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Biomedical subjects

C Villabona

Publications and source records attributed to C Villabona.

At least 19 recordsLinked to original sources

Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers.

OBJECTIVE: No consensus exists until now about the suitable dose of tetracosactin in the ACTH stimulation test for detecting adrenal insufficiency. Our aim was to characterize both the ACTH(1-24) and the cortisol profiles after standard high-dose test (250 microg) (HDT) and low-dose test (1 microg) (LDT) in healthy subjects in order to provide a deeper knowledge about the relationship between stimulus and response. DESIGN AND PATIENTS: ACTH tests were performed in 10 healthy volunteers (five men, five women) with at least 1 week of difference. MEASUREMENTS: Plasma ACTH(1-24) and ACTH(1-39) and serum cortisol were measured before tetracosactin i.v. injection and at 5, 15, 30, 45, 60, 75 and 90 min after stimulus. Area under the curve (AUC) of ACTH(1-24) and cortisol, as well as mean residence time (MRT) for ACTH(1-24) were calculated in both tests. RESULTS: Elimination of ACTH(1-24) was faster in HDT than in LDT (MRTs of 0.14 vs 0.37, respectively, P = 0.008), but plasma concentrations were higher up to 60 min cortisol production in HDT reaching a higher maximum concentration (Cmax: 1144 vs 960 nmol/l) but delayed in time (75 vs 52.5 min). No significant relationship was observed between AUC or Cmax of ACTH(1-24) and AUC, Cmax and increment of cortisol in any of the tests. However, a negative correlation of basal cortisol values was observed with relative cortisol increment (HDT: r = 0.77 P = 0.009; LDT: r = 0.94 P < 0.0001), but not so with Cmax (HDT: r = 0.22 P = 0.55; LDT: r = 0.57 P = 0.09). CONCLUSIONS: The elimination rate of ACTH in healthy volunteers was significantly lower in LDT than in HDT, but cortisol production rate appears to be identical in both tests, so that a maximum adrenal stimulation seems to exist. The use of LDT may be more adequate, although data from patients need studying.

Adrenal Cortex Function Tests↗

Water metabolism disturbances at different stages of primary thyroid failure.

The aim of the present study was to study salt and water metabolism in thyroid deficiency. We performed an oral water loading test (OWL) and a hypertonic 5% saline infusion test (HSI) in 16 patients with overt primary hypothyroidism before replacement treatment (PRE group) and after, in eight patients with subclinical hypothyroidism (SUB group) and in 16 normal individuals (CG group). In the PRE group, a lower free water clearance was detected in the OWL (P < 0.022), with lower plasma osmolality (OWL: P < 0.005; HSI: P < 0.001) and arginine vasopressin (AVP) (OWL: P < 0.001; HSI: P < 0.001) than the CG group, across both tests; they normalized with the replacement treatment. The same plasma abnormalities were detected in the SUB group with the HSI. Although the AVP and thirst thresholds did not differ between the groups, the lag between them was lower in the PRE (4.1+/-3.2 mOsm/kg) and SUB group (2.6+/-2.1 mOsm/kg) than in the CG group (13.3+/-9.2 mOsm/kg) (P < 0.05). There were no differences in atrial natriuretic hormone (ANH), plasma renin activity (PRA) and plasma aldosterone among the groups. These results indicate that plasma hypo-osmolality and low levels of AVP are present in primary hypothyroidism, and indeed are already present in the subclinical phase of the disease. An overlap between the thresholds of thirst and AVP seem to play a role in these abnormalities, but ANH, PRA and plasma aldosterone do not appear to contribute.

Adolescent↗

Establishment of reference values for standard dose short synacthen test (250 microgram), low dose short synacthen test (1 microgram) and insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in normal subjects.

OBJECTIVE: To assess the integrity of the hypothalamo-pituitary-adrenal(HPA) axis, many authors have proposed the short synacthen test (ACTH1-24, Tetracosactrin) as a replacement for the insulin tolerance test (ITT). The aim of this study was to compare the plasma cortisol response obtained with both short synacthen tests (high dose (HDT, 250 microgram) and low dose (LDT, 1 microgram)) with the peak reached during the ITT in healthy volunteers, and to establish the plasma cortisol cut-off level in each test. SUBJECTS AND METHODS: Thirty healthy subjects (16 F, 14 M), mean age 34 years, underwent both short synacthen tests. Twenty healthy subjects, 15 of whom (11 F, nine M) belonged to the above group, mean age 30 years, underwent an ITT. Plasma cortisol was measured using a chemiluminiscence immunoassay. RESULTS: There were no differences between plasma cortisol 30 minutes after both short synacthen tests (HDT: 684 +/- 123, LDT: 669 +/- 119 nmol/l) and the peaks reached with the LDT (691 +/- 123 nmol/l) and the ITT (673 +/- 99 nmol/l). The only difference (P < 0.001) was found in the comparison of plasma cortisol peak reached with the HDT (802 +/- 142 nmol/l) with the other tests. Plasma cortisol levels obtained in the 5th percentile in each test were: at + 30 minutes: (HDT: 537, LDT: 489 nmol/l), peak: (HDT 649, LDT 498, ITT: 539 nmol/l). CONCLUSIONS: Comparison of the plasma cortisol response at + 30 minutes with both short ACTH tests and the peak in the insulin tolerance test did not reveal differences. Each test, for each time point and for each biochemical method, requires its own minimum threshold of normality to assess the hypothalamo-pituitary-adrenal axis.

Adult↗

Blood volumes and renal function in overt and subclinical primary hypothyroidism.

INTRODUCTION: Thyroid dysfunction is associated with marked alterations in cardiovascular and renal functions. In hypothyroidism, myocardial contractility, cardiac output, and oxygen consumption are decreased, whereas peripheral resistance is increased. METHODS: We assessed blood volumes and effective renal plasma blood flow (ERPF) and glomerular filtration rate (GFR) in 17 patients with overt primary hypothyroidism and in 15 of these patients when in euthyroid state after substitutive therapy. We performed the same measurements in eight patients with subclinical hypothyroidism. RESULTS: In the hypothyroid state, the plasma volume measured by dilution of 125I-albumin (APV) was higher than the calculated plasma volume (CPV) from packed red cell mass, suggesting an extravascular escape of albumin. After substitutive therapy, the CPV showed a statistical increase (P < 0.05), whereas APV remained unchanged. Both ERPF and GFR increased after thyroxine therapy (p < 0.05). In the subclinical group, blood volumes and renal function were similar to those found in the other group of patients when in the euthyroid state. CONCLUSIONS: We conclude that in primary hypothyroidism, ERPF and GFR are low, but that these values improve with substitutive therapy. CPV is a better index of the current plasma volume than APV. The difference between these two parameters suggests that the escape of albumin into the extravascular space in primary hypothyroidism is terminated by treatment. There are no clear abnormalities either in blood volumes or in renal function in subclinical hypothyroidism.

Adolescent↗

[Usefulness of the genetic study in the diagnosis of medullary carcinoma of the thyroid].

Germ-line mutations in the RET proto-oncogene are associated with multiple endocrine neoplasia type 2A (MEN 2A) and with familial medullary thyroid carcinoma (FMTC). Detection of these mutations allows the identification of the affected kindred members, who will develop medullary thyroid carcinoma (MTC) in 100% of cases. We studied 24 patients of two kindreds (MEN 2A and FMTC). Basal calcitonin levels and pentagastrin-stimulated calcitonin were measured in all patients. The RET mutations were detected by DNA analysis. The RET mutations were identified in 14 patients. Two of them had been operated in the past, 2 refused operation and 4 were living abroad. In the 6 remaining, only one showed a thyroid mass, basal calcitonin was normal in all patients except one, and pentagastrin-stimulated calcitonin was negative in 2 patients. Total thyroidectomy was performed in all cases. Histology showed C-cell hyperplasia in all patients and MTC in 5 of them. In MEN 2A and FMTC DNA analysis allows the identification of RET mutation carriers, in which presymptomatic thyroidectomy allows and improvement in survival.

Adult↗

Inflammatory mediators are perpetuated in macrophages resistant to apoptosis induced by hypoxia.

A hypoxic/anoxic microenvironment has been proposed to exist within a vascular lesion due to intimal or medial cell proliferation in vascular diseases. Here, we examined whether hypoxia alters macrophage function by exposing murine macrophage-like RAW 264.7 (RAW) cells to hypoxia (2% O2). When cells were exposed to hypoxia, a significant number of RAW cells underwent apoptosis. Additionally, small subpopulations of RAW cells were resistant to hypoxia-induced apoptosis. Through repeated cycles of hypoxia exposure, hypoxia-induced apoptosis-resistant macrophages (HARMs) were selected; HARM cells demonstrate >70% resistance to hypoxia-induced apoptosis, as compared with the parental RAW cells. When heat shock protein (HSP) expression was examined after hypoxia, we observed a significant decrease in constitutive heat shock protein 70 (HSC 70) in RAW cells, but not in HARMs, as compared with the control normoxic condition (21% O2). In contrast, the expression level of glucose-regulated protein 78 (GRP 78) in RAW and HARM cells after hypoxia treatment was not altered, suggesting that HSC 70 and not GRP 78 may play a role in protection against hypoxia-induced apoptosis. When tumor necrosis factor alpha (TNF-alpha) production was examined after hypoxic treatment, a significant increase in TNF-alpha production in HARM but decrease in RAW was observed, as compared with cells cultured in normoxic conditions. HARM cells also exhibit a much lower level of modified-LDL uptake than do RAW cells, suggesting that HARMs may not transform into foam cells. These results suggest that a selective population of macrophages may adapt to potentially pathological hypoxic conditions by overcoming the apoptotic signal.

Animals↗

[Assessment of prognosis factors in the cure of Cushing's disease surgically treated via a +septotransphenoidal approach].

INTRODUCTION: In Cushing's disease (CD) pituitary surgery or radiotherapy has been proposed by some authors, when plasmatic cortisol after surgery is not clearly low. AIM: To assess if the different prognostic factors, specially plasmatic cortisol seven days after surgery and/or hypocortisolism phase are predictive of the CD outcome. METHODS: From 1988, 11 women with CD underwent 13 transsphenoidal microsurgery, because two patients relapsed. The mean age of patients was 27 years (11-52). Plasmatic cortisol was measured seven days after pituitary surgery, and since 45 days, every three-six months, basal plasmatic cortisol and after ACTH and urinary free cortisol were determined. RESULTS: Follow-up evaluations ranged from 18-84 months (median, 38 months). After pituitary surgery in 13 cases the cumulative remission was 100%, two cases relapsed. In 10 cases plasmatic cortisol seven days after surgery was less than 137 nmol/l and in three cases higher than 137 nmol/l. Three cases did not presented hypocortisolism phase. The two patients who relapsed, one was after eight months of pituitary surgery an previously showed low plasmatic cortisol and the other relapse 25 months after pituitary surgery without low cortisol plasmatic levels. CONCLUSION: Remission in CD can happen either low or normal plasmatic cortisol levels seven days posttreatment or without hypocortisolism phase. Ours findings ascribe new importance to the different presentations after treatment of CD, and patients with these findings are not a risk for relapse and pituitary surgery or irradiation would not be early indicated.

Adolescent↗

Expression of ICAM-1 in distant metastatic thyroid carcinoma.

Distant metastasis from follicular thyroid carcinoma developed in a 48-year-old woman 11 yr after the resection of the primary tumor. Distant metastasis consisted in invasion of the left infraspinatus muscle by malignant thyroid cells. After its surgical removal, in the following 6-8 months multiple metastasis to distant skeletal muscle and brain appeared, and despite chemotherapy and local radiotherapy, the patient finally died. Intercellular adhesion molecule-1 (ICAM-1), a single chain transmembrane glycoprotein, was detected on the surface of cells of the metastatic tissue. Although ICAM-1-positive staining has been recently described in primary tumors such as papillary adenocarcinoma, and metastatic tumors from skin, brain, thymus, liver, adrenal gland and prostate, to our knowledge its expression on distant metastasis from thyroid carcinoma has not been previously reported.

Adenoma↗

[The value of the parathyrin-related protein (PTH-RP) in the diagnosis of cancer-associated hypercalcemia].

BACKGROUND: The parathyrine related protein (PTH-RP) is very similar, both in structure and in function, to the PTH and is considered as a mediator in humoral hypercalcemia in cancer. The aim of this study was to know the clinical value of PTH-RP measurement. METHODS: Serum PTH-RP concentrations were studied in 22 healthy subjects, 13 patients with primary hyperparathyroidism, 9 patients with solid neoplasms and normocalcemia, 26 patients with solid neoplasms and hypercalcemia and 4 patients with hematologic neoplasms and hypercalcemia. The PTH-RP was quantified by a competitive radioimmunoassay technique using a specific antibody of the PTH-RP 1-40 fragment. Intact parathyrine (i-PTH) was quantified by an IRMA method using 2 polyclonal antibodies (INCSTAR). RESULTS: Fifteen (68%) of the healthy controls presented undetectable serum PTH-RP concentrations. The serum PTH-RP concentration was normal in all those patients with hyperparathyroidism. Elevated serum PTH-RP values were not found in patients with solid neoplasms and normocalcemia or in those with hematologic neoplasms and hypercalcemia. High values of PTH-RP were observed in 8 out of 9 (88%) of the patients with solid neoplasms and hypercalcemia with bone metastasis and in 7 out of 11 (63%) of the patients with bone involvement. CONCLUSIONS: Serum parathyrine-related protein was found to be high in a large proportion of patients with solid neoplasms and hypercalcemia. Serum PTH-RP determination is useful in the clinical investigation of patients with hypercalcemia. Even in patients with bone metastasis, hypercalcemia may have a humoral background.

Adult↗

Pituitary apoplexy into nonadenomatous tissue: case report and review.

Pituitary apoplexy into nonadenomatous tissue is extremely rare. The authors describe a 20-year-old woman with symptomatic pituitary hemorrhage into an apparently intrasellar malignant teratoma, which caused headache, visual impairment, involvement of III, IV, VI, and 1st division of the V cranial nerves, and hypopituitarism. Diabetes insipidus had developed previously. Magnetic resonance scans had a high-intensity signal in the pituitary on T1- and T2-weighted images, and lack of the signal of the posterior pituitary. Transsphenoidal approach, radiotherapy, and chemotherapy management did not preclude a fatal outcome.

Adult↗

Transient hypothyroidism after iodine-131 therapy for Grave's disease.

UNLABELLED: We studied 355 patients with Grave's disease to characterize transient hypothyroidism and its prognostic value following 131I therapy. METHODS: The patients received therapeutic 131I treatment as follows: 333 received a dose < 10 mCi (6.6 +/- 1.9 mCi) and 22 received a dose > 10 mCi (12.8 +/- 2.9 mCi). Diagnosis of transient hypothyroidism was based on low T4, regardless of TSH within the first year after 131I followed by recovery of T4 and normal TSH. RESULTS: After administration of < 10 mCi 131I, 40 patients developed transient hypothyroidism during the first year; transient hypothyroidism was symptomatic in 15. There was no transient hypothyroidism after high doses (> 10 mCi) of 131I. Iodine-131 uptake > 70% at 2 hr before treatment was a risk factor for developing transient hypothyroidism (Odds ratio 2.8, 95% confidence interval 0.9-9.4). At diagnosis of transient hypothyroidism, basal TSH levels were high (51%), normal (35%) or low (14%); therefore, the transient hypothyroidism was not centralized. If hypothyroidism developed during the first 6 mo after basal TSH > 45 mU/liter ruled out transient hypothyroidism. CONCLUSION: The development of transient hypothyroidism and its hormonal pattern did not influence long-term thyroid function. Since no prognostic factors reliably predicted transient hypothyroidism before 131I or at the time of diagnosis, if hypothyroidism appears within the first months after 131I, the reevaluation of thyroid function later is warranted to avoid unnecessary chronic replacement therapy.

Female↗

Accumulation of atherogenic remnants and lipoprotein(a) in the nephrotic syndrome: relation to remission of proteinuria.

Although lipoprotein abnormalities of the nephrotic syndrome are assumed to be related to the presence of proteinuria, this topic has not been investigated extensively. We measured lipoproteins from 19 nonuremic patients during and after remission of the nephrotic syndrome in an effort to determine the extent of their putative atherogenicity. As expected, disturbances involved primarily the apoprotein B-containing lipoproteins. No patient showed serum lipoprotein(a) [Lp(a)] < 300 mg/L during the acute phase. Lp(a) concentrations correlated significantly with those of apoprotein B, and both values decreased dramatically with the remission of the nephrotic syndrome. Surprisingly, despite the resolution of proteinuria, concentrations of intermediate-density lipoproteins and Lp(a) remained above normal in hypertriglyceridemic patients, suggesting a residual effect of nephrosis in the overall lipoprotein transport. Accumulation of atherogenic remnants should be considered a characteristic of the hyperlipidemia of the nephrotic syndrome, and aggressive treatment to reduce proteinuria is mandatory.

Adolescent↗

[Evaluation of salivary 17-hydroxyprogesterone and its clinical usefulness in the study of hirsutism and the partial deficiency of 21-hydroxylase].

BACKGROUND: The usefulness of the concentration of salivary 17-hydroxyprogesterone (17-OHPRG) in the diagnosis of congenital adrenal hyperplasia by partial deficiency of 21-hydroxylase was studied. As a biologic medium, saliva has important advantages such as facility in sample collection and the avoidance of the stress of venous puncture. METHODS: Salivary 17-OHPRG was measured by a direct solid phase radioimmunoassay. A control group made up of 28 males and 26 females was studied. The group of patients included 30 women, 10 of them with a previous diagnosis of partial deficit of 21-hydroxylase. Basal values were established in the control group and were compared with those found in the patients in whom a stimulation test with adrenocorticotropin (ACTH) was performed collecting blood and saliva samples. RESULTS: The levels of 17-OHPRG observed in the patients with partial deficiency of 21-hydroxylase were significantly higher than those found in the control group and in the group with hirsutism, including both basal levels and those following stimulation. The correlation between the values found in blood and saliva was very significant. CONCLUSIONS: The measure of 17-hydroxyprogesterone in saliva by a method of direct radioimmunoassay is a valid alternative test to serum measure in both basal conditions and following a stimulation test.

17-alpha-Hydroxyprogesterone↗

Giant intrasellar aneurysm presenting with panhypopituitarism and subarachnoid hemorrhage: case report and literature review.

A 52-year-old woman was admitted to our hospital presenting with subarachnoid hemorrhage, left ophthalmoplegia, and right hemiparesis. Previous symptoms and signs suggested the presence of panhypopituitarism. A giant intracranial aneurysm of the internal carotid artery, diagnosed by magnetic resonance imaging, showed the characteristic flow void phenomenon with black appearance. Analysis of endocrine function disclosed panhypopituitarism and hyperprolactinemia. After proximal balloon occlusion of the aneurysm, diabetes insipidus developed. Pituitary function reassessed 6 months after initial admission confirmed anterior and posterior hypopituitarism and hyperprolactinemia. Possible mechanisms are discussed. A review of the literature on pituitary dysfunction caused by carotid artery aneurysms discloses that the pituitary-gonadal axis is the most frequently involved (67.5% of cases), followed by the pituitary-adrenal axis (48.6%) and the pituitary-thyroid axis (40.5%). These frequencies are very similar to those described in other types of hypopituitarism.

Carotid Artery, Internal↗

Pattern of hyperlipoproteinemia in human nephrotic syndrome: influence of renal failure and diabetes mellitus.

Forty-two patients with the nephrotic syndrome were grouped according to the absence or presence of renal failure and/or diabetes mellitus. All patients had a similar degree of hypoalbuminemia and urinary protein losses. A lipid and apoprotein pattern was generated in serum and ultracentrifugally isolated lipoproteins. Low-density lipoprotein composition was essentially normal in uremic patients while in the other patients with the nephrotic syndrome, a considerable lipid enrichment was noted. The very-low-density lipoprotein content in lipids was uniformly increased in nephrotic patients irrespective of the presence of complications. High-density lipoprotein cholesterol and serum apolipoprotein A I and E concentration was significantly reduced in uremic patients with respect to normal subjects and to the other groups considered. Serum apolipoprotein A II and B levels were also decreased in uremics. All patients had increased serum apoprotein C II and C III concentration. We conclude that diabetes mellitus does not affect the pattern of hyperlipoproteinemia of nephrotic syndrome while the characteristic lipoprotein and apoprotein pattern of uremia is present irrespective of nephrosis in uremic, nondiabetic patients.

Apolipoproteins↗