Donatella Cortelazzi - Academia.edu (original) (raw)

Papers by Donatella Cortelazzi

Obstetrical & Gynecological Survey, 1995

Effects of long-term treatment with the gonadotropin-releasing hormone analog nafarelin in patien... more Effects of long-term treatment with the gonadotropin-releasing hormone analog nafarelin in patients with non\x=req-\ functioning pituitary adenomas. Eur J Endocrinol 1994;130:339\p=n-\45. ISSN 0804\p=n-\4643 The supposed origin of non-functioning pituitary adenomas (NFPA) from gonadotrophs prompted us to investigate the effects of the gonadotropin-releasing hormone (GnRH) analog nafarelin on hormonal and tumoral parameters in eight patients with NFPA, previously unsuccessfully operated and all hypogonadal. Nafarelin was administered intranasally for 1 year to all patients. Four patients received a dose of 1200 \g=m\g/day; the remaining four received 800 \g=m\g/day for 3 months, which was subsequently increased to 1200 \g=m\g/day. Basal gonadotropin and \g=a\-subunit (\g=a\SU)levels were low\p=n-\normal. In four patients (nos. 1,2,3,5) nafarelin significantly lowered luteinizing hormone (LH) levels, and also folliclestimulating hormone (FSH) in three of them (nos. 1,2,3). Persistent FSH stimulation occurred in three patients (nos. 6,7,8), with a transient slight LH increase only in patient no. 8. In one patient (no. 7), \g=a\SU levels were persistently stimulated. Hormonal responses to an acute GnRH test during nafarelin administration were generally blunted when compared to the pretreatment responses. Immunofluorescence results, obtained before treatment in five adenomas (nos. 2,3,4,6,7), had been as follows: positive for FSH-\g=b\ in all; negative for LH-\g=b\ in all, except a few positive cells in case no. 4; positive for \g=a\SU in three (nos. 2,3,7). No changes of visual field and tumor size occurred in any patient during treatment. However, one patient who showed a persistent increase in FSH levels exhibited left palpebral ptosis after 12 months of therapy and underwent a second transsphenoidal surgery. In conclusion: NFPA behave heterogeneously in terms of hormonal responses to GnRH analog therapy; long-term nafarelin treatment was unsuccessful in reducing the size of NFPA; and stimulation rather than inhibition of gonadotropin levels may suggest discontinuance of GnRH analog therapy in NFPA.

In order to evaluate the role of thyroid hormones on myocardial collagen synthesis we studied the... more In order to evaluate the role of thyroid hormones on myocardial collagen synthesis we studied the echoreflectivity of left ventricular wall in 6 hyperthyroid patients (fT3 = 21.7 \ub1 8.1 pmol/l) and 4 hypothyroid patients(fT3 = 2.9 \ub1 1.1 pmol/l), aged 38 \ub1 19 years, with recent (20 @? 90 days) symptoms of thyroid dysfunction, matched with 7 euthyroid controls (fT3 = 6.1 \ub1 0.8 pmol/l). The echo patterns were assessed by analyzing standard two-dimensional long-axis echocardiograms digitized off-line (standard TV phase alternation line) onto a personal computer, color-coded at 256 levels. The region for the analysis (5 x 5 mm) was set at end diastole in each patient in the mid portion of the interventricular septum. For each selection a color-level histogram representing the frequency distribution of pixels was derived using a software developed in our laboratory with estimates of the average pixel intensity (mean color scale) and broad band of the histogram that supports an index of fibrosis (derived collagen volume fraction; normal values up to 2%) directly correlated with the histologic assessed collagen content. Echo-derived parameters obtained were compared with corresponding values of TSH, fT3, fT4. A significant correlation was found between fT3 and mean color scale (r = 0.61), broad band (r = 0.78) and derived collagen volume fraction (r = 0.78); in particular with the decrease of fT3 an increase in echoreflectivity parameters and a leftward shift of the color histogram were observed with a significant increase of the derived indexes of fibrosis. These results suggest a direct inhibitory effect of triidothyironine on myocardial collagen synthesis confirming the observations made in animal models of hypothyroidism

Thyroid, Dec 1, 1995

Overt hyperthyroidism was found in a 35-year-old pregnant woman at the 13th week of gestation who... more Overt hyperthyroidism was found in a 35-year-old pregnant woman at the 13th week of gestation who was referred to us for tachycardia, tremors, and weight loss. Clinical signs, symptoms, and laboratory findings led to the diag¬ nosis of toxic thyroid nodule. She was treated with ultrasound guided percutaneous ethanol injection (PEI) and, af¬ ter 2 weeks of treatment, the woman was completely euthyroid. These findings suggest that during pregnancy PEI appears to be a rapid and safe therapy for toxic nodular goiter and an effective alternative to the administration of antithyroid drugs.

Acta medica Austriaca, 1992

The recent availability of both cordocentesis and ultrasensitive/highly specific immunometric ass... more The recent availability of both cordocentesis and ultrasensitive/highly specific immunometric assays for TSH and its subunit determination along with direct "two-step" assays for free thyroid hormone measurement, prompted us to study the maturation of hypothalamic-pituitary-thyroid axis in normal and anencephalic human fetuses from 17 to 26 weeks of gestation. In addition, TSH bioactivity was measured as cAMP accumulation in CHO cells transfected with recombinant human TSH receptor and TSH carbohydrate structure was studied by lectin chromatography. In both normal and anencephalic fetuses, circulating TSH and FT4 levels significantly increased from 17 to 26 weeks of gestation. Circulating FT3 concentrations were very low (0.5-3.1 pmol/l), while alpha-SU levels were very high (20-417 mg/l). Both FT3 and alpha-SU levels did not change from 17 to 26 weeks of gestation and, again, no differences between normal and anencephalic fetuses were recorded. Circulating TSH from both n...

Journal of Endocrinological Investigation, 1998

It has been reported that serum FSH bioactivity and inhibin levels can be used as markers of the ... more It has been reported that serum FSH bioactivity and inhibin levels can be used as markers of the presence of true gonadotropin-secreting pituitary adenoma (Gn-oma). To verify this hypothesis, we have investigated the bioactivity of FSH and serum inhibin a-a and a-~A levels in a series of patients with either Gn-oma or nonfunctioning pituitary adenoma (NFPA). Nine patients with Gn-oma (6 men and 3 women), 21 with NFPA (9 men and 12 women) and 30 normal subjects were included in the study. We studied FSH biological activity (FSH-B) by using Sertoli cell aromatase bioassay (SAB) and a-a and a-~A inhibin levels by two noncompetitive immunometric assays (lEMA). In male patients with Gn-oma, serum immunoreactive FSH (FSH-I) and FSH-B levels ranged from 5.1 to 35.5 UlL and from 8.3 to 48 UlL, respectively, FSH B/I ratio being elevated in 2 (2.5 and 4.1; normal male range: 0.3-1.5), while female patients with Gn-oma had serum FSH-I and FSH-B levels ranging from 43.2 to 162 UlL and from 41.2 to 112.8 UlI, respectively, with a nor

Journal of Endocrinological Investigation, 1992

In the present study, we report the uncommon case of a 9.6-yr-old girl with circulating anti-T 3 ... more In the present study, we report the uncommon case of a 9.6-yr-old girl with circulating anti-T 3 autoantibodies (T 3-Ab) and hyperthyroidism due to inappropriate secretion of TSH (IST). The diagnosis of IST was based on the findings of normal TSH levels (2.4 mUll) in the presence of high free T 4 (28.2 pmol/l) and free T 3 (FT 3) levels, as measured by direct measurement methods based on "one-step" analog tracer (28.0 pmo/l) and "twostep" Lisophase@ (13.3 pmo/l) techniques. The discrepancy between the two measurements suggested a methodological interference due to T 3-Ab in "one-step" technique, being the "two-step" methodology unaffected by the presence of such autoantibodies. T 3-Ab were documented by high nonspecific binding of serum to labeled T 3 (38.0% vs 4.3 ± 2.1 % in controls). The clinical picture of hyperthyroidism, the qualitatively normal TSH responses to TRH and T 3 suppression tests, the normal pituitary imaging and the values of some parameters of peripheral thyroid hormone action compatible with hyperthyroidism indicated that the pa

The Journal of Clinical Endocrinology & Metabolism, 1993

We have studied T3 sulfate (T3S) levels, blindly, in coded plasma samples from 21 normal and 3 hy... more We have studied T3 sulfate (T3S) levels, blindly, in coded plasma samples from 21 normal and 3 hypothyroid fetuses at different stages of gestation (19-42 weeks). Fetal plasma samples were obtained by cordocentesis. T3S was detectable in all samples studied, with values ranging from 50-294 (mean +/- SD, 130 +/- 62 pmol/L). Plasma T3S was low (&amp;lt; 45 pmol/L) in all 4 normal adult control subjects studied simultaneously; serum T3S ranged from less than 20 to 130 in another set of 18 control subjects (mean +/- SD, 63 +/- 32 pmol/L). Fetal T3S values were positively correlated with gestational age (r = 0.43; P &amp;lt; 0.05), but not with free T4 (FT4), FT3, or TSH values. In the 3 hypothyroid fetuses at 31, 38, and 40 weeks gestation, respectively, plasma TSH was elevated (26, 98, and 24 mU/L, respectively), FT4 was low (10, 6.7, and 7.5 pmol/L, respectively), and FT3 was normal or high (3.2, 8.2, and 2.2 pmol/L, respectively). However, T3S values in hypothyroid fetuses (88, 133, and 252 pmol/L, respectively) were similar to those in normal fetuses at corresponding gestational ages. We conclude that 1) T3S is detectable in fetal circulation from at least 19 weeks gestation, and its concentration increases with fetal-age; 2) plasma T3S concentrations in the fetus at 19-40 weeks gestation are at least comparable to but generally higher than those in the adult; and 3) plasma T3S levels in hypothyroid fetuses are similar to those in normal fetuses. Recent studies demonstrating the ability of some fetal rat tissues (e.g. cerebral cortex) to desulfate T3S to T3 have suggested a possible role of T3S as a source of T3. Normal T3S in fetal hypothyroidism suggests that T3S may contribute to attenuation of the effects of hypothyroidism during intrauterine life.

Clinical Endocrinology, 1996

OBJECTIVE Women experience an age‐related decline in fertility despite regular ovulatory cycles a... more OBJECTIVE Women experience an age‐related decline in fertility despite regular ovulatory cycles and normal production of ovarian steroids. Growth hormone and IGF‐I are both reported to decline with age, and there is evidence that both hormones promote intraovarian actions of gonadotrophins. The purpose of this study was to characterize circulating levels of GH and IGF‐I in normal, older reproductive age women with ovulatory cycles.DESIGN Prospective, controlled.PATIENTS Twenty‐eight regularly cycling older (n = 16) and younger (n = 12) women were recruited for daily blood sampling throughout a menstrual cycle.MEASUREMENTS Serum obtained from daily blood sampling was analysed for LH, FSH, oestradiol (E2) and progesterone (P). Serum obtained from frequent sampling during the admission was analysed for pulsatile GH secretion. IGF‐I and GH binding protein (GHBP) were also measured in subsets of the two age groups.RESULTS All subjects exhibited normal patterns of LH, FSH, E2 and P consis...

Clinical Endocrinology, Jul 15, 2003

OBJECTIVE Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma ... more OBJECTIVE Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are genetic diseases due to activating mutations of the RET proto-oncogene. Affected patients develop medullary thyroid carcinoma (100%), in an isolated form (FMTC) or in association with phaeochromocytoma (30-50%), and primary hyperparathyroidism (10-20%) (MEN 2A). The presence of cutaneous lichen amyloidosis (CLA) has been anecdotally described in few families harbouring RET proto-oncogene mutation in codon 634. The aim of the study was to evaluate the incidence of CLA in MEN 2A /FMTC families. PATIENTS AND DESIGN Ten MEN 2A/FMTC families were studied and RET gene mutations identified in all. Complete dermatological assessment was carried out in each family member. Skin biopsy for histological studies was performed in patients with CLA.

Thyroid, 2001

Experimental evidence suggests an involvement of thyroid hormones in myocardial nonmyocyte compon... more Experimental evidence suggests an involvement of thyroid hormones in myocardial nonmyocyte component growth. We evaluated the possible role of thyroid hormones in myocardial remodeling by ultrasonic tissue characterization (videodensitometry) in 8 hyperthyroid patients, in 10 hypothyroid patients, and in 2 patients with thyroid hormone resistance syndrome (RTH), before, 60, and 120 days after treatment (T0, T60, T120), and in 10 age-matched euthyroids. According to a previously described procedure, the derived collagen volume fraction (dCVF%, an echocardiographic index estimating the collagen content) was predicted from the pixel-level frequency distribution width (broadband, Bb) of the selected echocardiographic images. Thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed by immunometric method. QT interval dispersion (QTd) on basal electrocardiogram was measured as a marker of dyshomogeneous ventricular repolarization. At T0, Bb and dCVF% were normal in hyperthyroid and euthyroid patients, and slightly increased in RTH patients, whereas significantly higher values were found in hypothyroids. At T60, a significant reduction in Bb was observed in hypothyroids, with nearly normal dCVF% values. This trend was confirmed at T120 with complete normalization of echoreflectivity. No echoreflectivity changes were observed in hyperthyroid and RTH patients during treatment. QTd was significantly increased in hypothyroids at T0, while no significant differences were found among groups at T60 and T120. Because the different videodeonsitometric myocardial properties observed in hypothyroid versus hyperthyroid patients correspond to an increase of dCVF%, this study suggests that thyroid hormones exert an inhibitory effect on myocardial collagen synthesis in humans.

Thyroid, 1997

Page 1. THYROID Volume 7, Number 5, 1997 Mary Ann Liebert, Inc. Clinical and Hormonal Outcome Aft... more Page 1. THYROID Volume 7, Number 5, 1997 Mary Ann Liebert, Inc. Clinical and Hormonal Outcome After Two Years of Triiodothyroacetic Acid Treatment in a Child with Thyroid Hormone Resistance G. RADETTI,1 L. PERSANI ...

Thyroid, 1995

Overt hyperthyroidism was found in a 35-year-old pregnant woman at the 13th week of gestation who... more Overt hyperthyroidism was found in a 35-year-old pregnant woman at the 13th week of gestation who was referred to us for tachycardia, tremors, and weight loss. Clinical signs, symptoms, and laboratory findings led to the diagnosis of toxic thyroid nodule. She was treated with ultrasound guided percutaneous ethanol injection (PEI) and, after 2 weeks of treatment, the woman was completely euthyroid. These findings suggest that during pregnancy PEI appears to be a rapid and safe therapy for toxic nodular goiter and an effective alternative to the administration of antithyroid drugs.

Prenatal Diagnosis, 1999

We report the intra-uterine and postnatal thyroid status of a newborn, whose mother, affected wit... more We report the intra-uterine and postnatal thyroid status of a newborn, whose mother, affected with Hashimoto's thyroiditis superimposed on a previous Graves' disease, again became hyperthyroid during the third trimester of pregnancy. The mother had very high levels of anti-thyroid auto-antibodies, including TSH receptor auto-antibodies (TRAb) measured as TSH-binding inhibiting auto-antibodies (TBIAb). In order to exclude fetal thyroid dysfunction due to passive transplacental transfer of TRAb, fetal blood samples were obtained by cordocentesis at 21, 27 and 32 weeks of gestation. A transplacental transfer of TRAb was already seen at 21 weeks, but no alteration of fetal thyroid function was present at that time. In the following weeks, a rise in TRAb and circulating thyroid hormones was observed both in the fetus and mother, accompanied by overt hyperthyroidism in the mother and by growth retardation in the fetus. At birth, TRAb were shown to have stimulating activity both in the newborn and mother. This report documents the early transplacental passage of thyroid auto-antibodies and underlines the importance of close follow-up of pregnant women with auto-immune thyroid disorders.

Prenatal Diagnosis, 1996

Following the diagnosis of fetal goitre at 22 and 24 weeks' gestation in two hyperthyroid... more Following the diagnosis of fetal goitre at 22 and 24 weeks' gestation in two hyperthyroid pregnant women who underwent treatment with 400-500 mg of propylthiouracil in the first weeks of pregnancy, a total of seven fetal blood samplings were performed to evaluate thyroid function before and after the initiation of two different treatment regimens. L-Thyroxine (600 micrograms) was injected five times intra-amniotically in one woman and continuous maternal administration of the thyroid analogue 3, 5, 3'-triiodothyroacetic acid (Triac) was attempted in the other. Normalization of fetal thyroid function and reduction of fetal goitre were achieved in both fetuses and transplacental passage of Triac was indirectly demonstrated by high levels of free triiodothyronine in fetal blood. In cases of fetal hypothyroidism, direct or indirect prenatal therapy can be adopted successfully and safely.

Pediatric Research, 2000

The relationship between in utero fetal growth and fetal leptin concentrations was investigated b... more The relationship between in utero fetal growth and fetal leptin concentrations was investigated between 19 and 41 wk in 40 normal (appropriate for gestational age, AGA) fetuses, in 25 intrauterine growth-restricted (IUGR) fetuses, and in 18 fetuses from gestational diabetic mothers (GDM), representing different intrauterine growth patterns. Umbilical venous plasma leptin concentrations were determined at the time of either in utero fetal blood sampling or delivery. Plasma leptin was measurable as early as 19 wk of gestation. A significant difference was observed between umbilical venous and arterial plasma leptin concentrations (0.6 Ϯ 0.6 ng/mL; p Ͻ 0.01). In AGA and in IUGR fetuses, significant positive relationships were found between fetal leptin concentrations and both gestational age (p Ͻ 0.001) and fetal weight (p Ͻ 0.001). Leptin concentrations were significantly higher in AGA than IUGR only after 34 wk (p Ͻ 0.05), but leptin per kilogram fetal weight (leptin/kg) was not significantly different. In IUGR with abnormal umbilical arterial Doppler velocimetry and fetal heart rate, leptin/kg significantly higher than in IUGR with normal biophysical and biochemical parameters was found (p Ͻ 0.05). Both circulating plasma leptin and leptin/kg were significantly higher in GDM than in normal fetuses (p Ͻ 0.001) and correlated with abdominal fat mass measured by ultrasound. No gender differences were observed in any group of fetuses. These findings indicate a clear relationship between fetal leptin concentrations and fetal fat mass. Data in severe IUGR suggest the presence of increased leptin concentrations associated with in utero signs of fetal distress. (Pediatr Res 48: 646-651, 2000) Abbreviations AGA, appropriate for gestational age IUGR, intrauterine growth restricted LGA, large for gestational age GDM, gestational diabetes mellitus PI, pulsatility index FHR, fetal heart rate FBS, fetal blood sampling

Metabolism, 1996

Normal or elevated thyrotropin (TSH) levels in hyperthyroid patients are characteristic of rare T... more Normal or elevated thyrotropin (TSH) levels in hyperthyroid patients are characteristic of rare TSH-secreting pituitary adenoma (TSH-oma), which is easily detectable by computed tomographic (CT| scan or magnetic resonance imaging (MRI). Other diagnostic aids are an absent/impaired TSH response to thyrotropin-releasing hormone (TRH), discrepant TSH and ~-subunit responses to TRH, high sex hormone-binding globulin (SHBG) levels, high ~-subunit levels, and a high ~.subunit/TSH molar ratio. Familial studies help rule out thyroid hormone resistance (RTH). Surgical removal of TSH-oma leads to clinical and biochemical remission in most patients. In surgical failures, radiotherapy and octreotide treatment have a high success rate. Undetectable TSH 1 week postsurgery suggests a definitive cure, backed up by tests for cosecreted hormones from the adenoma and dynamic tests of TSH suppression.

Obstetrical & Gynecological Survey, 1995

Thyroid, Dec 1, 1995

Acta medica Austriaca, 1992

Journal of Endocrinological Investigation, 1998

Journal of Endocrinological Investigation, 1992

The Journal of Clinical Endocrinology & Metabolism, 1993

Clinical Endocrinology, 1996

Clinical Endocrinology, Jul 15, 2003

Thyroid, 2001

Thyroid, 1997

Thyroid, 1995

Overt hyperthyroidism was found in a 35-year-old pregnant woman at the 13th week of gestation who... more Overt hyperthyroidism was found in a 35-year-old pregnant woman at the 13th week of gestation who was referred to us for tachycardia, tremors, and weight loss. Clinical signs, symptoms, and laboratory findings led to the diagnosis of toxic thyroid nodule. She was treated with ultrasound guided percutaneous ethanol injection (PEI) and, after 2 weeks of treatment, the woman was completely euthyroid. These findings suggest that during pregnancy PEI appears to be a rapid and safe therapy for toxic nodular goiter and an effective alternative to the administration of antithyroid drugs.

Prenatal Diagnosis, 1999

Prenatal Diagnosis, 1996

Pediatric Research, 2000

Metabolism, 1996