Familial bilateral macronodular adrenal hyperplasia due to a novel ARMC 5 germline mutation: Clinical status and possible association with other neoplasms.

INTRODUCTION/OBJECTIVES: Mutations in the ARMC5 (armadillo repeat containing 5, OMIM 615549) gene, a putative tumor suppressor gene, have recently been identified as a common cause of sporadic and familial bilateral macronodular adrenal hyperplasia (BMAH). Familial BMAH is thought to be caused by two mutations, one germline and the other somatic, as suggested by the 2-hit theory. The objective is to describe a new mutation and develop its clinical characteristics and implications. METHODS, RESULTS AND CONCLUSIONS: We present an affected family with 11 members carrying a novel mutation of the ARMC5 gene (NM_001288767.1): c.2162T>C p. (Leu721Pro). Two of the carriers developed clinical Cushing's syndrome (CS), two mild autonomous cortisol secretion (MACS) and one presented with autonomous cortisol secretion (ACS). Four patients developed other tumors, three of whom died from this cause. It is not known whether these tumors could be related to the described mutation.

Difficulties of gender affirming treatment in trans women with BRCA1+ mutation: A case report.

Gender affirming treatment in transgender women is based on a combination of antiandrogens and estrogens, with the latter maintained over the long term. When prescribing these treatments, we must consider the possibility of developing estrogen-dependent breast cancer. In transgender women, a breast cancer incidence of 4.1 per 100,000 has been estimated, which would increase the risk by 46% in relation to cisgender men but decrease it by 70% in relation to cisgender women. It is known that certain gene mutations such as BRCA1 imply an increased risk of breast cancer, but at present the risk in transgender women with BRCA1 treated with estrogens is not well established. We present the case of a transgender woman with a family history of breast cancer and BRCA1 mutation and the therapeutic decisions made in a multidisciplinary team. Following this case, we review and discuss the published literature.

Bioavailability and systemic transport of oleanolic acid in humans, formulated as a functional olive oil.

Evidence of the pharmacological activity of oleanolic acid (OA) suggests its potential therapeutic application. However, its use in functional foods, dietary supplements, or nutraceuticals is hindered by limited human bioavailability studies. The BIO-OLTRAD trial is a double-blind, randomized controlled study with 22 participants that received a single dose of 30 mg OA formulated as a functional olive oil. The study revealed that the maximum serum concentration of OA ranged from 500 to 600 ng mL-1, with an AUC0-∞ value of 2862.50 ± 174.50 ng h mL-1. Furthermore, we discovered a physiological association of OA with serum albumin and triglyceride-rich lipoproteins (TRL). UV absorption spectra showed conformational changes in serum albumin due to the formation of an adduct with OA. Additionally, we demonstrated that TRL incorporate OA, reaching a maximum concentration of 140 ng mL-1 after 2-4 hours. We conjecture that both are efficient carriers to reach target tissues and to yield high bioavailability.

Outcomes of a multidisciplinary Diabetic Foot Day Unit.

OBJECTIVE: To analyse the main characteristics of patients and the health outcomes obtained and to evaluate the impact of peripheral artery disease (PAD) in patients treated in our multidisciplinary Diabetic Foot Unit. RESEARCH DESIGN AND METHODS: Observational prospective study. 273 patients from two different populations (with and without PAD - classified according to the presence of distal pulses) treated over a 14-month period in the multidisciplinary Diabetic Foot Unit were included. The data on patient characteristics and outcomes were analysed for the purpose of comparison. For the inference study, a comparison of medians with the non-parametric test for independent samples for the quantitative variables and a χ2 test for the comparison of proportions in qualitative variables were performed. RESULTS: Patients with PAD ulcers were older (60 (54-67) vs. 64 (75-81), p=0.000) and had a higher macrovascular burden (8.1% vs. 29% for ischaemic heart disease history, p=0.000; 6.7% vs. 18.1% for cerebrovascular disease history, p=0.004). Their Texas Score was higher (p=0.000) and their major amputation rate was higher (1.4% vs. 12.3%, p=0.001). They had less background of previous ulcers (52.6% vs. 26.8%, p=0.000), their episode duration was shorter (4 (0-10) vs. 0 (0-3) weeks, p=0.000), and their proportional need for antibiotic therapy was lower (64.4% vs. 51.4%, p=0.03). CONCLUSIONS: The differences found between ulcers with and without vascular involvement support the need for a different approach and for the inclusion of vascular surgeons on the team. The multidisciplinary care model for diabetic foot patients could be effective and improve health outcomes.

Telemedicine screening program for diabetic retinopathy in patients with type 1 diabetes mellitus.

PURPOSE: To analyze the results of the telemedicine screening program for diabetic retinopathy (DR) in patients with type 1 diabetes conducted by the Endocrinology and Nutrition Management Unit of Virgen del Rocío University Hospital. METHODS: This cross-sectional study comprised patients with type 1 diabetes mellitus (DM) in our DR screening program from January 2018 to November 2020. Fundus photographs are performed by trained nurses and reviewed by a trained endocrinologist. Those suggestive of pathology are sent to ophthalmology through a telematic program for review. RESULTS: Of the 995 fundus photographs evaluated, 646 (65.3%) showed no evidence of DR, 327 (33.1%) presented possible DR, and 16 (1.6%) were not gradable. The diagnosis was confirmed in 254 patients after reviewing by ophthalmology, and the screening program achieved a positive predictive value for DR of 77.7%. Seventy-three were excluded by ophthalmology due to the absence of DR (false positive rate - 22.3%). In 92.5% of the cases classified by the ophthalmologist, the degree of DR was mild or very mild. CONCLUSION: Our telemedicine screening program for DR in patients with type 1 DM is consistent with the literature. Effective screening for DR is performed, with patients diagnosed in the early stages. Telemedicine programs facilitate efficient communication among healthcare personnel.

Description of a Cohort of Type 1 Diabetes Patients: Analysis of Comorbidities, Prevalence of Complications and Risk of Hypoglycemia.

BACKGROUND: Despite major medical advances, Type 1 Diabetes (T1D) patients still have greater morbimortality than the general population. Our aim was to describe our cohort of T1D patients and identify potential risk factors susceptible to prevention strategies. METHODS: Cross-sectional, observational study, including T1D patients treated at our center, from 1 March 2017 to 31 March 2020. INCLUSION CRITERIA: T1D, age > 14 years and signed informed consent. EXCLUSION CRITERIA: diabetes other than T1D, age < 14 years and/or refusal to participate. RESULTS: Study population n = 2181 (49.8% females, median age at enrollment 41 years, median HbA1c 7.7%; 38.24% had at least one comorbidity). Roughly 7.45% had severe hypoglycemia (SH) within the prior year. Macro/microvascular complications were present in 42.09% (5.83% and 41.14%, respectively). The most frequent microvascular complication was diabetic retinopathy (38.02%), and coronary disease (3.21%) was the most frequent macrovascular complication. The risk of complications was higher in males than in females, mainly macrovascular. Patients with SH had a higher risk of complications (OR 1.42; 1.43 in males versus 1.42 in females). CONCLUSIONS: Our T1D population is similar to other T1D populations. We should minimize the risk of SH, and male patients should perhaps be treated more aggressively regarding cardiovascular risk factors.

Gender Incongruity in a Person with 46,XY and Complete Androgen Insensitivity Syndrome Raised as a Female.

We present the case of a patient with female sex assignment at birth whose parents consulted with a pediatrician when the child was 12 years old, indicating that despite female sex assignment, she felt that she (henceforth "he") had a male gender identity and was gynephilic. Medical examination revealed a 46XY karyotype, a primary amenorrhea and an appropriate testosterone increase after HCG stimulation test. The patient was diagnosed then with a 46,XY disorder of sex development with androgen insensitivity syndrome, but then he missed subsequent appointments. At the age of 24, he resumed medical follow-up to reaffirm his male gender identity through sex reassignment surgery. His physical examination showed a Tanner stage III-IV breast development, vulva, clitoris, normal-sized vagina, absence of uterus and ovaries on transvaginal ultrasound, bilateral cryptorchidism on abdominal-pelvic MRI and osteoporosis on bone densitometry. The results of the blood tests were LH 24.5 mIU/mL [normal range, 1.7-8.6 mIU/mL for men] and testosterone 8.8 nmol/L [8.7-33 nmol/L]; conversely, FSH, estradiol, progesterone, and prolactin levels were normal. The molecular genetic analysis revealed an androgen receptor gene mutation associated with complete androgen insensitivity syndrome. At present, the patient has undergone bilateral orchiectomy and has initiated treatment with topical testosterone and bisphosphonates. We have yet to evaluate the effects and decide the best therapy taking into account that he has a male gender identity but complete androgen insensitivity syndrome.

Discordant Genotypic Sex and Phenotype Variations in Two Spanish Siblings with 17α-Hydroxylase/17,20-Lyase Deficiency Carrying the Most Prevalent Mutated CYP17A1 Alleles of Brazilian Patients.

17α-hydroxylase/17,20-lyase deficiency is a rare form of congenital adrenal hyperplasia caused by mutations in CYP17A1. Two phenotypic female sisters, aged 17 and 15 years and with 46,XY and 46,XX karyotypes, respectively, presented with primary amenorrhea and absent secondary sexual characteristics. The elder sib also presented with high blood pressure. Both patients had elevated levels of ACTH, gonadotropins, progesterone, corticosterone, and deoxycorticosterone, and reduced levels of estradiol, testosterone, androstenedione, 17-OH-P, DHEA-S, cortisol, aldosterone, and renin activity. The CYP17A1 gene was sequenced, and polymorphic haplotypes were further analyzed in the Spanish family and in Brazilian patients. The 2 sisters were compound heterozygous for p.Arg362Cys and p.Trp406Arg mutations, previously described as the most prevalent mutations in Brazilian families of Spanish (p.Trp406Arg) or Portuguese (p.Arg362Cys) origin. Analysis of polymorphisms in CYP17A1 suggested that the paternal allele with p.Arg362Cys may share a common origin with the Brazilian carriers, while the maternal allele with p.Trp406Arg did not. Hydrocortisone and sex hormone replacement therapy was initiated in both patients. In conclusion, one CYP17A1 mutation (p.Arg362Cys) may share a common ancestry in Brazilian and our present Spanish patients, while p.Trp406Arg may have arisen separately. The elder patient (46,XY) developed a more severe phenotype and a poorer response to estradiol replacement therapy.

Ludwig's angina and ketoacidosis as a first manifestation of diabetes mellitus.

Ludwig's angina is a serious and rapidly progressive infectious process that spreads through the floor of the mouth and neck. In this paper we present an infrequent case of a patient who suffered an odontogenic infection with poor response to the previous treatment, which evolved towards a Ludwig's angina combined with ketoacidosis in the context of a diabetes mellitus not known before. According to the literature reviewed, this case report represents the first contribution of a Ludwig's angina and ketoacidosis as an initial manifestation of a diabetes mellitus. The airway management, the antibiotic prescription and the surgical drainage allowed the healing of the patient without medical complications. Factors of co-morbidity like the diabetes mellitus together with focus tooth of infection may eventually turn into serious medical complications as the diabetic ketoacidosis and develop potentially lethal cervical infections.

Long-term maintenance of low-dose antithyroid drugs versus drug withdrawal in patients with Graves' hyperthyroidism.

OBJECTIVE: The relapse rate of Graves' hyperthyroidism after finishing an antithyroid cicle is high. The objective of this work was to prospectively investigate the relapse rate of Graves' hyperthyroidism (GH) in patients with maintenance of a low dose of antithyroid drug (ATD) therapy. PATIENTS AND METHOD: From March 1997, all patients with GH consecutively attending the same center who remained euthyroid with low doses of synthetic ATD (carbimazole or methimazole: 2.5-5mg/day) on 2 consecutive follow-up visits (at 10-12 months) were included in this study. Instead of withdrawing ATD, the aim was to continue with this low dose for a 5-year period (group M: 53 patients). From March 1997, data were also collected from patients with GH who were consecutively followed-up and who, meeting the criteria for inclusion in group M, had stopped receiving ATD before the start of the study (March 1997) (group R: 31 patients). MAIN OUTCOME: GH relapse was observed in 12/53 patients in group M (22.64%) and in 24/31 patients in group R (77.42%) (p<0.000). CONCLUSIONS: The GH relapse rate was significantly lower with long-term maintenance of a low dose of ATD than with therapy withdrawal.