RESUMEN
OBJECTIVE: The purpose of this study was to evaluate the direct action of desmopressin (agonist of vasopressin) on the hypophysis and the three zones of the adrenal cortex in patients with different forms of hypercortisolism. DESIGN: Forty-three patients with hypercortisolism-21 with Cushing's disease (14 females, 7 males), 11 with extrapituitary, ectopic tumours (5 females, 6 males), and 11 with ACTH-independent Cushing's syndrome (6 females, 5 males)-were evaluated. The response of the pituitary and adrenal glands was assessed by measuring plasma levels of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, and dehydroepiandrosterone sulfate (DHEAS) at baseline and at 15, 30, 60, 90, and 120 min after the administration of desmopressin. RESULTS: We observed two main modes of secretory response: (1) elevation of the ACTH level followed by a rise of one, two or all three adrenal steroids, and (2) ACTH-independent elevation of adrenal steroids in various combinations. CONCLUSION: In a number of patients with hypercortisolism, the adrenal cortex responded to desmopressin administration by enhanced synthesis and secretion of glucocorticoids (cortisol), mineralocorticoids (aldosterone), and adrenal androgens (DHEAS) without a concomitant rise in ACTH. These findings suggest the presence of "ectopic" vasopressin receptors in the human adrenal cortex.
Asunto(s)
Corticoesteroides/sangre , Corteza Suprarrenal/efectos de los fármacos , Hormona Adrenocorticotrópica/sangre , Síndrome de Cushing/metabolismo , Desamino Arginina Vasopresina/farmacología , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Corteza Suprarrenal/metabolismo , Adulto , Aldosterona/sangre , Ritmo Circadiano , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiología , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Humanos , Hidrocortisona/sangre , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/metabolismo , Factores de TiempoRESUMEN
OBJECTIVE: To evaluate the effects of subclinical hyperthyroidism of variable etiology on bone mineral density (BMD) and bone metabolism in postmenopausal women. DESIGN: T he study included data of 88 postmenopausal women classified into four groups depending on the etiology of subclinical hyperthyroidism: (1) 20 with toxic multinodular goiter without history of clinical hyperthyroidism; (2) 25 on levothyroxine suppressive therapy after thyroidectomy due to differentiated thyroid cancer; (3) 21 with Graves' disease (GD) receiving antithyroid drugs; (4) 22 healthy women matched for age and duration of menopause. In all subjects biochemical markers of bone turnover and B MD were determined. RESULTS: Biochemical markers of bone turnover were significantly higher (p-value =0.001) in all patients with subclinical hyperthyroidism compared to the control group (group 4). T he women of group 1 had significantly lower B MD at all regions of the skeleton, whereas the women of group 3 had significantly lower B MD at Total Hip (p-value = 0.013) and Radius Total (p-value = 0.0003) compared to group 4. No significant differences in B MD between groups 2 and 4 were detected. CONCLUSION: The etiology of subclinical hyperthyroidism influences B MD in postmenopausal women. Endogenous subclinical hyperthyroidism might be considered as an additional risk factor for osteoporosis in postmenopausal women, especially for cortical bone, whereas exogenous subclinical hyperthyroidism has no effect on BMD.
Asunto(s)
Densidad Ósea , Huesos/metabolismo , Hipertiroidismo/patología , Osteoporosis Posmenopáusica/diagnóstico , Posmenopausia/metabolismo , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Hipertiroidismo/diagnóstico , Hipertiroidismo/etiología , Persona de Mediana Edad , Osteoporosis Posmenopáusica/etiologíaRESUMEN
The accurate measurement of testosterone remains a challenge. The determination of the blood testosterone concentrations in serum by conventional immunoassays is inaccurate in men and even more so in females and children. A new luminescence enzyme immunoassay (LIA) has been developed and validated. The high analytical (8.7 pmol/L) and functional (17.3 pmol/L) sensitivity allows the quantification of the very low concentration in saliva, as well as in serum, after 1/40 dilution. This study measured salivary testosterone levels and compared the results with the free levels calculated from total testosterone and sex hormone-binding globulin in eugonadal and hypogonadal men. Salivary testosterone concentrations in healthy men in morning hours were 369 pmol/L (mean), range 263-544 pmol/L, which was statistically significantly higher than that in men with androgen deficiency, 215 pmol/L (mean), range 51-249 pmol/L. Repetitive determination of free testosterone concentrations in saliva (once a week for 5 weeks) showed high stability of results over time, with coefficient of variation 9% (range 5-23%). In this study we showed that free salivary testosterone levels in morning samples correlated well with calculated free testosterone in blood, both in healthy men (R = 0.754, P = 0.001), and in patients with androgen deficiency (R = 0.889, P = 0.0001), though in cases with very low testosterone, salivary concentrations were systematically higher than calculated free testosterone levels in blood.
Asunto(s)
Andrógenos/deficiencia , Mediciones Luminiscentes , Saliva/metabolismo , Testosterona/análisis , Adulto , Alemania , Humanos , Inmunoensayo , Masculino , Persona de Mediana EdadRESUMEN
CONTEXT: Aromatase excess syndrome (AES) is a rare hereditary autosomal dominant disorder characterized by increased extraglandular aromatization of steroids and presented with heterosexual precocity in males and isosexual precocity in females. OBJECTIVE: The objective was to study the molecular basis of AES in a kindred with 16 affected subjects, both males and females. PATIENTS: The propositus, currently a 17-year-old boy, presented with breast enlargement in the first year of life, which persisted thereafter. Investigations at the age of 7.5 yr revealed growth acceleration (height sd score, 2.8), puberty staging Tanner P1B3, testicular volume 6 ml, and bone age 13 yr. The hormonal data were compatible with increased conversion of androgens to estrogens, which was independent of gonadotropin secretion. In the affected adults, there were short stature (height sd score ranged from -3.7 to -2), gynecomastia in males, and macromastia in females. DESIGN: Linkage analysis was performed using a polymorphic tetranucleotide (TTTA) repeat marker at nucleotide position 682 of CYP gene, as well as two additional STS markers, D15S123 (CA)n and D15S209 (CA)n, located within genetic distance of less than 5 cM from CYP19 gene. Using RNA extracted from the breast tissue of the propositus, a 5'-rapid amplification of cDNA ends (RACE) was performed with gene-specific primers corresponding to exon 2 of CYP19 gene. RESULTS: Linkage analysis with (TTTA)n, D15S123 (CA)n, and D15S209 (CA)n markers produced LOD scores 0.85, 1.5, and 1.17, respectively. 5'-RACE revealed a novel untranslated exon 1 composed by exon 1 of TRPM7 gene (Transient Receptor Potential Cation Channel, Subfamily M, member 7), which has ubiquitous expression. CONCLUSIONS: 5'-RACE finding points to a potential rearrangement between CYP19 and TRPM7 genes on chromosome 15q21.2 as a cause of AES.