represented by GH deficiency (GHD), in which, however, the specific role of GH on psychological functioning is frequently masked by the presence of associated hormonal deficiencies. Children with isolated GHD are reported to have specific educational deficits, in particular learning disability and attention-deficit disorders, which have been tentatively attributed to a compromised intellectual potential. The psychological effects of long-term GH treatment in children with GHD still remain controversial, with some retrospective studies describing a generally beneficial outcome. Since early experiences in school are closely related to success in adult life, the possible implications that GHD during childhood holds during adulthood have been recently considered. Although regional differences have been observed in subgroups of adults with GHD, it seems that these patients have normal cognitive functions and educational attainment, but are more likely to be unemployed (and unmarried) than members of the general population. In general, patients with GHD, who have been treated at centers where psychological counselling was an integral part of the treatment program, seem to be better adjusted in adult life. For these reasons, a multidisciplinary treatment approach could allow early detection of problems in academic achievement and psychosocial development in patients with short stature, being immediately able to provide the appropriate educational and counselling interventions.

Adult↗
PubMed1996

Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas.

The recorded number of patients with central hyperthyroidism due to TSH-secreting pituitary adenoma doubled in the last few years after the introduction of ultrasensitive TSH assays in the assessment of thyroid function; however, information about the results and the criteria for cure after pituitary surgery is scanty. Seventeen patients with a TSH-secreting adenoma, diagnosed on the basis of detectable TSH levels in the face of high free thyroid hormone concentrations and pituitary lesion at neuroimaging, underwent pituitary surgery. Hypersecretion of other pituitary hormones was diagnosed in 5 of 17 patients. Four patients were initially misdiagnosed and treated with thyroid surgery or radioiodine therapy. The majority (86%) of hyperthyroid patients normalized thyroid hormone concentrations and regained euthyroidism, although pituitary imaging, alpha-subunit, and alpha-subunit/TSH molar ratio normalized in only 47%, 54%, and 58% of patients, respectively. Moreover, TSH secretion was normally suppressed by T3 in 40% of the patients. Interestingly, the finding of undetectable TSH levels 7 days after surgery was highly predictive of successful outcome. During long term follow-up, there was one relapse of hyperthyroidism. Early diagnosis of TSH-secreting adenomas permits a high rate of remission of hyperthyroidism after surgery. However, normalization of thyroid function alone does not necessarily reflect complete removal of the tumor, and more comprehensive criteria of cure based on pituitary imaging, hormone measurement, and suppression of TSH during T3 administration should be used. Lastly, all patients need an accurate long term follow-up to monitor the possible recurrence of the adenoma.

Adenoma↗
PubMed1996

Three-step immunoscintigraphy with anti-chromogranin A monoclonal antibody in tumours of the pituitary region.

In the present paper we evaluated the ability of pretargeted immunoscintigraphy (ISG) with antichromogranin A (CgA) monoclonal antibody (Mc-ab A11) in visualizing pituitary masses. The results obtained in 23 patients are described along with those of [111In]pentetreotide scintigraphy (Octreoscan) in 18 cases. Positive ISG was obtained in 9/11 (82%) non-functioning, 1/4 growth hormone-, 1/2 prolactin-, 1/2 thyrotropin-, 1/1 follicle-stimulating hormone-, 0/1 adrenocortico-trophin-secreting pituitary adenomas. In one patient with a positive ISG scan of a non-functioning pituitary adenoma, an associated neurinoma of the acoustic nerve was not imaged. The same occurred in one patient with a pituitary deposit from a mammary carcinoma and in another one with a cyst of the Rathke's pouch. Chromogranin A immunohistochemistry, carried out in 10 tumours, was positive in eight pituitary adenomas and negative in two non-adenomatous lesions. A concordant ISG occurred in all cases except for two pituitary adenomas: one cystic and necrotized and one post-operative remnant very small in size. In 18 patients with pituitary adenoma both ISG and Octreoscan were positive in 61% of cases but with a different distribution among tumours. At variance with ISG, Octreoscan visualized only 5/10 (50%) non-functioning pituitary adenomas and all (4/4) somatotropinomas. In conclusion, ISG is able to image pituitary tumours and particularly non-functioning pituitary adenomas. In this respect, it may be helpful in discriminating non-neuroendocrine masses of the pituitary region from non-functioning pituitary adenomas.

Adolescent↗
PubMed1995

Galanin infusion restores the blunted GH responses to GHRH administration during GH treatment in children with constitutional growth delay.

GH responses to GHRH (in basal conditions), GHRH (after six months of recombinant GH therapy) and GHRH plus galanin administration (after GH therapy) were determined in six children with constitutional growth delay (CGD). Before treatment, GHRH administration caused a clear rise of GH levels (mean GH peak: 38.0 +/- 7.2 ng/ml); mean GH net incremental area under the curve/120 min (GH nAUC) was 2631.0 +/- 519.8 ng/ml/120 min. During GH treatment, both height velocity and IGF-I levels significantly increased from 4.3 +/- 0.1 cm/yr to 9.4 +/- 0.9 cm/yr (p < 0.001) and from 218.7 +/- 12.3 ng/ml to 328.0 +/- 28.2 ng/ml (p < 0.001), respectively. After 6 months of GH therapy, mean GH peak (21.7 +/- 2.2 ng/ml) and mean GH nAUC (847.7 +/- 109.8 ng/ml/120 min) after GHRH administration were significantly lower (p < 0.05) than in basal conditions. Galanin infusion (10 micrograms/kg/bw) was able to completely restore the reduced GH responsiveness to GHRH administration. In fact, mean GH peak and mean GH nAUC after GHRH plus galanin were similar to those recorded after basal GHRH administration (GH peak: 37.5 +/- 4.0 ng/ml; GH nAUC: 2279.8 +/- 430.5 ng/ml/120 min). In conclusion, this study shows that the reduction of pituitary responsiveness to GHRH administration during GH treatment is not dependent on the depletion of the promptly GH releasable pool, since somatotroph refractoriness to GHRH can be overriden by the concomitant administration of galanin.

Child↗
PubMed1995

GH responsiveness to repeated GHRH or hexarelin administration in normal adults.

GH responses, calculated as the net incremental area under the curve (GH nAUC/h), to two consecutive 1 microgram/kg/bw iv GHRH boluses (administered at 0 and 120 min, test a), to one 1 microgram/kg/bw iv GHRH bolus followed by a 1 microgram/kg/bw iv hexarelin bolus (administered at 0 and 120 min respectively, test b) and to two consecutive 1 microgram/kg/bw iv hexarelin boluses (administered at 0 and 120 min, test c) were evaluated in 6 normal adults. The first GHRH injection caused a clear rise in serum GH levels in all subjects (mean GH nAUC/h, test a: 832.1 +/- 59.4 ng/ml/h, range: 723.7-1074.0 ng/ml/h; test b: 859.2 +/- 122.9 ng/ml/h, range 618.0-1422.7 ng/ml/h). Hexarelin administration elicited a marked GH release (test c: 1424 +/- 208.2 ng/ml/h, range: 810.0-2154.0 ng/ml/h), which was significantly higher than those observed after GHRH (vs test a: p < 0.02, vs test b: p < 0.05). After the first GHRH bolus, the second GHRH injection (test a) was unable to sustain GH elevated levels (mean GH nAUC: 74.5 +/- 26.5 ng/ml/h, range: 9.7-182.2 ng/ml/h), while hexarelin administration (test b) caused a clear GH rise in all subjects (GH nAUC: 1049.7 +/- 105.2 ng/ml/h, range: 786.0-1356.0 ng/ml/h). Repeated hexarelin administration (test c) was associated with a significant (p < 0.02) reduction of GH responses to the second bolus (286.6 +/- 43.1 ng/ml/h), which were however significantly higher than those observed after the second GHRH bolus (p < 0.05). In conclusion, these results demonstrate that repeated hexarelin administration causes a reduction of GH responsiveness, which is less marked than that induced by repeated GHRH administration, probably due to the more potent GH-releasing effect of hexarelin. Moreover, when administered after GHRH, hexarelin has a sustained GH-releasing effect in contrast to the poor efficacy of GHRH, thus suggesting that the acute effect of hexarelin is probably not mediated through hypothalamic GHRH pathways.

Adult↗