Testicular volume in 268 children and adolescents followed-up for childhood obesity-a retrospective cross-sectional study.

CONTEXT: Prevalence of obesity in childhood has increased over the past few decades. The impact of obesity and of obesity-related metabolic disorders on testicular growth is unknown. OBJECTIVE: To evaluate the impact of obesity, hyperinsulinemia, and insulin resistance on testicular volume (TV) in pre-pubertal (<9 years), peri-pubertal (9-14 years), and post-pubertal (14-16 years) periods. METHODS: We collected data on TV, age, standard deviation score (SDS) of the body mass index (BMI), insulin, and fasting glycemia in 268 children and adolescents followed-up for weight control. RESULTS: Peri-pubertal boys with normal weight had a significantly higher TV compared to those with overweight or obesity. No difference was found in the other age ranges when data were grouped according to BMI. Pre- and post-pubertal children/adolescents with normal insulin levels had significantly higher TV compared to those with hyperinsulinemia. Peri-pubertal boys with hyperinsulinemia had significantly higher TV compared to those with normal insulin levels. Post-pubertal adolescents with insulin resistance had lower TV and peri-pubertal boys had higher TV compared to those without insulin resistance. No difference was found in pre-puberty. CONCLUSIONS: Closer control of the body weight and the associated metabolic alterations in childhood and adolescence may maintain testicular function later in life.

Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literature.

BACKGROUND: P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also associate with skeletal defects. However, the prevalence of these phenotypes is unknown. AIM: To evaluate the prevalence of CAH, DSD, and infertility of patients with POR gene pathogenic variants by a systematic review of the literature. METHODS: The literature search was performed through PubMed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases. All studies reporting information on CAH, DSD, testicular adrenal rest tumor (TARTs), and fertility in patients with POR gene pathogenic variants were included. Finally, the prevalence of abnormal phenotypes was calculated. RESULTS: Of the 246 articles initially retrieved, only 48 were included for a total of 119 (46 males and 73 females) patients with PORD. We also included the case of a male patient who consulted us for CAH and TARTs but without DSD. This patient, found to be a carrier of combined heterozygous POR mutation, reached fatherhood spontaneously. All the patients found had CAH. The presence of DSD was found in 65.2%, 82.1%, and 82.1% of patients with compound heterozygosity, homozygosity, or monoallelic heterozygous variants, respectively. The prevalence was significantly higher in females than in males. The prevalence of TARTs in patients with PORD is 2.7%. Only 5 women with PORD became pregnant after assisted reproductive techniques and delivered a healthy baby. Except for the recently reported proband, no other studies focused on male infertility in patients with POR gene variants. CONCLUSION: This systematic review of the literature reports the prevalence of CAH, DSD, and TARTs in patients with PORD. The unknown prevalence of POR gene pathogenetic variants and the paucity of studies investigating fertility do not allow us to establish whether PORD is associated with infertility. Further studies on both women and men are needed to clarify this relationship.

Pediatric leiomyoma of the glans: a case report.

OBJECTIVE: The leiomyoma is a benign mesenchymal tumor originating from smooth muscle cells therefore its location is ubiquitous. The genitourinary system is not a common site and the glans localization in pediatric age has been described only three times in the literature to date. CASE REPORT: We describe a case of an 11-year-old boy who presented with a painless, non-bleeding or itchy tumor of the glans. The surgical procedure consisted in the total removal of the mass. The histological study showed spindle cells with an eosinophilic cytoplasm while the immunohistochemical studies proved cells stained strongly positive for smooth muscle actin. The clinical follow-up for more than 5 years after surgery demonstrates the absence of recurrence and discomfort for the patient and a good aesthetic appearance of the glans. RESULTS: Leiomyoma is a benign tumor that can originate anywhere there is smooth muscle. However, localization at the level of the glans can be treated with a total excision due to the presence of a cleavage plane with the surrounding tissues that allows a good reconstruction of the glans itself. CONCLUSIONS: We propose that leiomyoma ought to be considered in the differential diagnosis of any glans mass in children.

TSH lowering effects of metformin: a possible mechanism of action.

Preliminary clinical evidence suggests that metformin has TSH lowering effects in patients with T2DM and hypothyroidism or in those with TSH serum levels in the upper normal value. Also, metformin may exert a protective role against thyroid nodules growth in patients without insulin-resistance. The cross-talk between tyrosine kinase receptors and the G protein-coupled receptors (which the TSHR belongs to) has been already shown and IRS1 may represent the hub link between TSHR and IR pathways. By influencing IRS1 phosphorylation pattern, metformin may sensitize TSHR to TSH, thus explaining the findings of clinical studies. However, the existence of this molecular pathway must be confirmed through proper studies and further prospective randomized placebo-controlled studies are needed to confirm this hypothesis.

Leukocytospermia in late adolescents: possible clinical interpretations.

BACKGROUND: No data are currently available on the implication of amicrobial leukocytospermia in male adolescents. Therefore, the primary aim of this study was to evaluate the prevalence of amicrobial leukocytospermia among non-smoker late adolescents who were exposed to other risky lifestyles for the andrological health. The main andrological clinical features of adolescents with leukocytospermia were also reported. METHODS: This is a cross-sectional study carried out in 80 boys. Each adolescent underwent a physical examination, and to the assessment of sperm conventional parameters, seminal leukocytes concentration and immature germ cell evaluation. A possible correlation between seminal leukocytes and immature germ cells and testicular volume (TV) was tested. RESULTS: The adolescents enrolled in this study had 18.0 ± 0.4 (range 18.1-18.9) years. Unprotected sexual intercourse was referred by 38% of them. Sexual dysfunctions were found in 25% and isolated hypoactive sexual desire in 12.5% of boys. Low TV and penile length in flaccidity were found in 44% and 30% of them, respectively. Only 41% had normozoospermia at the sperm analysis, whereas 19% had isolated oligozoospermia, 15% oligo-asthenozoospermia, and 25% oligo-astheno-teratozoospermia. Leukocytospermia occurred in 25% (20 out of 80) of adolescents. No seminal infection was detected in 19% (15 out of 80) of them. Adolescents with leukocytospermia had lower progressive sperm motility, percentage of normal forms, TV, and a higher percentage of immature germ cells compared to those without leukocytospermia. Semen leukocyte concentration correlated negatively with TV and positively with the percentage of immature germ cells in the ejaculate. CONCLUSION: Leukocytospermia, increased immature germ cell number, and low TV identify a distinct phenotype suggestive of testicular tubulopathy. Primary prevention of male infertility and the counselling for andrological risky lifestyles is mandatory and should be started as early as possible.

Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis.

PURPOSE: Low testosterone (T) in Klinefelter's syndrome (KS) can contribute to typical features of the syndrome such as reduced bone mineral density, obesity, metabolic disturbances and increased cardiovascular risk. The aim of the present study is to review and meta-analyze all available information regarding possible differences in metabolic and bone homeostasis profile between T treated (TRT) or untreated KS and age-matched controls. METHODS: We conducted a random effect meta-analysis considering all the available data from observational or randomized controlled studies comparing TRT-treated and untreated KS and age-matched controls. Data were derived from an extensive MEDLINE, Embase, and Cochrane search. RESULTS: Out of 799 retrieved articles, 21 observational and 22 interventional studies were included in the study. Retrieved trials included 1144 KS subjects and 1284 healthy controls. Not-treated KS patients showed worse metabolic profiles (including higher fasting glycemia and HOMA index as well as reduced HDL-cholesterol and higher LDL-cholesterol) and body composition (higher body mass index and waist circumference) and reduced bone mineral density (BMD) when compared to age-matched controls. TRT in hypogonadal KS subjects was able to improve body composition and BMD at spinal levels but it was ineffective in ameliorating lipid and glycemic profile. Accordingly, TRT-treated KS subjects still present worse metabolic parameters when compared to age-matched controls. CONCLUSION: TRT outcomes observed in KS regarding BMD, body composition and glyco-metabolic control, are similar to those observed in male with hypogonadism not related to KS. Moreover, body composition and BMD are better in treated than untreated hypogonadal KS. Larger and longer randomized placebo-controlled trials are advisable to better confirm the present data, mainly derived from observational studies.

Assessment of sexual and emotional distress in infertile couple: validation of a new specific psychometric tool.

BACKGROUND: The diagnosis of infertility strongly impacts on psychological and sexological couple health. In this regard, some feelings and psychological states were demonstrated in association with reproductive problems. Depression and anxiety are the most common psychopathologies associated with infertility, although also sexuality is strongly involved in infertility conditions. OBJECTIVES: The aim of this study is to develop a tool to probe and assess the emotional aspects, sexuality, and social relationships of the couple seeking medical care for infertility. MATERIALS AND METHODS: A self-reported questionnaire that we will refer to as SEIq (Sexuality and Emotions in Infertility questionnaire) was constructed and developed and, consequently, administered to 162 heterosexual couples (324 subjects) seeking help for reproductive problems. Hence, we performed a specific statistical analysis to assess and validate this new psychometric tool. RESULTS: About 60% of men and women (both partners in 43% of couples) declare that infertility has changed their life (Q10). Moreover, the incidence of sexual disorder declared by the subjects is quite rare in men (10%) but more frequent in women (29%) (p < 0.01). CONCLUSION AND DISCUSSION: The results of this pilot test show that the diagnosis of infertility impacts on the couple relationship affecting the emotional area, interpersonal relationships, and sexual functions of the couples. Moreover, the SEIq appears a valuable tool to coherently probe and relate sexological, psychological, relational, and emotive aspects in partners and couples facing the infertility diagnosis. The explorative factor analysis of SEIq data allows to understand the women, men, and couples' behavior in our sample, individuating a reduced set of factors, prone to an easier evaluation. On the whole, the psychometric evaluation through SEIq might be suitable for the couples during Assisted Reproductive Technologies treatments.

Effects of oral contraceptives on thyroid function and vice versa.

BACKGROUND: Thyroid gland dysfunction represents an epidemiologically relevant disease in the female gender, where treatment with oral contraceptives (OCs) is frequently prescribed. Although OCs are able to impact the thyroid gland function, scanty data have been released on this matter so far. AIM: The aim of this article was to review how hormonal OCs, including estrogen- or progesterone-only containing medications, interact with the hepatic production of thyroid-binding globulin (TBG) and, consequently, their effects on serum levels of thyroxine (T4) and triiodothyronine (T3). We also reviewed the effect of Levo-T4 (LT4) administration in women taking OCs and how they influence the thyroid function in both euthyroid women and in those receiving LT4. REVIEW: The estrogenic component of the pills is capable of increasing various liver proteins, such as TBG, sex hormone-binding protein (SHBG) and coagulation factors. On the other hand, the role of progestogens is to modulate estrogen-dependent effects mainly through their anti-androgenic action. In fact, a reduction in the effects of androgens is useful to keep the thromboembolic and cardiovascular risks low, whereas OCs increase it especially in women with subclinical hypothyroidism or in those treated with LT4. Accordingly, subclinical hypothyroidism is known to be associated with a higher mean platelet volume than normal and this increases cardiovascular risk due to platelet hyperactivity caused by incomplete thrombocytopoietic maturation.

FSH treatment for normogonadotropic male infertility: a synergistic role for metformin?

OBJECTIVE: The aim of this paper is to evaluate the effectiveness of follicle-stimulating hormone (FSH) administration in a cohort of insulin resistant (HOMA>2.5) patients with normogonadotropic idiopathic infertility. PATIENTS AND METHODS: We subdivided patients in two clinical groups basing on the adopted therapeutic scheme: group A (n=44) received 150 units of FSH three times a week for three months (group A); group B (n=35) received 150 units of FSH three times a week for three months and 500 mg of slow-release metformin once a day for three months (group B). We evaluated the post-treatment sperm parameters, sperm parameters normalization rate, spontaneous pregnancy rate, and sperm DNA fragmentation normalization rate. RESULTS: 40% of group A patients and 45% of group B patients became normozoospermic after the treatment, while 30% of group A patients and 32% of group B patients achieved a spontaneous pregnancy. B group patients also obtained higher sperm DNA fragmentation normalization rate (45% vs. 33%, p = 0.03). Compared to group A, group B showed a higher sperm concentration, progressive motility and morphology (p < 0.0001). CONCLUSIONS: The results of this study suggest that the addition of the low-dose slow-release metformin in insulin-resistant patients with normogonadotropic infertility improves the efficacy of FSH therapy.

High rate of detection of ultrasound signs of prostatitis in patients with HPV-DNA persistence on semen: role of ultrasound in HPV-related male accessory gland infection.

BACKGROUND: Papillomavirus (HPV) often occurs in the semen of patients with male accessory gland infection (MAGI). Ultrasound (US) evaluation has been suggested as a promising diagnostic tool for patients with HPV-related MAGI. No data on the spontaneous clearance of HPV-DNA have been reported so far in HPV-related MAGI. PURPOSE: The primary aim of the study was to assess the percentage of early HPV-DNA spontaneous clearance in patients with prostatitis. The secondary aim was to evaluate the frequency of spontaneous clearance of HPV-DNA among patients with prostatitis associated with the presence or absence of US abnormalities. METHODS: Patients with inflammatory MAGI and at least one suspicious criterion for HPV infection underwent semen HPV-DNA detection and prostate US. The presence of HPV-DNA was further investigated after a 6-month-long follow-up. MAIN RESULTS: Eighty patients satisfied the inclusion criteria and were recruited in the study. 69% of patients (55/80) showed HPV-DNA persistence in the semen. Among them, 82% (45/55) was positive for US signs of prostatitis, while they occurred only in 12% (3/25) of those patients with no sign of HPV-DNA persistence (p < 0.001). All patients with persistent high-risk HPV genotype (n = 30) showed at least two US signs of prostatitis. In 73% of patients (22/30), E6 and E7 mRNAs were detected. CONCLUSION: US signs of prostatitis more frequently occurred in patients with evidence of HPV-DNA persistence on semen, especially in those with high-risk genotypes. This highlights the importance of US in the framework of HPV-related MAGI.

Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE).

BACKGROUND: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. PURPOSE: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.

Non-hormonal treatment for male infertility: the potential role of Serenoa repens, selenium and lycopene.

OBJECTIVE: Male infertility is a wide spread disease among couple of childbearing age. Spermatozoa are highly susceptible to oxidative stress. Reactive oxygen species (ROS) are capable of damaging the sperm membrane and DNA, inducing lipid peroxidation and sperm DNA fragmentation (SDF). Antioxidant supplementation is currently suggested after a complete diagnostic work-up, as recognized by the Italian Society of Andrology and Sexual Medicine (SIAMS). Indeed, it has been showed to improve sperm quality, DNA fragmentation and pregnancy rate. The administration of Serenoa repens extracts (SrE), including free fatty acids (FFA), methyl and ethyl esters, glycerides, flavonoids and sterols, has never been investigated for male infertility. However, their antioxidant and anti-inflammatory properties provide the rational for their possible effectiveness. The aim of this review was to collect all the evidence supporting the potential usefulness of SrE, alone or in combination with other molecules with proven antioxidant effects, like selenium and lycopene (along with which they are often commercialized), to improve sperm parameters. MATERIALS AND METHODS: A systematic search was performed using Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar and Scopus databases. The search strategy included the following key words: Serenoa repens, selenium, lycopene, oligozoospermia, oxidative stress, DNA fragmentation, male infertility, pregnancy rate. CONCLUSIONS: By triggering multiple inflammatory and oxidative pathways, the combined administration of SrE, selenium and lycopene might likely improve the sperm quality. Proper studies are needed to test this hypothesis. Finally, since prostatitis can affect the sperm quality and considering the anti-estrogenic properties of SrE, we speculate about a possible specific indication in those patients with male infertility and "metabolic" prostatitis (where obesity and abnormal androgen/estrogen ratio concomitantly occur).

Thyroid function in Klinefelter syndrome: a multicentre study from KING group.

PURPOSE: The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between patients with KS and hypogonadism due to other causes (Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, iatrogenic hypogonadism and acquired hypogonadotropic hypogonadism after surgical removal of pituitary adenomas) called non-KS. Therefore, we evaluated thyroid function in KS and in non-KS hypogonadal patients. METHODS: This is a case-control multicentre study from KING group: Endocrinology clinics in university-affiliated medical centres. One hundred and seventy four KS, and sixty-two non-KS hypogonadal men were enrolled. The primary outcome was the prevalence of thyroid diseases in KS and in non-KS. Changes in hormonal parameters were evaluated. Exclusion criterion was secondary hypothyroidism. Analyses were performed using Student's t test. Mann-Whitney test and Chi-square test. RESULTS: FT4 was significantly lower in KS vs non-KS. KS and non-KS presented similar TSH and testosterone levels. Hashimoto's thyroiditis (HT) was diagnosed in 7% of KS. Five KS developed hypothyroidism. The ratio FT3/FT4 was similar in both groups. TSH index was 1.9 in KS and 2.3 in non-KS. Adjustment for differences in age, sample size and concomitant disease in multivariate models did not alter the results. CONCLUSIONS: We demonstrated in KS no etiopathogenic link to hypogonadism or change in the set point of thyrotrophic control in the altered FT4 production. The prevalence of HT in KS was similar to normal male population, showing absence of increased risk of HT associated with the XXY karyotype.

Genomic alterations in breast cancer: level of evidence for actionability according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT).

Better knowledge of the tumor genomic landscapes has helped to develop more effective targeted drugs. However, there is no tool to interpret targetability of genomic alterations assessed by next-generation sequencing in the context of clinical practice. Our aim is to rank the level of evidence of individual recurrent genomic alterations observed in breast cancer based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) in order to help the clinicians to prioritize treatment. Analyses of databases suggested that there are around 40 recurrent driver alterations in breast cancer. ERBB2 amplification, germline BRCA1/2 mutations, PIK3CA mutations were classified tier of evidence IA based on large randomized trials showing antitumor activity of targeted therapies in patients presenting the alterations. NTRK fusions and microsatellite instability (MSI) were ranked IC. ESR1 mutations and PTEN loss were ranked tier IIA, and ERBB2 mutations and AKT1 mutations tier IIB. Somatic BRCA 1/2 mutations, MDM2 amplifications and ERBB 3 mutations were ranked tier III. Seventeen genes were ranked tier IV based on preclinical evidence. Finally, FGFR1 and CCND1 were ranked tier X alterations because previous studies have shown lack of actionability.

Benign prostatic hyperplasia and intraprostatic inflammation are associated with liver inflammation: it's time for prevention.

Some evidences have supported the link between benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and inflammation. In this study, we aimed to evaluate the association between prostatic inflammation (PI) and non-alcoholic steatohepatitis (NASH) evaluated by a non-invasive scores in a cohort of patients affected by BPH/LUTS. Between January 2012 and January 2016, we conducted a prospective study in a single academic outpatient clinic on 132 consecutive patients who underwent surgery for lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO). A non-invasive non-alcoholic steatohepatitis score (NASH score) was calculated, and PI was evaluated through the Irani score. Patients with a NASH score > 1.05 had an average larger prostate volume (55 vs. 45 cc, p < 0.05), a greater waist circumference (103 vs. 93.5 cm, p < 0.01), and high values of blood glucose, triglycerides, insulin, and BMI compared to patients without NASH; 36% of patients with an Irani score ≥ 4 had NASH compared to 16.1% of patients who had a NASH score < 1.05 (p < 0.05). We found that non-alcoholic steatohepatitis (NASH ≥ 1.05) was an independent risk factor for Irani score ≥4 (OR: 3.24; p < 0.05) and of prostate volume ≥ 40 cc (OR: 13.99; p < 0.01). LUTS/BPH and NASH can be closely related, underlying common triggers of induction. In particular, inflammation seems to be associated with both conditions and with prostate gland overgrowth. Early identification of this class of patients could play a key role in preventing complications related to disease progression.

Does a male polycystic ovarian syndrome equivalent exist?

The occurrence of a genetic background in the etiology of polycystic ovarian syndrome (PCOS) represents the rational basis to postulate the existence of a male PCOS equivalent. Hormonal and metabolic abnormalities have been described in male relatives of women with PCOS. These males also have a higher prevalence of early onset (<35 years) androgenetic alopecia (AGA). Hence, this feature has been proposed as a clinical sign of the male PCOS equivalent. Clinical evidence has shown that men with early onset AGA have hormonal and metabolic abnormalities. Large cohort studies have clearly shown a higher prevalence of type II diabetes mellitus (DM II) and cardiovascular diseases (CVDs) in elderly men with early onset AGA. In addition, prostate cancer, benign prostate hyperplasia (BPH) and prostatitis have been described. These findings support the existence of the male PCOS equivalent, which may represent an endocrine syndrome with a metabolic background, and might predispose to the development of DM II, CVDs, prostate cancer, BPH and prostatitis later in life. Its acknowledgment would be helpful for the prevention of these long-term complications.

Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer.

Background: While deregulation of the cyclin D1-CDK4/6-retinoblastoma pathway is common in hormone receptor positive (HR+) breast cancer, Rb is usually intact in HR+ breast cancer, and targeted CDK 4/6 inhibitors that act upstream of Rb, are routinely being utilized in clinical practice. However, factors that can lead to clinical resistance to CDK 4/6 inhibitors are not known. Patients and methods: We identified patients who had pre- and post-genotyping in tissue and peripheral blood samples after receiving CDK 4/6 inhibitors. Genotyping was carried out in tumor tissue or blood collected before start of CDK 4/6 inhibitor and after disease progression on CDK 4/6 inhibitor, covering more than 90% of the coding region in RB1. Results: We identified detectable acquired RB1 mutations in circulating tumor DNA (ctDNA) after exposure to CDK4/6 inhibitor (palbociclib, palbociclib, ribociclib) for 5, 8, and 13 months, respectively, in three patients. The RB1 mutations included substitution in donor splicing site of exon 8 of the RB1 gene in patient #1; substitution in donor splicing site of exon 22 of RB1 gene, exon 19 deletion, exon 3 insertion in patient #2; and RB1 exon 16 H483Y mutation in patient #3. None of these RB1 mutations were present in the pre-CDK 4/6 specimen highlighting these molecular alterations, which lead to functional loss of Rb1, likely emerged under selective pressure from the CDK4/6 inhibitor potentially confering therapeutic resistance. Conclusion: This is the first clinical report to describe the emergence of somatic RB1 mutations after exposure to palbociclib or ribociclib, in patients with metastatic breast cancer. Further research is needed to validate these findings, identify how these mutations temporally emerge under selective pressure of CDK 4/6 inhibitor, and develop rational therapeutic strategies.

Dual-release hydrocortisone treatment: glycometabolic profile and health-related quality of life.

OBJECTIVE: Adrenal insufficiency (AI) is a chronic condition associated with increased mortality and morbidity. The treatment of AI in the last years has been object of important changes due to the development of a dual-release preparation of hydrocortisone. It differs from previous therapeutic strategy as it contemplates a once-daily tablet that allows more closely mimicking the physiological circadian cortisol rhythm. The aim of the study was to evaluate the effects of dual-release hydrocortisone treatment on the glycometabolic profile and health-related quality of life of patients with AI. DESIGN AND METHODS: In this clinical open trial, we enrolled ten patients with primary AI (41 ± 2.67 years) and nine patients with AI secondary to hypopituitarism (53.2 ± 17.7 years). We evaluated the glycometabolic profile before and 3, 6, 9 and 12 months after dual-release hydrocortisone administration. We also evaluated health-related quality of life, estimated by the AddiQol questionnaire. The mean dose administered of dual-release hydrocortisone was 28.33 ± 6.68 mg/day. RESULTS: One female hypopituitary patient dropped out from the study. After 12 months of treatment, the mean dosage administered of dual-release hydrocortisone was significantly lower (P < 0.05) and all patients reported improved quality of life and well-being. The glycometabolic profile improved and the glycosylated hemoglobin decreased significantly in patients with primary AI (6.25 ± 0.2 vs 5.35 ± 0.17, P < 0.05). In contrast, hypopituitary patients had worse glycometabolic profile and a trend toward hypertriglyceridemia. CONCLUSIONS: Dual-release hydrocortisone treatment improved the quality of life of patients with AI, and it allowed a decrease of cortisol dosage administered in the absence of side effects. The glycometabolic profile worsened in hypopituitary patients.