Biomedical subjects

A Colao

Publications and source records attributed to A Colao.

221 records · Page 13Linked to original sources

PubMedDate not supplied

Failure of long-term therapy with sodium valproate in Cushing's disease.

The aim of the current study was to evaluate the effectiveness of a long-term treatment with sodium valproate in 19 patients with Cushing's disease. Before therapy beginning, the patients were subjected to acute test with 600 mg sodium valproate. Then, they were subjected to a 3-month therapy with sodium valproate at the dose of 600 mg/day before surgery (presurgical study). The 7 patients not surgically cured were subjected again to a 3-month therapy with sodium valproate at the dose of 600 mg/day after surgery (postsurgical study). Circulating ACTH and cortisol and urinary free cortisol levels were evaluated before and monthly after the beginning of the therapy. A decrease of plasma ACTH and serum cortisol levels greater than 50% of baseline was considered as positive response to acute test whereas the normalization of plasma ACTH, serum cortisol and urinary free cortisol levels and the clinical remission were considered as positive response to the long-term treatment. At acute test, 8 patients were considered responders and 11 patients non-responders. In no patient plasma ACTH, serum cortisol and urinary free cortisol were normalized during the long-term treatment. Urinary free cortisol levels significantly decreased (483.2 +/- 33.8 vs 699.4 +/- 67.0 micrograms/24 h), whereas plasma ACTH (302.8 +/- 17.7 vs 183.3 +/- 25.0 ng/l) and serum cortisol (466.5 +/- 23.2 vs 356.7 +/- 19.6 micrograms/l) significantly increased during sodium valproate administration in the 19 patients enrolled in the presurgical study. Plasma ACTH (247.7 +/- 22.3 vs 168.6 +/- 15.0 ng/l), serum cortisol (387.4 +/- 35.8 vs 282.0 +/- 16.0 micrograms/l) and urinary free cortisol (370.9 +/- 70.6 vs 261.3 +/- 37.8 micrograms/24 h) levels significantly increased in the 7 patients enrolled in the postsurgical study. No patient had clinical remission of Cushing's disease. In conclusion, the current study showed that long-term therapy with sodium valproate is not useful in the therapeutic management of Cushing's disease neither as alternative nor as adjunctive therapy to surgery.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Occurrence of GH deficiency in adult patients who underwent neurosurgery in the hypothalamus-pituitary area for non-functioning tumour masses.

Hypothalamus-pituitary tumours and their treatments (neurosurgery and/or radiotherapy) are major causes of acquired hypopituitarism. Scientific and clinical evidences show the positive effect of GH replacement therapy in severe adult GH deficiency (GHD) pointed toward the need of diagnostic screening of conditions at high risk for GHD. We screened 152 adults (82 males, 70 females; age: 52.3+/-1.2 years, age-range: 20-80 years, BMI: 26.4+/-0.8 kg/m(2)) in order to disclose the presence of GHD after neurosurgery for hypothalamus-pituitary tumours. The whole group (studied at least 3 months after neurosurgery) included: 111 non-functioning pituitary adenomas and 41 peri-pituitary tumours (24 craniopharyngiomas, 7 meningiomas, 5 cysts, 2 chondrosarcomas, 1 colesteatoma, 1 germinoma and 1 hemangiopericitoma). In 14 patients who underwent both neurosurgery and radiotherapy due to a tumour remnant, the somatotroph function was evaluated again 6 months after the end of radiotherapy. GHD was assumed to be shown by GH peak <5 microg/L (severe <3 microg/L) after Insulin Tolerance Test (ITT) or <16.5 microg/L (severe <9 microg/L) after GH-releasing hormone+arginine test (GHRH+ARG) (3rd and 1st centile limits of normality, respectively), two widely accepted provocative tests. Before neurosurgery GHD was present in 97/152 (63.8%) and resulted severe in 66/152 (43.4%) patients. After neurosurgery GHD was present in 122/152 (80.2%) and severe in 106/152 (69.7%). While 26 patients developed severe GHD (GHD) as consequence of neurosurgery, only one patient who had been classified as GHD before neurosurgery showed normal GH response after surgery. After neurosurgery, 91.0% (81/89) of the pan-hypopituitaric patients showed severe GHD. Considering the 14 patients who underwent also radiotherapy after neurosurgery, 7/14 had GHD before neurosurgery while 12/14 became severe GHD after radiotherapy in a context of pan-hypopituitarism. IGF-I levels below the 3rd age-related normal limits were present in 39.0% of patients in whom severe GHD was showed by provocative tests. In conclusion, this study shows that the occurrence of acquired severe GHD is extremely common in adult patients bearing non-functioning tumour masses in the hypothalamus-pituitary area and further increases after neurosurgery. All patients bearing non-functioning hypothalamus-pituitary tumours should undergo evaluation of their somatotroph function before and after neurosurgery that represents a condition at obvious more than high risk for hypopituitarism.

Adenoma↗

PubMedDate not supplied

Cardiological aspects of growth hormone and insulin-like growth factor-I.

In recent years it has been demonstrated that both GH deficiency and excess include in their advanced clinical manifestations an impaired cardiovascular function, which may reduce life expectancy. This observation has allowed the investigation of the role played by the GH/IGF-I axis on cardiac structure and function. In particular, several recent experimental and clinical studies support the evidence implicating GH and/or IGF-I in the regulation of heart development. Acromegalic cardiomyopathy is characterized by myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis which often result in increased right and left ventricular mass and concentric hypertrophy. Conversely, patients with childhood or adulthood-onset GH deficiency (GHD) have a reduced left ventricular mass and ejection fraction and the indexes of left ventricular systolic function remained markedly depressed during exercise. In addition, a significant increase in the thickness of the vascular intima-media wall and a higher number of atheromatous plaques have been reported. These abnormalities of the cardiovascular system are partially reversed after normalization of GH and IGF-I levels, by octreotide in acromegaly or after GH replacement therapy in GHD patients. The evidence that GH is able to increase cardiac mass suggested its use in the treatment of idiopathic dilated cardiomyopathy. In a recent study on such patients, the administration of rhGH was demonstrated to increase myocardial mass and to reduce the size of the left ventricular chamber, resulting in an improvement in hemodynamics, myocardial energy metabolism and clinical status. These promising results might open a new field for GH treatment.

Acromegaly↗

PubMedDate not supplied

[Simultaneous and bilateral catheterization of inferior petrosal sinuses in the diagnosis of Cushing's syndrome: basal multiple sampling and after ACTH-releasing hormone test].

In 22 patients with ACTH-dependent Cushing's syndrome we have performed multiple ACTH evaluations, baseline and after ACTH-releasing hormone (CRH), during simultaneous bilateral inferior petrosal sinus sampling. The basal inferior petrosal sinus/periphery ratio for ACTH was > 2 in 11/22 patients, CRH challenge caused the appearance of an inferior petrosal sinus/periphery ratio > 3 in 6 other patients. An ACTH-secreting adenoma was surgically proven in 17 patients with ACTH inferior petrosal sinus/periphery ratio > 2 basally or > 3 after CRH and in 1 patient with an inferior petrosal sinus/periphery ratio < 2 basally or 3 after CRH. In 4 patients the very high peripheral ACTH levels, the inferior petrosal sinus/periphery ratio and the lack of ACTH increase after CRH indicated the presence of an ectopic ACTH syndrome. An ACTH intersinus gradient > 1.4 was found in 11 patients. Among these patients the adenoma was correctly localised in 6 and wrongly in 5 patients. In conclusion, the diagnostic accuracy of the inferior petrosal sinus sampling was of 95.4% (21/22 cases) considering basal and CRH-stimulated ACTH levels. The multiple basal ACTH evaluation does not seem to be necessary associated with CRH-test, but may be helpful in some cases.

Adenoma↗

PubMedDate not supplied

Beta-endorphin concentrations both in plasma and in cerebrospinal fluid in response to acute painful stimuli.

The beta-endorphin-like-immunoreactivity (beta-ELI) has been evaluated both in plasma and in cerebrospinal fluid (CSF) in 30 patients during trans-sphenoidal surgery. Blood and liquoral samples were collected in five conditions: (1) "reference", (2) "pain", (3) "analgesia", (4) "end", and (5) "24th hour". A significant rise of both plasma and liquoral beta-ELI levels (p less than 0.00001 and p less than 0.08, respectively) when compared to basal ones occurred following the painful stimulation due to the divarication of the nasal mucosa by speculum. A significant decrease (p less than 0.01) was noticed for plasma concentrations at the third sample followed by a new significant increase at the end of the operation, (p less than 0.05 when compared to the third sample and p less than 0.01 when compared to the reference sample). In CSF, beta-ELI levels decreased at the third sample (p less than 0.01 when compared to the painful levels) and at the end of surgery (p less than 0.01, p less than 0.01 and p less than 0.05 vs first, second and third samples, respectively). Twenty-four hours after surgery either plasma and liquoral beta-ELI levels decreased (p less than 0.05). The modifications of the opiatergic system after acute painful stimuli should be, hence, characterized by an early rise followed by a progressive decrease of beta-ELI concentrations. The increase of plasma beta-ELI levels, at the end of surgery, could be due to pituitary manipulation with massive release in the peripheral blood.

Acute Disease↗