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F Trimarchi

Publications and source records attributed to F Trimarchi.

At least 37 records · Page 2Linked to original sources
PubMed2002

Changes in the distribution of laminin alpha1 chain in psoriatic skin: immunohistochemical study using confocal laser scanning microscopy.

BACKGROUND: Recent studies have demonstrated the presence in psoriatic skin of ultrastructural and molecular alterations in the basement membrane and an altered polarized distribution of the integrins. Previous studies have demonstrated the existence of some epithelial cell lines synthesizing only laminin beta and gamma chains that, in the absence of the laminin alpha chain, do not form a distinct basal lamina. OBJECTIVES: To investigate a possible reduction/absence of the laminin alpha 1 chain in keratinocytes in psoriatic skin and to correlate this with fibronectin distribution. METHODS: Using monoclonal antibodies against the laminin alpha1 chain or human plasma fibronectin and using confocal laser scanning microscopy, we evaluated the immunohistochemical expression of these two proteins in cutaneous biopsies from involved and uninvolved skin of the sacral region of 12 men with extensive chronic plaque psoriasis. Site-matched biopsies of normal skin from four men without psoriasis were used as controls. RESULTS: In normal skin antilaminin alpha 1 chain antibodies stained the dermal-epidermal junction in a regular and continuous manner. In involved and uninvolved psoriatic skin large regions of discontinuous immunostaining were observed, mainly at the apex of the dermal papillae; in the same regions, clusters of keratinocytes appeared markedly reactive and fibronectin was overexpressed in the papillary dermis under the interruptions of the basement membrane. CONCLUSIONS: The present study defines the location of the laminin alpha1 chain in involved and uninvolved psoriatic skin and suggests a possible role of the alteration of this chain, together with T-cell lymphokines and fibronectin, in the dysregulation of cell morphological processes.

Adolescent↗
PubMed2002

Actin-associated proteins in ameloblast differentiation.

Focal contacts are systems of adherens junctions of the cell-extracellular matrix type, which allow the transfer of fundamental signals from the extracellular matrix to nuclear compartments, capable of regulating adhesion, proliferation, migration and differentiation of cells. Recently, many authors have concentrated their attention on epitheliomesenchymal interactions which guide organogenesis of dental germ, identifying numerous growth and differentiation factors and having the inner enamel epithelial cells of the enamel organ as a target. Given that the two cellular compartments in their tooth germ are separated by a basal membrane and by an extracellular matrix, which touches it, we wanted to evaluate the presence of focal contacts through the identification of talin and vinculin, proteins of the actin-associated protein complex. In this study we utilized the hemimandibles of young Wistar rats and we extracted the related odontogenic tooth organs present at their apical end. Specimens are processed with antibody against vinculin and talin. Results show that these junctional system proteins are present at the apical poles of both cellular compartments suggesting that putative epithelial-mesenchymal interactions, other than marker molecules, may use focal contacts as a system for transmission of signals.

Actins↗
PubMed2002

Immunoexpression of the hepatocyte growth factor (HGF), HGF-receptor (c-met) and STAT3 on placental tissues from malformed fetuses.

To characterize the possible relationship between the expression of the HGF/HGF-R system with transcription factor STAT3, responsible for morphogenetic response of HGF stimulation, and the embryonic development alterations, we investigated, by immunohistochemistry, the expression of HGF, c-met and STAT3 in 9 placentas from malformed fetuses and 9 control placentas from non-malformed fetuses. The major and distinct patterns of expression characterizing the placentas from malformed fetuses were a higher percentage mean of stromal cells stained for HGF, c-met and STAT3 antibodies (60%, 66% and 54%, respectively on fibroblast cells and 44%, 57% and 42%, respectively on myofibroblast cells) and a lower percentage mean of cytotrophoblast cells stained for the same antibodies (2%, 2% and 1%, respectively), than in control placentas. In fact, in this latter group, the stromal fibroblast cells were stained in a percentage mean of 27%, 22% and 7%, respectively; the stromal myofibroblast cells in a percentage mean of 5%, 6% and 2%, respectively and the cytotrophoblast cells in a percentage mean of 25%, 34% and 18%, respectively. The expression of each antibody on stromal cells in both groups suggests an alternative role of the HGF/HGF-R system activating the via STAT3 transdution and operating on placental tissues, overall in organogenesis alteration conditions. This immunohistochemical approach could be used in the diagnostic practice of pathologists on chorionic villi biopsy when genetic alterations are absent and ultrasound aspects are doubtful for malformations.

DNA-Binding Proteins↗
PubMed2002

[Deep lamellar keratoplasty].

INTRODUCTION: Deep lamellar keratoplasty (DLKP) is a surgical technique in which the entire corneal stroma is removed down to the Descemet membrane. METHODS: The difference between deep lamellar keratoplasty and classic lamellar keratoplasty is qualitative rather than quantitative. In the first technique, the anatomical cleavage plane provides clear separation of the stroma and the Descemet membrane. This plane has a clear and smooth surface. On the contrary, classic lamellar dissection down to 2/3 of the stroma results in a very rough and uneven surface with a risk of low visual acuity. PURPOSE: To compare the results of 200 cases treated with deep lamellar keratoplasty and 200 cases of penetrating keratoplasty (PK). RESULTS: No rejection episodes were recorded in the 200 patients who underwent DLKP surgery, whereas rejection occurred in 4% of the patients after PK. The number of endothelial cells, measured with a Konan instrument 1 month after removal of the sutures in patients who underwent deep lamellar keratoplasty, was double that in patients who underwent penetrating keratoplasty. CONCLUSION: The number of endothelial cells does not change after DLKP, but is substantially reduced after PK. The degree of astigmatism is greatly reduced and functional recovery is faster with the first technique. These are the main reasons why we think that DLKP could replace PK as the best procedure in all cases in which no endothelial damage is involved.

Cornea↗
PubMed2001

Re-evaluation of the thyroxine binding to human plasma lipoproteins using three techniques.

Using gel filtration chromatography (GFC), we found that human VLDL, LDL and HDL transport approximately 0.03, 0.2 and 3% of plasma T4. As T4 could dissociate from carriers during GFC, we evaluated [125I]T4 transport to lipoproteins (Lp) in 50 normolipidemic and euthyroid subjects by GFC and 2 independent methods: zone electrophoresis (ZE) and radioimmunoprecipitation (RIP). At GFC, VLDL+LDL transported less T4 (approximately 0.3%) than either ZE (approximately 1.3%) or RIP (approximately 1.5-2.0%). In contrast, GFC values for the HDL (approximately 3%) were close to the RIP values (approximately 3.5%), but lower than ZE (approximately 8.5%) because of partial co-migration with TBG. In conclusion, GFC underestimates T4 binding to VLDL and LDL, which, indeed, is of the same magnitude as binding of some steroid hormones to CBG and SHBG. Hence, the anti-atherosclerotic effects of T4 resulting from binding to the LDL should be greater than anticipated based on GFC data.

Adult↗
PubMed2001

Exercise-related female reproductive dysfunction.

Clinical or biochemical abnormalities of gonadal function, consisting of delayed puberty, luteal phase deficiency, oligo-amenorrhea or anovulation, occur in girls and women participating in strenuous sports. The evidence of a causal relationship between athletic activity and menstrual dysfunction has led to increased interest, also because the number of women who practice sports has increased rapidly. The pathogenesis of exercise-related female reproductive dysfunction (ERFRD) is not completely clarified. The heterogeneity of sports practice, the role of overtraining and other factors, as adequate calorie balance or the assumption of exogenous steroids, could play a primary role in the comprehension of the pathogenic mechanisms of reproductive dysfunction. The interest of physicians about ERFRD is also due to the consequences of reduced gonadal function on women's health. Apart from some short-term transient effects (i.e. on muscle, genito-urinary tract or behavior), hypoestrogenemia can induce long-term deleterious effects, as premature osteoporosis and lifelong impairment of skeletal structure. In view of the possible short-term (infertility) and long-term (osteoporosis) consequences of ERFRD, correct physical training and adequate diet approach are mandatory to prevent or to revert neuroendocrine abnormalities so frequently reported in girls and women participating in recreational or competitive athletic activities.

Energy Intake↗
PubMed2001

Nitric oxide synthase patterns in normal and varicocele testis in adolescents.

OBJECTIVE: To determine if the testes of normal adolescents can produce nitric oxide (NO), by assessing NO synthase (NOS) activity, and whether this activity changes in adolescents with left idiopathic varicocele. PATIENTS AND METHODS: After obtaining informed consent, testicular biopsies were obtained from eight adolescents (mean age 16.4 years; controls) who underwent surgery for inguinal hernia or hydrocele, and from 20 adolescents (mean age 16.2 years) operated for left idiopathic varicocele. Inducible and endothelial NOS (iNOS and eNOS) isoforms were investigated in the biopsy specimens by immunohistochemical localization and Western blot analysis using specific fluorescein-conjugated antibodies. RESULTS: Both normal and pathological samples expressed eNOS at the level of vessels and Leydig cells. The iNOS was expressed in Leydig cells of normal testes and over-expressed in Leydig cells of varicocele testes. CONCLUSION: Leydig cells of adolescent testes constitutively express iNOS. Under pathological conditions, e.g. varicocele, iNOS is up-regulated and is a possible source of NO overproduction. These results could be useful in explaining the pathogenesis of both testis and sperm dysfunction in varicocele.

Adolescent↗
PubMed2001

Nitric oxide production is increased in the spermatic veins of adolescents with left idiophatic varicocele.

BACKGROUND/PURPOSE: The existence of an excessive release of nitric oxide (NO) within dilated spermatic veins has been recorded in adults with varicocele suggesting a high oxidative stress. The authors investigated whether NO overproduction is already present in the dilated veins of adolescent varicocele and which enzymatic isoforms in the spermatic vein could be expressed. METHODS: The study group consisted of 10 adolescent patients affected by left idiophatic varicocele of grade II and III. The increase in NO production was established by determination of serum concentration of L-hydroxyarginine (L-NHA) and Nitrite/nitrate (NOx). Both endothelial and inducible NOsynthase (NOS) were investigated by Western blot analysis and by immunohistochemical localization using specific monoclonal fluorescein conjugated antibodies. RESULTS: Serum L-NHA levels were significantly greater in the spermatic veins when compared with the peripheral veins 176.8 +/- 32.3 micromol/L versus 3.38 +/- 0.64 micromol/L (P =.0004 Similarly, NOx levels were increased, respectively, 68.2 +/- 16.7 nmol/mL versus 12.9 +/- 2.65 nmol/mL (P =.029). Endothelial NOS was localized in the spermatic vein of varicocele patients, but not overexpressed; the inducible isoform was not detected. CONCLUSIONS: Adolescents with varicocele already present an increase in NO within dilated veins. The dilated spermatic vein is not the major source for the increase in NO level. These results could have an implication in the natural history of adolescent varicocele and in programming the ideal time for surgical treatment.

Adolescent↗
PubMed2001

Effectiveness of slow-release lanreotide in previously operated and untreated patients with GH-secreting pituitary macroadenoma.

The aim of this study was to verify whether treatment with slow-release lanreotide (SRL) before surgery is useful in the management of patients with GH-secreting pituitary macroadenoma. Twenty untreated acromegalics were enrolled randomly in two groups. Ten patients (group 1: 2 males and 8 females aged 44.5 +/- 4.3 years) underwent surgery via transsphenoidal access. Only one of them was cured by surgery, whereas the other nine were treated with SRL. In the other ten patients (group 2: 3 males and 7 females aged 43.2 +/- 12.3 years), transsphenoidal surgery followed SRL treatment. Surgery induced the normalization of GH and IGF-1 levels in four group 2 patients - three of them had shown an evident shrinkage of the tumor after SRL treatment. After surgery, group 1 showed a significant decrease of mean IGF-1 (580 +/- 63 vs. 789 +/- 64 ng/ml, p < 0.02), but not of GH values (26.1 +/- 9.8 vs. 44.8 +/- 19.3 ng/ml, NS); the cured patient was excluded from the following evaluations. Group 2 showed an evident, but not significant, decrease of both GH and IGF-1 values compared to values measured at the end of medical treatment (GH: 22.4 +/- 9.7 vs. 7.7 +/- 4.7 ng/ml, NS. IGF-1: 570 +/- 69 vs. 402 +/- 58 ng/ml, NS). Gonadal, thyroid and adrenal impairment was evident in six, four and no patients in group 1 and in three, two and one patients in group 2, respectively. SRL 30 mg was administered every 14 days for three months and then every 10 days until the 6th month. Before SRL treatment, mean GH and IGF-1 levels did not differ significantly in group 1 vs. group 2 (GH: 29.3 +/- 10.5 vs. 43.4 +/- 22.0 ng/ml; IGF-1: 633 +/- 38 vs. 778 +/- 83 ng/ml). In group 1, a significant decrease of serum GH, but not of IGF-1 levels, was achieved at the end of 1st trimester of SRL (GH: 17.6 +/- 5.4 ng/ml, p < 0.05. IGF-1: 540 +/- 48 ng/ml, NS), whereas a significant decrease in both GH and IGF-1 values was evident during the 2nd trimester (GH: 6.1 +/- 3.0 ng/ml, p < 0.05. IGF-1: 433 +/- 74 ng/ml, p < 0.02). Serum GH levels, measured during the 2nd trimester of SRL therapy, were also significantly lower than levels measured at the end of the 1st trimester (p < 0.05). Group 2 serum GH and IGF-1 levels were not significantly decreased at the end of the 1st trimester (GH: 27.2 +/- 12.1 ng/ml, NS. IGF-1: 698 +/- 74 ng/ml, NS), whereas only serum IGF-1 (570 +/- 69 ng/ml, p < 0.05) was significantly reduced during the 2nd trimester of SRL (GH: 22.4 +/- 9.7 ng/ml, NS). Serum GH and IGF-I fell in the normal range in 4 patients in group 1 and one in group 2 at the end of the second trimester of SRL therapy. Independently of the trial applied, the mean clinical score level ameliorated significantly in both groups (group 1: p < 0.0005; group 2: p < 0.0001). In both groups, the proportion of patients complaining of headache and tissue swelling and the score level of headache, tissue swelling and excessive sweating decreased significantly. In group 1 the score level of fatigue and arthralgia also decreased significantly. In conclusion, this study proves that in patients with GH-secreting pituitary macroadenoma: (i) surgery followed by SRL induces a better clinical and biochemical status than SRL alone; (ii) SRL treatment before surgery ameliorates the clinical and biochemical outcome and reduces the prevalence of hypopituitarism due to surgery.

Acromegaly↗
PubMed2001

Expression of CD30 ligand and CD30 receptor in normal thyroid and benign and malignant thyroid nodules.

Because the CD30 ligand (CD30L)/CD30 receptor (CD30) system is expressed in certain malignancies, but has not been studied in thyroid nodules, we investigated its immunohistochemical expression in 6 normal thyroids (NT) and 131 thyroid nodules: 28 colloid nodules (CN), 45 adenomas (15 oncocytic [OA], 30 follicular [FA]) and 58 carcinomas (15 follicular [FTC], 1 insular [ITC], 6 anaplastic [ATC], 30 papillary [PTC], and 6 medullary [MTC]). NT and CN expressed neither CD30L nor CD30 (CD30L-/CD30-). Forty percent of OA and 20% of FA showed epithelial coexpression of CD30L and CD30, and interstitial expression of CD30L, which was also observed in the surrounding normal tissue. Within malignancies, epithelial coexpression of CD30L and CD30 was observed in 7% of FTC, 33% of ATC, 67% of PTC, and 67% of MTC. Only PTC and MTC showed epithelial expression of CD30L in the perinodular tissue with similar frequency (80% PTC, 75% MTC). PTC and MTC had the highest proportion of CD30L+ or CD30+ cells, and together with OA, a thus far unreported nuclear location of CD30L. In PTC, the proportion of CD30L+ cells and the prevalence of nuclear location of CD30L correlated inversely and directly, respectively, with aggressiveness. In conclusion, CD30L/CD30 signaling is activated only past the colloid nodule stage, most frequently in an autocrine fashion.

CD30 Ligand↗
PubMed2001

Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial.

Old studies in animals and unblinded studies in a few hyperthyroid patients suggested that L -carnitine is a periferal antagonist of thyroid hormone action at least in some tissues. This conclusion was substantiated by our recent observation that carnitine inhibits thyroid hormone entry into the nucleus of hepatocytes, neurons, and fibroblasts. In the randomized, double-blind, placebo-controlled 6-month trial reported here, we assessed whether 2 or 4 g/d oral L-carnitine were able to both reverse and prevent/minimize nine hyperthyroidism- related symptoms. We also evaluated changes on nine thyroid hormone-sensitive biochemical parameters and on vertebral and hip mineral density (bone mineral density). Fifty women under a fixed TSH-suppressive dose of L -T(4) for all 6 months were randomly allocated to five groups of 10 subjects each. Group 0 associated placebo for 6 months; groups A2 and A4 started associating placebo (first bimester), substituted placebo with 2 or 4 g/d carnitine (second bimester), and then returned to the association with placebo. Groups B2 and B4 started associating 2 and 4 g/d carnitine for the first two bimesters, and then substituted carnitine with placebo (third bimester). Symptoms and biochemical parameters worsened in group 0. In group A, symptoms and biochemical parameters worsened during the first bimester, returned to baseline or increased minimally during the second bimester (except osteocalcin and urinary OH-proline), and worsened again in the third bimester. In group B, symptoms and biochemical parameters (except osteocalcin and urinary OH-proline) did not worsen or even improved over the first 4 months; they tended to worsen in the third bimester. In both the A and B groups, the two doses of carnitine were similarly effective. At the end of the trial, bone mineral density tended to increase in groups B and A (B > A). In conclusion, L-carnitine is effective in both reversing and preventing symptoms of hyperthyroidism and has a beneficial effect on bone mineralization. Because hyperthyroidism depletes the body deposits of carnitine and since carnitine has no toxicity, teratogenicity, contraindications and interactions with drugs, carnitine can be of clinical use.

Administration, Oral↗
PubMed2000

Immunofluorescence distribution of actin-associated proteins in human seminiferous tubules of adolescent testes, normal and pathologic.

The aim of our study on human seminiferous tubules of adolescent testes was to study the localization of two actin-associated proteins of the adherens junctions, such as vinculin and talin, and to verify if there were modifications in their pattern in varicocele, a frequent disease of the testis in adolescent age. The study group consisted of 8 biopsies from normal testes (i.e., adolescents operated on for hydrocele or inguinal hernia) and 20 biopsies from pathological testes (i.e., adolescents operated on for idiophatic left varicocele). Biopsies were evaluated by indirect immunofluorescence using anti-human vinculin and anti-human talin antibodies. Observation was recorded with a Leica TCS 4D upright confocal microscope. In the normal testes, there was a strong positive immunoreactivity for vinculin, which was localized in the interstitial cells of Leydig, and both basal pole and lateral cell surface of Sertoli cells; the pattern of talin immunoreactivity was the same except that the lateral cell surface of Sertoli cells was not stained. In the varicocele group the pattern was different. Vinculin immunoreactivity showed small patches of fluorescence only in the cytoplasm of Sertoli cells while talin immunoreactivity showed a scanty distribution at the basal surface of Sertoli cells. These results confirm that, similarly to other tissues, vinculin is expressed at cell-cell and cell-matrix adherens junctions, while talin is present at cell-matrix adherens junctions in human seminiferous tubules of normal adolescents. Varicocele alters the patterns of these two proteins both quantitatively and qualitatively.

Adherens Junctions↗
PubMed2000

Goiter and impairment of thyroid function in acromegalic patients: basal evaluation and follow-up.

AIMS: We evaluated morphological, biochemical and cytological thyroid parameters in acromegalic patients, investigated before and after treatment for acromegaly. PATIENTS: 28 acromegalics were investigated before and, in 18 cases, after 2-7 years of therapy. Fourteen patients were from areas of moderate iodine deficiency in Southern Italy. One patient underwent thyroidectomy before entering this study. RESULTS: 19 patients were euthyroid (FT4: 17.7 +/- 0.8 pmol/l and FT3 4.6 +/- 0.2 pmol/l), but TSH was undetectable in 5/19. Among them, TRH-stimulated TSH increase was absent/impaired or exaggerated/delayed in 9 and one cases, respectively. Decreased FT3 and/or FT4 values with low/normal TSH values were detected in 7 cases; TRH-stimulated TSH response was absent/impaired in 2 patients and exaggerated/delayed in another two. Increased free T4 and free T3 concentrations with undetectable TSH levels were found in one. Two euthyroid patients had high TPOAb levels. Goiter was diagnosed in 21 cases and nodules were found in 14/21. 99Tc scintiscan showed "cold" areas in 13/14 cases and a "hot" nodule in the hyperthyroid patient. Acromegalics from iodine deficient areas showed a not significant increase of prevalence of goiter (86 vs. 71 %) and of mean thyroid volume (35 +/- 7 vs. 28 +/- 4 ml, NS), compared to others. Thyroid volume (TV) did not correlate with GH, IGF-1 and TSH levels, the area under the curve of insulin-increase during OGTT, the age of patients or the duration of acromegaly. Fine needle aspiration biopsy (FNAB), performed in 11/14 patients with nodular goiter, showed colloid nodules in 8 cases, hyperplastic nodules in 2 and an adenomatous nodule in one. Neurosurgery, radiotherapy or medical treatment for acromegaly induced a significant decrease of mean GH and IGF-1 levels (21.5 +/- 8.5 vs. 12.9 +/- 9.6 ng/ml, p< 0.005 and 747 +/- 94 vs. 503 +/- 88 ng/ml, p < 0.02, respectively), but both GH and IGF-1 values normalized only in 3 cases. No significant variation of mean TSH levels was found. Although TV normalized in 3 patients, ultrasound evaluation showed a not significant decrease of mean TV and no changes in the diameter and number of nodules. FNAB was unchanged. CONCLUSIONS: Our results suggest that, despite no correlation between serum GH and IGF-1 levels and thyroid volume being found, a decrease in serum GH and IGF-1 levels has favourable effects on thyroid status.

Acromegaly↗
PubMed2000

Results of a two-year treatment with slow release lanreotide in acromegaly.

In this open sequential study we evaluated the long-term effectiveness and tolerability of the i.m. administration of slow release lanreotide 30 mg (SRL) in 18 acromegalics (7 M/11 F, age 50.9+/-12.7 yr). Baseline mean GH and IGF-1 levels were 15.8+/-6.6 ng/ml and 702+/-74 ng/ml, respectively. Four hours, 1, 7, and 14 days after SRL, mean GH levels were 8.9+/-5.9 (p < 0.005), 11.4+/-6.9 (p < 0.05), 9.1+/-4.5 (p < 0.05), and 9.1+/-4.1 ng/ml (p < 0.05), respectively; and the IGF-1 values at 1, 7, and 14 days were 624+/-77 (p < 0.05), 555+/-83 (p < 0.001), and 467+/-58 ng/ml (p < 0.0001), respectively. Four hours after SRL administration GH was < 2.5 ng/ml in 11 patients and decreased 85% of the basal value, without normalizing, in another case. In the following 2 weeks, 7 and 2 patients maintained GH < 2.5 ng/ ml or < 50% of baseline; 3 and 2 of them attained IGF-1 values in the normal range or < 50% of basal levels. A patient developed acute pancreatitis after the injection of the drug and therefore stopped the treatment. Another patient did not continue SRL, and she was turned on octreotide, s.c. administered (OCT), because only the latter treatment ameliorated significantly the headache. In 16/18 patients the treatment was continued until the 24th month. SRL was administered every 14 days until the 24th month in 3 cases, whereas in 13 patients the dose schedule was increased every 10 days since the 7th month because they did not normalize serum GH and IGF-1 levels. In these 16 patients baseline GH and IGF-1 levels were 10.0+/-2.5 ng/ml and 671+/-75 ng/ml, respectively. At the 1st, 3rd, and 6th month of treatment mean GH levels fell to 5.4+/-1.4 (p < 0.05), 5.3+/-1.8 (p < 0.05), and 5.0+/-1.6 (p < 0.05) ng/ml, respectively; and IGF-1 declined to 511+/-87 (p < 0.005), 565+/-85 (p < 0.05), and 525+/-94 (p < 0.01) ng/ml, respectively. Throughout the first semester GH was < 2.5 ng/ml in 5 patients and decreased > 50% in another three. IGF-1 levels normalized in 3/5. Throughout the following 18 months of treatment, mean GH (3.4+/-1.0 ng/ml) and IGF-1 (413+/-75 ng/ml) values decreased significantly in comparison with both the baseline concentrations (GH p < 0.01, IGF-1 p < 0.001) and the levels measured during the 1st semester of treatment (GH p < 0.05, IGF-1 p < 0.001). GH remained < 2.5 ng/ml in 11 patients, and in 8/11 cases IGF-1 fell in the normal range. Serum GH and IGF-1 levels decreased by more than 50% of baseline levels in 2 other cases. At MRI, pituitary adenoma was no longer evident in one patient previously treated with OCT and significantly decreased in another patient previously treated with surgery plus radiotherapy, as well as in a patient previously untreated. During treatment the percentage of patients complaining of headache and fatigue decreased significantly (chi2, p < 0.05 and p < 0.0005, respectively). Overall, the headache (p < 0.005), arthralgia (p < 0.05), and paresthesia (p < 0.01) ameliorated significantly. Ultrasound scan showed gallbladder sludge or sand-like stones in 5/11 patients. This study, which is one of the longest surveys on a relatively large series of acromegalics treated with SRL, confirms the long-term effectiveness of this drug for the treatment of patients with active acromegaly. SRL decreases significantly GH and IGF-1 in most cases and induces the shrinkage of the pituitary tumor in some patients previously either untreated or both treated for acromegaly. SRL improves significantly clinical symptoms and it is well tolerated.

Acromegaly↗
PubMed2000

Euthyroid hyperthyrotropinemia secondary to hyperestrogenemia in a male with congenital adrenal hyperplasia.

A 10-year-old boy with congenital adrenal hyperplasia and associated hyperplastic testicular adrenal rests had high serum concentrations of 17-OH progesterone (17-OHP), estradiol (E2), testosterone (T), and basal and TRH-stimulated TSH and PRL, but normal thyroid hormones (T3, T4, FT3, FT4) and thyroxine-binding globulin (TBG). Upon dexamethasone therapy, steroid hormones returned progressively toward normal as did both PRL and TSH; PRL declined faster than TSH. Serum E2 correlated better with PRL than with TSH. Therefore, the responsiveness of the thyrotrophs to the ambient concentration of E2 is lower and slower than that of the lactotrophs. In the context of the inconclusive data on the role of estrogens in controlling the secretion of TSH in humans, our case suggests that E2 does stimulate the secretion of basal and TRH-elicited both TSH and PRL, and that this positive action is unopposed by T. In contrast, T antagonizes the estrogen-induced increase in serum TBG. We also postulate that E2 might impair the bioactivity of TSH, in order to explain (i) the approximate 3-fold increase in serum TSH coexisting with a normally sized (rather than enlarged) thyroid and normal (rather than increased) serum thyroid hormones, and (ii) the inability of TRH-stimulated TSH to acutely raise FT3 serum levels.

17-alpha-Hydroxyprogesterone↗
PubMed2000

Myxedema coma of both primary and secondary origin, with non-classic presentation and extremely elevated creatine kinase.

Myxedema coma is a rare, often fatal endocrine emergency that concerns elderly patients with long-standing primary hypothyroidism; myxedema coma of central origin is exceedingly rare. Here, we report a 37-year-old woman in whom classical symptoms of hypothyroidism had been absent. Six years earlier, she had severe obstetric hemorrhage and, shortly after, two subsequent episodes of pericardial effusion. On the day of admission, pericardiocentesis was performed for the third episode of pericardial effusion. Because of the subsequent grave arrhythmias and unconsciousness, she was transferred to our ICU. Prior to the endocrine consultation, a silent myocardial infarction had been suspected, based on the extremely high serum levels of creatine kinase (CK) and isoenzyme CK-MB. However, based on thyroid sonography, pituitary computed tomography, elevated titers of antithyroid antibodies and pituitary stimulation tests, the final diagnosis was myxedema coma of dual origin: an atrophic variant of Hashimoto's thyroiditis and post-necrotic pituitary atrophy (Sheehan syndrome). Substitutive therapy caused a prompt clinical amelioration and normalization of CK levels. Our patient is the first case of myxedema coma of double etiology, and illustrates how its presentation deviates markedly from the one endocrinologists and physicians at ICU are prepared to encounter. In addition, cardiac problems as those of our patient should not discourage from substitutive treatment (using L-thyroxine and the gastrointestinal route of absorption), if the age is relatively low.

Adult↗
PubMed2000

Carnitine is a naturally occurring inhibitor of thyroid hormone nuclear uptake.

Carnitine (3-hydroxy-4N-trimethylammoniumbutanoate) is a naturally occurring quaternary amine that is ubiquitous in mammalian tissues (concentrations in the order of mM). Based on limited studies of approximately 40 years ago, carnitine was considered to be a peripheral antagonist of thyroid hormone (TH) action. These interesting observations have not been explored. To study the biologic basis of this effect, we tested the following possibilities in three TH-responsive cell lines: (1) inhibition of TH entry into cells; (2) inhibition of TH entry into the nucleus; (3) inhibition of TH interaction with the isolated nuclei; and (4) facilitated efflux of TH from cells. On a preliminary basis we had verified that these cell lines (human skin fibroblasts, human hepatoma cells HepG2, and mouse neuroblastoma cells NB 41A3) take up 14Ccarnitine; however, there was no 14Ccarnitine uptake into the nuclei. Concentrations of unlabeled carnitine as high as 100 mM did not affect (125I)T3 binding to isolated nuclei or exit of TH from cells, thus excluding possibilities numbered 3 and 4. At 10 mM camitine, (125I)T3 and (125I)T4 whole-cell uptake was inhibited by approximately 20% in fibroblasts and in HepG2, but by approximately 5% in NB 41A3 cells. Inhibition of T3 nuclear uptake was evaluated in HepG2 and NB 41A3 cells. At 10 mM carnitine, inhibition of T3 nuclear uptake was disproportionately higher, namely approximately 25% in neurons and 35% in hepatocytes. At 50 mM carnitine, there was a minimal additional decrease in whole-cell uptake of either hormone but a marked decrease in T3 nuclear uptake. The latter inhibition was approximately 60% in neurons and 70% in hepatocytes. We are aware of no inhibitor of TH uptake that has such a markedly different effect on the nuclear versus whole-cell uptake. Our data are consistent with carnitine being a peripheral antagonist of TH action, and they indicate a site of inhibition at or before the nuclear envelope.

Animals↗