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A Bellastella

Publications and source records attributed to A Bellastella.

At least 19 recordsLinked to original sources
PubMed2006

Natural and synthetic retinoids in prostate cancer.

Prostate cancer (PCa) is the most common cancer for men in Europe, North America, and some parts of Africa. Initially, growth of prostate cancer is usually androgen-dependent, but often it becomes androgen-independent after androgen-deprivation therapy. Managing hormone-refractory prostate carcinoma remains a difficult challenge for clinicians. Retinoids, vitamin A and its synthetic analogs are one of the most studied class of chemopreventive drugs for PCa. Retinoids play a key role in several vital functions as vision and development, and also exert anti-proliferative actions. Anti-proliferative effects of retinoids rely on the regulation of many biological processes, including differentiation, cell proliferation, and apoptosis. Retinoid actions are mediated by two classes of nuclear proteins called retinoic acid (RARalpha,beta and gamma and retinoic alpha,beta and gamma receptors, which are ligand-regulated transcription factors. Effects of both all-trans-retinoic acid (RA), the natural active derivative of vitamin A, and its synthetic derivatives, on prostate gland or prostate cell lines implicate retinoids in the regulation of prostate growth and suppression of PCa development. Deficient retinoid availability and action at the cellular level because of either decreased content or altered metabolism in PCa cells can play a key role in abnormal cellular differentiation pathways, and the loss of anti-proliferative effects. Here we review the in vitro and in vivo effects of retinoids in PCa.

Animals↗
PubMed2005

Serum antibodies to collagen XIII: a further good marker of active Graves' ophthalmopathy.

OBJECTIVE: In Graves' ophthalmopathy (GO) intercellular adhesion molecule-1 (ICAM-1) is thought to play a key role in lymphocyte infiltration into the orbit, and serum levels of its soluble form are positively correlated to clinical activity score (CAS). Serum antibodies against collagen XIII (CollXIIIAb), a plasma membrane protein expressed at a low level in almost all connective tissue-producing cells, have been detected in GO, but their significance is unclear. The aim of this study was to search for CollXIIIAb in Graves' patients with and without ophthalmopathy and to correlate their levels with CAS and with serum soluble ICAM-1 (sICAM-1) values. PATIENTS: We studied 66 patients with Graves' disease whose sera had been previously tested for sICAM-1 levels, grouped as follows: 28 with moderate and active ophthalmopathy (group 1), 12 of them hyperthyroid (group 1a) and 16 euthyroid (group 1b); 13 with mild and inactive ophthalmopathy and normal thyroid function (group 2); 25 without ophthalmopathy (group 3), 11 of them hyperthyroid (group 3a) and 14 euthyroid (group 3b). Finally, 26 sera of normal controls were studied. MEASUREMENTS: CollXIIIAb were evaluated by an enzyme-linked immunosorbent assay (ELISA) method. RESULTS: In group 1 patients, CollXIIIAb were detected at high levels in 8/12 (66.6%) in group 1a [optical density (OD) ranging from 0.529 to 0.894] and in 10/16 (62.5%) in group 1b (OD 0.560-0.855). In group 2 patients, CollXIIIAb were detected but at low levels (OD 0.205-0.260) in 4/13 patients (30.7%). In group 3 patients, CollXIIIAb were present at low levels in 6/11 (54.5%) of group 3a and in 5/14 (35.7%) of group 3b (OD 0.215-0.290 and 0.144-0.245, respectively). CollXIIIAb were detected in only 4/26 normal controls (15%) but at low levels (OD 0.150-0.185). CollXIIIAb values in both groups 1a and 1b were significantly higher than those of the remaining groups. A positive correlation between CollXIIIAb levels and CAS but not thyroid hormone levels was found in groups 1a, 1b and 2. Moreover, a positive correlation between CollXIIIAb levels and sICAM-1-values was also evidenced in all three groups. CONCLUSIONS: Our results suggest that CollXIIIAb could be considered as a further good marker of active inflammatory processes involving the adipose connective tissue in GO. In particular, the high levels of CollXIIIAb in sera of Graves' patients with active ophthalmopathy could reflect an increased expression of type XIII collagen on the membrane of activated fibroblasts in these patients. Thus, the evaluation of these antibodies could be added to other known markers as a useful and inexpensive tool in monitoring Graves' patients and in modulating the treatment of GO.

Acute Disease↗
PubMed2005

Sexuality in aging male.

A high percentage of men aged 60 or older have satisfactory sexual activity, even if reduced sexual desire, frequency of intercourses and erections, impaired satisfaction with sex and difficulty with orgasm, and decreased semen volume frequently occur. The present report analyses the following issues: erectile dysfunction, fertility, the role of hormones in influencing libido and erection mechanisms, and the therapeutic strategies suggested.

Aged↗
PubMed2004

Genetic prenatal RET testing and pregnancy management of multiple endocrine neoplasia Type II A (MEN2A): a case report.

Multiple endocrine neoplasia 2A (MEN 2A) is an inherited dominant syndrome characterised by medullary thyroid carcinoma, adrenal pheochromocytoma and hyperparathyroidism due to specific RET proto-oncogene mutations. Fertile MEN 2A women are at risk of complicated pregnancy because of unrecognised pheochromocytoma and transmission of RET mutation to the progeny. This condition may cause psychological distress in affected pregnant patients and their families. Here we describe the genetic prenatal testing, the pregnancy management and obstetric outcome in a MEN 2A patient with a right side adrenal hyperplasia and elevated calcitonin levels, a condition suspicious for possible recurrence of pheochromocytoma. We confirm that maternal or fetal complications are rare when MEN 2A diagnosis is made before pregnancy and an accurate monitoring is instituted. Furthermore, our results indicate that prenatal testing for RET mutations is highly recommended in making decisions and assuring parents on the lifelong risk of tumors. This will avoid the psychological distress that can further complicate the pregnancy of affected women.

Adrenal Hyperplasia, Congenital↗
PubMed2004

Extraocular muscle antibodies and the occurrence of ophthalmopathy in Graves' disease.

OBJECTIVE: The aim of this study was twofold: first to investigate the presence of extraocular muscle antibodies (EMAb) in sera of Graves' patients with ophthalmopathy characterized by clinical extraocular muscle (EM) involvement; second to evaluate in Graves' patients without ophthalmopathy whether longitudinal variations of EMAb have a predictive role for the development of eye disease. PATIENTS: We evaluated sera of Graves' patients previously tested for G2sAb and FpAb; in particular, sera of 32 patients with moderate or severe ophthalmopathy and EM involvement: 18 with active disease (group 1), 14 with inactive disease (group 2). Moreover, we evaluated longitudinally sera of 19 Graves' patients without ophthalmopathy previously tested for anti-GS2 (G2sAb) and antiflavoprotein antibodies (FpAb; group 3). During the 18-month follow-up, four of them did not develop ophthalmopathy (group 3a), and 15 did: seven developed eye disease (group 3b) with clinical EM involvement. In particular, moderate disease and clinical activity score (CAS) >/= 4 in four of them, severe ophthalmopathy and CAS </= 1 in three were observed. The remaining eight patients showed moderate ophthalmopathy and CAS >/= 4 without EM involvement (group 3c). MEASUREMENTS: EMAb were evaluated in all samples by indirect immunofluorescence method. RESULTS: EMAb were detected in 13 out of 18 patients (72.2%) in group 1 (titre 1/32-1/128) and in five out of 14 patients (35.7%) in group 2 (titre 1/2-1/8). As regards to group 3, at the start of the study EMAb were detected in 13 out of 19 patients (72%) at titres 1/2-1/8; during the follow-up they became or persisted negative in all patients in group 3a, while they increased at titres ranging from 1/64 to 1/128 in all patients in group 3b before the onset of ophthalmopathy. Finally, in group 3c, four patients showed a mild increase (1/8-1/16) of EMAb before the onset of eye disease, while four patients were negative during the entire follow-up. CONCLUSIONS: Our results indicate that EMAb are a good marker of ophthalmopathy with EM involvement and their titre is higher in patients with active than in those with inactive disease. Thus, even if our results must be confirmed on a larger cohort of patients, the increase of EMAb in patients with Graves' disease could be considered as a risk factor for the development of ophthalmopathy with subclinical/clinical EM impairment. In this connection we propose the evaluation of EMAb, in Graves' patients with subclinical and clinical ophthalmopathy, as a simple and sensitive marker of the EM inflammatory process.

Acute Disease↗
PubMed2003

Verapamil inhibits interleukin-6 and vascular endothelial growth factor production in primary cultures of keloid fibroblasts.

An increased secretion of cytokines and growth factors has been hypothesised to play a role in the abnormal growth of keloid fibroblasts. The aim of this study was to evaluate the effect of the calcium antagonist verapamil on the interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) secretion, as well as on cellular growth, in primary cultures of fibroblasts derived from the central part of keloid lesions. These cells grew faster than peripheral keloid and nonkeloid fibroblasts, and, in long-term cultures, became stratified assuming a three-dimensional structure. Compared with peripheral and nonkeloid fibroblasts, central keloid fibroblasts presented an increased production of both IL-6 and VEGF (P<0.03 and P<0.005, respectively). Verapamil (100 microM) decreased IL-6 and VEGF production (P<0.03 and P<0.005, respectively) in central keloid fibroblasts cultures at 72 h. Moreover, verapamil decreased cellular proliferation by 29% and increased apoptosis to an absolute value of 8%. The results of this study demonstrate that in primary cultures of central keloid fibroblasts verapamil reduces the sustained basal IL-6 and VEGF production and inhibits cell growth; these data may offer the link with the beneficial effect of calcium antagonists on keloid scars in vivo.

Analysis of Variance↗
PubMed2003

Sexual differentiation.

In humans, like as in other mammals, the gonads, the internal genital ducts, and the external genital structures all develop from bipotential embryologic tissues. Male or female phenotype develops through a cascade of processes which initiate with sex determination and follow with sex differentiation. The karyotype (46, XY or 46, XX) of the embryo (genetic sex) determines whether primordial gonad differentiates into a testis or an ovary, respectively (gonadal differentiation). A Y-related gene, SRY, acts as a switch signal for testis differentiation. Testis development process involves several steps controlled by other non-OY-linked genes, such as Wilms tumor gene 1 (WT1), EMX2, LIM1, steroidogenic factor 1(SF-1), SRY box-related gene 9 (SOX9). Since other genes, such as Wnt-4 and DAX-1, are necessary for the initiation of female pathway in sex determination, female development cannot be considered a default process. Hormonal production of differentiated gonads is relevant for differentiation of the internal and external genitalia during fetal life, and for the development of secondary sex characteristics at puberty. Antimullerian hormone (AMH) secreted by Sertoli cells inhibits the development of female internal genitalia (tube, uterus, upper part of vagina); testosterone secreted by Leydig cells induces stabilization of wolffian ducts and development of internal male genitalia. Differentiation of external male genitalia requires the transformation of testosterone to dihydrotestosterone by 5alpha reductase type 2 expressed in genital skin and urogenital sinus. The effects of androgens occur in presence of functional androgen receptor (AR) protein. Mutations of genes coding for steroidogenic enzymes, AMH, AMH receptor, AR and 5alpha reductase are all associated with impairment of sex differentiation and result in genital ambiguity.

Embryonic and Fetal Development↗
PubMed2002

Eight parathyroid glands incidentally discovered during a surgical intervention for secondary hyperparathyroidism: an unusual clinical finding.

Here we describe the uncommon case of a Caucasian male with secondary hyperparathyroidism due to 8 parathyroid glands discovered in the course of a surgical exploration. The patient (age 49 yr) with a 21-yr history of chronic renal failure came to our observation in June 1999 complaining of depression, muscle weakness, bone and joint pain, movement hindrance. The biochemical evaluation evidenced low-normal serum calcium, high phosphorus and PTH levels. The symptoms and the biochemical findings were suggestive for secondary hyperparathyroidism. The neck US revealed an increase of thyroid gland volume with diffuse hyperechogenity; two nodules of 20 and 25 mm as maximum diameter were found in the thyroid parenchyma, while 4 hypoechogenous nodules (maximum diameter ranging from 13.0 to 30.0 mm) with clean borders and anechogenous areas inside were evidenced in the rear side of the thyroid lobes. The parathyroid scan with 99mTc and 201 Tl demonstrated increased uptake bilaterally in the inferior side of the neck. The patient underwent a total parathyroidectomy with near total thyroidectomy in November 1999. Histological examination of surgical specimen evidenced 6 hyperplastic parathyroid glands in back side of the 2 lobes (3 on the right and 3 on the left), and the examination of the thyroid gland showed 2 hyperplastic parathyroids (5 mm and 15 mm maximum diameter) into the 2 nodules previously evidenced by US. The physiopathological and clinical and therapeutic implications of this observation are discussed.

Adult↗
PubMed2002

Longitudinal study of vasopressin-cell antibodies and of hypothalamic-pituitary region on magnetic resonance imaging in patients with autoimmune and idiopathic complete central diabetes insipidus.

Diagnosis of autoimmune central diabetes insipidus (CDI) is based on the presence of autoantibodies to AVP-secreting cells (AVPcAb) or the coexistence of other autoimmune polyendocrine syndromes; moreover, it can be also suggested by the presence of lymphocytic infundibulo-neurohypophysitis, evidenced by biopsy of pituitary stalk and/or by pituitary stalk thickening on magnetic resonance imaging (MRI). However, so far, in clinical CDI patients with lymphocytic infundibulo-neurohypophysitis, AVPcAb have not been investigated and in those with or without autoimmune polyendocrine syndromes (APS), longitudinal studies on the behavior of AVPcAb alone, or of both AVPcAb and hypothalamic pituitary imaging on MRI are lacking. Aim of this work was to investigate in these patients the occurrence of AVPcAb (by indirect immunofluorescence) and of pituitary stalk thickening (by MRI) and their longitudinal changes during a follow-up period. We studied 22 patients, aged 29-53, with APS and complete CDI, grouped as follows: 10 with recent onset (< or =1.5 yr) of CDI (group 1a) and 12 with CDI of long-term duration (> or = 7 yr) (group 1b); moreover, a group of 13 patients with apparent idiopathic CDI of recent onset (<1.5 yr) were studied. They were divided, on the basis of the detection of AVPcAb as follows: 5 AVPcAb positive patients (aged 19-26) classified as isolated autoimmune CDI (group 2) and 8 AVPcAb negative patients (aged 21-26), classified as true idiopathic CDI (group 3). All patients were evaluated yearly, along 5 yr, for AVPcAb and for hypothalamic-pituitary region imaging. At study entry, 8/10 (80%) of patients in group 1a and 7/12 (58.3%) in group 1b were positive for AVPcAb and persisted positive subsequently, during all the follow-up period, even if at lower titers. All patients in group 2 were positive and all those in group 3 were negative for AVPcAb and persisted positive and negative, respectively, for all the follow-up study. Among the AVPcAb-positive patients, only 5 in group 1a and 2 in group 2 showed also pituitary stalk thickening at the first observations, which however spontaneously disappeared subsequently indicating a possible lymphocytic infundibulo-neurohypophysitis. All patients in the studied groups showed loss of the hyperintense signal of the neurohypophysis on MRI at entry and during all the follow-up period. Results of this longitudinal study suggest: 1) AVPcAb, frequently present at high titers in recent phases of CDI, persist subsequently, even if at lower titers, several years after the onset of disease. 2) The occurrence of a lymphocytic infundibulo-neurohypophysitis suggested by the pituitary stalk thickening on MRI only in patients positive for AVPcAb confirms a further autoimmune variant of CDI also in these cases. 3) The longitudinal behavior of patients in group 3 suggests that the absence of AVPcAb at the onset of clinical idiopathic CDI is able to exclude a subsequent appearance of these antibodies and consequently an autoimmune involvement in CDI of these patients. Instead the finding of AVPcAb in several patients with only CDI, thought at first clinical observation as idiopathic, indicates that the prevalence of autoimmune CDI must be considered much higher than that so far reported.

Adult↗
PubMed2001

Estrogen receptor beta expression in human prostate tissue.

Estrogen receptor subtype beta (ERbeta) is highly expressed in rat prostate epithelium, but its presence in human prostate needs to be confirmed. Here we investigated the expression of ERbeta in five benign (normal and/or hyperplastic) and 10 malignant (Gleasons' score 2-7) prostate tissue specimens using immunohistochemistry. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections, using a commercially available ERbeta polyclonal antibody developed against the C-terminal amino acid residue. Nuclear ERbeta expression was found in the nuclei of glandular epithelium of benign prostate tissue specimens; faint nuclear ERbeta positivity was also present in a few stromal cells around normal epithelium. Nuclear ERbeta specific immunostaining was undetectable in all prostate cancer sections.

Animals↗
PubMed2001

Assessment of pituitary gonadotropin release to gonadotropin releasing hormone/thyroid-stimulating hormone stimulation in women with systemic sclerosis.

OBJECTIVE: To evaluate basal and dynamic levels of pituitary gonadotropin release in female systemic sclerosis (SSc) patients of childbearing age and in post-menopausal SSc patients. METHODS: We performed stimulation tests for gonadotropin-releasing hormone (GnRH) and thyroid-stimulating hormone (TRH) during the early follicular phase in 12 women of childbearing age [mean age (S.E.M.) 34.8 (2.4) yr] with SSc to determine serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin. Blood samples were also obtained from six post-menopausal women with SSc [mean age 46.8 (2.4) yr], after TRH stimulation; only serum prolactin concentration was determined, because elevated basal concentrations of FSH and LH were expected. Hormone concentrations were estimated by radioimmunoassay. Comparisons were made with healthy control women matched for age and reproductive status. RESULTS: In SSc patients of childbearing age, basal FSH, LH and oestradiol (E(2)) levels were not significantly different from those in controls, whereas basal prolactin concentration was significantly higher than in controls (P=0.0001). After the stimulation test, the peak concentrations of FSH (P=0.0001) and prolactin (P<0.0001) were significantly higher than in controls. The net integrated response curves [net area under the curve (AUC)] for FSH and LH did not differ significantly between SSc patients and controls. On the contrary, the net AUC for prolactin in response to TRH stimulation was significantly higher than in controls (P=0.001). In post-menopausal patients, basal E(2), FSH, LH and prolactin levels were not significantly different between women with SSc and controls. However, after TRH stimulation, peak levels and net AUC for prolactin were not significantly higher in patients than those in controls. No significant correlations were found between basal and stimulated FSH, LH and prolactin levels and the severity of involvement of various organ systems. Multiple regression analysis showed that basal and stimulated prolactin concentrations were associated with skin sclerosis and peripheral vascular and lung involvement. CONCLUSION: Our results suggest that subclinical primary hypogonadism can occur in SSc patients. They also confirm an alteration in the mechanism for prolactin secretion and release, which may not only contribute to further disturbance of the reproductive axis but may also have an influence on the disease.

Adult↗
PubMed2001

Time course of 21-hydroxylase antibodies and long-term remission of subclinical autoimmune adrenalitis after corticosteroid therapy: case report.

Subclinical Addison's disease is characterized by the presence of adrenal autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21OHAb) with or without adrenal function failure. In our previous longitudinal study some patients with high titers of ACA and at stage 2 of subclinical adrenocortical failure showed disappearance of ACA with recovery of normal adrenocortical function after corticosteroid treatment for Graves' ophthalmopathy. To investigate whether corticosteroid-induced modification of the adrenal autoimmune markers can also involve 21OHAb and to evaluate whether the remission of subclinical adrenocortical failure can persist over a long period of time, we followed-up for 100 months the levels of 21OHAb and ACA as well as the metabolic markers of adrenal function in one patient with Graves' ophthalmopathy and at stage 2 of subclinical adrenocortical failure before and after corticosteroid therapy. A 34-yr-old woman with Graves' disease and active ophthalmopathy who was found to be positive for ACA and to have high PRA, low aldosterone levels, and normal basal ACTH and cortisol levels, but impaired cortisol response to ACTH was studied. The patient was treated with oral corticosteroid therapy for 6 months. After corticosteroid therapy, 21OHAb, initially positive, became negative in concomitance with the disappearance of ACA and the restoration of normal adrenal function. The disappearance of both 21OHAb and ACA and their prolonged absence during the follow-up suggest that corticosteroid treatment can induce long-term remission of subclinical adrenal insufficiency and prevent the onset of the clinical phase of the disease. Our pilot study may pave the way to future trials aimed at preventing the onset of the clinical signs of Addison's disease in ACA/21OHAb-positive patients.

Adrenal Cortex Diseases↗
PubMed2001

Loss of estrogen receptor beta expression in malignant human prostate cells in primary cultures and in prostate cancer tissues.

The aim of this study was to investigate the expression of estrogen receptor (ER) beta and alpha genes in normal (N) and malignant (C) primary cultures of human prostate epithelial cells (PEC) and fibroblasts (PFC) and in the prostate tissue donors. Both ERbeta and ERalpha messenger ribonucleic acids were found by RT-PCR analysis in six NPECs and normal prostate tissues and in only one of six CPECs and in the respective cancer tissue donor. The other five CPECs and related cancer tissue donors and all normal and cancer PFCs expressed ERalpha messenger ribonucleic acid alone. Immunoblot analysis, using a polyclonal anti-ERbeta (C-terminal) antibody, demonstrated ERbeta protein in all NPEC lysates and in one of the six CPECS: ERalpha protein was expressed in both NPECs and CPECs when a polyclonal antibody directed against the ERalpha N-terminal domain was used. In contrast, ERalpha protein was not detected in two of the six CPEC lysates when ERalpha C-terminal monoclonal antibodies were used. Using a set of primers designed to amplify the region from exons 6-8, RT-PCR analysis demonstrated the absence of the expected transcript in these cells. The present study shows that the ERbeta gene is expressed together with ERalpha in normal prostates and NPECs, whereas it is barely detectable in prostate cancer and CPECS: Moreover, in some CPECs, the ERalpha gene may be transcribed in a changed protein, resulting from the expression of a deletion variant. Together, these data suggest that prostate malignancy is associated with a potential disorder of ER-mediated pathways.

Blotting, Western↗
PubMed2001

[Somatostatin and somatostatin receptors in the prostate].

Somatostatin (st) exerts a role in the control of prostate growth and function acting both at hypothalamus-hypophysis level and at glandular level. St analogues have been used to control prostate cancer (CaP) in clinical trials, with contradictory results. These data may be interpreted on the basis of st mechanism of action and tissue distribution of the five st receptors (sst1-5). Sts have been found in prostate tissue and, specifically, in the epithelial component. sst2 is preferentially expressed on normal prostate, sst1 and sst5 on CaP. st inhibits the proliferation of LNCaP and octreotide normal prostate epithelial cells in primary cultures. The lack of sst2 in CaP may explain the ineffectiveness of some selective st analogues in clinical trials. The use of other analogues actually developed with high affinities to ssts expressed mainly in CaP may represent a more rational approach.

Adenocarcinoma↗
PubMed2001

[Somatostatin receptor genes expression and effects of octreotide on orbital fibroblasts from Graves' ophthalmopathy].

BACKGROUND: Recent data demonstrated that somatostatin (SRIH) analogues octreotide is effective in Graves' ophthalmopathy (GO), but their mechanism of action in GO is still unclear. In this study we investigated the expression of SRIH receptor (sst1-5) genes and the effect of octreotide treatment on primary cultures of fibroblasts established from retroorbital tissue of GO patients and of control subjects. METHODS: Retro-orbital connective tissue was obtained from 10 patients with GO and from 6 control subjects undergoing eye surgery. Fibroblasts were established in MEM with 5-10% FCS. The expression of sst1-5 genes was studied by RT-PCR using specific primers and GAPDH as internal control. Cells were treated with octreotide (10-8M, 10-9M) for 48-72-96 h to evaluate cell growth by MTT, cAMP accumulation by RIA and apoptosis by TUNEL techniques. RESULTS: All primary cultures expressed one or more ssts genes that have a high affinity for the two analogues (class 1 sst). The sst2 transcript was found in 9, sst3 in 5 and sst5 in 8 out of 10 GO cell cultures. sst2 was detected in all 6, and sst3 in 4 of the 6 control cell cultures. Octreotide (10-6 and 10-7M) significantly inhibited cell growth (p<0,01-0,05), significantly decreased forskolin-induced-cAMP accumulation, and determined apoptosis (10-18%). CONCLUSIONS: Our study demonstrated that sst transcripts are expressed and functional in cultured retroorbital fibroblasts. The presence of class 1 sst in GO tissue and the inhibition exerted by octreotide on retroorbital cell growth and activity in vitro may account for the effects of SRIH analogue administration in vivo in GO.

Apoptosis↗
PubMed2000

Postintervention serum TSH levels may be useful to differentiate patients who should undergo levothyroxine suppressive therapy after thyroid surgery for multinodular goiter in a region with moderate iodine deficiency.

Recent studies have raised doubts about the efficacy of the postoperative use of levothyroxine (LT4) suppressive doses in patients who underwent thyroid surgery for multinodular goiter. The purpose of this retrospective study was to examine the efficacy of different doses of LT4 in preventing postsurgical recurrences of simple multinodular goiter and to identify a marker that could be useful in discriminating patients with a higher risk of developing recurrence. Two hundred thirty-two patients (57 male, 175 female) operated for nontoxic multinodular goiter were divided into two groups: (I) patients with normal postsurgery thyrotropin (TSH) levels (0.25 to 4.5 mU/L) and (II) patients with elevated postsurgery TSH levels (>4.5 mU/L). All patients were subjected to replacement (1.3 microg LT4/kg/day) or suppressive (1.7 microg LT4/kg/day) doses of LT4, and they were followed for a median period of 6 years (range 2 to 12). No statistical difference was found for sex, age, and postsurgery serum TSH between patients submitted to suppressive and replacement therapy. The ultrasound (US) detection of new postsurgery nodules of at least 0.5 cm maximum diameter was considered a recurrence of disease and was found in 10% of the cases studied. Patients with normal postsurgery serum TSH showed a high recurrence rate (30.4%) when submitted to lower daily doses of LT4. In patients with elevated postsurgery serum TSH, the rate of nodular goiter recurrence did not vary with different types of LT4 therapy. In conclusion, our results suggest that the postsurgical serum TSH is useful for prediction of nodular goiter recurrence, as it reflects the amount of residual functioning thyroid tissue in the cervical area. It may also be indicative of patients who might benefit from LT4 suppressive therapy.

Adult↗
PubMed2000

Recombinant growth hormone (GH) therapy in GH-deficient adults: a long-term controlled study on daily versus thrice weekly injections.

Currently, replacement recombinant GH (rGH) therapy in GH-deficient (GHD) adults is performed in daily injections. This modality of treatment is not complied with by the totality of GHD patients, who are supposed to receive life-long replacement. The aim of our study was to compare daily vs. thrice weekly (TIW) rGH injection effects on lipid profile, body composition, bone metabolism, and bone density in 34 GHD patients (13 women and 21 men; median age, 39 yr; range, 30-55 yr) randomly assigned to different therapeutic regimens. Group A included 18 patients receiving daily rGH injections, and group B included 16 patients receiving TIW injections of rGH. The starting dose of rGH was 10 microg/kg x day in both groups. Subsequently, the dose was adjusted to maintain serum insulin-like growth factor I (IGF-I) concentrations in the normal age-adjusted range. IGF-I levels were assessed before and after 1, 3, 6, and 12 months of rGH treatment, and lipid profile, body composition, bone metabolism, and bone density were evaluated before and after 6 and 12 months of treatment. Thirty-four healthy subjects served as controls. In the basal condition, lipid profile, body composition, bone metabolism, and bone density were significantly different in patients compared to controls. Conversely, patients included in groups A and B had similar serum IGF-I levels, lipid profile, body composition, bone metabolism, and bone density. After 3 months of rGH treatment, IGF-I levels were normalized in 15 of 18 patients (83.3%) in group A and in 7 of 16 patients (43.7%) in group B (chi2 = 4.21; P = 0.04). At this time point, serum IGF-I levels in patients in group A (202+/-57.5 microg/L) were significantly higher than those in patients in group B (155+/-45.1 microg/L; P = 0.001). After 6 months of therapy, serum IGF-I levels were normalized in all patients and were similar in both groups (223+/-35.2 vs. 212+/-41.4 microg/L, A vs. B, respectively). IGF-I levels remained normal until the 12-month follow-up. After 6 months of rGH replacement, total cholesterol, low density lipoprotein cholesterol, triglycerides, bioelectrical impedance, and body fat mass were significantly reduced, whereas high density lipoprotein cholesterol levels and lean body mass were significantly increased in both groups of patients, without any difference between them. No further change in lipid profile and body composition was observed after 12 months of treatment. Serum bone GLA protein and procollagen III levels were significantly increased after 6 months, and a downward trend was observed after 12 months of rGH replacement. However, a slight, but significant, increase in bone mineral density was observed in both groups only after 12 months (P = 0.0001). All patients in group B had good compliance to the TIW treatment, whereas 5 patients in group A had poor compliance to the treatment (chi2 = 3.2; P = 0.07). In conclusion, our randomized, prospective, and controlled study confirmed that rGH therapy with TIW injection regimen is effective in normalizing IGF-I levels and improving lipid profile, body composition, bone metabolism, and bone density. It also demonstrated that this efficacy is comparable to that observed in patients treated with daily rhGH therapy, with few side-effects and good compliance.

Adult↗