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- Gender-Affirming Hormone Therapy: Physical and Sociopsychological Effects, Impact and SatisfactionPublication . Santos, Rafael Baptista; Lemos, Carolina; Saraiva, MiguelBackground Gender dysphoria treatment includes gender-affirming hormone therapy (GAHT). Studies are still lacking on how to characterize its effects and impact on transgender people's lives more effectively. Aim To study the physical and psychological effects of GAHT on transgender individuals, assess its impact on their lives, and rate their overall satisfaction. Methods Participants (n = 114; ages 18-62 years; median age 24.0 (21.0 - 33.0) years) included transgender adults residing in Portugal who were undergoing or had undergone hormonal therapy for at least one uninterrupted year. Participants completed an original questionnaire. For most items, an ordinal Likert-style scale ranging from 0 (worst result) to 6 (best result) was used. Descriptive statistics and non-parametric tests, including Pearson's chi-squared test, Wilcoxon signed-rank test, and Mann-Whitney U test were used to analyze categorical and continuous variables, with a significance level set at 0.05. Outcomes The outcomes included desired physical changes rating (perception and satisfaction with changes); side effects of GAHT; the sociopsychological impact of GAHT (on self-esteem, body image, psychological wellbeing, social and family relations); overall satisfaction (with treatment results and medical follow-up). Results The changes classified as the most perceptible in those undergoing masculinizing treatment (Group M) were amenorrhea (6 (5.0-6.0) points) and clitoris enlargement (6 (5.0-6.0) points). These were also the ones rated as the most satisfactory (6 (6.0-6.0) points for amenorrhea and 6 (4.0-6.0) points for clitoris enlargement). On those undergoing feminizing therapy (Group F), the alteration voted as the most perceptible was sperm production decrease (6 (2.0-6.0) points), and the ones classified as the most satisfactory were sperm production decrease (6 (4.0-6.0) points) and spontaneous erections decrease (6 (5.0-6.0) points). Side effects were reported by 89.7% of Group M (mood swings were the most common) and 96.3% of Group F (decreased libido was the most frequent). The sociopsychological impact of hormonal treatment was significantly positive in all analyzed variables (p<0.001). Overall satisfaction with treatment results and medical follow-up were rated with 5 points and 4.5 points, respectively. Clinical implications This study provides clinicians with more evidence that GAHT may improve the physical, psychological and social health of transgender people seeking medical transition. Strengths and limitations The strengths of the current study include a high participant count relative to the target population, the acquisition of data on previously unexplored variables, and the significance of being one of the few investigations of its kind conducted in Portugal. However, the study has limitations, including differences in participant characteristics, a small sample size for some variables, potential bias due to the retrospective nature of the study, individualized treatment regimens, and the inclusion of participants from different countries, which limit the generalization of the results. Conclusions This study provides further evidence that GAHT is effective, and that its physical effects are satisfactory while resulting in mostly non-severe nor life-threatening side effects. GAHT is an important therapy in gender dysphoria and has consistent results in improving numerous sociopsychological variables.
- Application of the New “Points in Range” Metrics in the Assessment of In-Hospital Glycemic ControlPublication . Rosinha, Patrícia; Teixeira, Sofia; Amaral, Cláudia; Cardoso, Maria HelenaIntroduction Capillary blood glucose (CBG) monitoring remains the most used testing form in hospitals and allows for "points in range (PIR)" metric calculation. This study was conceived to evaluate the metabolic control in patients with diabetes mellitus (DM) at a hospital through PIR metrics. Methods This was an observational cross-sectional study conducted on October 9, 2020, that included non-critical adults admitted to Centro Hospitalar Universitário do Porto (except pregnant/postpartum women) with DM under CBG monitoring and a minimum of 24 hours of hospitalization. Glycemic control was evaluated by previous day CBG monitoring. Results The study sample consisted of 110 patients with DM (93.6% type 2) with a median number of CBG tests of 4.00 (1.00) and a median CBG of 166.20 (69.41) mg/dL, SD 41.93 ± 27.20 mg/dL, and variation coefficient of 22.56 ± 12.51%. Points below range were 0.5%, with 0% below 54 mg/dL. The points in ranges 70-140 mg/dL and 140-180 mg/dL were 32.8% and 22.0%, respectively, and the total number of patients with all points in range 70-180 mg/dL was 19 (17.3%), with only 3 (2.7%) having all points in range 140-180 mg/dL and 10 (9.1%) in range 70-140 mg/dL. Regarding points above range (PAR), 29.9% and 14.8% points were at levels 1 and 2 hyperglycemia, respectively, and 15 (13.6%) patients had all points above 180 mg/dL. Correlations were identified between PAR and the total number of CBG assessments (ρ = 0.689, p < 0.001). Conclusion We conclude that in-hospital glycemic control remains suboptimal: only few have adequate control according to the PIR metrics despite low glycemic variability. PIR metrics are a new, valuable, simple and valid way to take better advantage of CBG monitoring at no added cost.
- Six-Year Complete Remission of Type-1 Diabetes Mellitus in an Adult Treated With SitagliptinPublication . Benido Silva, Vânia; Pereira, Maria TeresaA "honeymoon" phase is a transient period of type 1 diabetes (T1D) remission, characterized by a significant reduction in insulin requirements and good glycemic control due to a temporary restoration of pancreatic β-cell function. This phenomenon occurs in about 60% of adults with this disease, is usually partial, and lasts for up to 1 year. We present a case of a 6-year complete remission of T1D in a 33-year-old man, the longest remission ever described in the literature to our knowledge. He was referred for presenting a 6-month history of polydipsia, polyuria, and weight loss of 5 kg. Laboratory studies confirmed the diagnosis of T1D (fasting blood glucose of 270 mg/dL; HbA1c of 10.6%, and positive antiglutamic acid decarboxylase), and the patient started intensive insulin therapy. After 3 months, a complete remission of the disease was assumed, he suspended insulin administration and since then, he has been under treatment with sitagliptin 100 mg daily, a low-carbohydrate diet, and regular aerobic physical activity. This work aims to highlight the potential role of these factors in delaying disease progression and preserving pancreatic β-cells when introduced at the time of presentation. More robust, prospective, and randomized studies will be needed to confirm its protective effect on the natural course of the disease and support its indication in adults with newly diagnosed T1D.
- Iatrogenic Cushing’s Syndrome: The Result of Cobicistat and Glucocorticoid Interaction in an HIV Patient After Bariatric SurgeryPublication . Benido Silva, Vânia; Cardoso, Joana; Esteves Brandão, Maria; Mesquita, Isabel; Pereira, Maria TeresaCobicistat, used as a pharmacokinetic booster in therapeutic combination with human immunodeficiency virus (HIV) protease inhibitors and integrase inhibitors, is a strong inhibitor of cytochrome P450 3A4 (CYP3A4). Since most glucocorticoids are metabolized by the isoenzyme of the cytochrome P450 pathway, their plasma concentrations can be highly increased in the presence of cobicistat-boosted darunavir, with subsequent risk of iatrogenic Cushing's syndrome (ICS) and secondary adrenal insufficiency. We report a case of a 45-year-old man with HIV-hepatitis C virus co-infection treated with raltegravir and darunavir/cobicistat since 2019. In May 2021, he underwent a sleeve gastrectomy due to morbid obesity (BMI: 50.9 kg/m2) with multiple comorbidities. Four months after surgery, he was diagnosed with asthma and was started on inhaled budesonide, which was later changed to fluticasone propionate. At the 12-month postoperative visit, the patient referred proximal muscle weakness and asthenia, and suboptimal weight loss (excess weight loss of 39%) and high blood pressure were documented. Moon facies, buffalo hump, and abdominal large vinous striae were evident on physical examination. Laboratory studies showed impaired glucose metabolism and hypokalemia. Cushing's syndrome was suspected and further investigation confirmed its iatrogenic origin. The diagnosis of ICS and consequent secondary adrenal insufficiency due to an interaction between the darunavir/cobicistat combination and budesonide/fluticasone was established. Darunavir/cobicistat therapy was replaced by dolutegravir/doravirine dual therapy, inhaled corticoid was switched to beclomethasone, and glucocorticoid substitutive therapy was introduced. This is a particular case of overt ICS due to cobicistat-inhaled corticosteroid interaction in a superobese patient, developed after he underwent bariatric surgery. The presence of morbid obesity, combined with the rarity of this pharmacological complication in individuals taking cobicistat, made the correct diagnosis even more challenging. A meticulous review of pharmacologic habits and potential interactions is essential to avoid serious harm to patients.
- Graves’ disease with spontaneous resolution following ocrelizumab in primary progressive multiple sclerosisPublication . Duarte, Diana Borges; Silva, Ana Martins; Freitas, Claudia; Cardoso, HelenaObjectives. Immune reconstitution therapies (IRT), which include antibody-based cell-depleting therapies targeting CD52+ (alemtuzumab) or CD20+ (rituximab, ocrelizumab) leukocytes, are approved for the treatment of multiple sclerosis. Thyroid autoimmunity is a common adverse effect of alemtuzumab treatment, Graves' disease (GD) being the most prevalent manifestation. To date, thyroid autoimmunity events have not been reported with CD20-targeting monoclonal antibodies. Case Report. A 59-year-old woman with primary progressive multiple sclerosis with no prior personal history of thyroid disease or autoimmunity, was diagnosed with GD 6 months following the first ocrelizumab infusion. She was asymptomatic and had no signs of ophthalmopathy. Due to the temporal association of GD diagnosis with ocrelizumab infusion, absence of symptoms and our experience with alemtuzumab-induced GD, we decided for an active surveillance strategy and antithyroid drugs were not started. She underwent spontaneous resolution of hyperthyroidism with thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) negativity and a mild and transitory period of subclinical hypothyroidism, while she continued the biannually ocrelizumab administration schedule. To present date, she has maintained close clinical and biochemical surveillance with normal TSH, free thyroxine (fT4) and free triiodothyronine (fT3) levels and undetectable TRAb. Conclusions. This is the first case of GD reported after ocrelizumab administration. The timing, onset and course of this case is similar to alemtuzumab-induced GD, usually interpreted as an "immune reconstitution syndrome"; however, ocrelizumab cell count depletion is inferior in severity, cell population affected and duration of depletion. This case highlights the importance of pre-screening and follow-up with thyroid function tests in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to unravel the causes of thyroid autoimmunity.
- Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious VariantPublication . Duarte, Diana Borges; Ferreira, Lia; Santos, Ana P.; Costa, Cláudia; Lima, Jorge; Santos, Catarina; Afonso, Mariana; Teixeira, Manuel R.; Carvalho, Rui; Cardoso, HelenaIntroduction: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor (MAX) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals. Case presentation: The first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene. Conclusion: This case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk.
- Nephrotic Syndrome as a Cause of Transient Clinical HypothyroidismPublication . Benido Silva, Vânia; Pereira, Maria Teresa; Leal Moreira, Carla; Santos Monteiro, Sílvia; Inácio, Isabel; Cardoso, HelenaNephrotic 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.
- Hypoglycemic episodes in hospitalized people with diabetes in Portugal: the HIPOS-WARD studyPublication . Alão, Sílvia; Conceição, João; Dores, Jorge; Santos, Lèlita; Araújo, Francisco; Pape, Estevão; Reis, Mónica; Chipepo, Árcia; Nascimento, Edite; Baptista, Ana; Pires, Vanessa; Marques, Carlos; Lages, Adriana De Sousa; Pelicano-Romano, João; de Jesus, Paula M.Background: We intended to estimate the proportion hypoglycemic/hyperglycemic emergency episodes in treated diabetes mellitus (DM) patients admitted to a hospital ward, and calculate the prevalence of risk factors for hypoglycemia and diabetic complications. Methods: In this cross-sectional, multicentered study, the observational data was collected by physicians from patient's hospitalization to discharge/death. Statistical tests were 2-tailed considering 5% significance level. Results: There were 646 ward admissions due to hyperglycemic emergencies and 176 hypoglycemic episodes with a ratio hypoglycemia/hyperglycemia 0.27 for all DM patients. In T2DM patients the ratio was 0.38. These were mainly female (55.1%), functionally dependent (61.4%) and retired/disabled (73.1%). Median age was 75 years and median duration of disease 11 years. Half the patients were on insulin-based therapy and 30.1% on secretagogue-based therapy. Approximately 57% of patients needed occasional/full assistance to manage the disease. The most frequent risk factor for hypoglycemia was polypharmacy (85.0%). Hypoglycemia in the 12 months before admission was higher in insulin-based therapy patients (66.1%; p = 0.001). Conclusions: Hyperglycemic emergencies are the most frequent cause of hospitalization in Portugal, although severe hypoglycemic events represent a health and social problem in elderly/frail patients. There is still the need to optimize therapy in terms of the potential for hypoglycemia in this patient group and a review of anti-hyperglycemic agents to add on to insulin.
- Apolipoprotein B and non-high-density lipoprotein cholesterol reveal a high atherogenicity in individuals with type 2 diabetes and controlled low-density lipoprotein-cholesterolPublication . Fonseca, Liliana; Paredes, Sílvia; Ramos, Helena; Oliveira, José Carlos; Palma, IsabelBackground: Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c) levels, although the cardiovascular disease (CVD) risk could be better reflected by other lipid parameters. This study aimed at comparing a comprehensive lipid profile between patients with type 2 diabetes mellitus (T2DM) with LDL-c concentration within and above target. Methods: A comprehensive lipid profile was characterized in 96 T2DM patients. The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. Results: In this population, only 28.1 and 16.7% of patients had mean LDL-c levels within target, as defined by the 2016 and 2019 guidelines, respectively. Applying the 2016 guidelines criteria, in patients with LDL-c within target, 22, 25 and 44% presented non-high-density lipoprotein cholesterol (non-HDL-c), Apolipoprotein B (ApoB) and oxidized LDL-c levels above the recommended range, respectively, whereas according to the 2019 guidelines criteria, 50, 39 and 44% of the patients with LDL-c within target had elevated high-density lipoprotein cholesterol (HDL-c), ApoB and oxidized LDL-c levels, respectively. LDL-c was strongly correlated with non-HDL-c (r = 0.850), ApoB (r = 0.656) and oxidized LDL-c (r = 0.508). Similarly, there was a strong correlation between non-HDL-c with both ApoB (r = 0.808) and oxidized LDL-c (r = 0.588). Conclusions: These findings emphasize the limitations of only considering LDL-c concentration for cardiovascular (CV) risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM patients. These data suggest that non-HDL-c, ApoB and oxidized LDL-c levels could be considered as an important part of these patients' evaluation allowing for a more accurate estimation of CV risk and hopefully better management of these high-risk patients.
- Hospitalization Costs Due to Hypoglycemia in Patients with Diabetes: A Microcosting ApproachPublication . Ferreira, João P.; Araújo, Francisco; Dores, Jorge; Santos, Lèlita; Pape, Estevão; Reis, Mónica; Chipepo, Árcia; Nascimento, Edite; Baptista, Ana; Pires, Vanessa; Marques, Carlos; Lages, Adriana S.; Conceição, João; Laires, Pedro A.; Pelicano-Romano, João; Alão, SílviaIntroduction: Hypoglycemia leading to hospitalization is associated with adverse economic outcomes, although the real burden is unknown. The HIPOS-WARD (Hypoglycemia In Portugal Observational Study-Ward) aimed to characterize ward admissions due to hypoglycemia episodes in treated patients with diabetes and assess their economic impact to the National Health System. Methods: Observational, cross-sectional study, conducted in 16 Portuguese centers for 22 months. The applied microcosting approach was based on healthcare resource data, collected from patients' charts upon ward admission until discharge, and unitary costs from official/public data sources. Absenteeism was also estimated for active workers on the basis of the human capital approach. Results: Of the 176 patients with diabetes mellitus enrolled, 86% had type 2 diabetes. Half of the patients (50.0%) were on insulin-based therapy, followed by 30.1% on a secretagogue-based regimen, 9.7% on non-secretagogue therapy, and 10.2% on a combination of insulin and secretagogue. Overall mean costs per patient were medication, 45.45 €; laboratory analysis, 218.14 €; examinations, 64.91 €; physician and nurse time, 268.55 € and 673.39 €, respectively. Bed occupancy was the main cost driver (772.09 €) and indirect cost averaged 140.44 €. Overall, the cost per hypoglycemia episode leading to hospitalization averaged 2042.52 € (range 194.76-16,762.87 €). Patients treated with insulin-based regimens (2267.76 €) and type 2 diabetes (2051.29 €) had the highest mean costs. The mean cost increased with repeated hypoglycemic events (2191.67 €), correlated complications (2109.26 €), and death (5253.38 €). Conclusion: HIPOS-WARD's findings confirm and support both the substantial clinical and economic impact of hospitalization due to hypoglycemia in Portugal.
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