[Oral carbohydrate tolerance and insulin response in thyrotoxicosis and hypothyroidism].
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Biomedical subjects
Publications and source records attributed to C Scandellari.
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The possibility that dietary-induced thermogenesis may be decreased in obesity has been proposed in recent years. However, the results of human studies so far obtained are conflicting. The present research was undertaken in order to clarify this question. We studied postprandial thermogenesis induced by ingestion of a mixed meal and of a carbohydrate mixture in 15 normal and 12 obese subjects. Blood glucose and plasma insulin levels were measured at the same time. The data obtained have shown that the mean resting metabolic rate (RMR) expressed as a function of body weight3/4, is almost the same in obese as in normal-weight subjects (0.115 +/- 0.018 vs 0.133 +/- 0.021 kj/min/kg3/4, respectively). Moreover, the increment of mixed-meal induced thermogenesis (MM-IT) was 48 +/- 22% in normal and -0.8 +/- 12% in obese subjects, respectively (p less than 0.01). Carbohydrate induced thermogenesis (CHO-IT) appeared slightly higher in normal-weight than in obese subjects (159 +/- 66 vs 98 +/- 46). After carbohydrate ingestion we observed a higher glycemic and insulinemic response in obesity. These results indicate that thermogenesis induced by ingestion of food is reduced in obese subjects; they are also compatible with the idea that insulin resistance could play a role in this phenomenon.
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In order to determine the endocrine and metabolic state of thyrotoxicosis we measured blood glucose and plasma insulin response to ingestion of a mixed meal in 19 euthyroid and 9 hyperthyroid subjects. Moreover concentrations of glucose, free fatty acids (FFA), glycerol, acetoacetate (AcAc) beta-hydroxybutyrate (beta-OHB), insulin and human growth hormone (hGH) were determined in the blood of both healthy and hyperthyroid patients after an overnight and a 39-h fast. In another group of thyrotoxics the overnight fasting respiratory quotient (RQ) was measured. After a mixed meal blood glucose and plasma insulin changes of FFA, AcAc and beta-OHB was significantly higher in thyrotoxics, whereas hGH increase did not appear significantly greater in these subjects. There was no statistical difference between the respiratory quotient mean values found in hyperthyroid and in control subjects. In conclusion, these data indicate that in thyrotoxicosis absolute insulin response to a mixed meal is normal and that food deprivation considerably increase lipid mobilization from adipose tissue and causes an exaggerated starvation ketosis. The RQ mean valoue suggests that in the hyperthyroid state lipid-derived fuel as well as carbohydrate-derived fuel contributes to the increased oxygen consumption.
After establishing the diagnosis of an insulinoma, most surgeons prefer preoperative localization. Selective arteriography is usually considered the gold standard for this purpose. Recently, computed tomography (CT) and preoperative US have contended the role to angiography. MRI has been used in few cases of endocrine pancreatic tumors, and its role in this particular field has to be defined. Between November 1988 and September 1990 we evaluated 7 adult patients who had had surgery in our Surgical Department. Eight tumors were resected in 6 patients who were cured; in an 18-year-old woman surgical treatment was unsuccessful. Arteriography, CT, preoperative US, MRI and intraoperative US detected 2, 6, 6, 5 and 6 tumors, respectively. Two insulinomas (0.2 and 0.7 cm) were found at histologic examination in resected specimen. The ability of intraoperative US and careful surgical exploration to resolve more than 90% of cases makes the preoperative use of arteriography and CT of questionable value. If further experience confirms these findings, US and MRI may suffice.
To study the opioid control on LH and FSH secretion in Klinefelter subjects (KS), the response of gonadotropin to an opioid antagonist, naloxone, was examined in 8 KS (age range 25-35 yrs) and in 8 age matched normal men. In 6 KS with low testosterone plasma levels, naloxone infusion were also performed after treatment with testosterone enanthate, 200 mg i.m. every 3 weeks for 4 months. FSH did not show any important variation in KS and in normal men during naloxone infusion. In KS the percentage of naloxone induced LH increase was significantly lower than in controls and there was no correlation between testosterone plasma levels and LH increase after naloxone infusion. LH increases after naloxone infusion were not significantly different before and after testosterone treatment. The increases of naloxone induced LH plasma levels, before and after testosterone treatment, correlated well between themselves (r = 0.93-p less than 0.01). Plasma levels decreased in all patients after testosterone treatment, but only in two was there a return to normal range. There is a clearly positive linear correlation between the percentage of LH decrease after testosterone treatment and LH increase after naloxone infusion (r = 0.81; p less than 0.01). After testosterone therapy FSH plasma levels fall by 63 +/- 15% in all patients and did not show any important variation after naloxone infusion. In conclusion, our data are in agreement with the hypothesis that in Klinefelter's syndrome an alteration of opioid control on gonadotropin secretion may exist. This alteration does not appear to be due to androgen deficiency, but rather it may be caused by genetic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
We determined the calcitonin (CT) levels in peripheral plasma and in seminal fluid of 15 normal human subjects: the concentration of the hormone in seminal fluid was about 30 times higher than the concentration found in peripheral plasma. We also studied the localization of calcitonin on human spermatozoa by means of an indirect immunofluorescent technique, using an anti-human CT rabbit serum and a fluorescein-isothiocyanate conjugated goat anti-rabbit immunoglobulins serum. A bright fluorescence was observed at the middle piece and neck, while the tail's principal piece was weakly stained. With an anti-human CT rabbit serum pre-absorbed with human CT no fluorescent staining was detectable. These findings demonstrate that calcitonin is localized onto spermatozoa and suggest a potential role for calcitonin in the calcium dependent-mechanisms of spermatozoa.
Ex-cryptorchid subjects are frequently affected by infertility, even if the usually determined seminal parameters are still within the normal range. We evaluated in this study, in 14 ex-unilateral cryptorchid adult males (22-28 years), with normal sperm concentration, morphology and viability, the resistance of sperm nuclear chromatin to denaturation, using the fluorochrome acridine orange, which fluorescences green when bound to native DNA (double stranded) and red when bound to denaturated DNA (single stranded). Our findings demonstrate that the percentage of green-stained cells with acridine orange was significantly lower in our patients than in controls (p less than 0.001). We therefore suggest that the chromatin of ex-cryptorchid subjects' spermatozoa has a decreased resistance to denaturation and we hypothesize that this finding may explain the infertility of these patients, when the common seminal parameters are still within the normal range.
An indirect immunofluorescence technique was used to detect and localize epidermal growth factor receptors (EGFR) in human testicular biopsies in different testicular diseases. Monolateral biopsies from twelve infertile subjects were studied from qualitative/quantitative points of view and were examined by immunofluorescence study with anti-EGFR monoclonal antibody. Two different patterns of EGFR expression were observed: a very weak presence of EGFR was detectable on Sertoli cells, peritubular basal structures, and interstitial compartment in testicular biopsies showing a normal spermatogenic status; and an important increase in EGFR expression was observed on the cytoplasm of Sertoli cells and on peritubular basal structures in biopsies exhibiting various degrees of hypospermatogenesis and in a case of Sertoli cells only syndrome. Germ cells did not show EGFR immunolocalization. EGFR seems to be present on different testicular target cells. EGFR expression increases on peritubular and Sertoli cells in the presence of significant tubular damage.
We investigated the possible role of Y chromosome microdeletions in regions previously shown to be important for male germ cell development in unilateral ex-cryptorchid subjects manifesting important bilateral testiculopathy, in order to clarify whether cryptorchidism could be the expression of an intrinsic congenital testicular abnormality. Microdeletion analysis of the Y chromosome long arm was performed by polymerase chain reaction and confirmed by Southern blot in 40 selected unilateral ex-cryptorchid patients with azoospermia or severe oligozoospermia sustained by severe bilateral testiculopathy (Sertoli cell-only syndrome and severe hypospermatogenesis, respectively), 20 unilateral ex-cryptorchid men with moderate oligozoospermia and normal function of the descended testis, 110 patients affected by severe idiopathic primary testiculopathies, 20 patients affected by moderate idiopathic testiculopathy and, as controls, 50 patients affected by known causes of testiculopathy and 50 fertile controls. Eleven out of the 40 (27.5%) unilateral ex-cryptorchid patients affected by bilateral testiculopathy and 28 out of 110 (25.4%) patients affected by severe idiopathic primary testiculopathy showed microdeletions in the Y chromosome long arm, while all other subjects were normal. Male relatives of patients with deletions were also normal. Microdeletions were distributed in different regions of the Y chromosome long arm, including known regions involved in spermatogenesis (DAZ and RBM genes, AZFa, b and c regions) and other still poorly defined loci. No difference in localization of deletions was evident between ex-cryptorchid and idiopathic patients. Microdeletions in the Y chromosome may be responsible for bilateral severe testicular damage: the clinical consequence, other than idiopathic azoospermia and severe oligozoospermia, may also be unilateral cryptorchidism, probably due to altered testicular responses to mechanisms regulating testicular descent.
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The continuing search for a cure for cancer has developed more aggressive therapies that may damage germ cells, leading to clinical disease in offspring of survivors. Standard therapy for the majority of cancer today consists in combinations of high doses of radiation and chemotherapy drugs. We investigated the effect of cancer treatments on the reproductive potential of men. Multicolor fluorescence in situ hybridization has been used to recognize chromosomes X, Y and 8 in sperm of 10 severely oligozoospermic subjects (sperm concentration < 5,000,000/mL) treated for cancer at least 5 years before the beginning of this study. As controls, we analyzed sperm aneuploidies in 20 fertile men (sperm concentration > 20,000,000/mL) and in 20 severe idiopathic oligozoospermic subjects (sperm concentration < 5,000,000/mL). In all subjects, X- and Y-bearing spermatozoa were present in a normal 1:1 ratio; nevertheless the frequency of 24,XY, 24,XX and 24,YY disomic sperm was significantly higher in patients treated for cancer and in idiopathic oligozoospermic subjects with respect to normozoospermic men. These results suggest that the increase in sperm aneuploidies in treated patients cannot be reported directly to precedent chemotherapy, but reflects the alteration of testicular structure, as in the case of severe idiopathic oligozoospermic subjects. With the advent of intra-cytoplasmic sperm injection, it is possible to offer the opportunity to conceive in men affected by severe oligozoospermia but it is also possible, when the spermatozoa of these subjects are used, to pass sex chromosome abnormalities on to the children. We therefore suggest caution before application of an artificial reproductive technique in severe oligozoospermic patients.
Microdeletions of the Y chromosome represent the most frequent cause of male infertility, being responsible for 10-15% of cases of azoospermia or severe oligozoospermia. Such mutations localize in one or more loci named azoospermia factor (AZF) a, b and c. Mutations more frequently involve the DAZ gene in AZFc, and could determine both azoospermia and severe oligozoospermia. It is therefore difficult to find a clear relationship between genotype and phenotype. DAZ is present in multiple copies in AZFc, and this causes the gene to be difficult to analyze. In fact, polymerase chain reaction, the principal technique utilized for detection of the deletions, cannot distinguish among the different copies of the gene. Furthermore, it is not clear if all the DAZ copies are expressed in the testis, and other genes, such as CDY1, map in AZFc; therefore their alteration may play a role in determining the phenotype. In this review we report the current knowledge on the function of the Y chromosome in human spermatogenesis. In particular we analyze some of our experimental studies on the role of the DAZ gene family. Expression studies allowed us to clarify that an altered expression of DAZ might cause infertility in patients with severe testiculopathies. Furthermore, we describe for the first time a deletion not involving all the DAZ copies in a patient with severe hypospermatogenesis and we clarify that CDY1 is not involved in the testicular damage observed in patients with deletions of DAZ. These studies elucidate the role of DAZ and have important clinical consequences in the diagnostic and therapeutic approach of the infertile patient, above all when he is a candidate for assisted reproduction techniques, due to the possibility of transmitting the genetic alteration to the offspring.
Anomalies in prostaglandin (PG) synthesis have been suggested in both experimental and human diabetes mellitus; increased levels of plasma and tissue eicosanoids has been recently reported by several investigators. One step in prostaglandin synthesis is the enzymatic hydrolysis of membrane phospholipids by Phospholipase A2 (PLA2). Nevertheless the alternative pathway involving Phospholipase C must be considered. An evaluation of PLA2 activity is therefore a useful method for studying prostaglandin synthesis in the peripheral target tissues of insulin activity. We studied PLA2 activity in normal and diabetic rat muscle. Streptozotocin-induced diabetic rats showed significantly higher muscular PLA2 activity when compared with controls (3.04 x 10(-2) +/- 0.50 x 10(-2) versus 1.34 x 10(-2) +/- 0.35 x 10(-2) arachidonic acid pMol.mg protein-1.min-1 (p less than 0.01). This effect was not observed in diabetic animals successfully treated with insulin (1.78 x 10(-2) +/- 0.5 x 10(-2) versus 1.34 x 10(-2) +/- 0.35 x 10(-2) arachidonic acid pMol.mg protein-1.min-1), and a significant correlation was found between blood glucose and muscular PLA2 activity (r = 0.42; p less than 0.05). Our results clearly show that in streptozotocin-induced diabetic rats muscular PLA2 activity is significantly higher. The relationship between blood glucose levels and muscular PLA2 activity and the decrease of PLA2 activity after insulin treatment suggest that these changes may be related to a defect in insulin effect.
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