Transit time flow measurement in off-pump surgery: is it a functional index of the biological graft integrity?

OBJECTIVE: Transit-time flow measurement (TTFM) represents a valid tool in the assessment of the quality of the anastomosis during coronary artery bypass graft (CABG). Nevertheless, a high variability limits its standardized use, lacking univocally accepted cut-off flow values. Our study analyzes TTFM data collected from a study population that underwent off-pump CABG (OP-CABG), with the aim to differentiate into subgroups according to the presence of diabetes mellitus. PATIENTS AND METHODS: Patients referred to the Cardiovascular Unit of S. Michele Hospital (Caserta, Italy) for coronary artery disease (CAD) and underwent OP-CABG between January 2015 and December 2019 were enrolled, and intraoperative TTFMs data were recruited and evaluated. Mean graft flow (MGF) and pulsatility index (PI) values were collected and analyzed. RESULTS: The study population was composed of 342 patients who underwent OP-CABG with TTFM data regarding 824 grafts. Diabetic patients shared a higher cardiovascular risk profile. The TTFM assessment showed better results for the use of the arterial grafts in diabetic patients, especially for those insulin-dependent; conversely, venous grafts showed worse data with lower MGF and higher PI values. In particular, the anastomoses of the saphenous vein graft with marginal obtuse (MO) coronary artery showed worse MGF results in the insulin-dependent rather than normoglycemic subgroup (28.66 vs. 38.44, p=0.003). CONCLUSIONS: Diabetic patients, especially in the insulin-dependent subgroups, have demonstrated lower MGF and higher PI values collected from venous anastomoses with, conversely, inverse results from the arterial one. These results might be correlated to an altered biological adaptability caused by the effects of the diabetic endocrine disorder.

Dramatic response to regorafenib in early glioblastoma progression: case report and review of the literature.

BACKGROUND: Glioblastoma (GBM) is a highly lethal disease despite integrated treatment comprising radiotherapy plus concomitant and adjuvant temozolomide, with a median overall survival of less than 15 months. For recurrent glioblastoma, there is yet no standard therapy, considering that Bevacizumab have failed to improve overall survival (OS) while regorafenib had a little benefit over standard chemotherapy. In addition, the disease control rate is almost exclusively stability, with a poor objective response rate. CASE REPORT: Here we present a case of rapid response to regorafenib in early glioblastoma progression at the end of adjuvant radiotherapy: after a single cycle of regorafenib the patient observed an impressive improvement in clinical condition, disappearance of headaches and a clear reduction of neoplastic tissue in MRI. A brief review about new radiological patterns in Magnetic Resonance Imaging (MRI) related to the introduction in clinical practice of antiangiogenic drugs and tyrosine kinase inhibitors has also been carried out. CONCLUSIONS: Regorafenib was certainly a first turning point in the second-line treatment of GBM, showing longer response rates and mostly disease stability than bevacizumab. A switch-maintenance strategy with tyrosine kinase inhibitors may represent a valid second-line therapeutic option.

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients.

BACKGROUND: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD). METHODS: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. RESULTS: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. CONCLUSIONS: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

Endocrine rhythms and sport: it is time to take time into account.

BACKGROUND: Studies of time-related biological phenomena have contributed to establishing a new scientific discipline, the chronobiology, which considers biological phenomena in relation to time. Sports activity profoundly affects the temporal organization of the organism and endocrine rhythms play a key role in the chronoorganization of individuals and are particularly important for correct physical activity. Correctly reading rhythmic hormonal variations of the human organism opens new horizons to sports medicine. OBJECTIVE: This review is aimed at clarifying the relationship between endocrine rhythms and sports activities on the basis of the latest data in the literature. METHOD: Data acquisition was obtained from three databases (PubMed, Scopus and SPORTDiscus), paying particular attention to reviews, meta-analysis, original and observational studies on this issue. RESULTS: After the description of the general characteristics and parameters of biological rhythms, the main endocrine rhythms will be described, highlighting in particular the interrelationships with sports activity and focusing on the factors which can affect negatively their characteristics and consequently the psychophysical performances of the athletes. CONCLUSION: Knowledge of this issue may allow establishing the best form of competitive or amateur activity, through the collaboration of an informed athlete and a sports physician attentive to biological rhythms. By taking into account that alteration of physiological rhythmic temporal organization can favour the onset of important diseases, including cancer, this will lead to the expected performances without impairing the correct chronoorganization of the athlete.

Vitamin D and autoimmunity: what happens in autoimmune polyendocrine syndromes?

PURPOSE: To evaluate the Vitamin D status of patients with a single autoimmune disease and of patients with several autoimmune diseases. METHODS: We enrolled 35 patients with isolated type 1 diabetes mellitus (T1DM), 60 with autoimmune polyendocrine syndromes (APS) including T1DM and 72 control subjects. Among patients with APS, 10 were classified as type 2 (Addison's disease + T1DM), whereas the other 50 as type 3 (autoimmune thyroid disease + T1DM + other autoimmune diseases). Vitamin D (25-OHD) levels were assessed by a chemiluminescent immunoassay in all patients and controls on samples drawn in the morning of the same months. RESULTS: Both groups of APS and T1DM patients showed 25-OHD levels significantly lower than healthy controls (p < 0.001 for both vs controls), without any significant difference between the two groups (p = 0.80). The highest prevalence of vitamin D deficiency (values <20 ng/ml) was observed in APS type 3 subgroup (8 out of 50 patients, 16%). CONCLUSIONS: Patients with APS present reduced vitamin D circulating levels, but the vitamin D status is not different between patients with single or multiple autoimmune diseases. The kind of autoimmune disease, rather than the association of several autoimmune diseases, may influence negatively the levels of vitamin D. Further prospective studies are needed to clarify if impaired vitamin D level is a causal factor in the pathogenesis of autoimmune diseases or a consequence of them.

Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism.

PURPOSE: Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. METHODS: Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. RESULTS: Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. CONCLUSIONS: The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.

Education on physical restraint reduction in dementia care: a review of the literature.

Dementia is a priority area for all countries as populations age and dementia prevalence increases. The use of physical restraint is a possible clinical practice for persons with dementia across settings when behaviours indicate a perceived need. Indeed, this may be the first choice in practice, occurring in part because of lack of education, safety concerns, perceived costs and staffing issues. This article reviews the literature on the issues surrounding, and use of, physical restraint for people with dementia, highlighting the rationales for use and the benefits and barriers to physical restraint. Recommendations include the importance of education and policy to reduce or eliminate physical restraint of persons with dementia to overcome identified barriers at the individual, cultural and organizational levels. An educational programme from the literature review is proposed specific to the reduction or elimination of physical restraint.

Total thyroidectomy without prophylactic central neck dissection combined with routine oral calcium and vitamin D supplements: is it a good option to achieve a low recurrence rate avoiding hypocalcemia? A retrospective study.

AIM: Routine central neck dissection for differentiated thyroid cancer (DTC) to prevent a future recurrence is still a matter of discussion, due to the increased risk of injury to parathyroid glands, without a clear demonstrable benefits in terms of long-term survival. Aim of this study was to investigate if, treating patients with total thyroidectomy (TT) without prophylactic central lymphadenectomy can minimize the risk of hypocalcemia by routine administration of oral calcium and vitamin D supplements, providing at the same time a low recurrence rate. METHODS: In the set of a retrospective study, 221 patients affected by DTC were enrolled. All of them underwent to TT without prophylactic central lymphadenectomy. In the early postoperative period, oral calcium 2g/d taken twice (1 g every 12 hours) and vitamin D 1 g/d taken twice (0.5 g every 12 hours) were administered; changes in serum calcium and hypocalcemia-related symptoms were recorded. Follow-up was based on neck ultrasound and monitoring of serum Tg and Tg-antibodies levels every 6 months during suppressive l-tiroxine treatment. RESULTS: Symptomatic hypocalcemia developed only in 6.3% of patients, whereas laboratory hypocalcemia developed in 10%. Hypocalcemic symptoms were minimal in 4 patients. Intravenous calcium was administered to 6 patients with severe hypocalcemic symptoms. Permanent hypocalcemia developed in two patients. CONCLUSION: Until a conclusive evidence of the actual benefit of prophylactic central lymphadenectomy in the treatment of DTC, it may be avoided. The oral calcium and vitamin D supplements can take a role in the prevention of postoperative hypocalcemia and for increasing the likelihood of a safe and early discharge from the hospital.

Seasonal variations of plasma gonadotropin, prolactin, and testosterone levels in primary and secondary hypogonadism: evidence for an independent testicular role.

BACKGROUND: Seasonal hormonal rhythmicity of the hypothalamic-pituitary-gonadal axis may influence reproductive and sexual activity in mammals. AIM: To investigate whether pituitary-gonadal axis secretion seasonality occurs in men with primary and secondary hypogonadism and whether a hierarchical machinery regulates these variations. SUBJECTS AND METHODS: Six adult males with Klinefelter's syndrome (KS), eight with idiopathic normosmic hypogonadotropic hypogonadism (HH) and ten sex- and age-matched healthy controls were studied longitudinally for one year. Every three months, three plasma samples for assay of testosterone, LH, FSH, and prolactin were drawn and the mean value was used for statistical analysis. RESULTS: Healthy males showed a significant seasonality in LH (zenith in spring) and testosterone (zenith in autumn) but not in FSH and prolactin concentrations. Patients with KS and those with HH showed a seasonal rhythmicity only of testosterone values, even if with small amplitude, with the zenith in spring and summer respectively. CONCLUSION: The lack of dependence of testosterone on gonadotropin variations in normal men and the persistence of seasonal testosterone but not gonadotropin variations both in primary and secondary hypogonadism seem to indicate a possible independent testicular regulation of this seasonality. The shift of testosterone peak in hypogonadal men with respect to controls suggests that LH variations could play a synchronizing, rather than pace-making, role in seasonal testosterone variations. Since hormonal seasonality may also influence gonadal activity in humans, replacement therapy in hypogonadism should be aimed also at restoring a normal seasonal rhythmicity of pituitary-gonadal hormone concentrations.

Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells.

CONTEXT: Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. OBJECTIVE: Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. DESIGN: We conducted a cross-sectional cohort study. PATIENTS: Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. MAIN OUTCOME MEASURES: AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. RESULTS: AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. CONCLUSION: The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

Prospective investigation of pituitary functions in patients with acute infectious meningitis: is acute meningitis induced pituitary dysfunction associated with autoimmunity?

Previous case reports and retrospective studies suggest that pituitary dysfunction may occur after acute bacterial or viral meningitis. In this prospective study we assessed the pituitary functions, lipid profile and anthropometric measures in adults with acute bacterial or viral meningitis. Moreover, in order to investigate whether autoimmune mechanisms could play a role in the pathogenesis of acute meningitis-induced hypopituitarism we also investigated the anti-pituitary antibodies (APA) and anti-hypothalamus antibodies (AHA) prospectively. Sixteen patients (10 males, 6 females; mean ± SD age 40.9 ± 15.9) with acute infectious meningitis were included and the patients were evaluated in the acute phase, and at 6 and 12 months after the acute meningitis. In the acute phase 18.7% of the patients had GH deficiency, 12.5% had ACTH and FSH/LH deficiencies. At 12 months after acute meningitis 6 of 14 patients (42.8%) had GH deficiency, 1 of 14 patients (7.1%) had ACTH and FSH/LH deficiencies. Two of 14 patients (14.3%) had combined hormone deficiencies and four patients (28.6%) had isolated hormone deficiencies at 12 months. Four of 9 (44.4%) hormone deficiencies at 6 months were recovered at 12 months, and 3 of 8 (37.5%) hormone deficiencies at 12 months were new-onset hormone deficiencies. At 12 months there were significant negative correlations between IGF-I level vs. LDL-C, and IGF-I level vs. total cholesterol. The frequency of AHA and APA positivity was substantially high, ranging from 35 to 50% of the patients throughout the 12 months period. However there were no significant correlations between AHA or APA positivity and hypopituitarism. The risk of hypopituitarism, GH deficiency in particular, is substantially high in the acute phase, after 6 and 12 months of the acute infectious meningitis. Moreover we found that 6th month after meningitis is too early to make a decision for pituitary dysfunction and these patients should be screened for at least 12 months. In addition, the occurrence of AHA and APA positivity due to acute infectious meningitis was demonstrated for the first time. Further longer-term prospective investigations need to be carried out on a larger cohort of patients to understand the role of autoimmunity in the pathogenesis of late hypopituitarism after acute infectious meningitis.

Simultaneous evaluation of the circulating levels of both Th1 and Th2 chemokines in patients with autoimmune Addison's disease.

BACKGROUND: Chemokines play a key role in the recruitment of the immune cells into the autoimmune process. Thus, the simultaneous evaluation of circulating levels of Th1-related chemokines, such as CX chemokine ligand 10 (CXCL10) and macrophage inflammatory proteins 1α (CCL3/MIP-1α), and Th2-related chemokines, such as macrophage inflammatory proteins 1 ß (CCL4/MIP-1ß) could be useful in the approach to some autoimmune diseases, including autoimmune Addison's disease (AAD). AIM: To evaluate plasmatic levels of MIP-1α, MIP-1ß, CXCL10 and adrenocortical antibodies in patients with AAD under treatment with corticosteroids. PATIENTS AND METHODS: Twelve women and 5 men (group 1) were divided in 2 subgroups: 9 subjects with isolated AAD (group 1a) and 8 with AAD associated with chronic autoimmune thyroiditis (group 1b). MIP-1α, MIP- 1ß and CXCL10 were evaluated in the serum of all patients and in 20 healthy controls, using a system for microarray suspension. RESULTS: The levels of MIP-1α, MIP-1ß and CXCL10 resulted significantly increased vs controls (p<0.001). An inverse significant correlation between the serum levels of MIP- 1ß and the duration of the disease was observed. CONCLUSION: High levels of MIP-1α and MIP-1ß associated with increased levels of CXCL10 in AAD seem to indicate a role of these chemokines in the autoimmune pathology of adrenal gland through the recruitment in loco of Th1 and Th2 cells. The simultaneous measurement of Th1-related chemokines (CXCL10 and MIP-1α) and of Th2-related chemokine MIP-1ß in the serum of patients with AAD would sustain a novel preliminary hypothesis on the immune microenvironment of chronic autoimmune inflammation within adrenal glands.

Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptor α and ß.

Raloxifene (RAL), a selective estrogen receptor (ER) modulator (SERM) seems to induce apoptosis in both androgen-dependent and -independent prostate cell (PC) lines via activation of ERß and an antagonistic effect on ERα. In this study, we evaluated the effects of RAL on epithelial PC growth using the two following in vitro models: the androgen-dependent cell line EPN which expressed both ERs; and a stabilized epithelial cell line derived from a prostate cancer specimen (CPEC), which expressed low levels of ERß and lacked ERα. In EPN cells, there was an increase in the pre-G1 apoptotic peak and a reduction in the S phase of the cell cycle with G0/G1 arrest after E2 or RAL treatment; bcl-2 mRNA and Bcl-2 protein levels were significantly reduced, while activated caspase-3 and Par-4 levels increased significantly after either E2 or RAL treatment; in addition, c-myc transcript was inhibited after 10(-6) M RAL treatment. A dose-dependent increase of metallothionein II gene RNA level was also induced by RAL in EPN. In CPEC, there was only a weak apoptotic peak associated with caspase-3 activation and Par-4 increase after either E2 or RAL treatment; while c-myc transcript level increased. RAL induced a rapid but transient phosphorylation of ERK 1/2 in EPN cells but generated a sustained effect in CPEC. These findings suggest that RAL effects on PC growth control in vitro are cell-specific, depending on ERß or ERß/ERα relative expression levels. Moreover, this study demonstrated that RAL affected both transcriptional regulation and non-genomic signals, which resulted in the modulation of multiple signaling pathways of apoptosis and of cell cycle progression.

Efficacy of recombinant human follicle stimulating hormone at low doses in inducing spermatogenesis and fertility in hypogonadotropic hypogonadism.

BACKGROUND: Recombinant-FSH (rFSH) added to hCG at dose of 450 IU weekly is effective in inducing spermatogenesis in patients with hypogonadotropic hypogonadism (HH), but there are no data on the use of lower doses. AIM: This observational retrospective study evaluated whether 150-225 IU of rFSH weekly were able to induce spermatogenesis in HH men who failed to start it with hCG alone. SUBJECTS AND METHODS: Thirty-four patients with pre-pubertal onset HH (20-44 yr old) without adverse fertility factors were considered for this study. After hCG pre-treatment they received also either rFSH (Group 1) or highly purified urinary FSH (hpFSH) (Group 2) 75 IU sc 2 or 3 times weekly. Semen analysis was performed every 3 months during pre-treatment and the 1st yr of combined therapy. Patients were also invited to refer pregnancies in their partners during the subsequent 12 months. RESULTS: Total sperm count/ejaculate did not show significant difference between 2 groups, while a significantly higher forward motility was observed in Group 1 (p<0.05). The median times to achieve sperm output thresholds (first sperm appearance, sperm concentration >1.5 or >5 mil/ml) were significantly lower in Group 1 (p<0.04, 0.03, and 0.001, respectively). A tendency to a shorter time to pregnancy was shown in partners of Group 1. CONCLUSIONS: Our data indicate that lower rFSH week dose than that so far used was able to induce potentially fertilizing sperm output in HH men previously treated with hCG. The rFSH effects are comparable to those of hpFSH but with a trend to a faster outcome achievement.

Long term predictors of post-partum glucose metabolism in women with gestational diabetes mellitus.

AIMS: The question asked by this study was whether ß-cell function expressed by insulin secretion/sensitivity measured during pregnancy in women with gestational diabetes (GDM) predicts post-partum long-term derangement in glucose metabolism. METHODS: Seventy-four Caucasian women with previous GDM were retested through a 75 g-2-h-OGTT after 8 [6] years (median[interquartile range]) from index pregnancy, measuring at pregnancy and follow-up insulin sensitivity, insulin secretion (1-h-incremental-insulin-area/incremental-glucose-area: ΔAUC60 (I)/ΔAUC60 (G)) as well as the product of Stumvoll-first-phase - secretion x insulin sensitivity (insulin-secretion-sensitivity index (ISSI). RESULTS: At follow-up 47 women were normotelerant to glucose and 27 had altered glucose metabolism (AGM:10 with type 2 diabetes and 17 with IGT). Women progressed to AGM had at their index pregnancy higher mean 2-h-OGTT-glucose area (1.15±0.09 VS. 1.09±0.09 mol l 2-h (-1);p=0.014), and lower ΔAUC60 (I)/ΔAUC60 (median [interquantile range]) (54.4 [51.7] vs. 73.4 [60] pmol mmol (-1)) and ISSI (2 977 [766] vs. 3 708 [1 141]; p<0.05 for both), but similar insulin sensitivity index 2.9 [2.5] VS. 3.2 [2.2] ml min (-1) m (-2);p=NS). Two-h-OGTT-glucose area, or decrease in ΔAUC60 (I)/ΔAUC60 (G) and ISSI were significantly associated with glucose tolerance impairment and with raised adjusted risk for AGM while insulin sensitivity at pregnancy did no predict AGM development. CONCLUSIONS: In this group of women increased post-load plasma glucose and impaired ß-cell function assessed during GDM pregnancy predict long-term post-partum AGM, while insulin sensitivity measured at the same time does not.

Evaluation of GH-IGF-I axis in adult patients with coeliac disease.

The aim of this study was to evaluate GH/IGF-I axis and other pituitary functions in adult patients with coeliac disease. For this purpose, twenty-eight adult coeliac patients [20M, 8F:19-74 years; body mass index (BMI): 18.5-28 kg/m (2)] were recruited. Basal thyroid, adrenal and gonadal function, serum IGF-I and PRL, and routine parameters were evaluated. Dynamic GH secretion was carried out by GHRH plus arginine test. In 20 patients, antipituitary antibodies (APA) were also evaluated. Seven out of 28 patients, independently from disease onset and the gluten-free diet (GFD), showed an impaired GH secretion (25%). All were males, 2 with severe growth hormone deficiency (GHD) and 5 with partial GHD. In patients with GHD, as compared to coeliac patients with normal GH secretion, HOMA (2.1+/-1.2 vs. 0.9+/-0.4) and QUICKI (0.35+/-0.03 vs. 0.39+/-0.02) levels were significantly higher and lower, respectively, while IGF-I levels were slightly lower (17.7+/-3.7 vs. 24.7+/-6.3, p=NS). APA were negative in all 20 patients studied. In conclusion, a significant number of adult coeliac patients show an impaired GH secretion, this alteration being predominant in males and independent from disease onset and diet regimen. Given the absence of APAs, the cause of this pituitary dysfunction remains unclear even if a previous autoimmune involvement in some cases cannot be excluded.

Growth hormone deficiency and antipituitary antibodies in a patient with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and T-lymphocytes dysfunction. Autoimmune diseases are frequent. A 10.7-yr-old female, diagnosed with CVID when 7 yr old, was referred because of short stature. She was pre-pubertal and short (height -2.86 SD score) with delayed bone age. Her intestinal absorption, routine biochemistry, heart, renal, liver, and thyroid functions were normal. Two stimulation tests for GH showed a maximum peak of 1.9 ng/ml (IGF-1: 154 ng/ml, 147-832). When the patient was 13 yr old (height -4.23 SD score, telarche and pubarche stage 2, bone age 6.25 yr), GH treatment was initiated. Despite poor compliance, the growth velocity showed improvement. Anti-thyrogobulin, anti-thyroperoxidase, anti-21-hydroxylase, and anti-tyrosine-phosphate antibodies were negative while anti- pituitary antibodies (APA) were positive. For the first time, the presence of APA (previously associated with GH deficiency in non-CVID subjects) is reported in a CVID patient. The possibility of an autoimmune involvement of the pituitary gland was previously debated for CVID patients, but had never been demonstrated. This case suggests that in CVID, the pituitary gland can be targeted by autoantibodies and thus a more comprehensive follow-up of these patients should be performed.

Antipituitary antibodies in dutch patients with idiopathic hypopituitarism.

BACKGROUND: Despite extensive research, in the majority of patients with isolated growth hormone deficiency (IGHD) and multiple pituitary hormone deficiency (MPHD), the cause of their clinical picture remains unknown. Recent articles suggest that some cases of idiopathic growth hormone deficiency might be explained by a silent form of autoimmune hypophysitis based on the presence of antipituitary antibodies (APA) at high titers (>1:8). METHODS: We collected clinical data and serum from 71 patients participating in the Dutch HYPOPIT study. APA screening in 40 IGHD patients and 31 MPHD patients was performed by an indirect immunofluorescence method. APA, when present, were related to clinical and morphological pituitary findings. RESULTS: APA were present at high titers in 7 of 31 MPHD patients (23%) and 1 of 40 IGHD patients (2.5%). Among APA-positive MPHD patients, apart from growth hormone deficiency, all patients of pubertal age had gonadotroph defi- ciency, all had thyroid hormone deficiency and 50% had ACTH deficiency. CONCLUSION: The high frequency of APA in our idiopathic MPHD population indicates that, in 23% of the patients diagnosed with idiopathic MPHD, the hormone deficiencies might actually be caused by a silent form of autoimmune hypophysitis. Screening for APA should therefore be considered in all patients with 'idiopathic' MPHD.

Seminal anti-Müllerian hormone level is a marker of spermatogenic response during long-term gonadotropin therapy in male hypogonadotropic hypogonadism.

BACKGROUND: In adult men, anti-Müllerian hormone (AMH) levels are higher in semen than in serum, but the significance and control of its seminal secretion are still unknown. This study evaluated seminal and serum AMH levels during long-term gonadotropin therapy in men with hypogonadotropic hypogonadism (HH). METHODS: A total of 20 men with never treated prepubertal-onset HH received i.m. hCG to normalize testosterone (T) and induce puberty. Afterwards, 11 of them, requiring fertility, were treated with HCG plus recombinant FSH (rFSH) (75 IU) twice a week, whereas 9 continued to receive hCG alone for 12 months. Before and during therapy, serum AMH, inhibin B and T levels were assessed. Semen samples were also collected during therapy for sperm count and seminal AMH assay. RESULTS: HCG alone decreased basal high serum AMH and stimulated T and inhibin B levels. rFSH plus hCG increased seminal AMH levels, which were consequently significantly higher than with hCG alone, and positively correlated to sperm densities and testicular volumes at 3 and 12 months (P < 0.001). CONCLUSIONS: Our data demonstrate that rFSH, added to hCG, stimulates seminal AMH and spermatogenesis in HH. Thus, seminal AMH levels are under T and FSH control and are closely related to progression of spermatogenesis. Our results also suggest that an early seminal AMH increase may be a marker of good future response to gonadotropin therapy in HH.