TANIA APARECIDA SARTORI SANCHEZ BACHEGA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
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article Weight-adjusted neonatal 17OH-progesterone cutoff levels improve the efficiency of newborn screening for congenital adrenal hyperplasia(2011) HAYASHI, Giselle; FAURE, Claudia; BRONDI, Maria Fernanda; VALLEJOS, Carla; SOARES, Daiana; OLIVEIRA, Erica; BRITO, Vinicius N.; MENDONCA, Berenice B.; BACHEGA, Tania A. S. S.Objective: To evaluate weight-adjusted strategy for levels of neonatal-17OHP in order to improve newborn screening (NBS) efficiency. Subjects and methods: Blood samples collected between 2-7 days of age from 67,640 newborns were evaluated. When N17OHP levels were >= 20 ng/mL, and a second sample was requested. We retrospectively analyzed neonatal-17OHP levels measured by Auto DELFIA-B024-112 assay, grouped according to birth-weight: G1: < 1,500 g, G2: 1,501-2,000 g, G3: 2,000-2,500 g and G4: > 2,500 g. 17OHP cutoff values were determined for each group using the 97.5th, 99th, 99.5th and 99.8th percentiles. Results: 0.5% of newborns presented false-positive results using the cutoff level >= 20 ng/mL for all groups. Neonates of low birthweight made up 69% of this group. Seven full-term newborns presented congenital adrenal hyperplasia (CAH) and, except for one of them, 17OHP levels were > 120 ng/mL. Only the 99.8th percentile presented higher predictive positive value (2%), and lower rate of false-positives in all groups. Conclusions: We suggest the use of 99.8th percentile obtained by weight-adjusted N17OHP values of healthy newborns to reduce the rate of false-positive results in NBS. Arq Bras Endocrinol Metab. 2011;55(8):632-7- Adverse Outcomes and Economic Burden of Congenital Adrenal Hyperplasia Late Diagnosis in the Newborn Screening Absence(2020) MIRANDA, Mirela Costa de; HADDAD, Luciana Bertocco de Paiva; MADUREIRA, Guiomar; MENDONCA, Berenice Bilharinho de; BACHEGA, Tania A. S. S.Objective: To establish short- and long-term adverse outcome frequencies related to a late diagnosis of congenital adrenal hyperplasia (CAH) in the absence of newborn screening (NBS) and to determine respective treatment costs, which have never been reported. Design: A retrospective analysis of a CAH cohort diagnosed without NBS. Methods: We evaluated medical record data concerning 195 patients (141 females) diagnosed with CAH through clinical suspicion and confirmed using hormonal and CYP21A2 analysis, who were followed from 1980 to 2016 at Sao Paulo University. We measured mortality, dehydration, mental impairment frequencies, and hospitalization length outcomes in the salt-wasting form; the frequency of genetic females raised as males in both forms, frequency of depot GnRh analog (GnRha) and GH therapies in the simple virilizing form, and related outcome costs were calculated. Results: Mortality rates and associated costs, varying from 10% to 26% and from $2,239,744.76 to $10,271,591.25, respectively, were calculated using the Brazilian yearly live-births rate, estimated productive life years, and gross domestic product. In the salt-wasting form, 76% of patients were hospitalized, 8.6% were mentally impaired, and 3% of females were raised as males (total cost, $86,230/salt-wasting patient). GnRha and growth hormone were used for 28% and 14% of simple virilizing patients, respectively, and 18% of females were raised as males (preventable cost, $4232.74/simple virilizing patient). Conclusions: A late CAH diagnosis leads to high mortality and morbidity rates, notably increasing public health costs, and may result in physical and psychological damage that is not easily measurable. (C) Endocrine Society 2019.
- Congenital Adrenal Hyperplasia, Ovarian Failure and Ehlers-Danlos Syndrome due to a 6p Deletion(2014) MOYSES-OLIVEIRA, Mariana; MANCINI, Tatiane I.; TAKENO, Sylvia S.; RODRIGUES, Andressa D. S.; BACHEGA, Tania A. S. S.; BERTOLA, Debora; MELARAGNO, Maria IsabelCryptic deletions in balanced de novo translocations represent a frequent cause of abnormal phenotypes, including Mendelian diseases. In this study, we describe a patient with multiple congenital abnormalities, such as late-onset congenital adrenal hyperplasia (CAH), primary ovarian failure and Ehlers-Danlos syndrome (EDS), who carries a de novo t(6;14)(p21;q32) translocation. Genomic array analysis identified a cryptic 1.1-Mb heterozygous deletion, adjacent to the breakpoint on chromosome 6, extending from 6p21.33 to 6p21.32 and affecting 85 genes, including CYP21A2,TNXB and MSH5. Multiplex ligation-dependent probe amplification analysis of the 6p21.3 region was performed in the patient and her family and revealed a 30-kb deletion in the patient's normal chromosome 6, inherited from her mother, resulting in homozygous loss of genes CYP21A1P and C4B. CYP21A2 sequencing showed that its promoter region was not affected by the 30-kb deletion, suggesting that the deletion of other regulatory sequences in the normal chromosome 6 caused a loss of function of the CYP21A2 gene. EDS and primary ovarian failure phenotypes could be explained by the loss of genes TNXB and MSH5, a finding that may contribute to the characterization of disease-causing genes. The detection of this de novo microdeletion drastically reduced the estimated recurrence risk for CAH in the family. (C) 2014 S. Karger AG, Basel
- Editorial: Molecular -genetic causes underlying primary adrenal insufficiency: Current insights into diagnosis and treatment(2022) V, Maria Candida B. Fragoso; BACHEGA, Tania A. S. S.; DAIN, Liliana
- Long-term cardiometabolic morbidity in young adults with classic 21-hydroxylase deficiency congenital adrenal hyperplasia(2023) RIGHI, Beatrice; ALI, Salma R.; BRYCE, Jillian; TOMLINSON, Jeremy W.; BONFIG, Walter; BARONIO, Federico; COSTA, Eduardo C.; GUARAGNA-FILHO, Guilherme; T'SJOEN, Guy; COOLS, Martine; MARKOSYAN, Renata; BACHEGA, Tania A. S. S.; MIRANDA, Mirela C.; IOTOVA, Violeta; FALHAMMAR, Henrik; CECCATO, Filippo; STANCAMPIANO, Marianna R.; RUSSO, Gianni; DANIEL, Eleni; AUCHUS, Richard J.; ROSS, Richard J.; AHMED, S. FaisalPurposeTo study the current practice for assessing comorbidity in adults with 21-hydroxylase CAH and to assess the prevalence of comorbidity in these adults.MethodsA structured questionnaire was sent to 46 expert centres managing adults with CAH. Information collected included current therapy and surveillance practice with a particular focus on osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity.ResultsOf the 31 (67%) centres from 15 countries that completed the survey, 30 (97%) screened for hypertension by measuring blood pressure, 30 (97%) screened for obesity, 26 (84%) screened for abnormal glucose homoeostasis mainly by using Hb1Ac (73%), 25 (81%) screened for osteoporosis mainly by DXA (92%), 20 (65%) screened for hyperlipidaemia and 6 (19%) screened for additional CV disease. Of the 31 centres, 13 provided further information on the six co-morbidities in 244 patients with a median age of 33 yrs (range 19, 94). Of these, 126 (52%) were females and 174 (71%) received fludrocortisone in addition to glucocorticoids. Of the 244 adults, 73 (30%) were treated for at least one comorbidity and 15 (21%) for more than 2 co-morbidities. Of 73, the patients who were treated for osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity were 43 (59%), 17 (23%), 16 (22%), 10 (14%), 8 (11), 3 (4%) respectively.ConclusionCardiometabolic and bone morbidities are not uncommon in adults with CAH. There is a need to standardise the screening for these morbidities from early adulthood and to explore optimal therapy through routine collection of standardised data.
- Adrenal crisis and mortality rate in adrenal insufficiency and congenital adrenal hyperplasia(2021) LOUSADA, Lia Mesquita; MENDONCA, Berenice B.; BACHEGA, Tania A. S. S.Primary adrenal insufficiency (PAI) is characterized by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids. Addison's disease (AD) and congenital adrenal hyperplasia (CAH) are the most frequent disorders in adults and children, respectively. Despite the diagnostic advances and the availability of glucocorticoid and mineralocorticoid replacements, adrenal crisis (AC) is still a potentially lethal condition contributing to the increased mortality, not only during the first year of life, but also throughout life. Failure in increasing glucocorticoid doses during acute stress, when greater amounts of glucocorticoids are required, can lead to AC and an increase morbimortality rate of PAI. Considering a mortality rate of 0.5 per 100 patient years, up to 1,500 deaths from AC are expected in Brazil in the coming decade, which represents an alarming situation. The major clinical features are hypotension and volume depletion. Nonspecific symptoms such as fatigue, lack of energy, anorexia, nausea, vomiting, and abdominal pain are common. The main precipitating factors are gastrointestinal diseases, other infectious disease, stressful events (e.g., major pain, surgery, strenuous physical activity, heat, and pregnancy), and withdrawal of glucocorticoid therapy. Suspected AC requires immediate therapeutic action with intravenous (iv) hydrocortisone, fluid infusion, monitoring support, and antibiotics if necessary. AC is best prevented through patient education, precocious identification and by adjusting the glucocorticoid dosage in stressor situations. The emergency card, warning about acute glucocorticoid replacement, has high value in reducing the morbidity and mortality of AC. Arch Endocrinol Metab. 2021;65(4):488-94
- Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency(2011) MOREIRA, Ricardo P. P.; JORGE, Alexander A. L.; GOMES, Larissa G.; KAUPERT, Laura C.; MASSUD FILHO, Joao; MENDONCA, Berenice B.; BACHEGA, Tania A. S. S.INTRODUCTION: 21-hydroxylase deficiency is an autosomal recessive disorder that causes glucocorticoid deficiency and increased androgen production. Treatment is based on glucocorticoid replacement; however, interindividual variability in the glucocorticoid dose required to achieve adequate hormonal control has been observed. OBJECTIVE: The present study aimed to evaluate the association between polymorphic variants involved in glucocorticoid action and/or metabolism and the mean daily glucocorticoid dose in 21-hydroxylase deficiency patients. METHODS: We evaluated 53 patients with classical forms of 21-hydroxylase deficiency who were receiving cortisone acetate. All patients were between four and six years of age and had normal androgen levels. RESULTS: The P450 oxidoreductase A503V, HSD11B1 rs12086634, and CYP3A7*1C variants were found in 19%, 11.3% and 3.8% of the patients, respectively. The mean +/- SD glucocorticoid dose in patients with the CYP3A7*1C and wild-type alleles was 13.9 +/- 0.8 and 19.5 +/- 3.2 mg/m(2)/d, respectively. We did not identify an association between the P450 oxidoreductase or HSD11B1 allelic variants and the mean glucocorticoid dose. CONCLUSION: Patients carrying the CYP3A7*1C variant required a significantly lower mean glucocorticoid dose. Indeed, the CYP3A7*1C allele accounted for 20% of the variability in the cortisone acetate dose. The analysis of genes involved in glucocorticoid metabolism may be useful in the optimization of treatment of 21-hydroxylase deficiency.
- Low Adrenomedullary Function Predicts Acute Illness in Infants With Classical Congenital Adrenal Hyperplasia(2022) WEBER, Jonathan; TANAWATTANACHAROEN, Veeraya K.; SEAGROVES, Amy; LIANG, Mark C.; KOPPIN, Christina M.; ROSS, Heather M.; BACHEGA, Tania A. S. S.; GEFFNER, Mitchell E.; SERRANO-GONZALEZ, Monica; BHULLAR, Gagandeep; KIM, Mimi S.Context: Youth with classical congenital adrenal hyperplasia (CAH) exhibit abnormal adrenomedullary function with decreased epinephrine levels noted in newborns and young infants. Little is known about how this relates to morbidity during the first year of life. Objective: This work aimed to study plasma epinephrine levels in infants with classical CAH and examine the clinical significance of epinephrine deficiency in the first year of life. Methods: This prospective cohort study comprised participants recruited from a pediatric tertiary care center: 36 infants with classical CAH due to 21-hydroxylase deficiency and 27 age-matched unaffected controls with congenital hypothyroidism. Main outcome measures included plasma epinephrine levels (N=27), CYP21A2 genotype (N=15), and incidence of acute illnesses from birth to age 1 year (N=28). Results: Epinephrine levels in CAH infants independently predicted illness incidence in the first year of life (beta=-0.018, R=-0.45, P=.02) and were negatively correlated with 17-hydroxyprogesterone at diagnosis (R=-0.51, P=.007). Infants with salt-wasting CAH exhibited lower epinephrine levels as newborns than simple-virilizing infants (P=.02). CAH patients had lower epinephrine as newborns than did controls (P=.007) and showed decreases in epinephrine from birth to age 1 year (P=.04). Null genotype was associated with lower newborn epinephrine and more illness in the first year of life, compared to less severe mutation categories. Conclusion: Lower epinephrine levels are associated with increased risk of illness among CAH infants. While not currently part of clinical standard of care, measuring epinephrine levels and assessing genotype may help predict acute illness in the first year of life.
conferenceObject Long-Term Cardiometabolic Morbidity in Young Adults with Classic 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia(2021) RIGHI, Beatrice; ALI, Salma R.; BRYCE, Jillian; TOMLINSON, Jeremy W.; BONFIG, Walter; BARONIO, Federico; COSTA, Eduardo C.; GUARAGNA FILHO, Guilherme; T'SJOEN, Guy; COOLS, Martine; MARKOSYAN, Renata; BACHEGA, Tania A. S. S.; MIRANDA, Mirela C.; IOTOVA, Violeta; FALHAMMAR, Henrik; CECCATO, Filippo; STANCAMPIANO, Marianna R.; RUSSO, Gianni; VUKOVIC, Rade; GIORDANO, Roberta; MAZEN, Inas; GUVEN, Ayla; DARENDELILER, Feyza; POYRAZOGLU, Sukran; VRIES, Liat de; ELLAITHI, Mona; DANIEL, Eleni; JOHNSTON, Colin; HUNTER, Steven J.; CARROLL, Paul V.; ADAM, Safwaan; PERRY, Colin G.; KEARNEY, Tara; ABRAHAM, Prakash; REES, D. Aled; LEESE, Graham P.; REISCH, Nicole; STIKKELBROECK, Nike M. M. L.; AUCHUS, Richard J.; ROSS, Richard J.; AHMED, S. Faisal- Effects of endocrine disruptors in the development of the female reproductive tract(2014) COSTA, Elaine Maria Frade; SPRITZER, Poli Mara; HOHL, Alexandre; BACHEGA, Tania A. S. S.Environmental agencies have identified a growing number of environmental contaminants that have endocrine disrupting activity, and these can become a major public health problem. It is suggested that endocrine disruptors could account for the higher-than-expected increase in the prevalence of some non-communicable diseases, such as obesity, diabetes, thyroid diseases, and some cancers. Several endocrine Disrupting Chemicals (EDCs), such as pesticides, bisphenol A, phthalates, dioxins, and phytoestrogens, can interact with the female reproductive system and lead to endocrine disruption. Initially, it was assumed that EDCs exert their effects by binding to hormone receptors and transcription factors, but it is currently known that they may also alter the expression of enzymes involved in the synthesis or catabolism of steroids. Biomonitoring studies have identified these compounds in adults, children, pregnant women, and fetuses. Among the diseases of the female reproductive tract associated with EDCs exposure are the following: precocious puberty, polycystic ovary syndrome, and premature ovarian failure. The different populations of the world are exposed to a great number of chemicals through different routes of infection; despite the various available studies, there is still much doubt regarding the additive effect of a mixture of EDCs with similar mechanisms of action.