Beta-thalassaemia major: Prevalence, risk factors and clinical consequences of hypercalciuria.

Regular transfusion and chelation therapy produces increased life expectancy in thalassaemic patients who may develop new complications. Since few data are available regarding hypercalciuria in ß-thalassaemia major (TM), the aim of our study was to evaluate its prevalence, risk factors and clinical consequences. We enrolled 176 adult TM patients followed at the Center of Thalassemia of Ferrara. Hypercalciuria was defined by a calciuria of 4 mg/kg/day or more in a 24-h urine sample. Anamnestic, biochemical and radiological data were collected. Hypercalciuria prevalence was reported in 69.3% of patients (females 52.5%). Hypercalciuric (HC) patients used deferasirox (DFX) more often than normocalciuric (NC) patients (47.5% vs 29.6%; p < 0.05). In HC subjects plasma parathyroid hormone (PTH) (24.1 ± 10.4 vs 30.1 ± 13.2 pg/ml) and phosphate levels (3.6 ± 0.5 vs 3.8 ± 0.7 mg/dl) were lower, whereas serum calcium (9.6 ± 0.4 vs 9.4 ± 0.4 mg/dl) and urinary 24-h phosphaturia (0.9 ± 0.4 vs 0.6 ± 0.3 g/day) were higher as compared to NC patients (p < 0.05 for all comparisons). Supplementation with oral calcium and cholecalciferol was similar between the groups. A higher rate of kidney stones was present in HC (14.8%) versus NC patients (3.7%) (p < 0.05). Hypercalciuria is a frequent complication in adequately treated adult TM patients. Hypercalciuria prevalence is increased in DFX users whereas haemoglobin level or calcium supplements play no role. A significant proportion of HC patients developed kidney stones.

Impact of the diagnostic delay of acromegaly on bone health: data from a real life and long term follow-up experience.

INTRODUCTION: Acromegaly is a chronic disease with systemic complications. Disease onset is insidious and consequently typically burdened by diagnostic delay. A longer diagnostic delay induces more frequently cardiovascular, respiratory, metabolic, neuropsychiatric and musculoskeletal comorbidities. No data are available on the effect of diagnostic delay on skeletal fragility. We aimed to evaluate the effect of diagnostic delay on the frequency of incident and prevalent of vertebral fractures (i-VFs and p-VFs) in a large cohort of acromegaly patients. PATIENTS AND METHODS: A longitudinal, retrospective and multicenter study was conducted on 172 acromegaly patients. RESULTS: Median diagnostic delay and duration of follow-up were respectively 10 years (IQR: 6) and 10 years (IQR: 8). P-VFs were observed in 18.6% and i-VFs occurred in 34.3% of patients. The median estimated diagnostic delay was longer in patients with i-VFs (median: 11 years, IQR: 3), in comparison to those without i-VFs (median: 8 years, IQR: 7; p = 0.02). Age at acromegaly diagnosis and at last follow-up were higher in patients with i-VFs, with respect to those without i-VFs. The age at acromegaly diagnosis was positively associated with the diagnostic delay (p < 0.001, r = 0.216). A longer history of active acromegaly was associated with a high frequency of i-VFs (p = 0.03). The logistic regression confirmed that patients with a diagnostic delay > 10 years had 1.5-folds increased risk of developing i-VFs (OR: 1.5; 95%CI: 1.1-2; p = 0.017). CONCLUSION: Our data showed that the diagnostic delay in acromegaly has a significant impact on VF risk, further supporting the clinical relevance of an early acromegaly diagnosis.

Multidimensional geriatric evaluation in acromegaly: a comparative cross-sectional study.

BACKGROUND: Improvement in acromegaly management increased disease survival and prevalence. Evidence regarding acromegaly in older adults are sparse. We aim to explore acromegaly impact on aging process quality. METHODS: Multicenter case-control study conducted on 42 older adults (≥ 65 years) acromegaly patients (ACRO) compared to an age- and gender-matched control group (CTR). Each participant underwent a multidimensional geriatric evaluation. RESULTS: Mean age in both groups was 73 ± 6 years and female gender was most represented (69%). All comorbidities were more frequent in ACRO than CTR. Thirteen ACRO were in remission and 29 had active disease controlled by medical therapy except for one patient. ACRO showed worse physical performance and mobility skills worsening with age as compared to CTR. ACRO performed poorly in functional status assessment, and age negatively correlated with instrumental and basic daily activities execution. Cognitive evaluation scores were significantly lower in ACRO vs. CTR, worsening with age. No difference was found concerning nutritional and psychological status. Musculoskeletal and bone diseases were more frequent in ACRO than in CTR (52% vs. 12%; 64% vs. 10%; P < 0.05) and independently associated with geriatric outcomes in ACRO. ACRO reported a less satisfactory quality of life concerning physical activity and pain, general health, vitality, social activities. CONCLUSIONS: Our study demonstrates increased frailty of older acromegaly patients as compared to non-acromegaly patients with a consequent negative impact on their quality of life. Therefore, it seems advisable to include physical, functional, cognitive, nutritional, and psychological status assessments in routine clinical practice. Further studies are needed to identify the most appropriate geriatric tools.

HypoparaNet: A Database of Chronic Hypoparathyroidism Based on Expert Medical-Surgical Centers in Italy.

Hypoparathyroidism is a rare disease characterized by low serum calcium levels and absent or deficient parathyroid hormone level. Regarding the epidemiology of chronic hypoparathyroidism, there are limited data in Italy and worldwide. Therefore, the purpose of this study was to build a unique database of patients with chronic hypoparathyroidism, derived from the databases of 16 referral centers for endocrinological diseases, affiliated with the Italian Society of Endocrinology, and four centers for endocrine surgery with expertise in hypoparathyroidism, to conduct an epidemiological analysis of chronic hypoparathyroidism in Italy. The study was approved by the Institutional Review Board. A total of 537 patients with chronic hypoparathyroidism were identified. The leading etiology was represented by postsurgical hypoparathyroidism (67.6%), followed by idiopathic hypoparathyroidism (14.6%), syndromic forms of genetic hypoparathyroidism (11%), forms of defective PTH action (5.2%), non-syndromic forms of genetic hypoparathyroidism (0.9%), and, finally, other forms of acquired hypoparathyroidism, due to infiltrative diseases, copper or iron overload, or ionizing radiation exposure (0.7%). This study represents one of the first large-scale epidemiological assessments of chronic hypoparathyroidism based on data collected at medical and/or surgical centers with expertise in hypoparathyroidism in Italy. Although the study presents some limitations, it introduces the possibility of a large-scale national survey, with the final aim of defining not only the prevalence of chronic hypoparathyroidism in Italy, but also standards for clinical and therapeutic approaches.

Pituitary side effects of old and new drugs.

INTRODUCTION: Pituitary function is influenced by several drugs, including anti-depressant, opioids, glucocorticoids, chemotherapeutic agents, immunomodulators and the newly developed tyrosine kinase inhibitors. In most instances, treatment with these drugs negatively affects pituitary function, but in rare cases an activation of specific hypothalamic-pituitary axes may be observed. Several of the observed pituitary side effects are reversible after drug withdrawal, but pituitary function deficiency may persist long-term. In addition to the well known drugs, recent evidence shows that also non-steroidal anti-inflammatory drugs impair gonadal axis at pituitary level, while antipsychotic phenothiazines alter TSH response to TRH and TSH levels. Atypical antipsychotics may decrease TRH-stimulated TSH. Tricyclic antidepressant drugs interfere with the hypothalamo-pituitary-thyroid axis by decreasing TSH response to TRH. Anabolic-androgenic steroids, marijuana, cocaine, methamphetamines, and opioid narcotics negatively impact fertility, also acting at hypothalamic-pituitary level. CONCLUSIONS: Many of the drugs administered routinely in the intensive care unit significantly impact the hypothalamic-pituitary axis. Therefore, an increased awareness on pituitary side effects of drugs commonly used in clinical practice is necessary in order to rule out possible pharmacological interference when assessing patients with pituitary deficiencies.

Venous Doppler flow patterns, venous congestion, heart disease and renal dysfunction: A complex liaison.

The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on. We focused our attention on venous congestion. In intensive care settings, it is now widely accepted that venous congestion is an important clinical feature worthy of investigation. Evaluating venous Doppler profile abnormalities at multiple sites could suggest adequate treatment and monitor its efficacy. Renal dysfunction could trigger or worsen fluid overload in heart disease, and cardio-renal syndrome is a well-characterized spectrum of disorders describing the complex interactions between heart and kidney diseases. Fluid overload and venous congestion, including renal venous hypertension, are major determinants of acute and chronic renal dysfunction arising in heart disease. Organ congestion from venous hypertension could be involved in the development of organ injury in several clinical situations, such as critical diseases, congestive heart failure, and chronic kidney disease. Ultrasonography and abnormal Doppler flow patterns diagnose clinically significant systemic venous congestion. Cardiologists and nephrologists might use this valuable, non-invasive, bedside diagnostic tool to establish fluid status and guide clinical choices.

Food insecurity and kidney disease: a systematic review.

BACKGROUND: The risk of developing and worsening chronic kidney disease (CKD) is associated with unhealthy dietary patterns. Food insecurity is defined by a limited or uncertain availability of nutritionally adequate and safe food; it is also associated with several chronic medical conditions. The aim of this systematic review is to investigate the current knowledge about the relationship between food insecurity and renal disease. METHODS: We selected the pertinent publications by searching on the PubMed, Scopus, and the Web of Science databases, without any temporal limitations being imposed. The searching and selecting processes were carried out through pinpointed inclusion and exclusion criteria and in accordance with the Prisma statement. RESULTS: Out of the 26,548 items that were first identified, only 9 studies were included in the systemic review. Eight out of the nine investigations were conducted in the US, and one was conducted in Iran. The studies evaluated the relationship between food insecurity and (i) kidney disease in children, (ii) kidney stones, (iii) CKD, (iv) cardiorenal syndrome, and (v) end stage renal disease (ESRD). In total, the different research groups enrolled 49,533 subjects, and food insecurity was reported to be a risk factor for hospitalization, kidney stones, CKD, ESRD, and mortality. CONCLUSIONS: The relationship between food insecurity and renal disease has been underestimated. Food insecurity is a serious risk factor for health problems in both wealthy and poor populations; however, the true prevalence of the condition is unknown. Healthcare professionals need to take action to prevent the dramatic effect of food insecurity on CKD and on other chronic clinical conditions.

Late orbital radiotherapy combined with intravenous methylprednisolone in the management of long-lasting active graves' orbitopathy: a case report and literature review.

PURPOSE: To present a case and review the literature on Orbital Radiotherapy (OR) combined with intravenous methylprednisolone, focusing on its late application in patients with long-lasting active Graves' Orbitopathy (GO). Additionally, we suggest emerging perspective for future research in this context. METHOD: Relevant literature (randomized controlled studies, retrospective studies and reviews) was explored on PubMed from January 1973 to January 2024, searching "orbital radiotherapy" & "Graves disease". RESULTS: OR is a well-established second-line treatment for moderate-to-severe active GO, providing response rates comparable to glucocorticoids. Its anti-inflammatory effect makes OR particularly suitable for early active GO, and when combined with glucocorticoids, outcomes are synergistically improved. The emergence of the new Volumetric Modulated Arc Image-Guided Radiation Therapy (VMAT-IGRT) technique enables precise radiation delivery to the target, significantly reducing associated toxicity. This technological advancement enhances the feasibility of radiotherapy in benign diseases like GO. A retrospective study indicated that late OR in patients with long-lasting active GO may improve diplopia and visual acuity, decreasing disease activity. Our case report supports this conclusion. CONCLUSIONS: This report and literature review underscores the importance of considering late OR combined with intravenous methylprednisolone as a viable treatment option for GO patients with prolonged disease activity, emphasizing the crucial role of personalized therapy in managing GO. However, further investigations are warranted to validate this approach in cases of long-lasting active GO.

Financial Toxicity in Renal Patients (FINTORE) Study: A Cross-Sectional Italian Study on Financial Burden in Kidney Disease-A Project Protocol.

Financial toxicity (FT) refers to the negative impact of health-care costs on clinical conditions. In general, social determinants of health, especially poverty, socioenvironmental stressors, and psychological factors, are increasingly recognized as important determinants of non-communicable diseases, such as chronic kidney disease (CKD), and their consequences. We aim to investigate the prevalence of FT in patients at different stages of CKD treated in our universal health-care system and from pediatric nephrology, hemodialysis, peritoneal dialysis and renal transplantation clinics. FT will be assessed with the Patient-Reported Outcome for Fighting Financial Toxicity (PROFFIT) score, which was first developed by Italian oncologists. Our local ethics committee has approved the study. Our population sample will answer the sixteen questions of the PROFFIT questionnaire, seven of which are related to the outcome and nine the determinants of FT. Data will be analyzed in the pediatric and adult populations and by group stratification. We are confident that this study will raise awareness among health-care professionals of the high risk of adverse health outcomes in patients who have both kidney disease and high levels of FT. Strategies to reduce FT should be implemented to improve the standard of care for people with kidney disease and lead to truly patient-centered care.

Long-term low-dose tolvaptan efficacy and safety in SIADH.

PURPOSE: Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved for the treatment of SIADH-related hyponatremia, but its use is limited. The starting dose is usually 15 mg/day, but recent clinical experience suggests a lower starting dose (<15 mg/day) to reduce the risk of sodium overcorrection. However, long-term low-dose efficacy and safety has not been explored, so far. Aim of our study is to characterize safety and efficacy of long-term SIADH treatment with low-dose Tolvaptan. METHODS: We retrospectively evaluated 11 patients receiving low-dose Tolvaptan (<15 mg/day) for chronic SIADH due to neurological, idiopathic and neoplastic causes. Plasma sodium levels were measured before and 1, 3, 5, 15 and 30 days after starting Tolvaptan and then at 3-month intervals. Anamnestic and clinical data were collected. RESULTS: Mean time spanned 27.3 ± 29.8 months (range 6 months-7 years). Mean plasma sodium levels were within normal range 1, 3 and 6 months after starting Tolvaptan as well as after 1, 2, 3, 5 and 7 years of therapy. Neither osmotic demyelination syndrome nor overcorrection were observed. Plasma sodium levels normalization was associated with beneficial clinical effects. Neurological patients obtained seizures disappearance, improvement in neurological picture and good recovery from rehabilitation. Neoplastic patients were able to start chemotherapy and improved their general condition. Patients did not show hypernatremia during long-term follow-up and reported mild thirst and pollakiuria. CONCLUSIONS: The present study shows that long-term low-dose Tolvaptan is safe and effective in SIADH treatment. No cases of overcorrection were documented and mild side effects were reported.

Systemic comorbidities of acromegaly in real-life experience: which difference among young and elderly patients?

INTRODUCTION: Acromegaly is a rare but potentially life-threatening disease, if not promptly managed, for the systemic complications due to the GH/IGF-I hypersecretion. According to the increased population life span, the number of older acromegaly patients is growing. We aim to investigate clinical features of elderly acromegaly (elderly-ACRO) and to identify the risk factors for the occurrence of comorbidities in elderly-ACRO. MATERIALS AND METHODS: A retrospective and multi-center study was performed on acromegaly patients. Acromegaly comorbidities were compared among elderly-ACRO (>65 years), young acromegaly patients (young-ACRO if ≤65 years) and a control group of age and gender-matched subjects. RESULT: Fifty of the 189 enrolled patients were elderly-ACRO (26.5%). Cardiovascular, metabolic, neurological/psychiatric and joint/articular disorders, nodular thyroid disease, sleep apnoea syndrome and skeletal fragility occurred more frequently in elderly-ACRO as compared to controls. Cardiovascular and metabolic disorders, nodular thyroid disease occurred significantly more frequently in elderly-ACRO as compared to young-ACRO and controls. On the other hand, neurological/psychiatric, joint/articular disorders and bone fragility occur with a similar frequency among elderly and young-ACRO. We found that elderly-ACRO had an increased risk for the occurrence of systemic arterial hypertension (p < 0.001, OR: 5.4 95%IC:2.6-10.9), left ventricular hypertrophy (p = 0.01, OR: 3 95%IC: 1.5-5.8) and metabolic disorders (p = 0.006, OR: 4.1 95%IC: 2-8.3). CONCLUSION: Our results may suggest that some acromegaly comorbidities may be predominantly due to acromegaly "per-se" rather than to aging. On the contrary, cardiovascular and metabolic disorders seem to be due to aging as well.

Glucose Metabolism Derangements and Thyroid Nodules: Does Sex Matter?

(1) Background: Glucose metabolism derangements (GMD) and thyroid nodules (TNs) are the most frequent endocrine disorders, and their relationship is still controversial; little evidence is reported regarding sex differences. We aim to evaluate the association between GMDs and TNs according to sex and the sex differences in glucose metabolism and insulin sensitivity (IS). (2) Methods: We evaluated 342 patients (268 females and 74 males) at high GMD risk undergoing an oral glucose tolerance test and a thyroid ultrasound. (3) Results: The TN prevalence was 61% (n = 210), with no significant differences according to sex and GMD classes. The TN presence is significantly associated with age and impaired fasting glucose (IFG) in females. Males and females with normal fasting glucose (NFG) had a significantly lower OR of having TNs than females with IFG. IFG females had a significantly higher predicted probability of having TNs than NFG males and females but not IFG males. Impaired glucose tolerance/Type 2 diabetes mellitus (IGT/T2DM) is significantly associated with age and male sex, while IFG is associated with age. Females had significantly lower HOMA-index values than males. (4) Conclusions: No significant association between IGT/T2DM and TNs according to sex was found. IFG seems to play a role in TN development independently of sex. Further studies are needed to explore the relationship between TNs and GMD to identify subgroups with a higher TN risk.

Googling Insomnia, Light, Metabolism, and Circadian: A Population Interest Simple Report.

Exposure to light at night, insomnia, and disrupted circadian patterns could be considered risk factors for developing noncommunicable diseases. Understanding the awareness of the general population about the abovementioned factors could be essential to predict noncommunicable diseases. This report aimed to investigate the general community's interest in circadian, insomnia, metabolism, and light using Google Trends, and to evaluate results from different geographic areas. Relative search volumes (RSVs) for the factors mentioned, filtered by the "Health" category, were collected between 2007 and 2021. Moreover, RSVs were analysed in five different European languages. Worldwide mean RSVs for "Circadian", "Insomnia", "Light", and "Metabolism" during the study period were 2%, 13.4%, 62.2%, and 10%, respectively. In different developed countries, searching for light, insomnia, and metabolism were different, suggesting a variable level of awareness. Limited knowledge about the circadian pattern of human activities was detected. The highest correlation coefficient was calculated. Our results suggest the potential role of extensive data analysis in understanding the public interest and awareness about these risk factors. Moreover, it should be interpreted as the onset of stimulus for researchers to use comprehensible language for reaching comprehensive media coverage to prevent sleep and circadian system disturbances.

Hypeprolactinemia: still an insidious diagnosis.

Hyperprolactinemia can have different causes: physiological, pharmacological, and pathological. When investigating the etiology of hyperprolactinemia, clinicians need to be aware of several conditions leading to misdiagnosis. The most popular pitfalls are: acute physical and psychological stress, macroprolactin, hook effect, even though antibodies interferences and biotine use have to be considered. A 52-year-old woman was referred to Endocrinology clinic for oligomenorrhoea and headache. She worked as a butcher. Hormonal evaluation showed very high PRL (305 ng/ml, reference interval: <24 ng/ml) measured with the ECLIA immunoassay analyzer Elecsys 170. The patient's pituitary MRI was normal and macroprolactin was normal. Hormonal workup showed LH: 71.5 mU/ml (2-10.9 mU/ml), FSH: 111.4 mU/ml (3.9-8.8 mU/ml), Estradiol: 110.7 pg/mL (27-122 pg/ml). Since an interference was suspected, the sample was sent to another laboratory using a different assay. After antibody blocking tubes treatment (Heterophilic Blocking Tube, Scantibodies) PRL was 28.8 ng/ml (reference interval < 29.2 ng/ml). Analytical interference should be suspected when assay results are not consistent with the clinical picture. Endogenous antibodies (EA) include heterophile, human anti-animal, autoimmune and other nonspecific antibodies, and rheumatoid factors, that have structural similarities and can cross-react with the antibodies employed by the immunoassay, causing hyperprolactinemia misdiagnosis. The patient's job (butcher), led us to suspect the presence of anti-animal antibodies. Clinicians should also carefully investigate the use of supplements. Biotin can falsely increase hormone concentration in competitive assays. Many clinicians are still not informed about these pitfalls that are not mentioned in some recent reviews on PRL measurement.

Hypoparathyroidism and pseudohypoparathyroidism in pregnancy: an Italian retrospective observational study.

BACKGROUND: Hypoparathyroidism (HypoPT) or pseudo-hypoparathyroidism (pseudo-HypoPT) during pregnancy may cause maternal and fetal/neonatal complications. In this regard, only a few case reports or case series of pregnant or lactating women have been published. The purpose of this study was to describe clinical and biochemical course, pharmacological management, and potential adverse events during pregnancy and post-partum in pregnant women with HypoPT or pseudo-HypoPT. This was a retrospective, observational, multicenter, study involving nine Italian referral centers for endocrine diseases affiliated with the Italian Society of Endocrinology and involved in "Hypoparathyroidism Working Group". RESULTS: This study identified a cohort of 28 women (followed between 2005 and 2018) with HypoPT (n = 25, 84% postsurgical, 16% idiopathic/autoimmune) and pseudo-HypoPT (n = 3). In HypoPT women, the mean calcium carbonate dose tended to increase gradually from the first to third trimester (+ 12.6%) in pregnancy. This average increase in the third trimester was significantly greater compared to the pre-pregnancy period (p value = 0.03). However, analyzing the individual cases, in 44% the mean calcium dosage remained unchanged throughout gestation. Mean calcitriol doses tended to increase during pregnancy, with a statistically significant increase between the third trimester and the pre-pregnancy period (p value = 0.02). Nevertheless, analyzing the individual cases, in the third trimester most women with HypoPT (64%) maintained the same dosage of calcitriol compared to the first trimester. Both mean calcium carbonate and calcitriol doses tended to decrease from the third trimester to the post-partum six months. Most identified women (~ 70%) did not display maternal complications and (~ 90%) maintained mean serum albumin-corrected total calcium levels within the low-to-mid normal reference range (8.5 ± 0.8 mg/dl) during pregnancy. The main complications related to pregnancy period included: preterm birth (n = 3 HypoPT women), and history of miscarriages (n = 6 HypoPT women and n = 2 pseudo-HypoPT women). CONCLUSION: This study shows that mean serum albumin-corrected total calcium levels were carefully monitored during pregnancy and post-pregnancy, with limited evaluation of other biochemical parameters, such as serum phosphate, 24 h urinary calcium, 25-OH vitamin D, and creatinine clearance. To avoid complications in mothers affected by (HypoPT) or (pseudo-HypoPT) and offspring, intense biochemical, clinical and pharmacological monitoring during pregnancy and breastfeeding is highly recommended.

Acromegaly in the elderly patients.

BACKGROUND: Acromegaly is a rare disease characterized by a chronic exposition to growth hormone (GH) and insulin-like growth factor-1 (IGF-1), caused in most cases by a pituitary GH-secreting adenoma. Chronic GH excess induces systemic complications (metabolic, cardiovascular, respiratory, neoplastic, and musculoskeletal) and increased mortality if not appropriately treated. Recent epidemiological data report an improved life span of patients with acromegaly probably due to better acromegaly management; additionally, the number of pituitary incidentaloma in general population also increased over time due to more frequent imaging. Therefore, the number of elderly patients, newly diagnosed with acromegaly or in follow-up, is expected to grow in the coming years and clinicians will need to be aware of particularities in managing these patients. PURPOSE: This review aims to explore different aspects of acromegaly of the elderly patients, focusing on epidemiology, diagnosis, clinical presentation, complications, and management options. METHODS: Available literature has been assessed through PubMed (data until August 2019) by specific keywords. CONCLUSIONS: Available data on acromegaly in the elderly patient are sparse, but point to important differences. Further studies are needed comparing elderly with younger patients with acromegaly to better define a tailored diagnostic and therapeutic management.

Dual-energy X-ray absorptiometry pitfalls in Thalassemia Major.

BACKGROUND: Low mineral mass and reduced bone strength with increased fracture risk are the main causes of morbidity in Thalassemia Major (TM). The pathogenesis is multifactorial and includes ineffective erythropoiesis with medullary expansion, multiple endocrine dysfunctions, direct iron bone deposition, deferoxamine-induced bone dysplasia, and reduced physical activity associated with disease complications. Dual-energy X-ray absorptiometry (DXA) is the "gold standard" for bone mineral density (BMD) assessment and for bone strength and quality evaluation. This method identifies patients at greater risk of fragility fractures, guiding treatment and monitoring response to therapy. In TM, DXA shows limitations concerning BMD calculation accuracy and fracture risk prediction. One of the main challenges in the assessment of bone health in patients with TM is the accurate interpretation of densitometric results. PURPOSE: This review investigates the major pitfalls in DXA implementation and interpretation in TM. METHODS: Available literature has been assessed. CONCLUSIONS: DXA shows limitations in assessing bone mineral "status" in TM, especially in the paediatric population, due to the peculiar characteristics of bone architecture and deformities associated with the disease. A radiological technique adjustment in this population is mandatory.

GH and IGF-I excess control contributes to blood pressure control: results of an observational, retrospective, multicentre study in 105 hypertensive acromegalic patients on hypertensive treatment.

CONTEXT: Approximately one-third of patients with acromegaly have concomitant hypertension. The outcome of hypertension after treatment of acromegaly is unknown. OBJECTIVE: To evaluate the role of GH and IGF-I control on systolic (SBP) and diastolic blood pressure (DBP) levels. PATIENTS: One hundred and five hypertensive patients (60 women, 45 men) with active disease receiving treatment for hypertension at their diagnosis of acromegaly. DESIGN: Observational, retrospective, multicentre. MEASUREMENTS: At diagnosis and after 24 months (median) of treatment we measured serum GH and IGF-I levels, blood pressure levels, left ventricular (LV) mass index (LVMi), early-to-late mitral flow velocity (E/A, as a measure of diastolic function) and LV ejection fraction (LVEF, as a measure of systolic function). RESULTS: At the diagnosis of acromegaly, hypertension was mild in 41.1% and severe in 58.9%. Serum GH and IGF-I levels did not differ in patients with mild or severe hypertension. After 24 months of treatment, all patients had a notable decrease in both GH and IGF-I levels, and achieved significantly lower levels of DBP, heart rate and LVMi; 76 patients (71%) had achieved control of GH and IGF-I levels. Only the patients with controlled acromegaly achieved significantly lower SBP levels and significantly improved cardiac systolic and diastolic function. A higher dose of antihypertensive drugs and/or an increased number of drugs to control hypertension were significantly greater in patients with uncontrolled (32.3%) than in those with controlled acromegaly (7.8%; P = 0.004). CONCLUSION: Hypertensive patients with controlled acromegaly achieved improved control of hypertension and of cardiac diastolic and systolic function. The use of antihypertensive drugs was significantly less in patients achieving control of acromegaly.

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame.

Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects.

Cyclooxygenase-2 inhibitors prevent the development of chemoresistance phenotype in a breast cancer cell line by inhibiting glycoprotein p-170 expression.

Breast cancer cells are usually sensitive to several chemotherapeutic regimens, but they can develop chemoresistance after prolonged exposure to cytotoxic drugs, acquiring a more aggressive phenotype. Drug resistance might involve the multi-drug resistance (MDR) 1 gene, encoding a transmembrane glycoprotein p-170 (P-gp), which antagonizes intracellular accumulation of cytotoxic agents, such as doxorubicin. We previously demonstrated that type 2 cyclooxygenase (COX-2) inhibitors can reverse the chemoresistance phenotype of a medullary thyroid carcinoma cell line by inhibiting P-gp expression and function. The aim of our study was to investigate the role of COX-2 inhibitors in modulating chemoresistance in a human breast cancer cell line, MCF7. MCF7 cells, expressing COX-2 but not MDR1, were treated with increasing doses of doxorubicin, and they became chemoresistant after 10 days of treatment, in association with MDR1 expression induction. This effect was reversed by doxorubicin withdrawal and prevented by co-incubation with N-[2-(cyclohexyloxy)4-nitrophenyl]-methanesulfonamide (NS-398), a selective COX-2 inhibitor. Treatment with NS-398 alone did not influence cell viability of a resistant MCF7 cell clone (rMCF7), but sensitized rMCF7 cells to the cytotoxic effects of doxorubicin. Moreover, treatment with NS-398 significantly reduced MDR1 expression in rMCF7 cells. Doxorubicin-induced membrane P-gp expression and function was also greatly impaired. Our data therefore support the hypothesis that COX-2 inhibitors can prevent or reduce the development of the chemoresistance phenotype in breast cancer cells by inhibiting P-gp expression and function.