Search PubMed⌕ Search

Biomedical subjects

D Pasquali

Publications and source records attributed to D Pasquali.

At least 19 recordsLinked to original sources
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↗
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

Loss of oestrogen receptor beta, high PCNA and p53 expression and aneuploidy as markers of worse prognosis in ovarian granulosa cell tumours.

AIMS: Ovarian granulosa cell tumour (OGCT) is a sex-cord stromal tumour with a general trend toward late relapse and/or metastasis. However, mortality rate corrected for long-term follow-up shows that about 50% of patients die within 20 years of diagnosis. Classical clinicopathological parameters are unable to predict the biological behaviour of OGCT. The involvement of a recently characterized subtype of oestrogen receptor, ERbeta, in ovarian carcinogenesis has been hypothesized. METHODS AND RESULTS: We examined by immunohistochemistry the expression of ERbeta, proliferating cell nuclear antigen (PCNA) and p53 in a selected series of 30 OGCT, to evaluate their role in the prognostic evaluation of this tumour. Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections. Results were compared with the DNA-ploidy of the tumours (evaluated by image analysis) and with the follow-up data of the patients. CONCLUSIONS: Loss of ERbeta expression, high PCNA expression and aneuploidy, characterized a subgroup of OGCT with a worse outcome. The identification of a high-risk subclass of OGCT may be of primary importance in addressing appropriate therapeutic strategies, offering the chance to prevent relapses and metastases by using adjunctive, specifically targetted, more aggressive therapies.

Adolescent↗
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↗
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

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

Sodium butyrate/retinoic acid costimulation induces apoptosis-independent growth arrest and cell differentiation in normal and ras-transformed seminal vesicle epithelial cells unresponsive to retinoic acid.

Retinoic acid (RA) and sodium butyrate (NaB) are regulators of cell growth and differentiation. We studied their effect on normal (SVC1) or v-Ki-ras-transformed (Ki-SVC1) rat seminal vesicle (SV) epithelial cell lines. The treatment of these cells with 10(-((7( M RA did not produce significant changes in the morphological and biochemical parameters analyzed. When RA was used in combination with 2 mM NaB, the treatment induced substantial morphological changes, apoptosis-independent growth arrest, up-regulation of tissue transglutaminase (tTGase), and down-regulation of beta and gamma RA receptor (RAR) mRNA expression. The same cells did not express RAR alpha either before or after NaB/RA treatment. A similar treatment did not change the amount of mRNA coding for the protein SV-IV (a typical differentiation marker of the SV epithelium) in normal or ras-transformed cells nor the level of v-Ki-ras mRNA in Ki-SVC1 cells. These findings suggest that a defective RA/RARs signaling pathway is probably the biochemical condition that underlies the unresponsiveness to RA of our in vitro culture system, and indirectly points to the possibility that the NaB/RA-induced effects were brought about by a cooperation at the transcription level between the histone deacetylase inhibitory activity of NaB and the ability of RA/RAR to modulate the expression of various genes involved in the control of cell growth and differentiation.

Animals↗
PubMed2000

Somatostatin receptor gene expression and inhibitory effects of octreotide on primary cultures of orbital fibroblasts from Graves' ophthalmopathy.

To explore the mechanism underlying the effects of the somatostatin (SST) analogue octreotide in Graves' ophthalmopathy (GO), we investigated the expression of SST and of SST receptor (sst(1-5)) genes in primary cultures of fibroblasts established from retroorbital tissue of GO patients and of control subjects. We determined also SST specific binding sites by competitive binding of [(125)ITyr(11)]SST-14 and the effect of octreotide on cell growth, cAMP accumulation, Bcl-2 intracellular levels and apoptosis in GO fibroblast primary cultures. All primary cultures expressed the SST gene transcript and one or more ssts that have a high affinity for the two analogues (class 1 sst. The sst(2) transcript was found in nine, sst(3) in five and sst(5) in eight out of ten GO cell cultures. Sst(2) was detected in all six, and sst(3) in four out of the six control cell cultures. Sst(4) was absent from all samples, and sst(1) was found only in six out of the ten GO samples. SST-14 and octreotide inhibited the binding of [(125)I-Tyr(11)]SST-14 with a half-maximal inhibition of binding (IC(50)) of 0.80+/-0.37 and 33. 7+/- 33.1 nmol/l respectively in GO cell cultures, and with an IC(50) of 0.9 and 1.5 nmol/l in control cultures. Octreotide (10(-6) and 10(-7) M) significantly decreased (P<0.001) forskolin-induced but not basal cAMP accumulation; at both doses for 72 h it inhibited cell growth (20 and 55% respectively), and induced apoptosis (20 and 40%), and abolished Bcl-2 protein in cell lysates. In conclusion, SST and 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 SST analogue administration in vivo in GO.

Apoptosis↗
PubMed1999

A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene.

We report a novel case of multiple endocrine neoplasia type 2A (MEN 2A) associated with two mutations of the protooncogene RET. One affects codon 634 and causes a cysteine to arginine substitution; the second at codon 640 causes an alanine to glycine substitution in the transmembrane region. The two mutations were present on the same RET allele and were detected in germline and tumor DNA. Both mutations were de novo, i.e. they were not found in the DNA of the parents or relatives. Immunohistochemical and RT-PCR analysis showed that the pheochromocytoma expressed calcitonin as well as both RET alleles. A cell line established from the tumor and propagated in culture sustained the expression of RET and calcitonin, as did the original pheochromocytoma. Because the patient presented with medullary thyroid carcinoma and pheochromocytoma without parathyroid gland involvement, we speculate that this clinical picture could be correlated with the two RET mutations and to the unusual calcitonin production. This is the first report of a MEN 2A case due to two mutations of the RET gene and associated with a calcitonin-producing pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1999

Changes in tissue transglutaminase activity and expression during retinoic acid-induced growth arrest and apoptosis in primary cultures of human epithelial prostate cells.

We treated primary epithelial cells from human normal prostate (NEPC) and prostate cancer (CEPC) with all-trans-retinoic acid (RA) to study whether it regulates the activity of tissue transglutaminase (tTGase), an enzyme that accumulates in cells undergoing apoptosis. tTGase activity was assessed by [14C]spermidine incorporation; tTGase, P53, Bcl-2, and p21 protein levels were evaluated by Western blotting; and RA receptors (RAR alpha, -beta, and -gamma), tTGase, retinol-binding protein (RBP), and cellular RBP type I transcripts were determined by semiquantitative RT-PCR. After 72-96 h of 10(-6) mol/L RA treatment, cell growth inhibition and apoptosis were associated with increased tTGase activity in both NEPC and CEPC, and with increased tTGase protein and messenger ribonucleic acid levels only in NEPC. Moreover, RA down-regulated RAR alpha and -beta and increased RBP messenger ribonucleic acid levels in NEPC, whereas it increased RAR beta gene expression and decreased Bcl-2 protein levels in CEPC. Our results suggest that RA induces tTGase gene expression and enzyme activity in normal prostate cells, and that RA-regulated pathways are impaired in cancer cells. Moreover, down-regulation of Bcl-2 protein and up-regulation of RAR beta suggest that retinoid may act on the genetic defect responsible for prostate cancer progression.

Apoptosis↗
PubMed1998

Endocrine secretions under abnormal light-dark cycles and in the blind.

Both endogenous and exogenous factors are involved in regulation of endocrine secretions. Among the exogenous ones, light plays an important role both in animals and in humans. Pineal gland mediates light action on the endocrine system, by means of variations of melatonin (MT) secretion. Here we discuss about the influence of abnormal light-dark cycles and in particular of blindness on pineal and pituitary secretions and on those of correlated glands. MT secretion is usually inhibited by light: thus it reaches the highest levels at night. Exposure to short or long photoperiod causes variations in circadian or infradian MT rhythmicity. Blind patients can show higher daytime levels with a phase-advanced or phase-delayed circadian rhythm. Lack of light stimulus affects cortisol rhythm shifting the zenith of secretion and inducing a free-running rhythm. Blindness can abolish nocturnal growth hormone (GH) peak and impair the GH response to some stimuli; moreover it impairs the growth of affected patients. Light stimulus influences favorably gonadal function both in animals and in man. In animals, sexual activity and gonadal function decline during the seasons with reduced luminosity. A similar finding has been described in women living in a region with a strong seasonal contrast in luminosity. Blindness can impair luteinizing hormone, follicle-stimulating hormone, prolactin and testosterone secretion in prepubertal boys causing pubertal delay or more severe hypogonadism; it can affect pubertal development and fertility in women. Light can influence thyroid function in animals. Lack of light stimulus in blind man seems to cause different effects on thyroid function before and after puberty. Increase of free thyroid hormone levels has been found in prepubertal but not in adult blind patients, probably due to a resetting of the threshold for thyrotropin feedback suppression after puberty in these patients.

Animals↗
PubMed1998

Pituitary deficiency and lack of gonads in an XY pseudohermaphrodite with beta 39/lepore haemoglobinopathy.

We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudohermaphrodite subject affected by beta-thalassemia. The patient, reared as female, diagnosed at 14 months of age as having a beta 39/Lepore hemoglobinopathy, treated with multiple transfusion therapy, was referred at age of 15 years because of delayed puberty. Complete endocrine evaluation showed low levels, both basal and after combined LHRH-TRH and hCG stimuli, of FSH, LH, TSH, estradiol (E2), testosterone (T), progesterone (P), androstenedione (A), and FT4 levels, and normal PRL, cortisol, 17OHP and ACTH levels. Imaging studies (ultrasound, magnetic resonance, radioisotope scanning and gonadal vessels phlebography) did not show internal genitalia and gonads. Karyotype resulted 46,XY. PCR amplification of the SRY gene confirmed the presence of the Y chromosome. Female genitalia without uterus in a subject with Y chromosome SRY gene, and no detectable testes indicate a condition of male pseudohermaphroditism associated with testicular regression. Low gonadotropin and sex steroid levels are suggestive of combined acquired hypothalamic-pituitary and gonadal impairment, due to iron deposition in both organs. We cannot exclude congenital failure of testosterone synthesis and action in this case, because lack of gonads is an unusual finding in thalassemic hypogonadic subjects.

Adolescent↗
PubMed1998

Antisperm antibodies in cryptorchidism before and after surgery.

PURPOSE: We verified the prevalence of serum antisperm antibodies at diagnosis in a large group of cryptorchid boys, and determined whether it may be influenced by orchiopexy. MATERIALS AND METHODS: We prospectively evaluated serum antisperm antibodies in 186 and 23 boys 0.67 to 14.25 years old with unilateral and bilateral cryptorchidism, respectively, before, and 3, 12 and 24 months after surgery. At diagnosis Tanner stage was 1 and 2 or 3 in 188 and 21 cases, respectively. During the 2-year followup 23 boys entered puberty. A total of 111 normal prepubertal (Tanner stage 1) and 54 pubertal (Tanner stage 2 or 3) boys served as controls. Antisperm antibodies were detected using the tray agglutination and indirect immunobead tests. RESULTS: At diagnosis 29 cryptorchid boys (13.8%) were antisperm antibody positive, including 21 of the 188 prepubertal (11.1%) and 8 of the 21 pubertal (38%) boys (significantly different, chi-square test p <0.001). In 27 cases the tray agglutination test was positive with titers between 1:16 and 1:512, in 18 the indirect immunobead test was positive for IgG with titers between 1:10 and 1:100, and in 16 both tests were positive. There was no statistical difference when antisperm antibody results were analyzed for unilateral and bilateral cryptorchidism or testis location. All normal boys were antisperm antibody negative. During the 2-year followup antisperm antibodies appeared in 1 previously negative case, and the antibody titer increased to 128 to 512 in the tray agglutination and to 1:100 in the indirect immunobead tests in 4 positive cases. In all of these cases pubertal changes were also observed. CONCLUSIONS: Our study indicates that cryptorchidism may elicit an autoimmune response against sperm antigen in childhood independent of testis location and orchiopexy. Moreover, patients of pubertal age appear to be at higher risk for antisperm antibody development.

Adolescent↗
PubMed1997

Twenty-four hour melatonin pattern in acromegaly: effect of acute octreotide administration.

We investigated the melatonin (MT) circadian rhythm before and after somatostatin (octreotide) acute administration in ten subjects (4 M, 6 F. 23-52 yr old) with active acromegaly due to pituitary microadenoma. Blood samples were drawn every 2 hours over a 48-h span; after 24-h basal blood collection, octreotide (Sandostatin, Sandoz) 100 micrograms sc/8 h was administered. As control, 7 healthy adult subjects (3M, 4F; 26-50 yr old) were studied in basal condition over a 24-h span. Plasma MT and GH levels were measured by RIA in each sample, IGF-1 levels were measured by immunoradiometric assay in basal and after octreotide morning samples. The comparisons were made by Mann-U-Withney and Wilcoxon test as appropriate; the existence of a MT circadian rhythm was validated by cosinor analysis; GH and MT values were correlated by Pearson's correlation coefficient. All of 7 control subjects and 2 of 10 acromegalics had significant 24-h MT rhythm. The area under curve (AUC), mesor and amplitude of the MT rhythms in acromegalics were significantly lower than in the controls (p < 0.001, 0.002 and 0.0006, respectively), with an earlier acrophase (median value: 22:14 vs 02:08 h of controls). Basal plasma IGF-1 levels and circadian GH concentrations were significantly increased in acromegalics in comparison with the control group. Octreotide administration significantly reduced GH, restoring a circadian MT rhythm in 5 of 10 acromegalics, with MT mean mesor and AUC not different from controls. Mean amplitude still remained lower than controls (p < 0.0006), with an earlier acrophase (median 00:01 h). No significant correlation was found between individual GH and MT levels. Our data indicate a reduction of MT circadian secretion in acromegaly, due especially to a blunted nocturnal increase with earlier MT peak; moreover, acute octreotide administration increase MT levels without modifying amplitude and phase of night-time secretion significantly. These findings suggest a negative interrelationship between GH and MT secretions or a facilitatory influence of somatostatin on daytime MT release only. This partial recovery of pineal secretion after octreotide in acromegalics could be a clinically significant contribution to improve their quality of life, considering that MT is involved in the regulation of several important functions.

Acromegaly↗