Chiara Diazzi

Premature decline of serum total testosterone in HIV-infected men in the HAART-era.

Background Testosterone (T) deficiency remains a poorly understood issue in men with Human Immunodeficiency Virus (HIV). We investigated the gonadal status in HIV-infected men in order to characterize T deficiency and to identify predictive factors for low serum T. Methodology/Principal Findings We performed a cross-sectional, observational study on 1325 consecutive HIV male outpatients, most of them having lipodystrophy. Serum total T<300 ng/dL was used as the threshold for biochemical T deficiency. Morning serum total T, luteinizing hormone (LH), estradiol, HIV parameters, and body composition parameters by CT-scan and Dual-Energy-X-ray-Absorptiometry were measured in each case. Sexual behavior was evaluated in a subset of 247 patients. T deficiency was found in 212 subjects, especially in the age range 40–59, but was frequent even in younger patients. T deficiency occurred mainly in association with low/normal serum LH. Adiposity was higher in subjects with T deficiency (p<0.0001) and both visceral adipose tissue and body mass index were the main negative predictors of serum total T. Osteoporosis and erectile dysfunction were present in a similar percentage in men with or without T deficiency. Conclusions/Significance Premature decline of serum T is common (16%) among young/middle-aged HIV-infected men and is associated with inappropriately low/normal LH and increased visceral fat. T deficiency occurs at a young age and may be considered an element of the process of premature or accelerated aging known to be associated with HIV infection. The role of HIV and/or HIV infection treatments, as well as the role of the general health state on the gonadal axis, remains, in fact, to be elucidated. Due to the low specificity of signs and symptoms of hypogonadism in the context of HIV, caution is needed in the diagnosis of hypogonadism in HIV-infected men with biochemical low serum T levels.

Human models of aromatase deficiency.

Estrogens exert a wide range of biological effects in both sexes also on non-reproductive systems and organs. Human congenital estrogen deficiency, due to an inactivating mutation of the aromatase gene, leads to the lack of the estrogen synthesis, with gonadotropins and circulating testosterone ranging from normal to elevated. The aromatese-deficient females show hyperandrogenism and virilization at birth with ambiguous genitalia. During childhood there are a dysfunction in the LHRH-LH/FSH axis and a progressive delay in bone age. At puberty they show primary amenorrhea, no breast development, worsening of the virilization and the absence of growth spurt. The clinical phenotype in the male affected subjects comprises tall stature, persistent linear growth and delayed bone age, osteopenia/osteoporosis, eunuchoid body proportion, different degrees of glucose-insulin and of fertility impairment. These phenotypes suggest the physiological role of estrogens on the skeleton, on pituitary function, on the reproductive system, on glucose metabolism, being the precise mechanism on each of these functions not yet known in detail. The estradiol replacement treatment leads to a complete epiphyseal closure and to the skeletal maturation. Moreover, the increasing knowledge on the role of estrogen in several metabolic pathways could be important for a better management of several metabolic diseases.

GH response to GHRH plus arginine is impaired in lipoatrophic women with human immunodeficiency virus compared with controls.

OBJECTIVE GH secretion is impaired in lipodystrophic human immunodeficiency virus (HIV) patients and inversely related to lipodystrophy-related fat redistribution in men. Less is known about the underlying mechanisms involved in reduced GH secretion in HIV-infected women. DESIGN A case-control, cross-sectional study comparing GH/IGF1 status, body composition, and metabolic parameters in 92 nonobese women with HIV-related lipodystrophy and 63 healthy controls matched for age, ethnicity, sex, and body mass index (BMI). METHODS GH, IGF1, IGF binding protein 3 (IGFBP3), GH after GHRH plus arginine (GHRH+Arg), several metabolic variables, and body composition were evaluated. RESULTS GH response to GHRH+Arg was lower in HIV-infected females than in controls. Using a cutoff of peak GH ≤ 7.5 μg/l, 20.6% of HIV-infected females demonstrated reduced peak GH response after GHRH+Arg. In contrast, none of the control subjects demonstrated a peak GH response ≤ 7.5 μg/l. Bone mineral density (BMD), quality of life, IGF1, and IGFBP3 were lowest in the HIV-infected females with a GH peak ≤ 7.5 μg/l. BMI was the main predictive factor of GH peak in stepwise multiregression analysis followed by age, with a less significant effect of visceral fat in the HIV-infected females. CONCLUSIONS This study establishes that i) GH response to GHRH+Arg is lower in lipoatrophic HIV-infected women than in healthy matched controls, ii) BMI more than visceral adipose tissue or trunk fat influences GH peak in this population, and iii) HIV-infected women with a GH peak below or equal to 7.5 μg/l demonstrate reduced IGF1, IGFBP3, BMD, and quality of life.

The Diagnostic Value of Calcitonin Measurement in Wash-Out Fluid from Fine-Needle Aspiration of Thyroid Nodules in the Diagnosis of Medullary Thyroid Cancer

OBJECTIVES The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy (FNAB) wash-out fluid (Ct-FNAB) for medullary thyroid cancer (MTC) remains to be determined. This prospective study aimed to assess the diagnostic value of Ct-FNAB in thyroid nodules in comparison with basal serum calcitonin (Ct), pentagastrin-stimulated Ct (Pg-sCt), and cytology. METHODS Among patients with goiter addressed with US-FNAB who had an initial clinical suggestion for thyroidectomy, 27 patients with thyroid nodule/s (n = 60) and normal, borderline, or increased Ct fulfilled the criteria for thyroidectomy. All 27 patients (enrolled according to exclusion/inclusion criteria) underwent ultrasonography (US), Ct, Pg-sCt, US-assisted FNAB of each patients nodule for both cytology, and Ct-FNAB before thyroidectomy. RESULTS Ct-FNAB always resulted in >1,000 pg/mL in MTC nodules at histology. For values between 36 and 1,000 pg/mL, MTCs and nodular or micronodular C-cell hyperplasia (CCH) results overlapped. Most of the nodules without MTC and/or CCH had Ct-FNAB ≤ 17 pg/mL. Ct-FNAB diagnostic power was superior to and similar to other diagnostic procedures (Ct, Pg-sCt, and cytology) in identifying both MTC and CCH, and MTC alone, respectively. CONCLUSION The diagnostic power of Ct-FNAB is valuable compared with other routine procedures. Ct-FNAB is highly reliable for the early detection and accurate localization of MTC in thyroid nodules, but it does not differentiate between MTC and CCH. Ct-FNAB is an extremely valuable diagnostic tool, especially considering that other diagnostic procedures do not provide a definitive diagnosis, and it can be included in the clinical work-up of thyroid nodules when MTC is suspected.

Differentiated Thyroid Carcinoma (DTC) in a Young Woman with Peutz-Jeghers Syndrome: Are these Two Conditions Associated?

AIMS Peutz-Jeghers Syndrome (PJS) is a rare dominantly inherited disease characterized by hamartomatous small bowel polyposis, mucocutaneous hyperpigmentation, and increased risk of cancer. Differentiated thyroid cancers (DTCs) present mainly as sporadic, but they may have also a familial component. We present a case of PJS in a caucasian 25 years-old woman, who developed a DTC. METHODS The patient had a palpable nodule in the right side of the thyroid region and an endocrinological evaluation, including hormonal assays, neck ultrasound (US) and fine needle aspiration (FNAB) of the nodule was performed. RESULTS US confirmed a single nodular lesion in the right thyroid lobe (14 mm). Cytological analysis at FNAB revealed a pattern compatible with papillary thyroid carcinoma. The histological analysis after total thyroidectomy confirmed the diagnosis of a Hurtle cell variant of papillary thyroid carcinoma, with follicular architecture. CONCLUSION Even though rare, the association between PJS and DTC can be possible. In clinical practice it must be borne in mind that the wide spectrum of possible cancer diseases occurring in PJS could also include DTC, that the latter can occur earlier in life in PJS population and with a more aggressive histological pattern. Furthermore, in patients with PJS, US of the thyroid should be performed whenever thyroid disease is suspected at physical examination or based on patients medical history. Due to lack of established data allowing for a real esteem of the association between PJS and DTC, US of the thyroid, should not be recommended as a routine screening for all subjects with PJS.

Are pre-miR-146a and PTTG1 associated with papillary thyroid cancer?

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with a steadily increasing incidence in the last few decades worldwide. The predisposition to developing this carcinoma by the heterozygous state of rs2910164 within the precursor of the miR-146a has been reported, but recently not confirmed. Interestingly, on the same chromosome, almost 50 kb separate the pre-miR-146a from the pituitary tumor-transforming gene 1 (PTTG1), a proto-oncogene involved in several tumors, including thyroid cancers. In this study, we analyzed, using a case–control design, the genetic association between PTC and the genomic region encompassing pre-miR-146a rs2910164 and PTTG1 rs1862391 and rs2910202. We enrolled 307 affected patients and 206 healthy controls. The possible presence of thyroid nodules in controls was excluded by ultrasonography. All the cases were submitted to single-nucleotide polymorphism (SNP) genotyping of pre-miR-146a and PTTG1, and risk association analyses were carried out. The genotypic and allelic frequencies of pre-miR-146a rs2910164 were not statistically different in the patients and controls, and this SNP was not in linkage disequilibrium with the investigated PTTG1 SNPs. Consistently, meta-analyses, the first including all the affected cases published to date, did not confirm the previously reported association of the heterozygous CG genotype with PTC. The PTTG1 SNPs exhibited the same allelic frequency in the patients and controls and were not associated with the disease. In conclusion, in a well-selected Italian population, neither pre-miR-146a rs2910164 nor PTTG1 rs1862391 and rs2910202 were found to be associated with the risk of developing PTC.

Gender differences in GH response to GHRH+ARG in lipodystrophic patients with HIV: a key role for body fat distribution

OBJECTIVE Gender influence on GH secretion in human immunodeficiency virus (HIV)-infected patients is poorly known. DESIGN AND METHODS To determine the effect of gender, we compared GH response to GH-releasing hormone plus arginine (GHRH+Arg), and body composition in 103 men and 97 women with HIV and lipodystrophy. The main outcomes were IGF1, basal GH, GH peak and area under the curve (AUC) after GHRH+Arg, body composition, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). RESULTS Men had lower GH peak and AUC than women (P<0.001). Of the study population, 21% of women and 37% of men had biochemical GH deficiency (GHD; GH peak <7.5 μg/l). VAT-to-SAT ratio was higher in men than in women with GHD (P<0.05). Unlike women, VAT, SAT, and trunk fat were greater in men with GHD than in men without GHD. IGF1 was significantly lower in women with GHD than in women without GHD, but not in men. At univariate analysis, BMI, trunk fat mass, VAT, and total adipose tissue were associated with GH peak and AUC in both sexes (P<0.05). BMI was the most significant predictive factor of GH peak, and AUC at multiregression analysis. Overall, abdominal fat had a less pronounced effect on GH in females than in males. CONCLUSIONS These data demonstrate that GH response to GHRH+Arg is significantly lower in HIV-infected males than females, resulting in a higher percentage of GHD in men. Adipose tissue distribution more than fat mass per se seems to account for GH gender differences and for the alteration of GH-IGF1 status in these patients.

Very high prevalence of ultrasound thyroid scan abnormalities in healthy volunteers in Modena, Italy

Background: Italy is characterized by high prevalence of goiter. To date, only limited data about the prevalence of goiter in the Italian adult population are available. Aim: To investigate the prevalence of thyroid ultrasound abnormalities in adults unaware of any thyroid disease and evaluate the rate of differentiated thyroid cancer (DTC) obtained by this intervention. Methods: Ultrasound (US) thyroid scan was performed in adult volunteers recruited by advertisement in Modena, Italy. One hundred and thirty-five women and 66 men (no.= 201), unaware of any thyroid disease (mean age of 46±10.7 yr) underwent their first thyroid US scan. Results: US thyroid abnormalities were found in 101 subjects (50.3%): 91 nodular goiters (45.2%) and 13 US-thyroiditis (6.5%) associated with positive auto-antibodies in 11 of them. Seventeen subjects (18%) with nodules underwent US-fine needle aspiration biopsy with the following cytological class (C) outcome: 14 patients C2 (82%), 1 patient C3 (6%), 2 patients had C4 (12%), the latter received histological confirmation. Conclusions: The prevalence of thyroid abnormalities is very high in subjects unaware of any thyroid disease. DTC was found in 1% of subjects and in 2% of those affected by nodular goiter. Compared to the detection rate of the well-established screening programs for breast (0.45%) and colorectal (0.27%) cancer, the prevalence of DTC seems to be much higher. Thyroid US screening could allow the detection of DTC in asymptomatic subjects and this diagnosis often includes DTC at an advanced stage. Thus, US screening not necessarily results in the over-diagnosis of clinically not relevant thyroid diseases.

Integration of Personalized Healthcare Pathways in an ICT Platform for Diabetes Managements: A Small-Scale Exploratory Study

The availability of new tools able to support patient monitoring and personalized care may substantially improve the quality of chronic disease management. A personalized healthcare pathway (PHP) has been developed for diabetes disease management and integrated into an information and communication technology system to accomplish a shift from organization-centered care to patient-centered care. A small-scale exploratory study was conducted to test the platform. Preliminary results are presented that shed light on how the PHP influences system usage and performance outcomes.

Clinical and radiological evidence of the recurrence of reversible pegvisomant-related lipohypertrophy at the new site of injection in two women with acromegaly: a case series.

IntroductionPegvisomant-related lipohypertrophy may revert when changing the site of injection, but the lipohypertrophy may recur at the new site of injection. The strength of evidence, however, is weak and comes from information obtained from physical examination only.Case presentationWe studied two Caucasian women with acromegaly, aged 51 and 71 years, with pegvisomant-related lipohypertrophy. Our two patients were evaluated at baseline, when the site of pegvisomant injection was the periumbilical abdominal region, and then four months after switching the injection site from the abdomen to both thighs. Both physical examination and radiological studies (magnetic resonance imaging and dual energy X-ray absorptiometry) demonstrated that the abdominal lipohypertrophy progressively reverted in both patients after switching the site of injection to the thighs. However, lipohypertrophy reappeared at the new site of injection. The radiological outcome confirmed the reversibility of pegvisomant-related lipohypertrophy and strengthened the body of evidence on this issue.ConclusionIn clinical practice, physical examination of the injection site or sites leads to an early detection of lipohypertrophy during pegvisomant treatment. Radiological procedures may be of help to confirm subcutaneous fat changes and for a precise monitoring of fat redistribution. Patients should get appropriate information about lipohypertrophy before starting pegvisomant treatment since the rotation of the site of injection may prevent lipohypertrophy.