Letizia Pasqui

The use of ultrasensitive thyroglobulin assays reduces but does not abolish the need for TSH stimulation in patients with differentiated thyroid carcinoma.

Measurement of serum Tg using ultrasensitive assays is proposed to replace TSH-stimulated Tg measurement in the follow-up of differentiated thyroid cancer (DTC). Aim of our study was to verify this possibility using two ultrasensitive Tg assays. We selected 215 DTC patients with undetectable (<1 ng/ml) basal serum Tg at the time of a recombinant human TSH (rhTSH) stimulation. According to standard criteria, 173 (80.4%) patients were considered free of disease, 17 (7.9%) had documented disease and 25 (11.7%) had no evidence of disease but detectable serum rhTSH-stimulated Tg (biochemical disease). The sera of these patients were re-assayed with two commercial ultrasensitive assays and the results were compared with the clinical data. Basal Access and E-Iason Tg assays were able to distinguish patients with persistent disease or free of disease with a sensitivity of 82.3 and 82.3%, specificity of 85.5 and 86.1%, positive predictive value (PPV) of 35.8 and 36.8%, negative predictive value (NPV) of 98 and 98.6%, respectively. With both assays the addition of neck ultrasound to basal Tg increased the sensitivity and the NPV to 100% and decreased the false negative rate to 0%. In patients with detectable basal Tg without evidence of disease, serum Tg converted from detectable to undetectable in about 80% of the cases during 2-yr follow-up. Our study indicates that the combination of neck ultrasound and basal ultrasensitive Tg allows to identify all patients free of disease and can decrease the need for rhTSH stimulation in nearly 80% of the patients.

Hormonal and clinical effects of GnRH agonist alone, or in combination with a combined oral contraceptive or flutamide in women with severe hirsutism

The objective of this prospective randomized study was to evaluate and compare the hormonal and clinical effects of long-acting gonadotropin-releasing hormone (GnRH) agonist and a combination of GnRH agonist with combined oral contraceptive (COC) or flutamide in women with polycystic ovary syndrome (PCOS). Thirty-five hirsute women with PCOS, ranging in age from 19–27 years, were randomly divided into three groups: group A treated with GnRH agonist (n = 12), group B (n = 12) treated with GnRH agonist plus COC and group C (n = 11) treated with GnRH agonist plus flutamide for 6 months. Before, at the end and 6 months after the end of treatment, blood samples were drawn from all women (in early follicular phase in those with menstrual cycles) to measure ovarian and adrenal androgens, gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), estradiol and estrone plasma levels. The results showed that all three protocols had good therapeutic efficacy. A significant reduction in hirsutism was observed in all patients after 6 months of therapy, the Ferriman–Gallwey scores dropping to 9 ± 3 in group A, 10 ± 4 in group B and 11 ± 5 in group C. Six months after the end of therapy, the hirsutism score continued to be significantly reduced in all groups. After 6 months of therapy, a reduction in plasma levels of LH, FSH, estrone, estradiol, testosterone, free testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) was observed in all groups although this was more pronounced in group B and group C. These therapies may be the basis of future treatments that quickly reduce hirsutism and remove its causes by reducing the secretion of ovarian and adrenal androgens and by blocking androgen receptors.

Prevalence of Parietal Cell Antibodies in a Large Cohort of Patients with Autoimmune Thyroiditis

BACKGROUND Autoimmune thyroiditis (AIT) may be associated with other organ-specific autoimmune disorders, including autoimmune gastritis, but the prevalence of this association is not entirely quantified. The aim of this study was to investigate the prevalence of parietal cell antibodies (PCA) in a large cohort of consecutive patients with AIT. METHODS We retrospectively studied 2016 consecutive women and 258 men with AIT seen at our referral center in the period from 2004 to 2008. All patients were screened for the presence of PCA in the serum. RESULTS The prevalence of serum PCA in female patients was 29.7% and progressively increased from 13% in the first-second decade of life to peak at 42% in the ninth decade. During follow up, 21.1% of the PCA-positive patients converted to PCA-negative status. Mean (±standard deviation) basal PCA levels in this group were significantly lower (32 ± 28 U/mL) compared with those remaining PCA positive (129 ± 200 U/mL). A similar prevalence (29.8%) with a similar age-dependency was found in male patients. CONCLUSIONS In conclusion, our study demonstrates a high, age-dependent prevalence of PCA in an unselected large population of patients with AIT.

Serum ghrelin levels in growth hormone-sufficient and growth hormone-deficient patients during growth hormone-releasing hormone plus arginine test

Background and aims: Ghrelin is an orexigenic hormone produced in the stomach and in other organs, exerting a wide range of metabolic functions, including stimulation of GH secretion. Ghrelin secretion is decreased by iv or oral glucose load as well as during euglycemic-hyperinsulinemic clamp and hypoglycemia. We evaluated the circulating ghrelin levels in GH-deficient (GHD) and in GH-sufficient (GHS) patients during GHRH plus arginine test. Materials and methods: The study group comprised 35 patients, including 20 with pituitary tumors, 12 with empty sella, 2 with short stature, and 1 with post-traumatic isolated GH deficiency. According to the results of GHRH plus arginine test, 14 patients were defined as GHD and 21 as GHS. Patients with central hypothyroidism, hypocorticism, and hypogonadism had been on replacement therapy for at least 3 months at the moment of the study. Blood samples were collected every 20 min up to 60 min after GHRH and arginine administration. Results: By definition, GH response to GHRH plus arginine was higher in GHS than GHD group (p<0.0001). Basal serum ghrelin levels were not different in the two groups and did not correlate with body mass index, GH, IGF-I and insulin concentrations. After GHRH plus arginine, serum ghrelin decreased significantly in both groups, with percent decreases ranging 13.3–66.6% in GHD patients (p=0.001) and 7.2–42.2% in GHS patients (p=0.004), with no significant difference in the two groups (p=0.12). Conclusion: Our results show that ghrelin secretion is not modulated by acute GH increase observed in GHS subjects during GHRH plus arginine infusion. The similar decrease of serum ghrelin after GHRH plus arginine stimulation in both GHS and GHD subjects demostrated that there is no negative feedback of GH on ghrelin secretion.

Effects of Acute Recombinant Human TSH on Serum Ghrelin Levels

Recent findings showed the presence of a reciprocal relationship between thyroid hormones and ghrelin, although the exact mechanism is not known. Design: Our study is addressed to evaluate the effect of acute exogenous rhTSH administration on serum ghrelin levels in athyreotic patients on replacement l-thyroxine therapy. The study group included 50 patients (16 males and 34 females) submitted to total thyroidectomy and 131-iodine remnant ablation for differentiated thyroid cancer on l-thyroxine therapy. Mean age was 47.5 ± 16.5 years and mean BMI was 25.6 ± 5.01 kg/m2. rhTSH was administrated at the dosage of 0.9 mg i.m. once daily for two consecutive days. Blood samples were taken between 08.00 and 09.00 after a overnight fasting for measurement of TSH, FT3, FT4, and ghrelin before the first administration of rhTSH and for measurement of TSH and ghrelin 24, 48, 72, and 96 h after the first administration of rhTSH. Results: Mean ± SD values of basal TSH were 0.54 ± 0.77 μU/ml without significant difference between females and males. As expected, after rhTSH administration TSH concentrations increased at 24 and 48 h with peak TSH values ranging from 20.20 to 313 μU/ml (mean ± SD 98.4 ± 66.7 μU/ml). Mean ± SD values of basal ghrelin were 1085 ± 373 pg/ml without significant difference between males and females. After rhTSH administration ghrelin concentrations decreased significantly (p < 0.01) at 24 h (mean ± SD 934 ± 314 pg/ml p < 0.01) and returned to pre-treatment levels at 96 h. Conclusion: Our study demonstrates that acute exogenous TSH administration has a suppressive effect on ghrelin secretion independent from changes in thyroid status.

Glucagon and insulin cord blood levels in very preterm, late preterm and full-term infants

Abstract Background: The cause of hyperglycemia, a frequent disorder of glucose homeostasis in very preterm infants, is still unknown. Objectives: Determine the glucagon and insulin plasma levels at birth in healthy, appropriate for gestational age (AGA) infants born by elective cesarean section (ECS), at different gestational age. Methods: Glucagon, insulin and the homeostasis model of assessment-insulin resistance (HOMA-IR) index were measured in cord blood in 52 AGA infants divided into three groups: ≤30 weeks, very preterm (VP, n=16); 35–37 weeks, late preterm (LP, n=18); ≥38 weeks, full term (FT, n=18). Results: In all enrolled infants, Apgar score at 5 min after birth was 7 to 9. In VP infants, glucagon levels were higher than those in LP (533±116 vs. 211±28 pg/mL) (p<0.001) and FT infants (533±116 vs. 226±20 pg/mL) (p<0.001). Insulin levels were higher in VP than in LP (8.61±2.48 vs. 3.98±0.94 mU/L) (p<0.001) and FT infants (8.61±2.48 vs. 4.56±1.2 mU/L) (p<0.001). HOMA-IR index was higher in VP than in LP and FT infants (30.6±10.2 vs. 11.9±3.04 and 13.5±1.6, respectively) (p<0.001). Conclusion: We concluded that very low gestational age is associated with high glucagon plasma levels and insulin-resistance, which could explain hyperglycemia in the very preterm infants.

Thyroid function in early pregnancy II: Paradoxical growth hormone response to thyrotropin-releasing hormone

A variant of growth hormone (GH) known as human placental growth hormone (hpGH) is found in maternal serum during pregnancy. It is well established that during the second half of normal pregnancy, pituitary GH secretion is suppressed; however, there are no data about maternal GH secretion during the first trimester of pregnancy. The present study reports the response of GH to thyrotropin-releasing hormone (TRH) in eight pregnant women in the trimester of pregnancy (weeks 6-9) who had previously requested voluntary interruption of pregnancy. The TRH test induced a significant paradoxical GH response with a peak of 9.4 +/- 0.5 ng/ml (mean +/- SD) at 30 min and a higher thyroid-stimulating hormone (TSH) response in pregnant women. The increment was observed until 120 min and no response was observed in the control group. These data show the paradoxical response of GH to TRH, a releasing factor to which the hormone does not normally respond. This paradoxical secretion may be due to direct pituitary stimulation and can be explained on the basis of a state of gestational hypothyroidism.

Effects of human chorionic gonadotropin administration on testicular testosterone secretion during prolonged exercise

A decrease in testosterone concentrations in men after prolonged exercise has been confirmed in many studies, although testosterone responses are somewhat variable and seem to depend on the duration and intensity of the exercise (1, 2). The decline in serum testosterone levels after prolonged exercise generally is ascribed to a decrease in the rate of secretion caused by a decrease in testicular blood flow, an increase in body temperature, and an increase in plasma concentrations of prolactin and cortisol. Data have shown that testicular secretion of testosterone may be influenced by prolonged exercise (3), but no direct evidence has yet been adduced.