Development and validation of the clinical report form for nodular thyroid pathologies

Abstract Objectives: The aim of this study is to develop and validate a novel clinical report form in the format of a structured interview to enable the characterization of the Portuguese population of the Baixo Vouga region with different subtypes of nodular thyroid pathologies (NTyPs). Materials and methods: A structured interview was developed and to the best of our knowledge, this is the first structured interview built and validated for that purpose in Portugal. Results: This structured interview enables the identification of possible correlations between each subtype of nodular lesions and sociodemographic data, consumption habits and lifestyle, endocrine history, and family predisposition. Conclusion: The novel structured interview will simultaneously, enable a detailed characterization of the group of patients with nodular thyroid lesions and will support future metabolomic studies.

Rare Coexistence of Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency and Turner Syndrome: A Case Report and Brief Literature Review

The coexistence of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and Turner syndrome (TS) is rare. We report on a 6-year-old Portuguese girl with mosaic TS [45,XO(39)/47,XXX(21)] presenting with premature pubarche at the age of 5 years. Laboratory findings showed elevated 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione and total testosterone, and her sex-determining region Y (SRY) was negative. CYP21A2 gene analysis revealed two mutations (c.[844G>T]; [CYP21A2del]), consistent with the non-classical form of CAH. Complete deletion of CYP21A2 allele occurred de novo. At 6 years and 4 months, she presented with accelerated growth velocity and hydrocortisone at a dose of 5 mg/m2/day was initiated. This case highlights the need to perform global examinations looking for virilization signs in TS patients' follow-ups. It also supports the reported genetic combination of TS and CAH. Therefore, CAH should be kept in mind in TS patients with SRY negative and virilization signs, even in the absence of short stature.

Development and validation of the clinical report form for nodular thyroid pathologies.

Objective: The aim of this study is to develop and validate a novel clinical report form in the format of a structured interview to enable the characterization of the Portuguese population of the Baixo Vouga region with different subtypes of nodular thyroid pathologies (NTyPs). Materials and methods: A structured interview was developed and to the best of our knowledge, this is the first structured interview built and validated for that purpose in Portugal. Results: This structured interview enables the identification of possible correlations between each subtype of nodular lesions and sociodemographic data, consumption habits and lifestyle, endocrine history, and family predisposition. Conclusion: The novel structured interview will simultaneously, enable a detailed characterization of the group of patients with nodular thyroid lesions and will support future metabolomic studies.

Gestational Diabetes: Which Clinical (Pre)gestational Features Are Able to Predict Failure of Lifestyle Intervention?

Background Controversy exists regarding risk factors in pregnant women that might be associated with a higher probability of failure of lifestyle intervention in the treatment of gestational diabetes (GD). These pregnant women's risk factors may highlight the need for closer surveillance at an early stage of pregnancy. Aims To identify predictors of pharmacological therapy need in early and late GD. Methods This was a retrospective observational study including women with GD diagnosed in the first (group 1) or second trimester (group 2) according to the criteria proposed by the International Association of Diabetes Pregnancy Study Group (IADPSG), singleton pregnancy and follow-up between January 2015 and December 2018, divided according to treatment (lifestyle intervention or pharmacological treatment (metformin and/or insulin)). Results A total of 278 and 273 women were included in groups 1 and 2, of which 48.6% and 55.3% underwent non-pharmacological treatment, respectively. In group 1, women requiring pharmacological therapy tended to be older and have previous GD or family history of diabetes, higher body mass index (BMI) and higher fasting blood glucose (FBG) levels. In group 2, pharmacological treatment need was associated with multiparity, previous GD, higher BMI, higher fasting glucose value in the oral glucose tolerance test (OGTT), and higher OGTT value at 60 minutes. The independent risk factors identified for pharmacological treatment requirement were maternal age (OR 1.10 (1.05-1.16), p<0.001), previous GD (OR 2.70 (1.10-6.58), p=0.029) and FBG (OR 1.07 (1.00-1.14), p=0.048) in group 1 while BMI (OR 1.07 (1.02-1.13), p=0.012) and fasting glucose value in the OGTT (OR 1.03 (1.01-1.05), p=0.006) were the factors identified in group 2. The cut-off values for FBG and fasting glucose value in the OGTT that predicted the necessity of pharmacological treatment were 95.50 mg/dL and 88.50 mg/dL, respectively. Conclusions In early GD, closer surveillance is necessary for older women with a previous GD and an FBG ≥ 95.50 mg/dL. In late GD, pre-gestational BMI and a fasting glucose value in the OGTT ≥ 88.50 mg/dL should prevail.

Subclinical Hypothyroidism in Pediatric Age: How Important Is Autoimmunity?

Background The natural history of subclinical hypothyroidism (SHT) is influenced by the underlying etiology, being the most common Hashimoto's thyroiditis (HT) and isolated hyperthyrotropinemia (IH). Additionally, controversy exists surrounding the need for pharmacological treatment. Methods A retrospective observational study that included patients diagnosed with SHT caused by HT or IH at pediatric age, under levothyroxine therapy and with follow-up at Centro Hospitalar Baixo Vouga between January/2014 and July/2019. Patients with follow-up time <12 months or missing records were excluded. This study aims to compare clinical, analytical and echographic parameters and levothyroxine dose between patients with SHT caused by HT or IH. Results Sample of 39 patients with 16.5 ± 3.4 years, 22 (56.4%) females. There was a preponderance of females in the HT group and males in the IH (p=0.001). Changes in thyroid ultrasound were more prevalent in the HT group (85.7% vs 16.7%, p<0.001). The median initial and final doses of levothyroxine were higher in the HT group (p=0.016, p=0.011). There was a trend towards a higher levothyroxine discontinuation rate in the IH group (22.2% vs 4.8%, p=0.162). Two positive and statistically significant correlations were found between the level of anti-thyroid peroxidase antibodies (TPOAbs) and both the final levothyroxine dose (ρ=0.544; p=0.004) and the final weight-adjusted levothyroxine dose (ρ=0.434; p=0.027). Conclusions HT was more common in females and was associated with higher levothyroxine requirements and less likelihood of treatment discontinuation, especially if high TPOAbs levels. These results can be useful in the difficult daily decision of starting therapy, especially in milder forms of SHT.

Characteristics and treatment outcomes of micromegaly - acromegaly with apparently normal basal GH: A retrospective study and literature review.

Objective. Micromegaly describes a subgroup of patients with clinically evident acromegaly and elevated insulin-like growth factor I (IGF-I) with apparently normal basal growth hormone (bGH) and often a glucose-suppressed growth hormone (GH) of <1 ng/mL at diagnosis. It is controversial whether this condition is a distinct clinical entity or a classic acromegaly in early stages. The aim of the present article was to characterize the prevalence, clinical and biochemical characteristics, and therapeutic outcomes of micromegaly. Methods. A retrospective study of patients with an acromegaly followed ≥1 year at a tertiary center from 1995 to 2019. Patients without IGF-I or GH measurements at diagnosis were excluded. At diagnosis, bGH was considered normal if <2 ng/mL. Results. From 74 patients with acromegaly, 6 (8.1%) had normal bGH levels. There was no difference in the gender distribution, median diagnostic delay, and follow-up time between patients with normal bGH and elevated bGH. Patients with normal bGH were significantly older at time of the first acromegalic manifestation and diagnosis they had significantly lower nadir post-glucose GH and IGF-I levels, and tended to have a higher prevalence of obesity than patients with the elevated bGH. The frequency of acromegalic symptoms, signs, and other comorbidities than obesity was similar between groups. Five patients (83.3%) with normal bGH presented microadenomas. Post-operative remission and outcomes at last visit were comparable between patients with or without normal bGH. Conclusions. Normal bGH acromegaly is relatively uncommon in our patients. These patients showed differentiating characteristics from the classical acromegaly with elevated bGH. Further studies are needed to extend the knowledge about its clinical behavior, therapeutic outcomes, morbidity, and mortality.

Cardiovascular Risk Prediction by the American Diabetes Association Risk-Assessment Tool and Novel and Traditional Cardiovascular Risk Factors in Young Adults With Type 1 Diabetes.

INTRODUCTION: Cardiovascular disease is an important cause of morbidity and mortality in individuals with type 1 diabetes (T1D). The American Diabetes Association (ADA) has the ADA risk-assessment tool for cardiovascular risk (CVR) prediction in individuals with T1D. This study aims to evaluate the prevalence of novel and traditional cardiovascular risk factors (CVRF) and the CVR by the ADA risk-assessment tool: 10-year risk for diabetes complications in young adults with T1D. METHODS: Cross-sectional observational study of T1D individuals aged 18-40 years and T1D duration ≥1 year. The ADA risk-assessment tool was applied to predict CVR. RESULTS: 75 individuals, 61.3% male, with a median age of 30 (26.0-36.0) and 13.0 (6.0-20.0) years of T1D duration. Hypertension was found in 16% of individuals and dyslipidemia in 75.0%. 21.3% were active smokers, 30.7% sedentary, and 42.7% were at least overweight. Most individuals had a 10-year risk <1% for all complications except myocardial infarction (MI). In individuals who were outside the honeymoon period (T1D duration ≥ 5 years), most had a 10-year risk <1% for all complications except MI and amputation. Non-traditional CVRF homocysteine, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, magnesium, and vitamin D correlated with the ADA risk-assessment tool. 10-year risk for MI ≥1% was significantly more frequent in men. CONCLUSION: To our knowledge, this is the first study to apply the ADA risk-assessment tool: 10-year risk for diabetes complications in T1D. Young adults with T1D have a worrying prevalence of CVRF and show suboptimal control. Most individuals with T1D duration ≥1 year have an estimated 10-year risk <1% for all complications, except for MI.

Body mass index and gestational weight gain: relevance in gestational diabetes and outcomes - A retrospective cohort study.

Objective: To evaluate the influence of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on blood glucose levels at diagnosis of gestational diabetes mellitus (GDM) and obstetric/neonatal outcomes. Methods: Retrospective cohort study including 462 women with GDM and singleton pregnancy delivered in our institution between January 2015 and June 2018 and grouped according to BMI/GWG. Results: The diagnosis of GDM was more likely to be established in the 1st trimester (T) in women with obesity than in normal-weight (55.8% vs 53.7%, p = 0.008). BMI positively and significantly correlated with fasting plasma glucose (FPG) levels in the 1stT (rs = 0.213, p = 0.001) and 2ndT (rs = 0.210, p = 0.001). Excessive GWG occurred in 44.9% women with overweight and in 40.2% with obesity (p < 0.001). From women with obesity, 65.1% required pharmacological treatment (p < 0.001). Gestational hypertension (GH) was more frequent in women with obesity (p = 0.016). During follow-up, 132 cesareans were performed, the majority in mothers with obesity (p = 0.008). Of the 17 large-for-gestational-age (LGA) birthweight delivered, respectively 6 and 9 were offsprings of women with overweight and obesity (p = 0.019). Maternal BMI had a predictive value only for macrosomia [aOR 1.177 (1.006-1.376), p = 0.041]. BMI and GWG positively correlated with birthweight (rs = 0.132, p = 0.005; rs = 0.188, p = 0.005). Conclusion: Maternal obesity is related with a major probability of diagnosis of GDM in 1stT, fasting hyperglycemia in 2ndT and a more frequent need for pharmacological therapy. Pre-gestational obesity is associated with GH, cesarean delivery and fetal macrosomia.

Hyperglycemia in hospitalized patients of a tertiary care hospital: prevalence and treatment in two cross-sectional evaluations (2011-2020)

ABSTRACT Objective: A study at Centro Hospitalar Universitário do Porto in 2011 revealed suboptimal control of inpatient hyperglycemia and a similar one was carried out in 2020. This study compares the results of 2011 and 2020 regarding prevalence of hyperglycemia, metabolic control, treatment and glycemic profile by infection/non-infection diagnosis. Subjects and methods: We performed two cross-sectional studies on 13th December 2011 and 9th October 2020 that included all non-critical adults with at least 24 hours of hospitalization, with no specific intervention between them. Glycemic control evaluated by minimum and maximum capillary blood glucose (CBG) in the previous day categorized as hypoglycemia (<70 mg/dL), normoglycemia (70-179 mg/dL) and hyperglycemia (≥180 mg/dL) (SPSS v.20). Results: A total of 418 and 445 patients were respectively included in 2011 and 2020 studies and the prevalence of hyperglycemia was similar. Glycemic control improved numerically although not significantly in 2020: increase in normoglycemia, reduction in hyperglycemia and reduction in hypoglycemia. There was an increase in the use of basal-bolus regimens (19.6% vs. 7.3%, p = 0.009) and a decrease in human basal (p < 0.01) and rapid-acting insulin use (p = 0.001) with a proportional increase in long-acting (p = 0.002) and rapid-acting analogs (p < 0.001) use. There was a higher prevalence of infection (39.8% vs. 23.1%, p = 0.006) in 2020 and, in the infection subgroup, there were higher insulinization rates (37.3% vs. 10.7%, p = 0.017) and a trend to glycemic control improvement. Conclusion: Despite the higher insulinization rates, the preference for new insulin analogs and a trend to better glycemic control, we have not yet reached targets, so education still remains necessary.

Body mass index and gestational weight gain: relevance in gestational diabetes and outcomes - A retrospective cohort study

ABSTRACT Objective: To evaluate the influence of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on blood glucose levels at diagnosis of gestational diabetes mellitus (GDM) and obstetric/neonatal outcomes. Subjects and methods: Retrospective cohort study including 462 women with GDM and singleton pregnancy delivered in our institution between January 2015 and June 2018 and grouped according to BMI/GWG. Results: The diagnosis of GDM was more likely to be established in the 1st trimester (T) in women with obesity than in normal-weight (55.8% vs 53.7%, p = 0.008). BMI positively and significantly correlated with fasting plasma glucose (FPG) levels in the 1stT (rs = 0.213, p = 0.001) and 2ndT (rs = 0.210, p = 0.001). Excessive GWG occurred in 44.9% women with overweight and in 40.2% with obesity (p < 0.001). From women with obesity, 65.1% required pharmacological treatment (p < 0.001). Gestational hypertension (GH) was more frequent in women with obesity (p = 0.016). During follow-up, 132 cesareans were performed, the majority in mothers with obesity (p = 0.008). Of the 17 large-for-gestational-age (LGA) birthweight delivered, respectively 6 and 9 were offsprings of women with overweight and obesity (p = 0.019). Maternal BMI had a predictive value only for macrosomia [aOR 1.177 (1.006-1.376), p = 0.041]. BMI and GWG positively correlated with birthweight (rs = 0.132, p = 0.005; rs = 0.188, p = 0.005). Conclusion: Maternal obesity is related with a major probability of diagnosis of GDM in 1stT, fasting hyperglycemia in 2ndT and a more frequent need for pharmacological therapy. Pre-gestational obesity is associated with GH, cesarean delivery and fetal macrosomia.

Hyperglycemia in hospitalized patients of a tertiary care hospital: prevalence and treatment in two cross-sectional evaluations (2011-2020).

Objective: A study at Centro Hospitalar Universitário do Porto in 2011 revealed suboptimal control of inpatient hyperglycemia and a similar one was carried out in 2020. This study compares the results of 2011 and 2020 regarding prevalence of hyperglycemia, metabolic control, treatment and glycemic profile by infection/non-infection diagnosis. Methods: We performed two cross-sectional studies on 13th December 2011 and 9th October 2020 that included all non-critical adults with at least 24 hours of hospitalization, with no specific intervention between them. Glycemic control evaluated by minimum and maximum capillary blood glucose (CBG) in the previous day categorized as hypoglycemia (<70 mg/dL), normoglycemia (70-179 mg/dL) and hyperglycemia (≥180 mg/dL) (SPSS v.20). Results: A total of 418 and 445 patients were respectively included in 2011 and 2020 studies and the prevalence of hyperglycemia was similar. Glycemic control improved numerically although not significantly in 2020: increase in normoglycemia, reduction in hyperglycemia and reduction in hypoglycemia. There was an increase in the use of basal-bolus regimens (19.6% vs. 7.3%, p = 0.009) and a decrease in human basal (p < 0.01) and rapid-acting insulin use (p = 0.001) with a proportional increase in long-acting (p = 0.002) and rapid-acting analogs (p < 0.001) use. There was a higher prevalence of infection (39.8% vs. 23.1%, p = 0.006) in 2020 and, in the infection subgroup, there were higher insulinization rates (37.3% vs. 10.7%, p = 0.017) and a trend to glycemic control improvement. Conclusion: Despite the higher insulinization rates, the preference for new insulin analogs and a trend to better glycemic control, we have not yet reached targets, so education still remains necessary.

Association Between Serum Magnesium and Glycemic Control, Lipid Profile and Diabetic Retinopathy in Type 1 Diabetes.

INTRODUCTION: Many studies have shown an association between decreased serum magnesium (Mg) levels and poor glycemic control and dyslipidemia in individuals with type 1 diabetes (T1D). Few studies evaluated the association between magnesium (Mg) levels and diabetic retinopathy (DR) in individuals with type 1 diabetes (T1D). METHODS: Retrospective study of adults with T1D, with an ophthalmological evaluation and a serum Mg level determination. According to Mg levels, the individuals were stratified into two groups: normal Mg levels (1.81-2.60 mg/dL) and low Mg levels (≤1.80 mg/dL). Exclusion criteria were individuals on diuretics or proton-pump inhibitors, malabsorption or diarrhea, oral magnesium supplementation in the recent past, pregnancy, or sepsis. RESULTS: 105 individuals, with median Mg levels of 1.96 (interquartile range 0.23) mg/dL. Hypomagnesemia (≤1.80 mg/dL) was detected in 20.0% individuals and 26.7% had DR. Individuals with hypomagnesemia had higher HbA1c (p = 0.014) and triglycerides (p = 0.024). Mg levels were negatively correlated with systolic blood pressure (r = -0.200, p = 0.041), HbA1c (r = -0.281, p = 0.004) and body mass index (BMI) (r = -0.197, p = 0.041). There was no significant difference between Mg levels or prevalence of hypomagnesemia in individuals with or without DR. Also, there was no significant difference between Mg levels and the severity of DR. CONCLUSION: Hypomagnesemia is a common problem in adults with T1D, and it was correlated with poor glycemic control, although we did not find a significant association between Mg levels and prevalence or severity of DR.

Metabolic Profile Characterization of Different Thyroid Nodules Using FTIR Spectroscopy: A Review.

Thyroid cancer's incidence has increased in the last decades, and its diagnosis can be a challenge. Further and complementary testing based in biochemical alterations may be important to correctly identify thyroid cancer and prevent unnecessary surgery. Fourier-transform infrared (FTIR) spectroscopy is a metabolomic technique that has already shown promising results in cancer metabolome analysis of neoplastic thyroid tissue, in the identification and classification of prostate tumor tissues and of breast carcinoma, among others. This work aims to gather and discuss published information on the ability of FTIR spectroscopy to be used in metabolomic studies of the thyroid, including discriminating between benign and malignant thyroid samples and grading and classifying different types of thyroid tumors.

Nephrotic Syndrome as a Cause of Transient Clinical Hypothyroidism.

Nephrotic syndrome may trigger the onset of hypothyroidism, promoting massive urinary protein losses including thyroxine (T4) and triiodothyronine (T3) along with their binding proteins. At an early stage, a clinical and biochemical euthyroid state is expected. However, in patients with prolonged and severe proteinuria, especially with concomitant low thyroid reserve, urinary losses of free and protein-bound thyroid hormones are sufficiently pronounced to induce a subclinical or overt hypothyroidism. Despite its high prevalence in clinical practice, the literature lacks case reports of newly diagnosed clinical hypothyroidism due to NS in adults, making this condition under-recognized. We report a case of a 23-year-old man with previous normal thyroid function who developed overt hypothyroidism due to a severe nephrotic syndrome, requiring supplementation with levothyroxine (LT). After the patient had undergone bilateral nephrectomy, treatment with LT was discontinued and thyroid function normalized.