[Hungry bone syndrome related to hyperthyroidism]. / Síndrome del hueso hambriento relacionado con hipertiroidismo.

Hungry bone syndrome is a common clinical entity which is accompanying of hypocalcemia, hypomagnesemia, and hipophosphatemia, results from an increase in bone formation. It is related to a pathological scenario which causes an imbalance between osteoclast-mediated bone resorption and osteoblast-mediates bone formation, favouring the latter. Its classic presentation occurs after parathyroidectomy in hyperparathyroydism's patients. Its clinical features are largely due to plasmatic calcium levels reduction. Hungry bone syndrome is frequent in hyperparathyroid's patients who have development bone disease before surgery. Even less frequent, it has also been described after thyroydectomy in patients with hyperthyroidism. We hereby report a case of hungry bone syndrome in one patient who suffers a Graves' disease. Then, we will provide a brief review of pathogenesis and therapeutic features.

Characterization of somatostatin binding sites in cytosolic fraction of rat intestinal mucosa.

Specific binding sites for somatostatin have been characterized in cytosolic fraction of rat intestinal mucosa by using 125I-labelled Tyr11-somatostatin and a variety of physicochemical conditions. The binding depended on time, temperature and pH, and was reversible, saturable and specific. At apparent equilibrium, the specific binding of 125I-Tyr11-somatostatin was competitively inhibited by native somatostatin in the 1 nM-4 microM concentration range. Binding studies suggested the presence of two classes of binding sites: a class with high affinity (Kd = 0.07 microM) and low capacity (4.6 pmol/mg protein) and a class with low affinity (Kd = 1.05 microM) and high capacity (277 pmol/mg protein) at 25 degrees C. Somatostatin exhibited competitive inhibition of tracer binding, while neuropeptides such as neurotensin, substance P, Leu-enkephalin, and vasoactive intestinal peptide were ineffective. The presence of somatostatin binding sites in cytosolic fraction of intestinal mucosa, together with the known occurrence of somatostatin in D-cells and nerve endings in the small intestine, strongly suggest that this peptide may be involved in the physiology and physiopathology of intestinal epithelium.

Decrease in number of somatostatin receptors in rat brain after adrenalectomy: normalization after glucocorticoid replacement.

The effects of adrenalectomy on somatostatin (SS) concentration and specific binding in cerebral cortex, hippocampus, striatum, and hypothalamus were examined using [125I-Tyr11]SS as the binding ligand. Adrenalectomy did not affect the concentration of SS-like immunoreactivity in the brain areas studied. Nevertheless, the number of SS receptors was significantly decreased in membrane preparations from hippocampus, striatum, and hypothalamus, but not in cerebral cortex. No significant differences in the apparent binding affinity values were seen after adrenalectomy. The adrenalectomy-induced decreases in [125I-Tyr11]SS receptors were completely reversed by glucocorticoid replacement with dexamethasone. These results demonstrate that adrenalectomy modulates SS receptors in discrete brain areas, suggesting the existence of a possible relationship between corticosteroids and SS in the neuronal activity of these structures. The physiological significance of these findings remains to be clarified.

Antagonistic effects of growth hormone-releasing factor and somatostatin on brain histamine.

Studies on the morphological distribution of histamine (HA)-secreting neurons and their hypothalamic projections suggest that HA may play a key role in regulating neuroendocrine functions, some of which have been recently elucidated. To investigate possible interactions between the somatotropinergic and histaminergic systems in the brain, the effects of GRF-44 [0.1-10 micrograms intracerebroventricular (icv)] and somatostatin (SS-14; 0.1-10 micrograms, icv) on HA in five different parts of the hypothalamo-hypophyseal system, and in the hippocampus and frontal cortex, were studied using a highly sensitive HPLC system for determination of HA. GRF-44 (1 microgram, icv) elicited significant (P less than 0.005) increases in the concentration of HA in the anterior hypothalamus, posterior hypothalamus, median eminence, adenohypophysis, neurohypophysis, frontal cortex, and, to a lesser extent, in the hippocampus, after a clear time-dependent pattern with maxima 15 min after injection. In contrast, SS-14 (1 microgram, icv) significantly (P less than 0.005) decreased the levels of HA in all areas studied, except in the neurohypophysis. The SS-induced HA levels reached minima 30 min after injection. The antagonistic effects of GRF-44 and SS-14 on the release of brain HA were dose dependent, showing an inverse linear correlation within the range 0.1-10 micrograms in the anterior hypothalamus (r = -0.59) and posterior hypothalamus (r = -0.75). Responses of HA to GRF-44 and SS-14 (range: 0.1-10 micrograms) also exhibited an inverse linear correlation in the median eminence (r = -0.90) and adenohypophysis (r = -0.58), while in the hippocampus and frontal cortex the antagonistic effects of GRF and SS displayed an inverse curvilinear correlation. SS-14 ED50 values ranged from 0.6 to 1.75 nmol with Emax of 0.65-6.10 nmol. GRF-44 ED50 values ranged from 0.02-0.3 nmol and the Emax values oscillated between 0.2 and 1.90 nmol in the regions studied. The greatest responses of HA to GRF-44 and SS-14 were obtained in the hypothalamo-hypophyseal system. Although brain HA is present in both the neuronal and the mast cell compartments, changes induced in the concentration of HA by centrally administered GRF-44 and SS-14 appear to occur mostly in the neuronal compartment. Therefore, it is likely that the somatotropinergic and histaminergic systems reciprocally interact at the central level to regulate still unknown neuroendocrine functions.

Exaggerated circadian variation in basal thyrotropin (TSH) and in the dopaminergic inhibition of TSH release in pathological hyperprolactinemia: evidence against a hypothalamic dopaminergic defect.

In order to delineate more accurately the dopaminergic control of anterior pituitary function in normal subjects and in patients with pathological hyperprolactinemia, we investigated the nature of the circadian variation in the dopaminergic inhibition of TSH release in such subjects. Ten euthyroid women with hyperprolactinemia due to presumed PRL-secreting microadenomas (aged 18-60 yr) were compared with 11 normal, euthyroid women (aged 18-32 yr). Each received the dopamine receptor blocking drug domperidone (10 mg, iv) at 1100 and 2300 h (tests randomized and separated by at least 1 week). Blood was sampled 10, 20, 30, 45, and 60 min after drug administration. Normal women had a greater TSH response to domperidone and, hence, greater dopaminergic inhibition of TSH release at 2300 than at 1100 h (sum of TSH increments; mU/liter mean +/- SE, 8.5 +/- 1.3 vs. 4.8 +/- 0.5, P less than 0.01), whereas there was no difference in the dopaminergic inhibition of PRL release at each time of day. Hyperprolactinemic women also had a significantly greater TSH response to domperidone at 2300 than at 1100 h (42.0 +/- 10.2 vs. 19.1 +/- 2.8, P less than 0.001). The hyperprolactinemic women had a greater TSH response to domperidone than normal women at each time of day studied (1100 h, 19.1 +/- 2.8 vs. 4.8 +/- 0.5, P less than 0.001; 2300 h, 42.0 +/- 10.2 vs. 8.5 +/- 1.3, P less than 0.001). The incremental PRL responses to domperidone were significantly less in hyperprolactinemic than in normal women and did not differ at each time of day. In conclusion, the circadian change in the dopaminergic inhibition of TSH secretion is specific for TSH and not PRL. This indicates that the dopaminergic control of TSH and PRL secretion can be dissociated in normal subjects. Second, hyperprolactinemic women with presumed PRL-secreting microadenomas had qualitatively normal but quantitatively exaggerated circadian pattern of dopaminergic inhibition of TSH release. These data argue against a hypothalamic dopaminergic defect in hyperprolactinemia and support the view that the established dopaminergic defect in the inhibition of PRL release is related specifically to PRL control and may well be at the anterior pituitary level.

Actions of growth hormone-release inhibiting hormone (somatostatin) on the renin aldosterone system.

Administration of growth hormone-release inhibiting hormone (GH-RIH, somatostatin), as a 90 minute infusion (10 mug/min), to 3 healthy young men under conditons of active renin secretion acheived by pretreatment with furosemide (80 mg daily for 5 days), caused a mean 30% fall in plasma renin activity, which returned to basal levels immediately after stopping the GH-RIH infusion. Plasma aldosterone levels were not affected during the course of this experiment.

Growth hormone responses to growth hormone-releasing factor (1-29) in euthyroid, hypothyroid and hyperthyroid rats.

In order to investigate whether the impaired GH secretion associated with hypothyroidism and hyperthyroidism is due to a hypothalamic or a pituitary disorder, we have studied plasma GH responses to GH-releasing factor (1-29) (GRF) in euthyroid, hypothyroid and hyperthyroid rats. Hypothyroid rats showed a significant (P less than 0.001) reduction in GH responses to GRF (5 micrograms/kg) at 5 min (350 +/- 35 vs 1950 +/- 260 micrograms/l), 10 min (366 +/- 66 vs 2320 +/- 270 micrograms/l) and 15 min after GRF injection (395 +/- 72 vs 1420 +/- 183 micrograms/l; mean +/- S.E.M.) compared with euthyroid rats. Hyperthyroid rats showed a significant (P less than 0.05) decrease in GH responses to 5 micrograms GRF/kg after 30 min (200 +/- 14 vs 325 +/- 35 micrograms/l) but not at other time-points, or after the administration of 1 microgram GRF/kg. These data indicate that in hypothyroidism and perhaps hyperthyroidism there is an alteration in the responsiveness of the somatotroph to GRF administration.

Recombinant human growth hormone therapy in malnourished dialysis patients: a randomized controlled study.

Recombinant human growth hormone (rhGH; Saizen, Serono, Spain) has been recently used as an anabolic agent in several catabolic states, including malnourished chronic dialysis patients. However, up-to-date, comparative studies with control groups of dialysis patients have not been reported. The aim of the present study was to assess the effects of rhGH on nutritional status in a group of malnourished adult chronic dialysis patients undergoing both continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). The patients were randomly assigned to the control group (nine patients; 6 women, 3 men; mean age, 58.3 +/- 5.6 years; seven undergoing CAPD, two undergoing HD) or the rhGH group (eight patients; three women, five men; mean age, 63.9 +/- 3.1 years; four undergoing CAPD, four undergoing HD). Both groups were similar at baseline. All patients were given dietary prescriptions (35 kcal/kg/d and 1 g protein/kg ideal body weight/d) during 4 weeks. In the rhGH group, rhGH was administered at 0.2 IU/kg/d subcutaneously (SC) during this period. Anthropometric and analytic parameters were assessed before (0 weeks) therapy and at 2 and 4 weeks after starting therapy. The rhGH group showed an increase of 1.238 kg in body weight from 64.3 +/- 4.3 (mean +/- standard error of the mean [SEM]) to 65.6 +/- 4.9 kg (P < 0.05). Serum insulin-like growth factor type 1 (IGF-1) concentrations increased from 216.6 +/- 42.5 to 581.2 +/- 171.5 ng/mL (4 weeks; P < 0.01) and transferrin levels increased from 271.2 +/- 16.3 to 314.5 +/- 21.2 mg/dL (4 weeks; P < 0.05). A significant reduction in blood urea nitrogen (BUN) level was observed (62.1 +/- 1.8 v 46.8 +/- 3.8 mg/dL; 4 weeks; P < 0.05). Mean daily protein intake, determined by individual dietary survey, at 0 and 4 weeks, remained constant in both groups. In conclusion, weight gain and IGF-1 and transferrin level increases and BUN level decreases, despite the constant oral intake, suggest that short-term rhGH administration is associated with an anabolic reaction in malnourished dialysis patients.

Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients.

OBJECTIVE: Our aim has been to evaluate the effects of i.v. infusion of recombinant human erythropoietin (rhEPO) on the responses of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation in acromegalic patients. METHODS: We studied 16 patients (8 females, aged 29-68 years) with active acromegaly and 12 control subjects (7 females, 24-65 years). All participants were tested with TRH (400 microg i.v. as bolus) and with TRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before TRH injection) on different days. Blood samples were obtained between -30 and 120 min for GH and PRL determinations, and between -30 and 90 min for TSH determinations. Hormone responses were studied by a time-averaged (area under the secretory curve (AUC)) and time-independent (peak values) analysis. RESULTS: Twelve patients exhibited a paradoxical GH reaction after TRH administration with great interindividual variability in GH levels. When patients were stimulated with rhEPO plus TRH there were no changes in the variability of GH responses or in the peak and AUC for GH secretion. Infusion with rhEPO did not induce any significant change in GH secretion in normal subjects. Baseline and TRH-stimulated PRL concentrations in patients did not differ from those values found in controls. When TRH was injected during the rhEPO infusion, a significant (P<0.05) increase in PRL concentrations at 15-120 min was found in acromegalic patients. Accordingly, the PRL peak and the AUC for PRL secretion were significantly increased in patients. Infusion with rhEPO had no effect on TRH-induced PRL release in control subjects. Baseline TSH concentrations, as well as the TSH peak and the AUC after TRH, were significantly lower in patients than in controls. Infusion with rhEPO modified neither the peak TSH reached nor the AUC for TSH secretion after TRH injection in acromegalic patients and in healthy volunteers. CONCLUSION: Results in patients with acromegaly suggest that (i) the paradoxical GH response to TRH is not modified by rhEPO infusion, (ii) rhEPO has no effect on TRH-induced TSH release, and (iii) acute rhEPO administration increases the TRH-induced PRL release in acromegalic patients.

Cholinergic and histaminergic involvement in the growth hormone releasing effect of an enkephalin analog FK 33-824 in man.

Studies were performed in healthy subjects to ascertain the neurotransmitter systems involved in the growth hormone (GH)-releasing effect of the potent enkephalin analog FK 33-824. Concomitant evaluation of prolactin (PRL) secretion was also performed in the same subjects. FK 33-824 at a dose of 0.5 mg IV elicited a clear-cut rise in plasma GH and PRL concentrations with peak levels at 45 min. Blockade of muscarinic cholinergic receptors by atropine (0.5 mg SC) or histaminergic H1 receptors by diphenhydramine (50 mg IV bolus plus 50 mg infusion) completely suppressed the GH release induced by FK 33-824, without significantly altering the PRL rise induced by the peptide. Pretreatment with the alpha-adrenergic antagonist phentolamine (0.5 mg IV/min for 120 min) or the dopamine receptor blocker metoclopramide (10 mg IV) did not alter the GH-releasing effect of FK 33-824. Phentolamine failed to alter the PRL rise induced by FK 33-824, while combined FK 33-824-metoclopramide administration induced a greater PRL increase than FK 33-824 alone. These results indicate that cholinergic and histaminergic H1 receptors play an important role in the GH-release induced by FK 33-824 in man, whereas this action seems to occur independently of catecholaminergic mediation. The same receptors are not involved in the PRL-releasing effect of the peptide.

Long-term effects of recombinant human erythropoietin therapy on growth hormone secretion in uremic patients undergoing peritoneal dialysis.

Recombinant human erythropoietin (rhEPO) is being successfully used for the treatment of uremic anemia. Short-term studies have proved that correction of anemia with rhEPO therapy is accompanied by several changes in growth hormone (GH) secretion in uremic patients. The present study aimed to assess the influence of long-term rhEPO therapy on baseline and stimulated GH concentrations in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Seven well-nourished and clinically stable CAPD patients were studied. Ten normal subjects were studied as controls. GH responses to direct pituitary stimulation with GH-releasing hormone (GHRH) (100 microg intravenously [i.v.]) and indirect hypothalamic stimulation with insulin-induced hypoglycemia (0.1 U/kg body weight i.v.) and clonidine (0.15 mg/m2 orally), were assessed before and after 3, 6, and 12 months of subcutaneously administered rhEPO therapy. After rhEPO administration, an increase of the hemoglobin concentration was observed in all patients and maintained at about 12 g/dL throughout the study period. rhEPO therapy did not induce any significant change in baseline concentrations of GH and insulin-like growth factor I. Correction of the anemia was accompanied by a clear increase in the area under the curve (AUC) and the area above the baseline (AAB) of GH secretion in response to GHRH stimulation. These changes were statistically significant after 3 and 6 months of therapy, although at 12 months no significant differences in relation to pretreatment values could be observed. rhEPO treatment was associated with a progressive decrement in the GH AUC and AAB in response to hypoglycemic challenge, reaching statistically significant values at months 6 and 12. On the other hand, compared with the control group, GH responses to clonidine were blunted at the start of the study in CAPD patients, and rhEPO therapy was not accompanied by any modification. In conclusion, long-term treatment with rhEPO in CAPD patients is associated with complex and profound effects on somatotrope cell function, characterized by diverse effects on GH responses to stimuli that release GH through different mechanisms. Some of these rhEPO-induced alterations in somatotrope function are dependent on the duration of treatment.

Evidence against prostaglandin-mediation of somatostatin-inhibition of gastric secretions.

The inhibitory activities of somatostatin and PGE2 against pentagastrin-stimulated gastric acid and pepsin secretions were investigated, with and without pretreatment with the cyclooxygenase inhibitor indomethacin, in conscious cats prepared with gastric fistulae. Somatostatin was a potent inhibitor of acid secretion in both vagus intact and vagotomized animals, and its effect was not diminished by indomethacin pretreatment. Somatostatin inhibition of pepsin secretion was diminished after indomethacin, but a similar effect was noted with exogenous PGE2, suggesting a mechanism unrelated to inhibition of prostaglandin synthesis. It is concluded that there is no evidence to implicate endogenous prostaglandins in somatostatin inhibition of feline gastric exocrine secretions.

Efficacy of octreotide in the regression of a metastatic carcinoid tumour despite negative imaging with In-111-pentetreotide (Octreoscan).

We present the case of a 52-year old patient diagnosed with carcinoid tumour of the rectum with liver metastases in which treatment with somatostatin analogues (octreotide) proved very effective in the disappearance of the symptomatology and dramatic efficacy in the regression of the tumour. Imaging by octreoscan was always negative. The role of octreotide in the treatment of carcinoid tumour and the usefulness of In-111-pentetreotide (octreoscan) in the localization and prediction of the response to treatment with octreotide is discussed. We conclude that the negative result of the scintigraphic image with octreoscan does not necessarily suppose the inefficacy of octreotide treatment. We believe that this may constitute an important issue since some patients may be denied octreotide treatment in the absence of a positive octreoscan result.

Growth hormone responses to pituitary and hypothalamic stimuli in CAPD patients treated with recombinant human erythropoietin.

Several alterations of growth hormone (GH) secretion have been described in patients with chronic renal failure. The effect of chronic treatment with recombinant human erythropoietin (rHuEPO) on GH secretion in uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The purpose of this study was to assess the GH responses to both direct and hypothalamic stimuli in CAPD patients chronically treated with rHuEPO. Eight clinically stable and well-nourished patients (age 19-59 yr) treated with subcutaneous rHuEPO, 96.5 +/- 72.1 U/kg/week, during 6-25 months were tested with GH-releasing hormone (GHRH, 100 micrograms iv in bolus). Insulin-induced hypoglycemia (0.1 U/kg iv in bolus) and clonidine (0.15 mg/m2 po) were used as indirect stimuli for GH release. Baseline concentrations of insulin-like growth factor I (IGF I) concentration was also determined. Five CAPD patients matched for age and sex and not previously treated with EPO were studied as a control group. There was no statistically significant difference in baseline IGF I concentrations in EPO treated patients in comparison with control group (2.6 +/- 0.7 vs 0.9 +/- 0.3 U/ml). GHRH administration was followed by a GH release in the treated group that did not differ significantly from that obtained in controls (peak: 10.6 +/- 3.7 vs 15.2 +/- 7.8 micrograms l, area under the curve [AUC]: 16.3 +/- 5.6 vs 24.0 +/- 11.4 micrograms.h/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone and cortisol secretion before and after erythropoietin therapy in CAPD patients.

Correction of anemia with recombinant human erythropoietin (rHuEPO) in patients with end-stage renal disease (ESRD) has been associated with improvement of several endocrine abnormalities. However, long-term effects of this therapy on pituitary secretion in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The aim of the present work was to assess the growth hormone (GH) and cortisol responses to insulin-induced hypoglycemia before and after the correction of anemia with rHuEPO therapy in CAPD patients. Five well-nourished and clinically stable patients were studied before and after 12-24 weeks of rHuEPO treatment. Seven normal volunteers were studied as controls. Insulin-induced hypoglycemia tests were performed prior to starting rHuEPO therapy and again after partial correction of anemia. Blood samples for GH, cortisol, and glucose were collected between -30 and 120 min after insulin (0.1 U/kg bw) administration. GH responses to hypoglycemic stress were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC) of GH responses in CAPD patients (10.6 +/- 4.8 micrograms/L and 15.4 +/- 6.1 micrograms h/L, respectively) did not differ from those obtained in control subjects (14.3 +/- 4.1 micrograms/L and 19.4 +/- 3.5 micrograms h/L, respectively). The study, after correction of anemia, showed an evident decrease of GH values at each time point on the response curve in 4 patients, and no modification in 1 patient. Mean values of GH peak and AUC were 8.8 +/- 2.8 micrograms/L and 9.6 +/- 2.3 micrograms h/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of recombinant human erythropoietin treatment on cortisol responses to insulin-induced hypoglycemia in CAPD patients.

The effect of chronic treatment with recombinant human erythropoietin (rHuEPO) on pituitary-adrenal axis responses to stress in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The purpose of this study was to assess the influence of rHuEPO treatment on corticotropin (ACTH) levels and cortisol responses to insulin-induced hypoglycemia in CAPD patients. Nine clinically stable and well-nourished patients (age 19-59 years) treated with subcutaneous rHuEPO, 34-208 U/kg BW/week, during 6-25 months were studied. Nine patients matched for age, sex, and duration of CAPD and not previously treated with rHuEPO were studied as the control group. Crystalline insulin (0.1 U/kg BW) was injected IV to the fasting subjects. Blood samples were collected before and 15, 30, 60, 90, and 120 minutes after insulin administration. In all blood samples serum cortisol and glucose concentrations were assessed. There were no statistically significant differences between both groups in hematocrit values and blood hemoglobin concentrations. Insulin administration induced a decrease in glucose levels that reached a nadir at 30 minutes in both groups (1.8 +/- 0.1 mmol/L in the rHuEPO group vs 2.1 +/- 0.2 mmol/L in the control group). After hypoglycemic stimuli cortisol levels clearly rose in rHuEPO-treated patients reaching a peak of 720 +/- 71 nmol/L at 60 minutes. However, in the control group the cortisol peak, which was not different from that observed in the rHuEPO group (676 +/- 44 nmol/L), occurred at 90 minutes. The areas under the secretory curve of cortisol did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[A dose-response study of the chronic effect of ketoconazole on androgen and cortisol secretion in women with hyperandrogenism]. / Estudio dosis-respuesta de la acción crónica del cetoconazol sobre la secreción androgénica y de cortisol en mujeres con hiperandrogenismo.

We have previously shown that ketoconazole may inhibit the androgen synthesis, but the risk to induce a blockade in the cortisol synthesis and/or hepatic abnormalities makes it mandatory to look for the least dose that is able to inhibit androgen production without inducing other abnormalities. To this end, we studied the levels of 17-alpha-hydroxyprogesterone (17, alpha-OH-P), dehydroepiandrosterone sulphate (DHEA-S), delta 4-androstenedione (delta 4-A), total (tT) and free (fT) testosterone, and the cortisol response to ACTH in 13 women with hyperandrogenism, before and after ketoconazole therapy at dosages of 400, 600, and 800 mg/day. Although with the 400 mg regimen a reduction in the levels of androstenedione and free and total testosterone was already observed, it was of small amount and it was not until the 600 mg regimen that androgen levels became normal. Thus, DHEAS-S was reduced from 3.672 +/- 1.013 to 2.216 +/- 756 ng/ml (p less than 0.05); delta 4-A was reduced from 392 +/- 80 to 283 +/- 79 ng/ml (p less than 0.01); tT was reduced from 1.5 +/- 0.78 to 0.7 +/- 0.1 ng/ml (p less than 0.05), and fT from 5.5 +/- 1.0 to 2.7 +/- 1.3 pg/ml (p less than 0.001). By contrast, 17 alpha-OH-P increased from 1.7 +/- 1.3 to 4.7 +/- 1.3 ng/ml (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Self-induced Cushing's syndrome due to dexamethasone abuse in nasal spray: clinical and biochemical study]. / Síndrome de Cushing autoinducido por abuso de dexametasona en spray nasal: estudio clínico y bioquímico.

We studied a 55-year-old woman with remarkable cushingoid features, which presented biochemical evidence of suppression of the hypothalamus-hypophysis-adrenal axis. In the detailed anamnesis, we discovered that the patient had used during more than two years a nasal spray containing dexamethasone. In the initial assessment of the suprarenal function, in addition to suppressed concentrations of cortisol and ACTH, we observed the absence of response to acute stimulus (insulinic hypoglycemia and short ACTH test), as well as a normal response to sustained ACTH stimulus. After discontinuing the intranasal administration of dexamethasone, the patient remained asymptomatic; the basal concentrations of ACTH and cortisol, as well as the levels of urinary free cortisol, were normal at 3 months and the responses of cortisol and ACTH to their stimulus were restored to normal levels at 6 months. We conclude that in the cases of Cushing's syndrome with suppression of the hypothalamus-hypophysis-adrenal axis, it is necessary to conduct a detailed investigation on the consumption of glucocorticoids through unusual ways. The presence of a normal response to the sustained stimulus with ACTH may be a quick recovery index of the suprarenal function.

[Diabetes mellitus induced by pentamidine, without previous episodes of hypoglycemia, in patients with AIDS]. / Diabetes mellitus inducida por pentamidina, sin episodios previos de hipoglucemia, en pacientes con SIDA.

The onset of a pneumonia by P. carinii in AIDS patients have force scientist to look for others therapies against this parasite. It is more necessary when the first line treatment which is cotrimoxazol produced secondary effects or not therapeutic effects. Pentamidine which is an agent usually used to treat leishmaniasis and trypanosomiasis, but it is an alternative for P. carinii infection. The problems are the frequent and severe secondary effects when administered by continuous infusions and less when it is inhaled. Between those effects are the changes in carbohydrate metabolism which are 9% of them. It is frequent observe hypoglycemia during infusion following by hyperglycemia in 5% of the cases which convert the patients in diabetic insulinodependent. A case of a patient who developed diabetes mellitus insulinodependent, 10 days after the end of pentamidine treatment, without previous episodes of hypoglycemia, is presented. The medical literature is reviewed.

Arterial hypertension as a complication of prolonged ketoconazole treatment.

Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.