Bone Health in Patients with Dyslipidemias: An Underestimated Aspect.

Beyond being aging-related diseases, atherosclerosis and osteoporosis share common pathogenetic pathways implicated in bone and vascular mineralization. However, the contributory role of dyslipidemia in this interplay is less documented. The purpose of this narrative review is to provide epidemiological evidence regarding the prevalence of bone disease (osteoporosis, fracture risk) in patients with dyslipidemias and to discuss potential common pathophysiological mechanisms linking osteoporosis and atherosclerosis. The effect of hypolipidemic therapy on bone metabolism is also discussed. Despite the high data heterogeneity and the variable quality of studies, dyslipidemia, mainly elevated total and low-density lipoprotein cholesterol concentrations, is associated with low bone mass and increased fracture risk. This effect may be mediated directly by the increased oxidative stress and systemic inflammation associated with dyslipidemia, leading to increased osteoclastic activity and reduced bone formation. Moreover, factors such as estrogen, vitamin D and K deficiency, and increased concentrations of parathyroid hormone, homocysteine and lipid oxidation products, can also contribute. Regarding the effect of hypolipidemic medications on bone metabolism, statins may slightly increase BMD and reduce fracture risk, although the evidence is not robust, as it is for omega-3 fatty acids. No evidence exists for the effects of ezetimibe, fibrates, and niacin. In any case, more prospective studies are needed further to elucidate the association between lipids and bone strength.

Unfavorable Hormonal and Psychologic Profile in Adult Women with a History of Premature Adrenarche and Pubarche, Compared to Women with Polycystic Ovary Syndrome.

If circulating adrenal androgens levels rise before the age of 8 years in girls, this phenomenon is termed premature adrenarche (PA), while the concomitant appearance of pubic hair is called premature pubarche (PP). Girls with PA-PP display an unfavorable hormonal profile compared to their normal peers and have an increased risk of developing polycystic ovary syndrome (PCOS) features peripubertally. However, the sequelae of premature adrenarche remains unclear. We assessed metabolic, hormonal, psychologic profiles, and ovarian morphology in 21 women of mean age (±SD) 21.3±3.3 years, BMI: 23.6±4.4 kg/m2 with PA-PP, 45 women with PCOS and 26 controls, matched for age and BMI. PA-PP women displayed a favorable lipid profile compared to PCOS and controls. Insulin resistance index (HOMA-IR), however, were similar in PA-PP and PCOS women (2.09±1.42, 2.08±0.83) and higher than controls (1.13±0.49, p <0.05). Circulating androstenedione levels did not differ between PA-PP and PCOS women (0.11±0.05 vs. 0.12±0.03), but was higher than that of controls (0.02±0.0 nmol/l, p <0,05). Ovarian volume was increased in PA-PP and PCOS (11.14±3.3 vs. 10.99±4.61) compared to controls (6.74±1.83 cm3). PA-PP women had a higher score of state/trait anxiety and depressive and eating disorder symptoms than controls, with a pattern that matched that of PCOS women. Only 14% of the PA-PP group fulfilled the Rotterdam PCOS criteria. Some women with a history of PA-PP displayed hormonal and psychologic profile similar to PCOS, and accordingly a regular monitoring of these girls during adulthood is advised.

Nonselective Beta-Blockers Do Not Affect Survival in Cirrhotic Patients with Ascites.

BACKGROUND: The role of nonselective beta-blockers in cirrhotic patients with ascites has been recently questioned; however, definitive evidence in this regard is still lacking. AIMS: To analyze published data on the influence of nonselective beta-blockers as compared to control group on survival of cirrhotic patients with ascites. METHODS: Computerized bibliographic search on the main databases was performed. Hazard ratios from Kaplan-Meier curves were extracted in order to perform an unbiased comparison of survival estimates. Secondary outcomes were mortality in patients with refractory ascites, pooled rate of nonselective beta-blockers interruption, spontaneous bacterial peritonitis and hepato-renal syndrome incidence. RESULTS: Three randomized controlled trials and 13 observational studies with 8279 patients were included. Overall survival was comparable between the two groups (hazard ratio = 0.86, 0.71-1.03, p = 0.11). Study design resulted as the main source of heterogeneity in sensitivity analysis and meta-regression. Mortality in refractory ascites patients was similar in the two groups (odds ratio = 0.90, 0.45-1.79; p = 0.76). No difference in spontaneous bacterial peritonitis (odds ratio = 0.78, 0.47-1.29, p = 0.33) and hepato-renal syndrome incidence (odds ratio = 1.22, 0.48-3.09; p = 0.67) was observed. Pooled rate of nonselective beta-blockers interruption was 18.6% (5.2-32.1%). CONCLUSIONS: Based on our findings, nonselective beta-blockers should not be routinely withheld in patients with cirrhosis and ascites, even if refractory.

Control of the onset of puberty.

PURPOSE OF REVIEW: The mechanism of puberty initiation remains an enigma, despite extensive research in the field. Pulsatile pituitary gonadotropin secretion under the guidance of hypothalamic gonadotropin-releasing hormone (GnRH) constitutes a sine qua non for pubertal onset. In turn, the secretion of GnRH in the human hypothalamus is regulated by kisspeptin and its receptor as well as by permissive or opposing signals mediated by neurokinin B and dynorphin acting on their respective receptors. These three supra-GnRH regulators compose the Kisspeptin, Neurokinin B and Dynorhin neurons (KNDy) system, a key player in pubertal onset and progression. RECENT FINDINGS: The recent discovery that makorin ring finger protein 3 is also involved in puberty initiation provided further insights into the regulation of the KNDy pathway. In fact, the inhibitory (γ-amino butyric acid, neuropeptide Y, and RFamide-related peptide-3) and stimulatory signals (glutamate) acting upstream of KNDy called into question the role of makorin ring finger protein 3 as the gatekeeper of puberty. Meanwhile, the findings that 'neuroestradiol' produced locally and endocrine disruptors from the environment may influence GnRH secretion is intriguing. Finally, epigenetic mechanisms have been implicated in pubertal onset through recently discovered mechanisms. SUMMARY: The exact molecular machinery underlying puberty initiation in humans is under intensive investigation. In this review, we summarize research evidence in the field, while emphasizing the areas of uncertainty and underlining the impact of current information on the evolving theory regarding this fascinating phenomenon.

Impact of a mindfulness stress management program on stress, anxiety, depression and quality of life in women with polycystic ovary syndrome: a randomized controlled trial.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder with a significant psychological burden throughout the life course of affected women. Thus, use of mindful awareness may be beneficial as an adjunct to conventional medical management of women with PCOS. A randomized, controlled trial was conducted at the Evgenideion Hospital of the Athens University Medical School to explore the impact of an 8-week mindfulness stress management program on measures of depression, anxiety and stress as well as on the quality of life in reproductive age women with PCOS. The study was approved by the Research Ethics Committee. Twenty-three and 15 women with PCOS were randomly allocated to the intervention or control group, respectively. All participants were administered DASS21, PSS-14, PCOSQ, Daily Life and General Life Satisfaction Questionnaires and provided three-timed daily samples of salivary cortisol, before and after the intervention. Intervention group participants were provided with the Credibility/Expectancy Questionnaire at the day of enrolment, to check for possible placebo effect on the outcome. Post-intervention, between-group results revealed statistically significant reductions in stress, depressive and anxiety symptoms, as well as in salivary cortisol concentrations, along with an increase in Life Satisfaction and Quality of Life scores in the intervention group only. There was no significant "placebo" effect on the outcome measures. Mindfulness techniques seem promising in ameliorating stress, anxiety, depression and the quality of life in women with PCOS and could be used as an adjunct method to the conventional management of these women.

Does visceral adiposity index signify early metabolic risk in children and adolescents?: association with insulin resistance, adipokines, and subclinical inflammation.

BACKGROUND: Visceral adiposity index (VAI) is a novel gender-specific index based on waist circumference (WC), BMI, and lipid parameters. Although VAI does not actually estimate visceral adiposity, it accurately reflects visceral fat function and insulin resistance. This index has not been studied in children thus far. This study aims to fill this gap. METHODS: In a cohort of Saudi children and adolescents, anthropometric measurements and metabolic/hormonal profile were obtained. RESULTS: A total of 543 subjects, 292 of whom were boys, were included (mean age: 11.9 ± 3.3 y; BMI: 19.8 ± 5.6 kg/m(2)). In all subjects, VAI was inferior to BMI and WC regarding its correlations with adiponectin, leptin, insulin resistance (homeostasis model of assessment-insulin resistance (HOMA-IR)), C-reactive protein (CRP) level, and systolic blood pressure, but it exhibited a stronger association with glucose in boys (r = 0.23; P < 0.01). In stepwise multivariate analyses, only BMI was consistent as an independent predictor of adiponectin, leptin, HOMA-IR, and CRP. VAI was the only index independently associated with glucose. CONCLUSION: Although VAI is related to glucose in children, it seems to be inferior to BMI in terms of association with insulin resistance, adipokines, and subclinical inflammation. Until specific studies can be performed in children, VAI should be extrapolated with caution in this age range.

Nutritional and exercise interventions to improve conception in women suffering from obesity and distinct nosological entities.

Infertility among women, particularly those living with obesity, presents a multifaceted challenge with implications for reproductive health worldwide. Lifestyle interventions, mainly focusing on weight loss, have emerged as promising strategies to improve fertility outcomes in this population. This review aims to explore the effectiveness of various lifestyle interventions, encompassing dietary modifications and exercise regimens, in enhancing fertility outcomes among women with obesity and associated conditions such as polycystic ovary syndrome, congenital adrenal hyperplasia, type 2 diabetes mellitus, premenopause, hypothyroidism and eating disorders. Methodology of study search encompass a broad spectrum, ranging from interventions targeting weight management through slow or rapid weight loss to dietary approaches emphasizing whole food groups, specific nutrients, and dietary patterns like low-carbohydrate or ketogenic diets, as well as the Mediterranean diet. By synthesizing existing findings and recommendations, this review contributes to the understanding of lifestyle interventions in addressing infertility, with an emphasis on the population of women of reproductive age with excess weight and known or unknown infertility issues, while promoting their integration into clinical practice to optimize reproductive health and overall well-being.

Long-Term Effects of 0.1 mg Recombinant-Human-Thyrotropin-Stimulated Fixed-Dose Radioiodine Therapy in Patients with Recurrent Multinodular Goiter after Surgery.

(1) Background: After thyroid malignancy is ruled out, treatment options for multinodular goiter patients include surgery, levothyroxine suppressive therapy, and 131-I therapy. Surgery effectively reduces goiter size but carries risks of surgical and anesthetic complications. 131-I therapy is the only nonsurgical alternative, but its effectiveness diminishes with goiter size and depends on iodine sufficiency. This study aimed to assess the efficacy and safety of 0.1 mg rhTSH as an adjuvant to a fixed dose of 131-I therapy in patients with a recurrence of large multinodular goiter, several years after the initial thyroidectomy. (2) Methods: 14 patients (13 females and 1 male), aged 59.14 ± 15.44 (range, 35-78 years) received 11mciu of 131-I, 24 h after the administration of 0.1 mg rhTSH. The primary endpoint was the change in thyroid volume (by ultrasound measurements) as well as in the diameter of the predominant nodule during a follow-up period of 10 years. Secondary endpoints were the alterations in thyroid function and potential adverse effects. (3) Results: A significant decrease in the volume of initial thyroid remnants (32.16 ± 16.66 mL) was observed from the first reevaluation (at 4 months, 23.12 ± 11.59 mL) as well as at the end of the follow-up period (10 years, 12.62 ± 8.76 mL), p < 0.01. A significant reduction in the dominant nodule was also observed (from 31.71 ± 10.46 mm in the beginning to 26.67 ± 11.05 mm). (4) Conclusions: Further investigation is needed since this approach could be attractive in terms of minimizing the potential risks of reoperation in these patients.

Color Doppler ultrasound and real-time elastography in patients with hypothyroidism for the prediction of levothyroxine replacement: a cross-sectional study of 338 patients.

AIMS: While hormonal assays are commonly used for thyroid function assessment, Doppler sonography provides valuable information on vascularization and blood flow. This study aimed to examine the potential associations between Doppler parameters and clinical characteristics of hypothyroid patients, such as the autoimmune nature of the disease and adequacy of LT4 replacement. METHODS: A total of 338 patients with hypothyroidism, primarily caused by autoimmune thyroiditis (AT), were enrolled in this study. Exclusion criteria comprised specific medical conditions, medication history, and nodular abnormalities of the thyroid gland. Patient demographics (age, sex, BMI), treatment parameters (LT4 daily dose), and thyroid hormone levels (TSH, fT4) were recorded. RESULTS: Among the enrolled patients, 85.2% had autoimmune thyroiditis. Suboptimal levothyroxine (LT4) replacement was observed in 20.1% of patients at the time of enrollment. Patients with autoimmune thyroiditis had increased elastography ratios compared to those without autoimmune disease and present a positive association of elastography ratios with vascularity. In patients without autoimmune thyroiditis, those with suboptimal LT4 replacement had lower total thyroid volume. Patients with suboptimal LT4 replacement had higher peak systolic velocity (PSV) and end-diastolic velocity (EDV) in the inferior thyroid artery and lower resistive index (RI). The severity of hypothyroidism, as indicated by LT4 dose/body mass index (BMI), was negatively correlated with thyroid volume and EDV values of superior and inferior thyroid arteries. PSV of the inferior thyroid artery can predict suboptimal LT4 replacement (sensitivity 81.8%, specificity 42%). CONCLUSIONS: In situations where obtaining blood tests may be challenging, utilizing color Doppler ultrasound can serve as an alternative method to assess treatment responses and identify patients who require further hormonal examinations.

Anastrozole monotherapy further improves near-adult height after the initial combined treatment with leuprorelin and anastrozole in early-maturing girls with compromised growth prediction: results from the second phase of the GAIL study.

Background: The first phase of the GAIL study ("Girls treated with an Aromatase Inhibitor and Leuprorelin," ISRCTN11469487) has shown that the combination of anastrozole and leuprorelin for 24 months is safe and effective in improving the predicted adult height (PAH) in girls with early puberty and compromised growth prediction by +1.21 standard deviation score (SDS; +7.51 cm) compared to inhibition of puberty alone, +0.31 SDS (+1.92 cm). Objectives and hypotheses: In the second phase of the GAIL study, we assessed the adult height (AH)/near-adult height (NAH) at the end of the first phase and, in addition, the efficacy of anastrozole monotherapy thereafter in further improving NAH. Methods: We measured the AH (age 16.5 years)/NAH [bone age (BA), 15 years] of the 40 girls included, divided into two matched groups: group A (20 girls on anastrozole + leuprorelin) and group B (20 girls on leuprorelin alone). Group A was further randomized into two subgroups: A1 and A2. Group A1 (n = 10), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until BA 14 years, with a 6-month follow-up. Group A2 (n = 10) and group B (n = 20), who received only the combined treatment and leuprorelin alone, respectively, were recalled for evaluation of AH/NAH. Results: AH or NAH exceeded the PAH at the completion of the 2-year initial phase of the GAIL study in all groups, but the results were statistically significant only in group A1: NAH-PAH group A1, +3.85 cm (+0.62 SDS, p = 0.01); group A2, +1.6 cm (+0.26 SDS, p = 0.26); and group B, +1.7 cm (+0.3 SDS, p = 0.08). The gain in group A1 was significantly greater than that in group A2 (p = 0.04) and in group B (p = 0.03). Anastrozole was determined to be safe even as monotherapy in Group A1. Conclusions: In early-maturing girls with compromised growth potential, the combined treatment with leuprorelin and anastrozole for 2 years or until the age of 11 years resulted in a total gain in height of +9.7 cm when continuing anastrozole monotherapy until the attainment of NAH, as opposed to +7.4 cm if they do not continue with the anastrozole monotherapy and +3.6 cm when treated with leuprorelin alone. Thus, the combined intervention ends at the shortest distance from the target height if continued with anastrozole monotherapy until BA 14 years.

Hypercalcemic Crisis Due to a Giant Intrathyroidal Parathyroid Adenoma, with Postsurgical Severe Hypocalcemia and Hungry Bone Syndrome: A Case Report.

BACKGROUND: Parathyroid adenoma is the most common cause of hypercalcemia and rarely leads to a hypercalcemic crisis, which is an unusual endocrine emergency that requires timely surgical excision. CASE PRESENTATION: A 67-year-old male was admitted to the ER of the Euroclinic Hospital, Athens, Greece, because of elevated calcium levels and a palpable right-sided neck mass, which were accompanied by symptoms of nausea, drowsiness, and weakness for six months that increased prior to our evaluation. A gradual creatinine elevation and decreasing mental state were observed as well. The initial laboratory investigation identified severely elevated serum calcium (3.6 mmol/L) levels consistent with a hypercalcemic crisis (HC) and parathyroid hormone PTH (47.6 pmol/L) due to primary hyperparathyroidism. Neck ultrasonography (USG) identified a large, well-shaped cystic mass in the right thyroid lobe. With a serum calcium concentration of 19.5 mg/dL and a PTH of 225.3 pmol/L, the patient underwent partial parathyroidectomy and total thyroidectomy, which decreased serum calcium and PTH to 2.5 mmol/L and 1.93 pmol/L, respectively. Histology revealed a giant intrathyroidal cystic parathyroid adenoma, which was responsible for the hypercalcemic crisis. Postoperatively, the patient developed severe biochemical and clinical hypocalcemia, with calcium concentrations as low as 1.65 mmol/L, consistent with hungry bone syndrome (HBS), which was treated with high doses of intravenous calcium gluconate and oral alfacalcidol, and a slow recovery of serum calcium. After discharge, parathyroid function recovered, and symptomatology resolved entirely in more than one month. DISCUSSION/CONCLUSIONS: We present a case involving an exceptionally large intrathyroidal parathyroid adenoma that is characterized by clinical manifestations that mimic malignancy. The identification and treatment of such tumors is challenging and requires careful preoperative evaluation and postoperative care for the risk of hungry bone syndrome.

Insulin-sensitizing agents for infertility treatment in woman with polycystic ovary syndrome: a narrative review of current clinical practice.

PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine, metabolic, and reproductive disorder which, according to the Rotterdam criteria, affects up to 24% of women of childbearing age. Although the prevalence of infertility in this subpopulation of women is high, the optimal treatment has not been fully established yet. Insulin resistance is considered to be an important mechanism involved in the development of PCOS; hence, the aim of this narrative review is to present an overview of the current pharmacological insulin-sensitizing treatment modalities for infertile women with PCOS. METHODS: A MEDLINE and PubMed search for the years 1990-2023 was performed using a combination of keywords. Clinical trials with insulin sensitizers used for infertility treatment as well as analyses of systematic reviews and meta-analyses were evaluated. When deemed necessary, additional articles referenced in the retrieved papers were included in this narrative review. RESULTS: Several insulin-sensitizing compounds and various therapeutical protocols are available for infertility treatment of women with PCOS. Metformin is the most common adjuvant medication to induce ovulation in infertile women with PCOS and is more frequently administered in combination with clomiphene citrate than on its own. Recently, inositol and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as possible options for infertility treatment in PCOS. CONCLUSION: The future of medical treatment of PCOS women with infertility lies in a personalized pharmacological approach, which involves various compounds with different mechanisms of action that could modify ovarian function and endometrial receptivity, ultimately leading to better overall reproductive outcomes in these women.

Visceral adiposity index is highly associated with adiponectin values and glycaemic disturbances.

BACKGROUND: Visceral Adiposity Index (VAI) is a gender-specific mathematical index estimated with the use of simple anthropometric (body mass index and waist circumference) and biochemical (triglycerides and high density lipoprotein cholesterol) parameters. Recent studies have shown that VAI reflects accurately the degree of visceral adiposity and insulin resistance. However, up to now, VAI has not been evaluated if it correlates with carbohydrate metabolism disorders, as well as with adipokine secretion from the fat mass. METHODS: In a cohort of 308 out of 414 adult Saudi subjects screened for the study, detailed personal medical history, anthropometrics and metabolic/hormonal profiles were obtained. Additionally, the circulating concentrations of several circulating adipokines, namely adiponectin, leptin, tumour necrosis factor-α (TNF-α) and resistin, were measured. RESULTS: Stepwise multivariate analysis showed that VAI was the sole determinant of adiponectin levels (R(2)  = 0·07, beta ± SE: -0·25 ± 0·05), while BMI and female gender predicted leptin levels (R(2)  = 0·26, 0·10 ± 0·01 and 0·61 ± 0·15, respectively). Furthermore, the presence of impaired fasting glucose (IFG)/diabetes was predicted only by age and VAI. CONCLUSIONS: We report for the first time the direct relations of VAI with adipose tissue secretion, as well as with functional glycaemic disorders. Because VAI is estimated easily with data obtained in everyday practice, it could be used as an indirect index of adiponectin levels and the risk of impaired glucose metabolism.

Vitamin D, Menopausal Health and COVID-19: Critical Appraisal of Current Data.

Inconsistency exists across studies conducted in postmenopausal women regarding the effect of vitamin D deficiency (VDD) and supplementation on several aspects of menopausal health, such as fractures, vasomotor symptomatology, cardiovascular disease (CVD), cancer and infections, including coronavirus disease 2019 (COVID-19). The aim of this review is to critically summarize the evidence provided by observational studies and randomized controlled trials (RCTs) of vitamin D supplementation in postmenopausal women with VDD. Observational studies have found that VDD is associated with an increased risk of falls and fractures after the menopause. VDD also has a negative effect on menopausal symptomatology. VDD, especially its severe form, is associated with an increased risk of CVD risk factors and CVD events. VDD is associated with increased risk and mortality from several cancer types and risk of infections. The evidence from RCTs regarding the effect of vitamin D supplementation on falls, fractures, menopausal symptoms, cardiovascular disease, cancer and infections is not robust. Thus, skeletal health may benefit only when vitamin D is co-administered with calcium, especially in those ≥70 years old and with severe VDD. There is no evidence of a favorable effect on menopausal symptoms or risk of CVD or cancer, except for a modest reduction in cancer-related mortality. Inconsistency still exists regarding its effect on infection risk, disease severity and mortality due to COVID-19.

Low Dose Monacolin K Combined with Coenzyme Q10, Grape Seed, and Olive Leaf Extracts Lowers LDL Cholesterol in Patients with Mild Dyslipidemia: A Multicenter, Randomized Controlled Trial.

Certain nutraceuticals, mainly containing red yeast rice, might be considered as an alternative therapy to statins in patients with dyslipidemia, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing a low dose of monacolin K combined with coenzyme Q10, grape seed and olive tree leaf extracts in patients with mild hypercholesterolemia. In total, 105 subjects with mild hypercholesterolemia (low-density lipoprotein cholesterol LDL-C levels 140-180 mg/dL) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of monacolin K (3 mg), and LM plus a high dosage of monacolin K (10 mg) and treated for 8 weeks. The primary endpoint was the reduction of LDL-C and total cholesterol (TC). LDL-C decreased by 26.46% on average (p < 0.001) during treatment with 10 mg of monacolin and by 16.77% on average during treatment with 3 mg of monacolin (p < 0.001). We observed a slight but significant reduction of the triglyceride levels only in the high-dose-treated group (mean -4.25%; 95% CI of mean -11.11 to 2.61). No severe adverse events occurred during the study. Our results confirm the LDL-C-lowering properties of monacolin are clinically meaningful even in lower doses of 3 mg/day.

A Nutritional Approach to Optimizing Pump Therapy in Type 1 Diabetes Mellitus.

Achieving optimal glucose control in individuals with type 1 diabetes (T1DM) continues to pose a significant challenge. While continuous insulin infusion systems have shown promise as an alternative to conventional insulin therapy, there remains a crucial need for greater awareness regarding the necessary adaptations for various special circumstances. Nutritional choices play an essential role in the efficacy of diabetes management and overall health status for patients with T1DM. Factors such as effective carbohydrate counting, assessment of the macronutrient composition of meals, and comprehending the concept of the glycemic index of foods are paramount in making informed pre-meal adjustments when utilizing insulin pumps. Furthermore, the ability to handle such situations as physical exercise, illness, pregnancy, and lactation by making appropriate adjustments in nutrition and pump settings should be cultivated within the patient-practitioner relationship. This review aims to provide healthcare practitioners with practical guidance on optimizing care for individuals living with T1DM. It includes recommendations on carbohydrate counting, managing mixed meals and the glycemic index, addressing exercise-related challenges, coping with illness, and managing nutritional needs during pregnancy and lactation. Additionally, considerations relating to closed-loop systems with regard to nutrition are addressed. By implementing these strategies, healthcare providers can better equip themselves to support individuals with T1DM in achieving improved diabetes management and enhanced quality of life.

Elevated Preoperative TPO Ab Titers Decrease Risk for DTC in a Linear Fashion: A Retrospective Analysis of 1635 Cases.

CONTEXT: For some, chronic lymphocytic thyroiditis (Hashimoto thyroiditis) is an important risk factor for differentiated thyroid cancer (DTC). Surgical cohort studies even suggested a potential role for thyroid peroxidase antibodies (TPO-Abs) on that risk. OBJECTIVE: Our clinical observations argued against that possibility. We designed the present study to evaluate the relationship of TPO-Abs and DTC in a large patient population. METHODS: We recruited individuals who underwent thyroidectomies at 4 different clinical sites (USA: 1 clinic, 2000-2013, and Greece: 3 clinics, 2007-2021). We gathered data on TPO-Abs titers measured with commercially available chemiluminescence immunoassays, and reviewed patients' data including surgical pathology. TPO-Abs of 34 IU/mL or greater was deemed positive (TPO+) and TPO-Abs less than 34 IU/mL was deemed negative (TPO-). Odds ratios (OR) for DTC were calculated with the Fisher exact test and P less than .05 was deemed significant. RESULTS: We reviewed data from 8461 consecutive thyroid surgery cases. TPO-Abs titers were available for 1635 individuals: DTC n = 716 (43.8%), benign pathology n = 919 (56.2%), TPO+ n = 540 (33.0%), and TPO- n = 1095 (67.0%). DTC was found at a lower frequency in TPO+ (198/540, 36.7%) compared to TPO- (518/1095, 47.3%) patients, OR 0.64 (0.52-0.80; P < .0001). Rising TPO-Abs titers conferred protection against DTC in a linear fashion: TPO-Abs less than 10 IU/mL: 59.3%, TPO-Abs less than 34 IU/mL: 47.4%, TPO-Abs 34 to 100 IU/mL: 42.6%, TPO-Abs 100 to 500 IU/mL: 32.0%, TPO-Abs greater than 1000 IU/mL: 19.4%; P less than .0001. CONCLUSION: Higher TPO-Ab titers appear protective against DTC in our large multicenter cohort of patients who underwent thyroidectomies. Rising preoperative TPO-Abs titers conferred linearly increasing protection against DTC.

The clinical significance of low dose biotin supplements (<300µg/day) in the treatment of patients with hypothyroidism: crucial or overestimated?

BACKGROUND: In the last decade, the combination of the widespread use of streptavidin-biotin technology and biotin-containing supplements (BCS) in the daily clinical practice, have led to numerous reports of erroneous hormone immunoassay results. However, there are no studies assessing the clinical and biochemical significance of that phenomenon, when treating patients with hypothyroidism. Therefore, a prospective study was designed to investigate the potential alterations in the measurement of thyroid hormone concentrations and clinical consequences in patients with hypothyroidism using low -dose BCS containing less than 300 µg/day. METHODS: Fifty-seven patients on thyroxine supplementation, as a result of hypothyroidism and concurrent use of BCS at a dose <300µg/day for 10 to 60 days were prospectively evaluated. Namely, TSH and free T4 (FT4) concentration measurements were performed, during BC supplementation and 10 days post BCS discontinuation and compared to 31 age-matched patients with supplemented hypothyroidism and without BCS. RESULTS: A statistically significant increase in TSH and decline in FT4 concentrations was observed after BCS discontinuation. However, on clinical grounds, these modifications were minor and led to medication dose adjustment in only 2/57 patients (3.51%) in whom TSH was notably decreased after supplement discontinuation. CONCLUSION: Our study suggests that changes in thyroid hormones profiling, due to supplements containing low dose biotin, are of minimal clinical relevance and in most cases don't occult the need to adjust the thyroxine replacement dose in patients with hypothyroidism. Larger, well-designed trials are required to further evaluate this phenomenon.

Assessment of Type 2 Diabetes Risk in Young Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) are at increased risk for dysglycemia and type 2 diabetes compared to healthy BMI-matched women of reproductive age: robust evidence exists supporting this notion. The presence of altered glycemic status in young women with the syndrome presents a distinct challenge for the clinician for several reasons. Firstly, the reported incidence of this disorder varies among the limited available studies. Furthermore, there is a lack of consensus on the best screening method, which women to screen, at what frequency, and which strategies need to be implemented to reduce the above risk. We provide data regarding the prevalence of dysglycemia in young women suffering from PCOS and the pathophysiological mechanisms underlying the disorder. In addition, we present evidence suggesting universal screening with the oral glucose tolerance test in young women with the syndrome, irrespective of age or BMI status, to identify and manage glycemic abnormalities in a timely manner. Regarding follow-up, oral glucose testing should be carried out at regular intervals if there are initial abnormal findings or predisposing factors. Finally, the efficacy of a well-balanced diet in conjunction with regular exercise and the use of non-pharmacologic agents in this specific population is discussed.

Intense Testing and Use of Vitamin D Supplements Leads to Slow Improvement in Vitamin D Adequacy Rates: A Cross-Sectional Analysis of Real-World Data.

BACKGROUND: Vitamin D testing (VDT) and supplement use (VDS) are on the rise, but most patients remain deficient (<30 ng/mL-VDD). We designed the present real-world study to assess this paradox. METHODS: We reviewed data from all patients visiting our clinics between 2014 and 2022. We estimated the rate of patients with vitamin D adequacy (≥30 ng/mL) (VDA) by year and month of testing, the dose of VDS (low (≤1200 IU/day), medium (1201-3000 I/day) and high dose (>3000 IU/day)), intake duration (short-term (<12 months) and long-term use (≥12 months)), and timing of use (current use, former use, no use). RESULTS: We enrolled n = 6912 subjects with vitamin D measurements: n = 5195 females (75.2%), age 44.0 ± 16.8 years, BMI 27.9 ± 6.5 kg/m2; never users: n = 5553 (80.3%), former users: n = 533 (7.7%), current users: n = 826 (12.0%). Current use of VDS was higher in females. VDT rose from 42.1% in 2014 to 92.7% in 2022, and VDA rose from 14.8% to 25.5% for the same time. VDA was found overall in n = 1511 (21.9%); Never users: n = 864 (15.6%), Former users: n = 123 (23.2%); and Current users: n = 370 (44.8%). The maximal VDA (67.9%) was found in subjects using high-dose VDS in the long term. CONCLUSIONS: Despite the significant rise in VDT and VDS use, VDA was found in a minority of patients. Prolonged use of high-dose supplements produces modest improvements in VDA.