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Biomedical subjects

A Colao

Publications and source records attributed to A Colao.

At least 145 records · Page 8Linked to original sources
PubMed1998

Bone mineral density and circulating cytokines in patients with acromegaly.

Acromegalic patients present an increase of osteoblastic and osteoclastic activity, showing a different effect on the axial and appendicular skeletal structures. At this regard controversial data about bone mineral density (BMD) have been published in literature. In fact an increase of BMD levels in femoral neck and Ward's triangle without any difference in lumbar spine has been described. On the other hand normal BMD levels at forearm and reduced BMD levels at lumbar spine were found. These patients seem to have a reduction of trabecular BMD similar to postmenopausal osteoporotic patients despite normal or slightly elevated cortical BMD. Recently, it has been described that cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), are implicated in the pathogenetic mechanism of postmenopausal osteoporosis. Taking into account that growth hormone (GH) can increase TNF-alpha and IL-1 secretion by mononuclear blood cells, the evaluation of possible relationship between the reduced BMD at lumbar spine and circulating cytokines levels was carried out in acromegalic patients. In addition we evaluated the effect of acute octreotide administration on serum TNF-alpha and IL-I concentrations. Eleven patients with active acromegaly and eleven healthy age-, sex-, weight- and heightmatched subjects were enrolled in this study. BMD was significantly reduced at lumbar spine (0.80 +/- 0.29 g/cm2 vs 1.02 +/- 0.11 g/cm2; p < 0.01), but not at femoral neck level or at Ward's triangle level (0.92 + 0.15 g/cm2 vs 0.97 + 0.11 g/cm2, p = NS; and 0.74 +/- 0.16 g/cm2 vs 0.85 +/- 0.1 g/cm2, p = NS) when compared to controls. Baseline serum levels of TNF-alpha and IL-1 were in the normal range both in patients and controls. After acute octreotide administration, no differences in circulating TNF-alpha and IL-1 levels were found. In conclusion, acromegalic patients present a reduced BMD at lumbar spine but not at femoral neck level and Ward's triangle. Circulating cytokines such as TNF-alpha and IL-1 are in the normal range. These data suggest that cytokines are not involved in the pathogenesis of GH-excess induced osteoporosis. The possibility that the GH excess might affect bone turnover inducing an increase of cytokines acting by a paracrine/autocrine mechanism cannot be ruled out.

Acromegaly↗
PubMed1998

Growth hormone deficiency in elderly patients with hypothalamo-pituitary tumors.

In 18 patients with hypothalamo-pituitary diseases aged over 60 years and in 18 sex, age- and BMI-matched healthy subjects, the results of plasma IGF-I and IGF-BP3 levels and the GH response to GHRH + arginine test (GHRH + ATT) were correlated to the results of body composition, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type I collagen (Ntx) and the bone mineral density (BMD). In 10 patients and 10 controls, the GH response to ITT was also evaluated. The GH response to GHRH + ATT and ITT was markedly reduced in patients compared to controls (3.1 +/- 0.7 vs. 23.2 +/- 2.3 micrograms/L, P < 0.001 and 1.1 +/- 0.3 vs. 6.4 +/- 0.8 micrograms/L, P < 0.001), so all patients were classified as GHD, though no significant difference was found in plasma IGF-I and IGF-BP3 levels between the two groups. Body composition analysis revealed a significant increase of fat mass (37.4 +/- 2.2 vs. 28.0 +/- 1.0%, P < 0.001), a significant decrease of lean mass (62.6 +/- 2.2 vs. 72.0 +/- 1.0%, P < 0.001) and total body water (45.7 +/- 1.5 vs. 52.5 +/- 1.1%, P < 0.001) in patients compared to controls. Serum OC levels were lower (1.9 +/- 0.1 vs. 4.6 +/- 0.4 micrograms/L, P < 0.001) in patients than in controls, whereas urinary Ntx levels were similar. BMD values in lumbar spine (0.81 +/- 0.02 vs. 0.90 +/- 0.02 g/cm2, P < 0.001) and femoral neck (0.70 +/- 0.02 vs. 0.82 +/- 0.02 g/cm2, P < 0.001) were significantly lower in patients than in controls. A significant inverse correlation was found between GHD duration and lumbar spine (r = -0.73, P&1t; 0.001) or femoral neck (r = -0.81, P&1t; 0.001) BMD values and a significant direct correlation was found between GH peak after GHRH + ATT and lumbar BMD (r = 0.69, p = 0.001) in GHD patients. In conclusion, GHD in patients over 60 yrs aged with a characteristic history of hypothalamus-pituitary pathology is distinct from the physiological decline in GH secretion associated with aging.

Aged↗
PubMed1998

Left ventricular function in young adults with childhood and adulthood onset growth hormone deficiency.

OBJECTIVE: The impairment of heart structure and function in adults with childhood onset GH deficiency has been recently described. However, previous echocardiographic studies have reported no differences in cardiac mass and function between adulthood onset GH deficient patients and healthy subjects. DESIGN: The aim of this study was to evaluate cardiac performance in adult patients with childhood and adulthood onset GH deficiency, using equilibrium radionuclide angiography, a method more accurate than echocardiography. PATIENTS: Eleven patients with childhood onset GH deficiency, 9 patients with adulthood onset GH deficiency and 12 age-, gender-, height- and weight-matched healthy subjects entered the study. MEASUREMENTS: All the study population underwent equilibrium radionuclide angiography at rest and during physical exercise. RESULTS: Both childhood and adulthood onset GH deficient patients had an impaired left ventricular systolic performance both at rest (ejection fraction was 55 +/- 6%, 55 +/- 10% and 66 +/- 6% in childhood and adulthood onset GH deficient patients and control group, respectively; P < 0.0001) and during physical exercise (ejection fraction was 54 +/- 9% in childhood onset GH deficient patients, 53 +/- 9% in adulthood onset GH deficient patients and 76 +/- 7% in normal subjects; P < 0.0001). Peak ejection rate was 3.2 +/- 0.8 end-diastolic volume/second, 3.0 +/- 0.6 end-diastolic volume/second and 3.9 +/- 0.8 end-diastolic volume/ second in childhood and adulthood onset GH deficient patients and control group, respectively (P < 0.01). Exercise-induced changes in end-systolic volume were increased in both groups of patients compared with healthy subjects. In contrast, exercise-induced end-diastolic volume changes were not different between GH deficient patients and controls. Resting peak filling rate was 2.6 +/- 0.7 end-diastolic volume/second, 2.5 +/- 0.7 end-diastolic volume/ second and 3.1 +/- 0.3 end-diastolic volume/second in the 2 groups of patients and healthy subjects, respectively (P < 0.05). Reduced exercise tolerance in all patients, as shown by the significantly lower values of peak workload (P < 0.0001), peak rate-pressure product (P < 0.01) and exercise duration (P < 0.0001) was observed. CONCLUSION: Patients affected by GH deficiency have left ventricular systolic dysfunction at rest and during physical exercise, suggesting that GH plays a physiological role in maintaining normal cardiac performance in humans. Furthermore, no difference between childhood and adulthood onset GH deficient patients was found indicating that both group of patients have an impairment of cardiac function.

Adult↗
PubMed1998

Effect of corticotrophin-releasing hormone on arginine vasopressin and atrial natriuretic factor in patients with Cushing's disease.

OBJECTIVE: To evaluate the effect of CRH administration on plasma AVP and ANF concentration in patients with Cushing's disease and healthy subjects. SUBJECTS: Fifteen patients with Cushing's disease and 15 sex- and age-matched healthy subjects entered the study. STUDY DESIGN: All subjects were randomly given i.v. 100 micrograms hCRH and placebo (NaCl 0.9%) on two non consecutive days. Blood samples for plasma AVP and ANF assay were taken before and every 15 min for 2 hr after CRH or placebo. Five out of the 15 patients with Cushing's disease underwent a repeat CRH test after surgical cure of the disease. RESULTS: At baseline evaluation, plasma ANF concentrations were significantly higher in patients with Cushing's disease compared to healthy subjects (15.0 +/- 0.8 vs 10.8 +/- 0.6 pmol/l, P < 0.001) whereas plasma AVP concentrations were similar between the two groups of subjects (8.0 +/- 0.4 vs 6.8 +/- 0.6 pmol/l). CRH administration induced a significant increase in plasma ANF concentrations both in patients with Cushing's disease (24.0 +/- 1.6 pmol/l, P < 0.05) and healthy subjects (29.4 +/- 1.5 pmol/l, P < 0.05). Conversely, a significant increase in plasma AVP concentrations was found only in patients with Cushing's disease (14.7 +/- 1.4 vs 8.0 +/- 0.4 pmol/l, P < 0.05). In addition, patients with Cushing's disease had an increase in ANF levels after CRH significantly lower than that observed in healthy subjects (peak/basal ratio: 1.7 +/- 0.1 vs 3.1 +/- 0.4, P < 0.01). In 5 patients re-tested after disease cure, CRH administration significantly increased plasma ANF levels (26.8 +/- 1.1 vs 10.7 +/- 0.4 pmol/l, P < 0.05) but it did not modify plasma AVP levels (8.4 +/- 0.4 vs 7.3 +/- 0.5 pmol/l). ANF response to CRH in patients cured from Cushing's disease was similar to that recorded in healthy subjects (peak/basal ratio: 2.6 +/- 0.2 vs 3.1 +/- 0.4). CONCLUSION: CRH stimulates ANF secretion both in patients with Cushing's disease and healthy subjects. Plasma ANF response to CRH is blunted in patients with Cushing's disease compared to patients cured from Cushing's disease and healthy subjects, probably because of hypercortisolism. By contrast, CRH stimulates AVP secretion only in patients with Cushing's disease, but not in patients cured from Cushing's disease and healthy subjects. This phenomenon could be related to the activity of the disease.

Adrenocorticotropic Hormone↗
PubMed1998

Effectiveness of chronic treatment with alendronate in the osteoporosis of Cushing's disease.

BACKGROUND: Osteoporosis is common in patients with Cushing's disease and is likely due to an imbalance between bone formation and resorption. Alendronate is an aminobisphosphonate that is able to increase bone mass mainly by inhibiting bone resorption. OBJECTIVE: We have evaluated the effect of chronic treatment with alendronate on bone mineral density (BMD) in patients with Cushing's disease. PATIENTS: 39 patients with Cushing's disease entered this study. 39 age-, sex- and BMI-matched normals served as controls for baseline evaluation. The 39 patients were divided into four groups: 1) 10 patients with active disease treated with alendronate and ketoconazole; 2) 11 patients with inactive disease treated with alendronate; 3) 8 patients with active disease treated with ketoconazole alone, 4) 10 patients with inactive disease received no treatment. TREATMENT PROTOCOL: Alendronate was given for 12 months in a dose of 10 mg orally once daily after fasting at 0800 h in the morning. Ketoconazole was given in a dose of 200-600 mg orally daily, when pituitary surgery was unsuccessful. STUDY DESIGN: Lumbar spine (L1-L4) and femoral neck BMD, serum osteocalcin (OC), urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were evaluated at study entry, in patients and controls, and were repeated after 6 and 12 months in the 39 patients. RESULTS: BMD values were lower in patients with Cushing's disease than in controls at both L1-L4 (0.72 +/- 0.4 vs. 1.01 +/- 0.6 g/cm2, P < 0.05) and femoral neck (0.69 +/- 0.3 vs. 0.96 +/- 0.6 g/cm2, P < 0.05). In the 39 patients with Cushing's disease considered as a whole, serum OC levels were lower (1.1 +/- 0.1 vs 1.5 +/- 0.1 nmol/l, P < 0.01), while Ntx values were higher than in controls (168 +/- 25 vs. 61 +/- 31 nmol BCE/mmol creatinine, P < 0.01). In the alendronate-treated groups, serum OC levels increased, while Ntx levels significantly decreased after 6 and 12 months of treatment without any significant difference between the two groups. BMD values measured at L1-L4 and femoral neck significantly increased after 12 months of therapy. In patients of group 4, a significant increase of serum OC levels and a significant decrease of Ntx levels were observed together with a slight increase of BMD values after 12 months. No significant change in either biochemical markers or BMD values was found in patients of group 3. CONCLUSIONS: Patients with Cushing's disease have osteoporosis which needs to be rapidly reversed to limit the risk of fracture. The results of the present study show that a 12 month treatment period with alendronate induced an improvement in bone mineral density greater than in untreated patients.

Acute Disease↗
PubMed1998

Correlation of scintigraphic results using 123I-methoxybenzamide with hormone levels and tumor size response to quinagolide in patients with pituitary adenomas.

The efficacy of dopaminergic agents in the medical treatment of pituitary adenomas is well known. Quinagolide is a nonergot derivative dopamine agonist, which binds dopamine D2 receptors with high affinity. The treatment with this drug is reported to suppress hormone levels and to cause tumor shrinkage in prolactinomas and in a few GH-secreting pituitary adenomas. In clinically nonfunctioning pituitary adenomas (NFPA), the efficacy of quinagolide treatment is controversial. The scintigraphy of the pituitary region using 123I-methoxybenzamide (123I-IBZM) allows us to visualize in vivo the expression of dopamine D2 receptors on pituitary tumors. In this study, the pituitary scintigraphy with 123I-IBZM was performed in 14 patients with macroadenoma before starting a long-term treatment with quinagolide: 6 NFPA with high circulating alpha-subunit levels, 4 PRL-secreting, and 4 GH-secreting adenomas. A 3-point score was used to grade the ligand accumulation within the pituitary adenomas: 0 = negative, 1 = moderate uptake (equal to that recorded in the cerebral cortex), and 2 = intense uptake (equal to that recorded in the basal nuclei). The treatment with quinagolide was carried out at the dose of 0.3-0.6 mg/day for 6-12 months. Clinical, biochemical and hormonal assessment was repeated monthly during the first 3 months, then quarterly. Sellar magnetic resonance imaging was performed before and after 6 and 12 months of quinagolide treatment, to evaluate tumor shrinkage (> 25% of baseline size). In all 14 patients, a significant positive correlation was found between the degree of 123I-IBZM uptake and the clinical response to quinagolide treatment (r = 0.90; P < 0.001). In particular, the normalization of serum alpha-subunit and PRL levels, respectively, was achieved in 3 patients with NFPA and in 2 patients with prolactinoma, who showed intense 123I-IBZM uptake in the pituitary region. In 4 of these 5 patients with positive scan, a significant tumor shrinkage occurred between 6 and 12 months after the beginning of quinagolide treatment. In all patients with GH-secreting adenoma, no significant uptake of 123I-IBZM was found and no significant decrease of circulating GH and/or insulin-like growth factor-I levels, and tumor shrinkage was obtained during long-term treatment with quinagolide. In conclusion, the pituitary scintigraphy with 123I-IBZM can be considered a useful tool to indicate adenomas with significant expression of functioning D2 receptors. This innovative technique may predict the response to long-term treatment with quinagolide in patients with NFPA, where the lack of pituitary hormone hypersecretion makes difficult the monitoring of medical treatment efficacy.

Adenoma↗
PubMed1998

Orbital scintigraphy with [111In-diethylenetriamine pentaacetic acid-D-phe1]-octreotide predicts the clinical response to corticosteroid therapy in patients with Graves' ophthalmopathy.

Corticosteroid treatment is successfully used in Graves' ophthalmopathy, and its effect varies according to the phase of the disease. The infiltration of the orbit by activated lymphocytes may explain the effectiveness of corticosteroid therapy. Scintigraphy with [111In-DTPA-D-Phe1]-octreotide was recently used to reveal the presence of activated lymphocytes in foci of autoimmune diseases, because elevated amounts of somatostatin receptors are expressed in the surface of these cells. The aim of the current study was to evaluate whether the degree of orbital [111In-DTPA-D-Phe1]-octreotide uptake is able to predict the response to corticosteroid therapy in patients with Graves' ophthalmopathy. Ten patients with Graves' ophthalmopathy entered the study. In all patients scintigraphy was performed, and subsequently, corticosteroid therapy (methylprednisolone, 1 g i.v. for 2 consecutive days a week for 6 weeks) was given. Clinical activity of Graves' ophthalmopathy was evaluated before and after treatment by calculating the ophthalmopathy index (OI). Planar and single photon emission computed tomography (SPECT) images of the head were obtained 24 h after the i.v. injection of 120-190 MBq of [111In-DTPA-D-Phe1]-octreotide. Radioligand uptake within each orbit (O) and brain (B) was measured using the region of interests (ROI) method and the O-to-B ratio was determined. According to the O-to-B ratio, the images were classified using the following three points score: 0 = O-to-B ratio < or =1; 1 = O-to-B ratio between 1 and 2.5; 2 = O-to-B ratio > or =2.5. The value of OI, measured before and after corticosteroid treatment, was correlated to the scintigraphic score. A significant change of OI was observed between posttreatment and pretreatment evaluation both in orbits with score 2 (OI: 15.4 +/- 1.5 vs. 9.6 +/- 0.5, P < 0.005) and in those with score 1 or 0 (OI: 12.9 +/- 1.5 vs. 11.5 +/- 1.4, P < 0.05) at the scintigraphy. However, when the OI was calculated excluding the changes in the soft tissue, which generally occur in all patients independently from the phase of the disease, a significant change of OI was observed only in the orbits with score 2 (OI: 12.9 +/- 1.3 vs. 8.3 +/- 0.5, P < 0.01) but not in those with score 0 or 1 (OI: 11.2 +/- 1.3 vs. 10.4 +/- 1.3). In particular, 6 weeks after corticosteroid treatment, the patients with orbital score 2 at the scintigraphy had a significant improvement of soft tissue changes, proptosis, lagophthalmos, extraocular muscle movements impairment, and diplopia, whereas patients with score 0 or 1 had only a significant improvement of the soft tissue inflammation. In conclusion, the current preliminary data suggested that [111In-DTPA-D-Phe1]-octreotide scintigraphy is able to predict the clinical response to corticosteroid treatment in patients with Graves' ophthalmopathy, and may be considered an useful approach to select the patients for the proper treatment.

Adult↗
PubMed1998

Adrenocorticotropin and cortisol hyperresponsiveness to hexarelin in patients with Cushing's disease bearing a pituitary microadenoma, but not in those with macroadenoma.

We previously reported that in Cushing's disease (CD) the ACTH- and cortisol (F)-releasing activity of Hexarelin (HEX), a GH secretagogue, is exaggerated with respect to that in normal subjects and is higher than that of human CRH (hCRH), but it is absent in Cushing's syndrome. Our aim was to extend the study about the effects of HEX (2.0 microg/kg, iv) on ACTH and F secretion in 21 patients with CD (3 men and 18 women, 16-68 yr old). Based on magnetic resonance imaging, 15 CD patients had pituitary microadenoma, and 6 had macroadenoma. The results in CD patients were compared with those in 27 normal age-matched controls (NS; 10 men and 17 women, 24-69 yr old). Basal ACTH and F levels in CD were similar in patients with microadenom (mean+/-SEM, 78.3+/-7.2 pg/mL and 237.1+/-23.6 microg/L, respectively) and macroadenoma (57.4+/-9.0 pg/mL and 196.9+/-20.1 microg/L, respectively) and were higher (P < 0.001) than those in NS (17.7+/-2.0 pg/mL and 115.3+/-6.7 microg/L, respectively). In microadenoma CD patients, HEX induced marked ACTH and F increases (delta peak, mean+/-SEM: 261.2+/-77.6 pg/mL and 226.1+/-87.2 microg/L, respectively), which were higher (P < 0.04) than those induced by hCRH (45.6+/-16.9 pg/mL and 84.6+/-25.7 microg/L, respectively). Moreover, in microadenoma CD patients, the ACTH and F responses to HEX were higher (P < 0.001) than those in NS (18.5+/-4.0 pg/mL and 36.1+/-6.8 microg/L, respectively). In macroadenoma CD patients, HEX induced a slight, but significant increase (P < 0.02) in ACTH and F levels (33.9+/-18.0 pg/mL and 89.6+/-34.3 microg/L, respectively), which was not significantly different from that elicited by hCRH (20.0+/-7.0 pg/mL and 54.8+/-21.3 microg/L, respectively). In macroadenoma CD patients, the ACTH and F responses to HEX and hCRH were, in turn, similar to those in NS. In conclusion, our findings demonstrate that the ACTH and F hyperresponsiveness to HEX is present in Cushing's disease with micro-, but not macro- ACTH-secreting pituitary adenoma. This finding agrees with other evidence pointing toward differences in the hormonal behavior between micro- and ACTH-secreting pituitary macroadenomas.

Adenoma↗
PubMed1998

Prostatic hyperplasia: an unknown feature of acromegaly.

This study was designed to investigate whether GH and insulin-like growth factor I (IGF-I) excess could lead to the development of benign prostatic hyperplasia and/or prostatic carcinoma. Prostatic diameters and volume as well as the occurrence of prostatic diseases were studied by ultrasonography in 10 untreated acromegalic patients less than 40 yr of age and 10 age- and body mass index-matched healthy males. Serum GH, IGF-I, PRL, testosterone, dihydrotestosterone, prostate-specific antigen, and prostatic acid phosphatase levels were assessed. All patients had secondary hypogonadism, as diagnosed by low testosterone levels, and 4 of 10 patients had hyperprolactinemia. After 1 yr of treatment with octreotide (0.3-0.6 mg/day), ultrasound scan and hormone parameters were repeated. The 4 hyperprolactinemic acromegalics were treated with octreotide and cabergoline (1-2 mg/week) to suppress PRL levels. Symptoms due to prostatic, seminal vesicle, and/or urethral disorders or obstruction were experienced by neither acromegalics nor controls. Digital rectal examination revealed no occurrence of prostatic nodules or other abnormalities. Compared to healthy subjects, a remarkable increase in transversal prostatic diameter and volume was observed in acromegalics. In healthy subjects, prostate volume ranged from 15.1-21.8 mL, whereas in acromegalics it ranged from 21.8-41.8 mL. Similarly, an increased median lobe was observed. In fact, the transitional zone diameter was just detectable in 5 of 10 controls, whereas it was measurable in all acromegalics (18 +/- 1.2 vs. 2.8 +/- 0.3 mm; P < 0.001). The prevalence of periurethral calcifications was more than doubled in acromegalics (50%) compared to that in controls (20%). Treatment with octreotide for 1 yr produced normalization of circulating GH and IGF-I levels in 7 of 10 patients. In these 7 patients, ultrasound evaluation showed a significant reduction of the antero-posterior diameter (26.1 +/- 1 vs. 28.9 +/- 1.6 mm; P < 0.01), the transversal diameter (44.9 +/- 2 vs. 48 +/- 2 mm; P < 0.01), and the cranio-caudal diameter (36.5 +/- 1 vs. 41.3 +/- 1.5 mm; P < 0.001), whereas the transitional zone diameter was unchanged (16.4 +/- 1.5 vs. 17.4 +/- 1.7 mm). As a consequence, a significant decrease in prostate volume was recorded (22.1 +/- 1.1 vs. 29.8 +/- 2.5 mL; P < 0.001). Prostate volume increased in 2 of the 3 patients who did not achieve normalization of GH and IGF-I after octreotide treatment. Finally, after treatment, serum testosterone levels were significantly increased (from 1.5 +/- 0.3 to 3.5 +/- 0.3 microg/L), whereas dihydrotestosterone, dehydroepiandrosterone sulfate, delta4-androstenedione, 17beta-estradiol, prostate-specific antigen, and prostatic acid phosphatase were unchanged. Serum PRL levels were suppressed after cabergoline treatment in all 4 hyperprolactinemic patients throughout the study period. In conclusion, prostate enlargement occurs in young acromegalics with a higher than expected prevalence of micro- and macrocalcifications. This suggests that a careful prostate screening should be included in the work-up and follow-up of acromegalic males.

Acromegaly↗
PubMed1998

Bone marker and bone density responses to dopamine agonist therapy in hyperprolactinemic males.

The aim of this prospective study was to evaluate the bone mineral density (BMD) at lumbar spine and femoral neck levels and biochemical parameters of bone turnover in 20 consecutive hyperprolactinemic males before and after an 18-month treatment with different dopamine agonists. Six patients received bromocriptine at a dose of 2.5-10 mg/day; 7 patients received quinagolide at a dose of 0.075-0.3 mg/day; 7 patients received cabergoline at a dose of 0.5-1.5 mg/week. BMD, serum PRL, testosterone, dihydrotestosterone, and osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured before and every 6 months during treatment. At study entry, BMD values were lower in patients than controls at both lumbar spine (0.82 +/- 0.03 vs. 1.18 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.85 +/- 0.02 vs. 0.92 +/- 0.02 g/cm2; P < 0.05) levels. Osteopenia or osteoporosis was diagnosed in 16 patients at the lumbar spine and in 6 of them at the femoral neck level. A significant inverse correlation was found between lumbar spine and femoral neck BMD values and both PRL levels and disease duration (P < 0.01). In the 20 patients, serum OC levels were significantly lower (2.1 +/- 0.1 vs. 9.3 +/- 2.4 microg/L; P < 0.01), whereas Ntx levels were significantly higher (157.8 +/- 1.1 vs. 96.4 +/- 7.4 nmol bone collagen equivalent/mmol creatinine; P < 0.001) than control values. A significant inverse correlation was found between serum PRL and OC (P < 0.01), but not Ntx, levels. After 18 months of treatment, serum PRL levels were suppressed, and gonadal function was restored in all 20 patients, as shown by the normalization of serum T (from 2.2 +/- 0.2 to 5.0 +/- 0.2 microg/L) and dihydrotestosterone (0.3 +/- 0.02 vs. 0.5 +/- 0.01 nmol/L) levels, without any significant difference among groups. A progressive significant increase in serum OC levels together with a significant decrease in Ntx levels were observed after 6, 12, and 18 months of treatment in the 3 groups of patients. A slight, although significant, increase in BMD values was recorded in all patients after 18 months of bromocriptine, quinagolide, and cabergoline treatment, serum OC levels were normalized after treatment, whereas neither urinary Ntx levels nor BMD values were normalized by 18 months of treatment with dopaminergic agents. In conclusion, treatment with bromocriptine, quinagolide, and cabergoline for 18 months, although successfull in suppressing serum PRL levels and restoring gonadal function, was unable to restore lumbar spine and femoral neck BMD and normalize Ntx levels. However, BMD was slightly increased during treatment, suggesting that additional bone loss was prevented after treatment of hyperprolactinemia.

Adult↗
PubMed1998

Reversibility of joint thickening in acromegalic patients: an ultrasonography study.

Axial and peripheral arthropathy affects the majority of patients with acromegaly, being a leading cause of morbidity and functional disability. Treatment with octreotide (OCT) improves symptoms and signs of acromegalic arthropathy, but objective detection of structural changes in bone and cartilage has not been reported to date. This open prospective study was designed to evaluate the effect of a long term treatment with OCT on acromegalic arthropathy assessed by ultrasonography examination. Articular cartilage thicknesses of shoulder, wrist, and knee as well as sizes of heel tendons were measured in 30 acromegalic patients (18 with active and 12 with inactive disease) and 18 sex-, age-, and body mass index-matched healthy subjects. The thicknesses of shoulder, wrists and knees articular cartilages and that of heel tendons were significantly increased in patients with active acromegaly compared to those in healthy subjects (P < 0.01). With the exception of shoulder cartilage, significant increases in wrist and knee cartilages (P < 0.01) and right and left heel tendon sizes (P < 0.05) were found in patients with active compared to those with inactive disease. After 6 months of OCT treatment, a significant decrease in shoulder, wrist, and left knee articular cartilage was found (P < 0.001). No significant change was recorded in right knee cartilage or heel tendon size. The decrease in thickness of shoulder and wrist cartilages was more pronounced than that measured at the level of left knee (26.3 +/- 3.3% and 27.2 +/- 4.2% vs. 14.2 +/- 4.2%, respectively; P < 0.05). Ultrasonography is able to reveal articular involvement in acromegalic patients and may be useful to monitor the effect of treatment.

Acromegaly↗
PubMed1998

Impairment of bone status in patients with central diabetes insipidus.

The aim of the current study was to evaluate the biochemical parameters of bone metabolism and the bone mineral density (BMD) in patients with central diabetes insipidus, either treated or not treated with endonasal desmopressin. Eighteen patients with central diabetes insipidus and 18 sex- and age-matched healthy subjects entered the study. The patients were divided into 2 groups: patients who did not receive treatment with desmopressin for at least 1 yr (group 1), and patients chronically treated with desmopressin since the diagnosis of diabetes insipidus (group 2). Serum osteocalcin and urinary cross-linked N-telopeptide of type I collagen levels were measured in all patients and controls using RIA and enzyme-linked immunosorbent assay kits, respectively. BMD was measured at the lumbar spine (L1-L4) and at the femoral neck in all subjects, using a Hologic QDR 1000 analyzer (Hologic Inc., Waltham, MA). Serum osteocalcin concentrations were significantly lower, both in patients of group 1 and group 2, compared with healthy subjects (5.1 +/- 0.6 and 4.5 +/- 0.3 vs. 7.9 +/- 0.2 micrograms/L, P < 0.05), whereas urinary cross-linked N-telopeptide of type I collagen concentrations were similar in the three groups of subjects (72.8 +/- 2.2, 71.6 +/- 2.7, and 64.6 +/- 1.7 nmol bone collagen equivalent/mmol creatinine). BMD was significantly decreased in patients of groups 1 and 2, compared with controls, both at lumbar spine (0.84 +/- 0.06 and 0.87 +/- 0.04 vs. 1.01 +/- 0.02 g/cm2, P < 0.05) and femoral neck (0.78 +/- 0.06 and 0.80 +/- 0.04 vs. 0.93 +/- 0.02 g/cm2, P < 0.05). A significant inverse correlation was found between disease duration and BMD values, evaluated as T scores, both at lumbar spine (group 1: r = -0.952, P < 0.005; group 2: r = -0.921, P < 0.001) and at femoral neck (group 1: r = -0.914, P < 0.05; group 2: r = -0.683, P < 0.05). In conclusion, patients with central diabetes insipidus had a significant bone impairment, compared with healthy subjects. Replacement with endonasal desmopressin at standard doses was not able to prevent or reverse the bone impairment. These findings suggest that, in patients with central diabetes insipidus, bone status analysis is mandatory; and a bone-loss preventing treatment might be beneficial.

Administration, Intranasal↗
PubMed1998

Prolactinomas in children and adolescents. Clinical presentation and long-term follow-up.

In this study, we report the clinical presentation, response to medical treatment, and long-term follow-up of 26 patients with prolactinoma (15 macro- and 11 micro-adenomas) diagnosed at the age of 7-17 yr. All patients were first treated with bromocriptine (BRC) at doses ranging from 2.5-20 mg/day orally. BRC was discontinued for intolerance and/or resistance to the drug and was replaced by quinagolide (CV) at doses ranging from 0.075-0.6 mg/day or by cabergoline at doses ranging from 0.5-3.5 mg/week orally. Two patients received external conventional radiotherapy after surgery. In 7 prepubertal males and 6 females with macroprolactinoma, headache and/or visual defects were the first symptoms. All females presented with primary or secondary amenorrhea. Growth arrest was observed in a male patient with microadenoma, whereas all the remaining patients had normal heights, and pubertal development was appropriate for their age. Spontaneous or provocative galactorrhea was observed in 12 patients (3 males and 9 females) and gynecomastia in 4 males. Mean serum PRL concentration (+/-SE) at the time of diagnosis was 1080 +/- 267 microg/L in patients with macroadenoma and 155 +/- 38 microg/L in patients with microadenoma. In 10 patients, BRC normalized PRL levels and caused variable, but significant, tumor shrinkage. CV normalized PRL concentrations and reduced tumor size in 5 patients. Cabergoline normalized PRL concentrations in 7 of 10 patients resistant to CV. Pregnancy occurred in 2 patients while on treatment. Pregnancies were uncomplicated, and the patients delivered normal newborns at term. Only 4 patients are still moderately hyperprolactinemic. Impairment of other pituitary hormone secretion was documented at the time of diagnosis in 7 patients, 5 of whom underwent surgery. Four patients became GH deficient in adult age. In conclusion, the medical treatment with dopaminergic compounds is effective and safe in patients with prolactinoma with onset in childhood, allowing preservation of the anterior pituitary function.

Adolescent↗
PubMed1998

Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic males: a comparison with bromocriptine.

This study evaluated the effects of chronic treatment with cabergoline (CAB), a new, potent and long-lasting ergoline-derived dopamine agonist, on seminal fluid parameters and sexual and gonadal function in hyperprolactinemic males in comparison with the effect of bromocriptine (BRC) treatment. Seventeen males with macroprolactinoma were treated with CAB at a dose of 0.5-1.5 mg/week (n = 7), or BRC at a dose of 5-15 mg/day (n = 10) for 6 months. Baseline prolactin (PRL) was 925.7 +/- 522.6 microg/l in the CAB-treated group and 1059.4 +/- 297.6 microg/l in the BRC-treated group. All the patients suffered from libido impairment, ten from reduced sexual potency, and six had infertility. In five patients provocative bilateral galactorrhea was found. Seminal fluid analysis, functional seminal tests and penis rigidity and tumescence, measured by nocturnal penile tumescence (NPT) using Rigiscan equipment, were assessed before and after 1, 3 and 6 months of CAB or BRC treatment. Hormone profiles were assessed before and after 15, 30, 60, 90 and 180 days of both treatments. Before treatment, all patients had a low sperm count with oligoasthenospermia, reduced motility and rapid progression with an abnormal morphology and decreased viability, and a low number of erections. After 1 month, serum PRL levels were significantly reduced in both groups of patients (20.6 +/- 6.6 microg/l during CAB and 256.3 +/- 115.1 microg/l during BRC treatment) and were normalized after 6 months in all patients (CAB: 7.9 +/- 2.2 microg/l; BRC: 16.7 +/- 1.8 microg/l). After 6 months, a significant increase of number, total motility, rapid progression and normal morphology was recorded in patients treated with both CAB and BRC. An increase in the number of erections during the first 3 months of both treatments was noted by NPT. However, the improvements in seminal fluid parameters and sexual function were more evident and rapid in patients treated with CAB. The number of erections was normalized after 6 months of treatment in all patients submitted to CAB treatment, and in all patients but one treated by BRC. In addition, a significant increase of serum testosterone (from 3.7 +/- 0.3 to 5.3 +/- 0.2 microg/l) and dihydrotestosterone (from 0.4 +/- 0.1 to 1.1 +/- 0.1 nmol/l) was recorded. At the beginning of treatment, mild side-effects were recorded in two patients after CAB and mild-to-moderate side-effects in five patients after BRC administration. The treatment with CAB normalized PRL levels, improving gonadal and sexual function and fertility in males with prolactinoma, earlier than did BRC treatment, providing good tolerability and excellent patient compliance to medical treatment.

Adult↗
PubMed1998

Treatment of prolactinomas.

The objectives of the treatment of hyperprolactinaemia are to suppress excessive hormone secretion and its clinical consequences, to remove tumour mass, to preserve the residual pituitary function and to prevent disease recurrence or progression. Prior to the advent of pharmacotherapy, therapy usually consisted of surgical resection and/or pituitary irradiation. In microprolactinomas, trans-sphenoidal surgical resection normalizes prolactin (PRL) levels, restores normal menses and produces the disappearance of galactorrhoea in a great majority of patients, but normalization of serum PRL levels varies from 35-70%. In macroprolactinomas, trans-sphenoidal surgery is less successful with only 32% of patients appearing to be cured initially. However, the recurrence rate is 19%, and the long-term cure rate is only 26%. In more than 80% of the patients with microprolactinoma, suppression of PRL levels and tumour shrinkage can be achieved with bromocriptine therapy given at doses of 2.5-5 mg per day. In 5-10% of the patients, the appearance of side-effects (nausea, dizziness and postural hypotension) is a limiting factor in continuing the treatment. Dopaminergic compounds cause notable tumour shrinkage in most macroprolactinomas. Treatment with cabergoline, a selective and long-lasting dopamine 2-receptor agonist at weekly doses of 0.5-2 mg has been shown to be effective both in normalizing PRL levels and in inducing tumour shrinkage. Pharmacotherapy with dopamine (DA) agonists is an appropriate first-line treatment for both micro- and macroprolactinomas. Surgery should be recommended for those patients who are severely intolerant of or resistant to DA agonists.

Clinical Trials as Topic↗
PubMed1997

Usefulness of power Doppler in the diagnostic management of hypoechoic thyroid nodules.

Objective: The usefulness of power Doppler (PD), a new color Doppler ultrasonography technique, namely in the diagnosis and management of hypoechoic thyroid nodules in comparison with color Doppler (CD) is investigated in this study. Patients and methods: 157 hypoechoic thyroid nodules were studied by CD and PD. The distribution of vascular patterns was compared with the results obtained at cytology and/or histology. Results: Three characteristic PD patterns were found: type A=ring sign, defined as the perilesional vascular signal; type B=complex ring sign, subdivided into B1 for the perilesional and moderate intralesional vascular signal with regular vessels course and B2 for the perilesional and high intralesional vascularization, with anarchic structure and winding vessels course; C=delta sign, defined as a small vascular perilesional halo with a large afferent vessel and winding course and flow. All tumors, benign and malignant, showed a pattern type B2, except one which showed a pattern type C and another with a type B1. All the lesions with patterns A and B1 were hyperplasias. Forty-six hyperplastic lesions showed a pattern B2: in these cases the analysis of flow indices predicted the negative cytology. In fact, Doppler measurements showed that all 117 nodules with CD pattern type II and III had systolic peak velocity (Pv)<50 cm/s, 116/117 had resistance index (RI)</=0.75; all ten adenomas had Pv>50 cm/s and 9/10 had RI</=0.75; 7/10 carcinomas had Pv>50 cm/s and among these, four had RI>0.75 and two <0.75, while the patients with Pv<50 cm/s had RI>0.75. In this series of 157 thyroid nodules, both sensitivity and specificity of PD were higher than CD technique (95% versus 75% and 66.4% versus 38.7%). Conclusions: PD, when compared with CD allowed a more accurate characterization of hypoechoic thyroid nodules. Copyright 1997 Elsevier Science Ireland Ltd.

Journal Article↗
PubMed1997

Different sensitivity to sodium valproate in healthy, non-tumoral and tumoral hyperprolactinemic subjects.

GABAergic drugs affect PRL secretion in both rat and man. Sodium valproate (SV) inhibits GABA transaminase so increasing the endogenous GABAergic tone. The aim of this study was to evaluate the effects of SV at low and high doses on PRL release in healthy subjects and hyperprolactinemic patients. Fifteen patients with prolactinomas, 8 patients with non-tumoral hyperprolactinemia and 10 healthy subjects were studied: in non consecutive days, all subjects received placebo and SV at the dose of 400 and 800 mg po. Serum PRL levels were assessed 30, 15 and 5 min before and every 30 min for 4 hours after administration. SV at the dose of 400 mg induced a significant decrease of serum PRL in healthy subjects (p < 0.05), whereas no effect was noted in both tumoral and non-tumoral hyperprolactinemia. The administration of 800 mg SV induced a significant decrease of PRL levels in healthy subjects and in patients with non-tumoral hyperprolactinemia (p < 0.05). Conversely, in prolactinomas a paradoxical increase of serum PRL concentration (p < 0.05) was observed 120 min after the administration of the drug. These data confirm the inhibitory activity of SV on PRL release in healthy subjects, and suggest the existence of a partial resistance to GABA in non-tumoral hyperprolactinemia. In prolactinomas, the paradoxical PRL increase after high dose of SV suggests the existence of a complete pituitary resistance to GABA. This finding might be explained by the appearance of the stimulatory effect of GABA at hypothalamic level that could have been unmasked by the lack of pituitary GABA effects on adenomatous lactotrophs.

Adolescent↗