PubMed Health⌕ Search

Biomedical subjects

H F Escobar-Morreale

Publications and source records attributed to H F Escobar-Morreale.

At least 37 records · Page 2Linked to original sources
PubMed1999

The presence of the 21-hydroxylase deficiency carrier status in hirsute women: phenotype-genotype correlations.

OBJECTIVE: To determine the role of heterozygosity for mutations in the 21-hydroxylase gene (CYP21) in the pathogenesis of hyperandrogenism. DESIGN: Controlled clinical study. SETTING: Tertiary care institutional hospital. PATIENT(S): Forty hirsute women and 13 healthy control women. INTERVENTION(S): The source of androgen excess was determined by the changes in serum testosterone levels in response to a single 3.75-mg i.m. dose of triptorelin. MAIN OUTCOME MEASURE(S): CYP21 molecular genetic analysis and serum 17-hydroxyprogesterone levels. RESULT(S): Eight patients and one control were heterozygous carriers of CYP21 mutations. Two patients with adrenal hyperandrogenism and one patient with ovarian hyperandrogenism, who carried the V281L mutation had an increased ACTH-stimulated 17-hydroxyprogesterone level (>4.1 ng/mL) that persisted during gonadal suppression. Another patient with adrenal hyperandrogenism carried the V281L mutation, and her ACTH-stimulated 17-hydroxyprogesterone level was elevated only during gonadal suppression. Four patients (three with idiopathic hirsutism, one with ovarian hyperandrogenism) and one control were carriers of CYP21 mutations typically associated with classic congenital adrenal hyperplasia but had normal basal and ACTH-stimulated 17-hydroxyprogesterone levels. Nine patients without CYP21 mutations had increased ACTH-stimulated 17-hydroxyprogesterone levels; these decreased to normal in six of the patients during gonadal suppression. CONCLUSION(S): The response of serum 17-hydroxyprogesterone to ACTH does not predict CYP21 carrier status. No clear concordance was found between the CYP21 genotype and the functional origin of androgen excess.

17-alpha-Hydroxyprogesterone↗
PubMed1999

Tissue-specific patterns of changes in 3,5,3'-triiodo-L-thyronine concentrations in thyroidectomized rats infused with increasing doses of the hormone. Which are the regulatory mechanisms?

We have measured 3,5,3'triiodothyronine (T3) in 12 tissues from thyroidectomized (Tx) rats infused with increasing doses of T3, and related them to their corresponding plasma levels. Young adult Wistar rats were surgically Tx. After 4 weeks, the animals were infused with placebo or T3 (0.25, 0.50, 0.75, 1.00 or 2.00 microg/100 g body weight/day). Placebo-infused intact rats served as euthyroid controls. Plasma and samples of cerebral cortex, cerebellum, brown adipose tissue (BAT), pituitary, liver, heart, lung, kidney, spleen, skeletal muscle, ovary and adrenal were obtained after 12-13 days of infusion. We determined plasma T3 and thyrotropin (TSH), and tissue T3 and thyroxine (T4), the latter being virtually undetectable. Results were compared with the relationships between tissue and plasma T3 in Tx rats on T4 infusions. Most tissues presented changes which paralleled those in plasma T3, irrespective of its source (infusion of T3, or generation from infused T4). However, at similar plasma T3 concentrations, cerebral cortex, cerebellum and BAT (containing type II 5' iodothyronine deiodinase (DII) activity), reached much lower T3 levels in the T3-infused Tx rats, than in Tx rats on T4, and required elevated plasma T3 levels for normal tissue T3. In these tissues, and in the pituitary, T3 concentrations were always lower than expected from plasma T3 levels. On the contrary, the lung and ovary of the T3-infused Tx rats contained more T3 than expected from plasma T3. Unexpectedly, both the ovary and adrenal attained higher tissue T3 concentrations in Tx rats on T3 than on T4 at comparable plasma T3 levels. In conclusion, the patterns of changes of the concentrations of T3 as a function of increasing plasma T3 are not only tissue-specific when T4 is provided, but also when circulating T3 is the only source of this iodothyronine. Further studies are needed to identify the mechanisms involved in the regulation of tissue T3 concentrations.

Animals↗
PubMed1998

Abnormalities in the serum insulin-like growth factor-1 axis in women with hyperandrogenism.

OBJECTIVE: To study the insulin-like growth factor-1 (IGF-1) axis in hirsute women. DESIGN: Controlled clinical study. SETTING: Tertiary care institutional hospital. PATIENT(S): Forty hirsute women and 17 women with normal menstrual cycles. INTERVENTION(S): Basal and ACTH-stimulated samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after a single 3.75-mg IM dose of triptorelin. Controls did not receive triptorelin for ethical reasons. MAIN OUTCOME MEASURE(S): Serum GH, IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, glucose, total testosterone, sex hormone-binding globulin, E2, and gonadotropin levels. Basal and ACTH-stimulated steroid precursors were measured. RESULT(S): Patients with idiopathic hirsutism were identified by normal serum androgen levels (n=17). Those with functional ovarian hyperandrogenism (n=15) were identified by an increase in the serum testosterone level that normalized during gonadal suppression, whereas those with functional adrenal hyperandrogenism (n=8) were identified by an initial increase in the testosterone level that persisted during gonadal suppression. The adrenal hyperandrogenism group had increased IGF-1 levels compared with the control, idiopathic hirsutism, and ovarian hyperandrogenism groups. Patients with ovarian hyperandrogenism had normal TGF-1 concentrations, but their IGFBP-3 concentrations were lower than those of controls. No differences were observed in GH levels between any of the groups. These results persisted when the influence of age was corrected for. CONCLUSION(S): The IGF-1 axis appears to be involved in the pathogenesis of hyperandrogenism, especially in patients with adrenal hyperandrogenism, who have a clear increase in IGF-1 levels. Moreover, patients with ovarian hirsutism have decreased IGFBP-3 concentrations, which might enhance IGF-1 bioavailability.

Adrenal Cortex Hormones↗
PubMed1998

Insulin resistance, dehydroepiandrosterone sulfate and sex hormone-binding globulin in essential hypertension.

OBJECTIVE: To evaluate insulin sensitivity, and serum levels of sex hormone-binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEA-sulfate), in patients with essential hypertension. DESIGN AND METHODS: In 15 non-treated hypertensive patients, insulin resistance was measured by an insulin suppression test (IST). Serum levels of DHEA-sulfate and SHBG were measured at the beginning and at the end of the IST. The results were compared to those of a control group of 10 healthy normotensive subjects matched for age, sex and body mass index (BMI).

Aged↗
PubMed1998

The increased circulating prostate-specific antigen concentrations in women with hirsutism do not respond to acute changes in adrenal or ovarian function.

Serum prostate-specific antigen (PSA) is produced in several female tissues and appears to be up-regulated by androgens. We have studied serum PSA concentrations in women with different forms of hyperandrogenism, focusing on the influence of changes in ovarian and adrenal function on these concentrations. Thirty-seven hirsute women were studied in the follicular phase of the menstrual cycle. Basal and ACTH-stimulated plasma samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after receiving a single im 3.75-mg dose of triptorelin. Eleven nonhyperandrogenic women served as controls. Hirsute women had increased PSA levels compared to controls. When considering the source of the hyperandrogenism, ovarian patients (those with increased serum androgen levels that normalized during gonadal suppression) and adrenal patients (those with increased androgen levels that remained elevated during gonadal suppression) presented increased PSA values, whereas hirsute patients without hyperandrogenemia had normal PSA levels. PSA levels did not change during ovarian or adrenal stimulation or during gonadal suppression with respect to initial values. Basal PSA levels showed significant correlations with basal total testosterone (r = 0.59; P < 0.001), free androgen index (r = 0.68; P < 0.001), sex hormone-binding globulin (r = -0.58; P < 0.001), dehydroepiandrosterone sulfate (r = 0.39; P < 0.01), 17-hydroxyprogesterone (r = 0.32; P < 0.05), and age (r = -0.33; P < 0.05) when patients and controls were considered as a whole. In conclusion, basal PSA levels are increased in hirsute patients and correlate with the degree of hyperandrogenism when patients and controls are considered as a whole. The adrenal and the ovary do not appear to be the source of PSA, suggesting that hyperandrogenism induces PSA secretion in tissues other than the adrenal and the ovary.

Adolescent↗
PubMed1997

Circulating leptin concentrations in women with hirsutism.

OBJECTIVE: To evaluate serum leptin concentrations in hirsute women. DESIGN: Controlled clinical study. SETTING: Tertiary institutional hospital. PATIENT(S): Thirty-three hirsute women and 11 healthy female controls. INTERVENTION(S): Serum samples were obtained at baseline and on day 1 (gonadal stimulation) and day 21 (gonadal suppression) after the IM injection of a single 3.75-mg dose of triptorelin. MAIN OUTCOME MEASURE(S): Leptin, T, sex hormone-binding globulin (SHBG), insulin, and glucose levels and free androgen index. RESULT(S): Leptin levels were increased in hirsute women in comparison with control subjects at baseline and on day 1. Leptin levels increased on day 1 compared with baseline and then decreased to baseline by day 21. Leptin levels correlated with body mass index (r = 0.76), SHBG levels (r = -0.52), free androgen index (r = 0.38), insulin levels (r = 0.46), and the glucose/insulin ratio (r = -0.38). When the effect of obesity on these results was removed by analysis of covariance and partial correlation analysis, leptin levels remained elevated only on day 1 and the only correlations that remained significant were those of leptin with insulin (r = 0.24) and the glucose/insulin ratio (r = -0.24). CONCLUSION(S): The increased leptin levels found in hirsute women are related mainly to obesity and also to insulin resistance. Leptin levels increased during gonadal stimulation and returned to baseline during gonadal suppression, suggesting that leptin also is influenced by the gonadal axis.

Adrenocorticotropic Hormone↗
PubMed1997

Lack of an ovarian function influence on the increased adrenal androgen secretion present in women with functional ovarian hyperandrogenism.

OBJECTIVE: To evaluate whether ovarian function might have an influence on the adrenal hyperandrogenism present in patients with functional ovarian hyperandrogenism. DESIGN: Controlled clinical study. SETTING: Tertiary institutional hospital. PATIENT(S): Twenty-nine hirsute women with functional ovarian hyperandrogenism and 12 normal controls. INTERVENTION(S): The ACTH and GnRH tests were performed before and during triptorelin-induced ovarian suppression in patients. The normal women served as controls for the ACTH test. MAIN OUTCOME MEASURE(S): Basal and ACTH-stimulated steroid values. RESULT(S): All patients presented elevated T and free androgen index, which normalized after triptorelin. Patients with functional ovarian hyperandrogenism and adrenal hyperandrogenism, defined by elevated basal DHEAS (n = 10), presented enhanced delta 4-17, 20-lyase activity, which persisted during ovarian suppression. delta 4-17,20-lyase activity was normal in the functional ovarian hyperandrogenism patients without adrenal hyperandrogenism (n = 19). No correlation was observed between the any of the indexes of the adrenal enzymatic activities evaluated and plasma E2 or T. CONCLUSION(S): Increased adrenal delta 4-17,20-lyase activity is present in functional ovarian hyperandrogenism women with adrenal hyperandrogenism. No influence of the excess ovarian androgens or estrogens was found on any of the adrenal enzymatic pathways explored.

Adolescent↗
PubMed1997

Mild adrenal and ovarian steroidogenic abnormalities in hirsute women without hyperandrogenemia: does idiopathic hirsutism exist?

To study ovarian and adrenal steroid profiles of women with idiopathic hirsutism, we compared sex steroid and basal and corticotropin (ACTH)-stimulated adrenal steroid levels before and after ovarian suppression induced by a long-acting gonadotropin-releasing hormone agonist analog (GnRH-a) in 24 hirsute women without hyperandrogenemia. Twelve healthy women served as controls for basal and ACTH-stimulated adrenal steroid levels. Serum levels of testosterone (T), sex hormone-binding globulin (SHBG), estradiol (E2), basal and ACTH-stimulated 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), delta 4-androstenedione (delta 4-A), 11-deoxycortisol (S) and cortisol (F), and basal and luteinizing hormone-releasing hormone (LHRH)-stimulated gonadotropin levels were measured before and 21 days after 3.75 mg intramuscular triptorelin in hirsute women. Basal T levels and basal and ACTH-stimulated delta 4-A, DHEA, and DHEAS levels were not different in hirsute women with respect to controls. Basal and ACTH-stimulated 17OHP was elevated, and decreased to normal after ovarian suppression with triptorelin. Although basal and ACTH-stimulated delta 4-A levels were normal, the delta delta 4-A/delta F and delta delta 4-A/delta 17OHP ratios were elevated and remained elevated after ovarian suppression, suggesting enhanced adrenal delta 4-17,20-lyase activity. T, F, S, and DHEAS levels were not affected by ovarian suppression. Basal and ACTH-stimulated 17OHP and delta 4-A, and stimulated DHEA concentrations were reduced with ovarian suppression, but their net increment and ratio to the increase of F in response to ACTH remained unchanged, reflecting the ovarian contribution to the secretion of these steroids. We conclude that idiopathic hirsute women with normoandrogenemia show an increase in ovarian secretion of 17OHP and a minimally increased adrenal delta 4-17, 20-lyase activity, suggesting that mild forms of ovarian and adrenal functional hyperandrogenism may be present in these patients with otherwise unexplained hirsutism.

17-alpha-Hydroxyprogesterone↗
PubMed1997

Methimazole-induced severe aplastic anemia: unsuccessful treatment with recombinant human granulocyte-monocyte colony-stimulating factor.

Aplastic anemia is a rare but severe complication of thionamide therapy. Although colony-stimulating factors have been used extensively in thionamide-induced agranulocytosis with good results, the same might not apply to aplastic anemia. We present a case of a patient with methimazole-induced aplastic anemia in which, as administration of recombinant human granulocyte-monocyte colony-stimulating factor for a week did not result in an increase in peripheral blood cell count, standard immunosuppressive treatment was needed to restore normal hematopoiesis. The clinical characteristics of this patient are compared with those of previous cases of thionamide-induced aplastic anemia, especially with the only other reported patient in which colony-stimulating factors were used.

Anemia, Aplastic↗
PubMed1997

Thyroid hormones influence serum leptin concentrations in the rat.

Leptin, the product of the ob gene, is secreted by adipocytes and has been shown to decrease appetite and increase energy expenditure. Leptin mRNA in adipocytes correlates with body wt, and serum leptin levels correlate with body fat. Alterations in thyroid status are frequently associated with changes in body wt. To evaluate the possible influence of thyroid status on the leptin system, we have measured serum leptin concentrations in thyroidectomized rats infused either with placebo, or with different doses of T4 (0.8 to 8.0 microg/100 g body wt per day) or T3 (0.25 to 2.0 microg/100 g body wt per day), covering a wide range of thyroid hormone concentrations, from overt hypothyroidism to hyperthyroidism. Intact animals infused with placebo were used as euthyroid controls. Infusion of T4 or T3 into thyroidectomized rats resulted in a decrease in serum leptin levels with respect to the thyroidectomized animals infused with placebo. When compared to the control group, serum leptin levels were decreased in the groups infused with the higher T4 and T3 doses, and tended to be elevated in the thyroidectomized animals infused with placebo. The leptin/body wt ratio was markedly increased in thyroidectomized rats infused with placebo, and decreased in the animals infused with the higher thyroid hormone doses. In conclusion, thyroid hormones exert a negative influence on serum leptin concentrations, which is greater than expected by the changes in body wt The precise mechanism of this influence remains to be elucidated.

Analysis of Variance↗
PubMed1997

Regulation of iodothyronine deiodinase activity as studied in thyroidectomized rats infused with thyroxine or triiodothyronine.

To provide new insights into the in vivo regulation of iodothyronine deiodinases in the different tissues of the rat, we have evaluated the effects on these enzymatic activities of T4 or T3 infusions into thyroidectomized rats. Thyroidectomized rats were infused with placebo, T4, or T3. Placebo-infused intact rats served as euthyroid controls. Plasma and samples of cerebral cortex, brown adipose tissue, pituitary, liver, and lung were obtained after 12-13 days of infusion. Plasma TSH, plasma and tissue T4 and T3, and iodothyronine deiodinase activities were determined. Type II 5'-deiodinase (DII) was increased in cortex, brown adipose tissue, and pituitary from animals infused with placebo. DII activity returned to normal only with T4 infusion, remaining elevated in the animals infused with T3 alone despite normal tissue T3 concentrations. Cortex type III 5-deiodinase was only increased when hyperthyroidism was induced by infusion of T3. Liver type I 5'-deiodinase (DI) paralleled the changes in plasma and tissue T3 regardless of whether T4 or T3 was infused. On the contrary, the increase in lung DI, proportional to the increases in plasma and tissue T3, was higher when T4 was infused. As a rule, the tissues with DII presented a tighter homeostasis in their T3 concentrations than the tissues with DI. In conclusion, the regulation of iodothyronine deiodinases depends on the hormone infused into the thyroidectomized animals and on the tissue in which the deiodinase is studied, demonstrating the existence of tissue-specific regulation of its thyroid hormone concentrations.

Adipose Tissue, Brown↗
PubMed1997

Cardiac involvement in acromegaly: specific myocardiopathy or consequence of systemic hypertension?

To evaluate the relative contributions of past or present GH hypersecretion and of hypertension to the cardiac abnormalities present in acromegaly, we have studied the serum GH and insulin-like growth factor I concentrations, systolic and diastolic blood pressures, and morphological and functional cardiac indexes as measured by echocardiography-Doppler, in 39 patients with active or cured acromegaly, 16 hypertensive controls, and 17 normotensive controls. Hypertension was present in 42.8% of patients with active acromegaly and in 28.0% of patients in which acromegaly was cured. Hypertension was independently related to an increase in indexes of cardiac morphology (left ventricular mass, left ventricular posterior wall thickness, interventricular septum thickness, relative wall thickness with respect to the diastolic diameter of the left ventricle, and left atrial end-systolic diameter), systolic function (stroke volume, fractional shortening, and end-systolic stress), and diastolic function (isovolumic relaxation time and maximal late diastolic flow velocity) and to a reduction in the early to late maximal diastolic flow velocity ratio. Acromegaly was related to an increase in left ventricular mass, stroke volume, cardiac output, and isovolumic relaxation time, which were independent from the presence of hypertension. End-systolic stress was reduced by acromegaly. In the five patients in which active acromegaly was successfully treated, left ventricular mass and left ventricular posterior wall thickness were reduced 1 yr later. In conclusion, the asymptomatic morphological and functional cardiac abnormalities present in acromegalic patients are independently related to acromegaly and hypertension, pointing to the existence to a specific acromegalic myocardiopathy that might be aggravated by the coexistence of hypertension.

Acromegaly↗
PubMed1997

Neonatal hypothyroxinemia: effects of iodine intake and premature birth.

We have investigated the effects of iodine (I) intake on urinary I excretion in preterm (PT) babies up to 2 months after birth and its effect on serum T4, free T4 (FT4), T3, TSH, and thyroglobulin (Tg) levels compared to those in term (T) newborns. Very premature and very sick infants were in negative I balance for the first weeks after birth. Later, these same infants, as well as the other PT and T newborns, were in positive balance; 75- 80% of the ingested I was not accounted for in the urine. The urinary I levels of PT and T neonates cannot be equated to their I intakes. T4, FT4, and T3 levels in PT and T neonates increased with postmenstrual age, whereas Tg decreased and TSH did not change. Serum FT4, T3, Tg, and TSH levels in PT neonates were affected negatively, independently from age, by a low I intake. PT birth also affected T4, FT4, and Tg negatively, independently from I intake and postmenstrual age, for at least 6-8 weeks after birth. Care should be taken to avoid I deficiency in PT neonates. However, even when I intake is adequate, PT newborns are hypothyroxinemic compared to T babies during an important period of brain development. This suggests the possible convenience of interventions that might mimic the intrauterine hormone environment and accelerate maturation.

Creatinine↗
PubMed1996

Effects of L-arginine infusion on renal hemodynamics and sodium excretion during hypo-, normo-, and hyperinsulinemia, as studied in dogs.

The response of renal hemodynamics and sodium excretion (NaU) to an infusion of L-arginine, in the presence (experiment I) or absence (experiment II) of endogenous insulin secretion and during a sustained hyperinsulinemic euglycemic state (experiment III), was studied in 10 age-matched beagle dogs. The experiments were preceded by a standard oral glucose tolerance test (OGTT), performed 1 week before experiment I. One week resting periods were allowed between experiments I, II, and III. No differences in renal hemodynamics and NaU were observed between basal (experiment I) and insulin secretion suppressed states (experiment II). L-Arginine infusion increased renal plasma flow (RPF), glomerular filtration rate (GFR), and NaU to a similar extent in both experiments. The hyperinsulinemic-euglycemic state (experiment III) induced a decrease in renal hemodynamics and NaU. In this situation, the infusion of L-arginine increased NaU, but was unable to increase RPF and GFR. Our data suggest that a sustained hyperinsulinemic state can interact with the physiological vasoactive mechanisms involved in the regulation of renal vasculature. These results may be pertinent to human disease, especially in pathological conditions in which insulin resistance is present.

6-Ketoprostaglandin F1 alpha↗