RESUMO
OBJECTIVE: To determine the frequency of "invalid" 1-mg overnight dexamethasone (Dex) suppression tests (DSTs) (1-mg DST) on a large series of patients investigated for hypercortisolism and examine the interference of substances and clinical conditions that may explain low serum Dex levels. METHODS: A retrospective analysis of 1300 Dex-controlled 1-mg DST applied to patients screened for Cushing syndrome or mild autonomous cortisol secretion in a single center for which there were identified invalid tests and distinctive characteristics that may have interfered with the outcome. RESULTS: Among all tests, 146 (11.2%) were considered invalid (serum Dex levels <140 ng/dL, 36 [24.7%] of which were undetectable [<19.5 ng/dL]). In the Dex-undetectable group, 17% failed to take Dex correctly, 25% were on glucocorticoids (GCs), and 20% were on anticonvulsants and moderate CYP3A4 inducers. In the remaining 110 tests (serum Dex 20-140 ng/dL), 6.5% did not take Dex or were using GC, 22% were on anticonvulsants or CYP3A4 inducers, and another 13% had previous gastrointestinal tract abnormalities impairing drug absorption. CONCLUSION: Inappropriately low serum Dex levels during the 1-mg DST may lead to false-positive results. This is associated with recurrent use of CYP3A4-inducing drugs and/or gastrointestinal abnormalities. When serum Dex is undetectable, the key reason is failure to take the medication or the use of GC (when cortisol is suppressed). Simultaneous measurement of serum cortisol and Dex allows for DST validation, improving its accuracy and avoiding unnecessary repetitions. Adherence to verbal/written recommendations and actual use of medication are critical for interpreting the test.
Assuntos
Síndrome de Cushing , Humanos , Síndrome de Cushing/diagnóstico , Hidrocortisona , Dexametasona/uso terapêutico , Estudos Retrospectivos , Anticonvulsivantes/uso terapêutico , Indutores do Citocromo P-450 CYP3ARESUMO
INTRODUCTION: Heterozygotes (HZs) for 21-hydroxylase deficiency (21OHD) are highly prevalent, ranging from 1:60 to 1:11 for classic and nonclassic (NC) forms, respectively. Detection of HZ and asymptomatic NC by CYP21A2 genotyping is valuable for genetic counselling, but costly, complex and narrowly available. Adrenocorticotropic hormone (ACTH)-stimulated serum 17-hydroxyprogesterone (17P) and 21-deoxycortisol (21DF) discriminate 21OHD phenotypes effectively, notably if measured simultaneously by liquid chromatography-tandem mass spectrometry (LC-MS/MS). OBJECTIVE: This study was performed to reassess former LC-MS/MS-defined post-ACTH 21DF, 17P and cortisol (F) cutoffs in family members at risk for 21OHD. DESIGN AND PATIENTS: Prospective study in which we screened 58 asymptomatic relatives from families with 21OHD patients and compared post-ACTH steroid phenotypes with subsequent genotypes. RESULTS: Post-ACTH 21DF, 17P, F and (21DF + 17P)/F ratio segregate NC, HZ and wild-type (WT) phenotypes (subsequently genotyped) with some overlap. New receiver operating characteristic curve-defined cutoffs for post-ACTH 21DF, 17P and (21DF + 17P)/F ratio are 60 ng/dl, 310 ng/dl and 12 (unitless). Twenty-six of 33 HZ and all 6 NC (82.1%) had post-ACTH 21DF > 60 and 17P > 310 ng/dl, whereas 17/19 WT (89.5%) had values below cutoffs. Post-ACTH 21DF and 17P had a strong positive correlation (r = .9558; p < .001). A (21DF + 17P)/F ratio > 12 correctly identified 36 of 39 HZ plus NC (92.3% sensitivity) with 84.2% specificity (16 of 19 WT). Given the high frequency of 21OHD HZ, the negative prediction of ratio values below 12 excludes heterozygosity in 99.8% and 99.1% for classic and NC mutations, respectively. CONCLUSIONS: Reassessed ACTH-stimulated 21DF and 17P cutoffs by LC-MS/MS (60 and 310 ng/dl, respectively) correctly recognised 82.5% HZ plus NC, but combined precursor-to-product ratio ([21DF + 17P]/F) cutoff of 12 was superior, identifying 92.3% HZ plus NC. Since one WT subject is an outlier (potential HZ), these values would be somewhat better reinforcing their utility for screening asymptomatic relatives at risk for 21OHD.
Assuntos
Hiperplasia Suprarrenal Congênita , Hormônio Adrenocorticotrópico , 17-alfa-Hidroxiprogesterona , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/genética , Cromatografia Líquida , Cortodoxona , Heterozigoto , Humanos , Estudos Prospectivos , Esteroide 21-Hidroxilase/genética , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: Describe the secretion and profile of adrenal steroids in patients with adrenal incidentalomas compared to control subjects. DESIGN, SETTING AND PARTICIPANTS: A prospective study, 73 patients with adrenal incidentalomas, 21 bilateral and 52 unilateral and 34 matched controls in University Hospital. METHODS: Collect fasting blood sample before and 60 min after ACTH test (250 µg IV). One week later, perform overnight 1 mg dexamethasone test. The following steroids were measured by liquid chromatography-mass spectrometry (LC-MS): pregnenolone, 17-OH pregnenolone, 17-OH progesterone, 11-deoxycorticosterone, 11-deoxyortisol, 21-deoxycortisol, corticosterone, cortisol, androstenedione and aldosterone. RESULTS: Mean baseline serum cortisol was higher in incidentalomas, bilateral 361 ± 124, (range 143-665) nmol/L,(p < .0001), unilateral 268 ± 89 3.2 (range 98-507) nmol/L (p < .019) compared to controls 207 ± 100 (range 72-502) nmol/L. ACTH stimulation showed significantly higher levels in bilateral and unilateral cases compared to controls. After dexamethasone, mean serum cortisol levels suppressed in bilaterals 89 ± 69 (range 30-3) nmol/L (p < .0001), 58 ± 52 (range 16-323) nmol/L in unilateral (p < .01) compared to 26 ± 9 (range 7-46) nmol/L in controls. Mean baseline serum corticosterone was higher in bilateral 9.3 ± 4.8 (range 2.4-18.4) nmol/L (p < .005) and unilateral 7.3 ± 5.7 (range 0.1-30.3) nmol/L (p < .01) compared to controls 4.2 ± 2.4 (range 1.1-10.2) nmol/L, after ACTH stimulation significantly increased to higher levels in bilateral (p < .0002) and unilateral cases (p < .044) compared to controls. After dexamethasone, mean levels were 2.5 ± 2.6 (range 0.5-12.5) nmol/L in bilateral (p < .0006), 1.5 ± 1.6 (range 0.3-9.3) nmol/L in unilateral (p < .09) and 0.75 ± 0.46 (range 0.1-2.1) nmol/L in controls. Mean baseline serum 11-deoxycorticosterone (DOC) was higher in bilaterals 0.32 ± 0.23 (range 0.08-1.1) nmol/L (p < .03) compared to controls 0.15 ± 0.21 (range 0.08-1.1) nmol/L. ACTH stimulation increased levels to 3.27 ± 1.72 (range 0.5-7.4) nmol/L in bilateral cases compared to controls 1.369 ± 1.53 (range 0.1-7.1) nmol/L (p < .0001). Dexamethasone decreased levels to baseline (p ns). There were significant differences in serum 21-deoxycortisol (p < .0002) and serum pregnenolone (p < .004) only after ACTH stimulation. CONCLUSIONS: There is increased activity in several steroid biosynthesis pathways and higher steroid levels in bilateral compared to unilateral cases and evidence of hypercortisolism in 30% unilateral and 62% of bilateral incidentalomas.
Assuntos
Neoplasias das Glândulas Suprarrenais , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Hormônio Adrenocorticotrópico , Cromatografia Líquida , Dexametasona , Humanos , Hidrocortisona , Espectrometria de Massas , Estudos Prospectivos , EsteroidesRESUMO
OBJECTIVE. Adrenal incidentalomas occur in 5% of adults and can produce autonomous cortisol secretion that increases the risk of metabolic syndrome and cardiovascular disease. The objective of our study was to evaluate the relationship between adrenal nodule size measured on CT and autonomous cortisol secretion. SUBJECTS AND METHODS. In a prospective study of 73 patients 22-87 years old with incidentalomas, unilateral in 52 patients and bilateral in 21 patients, we measured maximum nodule diameter on CT and serum cortisol levels at 8:00 am, 60 minutes after the adrenocorticotropic hormone stimulation test, and after the dexamethasone suppression test. We also studied 34 age-, sex-, and body mass index-matched control subjects. Statistics used were Spearman correlation coefficients, t tests, ANOVA test, and multivariate analysis. RESULTS. The mean maximum diameter of unilateral nodules measured on CT was larger on the right (2.47 ± 0.98 [SD] cm) than on the left (2.04 ± 0.86 cm) (p = 0.01). In the bilateral cases, the mean diameter of the right nodules was 2.69 ± 0.93 cm compared with 2.13 ± 0.89 cm on the left (p = 0.06). Mean baseline serum cortisol level was significantly higher in the patients with incidentalomas (bilateral, 13.1 ± 4.5 mcg/dL [p < 0.001]; unilateral, 9.7 ± 3.2 mcg/dL [p = 0.019]) than in the control subjects (7.5 ± 3.6 mcg/dL). After dexamethasone suppression test, serum cortisol levels were suppressed to less than 1.8 mcg/dL in 100% of control subjects, 33% of patients with bilateral incidentalomas, and 62% of patients with unilateral incidentalomas (p < 0.001). There were significant correlations between maximum nodule diameter on CT and serum cortisol levels after the dexamethasone suppression test (ρ = 0.500; p < 0.001) and at baseline (ρ = 0.373; p = 0.003). CONCLUSION. Increasing size of adrenal nodules is associated with more severe hyper-cortisolism and less dexamethasone suppression; these cases need further evaluation and possibly surgery because of increased risks of metabolic syndrome and cardiovascular mortality.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Neoplasias das Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Exercise is known to induce multiple beneficial conditioning processes. Conversely, although exercise may generate several hormonal effects, an intrinsic hormonal conditioning process has not been reported. In the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, we observed inherent and independent conditioning processes of the hypothalamic-pituitary axes in athletes. Our objective is to describe the theory of the novel hormonal conditioning mechanism using the findings from the EROS study. METHODS: In this cross-sectional study, we selected 25 healthy athletes (ATL) and 12 non-physically active healthy controls (NPAC), 18-50 years old, males, with BMI 20-30 kg/m2, with similar baseline characteristics, who underwent gold-standard exercise-independent tests: cosyntropin stimulation test (CST) and insulin tolerance test (ITT), to evaluate cortisol response to CST, and ACTH, cortisol, GH, and prolactin responses to an ITT. RESULTS: Responses to ITT were significantly earlier and higher in ATL than NPAC for cortisol [Mean ± SD: 21.7 ± 3.1 vs 16.9 ± 4.1 µg/dL; p < 0.001], GH [Median (95% CI): 12.73 (1.1-38.1) vs 4.80 (0.33-27.36) µg/L; p = 0.015], and prolactin [24.3 (10.5-67.45) vs 10.50 (6.21-43.44) ng/mL; p = 0.002]. Cortisol response to CST was similar between ATL and NPAC. During ITT, cortisol, GH, and ACTH mean increase in ATL were 52.2, 265.2, and 18.6% higher than NPAC, respectively. Prolactin response was absent in NPAC, while present in ATL. CONCLUSIONS: We found sufficient evidence to propose the existence of a diffuse enhancement of the hypothalamic-pituitary activity in athletes, not restricted to any axis, showing an intrinsic and independent process of "hormonal conditioning" in athletes, similar to those observed in the cardiovascular and neuromuscular systems. This novel conditioning process may be the missing link for understanding the improved responses observed in athletes to harmful situations, traumas, infections, inflammations, and psychiatric conditions.
Assuntos
Atletas/estatística & dados numéricos , Cosintropina/administração & dosagem , Exercício Físico , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Insulina/administração & dosagem , Sistema Hipófise-Suprarrenal/metabolismo , Adolescente , Adulto , Estudos Transversais , Teste de Esforço , Feminino , Hormônios/administração & dosagem , Humanos , Hipoglicemiantes/administração & dosagem , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Prolactina/metabolismo , Adulto JovemRESUMO
The metabolic and hormonal consequences of high-intensity functional training regimens such as CrossFit® (CF) are unclear. Little is known about the triggers and clinical and biochemical features of CF-related overtraining syndrome (OTS). The EROS study compared endocrine and metabolic responses, and eating, social, psychological and body characteristics of OTS-affected (OTS) and healthy athletes (ATL), and non-physically active controls (NPAC). The current study is a post-hoc analysis of the CF subgroups of the EROS study, to evaluate specific characteristics of CF in ATL and OTS. Parameters were overall and pairwise compared among OTS-affected (CF-OTS) and healthy (CF-ATL) athletes that exclusively practiced CF, and NPAC. CF-ATL yielded earlier and enhanced cortisol, GH, and prolactin responses to an insulin tolerance test (ITT), increased neutrophils, lower lactate, increased testosterone, improved sleep quality, better psychological performance, increased measured-to-predicted basal metabolic rate (BMR) ratio and fat oxidation, and better hydration, when compared to NPAC. Conversely, more than 90% of the adaptive changes in CF were lost under OTS, including an attenuation of the hormonal responses to an ITT, increased estradiol, decreased testosterone, and decreased BMR and fat oxidation; the most remarkable trigger of OTS among "HIFT athletes" was the long-term low carbohydrate and calorie intake.
Assuntos
Transtornos Traumáticos Cumulativos/etiologia , Transtornos Traumáticos Cumulativos/metabolismo , Condicionamento Físico Humano/efeitos adversos , Condicionamento Físico Humano/métodos , Adolescente , Adulto , Afeto/fisiologia , Biomarcadores/metabolismo , Fenômenos Biomecânicos , Catecolaminas/urina , Transtornos Traumáticos Cumulativos/fisiopatologia , Técnicas de Diagnóstico Endócrino , Estradiol/sangue , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/análise , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/fisiologia , Insulina/sangue , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiologia , Prolactina/sangue , Saliva/química , Sono/fisiologia , Testosterona/sangue , Adulto JovemRESUMO
OBJECTIVE: 17α-Hydroxylase deficiency (P450c17D) is characterized by hypogonadism and mineralocorticoid hypertension. We aimed to estimate the relative incidence and spectrum of preliminary misdiagnoses in Brazilian P450c17D patients. METHODS: In this cross-sectional study, we reviewed, updated, and analyzed data of 40 P450c17D patients (21 XY, 19 XX). RESULTS: Complete data were unavailable for 2 patients. Seven patients were relatives of an index case. Of the 31 index cases, 29 (94%) received a total of 16 misdiagnoses (1-4 per patient) before confirmation of P450c17D. Essential hypertension (55%), pure gonadal dysgenesis (35%), and androgen resistance syndrome (21%) were the most frequent misdiagnoses. Median ages at initial and final diagnosis were 13.2 and 16.5 years, respectively, with an average interval to diagnosis of 3.2 years. Initially, 38 (95%) patients had hypertension, and 75% had hypokalemia. Primary amenorrhea and sexual infantilism were present in 95% patients, and 73% were at Tanner stage I. All had low-to-undetectable estrogens and androgens with elevated gonadotropins and progesterone (580 ± 53 ng/dL). Several had recurrent infections in childhood and neurological issues prior to final diagnosis and/or had siblings who died of infectious diseases or unknown causes before puberty. CONCLUSION: The high percentage of prior misdiagnoses in P450c17D patients may be attributable to the rarity of and relative unfamiliarity with the disease, its varied clinical presentation, and the limited access to critical steroid dosages and genotyping. Reduced sex steroids, and elevated gonadotropins and progesterone levels, in addition to mineralocorticoid hypertension, are pathognomonic of P450c17D. CYP17A1 gene mutations provide a definitive diagnosis. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CAH = congenital adrenal hyperplasia CYP17A1 = 17α-hydroxylase enzyme DOC = deoxycorticosterone HH = hypergonadotropic hypogonadism P450c17D = 17α-hydroxylase deficiency TS = Tanner stage.
Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/genética , Erros de Diagnóstico/estatística & dados numéricos , Esteroide 17-alfa-Hidroxilase/genética , Adolescente , Hiperplasia Suprarrenal Congênita/epidemiologia , Adulto , Brasil/epidemiologia , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Adulto JovemRESUMO
Overtraining syndrome (OTS) is caused by an imbalance between training, nutrition and resting, and leads to decreased performance and fatigue; however, the precise underlying triggers of OTS remain unclear. This study investigated the body composition, metabolism, eating, sleeping patterns and mood states among participants with OTS. Selected participants were divided into OTS-affected athletes (OTS, n = 14), healthy athletes (ATL, n = 25), and healthy non-physically active controls (NCS, n = 12). Compared to ATL, OTS showed decreased sleep quality (p = 0.004); increased duration of work or study (p < 0.001); decreased libido (p = 0.024); decreased calorie (p < 0.001), carbohydrate (p < 0.001) and protein (p < 0.001) intakes; decreased mood states (p < 0.001); decreased basal metabolic rate (p = 0.013) and fat burning (p < 0.001); increased body fat (p = 0.006); decreased muscle mass (p = 0.008); and decreased hydration (p < 0.001). Levels were similar between OTS and NCS, except for worsened fatigue (p < 0.001) and vigour (p = 0.001) in OTS. Reduced calorie intake, worsened sleep, and increased cognitive activity are likely OTS triggers. OTS appears to induce dehydration, increase body fat, decrease libido, and worsen mood.
Assuntos
Composição Corporal , Transtornos Traumáticos Cumulativos/fisiopatologia , Transtornos Traumáticos Cumulativos/psicologia , Metabolismo Energético , Comportamento Alimentar , Sono , Afeto , Ingestão de Energia , Fadiga/etiologia , Humanos , Fenômenos Fisiológicos da Nutrição EsportivaRESUMO
Post-menopause hyperandrogenism is a condition that needs careful evaluation. Aromatase inhibitors (AI), which are important in the management of positive estrogen breast cancer, and chronic kidney disease (CKD) can puzzle the evaluation of this condition. A postmenopause female with type-2 diabetes and advanced CKD was attended due to progressive virilization, which has started after the introduction of an AI for breast cancer 5 years earlier. Clinical and radiological investigation has confirmed a pure Leydig cell tumor as source of hyperandrogenism. Re-evaluation of the breast tumor immunohistochemistry has shown positive androgen receptor expression and negative expression for estrogen, progesterone and HER-2 receptors. Even though an ovarian tumor was the source of androgen excess, we discuss that AI could exert a slight contribution to patient's virilization by reducing estradiol counterbalance. Also, although the onset of hyperandrogenic symptoms was unclear, we could not exclude that the ovarian tumor had produced enough androgens to play a role in breast tumor progression. This case report supports the literature regarding the possible association between Leydig cell tumor and androgen-receptor-positive breast cancer development. Finally, progressive hyperandrogenic symptoms in postmenopause, even under AI therapy or the presence of advanced CKD, impose a more detailed investigation.
Assuntos
Neoplasias da Mama/patologia , Tumor de Células de Leydig/patologia , Neoplasias Ovarianas/patologia , Idoso , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Hiperandrogenismo/etiologia , Tumor de Células de Leydig/complicações , Neoplasias Ovarianas/complicações , Pós-Menopausa , Virilismo/etiologiaRESUMO
OBJECTIVE: The objective of this study was to establish the suitability of the apparent diffusion coefficient (ADC) as a parameter for evaluating early treatment response after percutaneous ablation of functional adrenal adenomas. SUBJECTS AND METHODS: Seventeen adult patients with functioning adrenal adenomas underwent radiofrequency ablation. Serum hormone levels were analyzed before and up to 6 months after ablation. MRI findings (nodule size in cm, signal intensity index, ADC maps, and nodule-to-muscle ADC ratio) were analyzed before and up to 30 days after ablation. A consensus review of all scans was performed by two attending abdominal imaging radiologists. The procedure was considered successful if serum hormone levels normalized and no contrast enhancement of the adrenal lesion was seen on follow-up MRI. RESULTS: Of 17 patients who underwent radiofrequency ablation, complete response was achieved in 16 patients with partial response in one patient. Of the four parameters of interest, only ADC maps and nodule-to-muscle ADC ratio showed statistically significant differences (p < 0.05). CONCLUSION: This prospective study suggests that apparent diffusion coefficient values may help radiologists monitor early treatment response after CT-guided radiofrequency ablation of functioning adrenal adenomas.
RESUMO
BACKGROUND: The term "adrenal fatigue" ("AF") has been used by some doctors, healthcare providers, and the general media to describe an alleged condition caused by chronic exposure to stressful situations. Despite this, "AF" has not been recognized by any Endocrinology society, who claim there is no hard evidence for the existence. The aim of this systematic review is to verify whether there is substantiation for "AF". METHODS: A systematic search was performed at PUBMED, MEDLINE (Ebsco) and Cochrane databases, from the beginning of the data until April 22nd, 2016. Searched key words were: "adrenal" + "fatigue", "adrenal" + "burnout", "adrenal" + "exhaustion", "hypoadrenia", "burnout" + "cortisol", "fatigue" + "cortisol", "clinical" + "burnout", "cortisol" + "vitalility", "adrenal" + "vitality", and "cortisol" + "exhaustion". Eligibility criteria were: (1) articles written in English, (2) cortisol profile and fatigue or energy status as the primary outcome, (3) performed tests for evaluating the adrenal axis, (4) absence of influence of corticosteroid therapy, and (5) absence of confounding diseases. Type of questionnaire to distinct fatigued subjects, population studied, tests performed of selected studies were analyzed. RESULTS: From 3,470 articles found, 58 studies fulfilled the criteria: 33 were carried in healthy individuals, and 25 in symptomatic patients. The most assessed exams were "Direct Awakening Cortisol" (n = 29), "Cortisol Awakening Response" (n = 27) and "Salivary Cortisol Rhythm" (n = 26). DISCUSSION: We found an almost systematic finding of conflicting results derived from most of the studies methods utilized, regardless of the validation and the quality of performed tests. Some limitations of the review include: (1) heterogeneity of the study design; (2) the descriptive nature of most studies; (3) the poor quality assessment of fatigue; (4) the use of an unsubstantiated methodology in terms of cortisol assessment (not endorsed by endocrinologists); (5) false premises leading to an incorrect sequence of research direction; and, (6) inappropriate/invalid conclusions regarding causality and association between different information. CONCLUSION: This systematic review proves that there is no substantiation that "adrenal fatigue" is an actual medical condition. Therefore, adrenal fatigue is still a myth.
Assuntos
Doenças das Glândulas Suprarrenais/diagnóstico , Fadiga/diagnóstico , Esgotamento Profissional/diagnóstico , Esgotamento Profissional/fisiopatologia , Ritmo Circadiano , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/fisiopatologia , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Saliva , Estresse Psicológico/fisiopatologiaRESUMO
We report a case of gender dysphoria (GD) in a 62-year-old genetic female patient, raising the pros and cons of performing corrective surgery later in life. This 46,XX DSD patient was registered and reared as a girl; CAH was diagnosed late in childhood. Poor adherence to treatment and lack of proper psychological management contributed to evident GD. Living for years as a male, the patient applied for a legitimate male identification document in his late 50s; thereafter, he requested a sex-reassignment surgery "to disguise his female body upon his death." We informed the patient and family about surgery hazards, while analytical therapy allowed the group to evaluate the actual wish for surgery. When the wish was brought up, the role of death urged the group to rethink the course of treatment. During the process, it became clear that the patient's desire for surgery, more than a wish for changing the genitalia, expressed an impulse related to issues of endorsement and acceptance of his male identity. This report raises interesting questions about sexuality in a social context and prompts the idea that sexuality is broader than sex itself, raising new questions on the psychological risks faced when considering a body change after years of living with a disorder of sex development.
Assuntos
Hiperplasia Suprarrenal Congênita/psicologia , Disforia de Gênero/diagnóstico , Identidade de Gênero , Autoimagem , Procedimentos de Readequação Sexual/psicologia , Feminino , Disforia de Gênero/cirurgia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hypertension (HT) during pregnancy is not an infrequent obstetric problem, reaching a prevalence of 5-10%. This condition is highly associated with both maternal and fetal complications if not precisely diagnosed and managed. Even though primary HT, obesity, and preeclampsia are the main causes of HT in this period, other less familiar conditions must be considered during the investigation. Pheochromocytoma and paraganglioma (PPGL) are chromaffin cell tumors that produce, store, and secrete catecholamines, leading to HT and other adrenergic manifestations. Recognition of PPGL is crucial since misdiagnosis and improper management can lead to high morbidity and mortality, particularly during pregnancy. We report on two cases of PPGL diagnosed during pregnancy with different managements. Case 1 is a 25-year-old female at 31 weeks of first pregnancy, whose severe HT and life-threatening symptoms prompted an emergency delivery without previous confirmation or medical treatment of a suspected PPGL. After confirmation, a right adrenal PPGL was surgically resected 4 months later, following 15 days of medical therapy. Case 2 is a 22-year-old female at 18 weeks of pregnancy whose symptomatic PPGL was resected in the second trimester. A next-generation sequencing panel, including 23 PPGL-related genes, found no germline pathogenic variants (GPVs) in case 1 and an exon 1-4 germinative heterozygous deletion of the MAX gene in case 2. Despite the different medical approaches, both cases had satisfactory outcomes. Although uncommon, PPGL should be considered in the differential diagnosis of HT in pregnancy since missing the diagnosis and failing to introduce appropriate and timely treatment may lead to dramatic consequences for the mother and fetus. PPGL diagnosed during reproductive age is likely to result from GPV, prompting genetic investigation and counseling.
RESUMO
Pheochromocytoma and paragangliomas (PPGLs) are rare neuroendocrine tumors carrying 25-40% pathogenic germline gene variants (PGVs). We evaluated clinical, laboratory, and germline molecular profile of 115 patients with pathologic (14 patients were relatives from 8 different families recruited for genetic survey) confirmed PPGL followed in our institution. Patients with classic MEN2A/MEN2B phenotypes and at-risk relatives underwent direct analysis of RET proto-oncogene, and the remaining had samples submitted to complete next-generation sequencing aiming 23 PPGL-related genes: ATM, ATR, CDKN2A, EGLN1, FH, HRAS, KIF1B, KMT2D, MAX, MDH2, MERTK, MET, NF1, PIK3CA, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TP53, and VHL. We also developed a clinical judgment score (CJS) to determine the probability of patients having a potentially hereditary disease. The resulting genetic landscape showed that 67 patients (58.3%) had variants in at least one gene: 34 (50.7%) had exclusively pathogenic or likely pathogenic variants, 13 (19.4%) had pathogenic or likely pathogenic variants and variant of undetermined significance (VUS), and 20 (29.8%) carried only VUS. PGVs were found in RET (n = 18; 38.3%), VHL (n = 10; 21.3%), SDHB and NF1 (n = 8; 17% each), and MAX, SDHD, TMEM127, and TP53 (n = 1; 2.1% each). Direct genetic testing disclosed 91.3% sensitivity, 81.2% specificity, and 76.4% and 93.3% positive predictive value (PPV) and negative predictive values (NPV), respectively. The CJS to identify patients who would not benefit from genetic testing had 75% sensitivity, 96.4% specificity, and 60% and 98.2% PPV and NPV, respectively. In summary, the landscape of PPGL germline gene variants from 115 Brazilian patients resulted in slightly higher prevalent pathogenic and likely pathogenic variants, especially in the RET gene. We suggest a CJS to identify PPGL patients who would not require initial genetic evaluation, improving test specificity and reducing costs.
RESUMO
High blood pressure (BP) is not restricted to adults; children and adolescents may also be affected, albeit less frequently. Aside from unfavorable environmental factors, such as obesity and sedentary life leading to early-onset essential hypertension (HT), several secondary causes must be investigated in the occasional hypertensive child/adolescent. Endocrine causes are relevant and multiple, related to the pituitary, thyroid, parathyroid, gonads, insulin, and others, but generally are associated with adrenal disease. This common scenario has several vital components, such as aldosterone, deoxycorticosterone (DOC), cortisol, or catecholamines, but there are also monogenic disorders involving the kidney tubule that cause inappropriate salt retention and HT that simulate adrenal disease. Finally, a blood vessel disease was recently described that may also participate in this vast spectrum of pediatric hypertensive disease. This review will shed some light on the diagnosis and management of conditions, focusing on the most prevalent adrenal (or adrenal-like) disturbances causing HT.
Assuntos
Hipertensão , Adulto , Adolescente , Humanos , Criança , Hipertensão/etiologia , Aldosterona , HidrocortisonaRESUMO
Adrenal steroid biosynthesis and its related pathology are constant evolving disciplines. In this paper, we review classic and current concepts of adrenal steroidogenesis, plus control mechanisms of steroid pathways, distribution of unique enzymes and cofactors, and major steroid families. We highlight the presence of a "mineralocorticoid (MC) pathway of zona fasciculata (ZF)", where most circulating corticosterone and deoxycorticosterone (DOC) originate together with 18OHDOC, under ACTH control, a claim based on functional studies in normal subjects and in patients with 11ß-, and 17α-hydroxylase deficiencies. We emphasize key differences between CYP11B1 (11ß-hydroxylase) and CYP11B2 (aldosterone synthase) and the onset of a hybrid enzyme - CYP11B1/CYP11B2 -, responsible for aldosterone formation in ZF under ACTH control, in "type I familial hyperaldosteronism" (dexamethasone suppressible). In "apparent MC excess syndrome", peripheral conversion of cortisol to cortisone is impaired by lack of 11ß-hydroxysteroid dehydrogenase type 2, permitting free cortisol access to MC receptors resulting in severe hypertension. We discuss two novel conditions involving the synthesis of adrenal androgens: the "backdoor pathway", through which dihydrotestosterone is formed directly from androsterone, being relevant for the fetoplacental setting and sexual differentiation of male fetuses, and the rediscovery of C19 11-oxygenated steroids (11-hydroxyandrostenedione and 11-ketotestosterone), active androgens and important markers of virilization in 21-hydroxylase deficiency and polycystic ovaries syndrome. Finally, we underline two enzyme cofactor deficiencies: cytochrome P450 oxidoreductase which partially affects 21- and 17α-hydroxylation, producing a combined clinical/hormonal picture and causing typical skeletal malformations (Antley-Bixler syndrome), and PAPSS2, coupled to SULT2A1, that promotes sulfation of DHEA to DHEAS, preventing active androgens to accumulate. Its deficiency results in reduced DHEAS and elevated DHEA and androgens with virilization. Future and necessary studies will shed light on remaining issues and questions on adrenal steroidogenesis.
Assuntos
Hiperplasia Suprarrenal Congênita , Hiperaldosteronismo , Hiperplasia Suprarrenal Congênita/metabolismo , Androgênios , Citocromo P-450 CYP11B2 , Humanos , Masculino , EsteroidesRESUMO
The cortisol awakening response (CAR) is a distinct component of the circadian cortisol profile and has promise as a biomarker for the monitoring of athlete readiness and training status. Although some studies have suggested the CAR may be affected by the development of overtraining syndrome (OTS), this has yet to be systematically investigated. PURPOSE: To compare the CAR and diurnal cortisol slope between athletes diagnosed with OTS, healthy athletes, and sedentary controls. METHODS: This study was a secondary analysis of data from the Endocrine and Metabolic Responses on Overtraining study. Male participants were recruited to either OTS, healthy athlete, or sedentary control groups. The participants produced saliva samples immediately after waking (S1), 30 minutes after waking (S2), at 16:00 hours, and at 23:00 hours. Salivary cortisol concentration was determined by an electrochemiluminescence assay. Mixed-effects models were used to assess the conditional effect of group (sedentary controls, OTS, and healthy athletes) on the change in cortisol over time. Separate models were fit for the awakening samples (S1 and S2) and for the diurnal slope (linear change across S1, 16:00 h, and 23:00 h). RESULTS: The models demonstrated significant time-by-group interaction for OTS for the 2 cortisol concentrations collected during the awakening period (ß = -9.33, P < .001), but not for the diurnal cortisol slope (ß = 0.02, P = .80). CONCLUSIONS: These results suggest the CAR may be associated with OTS and should be considered within a panel of biomarkers. Further research is necessary to determine whether alterations in the CAR may precede the diagnosis of OTS.
Assuntos
Hidrocortisona , Saliva , Atletas , Biomarcadores , Ritmo Circadiano , Humanos , MasculinoRESUMO
PURPOSES: Overtraining syndrome (OTS) is an unexplained underperformance syndrome triggered by excessive training, insufficient caloric intake, inadequate sleep, and excessive cognitive and social demands. Investigation of the recovery process from OTS has not been reported to date. The objective was to unveil novel markers and biochemical and clinical behaviors during the restoration process of OTS. METHODS: This was a 12-week interventional protocol in 12 athletes affected by OTS, including increase of caloric intake, transitory interruption of training, improvement of sleep quality, and management of stress, followed by the assessment of 50 parameters including basal and hormonal responses to an insulin tolerance test and nonhormonal biochemical markers, and body metabolism and composition. RESULTS: Early cortisol (P = .023), late ACTH (adrenocorticotrophic hormone) (P = .024), and early and late growth hormone (P = .005 and P = .038, respectively) responses, basal testosterone (P = .038), testosterone:estradiol ratio (P = .0005), insulinlike growth factor 1 (P = .004), cortisol awakening response (P = .001), and free thyronine (P = .069) increased, while basal estradiol (P = .033), nocturnal urinary catecholamines (P = .038), and creatine kinase (P = .071) reduced. Conversely, markers of body metabolism and composition had slight nonsignificant improvements. CONCLUSION: After a 12-week intervention, athletes affected by actual OTS disclosed a mix of non-, partial, and full recovery processes, demonstrating that remission of OTS is as complex as its occurrence.