Comorbidities and Medical Complications in Hospitalized Subarachnoid Hemorrhage Patients.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating condition with a case fatality of 36% at 30 days. Risk factors for mortality in SAH patients include patient demographics and the severity of the neurological injury. Pre-existing conditions and non-neurological medical complications occurring during the index hospitalization are also risk factors for mortality in SAH. The magnitude of the effect on mortality of pre-existing conditions and medical complications, however, is less well understood. In this study, we aim to determine the effect of pre-existing conditions and medical complications on SAH mortality. METHODS: For a 25% random sample of the Greater Montreal Region, we used discharge abstracts, physician billings, and death certificate records, to identify adult patients with a new diagnosis of non-traumatic SAH who underwent cerebral angiography or surgical clipping of an aneurysm between 1997 and 2014. RESULTS: The one-year mortality rate was 14.76% (94/637). Having ≥3 pre-existing conditions was associated with increased one-year mortality OR 3.74, 95% CI [1.25, 9.57]. Having 2, or ≥3 medical complications was associated with increased one-year mortality OR, 2.42 [95% CI 1.25-4.69] and OR, 2.69 [95% CI 1.43-5.07], respectively. Sepsis, respiratory failure, and cardiac arrhythmias were associated with increased one-year mortality. Having 1, 2, or ≥3 pre-existing conditions was associated with increased odds of having medical complications in hospital. CONCLUSIONS: Pre-existing conditions and in-hospital non-neurological medical complications are associated with increased one-year mortality in SAH. Pre-existing conditions are associated with increased medical complications.

For Debate: Assessment of HbA1c in Transfusion Dependent Thalassemia Patients.

At present, assessment of haemoglobin A1c (HbA1c) is widely used for the diagnosis and monitoring of treatment in diabetes mellitus (DM). However, the HbA1c level is affected by many factors such as those influencing the lifespan of red blood cells and the structure, function and amount of normal HbA. Therefore, the clinical significance of HbA1c assessment in thalassemia patients needs careful consideration, especially in transfusion dependent thalassemia patients (TDT) in whom circulating Hb is that of blood donors. Preliminary reports have documented that HbA1c estimation in efficiently transfused patients seems valuable in diagnosis and monitoring of treatment in DM and other glucose disturbances in TDT patients. Herein, a short review of HbA1c measurement in anemias, blood transfusions and hemoglobinopathies, and the debate of the credibility of Hb A1c assessment in TDT patients is reported.

For Debate: Testicular Volume Development along Ages: Evaluation by Different Methods.

In the last five decades an increasing number of studies and clinical reports demonstrated the importance of testicular volume assessment in pediatric and adolescent population. Reliable and accurate determination of testicular volume (TV) through infancy and adolescence is of great importance for assessing normal pubertal development to diagnose disturbances in development and to suspect certain genetic and endocrine diseases. Various approaches are available for the assessment of TV, including orchidometry, rulers, callipers, and ultrasonography (USG). Our report focuses on the importance of the evolution of TV from birth to adulthood and debates the main factors influencing the accuracy of different TV measurements. We endorse that any method for the evaluation of TV must satisfy certain criteria: a. be applicable to persons of all ages from pre-adolescence, through the pubertal spurt to full maturity, b. be simple to use, c. be free from observer error as possible, and d. have a high degree of correlation with other observable developmental characteristics.

The Management of Permanent Primary Hypoparathyroidism in Children and Adolescents: A Complex Task.

Management of hypoparathyroidism (hypoPT), depends on the etiology and the severity of hypocalcemia. Treatment goals include control of hypocalcemic symptoms preserving serum calcium in the low-normal range and phosphate in the high normal range. While correction of serum calcium to low-normal range does not fully correct mineral and bone metabolism it may be associated with increased risk of complications such as nephrolithiasis, nephrocalcinosis and soft tissue calcifications. Therefore, it is imperative to find out ways to individualize treatment of patients with hypoPT to achieve the best prognosis while minimizing complications. Replacement therapy with recombinant human PTH (rhPTH) was recently tested for optimizing treatment of hypoPT in a small number of patients. For children and adolescents, further studies are needed to evaluate the long-term effects and safety of rhPTH. In this short review we summarize current knowledge on the management of hypoPT and debate our gaps on the long-term management of children and adolescents with hypoPT.

For Debate: Should We Worry about Hematospermia in Adolescents and Young Men? A Report of Six Cases and Review of the Literature.

Hematospermia or hemospermia is defined as the presence of blood in ejaculate. The true prevalence of the condition is unknown because many cases escape the patient's notice, and remain unrecognized and unreported. There are two main aims in the patient evaluation: first, to ensure that there is no specific condition that is treatable; second, to reassure the patient's parents that no causative factor is present. Many physicians are unfamiliar with this disorder and this forms the basis for our current review. We performed an essentially English language search (Medline since 1966 to present and reference list of articles) for "hematospermia", or "hemospermia" in combination with "adolescents", "young adults", "genital diseases", "management" and "review". The authors' personal experience with 6 adolescents and young men (up to the age of 20 years) is also reported. Several anatomical structures contributing to the ejaculate may be the source of the hematospermia: seminal vesicles, prostate, testis and epididymis. Hematospermia is a generally benign and self-limited condition that is infrequently associated with significant underlying pathology. Once the diagnosis is clear, it is important to reassure the adolescent about the benign nature and self-limiting course of the condition and to provide appropriate treatment to help ensure the adolescent's normal sexual development.

Is the Second to Fourth Digit Ratio (2D:4D) a Biomarker of Sex-Steroids Activity?

The second-to-fourth digit ratio (2D:4D) has been used as an indirect method to investigate the putative effects of prenatal exposure to androgens, and has been reported to be smaller in males than in females. This gender difference in digit length ratios has been linked with the in utero balance of androgens to oestrogen. This sexual dimorphism in 2D:4D ratios is apparent by 2 years of age and seems to be established early in life, possibly by the 14th week of gestation. Digits in females attain their maximum length at about 2.2 years (dextral subjects) or 5.1 years (sinistral subjects) earlier than those in males and increase slightly with age. It has also been reported that the 2D:4D ratio is correlated negatively with prenatal testosterone levels. This tentative theory is partially supported by lower 2D:4D in girls with congenital adrenal hyperplasia (CAH), higher 2D:4D in individuals with complete androgen insensitivity syndrome (CAIS) and a relationship between 2D:4D and polymorphisms in the androgen receptor. In contrast, individuals with Klinefelter syndrome (KS), who have reduced testosterone secretion throughout life, have a mean 2D:4D value similar to those found in female population norms. Nevertheless, its validity has not yet been conclusively demonstrated and is currently debated. In this context, our aim was to review and debate the relationship between 2D:4D ratio and sex-steroids activity in children, adolescents and young adults.

Thyroid Hemiagenesis from Childhood to Adulthood: Review of Literature and Personal Experience.

Thyroid hemiagenesis (TH) is a rare congenital abnormality of the thyroid gland, characterised by the absence of one lobe. The true prevalence of this congenital abnormality is not known because the absence of one thyroid lobe usually does not cause clinical symptoms by itself. Between 1970 and 2010, 329 cases of TH have been reported. It is interesting to note that most cases have an agenesis of the left lobe (80% of cases) followed by the isthmus (44-50% of cases). Although the female to male ratio was 1:1.4 in 24,032 unselected 11-to 14-yr-old schoolchildren from South-eastern Sicily, several other reports have documented a higher prevalence in women, which may indicate a possible gender association. Most cases of TH are diagnosed when patients present a lesion in the functioning lobe. The functioning lobe of the thyroid gland can be a site of pathological changes similar to a normally developed gland and may present a spectrum of diseases like multinodular goiter, colloid goiter, follicular adenoma, thyroiditis, hypothyroidism and hyperthyroidism. In three of our patients, TH was associated with Hashimoto thyroiditis (n = 1) and with subclinical hypothyroidism (n = 2). The frequency of thyroid abnormalities in patients with TH varies with age, due to the longer exposure of the hemi-agenetic gland to TSH overstimulation in older patients. This could explain the controversy about the benign character of this anomaly. Other extrathyroidal lesions, such as parathyroid adenoma or hyperplasia, cervical thymic cysts, ectopic sublingual thyroid gland and thyroglossal duct cyst have been reported with TH. Therefore, systematic follow-up of all identified cases is recommended.

Are the new automated methods for bone age estimation advantageous over the manual approaches?

Bone Age Assessment (BAA) is performed worldwide for the evaluation of endocrine, genetic and chronic diseases, to monitor response to medical therapy and to determine the growth potential of children and adolescents. It is also used for consultation in planning orthopedic procedures, for determination of chronological age for adopted children, youth sports participation and in forensic settings. The main clinical methods for skeletal bone age estimation are the Greulich and Pyle (GP) and the Tanner and Whitehouse (TW) methods. Seventy six per cent (76%) of radiologists or pediatricians usually use the method of GP, 20% that of TW and 4% other methods. The advantages of using the TW method, as opposed to the GP method, are that it overcomes the subjectivity problem and results are more reproducible. However, it is complex and time consuming; for this reason its usage is just about 20% on a world-wide scale. Moreover, there are some evidences that bone age assignments by different physicians can differ significantly. Computerized and Quantitative Ultrasound Technologies (QUS) for assessing skeletal maturity have been developed with the aim of reducing many of the inconsistencies associated with radiographic investigations. In spite of the fact that the volume of automated methods for BAA has increased, the majotity of them are still in an early phase of development. QUS is comparable to the GP based method, but there is not enough established data yet for the healthy population. The Authors wish to stimulate the attention on the accuracy, reliability and consistency of BAA and to initiate a debate on manual versus automated approaches to enhance our assessment for skeletal matutation in children and adolescents.

Is priming with sex steroids useful for defining patients who will benefit from GH treatment?

Classic criteria for diagnosing GHD include: short stature (height below the third percentile), slow growth velocity, delayed bone age and failure to produce growth hormone in response to two provocative tests. While provocation tests can diagnose complete GHD, debate still exists about of what constitutes a normal or a subnormal GH response in subjects with "idiopathic" short stature or constitutional delay of growth and puberty. It has been suggested that in children with intermediate GH responses to pharmacologic stimuli, a pre-treatment with sex steroids priming may be of value in enhancing the GH response and in helping to clarify the diagnosis, particularly in children with delayed onset of puberty. Nevertheless, the use of priming with sex steroids prior to GH stimulation test in the peripubertal period is still controversial because it is considered an "unphysiologic method" and may mask children with transient GHD. Further studies and uniform guidelines are needed before solving this intriguing puzzle.

Longitudinal study of ICET-A on glucose tolerance, insulin sensitivity and ß-cell secretion in eleven ß-thalassemia major patients with mild iron overload.

BACKGROUND: Iron chelation therapy (ICT) is the gold standard for treating patients with iron overload, though its long-term effects are still under evaluation. According to current recommendations regarding  transfusion-dependent  (TD)  ß-thalassemia major (ß-TM) patients, their serum ferritin (SF) levels should be maintained below 1,000 ng/mL and ICT should be discontinued when the levels are <500 ng/mL in two successive tests. Alternatively, the dose of chelator could be considerably reduced to maintain a balance between iron input and output of  frequent transfusions. STUDY DESIGN: Due to the paucity of information on long-term effects of ICT  in ß-TM with low SF levels on glucose homeostasis, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) promoted a retrospective and an ongoing prospective observational study with the primary aim to address the long-term effects of ICT on glucose tolerance and metabolism (ß-cell function and peripheral insulin sensitivity) in adult ß-TM patients with persistent SF level below 800 ng/mL. PATIENTS AND METHODS: 11 ß-TM patients (mean age: 35.5 ± 5.5 years; SF range: 345-777 ng/mL) with normal glucose tolerance test (OGTT) or abnormal glucose tolerance (AGT) for a median of 5.3(1.1-8.3) years. RESULTS: Abnormal glucose tolerance (AGT) was observed in 7 patients (63.6%) at first observation and ) persisted in 6 patients (54.5%) at last observation. None of them developed diabetes mellitus. AGT was reversed in two patients. One patient with NGT developed early glucose intolerance (1-h PG ≥155 and 2-h PG <140 mg/dL). Three out of  5 patients with isolated impaired glucose tolerance presented a variation of  ATG. Stabilization of low indices for ß-cell function and insulin sensitivity/resistance was observed. One patient developed hypogonadotrophic hypogonadism. Three out of 6 patients with SF below 500 ng/dL had hypercalciuria. CONCLUSION: Despite low SF level, the burden of endocrine complications remains a challenge in ß-TM patients. The ability to keep iron at near "normal" level with acceptable risks of toxicity remains to be established.

Retrospective study on long-term effects of hormone replacement therapy (HRT) and iron chelation therapy on glucose homeostasis and insulin secretion in female ß- thalassemia major (ß-TM) patients with acquired hypogonadotropic- hypogonadism (AHH).

BACKGROUND AND AIM: Hypogonadism and abnormalities of glucose homeostasis, resulting from iron-induced pituitary and pancreatic ß-cell dysfunction respectively, are the most frequently reported endocrine abnormalities in patients with ß-thalassemia major (ß-TM), also identified as transfusion-dependent thalassemia (TDT). STUDY DESIGN AND PATIENTS: The aim of the present retrospective study was to evaluate the long-term effects of hormone replacement therapy (HRT) on glucose metabolism and insulin secretion/sensitivity during 3-h oral glucose tolerance test (OGTT) in adolescent and young ß-TM women with acquired hypogonadototropic -hypogonadism (AHH).Twelve hypogonadal ß-TM females with AHH on HRT were followed for 8.26 ± 1.49 years. RESULTS: At baseline, 10 patients (83.3%) had normal OGTT, 1 patient presented with impaired glucose tolerance (IGT) and 1 patient had an isolated PG level of 165 mg/dL at 1-h during OGTT (H-NGT). At last evaluation, 7 patients (58.4 %) had normal OGTT, while 5 patients (41.6%) had abnormal OGTT. Reduced insulin sensitivity and impaired first-phase insulin secretion were also documented. Three of 4 ß-TM patients on treatment with estradiol hemihydrate MX 50 patches plus oral medroxyprogesterone acetate (MPA), associated with a very effective iron chelation therapy, maintained normal glucose tolerance from baseline to last evaluation. Significant adverse events due to HRT or additional endocrine complications were not documented in any cases during the follow-up. CONCLUSION: Deterioration of glycemia (dysglycemia) occurred in 45.4% (5/11) of thalassemic females on long-term HRT. Additional studies are needed to elucidate the validity of our preliminary observations.

Unilateral breast enlargement in males during adolescence (10-19 years): Review of current literature and personal experience.

Idiopathic unilateral breast enlargement (UBE) in males is a, commonly overlooked, diagnosis of exclusion that requires careful history, meticulous physical examination, and pertinent laboratory studies to exclude the possible pathologic causes. The aims of the present update are to review the current literature on UBE in subjects during adolescent age (10-19 years) in 18 cases, and to report the personal experience in 13 adolescents referred to our unit during the last four decades. In total, our survey and personal experience include 31 UBE cases, 10 of whom (32.2 %) being idiopathic or familial gynecomastia (GM). In 3/31 (9.6%) UBE was due to breast sarcoma/ carcinoma; one patient (11-years old) had a 5-year history of painless lump in the right breast, which increased gradually in size followed by bloody nipple discharge. In the personal cases of 13 adolescents, a moderate to marked UBE was secondary to: treatment with androgens (2 ß-thalassemic patients with hypogonadism), high estrogen/androgen ratio in 2 Klinefelter syndrome patients, peripheral aromatization of androgens in 1 patient with non-classical 21-hydroxylase deficiency (NC-21-OH-D). One patient had subareolar hematoma due to injury. In 2 patients (15,3%) marked UBE was due to cystic lymphangioma (histologically proved). Furthermore, 5 patients were characterized as idiopathic UBE In clinical practice, the persistence of UBE for long period before diagnosis necessitates attention and further evaluation. Underlying causes should be treated, when possible, while surgery can be offered to patients with persistent or atypical signs and/or symptoms of UBE. For the optimal management of this condition, better collaboration between primary care physician and specialists is mandatory.

Assessment of glucose homeostasis in young adult female ß-thalassemia major patients (ß-TM) with acquired hypogonadotropic hypogonadism (AHH) never treated with sex steroids compared to eugonadal ß-TM patients with spontaneous menstrual cycles.

BACKGROUND: Acquired ypogonadotropic hypogonadism (AHH) is the most prevalent endocrine complication in thalassemia major (TM). STUDY DESIGN: Considering the detrimental effect of estrogen deficiency on glucose metabolism, the ICET-A Network promoted a retrospective study on the long-term effects of estrogen deficiency on glucose homeostasis in female ß-TM patients with HH without hormonal replacement therapy (HRT). PATIENTS AND METHODS: Seventeen ß-TM patients with AHH (4 had arrested puberty; Tanners' breast stage 2-3), never treated with sex steroids, and 11 eugonadal ß-TM patients with spontaneous menstrual cycles at the time of referral were studied. A standard 3-h OGTT was performed in the morning, after an overnight fast. Six-point plasma glucose and insulin level determinations, indices of insulin secretion and sensitivity, early-phase insulin insulinogenic index (IGI), HOMA-IR and ß-cell function (HOMA-ß), oral disposition index (oDI), glucose and insulin areas under the OGTT curves were evaluated. RESULTS: Abnormal glucose tolerance (AGT) or diabetes was observed in 15 (88.2%) of 17 patients with AHH and 6 (54.5%) of 11 patients with eumenorrhea. The difference between the two groups was statistically significant (P: 0.048). However, the group of eugonadal patients was younger compared to AHH patients (26.5 ± 4.8 years vs. 32.6 ± 6.2 years ; P: 0.010). Advanced age,  severity of iron overload, splenectomy, increased ALT levels and reduced IGF-1 levels were the main clinical and laboratory risk factors for glucose dysregulation observed in ß-TM with AHH compared to eugonadal ß-TM patients with spontaneous menstrual cycles. CONCLUSION: These data further support the indication for an annual assessment of OGTT in patients with ß-TM. We believe that a registry of subjects with hypogonadism is necessary for a better understanding of the long-term consequences of this condition and  refining treatment options.

Glucose Homeostasis and Assessment of ß-Cell Function by 3-hour Oral Glucose Tolerance (OGTT) in Patients with ß-Thalassemia Major with Serum Ferritin below 1,000 ng/dL: Results from a Single ICET-A Centre.

Aims: The primary aim of this study was to evaluate retrospectively the glucose homeostasis and surrogate indices of insulin sensitivity and resistance, during a 3-hour oral glucose tolerance test (OGTT), in ß-thalassemia major patients (ß-TM) with serum ferritin (SF) below 1,000 ng/mL. Patients and methods: The retrospective cohort study evaluated the medical records of 24 ß-TM patients from 2010 to 2022. At the year of study the mean age of patients was 31.0 ± 4.1 (20-37.11) years; 13 (54.1%) were females. The most commonly used iron chelator was deferoxamine (DFO: 75%), followed by deferiprone (DFP:12.5%) and deferasirox (DFX: 12.5%). Insulin sensitivity and resistance indices were derived from OGTT. A liver iron concentration (LIC) < 3 mg/g d.w. and a global heart T2* value > 20 ms were considered as conservative cut-off values for insignificant iron overload (IOL). Results: The mean SF levels in the whole study cohort population at the age of evaluation was 549.6 ± 232.3 ng/mL. Based on the SF levels, two groups were identified: Group A (N = 14) < 500 ng/mL and Group B (N=10) 500-1,000 ng/mL. Normal glucose tolerance (NGT) during OGTT was observed in 4 patients of Group A (28.5 %) and in 5 patients of Group B (50%) (P: 0.29). The remaining 15/24 patients (62.5%) had glucose dysregulation (GD). The mean age at starting iron chelation therapy (ICT) and the mean SF peak in Group A versus Group B were significantly higher in group A. The GD was associated with significantly attenuated IGI (first phase of insulin response) and impaired oral disposition index (oDI). Hypogonadotropic hypogonadism (HH) was the most common associated endocrine complication in both groups of patients. Conclusions: This study showed that efficient iron chelation monotherapy in patients with ß-TM and SF < 1,000 ng/ml did not entirely prevent glucose metabolism disorders, abnormalities of insulin secretion and sensitivity, and development of acquired hypogonadism.

A prospective guide for clinical implementation of selected OGTT- derived surrogate indices for the evaluation of ß- cell function and insulin sensitivity in patients with transfusion-dependent ß- thalassaemia.

The gold standard for the measurement of insulin secretion is the hyperglycemic clamp and for insulin sensitivity the hyperinsulinemic euglycemic clamp, respectively. A number of surrogate indices, derived from plasma glucose and insulin levels at a fasting state or after oral glucose load, have been proposed to estimate ß-cell response, and the ability of ß-cells to compensate for changes of insulin sensitivity by modulating insulin secretion (disposition index). Starting from the current recommendations for the annual screening of glucose dysregulation in patients with transfusion dependent ß-thalassemia (ß-TDT), this article summarizes the most frequently used indirect indices of insulin secretion and resistance derived from the oral glucose tolerance test (OGTT) and discusses the strengths and weaknesses of selected indices and the basic concepts underlying each method for the appropriate evaluation of glucose regulation. Basal indices for ß-cell function and insulin sensitivity, albeit simple and cheap, have limited usefulness due to a high coefficient variation and the lack of data about response to glucose load. Therefore, measurement of indices during an OGTT, despite being costly and time-consuming, is suggested since it can detect, even subtle, dynamic changes in insulin secretion and glucose handling. In patients with ß-TDT, the indices derived from OGTT may offer an additional factor to evaluate the efficiency of iron chelation therapy and detect patients who may need intensification of iron chelation therapy and/or pharmacological intervention.

A Multicenter ICET-A Study on Age at Menarche and Menstrual Cycles in Patients with Transfusion-Dependent Thalassemia (TDT) who Started Early Chelation Therapy with Different Chelating Agents.

Introduction: To evaluate the effect of early chelation therapy (≤ 3 years) with a variety of chelating agents on age at menarche and menstrual characteristics in patients with transfusion-dependent thalassemia (TDT). Design: A retrospective multicenter study promoted by the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A). Setting: Eight of 13 International Thalassemia Centers (61.5%) in the ICET-A Network participated. Patients: Fifty-seven female TDT patients, aged 11 to 26 years, and with early iron chelation therapy, were eligible for the present study. They were enrolled from one center from Iran (33 patients), 3 centers from Bulgaria (9), 1 from Greece (8), one from Oman (4), 1 from Cyprus (2), and 1 from Italy (1). Seven patients were excluded, four still prepubertal (age 12-14 years) and 3 with primary amenorrhea. Therefore 50 patients were finally enrolled. Results: All fifty TDT patients developed spontaneous menarche at a mean age of 14.2 ± 2.24 years (range 9 - 20). A significant positive correlation was observed between age at menarche and serum ferritin levels (r: 0. 41, p=0.005). Regular menstrual cycles were reported from 32 (64%) patients, of whom 28 (83.3%) get menarche at age ≤ 14 years. Complications were more frequent in patients older than 14 years at menarche and in those with secondary amenorrhea. Conclusions: Age at menarche greater than 14 years was a forerunner of menstrual irregularities and associated complications in 36% of patients despite precocious chelation therapy. The poor adherence to treatment, to be demonstrated in future studies, could explain the finding.

Oral glucose tolerance test: Ηow to maximize its diagnostic value in children and adolescents.

BACKGROUND: Recently, the validity of the oral glucose tolerance test (OGTT) as a gold-standard test for the diagnosis of glucose dysregulation (GD) has been questioned due to the pre-analytical, analytical, and post-analytical variables which can potentially affect its reproducibility and accuracy. AIMS: In this short update, the many  variables that affect the reproducibility and accuracy of the OGTT are described and discussed aiming to enhance its diagnostic value  in  clinical practice. SEARCH STRATEGY: A systematic search was implemented in June 2022, using Scopus, PubMed, Embase and Google Scholar focusing on OGTT relevant  papers published in the last 10 years. Moreover,  the reference lists of these  articles were checked for additional pertinent studies. The research and selection of articles was also supported by the long-term authors' experience in the use of OGTT for the diagnosis of GD in children and adolescents. CONCLUSION: The complexity of diagnosing GD presupposes that clinicians have specific knowledge and experience to perform rigorous assessment of glucose metabolism. It is worth mentioning that during OGTT, subjects with glucose levels  close to the cut-off values proposed  by WHO (World Health Organization)/ADA (American Diabetes Association) require careful evaluation in order to avoid misclassification and unnecessary interventions. For this reason, ADA recommends a second test to confirm the diagnosis of diabetes.

Hypomenorrhea in Adolescents and Youths: Normal Variant or Menstrual Disorder? Revision of Literature and Personal Experience.

Menstrual health affects a large number of women throughout reproductive life since adolescence. Knowledge of the duration and variation of the menstrual cycle is necessary for patient education and to identify deviations from normal  to guide clinical evaluation. The average duration of menstrual flow is between 4 to 6 days, with anormal range from 2 up to 8 days ; the mean blood loss per menstrual cycle is 25- 30 mL. In general, descriptive data falling outside the normal range are considered to be indicative of menstrual disorders. Although the American Academy of Pediatrics and American College of Obstetricians and Gynecologists advocate for clinicians to consider the menstrual cycle as a vital sign in adolescents, the identification of subjects with hypomenorrhea is neither well defined nor routinely practiced. In this paper we have summarized the published prevalence of hypomenorrhea (lighter and/or shorter menstrual bleeding) in adolescents and youths in different countries and report the personal experience in four adolescents.

Screening for glucose dysregulation in ß-thalassemia major (ß-TM): An update of current evidences and personal experience.

Glucose dysregulation (GD) in patients with ß-thalassemia major (ß-TM) usually develops gradually. Prediabetes consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), the latter detected by a standardized oral glucose tolerance test (OGTT). Diagnosis of prediabetes is essential for an early identification of high-risk individuals who will benefit from intensive iron chelation therapy and lifestyle modification. Therefore, patients with ß-TM should undergo annual screening for glucose abnormalities, according to international recommendations, starting from the age of 10 years. OGTT remains the preferred screening method as it is more sensitive for GD than fasting plasma glucose (FPG), although it is poorly reproducible. The use of HbA1c measurement has limited use as it is generally considered unreliable in patients with thalassemia. Continuous glucose monitoring system (CGMS) is an accurate method to detect the variability of glucose fluctuations and offers the opportunity for better assessment of glucose homeostasis in a selected group of ß-TM patients. Pancreatic Magnetic Resonance Imaging (MRI) associated with insulin secretion-sensitivity index-2 (ISSI-2) could be a complementary test, minimizing the necessity for OGTT and identifying high-risk patients before irreversible pancreatic damage occurs. The aims of this short report are to give practical guidance for an early identification of GD in ß-TM patients, to summarise our experience, and to offer an impetus for further research in the field.

Insulin-Like Growth Factor -1 (IGF-1) and Glucose Dysregulation in Young Adult Patients with ß-Thalassemia Major: Causality or Potential Link?

BACKGROUND: Insulin-like growth factor-1 (IGF-1) has been shown to lower blood glucose through stimulating glucose transport to fat and muscle and inhibiting hepatic glucose output. Although previous cross-sectional reports reported an association between low circulating concentrations of IGF-1 and glucose dysregulation (GD), its role is still debated. AIMS OF STUDY: The present retrospective study was designed to assess the circulating IGF-1 levels in ß-thalassemia major (ß -TM) patients with normal oral glucose tolerance test (NGT-OGTT) and (GD) referred for an endocrine evaluation to explore the potential link between low IGF-1 and GD. STUDY DESIGN AND METHODS: Our study included 34 young adult patients with ß-TM; 12 patients with NGT after OGTT, 7 with impaired glucose tolerance (IGT), 9 with impaired fasting glucose (IFG) plus IGT, and 6 patients with ß-TM-related diabetes mellitus (ß-TM- DM). RESULTS: Twenty-two ß-TM patients with GD or ß-TM- DM and 1 patient with NGT had IGF-1 levels below the 2.5th percentile. Correlation of IGF-1 with fasting plasma glucose, HOMA-IR (homeostatic model assessment for insulin resistance) and OGIS (oral glucose insulin sensitivity) was found. Moreover, a negative correlation was documented between ALT and the Insulinogenic Index (IGI) and a positive correlation between serum ferritin and PG 2-h after OGTT. CONCLUSION: This study reports for the first time an association between low levels of IGF-1 and GD in ß-TM patients. Despite some limitations, our study can serve to generate proposals for more convenient and efficient methods to identify and treat early GD in patients with ß-TM, and to conduct more extensive studies. www.actabiomedica.it).