AdultCarbQuiz for the Portuguese population with type 1 diabetes mellitus: translation, cultural adaptation and validation of its metabolic impact.

AIMS: In type 1 diabetes mellitus (T1DM), functional insulin therapy, based on carbohydrate (CH) counting and individualized insulin-to-carbohydrate ratio, is essential to achieve an adequate metabolic control. However, to date, few tools have been validated to assess patients' knowledge about CH counting, with the AdultCarbQuiz questionnaire having proved to be a reliable method in an American cohort. The aim of this study was to translate, culturally adapt and validate the AdultCarbQuiz questionnaire for the Portuguese population.  METHODS: This was a cross-sectional study of patients with T1DM on functional insulin therapy through continuous subcutaneous insulin infusion (CSII). Prior to its application, the AdultCarbQuiz questionnaire was translated and culturally adapted to the Portuguese context. Statistical analyses include descriptive, correlation and intern consistency analysis using IBM® SPSS® Statistics, version 27. RESULT: One hundred patients were included, 58% of female sex, with a mean age of 31.09 ± 10.77 years. Mean disease duration was 15.04 ± 9.23 years, and mean CSII usage time was 4.02 ± 3.90 years. The average value of glycated haemoglobin (HbA1c), time in range (TIR), time above range (TAR) and time below range was, respectively, 7.32 ± 0.87, 59.75 ± 14.13, 34.38 ± 15.40 and 5.75 ± 6.58%. The average score of the questionnaire was 30.86 points ± 3.58 points, considered high. The Kuder-Richardson 20 coefficient value was 0.63 for the total score, with a Spearman-Brown value for the half-split of 0.63. Individuals with lower HbA1c values scored significantly higher on knowledge about hypoglycaemia prevention and correction (r = - 0.269, p = 0.007) and on the total questionnaire score (r = - 0.205, p = 0.041). A higher TIR and a lower TAR were also associated with a higher total score (r = 0.274, p = 0.007 and r = - 0.274, p = 0.007, respectively). CONCLUSIONS: In this study, the AdultCarbQuiz questionnaire, translated and culturally adapted to the Portuguese context, proved to be a useful tool in assessing knowledge about CH counting in patients with T1DM, allowing to optimize, individually, the therapeutic strategy in consultation.

Preventive strategies for hypercoagulation in Cushing's syndrome: when and how.

PURPOSE: The endogenous hypercortisolism that characterizes Cushing's syndrome (CS) is associated with a state of hypercoagulability that significantly increases the risk of thromboembolic disease, especially, venous events. Despite this certainty, there is no consensus on the best thromboprophylaxis strategy (TPS) for these patients. Our aim was to summarize the published data about different thromboprophylaxis strategies, and to review available clinical tools assisting thromboprophylaxis decision making. METHODS: Narrative review of thromboprophylaxis strategies in patients with Cushing's syndrome. A search was carried out on PubMed, Scopus and EBSCO until November 14th, 2022, and articles were selected based on their relevance and excluded in case of redundant content. RESULTS: Literature is scarce regarding thromboprophylaxis strategies to be adopted in the context of endogenous hypercortisolism, most often being a case-by-case decision according to the centre expertise. Only three retrospective studies, with a small number of patients enrolled, evaluated the use of hypocoagulation for the thromboprophylaxis of patients with CS in the post-operative period of transsphenoidal surgery and/or adrenalectomy, but all of them with favourable results. The use of low molecular weight heparin is the most frequent option as TPS in CS context. There are numerous venous thromboembolism risk assessment scores validated for different medical purposes, but just one specifically developed for CS, that must be validated to ensure solid recommendations in this context. The use of preoperative medical therapy is not routinely recommended to decrease the risk of postoperative venous thromboembolic events. The peak of venous thromboembolic events occurs in the first three months post-surgery. CONCLUSION: The need to hypocoagulate CS patients, mainly in the post-operative period of a transsphenoidal surgery or an adrenalectomy, is undoubtable, especially in patients with an elevated risk of venous thromboembolic events, but the precise duration and the hypocoagulation regimen to institute is yet to be determined with prospective studies.

Autoimmune hypothyroidism and trastuzumab therapy: a rare association.

Summary: We report a case of a woman with a diagnosis of breast cancer who unintentionally started gaining weight, feeling tired, and constipated 44 weeks after the initiation of trastuzumab. Hypothyroidism secondary to an autoimmune thyroiditis associated with trastuzumab was diagnosed, the first case described in Portugal and the fourth case described worldwide. Our intention regarding the publication of this case report is to alert the clinicians treating people with trastuzumab that they should ask the patients about symptoms of hypothyroidism and should screen the thyroid function of the patients before, during, and after the initiation of trastuzumab. Learning points: Trastuzumab is a humanized MAB used in HER2-positive breast and gastric cancer. Trastuzumab-associated autoimmune thyroid disease (AITD) is rare (incidence rate in an RCT of 0.3%). Manifestations of autoimmune thyroiditis associated with trastuzumab resemble those of hypothyroidism in other clinical contexts, but the presence of goiter is highlighted as a reason for medical evaluation. Biochemically, it is characterized by an increased thyroid-stimulating hormone (TSH) with or without a low FT4/FT3, and sonographically with a pattern of thyroiditis. The treatment consists of levothyroxine, in a dose of 1.6-1.8 µg/kg/day, with re-evaluation of the thyroid function in 4-6 weeks. We report the first case of autoimmune thyroiditis secondary to trastuzumab in Portugal. It is important to evaluate the thyroid function before, during, and after the initiation of this therapeutic agent.

Therapeutics That Can Potentially Replicate or Augment the Anti-Aging Effects of Physical Exercise.

Globally, better health care access and social conditions ensured a significant increase in the life expectancy of the population. There is, however, a clear increase in the incidence of age-related diseases which, besides affecting the social and economic sustainability of countries and regions around the globe, leads to a decrease in the individual's quality of life. There is an urgent need for interventions that can reverse, or at least prevent and delay, the age-associated pathological deterioration. Within this line, this narrative review aims to assess updated evidence that explores the potential therapeutic targets that can mimic or complement the recognized anti-aging effects of physical exercise. We considered pertinent to review the anti-aging effects of the following drugs and supplements: Rapamycin and Rapamycin analogues (Rapalogs); Metformin; 2-deoxy-D-glucose; Somatostatin analogues; Pegvisomant; Trametinib; Spermidine; Fisetin; Quercetin; Navitoclax; TA-65; Resveratrol; Melatonin; Curcumin; Rhodiola rosea and Caffeine. The current scientific evidence on the anti-aging effect of these drugs and supplements is still scarce and no recommendation of their generalized use can be made at this stage. Further studies are warranted to determine which therapies display a geroprotective effect and are capable of emulating the benefits of physical exercise.

A variant in the CASR gene (c.368T>C) causing hypocalcemia refractory to standard medical therapy.

SUMMARY: Hypoparathyroidism is characterized by low or inappropriately normal parathormone production, hypocalcemia and hyperphosphatemia. Autosomal dominant hypocalcemia (ADH) type 1 is one of the genetic etiologies of hypoparathyroidism caused by heterozygous activating mutations in the calcium-sensing receptor (CASR) gene. Current treatments for ADH type 1 include supplementation with calcium and active vitamin D. We report a case of hypoparathyroidism in an adolescent affected by syncope without prodrome. The genetic testing revealed a variant in the CASR gene. Due to standard therapy ineffectiveness, the patient was treated with recombinant human parathyroid hormone (1-34), magnesium aspartate and calcitriol. He remained asymptomatic and without neurological sequelae until adulthood. Early diagnosis and treatment are important to achieve clinical stability. LEARNING POINTS: Autosomal dominant hypocalcemia (ADH) type 1 is one of the genetic etiologies of hypoparathyroidism caused by heterozygous activating mutations in the calcium-sensing receptor (CASR) gene. The variant c.368T>C (p.Leu123Ser) in heterozygosity in the CASR gene is likely pathogenic and suggests the diagnosis of ADH type 1. Teriparatide (recombinant human parathyroid hormone 1-34) may be a valid treatment option to achieve clinical stability for those individuals whose condition is poorly controlled by current standard therapy.

Late diagnosis of classic congenital adrenal hyperplasia: long-term consequences during adulthood.

SUMMARY: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to enzyme deficiencies in the adrenal steroidogenesis pathway leading to impaired corticosteroid biosynthesis. Depending on the extension of enzyme defect, there may be variable severities of CAH - classic and non-classic. We report the case of a 37-year-old male patient with a previously unknown diagnosis of classic CAH referred to Endocrinology evaluation due to class III obesity and insulin resistance. A high diagnostic suspicion was raised at the first Endocrinology consultation after careful past medical history analysis especially related to the presence of bilateral adrenal myelolipomas and primary infertility. A genetic test confirmed the presence of a variant of the CYP21A2 in homozygous with an enzymatic activity of 0-1%, corresponding to a classic and severe CAH form. Our case represents an unusually late definitive diagnose of classic CAH since the definition was established only during adulthood in the fourth decade of life. The missing diagnosis of classic 21 hydroxylase deficiency during infancy led to important morbidity, with a high impact on patients' quality of life. LEARNING POINTS: Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive enzyme disorders responsible for an impaired cortical adrenal hormonal synthesis. CAH may be divided into two major forms: classic and non-classic CAH. If untreated, CAH may be fatal or may be responsible for important multi-organ long-term consequences that can be undervalued during adulthood. Adrenal myelolipomas are associated with chronic exposure to high ACTH levels and continuous androgen hyperstimulation typically found in undertreated CAH patients. Testicular adrenal rest tumours (TART) and primary infertility can be the first manifestation of the disease during adulthood.

Aging Hallmarks: The Benefits of Physical Exercise.

World population has been continuously increasing and progressively aging. Aging is characterized by a complex and intraindividual process associated with nine major cellular and molecular hallmarks, namely, genomic instability, telomere attrition, epigenetic alterations, a loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. This review exposes the positive antiaging impact of physical exercise at the cellular level, highlighting its specific role in attenuating the aging effects of each hallmark. Exercise should be seen as a polypill, which improves the health-related quality of life and functional capabilities while mitigating physiological changes and comorbidities associated with aging. To achieve a framework of effective physical exercise interventions on aging, further research on its benefits and the most effective strategies is encouraged.

Endoscopic ultrasound-guided ethanol ablation therapy for pancreatic insulinoma: an unusual strategy.

SUMMARY: Insulinomas are the most frequent cause of hyperinsulinaemic hypoglycaemia. Although surgical enucleation is the standard treatment, a few other options are available to high-risk patients who are elderly or present with co-morbidities. We present a case report of an 89-year-old female patient who was admitted to the emergency department due to recurrent hypoglycaemia, especially during fasting. Laboratory work-up raised the suspicion of hyperinsulinaemic hypoglycaemia, and abdominal CT scan revealed a 12 mm nodular hypervascular lesion of the pancreatic body suggestive of neuroendocrine tumour. The patient was not considered a suitable candidate for surgery, and medical therapy with diazoxide was poorly tolerated. Endoscopic ultrasound-guided ethanol ablation therapy was performed and a total of 0.6 mL of 95% ethanol was injected into the lesion by a transgastric approach; no complications were reported after the procedure. At 5 months of follow-up, no episodes of hypoglycaemia were reported, no diazoxide therapy was necessary, and revaluation abdominal CT scan revealed a pancreatic nodular lesion with a size involution of about half of its original volume. The patient is regularly followed-up at the endocrinology clinic and shows a significant improvement in her wellbeing and quality of life. LEARNING POINTS: Insulinomas are the most frequent cause of hyperinsulinaemic hypoglycaemia.Surgical enucleation is the standard treatment with a few other options available to high-risk patients.Endoscopic ultrasound-guided ethanol ablation therapy is one feasible option in high-risk patients with satisfactory clinical outcomes, significant positive impact on quality of life and low complication rates related to the procedure.

Diffuse large B-cell lymphoma of the adrenal gland: a rare cause of primary adrenal insufficiency.

Although it is a rare entity, primary lymphoma of the adrenal gland should be considered in the differential diagnosis of bilateral nodular adrenal lesions, particularly when there is evidence of associated adrenal insufficiency. We describe the case of an 83-year-old woman admitted to the emergency department due to a month's history of asthenia, weight loss, anorexia and nausea. Abdominopelvic CT showed bilateral nodular lesions of adrenal glands and a stimulation test with tetracosactide was compatible with primary adrenal insufficiency. CT-guided biopsy of the left adrenal gland was performed, and histopathological results were consistent with diffuse large B-cell lymphoma. Positron emission tomography (18)F-fluorodeoxyglucose detected two intensely hypermetabolic lesions limited to both adrenal glands. Replacement therapy with hydrocortisone 15 mg/day and fludrocortisone 0.1 mg/day was promptly started and chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone was initiated after haematology-oncology consultation.

Primary mediastinal (thymic) B-cell lymphoma presenting as cutaneous vasculitis.

Cutaneous small vessel vasculitis is a severe neutrophilic vascular inflammation mediated by immune complexes that involves the dermal postcapillary venules. Neoplasms represent 2-5% of all causes of secondary cutaneous vasculitis. We present a case of a 52-year-old man who was admitted due to a 10-day history of respiratory symptoms and myalgia. From the third day of symptoms onwards, the patient noticed the appearance of cutaneous lesions in the lower limbs with palpable purpura and erythematous papules. Additionally, he reported of asthenia, anorexia and weight loss during the prior month. Chest radiography showed an enlarged mediastinum and thoracoabdominal-pelvic CT scan revealed a bulky left hilar mass. Biopsy of the left superior lobar bronchus' mucosa allowed for the histological diagnosis of diffuse large B-cell lymphoma (DLBL) of the thymus. The patient received symptomatic treatment with improvement of the purpuric lesions and a multiagent chemotherapy regimen was initiated.