Pituitary Stalk Thickening

MRI revealed enlargement of the pituitary stalk in two patients with different clinical presentations. A 60 y/o female had autoimmune hypothyroidism associated with blunted cortisol response to ACTH, while the other, a 30 y/o female had amenorrhea and polyuria with high plasma and low urinary osmolality.Fil: Arregger, Alejandro Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Cardoso, Estela M. del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Contreras, Liliana Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Benzidine staining: method to detect neutrophils in whole saliva of patients with renal disease

Benzidine staining allows for the quantification of peroxidise positive polymorphonuclear leukocytes in whole saliva from patients with renal disease. This is a practical tool for monitoring oral health in this high risk population.Fil: Cardoso, Estela M. del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Arregger, Alejandro Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Budd, D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Elverdín, Juan Carlos. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Tumilasci, G.. Universidad de Buenos Aires. Facultad de Odontología; ArgentinaFil: Contreras, Liliana Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología; Argentin

Standardization of a simple method to study whole saliva: clinical use in different pathologies.

En este trabajo se describe la normatización de un método para determinar flujo salival en humanos utilizando saliva total obtenida del piso de la boca mediante un eyector dental descartable y una bomba de vacío (equipo dental). En este estudio se evaluaron 40 sujetos sanos de ambos sexos y 51 pacientes con diversas patologías (Síndrome de Sjögren, Disfunción Tiroidea, Diabetes Mellitus). Se demostró que el flujo salival basal era estable a partir de los primeros 5 minutos de colocado el eyector en la cavidad bucal. No se encontraron diferencias significativas en el flujo salival basal comparando los sexos, siendo independiente de la intensidad del vacío efectuado por la bomba. El flujo de saliva total estimulada fue determinado durante 3 minutos, luego de los primeros 5 minutos de colocado el eyector en la boca. El estímulo se efectuó adosando en la cara dorsal de la lengua discos de papel absorbente, embebidos en ácido cítrico al 2 %. El uso de este método en pacientes con Síndrome de Sjögren confirmó la reducción del flujo salival respecto a los sujetos sanos. Los pacientes hipotiroideos y con neuropatía diabética demostraron disminución del flujo salival.The present study describes a methodology to assess the salivary flow rate in humans. Whole saliva was obtained from the floor of the mouth with a plastic dental ejector and a vacuum pump. Forty healthy subjects of both sexes and 51 patients with different pathologies (Sjögren Syndrome, Thyroid Dysfunction, Diabetes Mellitus) were included in the study. It was demonstrated that basal salivary flow rate was stable five minutes after the insertion of the oral ejector. Salivary flow rate did not show significant differences between sexes and was independent of the negative pressure level of the vacuum pump. Stimulated salivary flow rate was quantified over a period of 3 minutes, starting 5 minutes after the introduction of the oral device. The stimulus was paper filter disks soaked in citric acid (2%) placed on the tongue dorsum. The use of this method confirmed the reduction of salivary flow rate in patients with Sjögren Syndrome. In addition, a significant reduction in salivary flow rate was observed in patients with primary thyroid insufficiency and peripheral neuropathy secondary to Diabetes Mellitus.Fil: Tumilasci, Omar Rene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Cardoso, Estela M. del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Contreras, Liliana Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Belforte, Juan Emilio. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Arregger, Alejandro Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Ostuni, Mariano A.. Inserm; Franci

The Overnight 1mg Dexamethasone Test in Healthy Subjects with Normal Weight, Overweight and Obesity: a Multicentric Study

La prueba de supresión con dexametasona-1mg oral nocturna evalúa la conservación del mecanismo de retroalimentación negativa normal ejercido por los glucocorticoides sobre el eje hipotálamo-hipófiso-adrenal (HH-A), siendo ampliamente utilizada en el algoritmo diagnóstico de sospecha de síndrome de Cushing (SC). Pero la concentración de cortisol sérico matinal postinhibición que define la supresiblidad normal ha sido motivo de controversia, con valores variables desde el original ≤5 ug/dl (≤138 nmol/L) hasta una cifra ≤1,8 ug/dl (≤50 nmol/L) últimamente. Asimismo, es controvertida la respuesta en la obesidad, donde está descripta una alteración del eje H-H-A. Por lo tanto, el Departamento de Suprarrenal de SAEM llevó a cabo este estudio multicéntrico con el objetivo de definir la concentración de cortisol sérico obtenida luego de la administración de dexametasona 1mg nocturna, en una población de sujetos sanos de nuestro país con peso normal; concomitantemente, se evaluaron individuos con sobrepeso y con obesidad simple para comparar su respuesta respecto de los sujetos normopeso. Se estudiaron 80 individuos sanos, 60 mujeres y 20 hombres, de 15 a 66 años de edad, que fueron divididos en tres grupos según el índice de masa corporal (IMC): Normopeso, IMC=19-24,9 kg/m2, n=39; Sobrepeso, IMC=25-29,9 Kg/m2, n=21; y Obesos, IMC ≥ 30 kg/m2, n=20. Se administró dexametasona 1 mg vía oral a las 23 hs. y se determinó la cortisolemia a las 8hs. de la mañana siguiente. Las determinaciones se centralizaron en un solo laboratorio y fueron realizadas por el equipo de radioinmunoensayo (RIA) de DSL, sensiblidad analítica de 0,5 ug/dl. Paralelamente en 10 sujetos, se determinó la cortisolemia postinhibición en las mismas muestras con otro equipo analítico, RIA-DPC. Resultados: Los resultados de la cortisolemia postsupresión en los tres grupos estudiados se expresan como X± DS (rango): en el grupo normopeso fue de 2,10± 0,77 ug/dl (0,78-3,40); en el sobrepeso, 1,94± 0,66 ug/dl (0,96- 2,90); y en los obesos, 1,86 ± 0,63 ug/dl (0,85-3,30), no observándose diferencias significativas entre los tres grupos estudiados (test de Kruskall Wallis Dunn, p=0,319). En los 10 sujetos cuyas muestras fueron simultáneamente analizadas por RIA-DSL y por RIA-DPC, se observaron marcadas diferencias en 8/10, siendo la mediana de cortisol sérico obtenida por RIA-DPC de 0,5µg/dl, significativamente menor a la obtenida por RIA-DSL, de 2,2 µg/dl (test de Wilcoxon, p=0,002). Conclusiones: Debemos destacar que este es el primer estudio multicéntrico que evalúa la respuesta a la inhbibición con dexametasona 1 mg en nuestro medio. En esta primera etapa, demostramos que una concentración de cortisol sérico post 1 mg de dexametasona oral nocturna ≤ 3,4 µg/dl (≤ 93,8nmol/l), determinada por RIA-DSL, caracteriza la respuesta normal de nuestra población de sujetos sanos. Ello es independiente del peso corporal, ya que los sujetos con normopeso, sobrepeso y obesidad suprimieron a valores similares. No se observó falta de supresión en ningún caso estudiado. Por otra parte, dadas las marcadas diferencias de valores halladas en las mismas muestras cuando son analizadas por equipos diferentes de RIA, es fundamental referir los resultados al método y equipo utilizados y estandarizar las pruebas clínicas con la metodología específica empleada en cada laboratorio.The overnight oral dexamethasone test assesses the normal negative feedback of cortisol on the hypothalamic-pituitary-adrenal axis (H-P-A) 1. It is widely used in the screening of Cushing’s Syndrome (CS) 3,4,5. But the cut-off values for the normal response remains controversial: originally it was considered as 5 ug/dl and in the last years it was reported as 1.8 ug/dl 4. Likewise, there is no agreement about the suppression values in obesity, where a hyperactivity of the H-P-A axis has been reported. Therefore, the Adrenal Department of the Argentine Society of Endocrinology and Metabolism (SAEM) studied 80 healthy subjects recruited from ten hospitals of Buenos Aires in order to assess the normal response in our population. Sixteen women and twenty men, aged 15-66 years old (X = 39.2ys), were classified into three groups, according to their body mass index (BMI): normal weight, BMI- 19-24.9 kg/m2 (n= 39); overweight, BMI- 25-29.9 kg/m2 (n=21) and obese subjects, BMI> 30 kg/m2 (n=20). They had to be euthyroid and free of corticosteroid treatment, contraceptive pills, hormone replacement therapy, rifampicin and psychotropic drugs at the time of the study. Subjects referring drug abuse, alcoholism, depression, cardiovascular, and renal disorders and,obviously, adrenal diseases were excluded from the study. Dexamethasone 1mg per os was administered at 11p.m. and blood was withdrawn at 8 a.m. on the next morning to determine plasma cortisol concentration. Determinations were centralized in one laboratory and the RIA-DSL (Diagnostic System Laboratories-radioimmunoassay) was used. Additionally, in ten subjects plasma cortisol was also determined in the same blood samples by another radioimmunoassay kit, RIA-DPC (Diagnostic Products Corporation). The Kruskall-Dunn test was used to compare the plasma cortisol levels post-1mg dexamethasone among the three groups studied. In the 10 patients whose determinations were made in the same blood samples by two different RIA-kits (DSL and DPC),the Wilcoxon test was used to compare the results of plasma cortisol between RIA-DSL and RIA-DPC. Results: The results are expressed as X ± SD ug/dl (range). Plasma cortisol levels after 1mg-dexamethasone were: 2.10 ± 0.77 ug/dl ( 0.78- 3.40 ug/dl) in the normal weight goup; 1.94 ± 0.66 ug/dl (0.96-2.90) in the overweight group and 1.86 ± 0.63 ug/dl (0.85-3.30) in the obese subjects (Table I); no significant differences were observed among the three groups (p=0.319). According to these results, the cut-off value for plasma cortisol post-dexamethasone in the normal weight subjects was considered as ≤ 3.4 ug/dl (93.8 nmol/L) using RIA-DSL. Similar suppression values were obtained in the overweight and obese subjects - 2.9 and 3.3 ug/dl, respectively. No false positive results were observed, either individually or in each group (Fig 1). In the 10 subjects whose blood cortisol was simultaneously determined in the same samples by RIA-DSL and RIA-DPC, the median for plasma cortisol was 2.2 ug/dl for the first and 0.5 ug/dl for the latter, respectively, with a significant difference between both RIA kits (p=0.002). (Table II). Conclusions: In this first stage, the present multicentric study shows that a plasma cortisol level post - 1mg dexamethasone suppression of ≤ 3.4 ug/dl ( 93.8 nmol/L) defines our normal population response, with no significant differences among normal weight,overweight and obese subjects. Furthermore, we wish to point out that the cortisol values must be referred to the method and commercial kits used in each laboratory, since significant differences can be observed in the same blood samples when different kits are used, such as we and other authors have observed. We wish to remark the importance of our study, which is the first in its characteristics in Argentina. Furthermore, in a second stage, we plan to enlarge the sample number and to determine blood cortisol in the same samples by using different methods, in order to obtain a standardized cortisol suppression level. We also plan to study patients with confirmed CS and pseudocushing states in order to assess the sensitivity and specificity of the 1mg-dexamethasone suppression test in our population.Fil: Pardes, Ester. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Belli, Susana Haydee. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Agudos Carlos Durand.; ArgentinaFil: Baña, Fabiana. Hospital Central de San Isidro Dr. Melchor Ángel Posse; ArgentinaFil: Contreras, Liliana Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Cardoso, Estela M. del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Costa, Liliana Teresa. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Cornaló, Dora. Hospital General de Agudos Bernardino Rivadavia; ArgentinaFil: Leal, Mariela. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Martínez, Marcela. Unidad Asistencial "Dr. César Milstein"; ArgentinaFil: Nofal, María Teresa. Clínica Bazterrica; ArgentinaFil: Ruibal, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; Argentin

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Assessment of Corticoadrenal Reserve Through Salivary Steroids

Recent reports have reinforced the usefulness of salivary cortisol (SAF) in the evaluation of cortisol dynamics and the diagnosis of Cushing syndrome. However few data are available on the usefulness of SAF and salivary aldosterone (SAL) in response to corticotrophin (ACTH) stimulus. The aim of the authors ‘ study was to standardize the response of SAF and SAL to the intramuscular injection of 250 mg of synthetic human ACTH in 21 healthy patients. Salivary samples were obtained in baseline conditions and during 30,60,90,120 minutes after ACTH administration. The results showed that all healthy  volunteers achieved SAF and SAL concentrations of at least 40.0 nmol/L and 100.0 pmol/L , respectively , after the stimulus. The clinical usefulness of this test was confirmed when patients with known adrenal dysfunction were studied. In three patients with primary adrenal insufficiency, blunted SAF and SAL responses were obtained. Six patients with secondary adrenal insufficiency demonstrated subnormal or blunted SAF and normal SAL responses after ACTH stimulation. Corticoadrenal reserve can be easily , noninvasively, and accurately investigated through the simultaneous measurement of salivary cortisol and aldosterone in response to corticotrophin. Salivary aldosterone was helpful in the differential diagnosis of adrenocortical hypofunction.Fil: Cardoso, Estela M. del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Persi, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Arregger, Alejandro Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Contreras, Liliana Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Diagnostic value of salivary cortisol in Cushing's syndrome (CS)

Objective: The diagnosis of Cushing's syndrome (CS) remains a challenge in clinical endocrinology. The aim of this study was to determine the reproducibility and diagnostic value of late‐night salivary cortisol (SAF23) for CS and its utility along the follow‐up of treated patients. In addition, using the same radioimmunoassay reactives, the cut‐off values for saliva and serum cortisol, assessed synchronically after the overnight 1 mg dexamethasone suppression test (DST), were defined. Design: Twenty‐one patients with confirmed CS and 121 volunteers were studied. All the subjects collected 24‐h urine for cortisol (UFC). On the same day whole saliva was obtained from the subjects at 23 h for SAF23. The intraclass coefficient of correlation (ICC) of SAF23 was estimated in 47 subjects (21 CS and 26 C). At 8 h, after DST, simultaneous saliva and serum samples for cortisol (SAFdex and Fdex, respectively) were obtained in 51 subjects (17 CS and 34 C). After specific therapy, 18 patients with CS were followed with SAF23 measurements. SAF and F were expressed as nm. Results: The intraclass coefficient of correlation of SAF23 was 0·89 in CS and 0·83 in C. SAF23 > 3·8 nm showed a sensitivity and specificity of 100% and 97·5%, respectively, for diagnosing CS. SAF23 correlated positively with UFC (r = 0·685; P = 0·0001). After DST, SAFdex significantly correlated with Fdex (r = 0·61, P 2·0 nm and Fdex > 50·0 nm detected CS with 100% sensitivity and specificity. After successful surgical therapy, 13 patients with CS had SAF23 levels < 3·8 nm (1·4 ± 0·8 nm). Conclusions: SAF23 and SAFdex seem to be good screening tools based on their noninvasive nature, remarkable reproducibility and diagnostic performances.Fil: Cardoso, Estela M. del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Arregger, Alejandro Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tumilasci, Omar Rene. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Contreras, Liliana Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Diagnostic value of salivary cortisol in end stage renal disease

Objectives: Salivary cortisol has been proposed a surrogate marker for free serum cortisol measurements. The aim of this study was to ascertain the diagnostic value of basal and stimulated salivary cortisol for the detection of adrenal insufficiency (AI) in hypotensive end stage renal disease (ESRD) patients. Basal salivary cortisol and basal total serum cortisol were studied in order to determine the accuracy of both biomarkers in predicting AI. Patients and methods: Twenty-nine ESRD patients with sustained hypotension were investigated for possible AI. Salivary cortisol was assessed at baseline and 30 min after 25 μg ACTH i.m. (LDTs). The dosage of salivary aldosterone was performed in salivary cortisol hypo-responders. Basal blood samples were drawn for steroids, renin and ACTH measurements. Results: A clear separation between patients with normal and impaired adrenal function was obtained through salivary cortisol levels at 30 min after ACTH. AI was detected in six cases (21%) through impaired salivary cortisol responses; stimulated salivary aldosterone helped to differentiate primary (n = 3) from secondary AI (n = 3). ROC curves showed that cutoff values for basal SAF ≤4.4 nM and serum cortisol ≤232.0 nM suggest AI (sensitivities: 93% and 69%; specificities: 86.4% and 91%, respectively). Conclusions: We conclude that ACTH stimulated SAF is an accurate biomarker for the diagnosis of AI in hypotensive ESRD patients. Neither basal salivary cortisol nor serum cortisol showed 100% sensitivities for the detection of AI.Fil: Arregger, Alejandro Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cardoso, Estela M. del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Tumilasci, Omar Rene. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Contreras, Liliana Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

A new less-invasive and more informative low-dose ACTH test: salivary steroids in response to intramuscular corticotrophin

Objective: The intravenous low‐dose ACTH test has been proposed as a sensitive tool to assess adrenal function through circulating steroids. The aims of this study were to: (a) find the minimal intramuscular ACTH dose that induced serum and salivary cortisol and aldosterone responses equivalent to those obtained after a pharmacological dose of ACTH; and (b) define the minimum normal salivary cortisol and aldosterone responses in healthy subjects to that dose of ACTH. We also compared the performances of the standard‐ and low‐dose ACTH intramuscular tests to screen patients with known hypothalamo–pituitary–adrenal impairments. Design: Rapid ACTH tests were performed in individuals using various intramuscular doses (12·5, 25 and 250 µg) at 2‐week intervals. Subjects: Twenty‐one healthy volunteers and 19 patients with primary (nine cases) and secondary (10 cases) adrenal insufficiency. Measurement: Serum and salivary cortisol and aldosterone concentrations were measured at baseline and after ACTH. Serum cortisol ≥ 552·0 nmol/l and aldosterone ≥ 555·0 pmol/l concentrations at 30 min after 250 µg of ACTH were defined as normal responses. Results: In healthy volunteers cortisol and aldosterone responded to ACTH in a dose‐dependent manner. The time to peak in saliva for each steroid was delayed as the dose of ACTH increased. The minimum ACTH dose that produced equivalent steroid responses at 30 min to 250 µg of ACTH (standard‐dose test; SDT) was 25 µg (low‐dose test; LDT). Saliva collection 30 min after LDT and SDT showed cortisol and aldosterone concentrations of at least 20·0 nmol/l and 100·0 pmol/l, respectively. These values were defined as normal steroid responses. Blunted salivary steroid responses to LDT and SDT were found in all patients with primary adrenal insufficiency. Subnormal salivary cortisol levels in response to LDT and SDT were found in all patients with secondary adrenal insufficiency. In five patients full recovery of adrenal function was demonstrated by both tests after steroid withdrawal. In the follow‐up of four patients studied during the recovery period, subnormal SAF response after LDT and normal after SDT was demonstrated. Preservation of the adrenal glomerulosa was found in all the patients with secondary adrenal insufficiency through the normal rise in salivary aldosterone after both LDT and SDT. Conclusions: Adrenal function can be accurately investigated with simultaneous measurements of salivary cortisol and aldosterone in response to 25 µg of corticotrophin injected into the deltoid muscle. Our data suggest that this may become a useful and relatively noninvasive clinical tool to detect subclinical hypoadrenal states.Fil: Contreras, Liliana Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Arregger, Alejandro Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Persi, Gabriel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Gonzalez, Soledad Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Cardoso, Estela M. del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Salivary testosterone: a reliable approach to the diagnosis of male hypogonadism

Summary Objetive The purpose of this study was to demonstrate that Sal-T is a reliable biomarker of androgen status in the diagnosis of male hypogonadism. Design In order to validate the salivary testosterone assay (Sal-T), its reproducibility , the agreement with serum free testosterone levels (Free-T) , the correlation with other circulating androgen markers ( bioavailable testosterone , total testosterone) and  cut off values were defined. Patients and Methods We studied 52 eugonadic (E) and 20 hypogonadic (Hy) men. Sal-T was assayed using an adapted radioimmunoassay for serum testosterone. Sal-T concentrations were compared in 9 cases before and after citric acid stimulation of salivary flow-rate.  Free-T and bioavailable testosterone (Bio-T) were calculated by Vermeulen equation  and SHBG were determined by binding assay. Results Sal-T did not depend on  salivary flow-rate and morning samples from 7.00 to 9.00 h were stable. Agreement between Sal-T and Free-T measurements was confirmed in all subjects .  Sal-T levels correlated positively with  all circulating androgens , showing the best correlation with Free-T in E (r=0.92) as well as in Hy (r=0.97).A cutoff value  for Sal-T  £ 0.195 nM  showed 100% of sensibility and specificity to rule out hypogonadism. Conclusions Our data showed  that Sal-T is a reliable marker of testosterone bioavailability. The results support the inclusion of this biomarker as a non invasive approach in the diagnosis of male androgen deficiency.Fil: Arregger, Alejandro Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Contreras, Liliana Noemí. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Tumilasci, Omar Rene. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aquilano, Daniel R. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Cardoso, Estela M. del Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin