Bone mass, fracture risk, and associated factors in postmenopausal women living with HIV.

OBJECTIVE: The aim of this study was to assess the prevalence of low bone mass (osteopenia/osteoporosis), the factors associated with low bone mass, and the risk of fractures in Brazilian postmenopausal women living with HIV (WLH) in the Amazon region. METHODS: This is a cohort study with a cross-sectional assessment at baseline conducted between March 2021 to August 2022 with 100 postmenopausal WLH undergoing antiretroviral therapy (ART) between 45 and 60 years of age and 100 age-matched HIV-negative women. Data on bone mineral density in the lumbar spine (LS) and femoral neck (FN) were collected using dual x-ray absorptiometry and the 10-year risk of hip and major osteoporotic fractures was assessed using the Fracture Risk Assessment tool (FRAX). RESULTS: The age of menopause onset occurred earlier in WLH ( P < 0.001). No differences in prevalence of osteoporosis and osteopenia in LS and FN were observed except for a lower T score in FN in WLH ( P = 0.039). The FRAX for major osteoporotic fracture and hip fracture were low in both groups, despite the mean of both FRAX scores was higher in WLH ( P < 0.001). Multivariate analysis showed that years since menopause onset, higher body mass index and higher FRAX major osteoporotic fracture were associated with the WLH group, while a higher frequency of physical activity was registered in the HIV-negative group. Multivariate analysis also showed that in WLH, a lower T score in FN was associated with years since menopause onset and body mass index and that the number of years since menopause onset was associated with a lower T score in the LS and a higher score in the FRAX hip fracture. CONCLUSIONS: Our findings show a high prevalence of low bone mass (osteopenia/osteoporosis) in Brazilian postmenopausal women from the Amazon region. Women living with HIV have higher FRAX scores than HIV-negative women and a lower T score in the FN.

Thiazolidine derivatives: In vitro toxicity assessment against promastigote and amastigote forms of Leishmania infantum and ultrastructural study.

Neglected diseases, such as Leishmaniasis, constitute a group of communicable diseases that occur mainly in tropical countries. Considered a public health problem with limited treatment. Therefore, there is a need for new therapies. In this sense, our proposal was to evaluate in vitro two series of thiazolidine compounds (7a-7e and 8a-8e) against Leishmania infantum. We performed in vitro evaluations through macrophage cytotoxicity assays (J774) and nitric oxide production, activity against promastigotes and amastigotes, as well as ultrastructural analyzes in promastigotes. In the evaluation of cytotoxicity, the thiazolidine compounds presented CC50 values between 8.52 and 126.83 µM. Regarding the evaluation against the promastigote forms, the IC50 values ranged between 0.42 and 142.43 µM. Compound 7a was the most promising, as it had the lowest IC50. The parasites treated with compound 7a showed several changes, such as cell body shrinkage, shortening and loss of the flagellum, intense mitochondrial edema and cytoplasmic vacuolization, leading the parasite to cell inviability. In assays against the amastigote forms, the compound showed a low IC50 (0.65 µM). These results indicate that compound 7a was efficient for both evolutionary forms of the parasite. In silico studies suggest that the compound has good oral bioavailability. These results show that compound 7a is a potential drug candidate for the treatment of Leishmaniasis.

Effects of intrauterine infusion of Escherichia coli lipopolysaccharide on uterine mRNA gene expression and peripheral polymorphonuclear leukocytes in Jersey cows diagnosed with purulent vaginal discharge.

The objectives of the current experiment were to investigate the effects of intrauterine treatment of cows with purulent vaginal discharge (PVD) using lipopolysaccharide (LPS) from Escherichia coli on uterine mRNA expression of genes related to inflammatory responses, peripheral polymorphonuclear leukocyte (PMN) function, hematological parameters, and blood concentrations of cortisol, haptoglobin, and progesterone (P4). Jersey cows (n = 3,084) were examined for PVD at 35 ± 6 d postpartum using the Metricheck device (Simcro, Hamilton, New Zealand). At examination, 310 cows had PVD (10.1%), but to ensure proper collection and processing of samples, 267 cows were used in this experiment. Cows were balanced for lactation number, body condition score, and milk yield, and randomly assigned to the control treatment [intrauterine infusion of 20 mL of phosphate-buffered saline (PBS); n = 87] or to receive intrauterine infusion of 20 mL of PBS containing 150 µg (LPS150; n = 91) or 300 µg (LPS300; n = 89) of E. coli LPS. Uteri were biopsied in a subgroup of cows at 6 h after infusion and in another subgroup of cows at 24 h after infusion. Peripheral PMN expression of adhesion molecules (L-selectin and MAC-1) and phagocytosis and oxidative burst were evaluated at 0, 2, and 6 h after infusion. Blood sampled 0, 2, 6, 24, 48, and 168 h after infusion was used for complete hemogram and to determine concentrations of cortisol, haptoglobin, and P4. Treatment did not affect uterine mRNA expression of adhesion molecules [endothelial leukocyte adhesion molecule (E-selectin), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1)], cytokines (tumor necrosis factor-α, IL-1ß, IL-6, IL-8, and IL-10), and toll-like receptor-4. Treatment did not affect PMN expression of L-selectin, but intensity of expression of MAC-1 was higher for LPS150 cows than PBS cows, and tended to be higher in LPS150 than LPS300 cows. Furthermore, a greater percentage of PMN from LPS300 cows were positive for phagocytosis and oxidative burst compared with PBS and LPS150 cows. No effects were observed of treatment on hematological parameters and concentrations of cortisol, haptoglobin, and P4. These observations suggest that intrauterine infusion of E. coli LPS moderately stimulates peripheral PMN function, but further research is needed to better understand the immunomodulatory effects of LPS in the uterus of cows with PVD.

Effects of intrauterine infusion of Escherichia coli lipopolysaccharide on uterine health, resolution of purulent vaginal discharge, and reproductive performance of lactating dairy cows.

The objectives of the current experiment were to evaluate the effects of intrauterine infusion of Escherichia coli lipopolysaccharide (LPS) in cows diagnosed with purulent vaginal discharge (PVD) on intrauterine cell population, resolution of PVD, uterine health, and reproductive performance. Jersey cows (n = 3,084) were examined using the Metricheck device to diagnose PVD at 35 ± 6 d postpartum. Purulent vaginal discharge was defined as the presence of purulent (≥50% pus) discharge detectable in the vagina. Of the 310 cows positive for PVD, 267 cows were enrolled in the current experiment. To ensure proper timing of treatment and collection of samples, only 9 PVD-positive cows were treated per day. Selected cows were balanced at 35 ± 6 d postpartum for lactation number, body condition score, and milk yield and were randomly assigned to receive an intrauterine infusion of 20 mL of phosphate-buffered saline (PBS; control, n = 87), 20 mL of PBS with 150 µg LPS (LPS150, n = 91), or 20 mL of PBS with 300 µg of LPS (LPS300, n = 89). Uterine cytology was performed immediately before treatment and 1, 2, and 7 d after treatment to evaluate the effect of LPS treatment on intrauterine cell population. Cows were examined with the Metricheck device at 7 and 28 d after treatment to evaluate the effects of treatment on resolution of PVD. Reproductive status was recorded up to 200 d postpartum. Cows diagnosed with PVD had greater incidence of twinning, dystocia, retained placenta, and metritis after calving than cows without PVD. Count of polymorphonuclear leukocytes (PMNL) in uterine cytology 1, 2, and 7 d after intrauterine infusion was not statistically different among treatments. From d 0 to 1, however, PMNL count in uterine cytology of PBS cows increased by 5%, whereas the PMNL count in uterine cytology of LPS150 and LPS300 cows increased by 54 and 48%, respectively. Treatment did not affect the likelihood of cows being diagnosed with PVD 7 and 28 d after intrauterine infusion. Cows without PVD and LPS150 cows were more likely to be pregnant after the first postpartum AI than PBS cows. After the second postpartum AI, cows without PVD were more likely to be pregnant than PBS and LPS300 cows. Hazard of pregnancy up to 200 d postpartum was decreased for PBS and LPS300 cows compared with cows without PVD, and it tended to be decreased for LPS150 cows compared with cows without PVD. Intrauterine treatment with 150 µg of E. coli LPS of cows diagnosed with PVD improved likelihood of pregnancy after the first postpartum AI, but further research is needed to elucidate the mechanism by which LPS treatment improved fertility.

Association between Prepartum Feeding Behavior and Periparturient Health Disorders in Dairy Cows.

The objective of this study was to investigate the relationship between prepartum feeding behavior, measured as time spent feeding per day, and periparturient health disorders, milk yield, milk composition, and milk somatic cell count in Jersey cows. Pregnant Jersey cows were marked with unique alphanumeric symbols and were moved into a prepartum group 4 weeks prior to their expected calving date. At enrollment, cows with a body condition score <2 or >4 or a locomotion score >3 were not included. Time spent feeding was measured using 10-min video scan sampling for 24-h periods of 2-4 days per week of the study. A total of 925 cows were eligible for analysis. Parity was based on lactation number at the time of enrollment and classified as nulliparous (cows pregnant with their first calf), primiparous (cows pregnant with their second calf), and multiparous (lactation ≥2). Multiparous cows with two or more health disorders spent approximately 10% less time feeding prepartum than cows that did not have any health disorders. Multiparous cows subsequently diagnosed with metritis had a tendency to spend 5% less time feeding prepartum than healthy counterparts. Primiparous cows with retained placenta had a 10% reduction in feeding time compared to healthy primiparous cows. Monitoring time spent feeding prepartum by primiparous and multiparous cows, even on a limited number of days, appeared to be beneficial in predicting cows at risk for periparturient health disorders. Real-time daily feeding behavior monitoring technologies that can be used by dairy farms are now available, which might prove to be even more helpful in identifying cows at risk for periparturient cow health disorders as more data points can be recorded for each cow and compared to her own behavior or that of specific cohorts.

Social stressors and their effects on immunity and health of periparturient dairy cows.

Management practices during the periparturient period have been the focus of much research recently because during this period immune function, metabolism, and health of cows are severely challenged. Responses to stress are often classified as behavioral, immunological, neuroendocrine, and autonomic. In production systems, understanding all facets of stress response is important to correctly predict the consequences of stressors to the health and performance of animals and to prevent costly managerial changes that have minimal effect on animal well-being and performance. Common social stressors faced by periparturient animals are regrouping, overstocking, and for nulliparous animals, commingling with parous animals. In conventional dairies, feeding strategies during the periparturient period often require several group changes during the most challenging period of an animal's life. Traditional weekly regrouping of prepartum cows increases competitive behavior at the feed bunk but it does not affect immune and metabolic responses, health and production, as long as stocking density is not overwhelming, and nulliparous and parous animals are housed separately. Stocking density of prepartum animals may be overlooked because these are nonproductive animals. Severe overstocking (200% of feeding space) of commingled nulliparous and parous pregnant animals produces neuroendocrine and metabolic changes. On the other hand, when prepartum nulliparous and parous animals are housed separately, stocking densities of up to 120% do not seem to affect innate and adaptive immunity, metabolic responses, milk yield, and reproductive performance, despite increasing negative behavior among cows. In recent experiments, when animals were ranked based on feed bunk displacement, dominant animals were more likely to be diagnosed with metritis than subordinate animals. Importantly, dominant animals with large number of interactions with pen mates (displacement at the feed bunk) were considerably more likely to be diagnosed with uterine diseases (retained placenta and metritis) and to be removed from the herd within 60d postpartum. Much has been learned about behavioral responses of cows to stressful conditions, but our understanding of neuroendocrine and immune responses to such conditions is somewhat limited. A multidisciplinary approach to research that encompasses several responses to stress and biological functions is critical.

Short communication: Plasma progesterone concentration and ovarian dynamics of lactating Jersey cows treated with 1 or 2 intravaginal progesterone inserts.

The objectives of the current experiment were to determine circulating progesterone concentrations and ovarian follicle development of lactating Jersey cows treated with 1 or 2 controlled internal drug release (CIDR) insert containing 1.38 g of progesterone during proestrus. Cows were enrolled in the experiment at 34 ± 3 d in milk and were paired by parity, body condition score, body weight, and milk yield. Estrous cycles were presynchronized with an injection of GnRH concurrent with a new CIDR insert (study d -7) and 2 injections of PGF2α given 5 and 6 d after the GnRH injection (study d -2 and -1, respectively). Cows assigned to the 1CIDR treatment (n=30) or 2CIDR treatment (n=30) received 1 and 2 CIDR inserts, respectively, from study d 0 through 7. Control cows (n=10) did not receive further treatment. On study d -2 and daily from study d 0 through 7, ovaries were examined by transrectal ultrasound and blood samples were collected for determination of progesterone. On study d 7, CIDR inserts were removed after ultrasound exam and blood sample collection. Progesterone concentration from study d 0 through 7 was greatest for 2CIDR cows (2.17 ± 0.09 ng/mL), followed by 1CIDR cows (1.37 ± 0.10 ng/mL) and control cows (0.62 ± 0.21 ng/mL). The interaction between treatment and study day affected progesterone concentration from study d 0 through 7. The average increase in progesterone concentration from study d 1 through 7 was 0.80 ng/mL for 1CIDR and 1.72 ng/mL for 2CIDR cows compared with control cows. The percentage of cows that ovulated between study d 0 and 7 was greatest for control cows (80%), but it did not differ between 1CIDR (12%) and 2CIDR (3.7%) cows. Growth of class III follicles (10-17 mm) identified on study d 0 was affected by treatment because 1CIDR cows had larger class III follicles than 2CIDR cows on study d 5, 6 and 7. A larger proportion of control cows developed a new follicular wave between study d 0 and 7 (control=60.0%, 1CIDR=12.0%, 2CIDR=7.4%). Treatment of lactating Jersey cows with 1 and 2 CIDR inserts resulted in a 1 and 2 fold increase, respectively, in circulating progesterone concentration. Growth class III follicles from cows treated with 2 CIDR inserts was reduced compared with untreated cows and cows treated with 1 CIDR insert.

Chemopreventive effects of pequi oil (Caryocar brasiliense Camb.) on preneoplastic lesions in a mouse model of hepatocarcinogenesis.

Pequi (Caryocar brasiliense Camb.), a fruit from Brazil's central region, was evaluated for its chemopreventive effects on preneoplastic liver lesions induced by the carcinogen diethylnitrosamine (DEN) in mice. BALB/c mice, 14 days of age, received an intraperitoneal injection at 10 µg/g of DEN. The mice received either of two doses of pequi oil (100 or 400 mg/kg) daily from the age of 30 days and were killed at the age of 189 days. Stereological parameters, including the volume density (Vv) and the total volume (Vtot) of the lesions (preneoplastic and adenomas), were measured and the expression of cytokeratins CK8/18 was evaluated. The total volume of lesions and adenomas was reduced by 51% in the group treated with the carcinogen and 400 mg/kg of pequi oil administered daily by an oral gavage for 25 consecutive weeks. In addition, some mice in this group did not develop lesions. Among the remaining preneoplastic lesions in this group, the number of remodelled profiles increased by 2.4-fold in the 400-mg pequi oil-treated mice relative to the 100-mg-treated mice. Our results show that pequi oil exerts a hepatoprotective effect against DEN-induced development of preneoplastic lesions and adenoma in mice and the potential for its use in the prevention of liver cancer.

Characterization of peripartum rumination and activity of cows diagnosed with metabolic and uterine diseases.

The objectives of the current experiment were to characterize the correlation among total serum Ca, nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHBA), and haptoglobin concentrations and daily rumination time (DRT) and activity of periparturient cows and to determine the association between periparturient events and peripartum DRT and activity. Holstein animals (nulliparous = 77, parous = 219) were enrolled in the experiment approximately 21 d before expected calving date. Cows were fitted with individual Heat Rumination Long Distance collars (HRLD, SCR Engineers Ltd., Netanya, Israel) from enrollment until approximately 21 ± 3 d postpartum. Blood samples collected weekly from enrollment to 21 d postpartum were used to determine concentrations of NEFA, BHBA, and haptoglobin. Blood samples collected within 72 h after calving were used to determine total serum Ca concentration. Subclinical ketosis was characterized by BHBA > 1,000 µmol/L in any sample, and subclinical hypocalcemia was characterized by Ca < 8.55 ng/dL within 72 h after calving. Cows were examined 1, 7 ± 3, and 14 ± 3 d postpartum for diagnosis of retained fetal membrane and metritis. Total Ca (r = 0.15), NEFA (r = -0.27), and haptoglobin (r = -0.18) concentrations were weakly correlated with DRT. Concentration of BHBA (r = -0.14) was weakly correlated with activity. Postpartum DRT was reduced among cows that delivered twins compared with cows that delivered singletons (437.9 ± 4.8 vs. 385.9 ± 17.1 min/d). Prepartum (465.8 ± 4.1 vs 430.8 ± 14.9 arbitrary units) and postpartum (536.5 ± 5.5 vs. 480.3 ± 19.4 arbitrary units) activity were reduced among cows that delivered twins compared with cows that delivered singletons. Delivery of stillborn calves was associated with reduced DRT prepartum (478.0 ± 5.9 vs. 417.0 ± 23.4 min/d) and postpartum (437.2 ± 4.8 vs. 386.5 ± 19.3 min/d). On the other hand, cows delivering stillborn calves had increased activity prepartum compared with cows delivering live calves (499.3 ± 16.2 vs. 461.3 ± 4.1 arbitrary unit). Occurrence of retained fetal membrane tended to and was associated with reduced prepartum (444.3 ± 11.0 vs. 466.5 ± 4.3 arbitrary unit) and postpartum (488.2 ± 14.5 vs. 538.8 ± 5.7 arbitrary unit) activity, respectively. Cows diagnosed with metritis had reduced postpartum DRT (415.9 ± 10.1 vs. 441.0 ± 5.2 min/d) and activity (512.5 ± 11.5 vs. 539.2 ± 6.0 arbitrary unit). Postpartum activity was reduced among cows that were diagnosed with subclinical ketosis (502.20 ± 16.5 vs. 536.6 ± 6.2 arbitrary unit). Although differences in DRT and activity between populations of cows that developed periparturient diseases and healthy cows were observed, further experiments are necessary to determine how DRT and activity data may be used to precociously diagnose individuals that will develop such periparturient diseases.

Cerebral tuberculomas in AIDS patients: a forgotten diagnosis?

The human immunodeficiency virus (HIV) infection epidemics increased the prevalence, multi-drug resistance and disseminated forms of tuberculosis. The central nervous system (CNS) tuberculosis has high mortality and morbidity, and it is usually divided into diffuse (meningitis) and localized (tuberculoma and abscess) forms. We report three cases of cerebral tuberculomas in AIDS patients: one with definitive diagnosis, confirmed with histopathology, and two with probable diagnosis, based on clinical information, radiological images, Mycobaterium tuberculosis isolation out of the CNS and adequate response to antituberculous treatment. Further, we discuss diagnostic, therapeutic and prognostic issues of tuberculomas, with emphasis in the distinction from cerebral tuberculous abscesses. Despite of their infrequent presentation, tuberculomas should be considered in the differential diagnosis of cerebral expansive lesions in patients with AIDS.

Cerebral tuberculomas in AIDS patients: a forgotten diagnosis?

A epidemia da infecção pelo vírus da imunodeficiência humana (HIV) aumentou a prevalência, multiresistência e formas disseminadas da tuberculose. O acometimento neurológico da tuberculose apresenta elevada morbidade e mortalidade, classificando-se em formas difusas (meningite) e localizadas (tuberculoma e abscesso). Relatamos três casos de tuberculomas cerebrais em pacientes com AIDS: um deles com diagnóstico definitivo, confirmado com histopatologia e dois com diagnóstico provável, baseado em informação clínica, radiológica, isolamento de Mycobaterium tuberculosis fora do sistema nervoso central e adequada resposta ao tratamento tuberculostático. Discutimos também aspectos diagnósticos, terapêuticos e prognósticos dos tuberculomas, enfatizando suas diferenças com os abscesos tuberculosos cerebrais. Apesar de serem relatados de forma infreqüente, os tuberculomas devem sempre ser considerados no diagnóstico diferencial das lesões expansivas cerebrais em pacientes com AIDS.

Tuberculous brain abscess in a patient with AIDS: case report and literature review.

Tuberculous brain abscesses in AIDS patients are considered rare with only eight cases reported in the literature. We describe the case of a 34-year-old woman with AIDS and previous toxoplasmic encephalitis who was admitted due to headache and seizures. A brain computed tomography scan disclosed a frontal hypodense lesion with a contrast ring enhancement. Brain abscess was suspected and she underwent a lesion puncture through a trepanation. The material extracted was purulent and the acid-fast smear was markedly positive. Timely medical and surgical approaches allowed a good outcome. Tuberculous abscesses should be considered in the differential diagnosis of focal brain lesions in AIDS patients. Surgical excision or stereotactic aspiration, and antituberculous treatment are the mainstay in the management of these uncommon lesions.

Liver abscess due to Salmonella enteritidis in a returned traveler with HIV infection: case report and review of the literature.

Bacteremia due to non-typhi Salmonella is more frequent in patients infected with the human immunodeficiency virus (HIV). However, focal complications have been rarely described. We report a case of liver abscess due to Salmonella enteritidis in an HIV-infected patient who recently returned to Sao Paulo, Brazil, from a trip in the Caribbean. A good clinical and radiological response was seen with both percutaneous catheter drainage and antibiotic treatment. To our knowledge, this is the first culture proven case of non-typhi Salmonellaliver abscess in an HIV-infected patient in Brazil.

Tuberculous brain abscess in a patient with AIDS: case report and literature review

Tuberculous brain abscesses in AIDS patients are considered rare with only eight cases reported in the literature. We describe the case of a 34-year-old woman with AIDS and previous toxoplasmic encephalitis who was admitted due to headache and seizures. A brain computed tomography scan disclosed a frontal hypodense lesion with a contrast ring enhancement. Brain abscess was suspected and she underwent a lesion puncture through a trepanation. The material extracted was purulent and the acid-fast smear was markedly positive. Timely medical and surgical approaches allowed a good outcome. Tuberculous abscesses should be considered in the differential diagnosis of focal brain lesions in AIDS patients. Surgical excision or stereotactic aspiration, and antituberculous treatment are the mainstay in the management of these uncommon lesions

Liver abscess due to Salmonella enteritidis in a returned traveler with HIV infection: case report and review of the literature

Bacteremia due to non-typhi Salmonella is more frequent in patients infected with the human immunodeficiency virus (HIV). However, focal complications have been rarely described. We report a case of liver abscess due to Salmonella enteritidis in an HIV-infected patient who recently returned to Sao Paulo, Brazil, from a trip in the Caribbean. A good clinical and radiological response was seen with both percutaneous catheter drainage and antibiotic treatment. To our knowledge, this is the first culture proven case of non-typhi Salmonellaliver abscess in an HIV-infected patient in Brazil

Magnetic resonance imaging study of pituitary morphology in subjects homozygous and heterozygous for a null mutation of the GHRH receptor gene.

OBJECTIVE: Somatotrophs represent the majority of cells in the anterior pituitary, and their numeric reduction can cause anterior pituitary hypoplasia (APH). Small numbers of patients with familial isolated GH deficiency (IGHD) due to bi-allelic mutations in the GHRH receptor (GHRHR) gene (GHRHR) have been reported to have APH. We tested if APH was present in a large cohort of patients homozygous and heterozygous for a GHRHR mutation. DESIGN: We studied pituitary morphology in adult and pediatric age subjects (8 years of age and older) belonging to a large extended Brazilian kindred with a high prevalence of IGHD due to a null GHRHR mutation. METHODS: We performed brain magnetic resonance imaging (MRI) in 38 subjects, divided into four groups: group I: normal adults (five males, four females, age 38+/-11.7 years); group II: heterozygous adults (six males, seven females, age 42.23+/-8.8 years); group III: homozygous GH-naive affected adults (three males, five females, age 41.4+/-15.0 years); group IV: homozygous affected children (three males, five females, age 11.9+/-2.5 years). Results are expressed as means+/-s.d. RESULTS: Pituitary height (mm) was not different between groups II and I (4.61+/-1.55 and 4.41+/-0.62 respectively), but it was significantly reduced in groups III (2.67+/-0.87, P<0.001) and IV (2.87+/-0.79, P<0.001) compared with group I. Pituitary volume (mm(3)) was normal in group II (417.12+/-140.86), but it was significantly reduced in groups III and IV (124.06+/-64.27 and 155.68+/-39.79 respectively vs 414.56+/-71.57; both P<0.001). The volume ratio (calculated by multiplying the pituitary volume by 1000 and dividing it by cranial volume) was significantly lower in the affected subjects (groups III and IV) (0.06+/-0.02) than in unaffected (groups I and II) (0.15+/-0.04; P<0.0001), demonstrating that APH is not due to reduction of cranial volume. CONCLUSIONS: APH is present from childhood in patients homozygous for an inactivating GHRHR mutation, but it does not occur in heterozygous subjects. In our cohort, the presence of normal anterior pituitary size by MRI rules out homozygosity for a GHRHR mutation in subjects who are 8 years of age or older.

Diagnóstico da deficiência de hormônio de crescimento, a rigor de IGF-1 / Diagnosis of growth hormone deficiency, in severity of IGF-1

O diagnóstico da deficiência de IGF-1 por anormalidade do eixo GH-IGF deve utilizar os parâmetros diagnósticos mais adequados para cada faixa etária e estágio puberal. Propomos o diagnóstico da deficiência de GH (DGH) baseado em uma hierarquia de dados clínicos e laboratoriais. A avaliaçäo clínica e os exames laboratoriais gerais, incluindo funçäo tireoideana, permitem excluir etiologias de deficiência de IGF que näo as intrínsecas ao eixo GH-IGF. Nestas, a dosagem do IGF-1 sérico deve ser o primeiro hormônio a ser dosado nos grupos pré-púberes, púberes e idosos. No grupo de adultos jovens, a dosagem do ALS livre é a mais adequada. As concentraçöes de IGF-1 podem caracterizar 4 situaçöes: muito reduzido, reduzido, normal e elevado. IGF-1 menor que 35pg/L ou -2 DP da média para a idade cronológica (EDP-IC) permite o diagnóstico de deficiência de IGF-1. Nesta situaçäo, a realizaçäo de apenas um teste de secreçäo de GH é necessária para diferenciar deficiência e resistência ao GH. O teste de geraçäo de IGF-1 ajuda a confirmar o diagnóstico de resistência ao GH. IGF-1 menor que 70Ng/L em pré-púberes ou adultos e menor que 170pg/L em indivíduos púberes, ou entre -2 e -1 EDP-IC indicam provável deficiência de IGF-1. A realizaçäo de 2 testes de secreçäo de GH é recomendada; resposta sub-normal em ambos indica DGH. Exame de imagem da regiäo hipotáiamo-hipofisária deve ser realizado nos casos de DGH. Resposta normal ao teste de secreçäo do GH frente à forte suspeita clínica e laboratorial de deficiência de IGF-1 indica a realizaçäo de perfil noturno de GH para afastar o diagnóstico de disfunçäo neurossecretora de GH. IGF-1 maior que -1 DP, mas menor que a média para idade cronológica sugere ausência de deficiência de IGF-1. Concentraçöes altas de IGF-1 impöem a dosagem das IGFBPs e consideraçäo da resistência ao IGF-1. Apesar das dificuldades, todo o esforço deve ser feito no sentido de diagnosticar adequadamente as alteraçöes do eixo GH-IGF para instituir a terapia apropriada.