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Biomedical subjects

G Lombardi

Publications and source records attributed to G Lombardi.

At least 127 records · Page 7Linked to original sources

Long-term effects of depot long-acting somatostatin analog octreotide on hormone levels and tumor mass in acromegaly.

The effects of a 12- to 24-month treatment with depot long-acting octreotide (OCT-LAR) on hormone profile, tumor mass, and clinical symptoms were reported in 36 patients with active acromegaly [GH, 34.2 +/- 5.6 microg/L; insulin-like growth factor I (IGF-I), 784.5 +/- 40.4 microg/L]. Fifteen patients were de novo whereas 21 had previously undergone unsuccessful surgery. Serum GH (P < 0.0001) and IGF-I levels (P < 0.0001) significantly decreased as early as after the first injection of OCT-LAR and progressively declined during the 12-24 months of treatment both in de novo and in operated patients. At the last follow-up, GH hypersecretion was controlled (< or =2.5 microg/L) in 69.4% whereas normal IGF-I levels were achieved in 61.1% of patients. GH and IGF-I suppression during OCT-LAR treatment was similar in de novo and operated patients as shown by nadir GH (2.3 +/- 0.6 vs. 2.2 +/- 0.6 microg/L) and IGF-I (323.1 +/- 34.9 vs. 275.5 +/- 33.0 microg/L), percent suppression of GH (92.7 +/- 2.0 vs. 85.9 +/- 3.3%) and IGF-I (57.4 +/- 4.9 vs. 61.5 +/- 4.6%), and prevalence of GH (73.3 vs. 76.2%) and IGF-I (53.3 vs. 71.4%) control. A decrease in tumor volume was observed in 12 of 15 de novo patients, whereas no shrinkage was detected in 4 of 9 operated patients. No patient had tumor reexpansion during OCT-LAR treatment. Significant clinical improvement was obtained in all patients; heart rate, systolic blood pressure, and diastolic blood pressure significantly decreased in the entire population. A mild but significant increase of blood glucose levels, followed by a decrease of serum insulin levels, was observed after 3 months of treatment: this effect subsided with treatment continuation. OCT-LAR treatment was well tolerated by most patients. In conclusion, long-term treatment with OCT-LAR was effective in controlling GH and IGF-I hypersecretion in most patients with acromegaly, when applied either as primary therapy or as adjunctive therapy after surgery. Tumor shrinkage was observed in de novo patients during OCT-LAR treatment, suggesting that it can be successfully applied as primary therapy in patients bearing invasive tumors, who are less likely to be cured after surgery.

Acromegaly↗

Usefulness of different biochemical markers of the insulin-like growth factor (IGF) family in diagnosing growth hormone excess and deficiency in adults.

The diagnostic approach to acromegaly and GH deficiency frequently includes measurement of several components of the insulin-like growth factor (IGF) system. IGF-I levels are reported to be good predictors of active and cured acromegaly, but are commonly found within the normal age-adjusted range in adult GH-deficient (GHD) patients. Circulating concentrations of IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and free IGF-I reflect the GH secretory status, but their diagnostic accuracy is still debated. In this study serum levels of total and free IGF-I, IGFBP-3, ALS, and IGFBP-3-IGF-I and IGFBP-3-ALS complexes were determined in patients previously diagnosed with active (n = 67) or inactive (n = 16) acromegaly and adult GHD (n = 34) and compared with results obtained in 58 healthy controls. In healthy subjects, IGF-I, IGFBP-3, ALS, and both IGFBP-3 complexes declined with age; a correlation was found between IGF-I and IGFBP-3 (r = 0.59; P < 0.001), ALS (r = 0.67; P < 0.001), and free IGF-I (r = 0.40; P < 0.05). Active acromegalic patients showed a significant increase in all parameters tested. IGF-I concentrations were above +2 SD in 100% of patients, whereas slightly lower sensitivities were shown for IGFBP-3 (85%), ALS (88%), and free IGF-I (94%). In this group, IGF-I exhibited a slightly higher correlation with IGFBP-3 (r = 0.83; P < 0.001) than with ALS levels (r = 0.78; P < 0.001). In cured acromegalic patients, we observed the normalization of all parameters but free IGF-I levels. Adult GHD patients showed a significant reduction of all hormones. Unlike active acromegalic patients, all parameters had only a modest sensitivity in GHD; suppression below -2 SD was observed in 41% of GHD patients for IGF-I, 47% for IGFBP-3, 32% for ALS, and 35% for free IGF-I measurements. Previous radiotherapy and GH peak response below 3 microg/L were associated with significantly lower IGF-I, IGFBP-3, and ALS levels. IGF-I levels were significantly correlated to ALS (r = 0.68; P < 0.001) and IGFBP-3 (r = 0.64; P < 0.001) as well as with free IGF-I (r = 0.67; P < 0.001) levels. By multiple regression analysis, the number of anterior pituitary hormones impaired was the most predictive indicator of IGF-I, IGFBP-3, and free IGF-I levels in GHD patients; conversely, the GH peak response better anticipated ALS concentrations. The pattern of IGFBP-3 complexes paralleled previous hormonal findings. In active acromegalic patients, IGFBP-3-IGF-I levels were 5.4-fold higher than in controls and were above +2 SD in 95% of patients, whereas IGFBP-3-ALS levels were elevated in 15% of cases. On the other hand, both IGFBP-3 complexes were able to predict GHD in only a minority of cases. Taken together, these data support the diagnostic role of IGF-I in acromegaly and suggest that free IGF-I and the IGFBP-3-IGF-I complex can assist diagnostic strategies in this condition. All markers are of limited predictive value in adult GHD, as hormonal values are commonly found within the normal limits. In these patients, low IGFBP-3 and IGF-I concentrations can add further clinical information on the residual GH activity.

Acromegaly↗

Inferior petrosal sinus sampling in the differential diagnosis of Cushing's syndrome: results of an Italian multicenter study.

OBJECTIVE: To evaluate the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in the differential diagnosis of ACTH-dependent Cushing's syndrome as compared with pituitary imaging techniques. DESIGN AND METHODS: We retrospectively studied the diagnostic accuracy of basal and post corticotropin-releasing hormone (CRH) IPSS, magnetic resonance imaging and computed tomography in distinguishing pituitary from ectopic ACTH secretion in 97 Cushing's syndrome patients: 74 with Cushing's disease (CD) and 10 with ectopic ACTH secretion (EAS). Thirteen patients were excluded because of unconfirmed diagnosis. The difference between IPSS and pituitary imaging techniques in the correctly localized pituitary adenoma in the patients with CD was also investigated. RESULTS: The basal ACTH inferior petrosal sinus:periphery (IPS:P) ratio was > or = 2 in 63/74 patients with CD (85%), and in 1/10 EAS patients (10%); after stimulation with CRH, the ratio was > or = 3 in 60/68 patients with CD (88%) and < 3 in all patients with EAS. The basal and post-CRH ACTH IPS:P ratios had a diagnostic accuracy of 86% and 90% respectively. The diagnostic accuracy of IPSS with both ratios was significantly higher than magnetic resonance imaging (50%) and computed tomography (40%). The IPS:P ratio suggested by receiver-operator characteristic (ROC) analysis that better distinguished CD from EAS was 2.10 for the basal and 2.15 for the post-CRH ratios. Using these cut-offs, the specificity of basal ratio and the sensitivity of the post-CRH test rose to 100% and 93% respectively. Diagnostic accuracy remained substantially unchanged for the basal ratio (87% vs 86%), while it rose from 90% to 94% for the post-CRH ratio. The sensitivity of IPSS was significantly higher than that of magnetic resonance and computerized tomography. IPSS was less reliable in identifying the adenoma site found at surgery than magnetic resonance imaging or computed tomography (65% vs 75% and 79% respectively). CONCLUSION: In conclusion, IPSS improved the diagnostic performance of imaging techniques. It can help in excluding transsphenoidal surgery in EAS patients. More striking results were obtained when a > or = 2.1:1 basal ratio or a > or = 2.15:1 post-CRH ratio were considered as criteria to distinguish between patients with CD and EAS. To establish correctly the location of the pituitary adenoma, IPSS is less reliable than imaging techniques.

Adrenocorticotropic Hormone↗

Bone loss determined by quantitative ultrasonometry correlates inversely with disease activity in patients with endogenous glucocorticoid excess due to adrenal mass.

OBJECTIVE: Glucocorticoid excess is widely recognized as one of the most important causes of bone loss. The mechanism of glucocorticoid-induced osteoporosis is presumably multifactorial, and consists of the loss of organic and non-organic compounds. Efforts have been made to develop simple physical methods for the assessment of bone tissue for the screening of subjects at high risk of osteoporosis, without the use of radioactive sources or ionizing radiation. Quantitative ultrasonometry (QUS) has been suggested as a useful method for monitoring patients undergoing glucocorticoid therapy, which is the most common cause of glucocorticoid excess. QUS appears to detect more structural bone changes than the traditional methods and allows assessment of bone density and elasticity, both characteristics influenced by organic and non-organic bone compounds. However, the use of QUS has not yet been extensively investigated in subjects with endogenous cortisol excess. The aim of this study was to evaluate the usefulness and predictive power of QUS in assessing bone loss in subjects with differing degrees of endogenous cortisol excess due to adrenal mass. DESIGN: Thirty-four patients (20 women and 14 men) aged between 21 and 59 years were evaluated; fifteen (9 women and 6 men; median age, 42 years) were affected by overt Cushing's syndrome (CS) and nineteen (11 women and 8 men; median age, 44 years) by subclinical CS, defined as lacking clinical signs of hormone excess despite the presence of at least two abnormalities in hypothalamic-pituitary-adrenal axis function, as assessed by routine endocrine tests. All women included were eumenorrhoic. METHODS: QUS measurement of amplitude-dependent speed of sound was performed on the 2nd to 5th proximal phalanges of the non-dominant hand using a DBM Sonic 1200R bone profiler (Igea S.r.l, Italy). The results were compared with bone density assessed on lumbar vertebrae (L1-L4) and femoral neck sites by dual-energy X-ray absorptiometry (DEXA). RESULTS: A strongly significant bone loss was detected by finger QUS measurement when the patients were considered either all together or as two subgroups (P<0.001, all). The bone density decrease in the fingers was similar to that found at the lumbar spine and femoral neck by the DEXA technique. Lumbar and finger Z-scores correlated inversely with 24 h urinary free cortisol (UFF) excretion (P<0.01, both). Finger Z-scores also correlated inversely with the estimated duration of subclinical CS (P<0.05). Concerning disease activity, only UFF was confirmed by multivariate analysis to be an independent factor influencing bone loss (P<0.05). A positive correlation between the results of the two techniques was found in controls (P<0.05) but not in patients. The lack of correlation between the two techniques in patients can probably be attributed to the different parameters of bone alteration measured by the techniques. CONCLUSIONS: The detection of bone loss in subclinical CS similar to that in overt CS suggests that all subjects with endogenous cortisol excess should be evaluated for bone mass. QUS measurement appears to be a reliable, radiation-free, simple and fast tool for the identification of bone alteration in subjects with endogenous cortisol excess.

Absorptiometry, Photon↗

Analysis of color Doppler signal intensity variation after levovist injection: a new approach to the diagnosis of thyroid nodules.

The objective of this study was to evaluate the usefulness of a galactose-based ultrasonographic contrast agent, Levovist (Schering AG, Berlin, Germany), in differentiating benign from malignant thyroid nodules by analysis of the time-intensity curves correlating the variation of the intensity signal value during the contrast transit time. Fifty-four patients scheduled for surgical removal of a nodule or the thyroid gland or both after cytologic examination were enrolled in this study; all of the nodules underwent a baseline color and power Doppler evaluation and then to a color Doppler examination after an intravenous bolus injection of Levovist. The time-intensity curves were analyzed with respect to the histologic results. Carcinomas showed a significantly earlier arrival time of Levovist than nodular hyperplastic benign nodules and adenomas (8.1 +/- 1.41 versus 19.6 +/- 2.2 and 16.1 +/- 2.8 seconds; P < .0001), although no significant difference occurred between hyperplastic benign nodules and adenomas; carcinomas and adenomas showed an earlier time to peak than hyperplastic benign nodules (14.6 +/- 1.2 and 23.1 +/- 3.8 versus 33.0 +/- 3.0 seconds; P < .0001). No significant difference was found in baseline, peak, final intensity signal, and percent variation of intensity signal among hyperplastic benign nodules, adenomas, and carcinomas. Although cytologic examination still remains the standard of reference for the presurgical diagnosis of thyroid nodules, the preliminary data of this pilot study demonstrate that the analysis of time-intensity curves after Levovist injection might provide useful, complementary, and quantitative information to differentiate benign from malignant thyroid nodules.

Adult↗

Priming effects of substance P on calcium changes evoked by interleukin-8 in human neutrophils.

The neurokinin (NK) substance P (SP), which is a mediator of neurogenic inflammation, has been reported to prime human polymorphonuclear neutrophils (PMNs). The priming effects of SP on PMNs activated by recombinant interleukin-8 (rIL-8) were investigated. SP enhanced, in a dose- and time-dependent way, the rise in cytosolic free-calcium concentration, [Ca(2+)]i, evoked by the chemokine. The priming effects of SP were abolished by exposing PMNs to a calcium-free medium supplemented with EGTA. The C-terminal peptides SP(4-11) and SP(6-11) but not the N-terminal peptide SP(1-7) shared the priming effects of SP. The selective NK-1 receptor agonist [Sar-9, MetO2-11]SP mimicked the effects of SP, which were not reproduced by the selective NK-2 receptor agonist [betaAla-8]-NKA(4-10) or the selective NK-3 agonist senktide. Two selective NK-1 antagonists, CP96,345 and L703,606, dose dependently inhibited SP priming effects. These results demonstrated that SP primes PMNs exposed to rIL-8 and suggested that SP priming effects are receptor mediated.

Adult↗

[Somatostatin receptors in immune system cells].

Many hormones and some neuropeptides and neurotransmitters play a key role in regulating numerous lymphoid cell functions. In particular, somatostatin (ss), substance P (sp) and vasoactive intestinal polypeptide (vip) appear to be involved in numerous regulating mechanisms of cell activities in the immune system under both physiological and pathological conditions. ss may be produced by lymphoid cells and accessories as part of the immune system. The distribution of somatostatin receptors (ssr) in the normal human thymus has prompted the hypothesis that ss, and probably other neuropeptides, may play an important role in cell homeostasis in this organ, as well as being one of the processes that regulates the maturation of T lymphocytes. The advent of molecular biology has showed a variable expression of ssr on the various T and B cell lines or lines deriving from lymphoma/ leukemia and human myeloma. Using autoradiographic studies, ssr have been predominantly found in lymphoblastic areas of lymphoma, which represent the active part of the tumour. The expression of ssR has been found in vivo and in vitro, also in pathological sites in patients with autoimmune and granulomatous diseases like rheumatoid arthritis and sarcoidosis.

Animals↗

[Somatostatin analogs in the clinical management of pituitary neoplasms].

The medical approach to patients with secreting or clinically non-functioning pituitary adenoma as made considerable progress thanks to the use of new somatostatin analogs. They were first used to treat acromegaly in the mid 1980s and numerous studies have shown a reduction in GH concentration in over 90% of acromegalic patients. Good results were obtained using slow-release analog treatment also in TSH-secreting adenomas, whereas the therapeutic efficacy of these peptides in clinically non-functioning adenomas is still controversial. Treatment with somatostatin analogs improves symptoms, normalises hormone secretion and in some cases may induce a reduction in the volume of pituitary adenomas. Scintigraphy with octreotide may help to select patients who respond to this form of treatment.

Acromegaly↗

[New therapeutic strategies in gastroenteropancreatic neuroendocrine tumours].

Neuroendocrine tumours are frequently malignant and have often reached an advanced stage by the time of diagnosis when they are inoperable, accompanied by severe symptoms, sometimes of an endocrine nature. Current therapeutic procedures include surgery, embolisation of hepatic metastases, local radiotherapy, biotherapy and chemotherapy. Over the years somatostatin analogs, of which octreotide is the first form, have become increasingly important in the treatment of patients with neuroendocrine tumours. A major step forward in analog treatment is represented by the development of slow-release formulas which do not require multiple daily injections and reduce the onset of resistance. The treatment of neuroendocrine tumours in the future will be based on the increased use of somatostatin analogs alone or in association with interferon or chemotherapy, and will also include surgery, radiometabolic therapy and targeted irradiation of the tumour.

Antineoplastic Agents, Hormonal↗

Type 1 IFN maintains the survival of anergic CD4+ T cells.

Anergic T cells have immunoregulatory activity and can survive for extended periods in vivo. It is unclear how anergic T cells escape from deletion, because both anergy and apoptosis can occur after TCR ligation. Stimulation of human CD4+ T cell clones reactive to influenza hemagglutinin peptides can occur in the absence of APCs when MHC class II-expressing, activated T cells present peptide to each other. This T:T peptide presentation can induce CD95-mediated apoptosis, while the cells that do not die are anergic. We found that the death after peptide or anti-CD3 treatment of a panel of CD4+ T cell clones is blocked by IFN-beta secreted by fibroblasts and also by IFN-alpha. This increases cell recovery after stimulation, which is not due to T cell proliferation. This mechanism for apoptosis inhibition rapidly stops protein kinase C-delta translocation from the cytoplasm to the nucleus, which is an early event in the death process. A central observation was that CD4+ T cells that are rescued from apoptosis after T:T presentation of peptide by IFN-alphabeta remain profoundly anergic to rechallenge with Ag-pulsed APCs. However, anergized cells retain the ability to respond to IL-2, showing that they are nonresponsive but functional. The prevention of peptide-induced apoptosis in activated T cells by IFN-alphabeta is a novel mechanism that may enable the survival and maintenance of anergic T cell populations after TCR engagement. This has important implications for the persistence of anergic T cells with the potential for immunoregulatory function in vivo.

Antigen-Presenting Cells↗

Peptide analogues as a strategy to induce tolerance in T cells with indirect allospecificity.

BACKGROUND: It has been demonstrated that indirect recognition of allogeneic MHC molecules might play an important role in provoking graft rejection. Although direct recognition of allogeneic molecules on antigen presenting cells of the graft may induce a state of tolerance, the continuous presentation of processed alloantigens by specialized antigen presenting cells does not allow the same phenomenon to occur. Tolerance to interleukin-2 secreting T cells can be achieved in different ways, among these is the exposure to mutants of the wild type allopeptide. We have investigated whether peptide analogues of the allopeptide can induce tolerance in T cells with indirect allospecificity. METHODS: T cell clones with indirect anti-HLA-A2-specificity generated from a HLA-A2-DRB1*1502+ patient who chronically rejected a HLA-A2-expressing kidney allograft were used for this study. Nine peptide analogues of HLA-A2 (residues: 103-120) were produced with single amino acid substitutions at the putative T cell receptor for antigen contact positions. Their effect on the proliferation of a panel of T cell clones was evaluated. RESULTS: Peptide analogues and wild type peptide had similar capacity to bind to the restriction molecule HLA-DRB1*1502. Co-presentation of the peptide analogues 111R/A, H, K and 114H/K, with the wild type peptide inhibited T cell responses, indicative of antagonism. In addition, one analogue 112G/S induced unresponsiveness in the T cells to subsequent culture with the wild type peptide. CONCLUSIONS: The data presented here suggest that using reagents such as altered peptides may represent a strategy to prevent the activation of T cells with indirect alloreactivity and allograft rejection in vivo.

Amino Acid Sequence↗

Anergic T cells inhibit the antigen-presenting function of dendritic cells.

The phenomena of infectious tolerance and linked-suppression are well established, but the mechanisms involved are incompletely defined. Anergic T cells can inhibit responsive T cells in vitro and prolong skin allograft survival in vivo. In this study the mechanisms underlying these events were explored. Allospecific mouse T cell clones rendered unresponsive in vitro inhibited proliferation by responsive T cells specific for the same alloantigens. The inhibition required the presence of APC, in that the response to coimmobilized anti-CD3 and anti-CD28 Abs was not inhibited. Coculture of anergic T cells with bone marrow-derived dendritic cells (DC) led to profound inhibition of the ability of the DC to stimulate T cells with the same or a different specificity. After coculture with anergic T cells expression of MHC class II, CD80 and CD86 by DC were down-regulated. These effects did not appear to be due to a soluble factor in that inhibition was not seen in Transwell experiments, and was not reversed by addition of neutralizing anti-IL-4, anti-IL-10, and anti-TGF-beta Abs. Taken together, these data suggest that anergic T cells function as suppressor cells by inhibiting Ag presentation by DC via a cell contact-dependent mechanism.

Animals↗

Significant frequencies of T cells with indirect anti-donor specificity in heart graft recipients with chronic rejection.

BACKGROUND: The purpose of this study was to determine whether T cells with indirect allospecificity could be detected in heart transplant recipients with chronic rejection. METHOD AND RESULTS: Human T-cell clones were used to determine the most effective way to deliver major histocompatibility complex alloantigens for indirect presentation. Seven allograft recipients with evidence of progressive, chronic rejection were selected. Four heart graft recipients with no evidence of chronic rejection were used as controls. Peripheral blood T cells and antigen-presenting cells from the recipients were cultured with frozen/thawed stored donor cells or major histocompatibility complex class I-derived synthetic peptides in limiting dilution cultures and then compared with controls using tetanus toxoid and frozen/thawed third-party cells with no human leukocyte antigens in common with the donor. In 5 of 7 patients analyzed who had chronic rejection, elevated frequencies of T cells with indirect, anti-donor specificity (iHTLf) were detected. No such elevated iHTLf were detected in recipients without chronic rejection. DISCUSSION: iHTLf can be obtained from human transplant recipients, which supports the contention that the indirect pathway is involved in chronic transplant rejection.

Animals↗

Human T cells elicit IFN-alpha secretion from dendritic cells following cell to cell interactions.

Major insights into events that control Th1/Th2 differentiation have been acquired recently, and highlight the role of Type I IFN in Th1 generation, by inducing up-regulation of the IL-12 receptor beta(2) subunit. IFN-alpha induces responsiveness to IL-12, and here we have investigated the source and the circumstances under which IFN-alpha is produced, in the absence of viral infections. Human dendritic cells (DC) were co-cultured with autologous T cells activated by cross-linking the CD3 complex. DC were also cultured with L cells expressing human CD40 ligand (CD40L). Our results show that large amounts (>200 IU IFN-alpha from 2.5x10(4) cells) of IFN-alpha are produced by DC following interaction with stimulated T cells. Similar effects were observed when DC were cultured with CD40L-expressing transfectants, although the amount of IFN-alpha produced was reduced, suggesting that the CD40-CD40L interaction may be important. These results show that stimulated T cells can solicit the signals from DC that allow their polarization towards a Th1 phenotype. Type I DC produce Type I IFN not only following viral infection but also during an immunological interaction and this may be the basic mechanism that assists in the development of a Th1 response.

Animals↗

Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: clinical role and review of the literature.

PURPOSE: Perinuclear antineutrophil cytoplasmic antibodies have been found consistently in patients with ulcerative colitis; however, their pathogenetic and clinical role is still uncertain. In this study we tested the prevalence of perinuclear antineutrophil cytoplasmic antibodies in a large population of patients with ulcerative colitis and Crohn's disease, with particular attention to the possible correlation with clinical features. METHODS: Perinuclear antineutrophil cytoplasmic antibody reactivity was investigated with indirect immunofluorescence in 279 patients with ulcerative colitis, 110 patients with Crohn's disease, and 252 unrelated healthy subjects. RESULTS: Perinuclear antineutrophil cytoplasmic antibodies were found in 84 of 279 patients with ulcerative colitis (30 percent), 10 of 110 patients with Crohn's disease (9 percent), and 2 of 252 healthy subjects (<1 percent; P < 0.001), respectively. Perinuclear antineutrophil cytoplasmic antibodies were significantly more frequent in patients with ulcerative colitis with higher relapse rate (43 vs. 27 percent; P < 0.002), and patients with Crohn's disease with colitis (27 vs. 2.5 percent; P < 0.0003). Perinuclear antineutrophil cytoplasmic antibodies were also significantly less frequent in patients with ulcerative colitis in remission (18 vs. 34 percent; P < 0.0025). CONCLUSIONS: In this study we confirm the relative specificity of perinuclear antineutrophil cytoplasmic antibodies, either for ulcerative colitis or for Crohn's disease involving the colon. Perinuclear antineutrophil cytoplasmic antibodies were more frequently found in patients with ulcerative colitis with a more aggressive clinical behavior; however, their presence had a limited value in identifying homogeneous subgroups of patients in our population.

Adolescent↗

FSH treatment improves sperm function in patients after varicocelectomy.

One-hundred and eighty-three patients affected with idiopathic left varicocele, aged between 18 and 45 years, surgically treated have been studied. They were divided in 3 subsets according to sperm count: group A: <10 x 10(6)/ml, group B: 10-20 x 10(6)/ml, group C: >20 x 10(6)/ml. Six months after surgery 115 patients were treated for 3 months with pure human FSH: 75 IU i.m. every other day, while 68 patients treated with placebo served as control group. After therapy, group A showed a significant clear-cut improvement of sperm parameters: count, forward progression, swollen tails and cervical mucus penetration test (CMPT). In group B a significant improvement of sperm motility, viability, DNA integrity and CMPT was observed, while in group C only a significant improvement of CMPT was observed. In conclusion, it can be suggested that FSH treatment in patients after varicocelectomy could improve spermatogenesis, particularly in those who previously have more compromised sperm quality. On the contrary, no significant difference of sperm patterns was recorded in the control group before and after placebo.

Adolescent↗

Female pseudohermaphroditism and inefficient peak bone mass in an untreated subject affected by 21-hydroxylase congenital adrenal hyperplasia.

Here we describe a subject with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-CAH), in its classical virilizing form, who presented at birth ambiguous genitalia and subsequently was assigned by the parents as male. At the age of 8 years, he underwent a two-step surgical correction of hypospadia and at 22 years old, uterus and ovaries were removed and a bilateral testicular prothesis was surgically placed in scrotum. He refused any chronic glucocorticoid therapy, that was given only acutely to prevent adrenal crises during stress, trauma surgery or severe illness. The patient is now 38 years old, he is genotypically female but phenotypically male, with high endogenous levels of androgen, all of adrenal origin, and with an apparent male sexual life. He had severe osteopenia, probably due to the lack of estrogen/androgen-induced increase in bone mineral density, although periferal estrogen conversion was normal. His skeletal mass, in fact, normally acquired during adolescence and early adult life, could in this case be inefficient, for the precocious pseudopuberty, that caused an inefficient peak bone mass in adolescence period.

Adrenal Hyperplasia, Congenital↗