Screening of endocrine organ-specific humoral autoimmunity in 47,XXY Klinefelter's syndrome reveals a significant increase in diabetes-specific immunoreactivity in comparison with healthy control men.

The aim of this study was to evaluate the frequency of humoral endocrine organ-specific autoimmunity in 47,XXY Klinefelter’s syndrome (KS) by investigating the autoantibody profile specific to type 1 diabetes (T1DM), Addison’s disease (AD), Hashimoto thyroiditis (HT), and autoimmune chronic atrophic gastritis (AG). Sixty-one adult Caucasian 47,XXY KS patients were tested for autoantibodies specific to T1DM (Insulin Abs, GAD Abs, IA-2 Abs, Znt8 Abs), HT (TPO Abs), AD (21-OH Abs), and AG (APC Abs). Thirty-five of these patients were not undergoing testosterone replacement therapy TRT (Group 1) and the remaining 26 patients started TRT before the beginning of the study (Group 2). KS autoantibody frequencies were compared to those found in 122 control men. Six of 61 KS patients (9.8 %) were positive for at least one endocrine autoantibody, compared to 6.5 % of controls. Interestingly, KS endocrine immunoreactivity was directed primarily against diabetes-specific autoantigens (8.2 %), with a significantly higher frequency than in controls (p = 0.016). Two KS patients (3.3 %) were TPO Ab positive, whereas no patients were positive for AD- and AG-related autoantigens. The autoantibody endocrine profile of untreated and treated KS patients was not significantly different. Our findings demonstrate for the first time that endocrine humoral immunoreactivity is not rare in KS patients and that it is more frequently directed against type 1 diabetes-related autoantigens, thus suggesting the importance of screening for organ-specific autoimmunity in clinical practice. Follow-up studies are needed to establish if autoantibody-positive KS patients will develop clinical T1D

Endocrine and metabolic evaluation of classic Klinefelter syndrome and high-grade aneuploidies of sexual chromosomes with male phenotype: are they different clinical conditions?

Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy in males. As well as classic KS, less frequent higher-grade aneuploidies (HGAs) are also possible. While KS and HGAs both involve testicular dysgenesis with hypergonadotropic hypogonadism, they differ in many clinical features. The aim of this study was to investigate the endocrinal and metabolic differences between KS and HGAs.Objective: Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy in males. As well as classic KS, less frequent higher-grade aneuploidies (HGAs) are also possible. While KS and HGAs both involve testicular dysgenesis with hypergonadotropic hypogonadism, they differ in many clinical features. The aim of this study was to investigate the endocrinal and metabolic differences between KS and HGAs. Design: Cross-sectional, case-control study. Methods: 88 patients with KS, 24 with an HGA and 60 healthy controls. Given the known age-related differences all subjects were divided by age into subgroups 1, 2 and 3. Pituitary, thyroid, gonadal and adrenal functions were investigated in all subjects. Metabolic aspects were only evaluated in subjects in subgroups 2 and 3. Results: FT4 and FT3 levels were significantly higher in HGA than in KS patients in subgroups 1 and 2; in subgroup 3, FT4 was significantly higher in controls than in patients. Thyroglobulin was significantly higher in HGA patients in subgroup 1 than in KS patients and controls. Hypergonadotropic hypogonadism was confirmed in both KS and HGA patients, but was more precocious in the latter, as demonstrated by the earlier increase in gonadotropins and the decrease in testosterone, DHEA-S and inhibin B. Prolactin was significantly higher in HGA patients, starting from subgroup 2. Total and LDL cholesterol were significantly higher in HGA patients than in KS patients and controls, while HDL cholesterol was higher in controls than in patients. Conclusions: KS and HGAs should be considered as two distinct conditions

Ormone anti-mülleriano (AMH): funzione e livelli nell’uomo e nella donna

L’ormone anti-Mülleriano (AMH) è una glicoproteina appartenente alla superfamiglia del TGF-β, inizialmente identificato come responsabile della differenziazione dell’apparato genitale maschile. L’AMH è prodotto come pro-ormone costituito da due monomeri, uniti mediante ponti disolfuro, che subiscono un clivaggio proteolitico a formare due omodimeri: il primo costituito dalle pro-regioni N-terminali e l’altro dalle regioni mature C-terminali. Questi rimangono legati in maniera non-covalente a formare un complesso circolante di 140 kDa

Inibina come marker di qualità seminale

L’inibina (Inh) è un ormone glicoproteico, della superfamiglia del TGF-β, che nell’adulto down-regola la produzione di FSH da parte delle cellule gonadotrope dell’adenoipofisi. E’ un eterodimero di 31–33 kDa composto da due subunità: la subunità-α (αC) e la subunità-β (βAo βB) unite da due ponti disolfuro a formare, rispettivamente, l’InhA o l’InhB. Ciascuna possiede un peculiare profilo di produzione, azione ed integrazione nel complesso sistema che regola l’asse ipotalamo-ipofisi-gonadi. Attualmente disponiamo di tecniche ELISA, che si basano su metodiche a sandwich con doppio anticorpo, dotate di buona sensibilità (fino a 4 pg/mL per l’InhB) e notevole specificità, in grado di discriminare le subunità-αC, -βA o -βB. Nell’uomo si trova solo l’InhB che viene prodotta essenzialmente nella gonade, come dimostrano i dati nei pazienti anorchidi dove l’ormone risulta costantemente indosabile. La fisiologia della secrezione dell’ormone spiega perché, nell’uomo adulto, sia stata dimostrata da diversi autori una forte correlazione positiva tra spermatogenesi, in termini di concentrazione per ml e numero totale per eiaculato e livelli sierici di InhB. Numerosi studi di popolazione hanno indicato come limite inferiore di riferimento per questo ormone in soggetti normozoospermici valori variabili tra 48 e 105 pg/mL, anche se prendendo in considerazione la normalità di tutti i parametri seminali il valore ottimale dovrebbe essere di 80–90 pg/mL

Evidence of increased humoral endocrine organ-specific autoimmunity in severe and classic X-chromosome aneuploidies in comparison with 46,XY control subjects

In literature, the importance of X-linked gene dosage as a contributing factor for autoimmune diseases is generally assumed. However, little information is available on the frequency of humoral endocrine organ-specific autoimmunity in X-chromosome aneuploidies. In our preliminary study, we investigated the endocrine organ-specific humoral autoimmunity relative to four different organ-specific autoimmune diseases in a group of adult 47,XXY KS patients and in adults 46,XY control males (type 1 diabetes, T1DM; Addison's disease, AD; Hashimoto thyroiditis, HT; autoimmune chronic atrophic gastritis, AG). The aim of the present study is to evaluate the frequency of autoantibodies (Abs) specific for T1DM, AD, HT, and AG in rarer higher grade X-chromosome aneuploidies (HGA) and in 47,XXY children

A multicenter evaluation of immunoassays for follicle-stimulating hormone, luteinizing hormone and testosterone: Concordance, imprecision and reference values

Background: Numerous laboratories in Italy use radioimmunoassay to determine concentrations of sex hormones (FSH, LH, testosterone). A comparison of assay methods is thus an important starting point for the achievement of universally accepted reference values. Aim: To carry out an external quality assessment for FSH, LH, and testosterone. Materials and methods: Fifteen aliquots from 5 serum pools were assayed in multiple replicates by 16 Italian laboratories with 5 automated immunoassays (Abbott Architect, DiaSorin Liaison, Perkin-Elmer AutoDelfia, Roche Elecsys, Siemens Immulite 2000), and 1 radioimmunoassay (Adaltis). Results: The variance was below 12% for FSH, between 11.61% and 14.76% for LH, and between 9.57% and 12.48% for testosterone. Assay precision was good, except for Elecsys at low concentrations of FSH and for Immulite at low concentrations of LH and testosterone. ARCHITECT showed a negative bias for FSH and LH and a positive bias for testosterone; Liaison a positive bias for LH; Elecsys a positive bias for FSH and a negative bias for testosterone; Immulite a positive bias for FSH; AutoDelfia a negative bias for FSH and a positive bias for testosterone. Reference ranges at the low end varied widely, even among laboratories using the same assay. Conclusions: The analytical performances of widely used immunoassays for FSH, LH, and testosterone show a fair to strong degree of consistency. A careful evaluation of reference ranges by clinical and laboratory experts needs to be carried out, in order to reach a (C) 2013, Editrice Kurti

A combined form of hypothyroidism in pubertal patients with non-mosaic Klinefelter syndrome

Klinefelter syndrome has been associated with thyroid abnormalities, the genesis of which is not yet fully clear. The aim of this study was to evaluate thyroid function in Klinefelter syndrome subjects during the pubertal period. Chemiluminescent microparticle immunoassay was used to analyze Thyroid-Stimulating Hormone, fT3 and fT4 concentration in serum samples from 40 Klinefelter syndrome pubertal boys with classic 47,XXY karyotype and 157 healthy age-matched controls. 13 Klinefelter syndrome patients also underwent Thyrotropin-Releasing Hormone testing to evaluate hypothalamic-pituitary function. fT3 levels were significantly lower in Klinefelter syndrome patients than in age-matched controls (p < 0.001). No significant differences were found for Thyroid-Stimulating Hormone (p = 0.138) or fT4 (p = 0.274), but the serum levels of Klinefelter syndrome patients tended to cluster around the lower part of the reference range for the assay. Three of the thirteen Klinefelter syndrome patients undergoing the Thyrotropin-Releasing Hormone test had an adequate response, one had a prolonged response at 60 min and nine responded inadequately. This study demonstrated for the first time that pubertal Klinefelter syndrome patients have significantly lower fT3 serum levels than do healthy age-matched boys, whereas Thyroid-Stimulating Hormone and fT4 are normal, albeit at the lower end of the reference range. Most patients showed an inadequate/prolonged response to pituitary stimulation with Thyrotropin-Releasing Hormone. These findings suggest a combined form of both central and peripheral hypothyroidism in Klinefelter syndrome boys during pubertal development

Inhibin B: are modified ranges needed for orchiectomised testicular cancer patients?

Inhibin B is a gonadal hormone that downregulates the pituitary production of follicle-stimulating hormone (FSH). In recent years, inhibin B has proved to be an excellent marker of spermatogenesis and even a predictive factor for the recovery of fertility in patients undergoing orchiectomy and antineoplastic treatments. We propose to study inhibin B levels in orchiectomised testicular cancer patients, in order to identify a minimum value representative of normal semen quality. This retrospective study evaluates hormonal and semen parameters of 290 normozoospermic patients attending the Laboratory of Seminology - Sperm Bank “Loredana Gandini” (Rome, Italy) for cryopreservation of seminal fluid following a diagnosis of testicular cancer (TC group) and 117 healthy, normozoospermic men as a control group (CTR group). The percentile distribution of gonadotropin and inhibin B values in the TC and CTR groups was analyzed. There was a statistically significant difference between the two groups in the levels of all hormones (P ≤ 0.001) and in all semen parameters (P &lt; 0.05). About 20% of TC patients revealed inhibin B levels below the 5th percentile of CTR group, despite normozoospermia, and 31.4% had normal spermatogenesis in the presence of FSH values &gt;95th percentile of CTR group. Orchiectomised patients for testicular cancer presented inhibin B levels lower than healthy patients, despite normozoospermia. Our study revealed the poor sensitivity of the current inhibin B reference range when applied to monorchidic patients, suggesting the need to establish more representative ranges to enable more appropriate counseling in relation to the patient’s new endocrine condition