Screening for primary aldosteronism in an argentinian population: a multicenter prospective study

Objectives Primary aldosteronism (PA) is characterized by the autonomous overproduction of aldosterone. Its prevalence has increased since the use of the aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off values (COV) and their diagnostic concordance (DC%) in the screening for PA in an Argentinian population.Design multicenter prospective study.Subjects and methods We studied 353 subjects (104 controls and 249 hypertensive patients). Serum aldosterone, PRA and ARR were determined. In 220 randomly selected subjects, 160 hypertensive patients and 60 controls, plasma renin concentration (PRC) was simultaneously measured and ARC was determined.Results According to the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for ARC, with ALD ≥ 15 ng/dL. In 31/249 hypertensive patients, ARR was ≥ 36. PA diagnosis was established in 8/31 patients (23/31 patients did not complete confirmatory tests). DC% between ARR and ARC was calculated. A significant correlation between ARR and ARC (r = 0.742; p < 0.0001) was found only with PRA > 0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was 79.1%, respectively.Conclusion This first Argentinian multicenter study determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR ≥ 36 in the hypertensive group, we confirmed PA in a higher percentage of patients than the previously reported one in our population. As for ARC, further studies are needed for its clinical application, since DC% is acceptable only for medium range renin values.

Screening for primary aldosteronism in an argentinian population: a multicenter prospective study.

OBJECTIVES: Primary aldosteronism (PA) is characterized by the autonomous overproduction of aldosterone. Its prevalence has increased since the use of the aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off values (COV) and their diagnostic concordance (DC%) in the screening for PA in an Argentinian population.Design multicenter prospective study. SUBJECTS AND METHODS: We studied 353 subjects (104 controls and 249 hypertensive patients). Serum aldosterone, PRA and ARR were determined. In 220 randomly selected subjects, 160 hypertensive patients and 60 controls, plasma renin concentration (PRC) was simultaneously measured and ARC was determined. RESULTS: According to the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for ARC, with ALD ≥ 15 ng/dL. In 31/249 hypertensive patients, ARR was ≥ 36. PA diagnosis was established in 8/31 patients (23/31 patients did not complete confirmatory tests). DC% between ARR and ARC was calculated. A significant correlation between ARR and ARC (r = 0.742; p < 0.0001) was found only with PRA > 0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was 79.1%, respectively. CONCLUSION: This first Argentinian multicenter study determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR ≥ 36 in the hypertensive group, we confirmed PA in a higher percentage of patients than the previously reported one in our population. As for ARC, further studies are needed for its clinical application, since DC% is acceptable only for medium range renin values.

Adrenocortical function in hypotensive patients with end stage renal disease.

BACKGROUND: Sustained hypotension among patients with end stage renal disease on dialysis (ESRDh) varies from 5.0% to 12.0%. Despite their role in the regulation of blood pressure (BP) corticoadrenal hormones have been poorly investigated. OBJECTIVES: This study aims to detect adrenal insufficiency in ESRDh and follow their clinical outcome. METHODS: Fifty ESRDh and 30 healthy volunteers were studied. In all cases basal blood and saliva were obtained. Synthetic ACTH (25µg) was injected intramuscularly and at 30min saliva was collected. Circulating ACTH, renin, cortisol and aldosterone were measured and steroids were also assessed in saliva by immunoassay. RESULTS: Fifteen ESRDh achieved steroid responses not different than healthy volunteers; four had primary adrenal insufficiency; six had secondary adrenal insufficiency; nine had selective hypoaldosteronism and sixteen secondary hyperaldosteronism. The years on dialysis did not differ among subgroups. ROC analysis defined the following cut-offs for basal cortisol to predict adrenal insufficiency: in serum ⩽232.0nM (sensitivity (S) 100.0% and specificity (E) 90.0%); in saliva ⩽4.4nM (100.0% S and E). Basal aldosterone cut-off values to predict hyperaldosteronism were: in serum >500.0pM and saliva >60.0pM (100.0% S and E, for both). For the prediction of hypoaldosteronism the basal serum aldosterone was ⩽260.0pM (100% S; 53% E) and in saliva it was ⩽20.1pM (100% S; 58.5% E). Three patients with primary adrenal insufficiency and six with secondary adrenal insufficiency improved general clinical condition and normalized BP on steroids. One patient died before initiation of steroid therapy. CONCLUSION: Adrenal function should be assessed in ESRDh in order to unmask adrenal insufficient states.

Hormonal secretion and quality of life in Nelson syndrome and Cushing disease after long acting repeatable octreotide: a short series and update.

Clinical management of persistent adrenocorticotropin hormone (ACTH) excess in Nelson syndrome (NS) and Cushing disease (CD) remains a challenge. Somatostatin and its analogs as octreotide decrease ACTH secretion through somatostatin receptors of pituitary cells. To our knowledge, there are no reports on the effect of long-acting repeatable octreotide (oct-lar) on hormonal secretion and quality of life in patients with NS and CD who failed conventional therapy. Herein, we describe the effects of treatment with oct-lar (20 mg/month intramurally) in 1 woman with NS and 2 women with persistent CD. Oct-lar therapy reduced ACTH secretion and improved the quality of life in NS patient. By contrast, in CD patients, it failed to control ACTH and cortisol secretion, and the quality of life remained unchanged.

An accurate, non-invasive approach to diagnose Cushing's syndrome in at-risk populations.

BACKGROUND: The prevalence of Cushing's syndrome (CS) in at-risk populations in developing countries remains uncertain. Evening urinary cortisol (UFC(22-23)) and salivary cortisol after treatment with 1-mg DST (SAFdex) have seldom been used as diagnostic tools in these populations. OBJECTIVES: (1) To establish the prevalence of CS in adults with cortisol-related morbidities using UFC22-23 and SAFdex as markers along with all first-line diagnostic tests recommended for CS; and (2) to assess the performance of each test and define a non-invasive diagnostic approach for CS in at-risk outpatient subjects. METHODS: A total of 128 outpatients were evaluated, including type 1 and 2 diabetic patients with poor metabolic control (DM1 and DM2), hypertensive subjects with central obesity (HBP) and premenopausal women with osteoporosis (OS). Controls included 100 healthy volunteers and 23 patients with CS. Total urinary cortisol (UFC), UFC(22-23), late-night salivary cortisol (SAF23) and suppression of cortisol levels in saliva (SAFdex) and serum (Fdex) after treatment with 1-mg DST were assessed. RESULTS: CS was diagnosed in one DM2 and one HBP patient; both women exhibited central obesity. Among CS patients, UFC showed more within-person variability than UFC(22-23) or SAF23. UFC(22-23) and SAF23 were positively and significantly correlated in all groups (r > or = 0.70; p < or = 0.0001). UFC(22-23) > 44.0 ng/mg creatinine or SAF23 > 3.8 nM were 100% sensitive (S) and specific (E) for CS. Furthermore, SAFdex > 2.0 nM or Fdex > 50.0 nM were 100% S and 97.3% E for CS. CONCLUSION: CS was diagnosed in 1.5% of at-risk patients. The combination of UFC(22-23) or SAF23 with SAFdex offers a non-invasive diagnostic tool to assess cortisol nadir and feed-back status in outpatients.

Salivary testosterone for the diagnosis of androgen deficiency in end-stage renal disease.

BACKGROUND: Hypogonadism is frequent in patients with end-stage renal disease (ESRD). Salivary testosterone (Sal-T) is a non-invasive tool to screen androgen deficiency in adult male with normal renal function. However, available data on its utility in ESRD are not conclusive. OBJECTIVES: The objectives of the study were: (i) to compare free testosterone fractions in saliva (SAL-T) and serum (Free-T); (ii) to establish the correlation of Sal-T with circulating total (TT) and bioavailable testosterone (Bio-T); (iii) to detect androgen deficiency through Sal-T; (iv) to determine the correlation of Sal-T with clinical parameters. METHODS: The study included: 60 adult ESRD men on haemodialysis (20-60 years old) with decreased libido referred from two dialysis centres; 112 eugonadic and 40 hypogonadic adult men with normal renal function as controls. Simultaneous morning saliva and serum samples were obtained for testosterone measurements by liquid RIA (SAL-T; TT). Free-T and Bio-T were calculated by the Vermeulen equation. RESULTS: Sal-T (0.338±0.177 nM) and Free-T (0.338±0.165 nM) did not differ (P>0.900) in ESRD as well as in control (0.337±0.182 and 0.337±0.172 nM, respectively; P>0.900). Sal-T levels correlated positively (P<0.0001) with Free-T (r=0.95), TT (r=0.80) and Bio-T (r=0.76) in ESRD. Sal-T negatively correlated with age and years on dialytic therapy. Sal-T showed 100% sensitivity and specificity to differentiate patients with androgen deficiency (22%) from those with normal androgen levels (78%). Hypogonadism was hypergonadotrophic in 69% cases and hypogonadotrophic in 31%. CONCLUSIONS: These data demonstrate the value of morning Sal-T testing as a non-invasive approach to screen androgen status in ESRD patients.

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 (SAF(23)) 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 SAF(23). The intraclass coefficient of correlation (ICC) of SAF(23) was estimated in 47 subjects (21 CS and 26 C). At 8 h, after DST, simultaneous saliva and serum samples for cortisol (SAF(dex) and F(dex), respectively) were obtained in 51 subjects (17 CS and 34 C). After specific therapy, 18 patients with CS were followed with SAF(23) measurements. SAF and F were expressed as nM. RESULTS: The intraclass coefficient of correlation of SAF(23) was 0.89 in CS and 0.83 in C. SAF(23) > 3.8 nM showed a sensitivity and specificity of 100% and 97.5%, respectively, for diagnosing CS. SAF(23) correlated positively with UFC (r = 0.685; P = 0.0001). After DST, SAF(dex) significantly correlated with F(dex) (r = 0.61, P < 0.0001). A cut-off value of SAF(dex) > 2.0 nM and F(dex) > 50.0 nM detected CS with 100% sensitivity and specificity. After successful surgical therapy, 13 patients with CS had SAF(23) levels < 3.8 nM (1.4 +/- 0.8 nM). CONCLUSIONS: SAF(23) and SAF(dex) seem to be good screening tools based on their noninvasive nature, remarkable reproducibility and diagnostic performances.

Assessment of salivary urea as a less invasive alternative to serum determinations.

OBJECTIVE: Experimental studies describe how urea is excreted through salivary glands and correlates with serum levels independently of salivary flow rate. This study confirms that salivary urea (SaU) is a reliable biomarker of uraemic state. In order to validate the SaU methodology, the following factors were taken into account: the independence of urea levels from saliva flow rate in healthy subjects and patients with chronic renal failure and the agreement between SaU and serum urea (U) levels in the entire population. In addition, reference intervals and cut-off values for SaU and U were established. MATERIAL AND METHODS: Urea levels were determined in 268 matched whole saliva (SaU) and serum (U) samples obtained simultaneously from 78 healthy individuals and 154 patients with chronic renal failure. A serum enzymic colorimetric assay was adapted to SaU determinations. RESULTS: SaU was independent of salivary flow rate. The agreement between SaU and U was confirmed by Bland-Altman analysis with a significant correlation between them (r = 0.91, p = 0.0001). The reference interval of SaU ranged from 1.66 to 7.5 mM. The cut-off values for SaU and U were 7.5 mM and 8.2 mM, respectively (sensitivity and specificity 100% for both). CONCLUSIONS: SaU testing is harmless and useful for ruling out azotemic states in outpatients. Our results support the inclusion of SaU as a diagnostic test in the clinical laboratory.

Effect of translocator protein (18 kDa)-ligand binding on neurotransmitter-induced salivary secretion in rat submandibular glands.

BACKGROUND INFORMATION: TSPO (translocator protein), previously known as PBR (peripheral-type benzodiazepine receptor), is a ubiquitous 18 kDa transmembrane protein that participates in diverse cell functions. High-affinity TSPO ligands are best known for their ability to stimulate cholesterol transport in organs synthesizing steroids and bile salts, although they modulate other physiological functions, including cell proliferation, apoptosis and calcium-dependent transepithelial ion secretion. In present study, we investigated the localization and function of TSPO in salivary glands. RESULTS: Immunohistochemical analysis of TSPO in rat salivary glands revealed that TSPO and its endogenous ligand, DBI (diazepam-binding inhibitor), were present in duct and mucous acinar cells. TSPO was localized to the mitochondria of these cells, whereas DBI was cytosolic. As expected, mitochondrial membrane preparations, which were enriched in TSPO, exhibited a high affinity for the TSPO drug ligand, (3)H-labelled PK 11195, as shown by B(max) and K(d) values of 10.0+/-0.5 pmol/mg and 4.0+/-1.0 nM respectively. Intravenous perfusion of PK 11195 increased the salivary flow rate that was induced by muscarinic and alpha-adrenergic agonists, whereas it had no effect when administered alone. Addition of PK 11195 also increased the K(+), Na(+), Cl(-) and protein content of saliva, indicating that this ligand modulated secretion by acini and duct cells. CONCLUSIONS: High-affinity ligand binding to mitochondrial TSPO modulates neurotransmitter-induced salivary secretion by duct and mucous acinar cells of rat submandibular glands.

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 30min after 25microg 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 30min 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 < or =4.4nM and serum cortisol < or =232.0nM 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.

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

OBJECTIVE: 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 nine 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 07.00 h to 09.00 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 cut-off value of Sal-T < or = 0.195 nm showed 100% 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 noninvasive approach in the diagnosis of male androgen deficiency.

Assessment of adrenal function by measurement of salivary steroids in response to corticotrophin in patients infected with human immunodeficiency virus.

OBJECTIVE: Adrenal insufficiency has been reported among critically ill HIV-infected patients. This is the first study that attempts to detect subclinical hypoadrenal states in non-critical HIV patients through salivary steroids in response to intramuscular low-dose ACTH injection. PATIENTS AND METHODS: We studied 21 ambulatory adult HIV-infected patients without specific clinical signs or symptoms of adrenal insufficiency. Normal salivary flow-rate and salivary alpha-amylase activity confirmed adequate salivary gland function. Salivary cortisol (SAF) and salivary aldosterone (SAL) were obtained at baseline and 30 min after the injection of 25 microg of ACTH in the deltoid muscle (LDT(s)). Assessment of salivary steroids after stimulation with 250 microg of intramuscular ACTH (HDT(s)) was performed on those who hyporesponded to LDT(s). Basal blood samples were drawn for steroids, renin and ACTH measurements. RESULTS: At baseline SAF and SAL correlated significantly (p=0.0001) with basal serum cortisol and aldosterone (r=0.70 and 0.91, respectively). Plasma ACTH and renin concentrations were within the normal range in all patients. Eight of the twenty-one HIV(+) patients were LDT(s) hyporesponders in either SAF (n:1) or SAL (n:7). LDT(s) repeated in six cases after a year reconfirmed the impairment of aldosterone secretion. LDT(s) hyporesponders had normal steroid responses to HDT(s). CONCLUSIONS: LDT(s) is a simple, safe, well-accepted and non-invasive approach to assess adrenal function in HIV-infected ambulatory patients. It revealed subnormal cortisol (5%) and aldosterone responses (33%) when HDT(s) results were normal.

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

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 Sjiigren Syndrome. In addition, a significant reduction in salivary flow rate was observed in patients with primary thyroid insufficiency and peripheral neurpathy secondary to Diabetes Mellitus.

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

En este trabajo se describe la normatización de un método paradeterminar 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 Sjõgren, 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 intensidaddel 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 por ciento. El uso de este método en pacientes con Síndrome de Sjõgrenconfirmó 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.

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

En este trabajo se describe la normatización de un método paradeterminar 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 Sj§gren, 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 intensidaddel 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 por ciento. El uso de este método en pacientes con Síndrome de Sj§grenconfirmó la reducción del flujo salival respecto a los sujetos sanos. Los pacientes hipotiroideos y con neuropatía diabética demostraron disminución del flujo salival (AU)

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 (Sj÷gren 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 Sj÷gren 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.(AU)

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 microg) 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 > or = 552.0 nmol/l and aldosterone > or = 555.0 pmol/l concentrations at 30 min after 250 microg 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 microg of ACTH (standard-dose test; SDT) was 25 microg (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 microg 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.

Alteraciones de la función tiroidea producidas por la amiodarona / Changes of thyroid function induced by amiodarone

Se estudiaron los efectos de la amiodarona sobre la secreción tiroidea de tiroxina (T4) y su metabolismo periférico, en 8 pacientes crónicos (200-800mg amiodarona/día durante 1-5 años) y en 5 sujetos normales (400mg/día, 5-8 días). Cada sujeto recibió por vía iv 150uCi de 125I-T4, obteniéndose luego muestras diarias de sangre durante 8 días. El estudio agudo en sujetos normales fue precedido de un estudio control sin amiodarona, en tanto que en los pacientes crónicos la investigación finalizó al octavo día de la inyección del radioisótopo. La pendiente de secreción tiroidea se obtuvo de la relación 127I-T4 en cada muestra de suero, mientras que la cinética periférica de 125I-T5 se determinó a partir de la curva de regresión plasmática de PB125I-T4. En los 8 pacientes crónicos, la pendiente tiroidea fue de 0,063ñ0,033 (DS) versus 0,110ñ0,030 en los normales (NS). La fracción de recambio de la T4 fue del 70% (p<0,005), la depuración metabólica 80% (p<0,05) y la degradación 79% (NS) del respectivo valor en sujetos normales. En el estudio agudo la amiodarona no produjo alteraciones significativas de estos parámetros, aunque se observó un aumento de la T4 sérica (p<0,05) y de la T3 reversa (p<0,005) y un descenso no significativo de la T3 sérica. La TSH sérica basal estuvo levemente aumentada (NS) pero la respuesta al TRH disminuyó (NS). Se concluye que la amiodarona tiene una acción moderadamente depresora de la función tiroidea (AU)