Is long-term use of a calcium channel blocker associated with an exacerbated response of an insulinoma during selective intraarterial calcium stimulation?
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Adult↗
Biomedical subjects
M Vaisman
Publications and source records attributed to M Vaisman.
Comparative bioavailability of two oral L-thyroxine formulations after multiple dose administration in patients with hypothyroidism and its relation with therapeutic endpoints and dissolution profiles.
The aim of the present study was to evaluate the bioequivalence and therapeutic equivalence of the two most commonly prescribed L-thyroxine (monsodium L-thyroxine hydrate, CAS 25416-65-3) formulations in Brazil in patients treated for hypothyroidism. Twenty-four patients received 100 micrograms L-thyroxine daily of either Puran T4 (test) or the Brazilian reference formulation (reference) during 42 days, in a two-period crossover design. Serum samples obtained over a 24-h interval were analyzed for their total T4 concentration by a chemiluminescent immunoassay. Content and uniformity of the tablets and dissolution studies were also assessed according to USP 24 monograph using an isocratic HPLC-UV system and a rotating-paddle method. The mean pharmacokinetic parameters for total T4, expressed as geometric means (CV), for the test and reference were, respectively: Cmax (microgram/dl) 9.8 (14.3%) and 10.8 (14.9%); AUC0-24 h (microgram/dl.h) 206.8 (13.9%) and 230.4 (14.9%). Median values (90% CI) for Tmax (h) were 3 (2-3) and 2 (2-4) for the test and reference, respectively. 90% CI for ratios of LogCmax and LogAUC0-24 h were 86.6-94.9 and 86.3-93.4, respectively. Although the test exhibited values of Cmax and AUC0-24 h around 10% lower than the reference, these formulations must be considered bioequivalent since the 90% CI for both Cmax and AUC0-24 h mean ratio were within the 80-125% interval as proposed by the US Food and Drug Administration and the Brazilian legislation. TSH dosages within the normal range further support therapeutic equivalence between the two formulations. Dissolution data were roughly in agreement with in vivo results since both formulations comply with the USP dissolution criteria although the test tablets had a slower dissolution rate than the reference tablets. As a conclusion, the two oral formulations of L-thyroxine are both bioequivalent and therapeutically equivalent although presenting a small difference in their extent of absorption. Noteworthy, the dissolution profiles of the tablets correlate well with their bioavailability in the present experimental conditions.
Adult↗
Goiter and hypothyroidism in two siblings due to impaired Ca(+2)/NAD(P)H-dependent H(2)O(2)-generating activity.
We report herein the study of two siblings (DESM and DSM) with hypothyroidism, goiter, and positive perchlorate discharge tests (50% and 70%) in a family (M) with no history of consanguinity. Thyroid gland histology showed a predominance of hyperactive follicles, with high epithelial cells and variable colloid content. Thyroid peroxidase iodide oxidation (DESM, 1034; DSM, 1064 U/g protein) and albumin iodination (DESM, 16; DSM, 8 nmol I/mg protein) activities were within the normal range. Tg content was normal in both glands compared with that in diffuse toxic goiter (DESM, 28; DSM, 17; diffuse toxic goiter, 19 mg/g tissue), and Tg could be normally iodinated by thyroid peroxidase in vitro (DESM, 3.4; DSM, 4.3; diffuse toxic goiter, 6.3 nmol I/mg Tg). Thyroid cytochrome c reductase activities in these goiters were higher than that in paranodular tissues (DESM, 473; DSM, 567; paranodular tissues, 78 nmol NADP(+)/h/mg protein). However, thyroid NADPH oxidase activities were very low both in the particulate 3,000 x g (DESM, 4.8; DSM, 44; paranodular tissues, 224 nmol H(2)O(2)/h/mg protein) and in the particulate 100,000 x g fractions (DESM, 40; DSM, 47; paranodular tissues, 200 nmol H(2)O(2)/h/mg protein). Thus, a decreased Ca(2+)/NAD(P)H-dependent H(2)O(2) generation is the probable cause of the organification defect in these goiters.
Adolescent↗
Ca(2+)/nicotinamide adenine dinucleotide phosphate-dependent H(2)O(2) generation is inhibited by iodide in human thyroids.
A calcium and NAD(P)H-dependent H(2)O(2)-generating activity has been studied in paranodular thyroid tissues from four patients with cold thyroid nodules and from nine diffuse toxic goiters. H(2)O(2) generation was detected both in the particulate (P 3,000 g) and in the microsomal (P 100,000 g) fractions of paranodular tissue surrounding cold thyroid nodules (PN), with the same biochemical properties described for NADPH oxidase found in porcine and human thyroids. In PN tissues, the particulate NADPH oxidase activity (224 +/- 38 nmol H(2)O(2) x h(-1) x mg(-1) protein) was similar to that described for the porcine thyroid enzyme. However, no NADPH oxidase activity was detectable in the particulate fractions from eight diffuse toxic goiter patients treated with iodine before surgery; all but one also received propylthiouracil or methimazole in the preoperative period. Thyroid cytochrome c reductase (diffuse toxic goiters = 438 +/- 104 nmol NADP(+) x h(-1) x mg(-1) protein; PN = 78 +/- 10 nmol NADP(+) x h(-1) x mg(-1) protein) and thyroperoxidase (diffuse toxic goiters = 621 +/- 179 U x g(-1) protein; PN = 232 +/- 121 U x g(-1) protein) activities were unaffected by iodide. Thus, the human NADPH oxidase seems to be inhibited by iodinated compounds in vivo and probably is an enzyme involved in the Wolff-Chaikoff effect. Our findings reinforce the hypothesis that thyroid NADPH oxidase is responsible for the production of H(2)O(2) necessary for thyroid hormone biosynthesis.
Adult↗
[Hormonal dysfunction of nonpituitary lesions from midline and perisellar area].
OBJECTIVE: To analyse clinical and/or laboratorial preoperative hormonal dysfunction, of the nonpituitary intracranial lesions from midline and parasellar area. METHOD: Forty-four patients were evaluated with nonpituitary intracranial lesions, who had images studies (computed tomography or magnetic resonance) and preoperative basal hormonal level; 16 had preoperative hypothalamus-hypophysial function tests (megatests). These patients were divided in two groups. Group I - 34 lesions from midline: 11 craniopharyngiomas, 8 meningiomas, 3 germinomas, 3 tumors of sphenoid sinus, 2 empty sella syndrome, 2 pylocitic astrocytomas, 1 giant aneurysm, 2 mucoceles, 1 III ventricle diverticulum and 1 Rathke's cleft cyst; Group II - 10 lesions from parasellar area: 9 meningiomas and 1 giant aneurysm. RESULTS: In group I, 25/34 (73.5%) patients showed laboratorial hormonal deficit (14 without clinical manifestations) 18/34 (52.9%) hyperprolactinemia (5 with galactorreia) and 8 (53.3%) showed growth hormone deficiency in 15 megatests available in this group; 3 (8.8 %) patients presented central diabetes insipidus (CDI). In group II, 6/10 (60%) patients showed laboratorial hormonal deficit (5 without clinical manifestations), 1 (10%) hyperprolactinemia and 1 growth hormone deficiency (single megatest realized in this group); no patient had preoperative CID. CONCLUSIONS: The presence of nonspecific or poorly valorized clinical manifestations, does not indicate absence of hormonal dysfunction; in this present serie, 19/38 (50%) patients with laboratorial abnormalities, didn't show clinical manifestations. Hormonal dysfunction is frequent in sellar and perisellar nonpituitary lesions, specially involving midline.
Adolescent↗
A case of laryngeal carcinoma appearing as a goiter.
We describe the case of a 41-year-old man with hoarseness and a hard, fixed mass in the anterior cervical region. He was referred to our endocrinology service for evaluation of possible thyroid cancer. The results of laboratory tests of thyroid function were normal. Indirect laryngoscopy revealed paralysis of the left hemilarynx and the presence of a large vegetating lesion. Computed tomography of the neck disclosed the presence of a mass in the anterior region, along with invasion and destruction of the adjacent structures. The cytologic diagnosis was established by analysis of a fine-needle aspiration biopsy specimen, which revealed a squamous cell carcinoma. The final diagnosis was carcinoma of the larynx.
Adult↗
Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12.
The majority of somatotropinomas are sporadic, although a small number occur with a familial aggregation, either as a component of an endocrine neoplasia complex that includes multiple endocrine neoplasia type 1 (MEN-1) and Carney complex (CNC) or as isolated familial somatotropinomas (IFS). IFS is defined as the occurrence of at least two cases of acromegaly or gigantism in a family that does not exhibit MEN-1 or CNC. This rare disease is associated with loss of heterozygosity (LOH) on chromosome 11q13, the locus of the MEN-1 gene, although the MEN-1 sequence and expression appear normal. These data suggest the presence of another tumor suppressor gene located at 11q13 that is important in the control of somatotrope proliferation. To establish linkage of IFS to 11q13 and to define the candidate interval of the IFS gene, we performed haplotype and allelotype analyses on two families with IFS. Collectively, allelic retention in one tumor and a recombinant haplotype in an affected individual mapped the tumor suppressor gene involved in the pathogenesis of IFS to a region of 8.6 cM between polymorphic microsatellite markers D11S1335 and INT-2 located at chromosome 11q13.1-13.3. Maximum two-point LOD scores for five markers within this region were 3.0 or more at theta = 0.0. As somatotropinomas are the predominant pituitary tumor subtype associated with CNC and arise before 30 yr of age, which is strikingly similar to the age at diagnosis for IFS, we explored the possibility that the putative CNC genes might also contribute to the pathogenesis of IFS. Although the genetic defect responsible for the complex is unknown, CNC has been mapped by linkage analysis to chromosomes 2p15-16 and 17q23-24 in different kindreds. Two-point LOD scores less than -2.0 were obtained using marker D17S949 from chromosome 17q23-24, excluding linkage. However, LOD scores of 2.5 were obtained for markers within 2p16-12; therefore, linkage of IFS to chromosome 2p cannot be excluded. This report establishes linkage of the tumor suppressor gene involved in the pathogenesis of IFS to chromosome 11q13.1-13.3 and identifies a potential second locus at chromosome 2p16-12.
Acromegaly↗
Loss of heterozygosity on chromosome 11q13 in two families with acromegaly/gigantism is independent of mutations of the multiple endocrine neoplasia type I gene.
Familial acromegaly/gigantism occurring in the absence of multiple endocrine neoplasia type I (MEN-1) or the Carney complex has been reported in 18 families since the biochemical diagnosis of GH excess became available, and the genetic defect is unknown. In the present study we examined 2 unrelated families with isolated acromegaly/gigantism. In family A, 3 of 4 siblings were affected, with ages at diagnosis of 19, 21, and 23 yr. In family B, 5 of 13 siblings exhibited the phenotype and were diagnosed at 13, 15, 17, 17, and 24 yr of age. All 8 affected patients had elevated basal GH levels associated with high insulin-like growth factor I levels and/or nonsuppressible serum GH levels during an oral glucose tolerance test. GHRH levels were normal in affected members of family A. An invasive macroadenoma was found in 6 subjects, and a microadenoma was found in 1 subject from family B. The sequence of the GHRH receptor complementary DNA in 1 tumor from family A was normal. There was no history of consanguinity in either family, and the past medical history and laboratory results excluded MEN-1 and the Carney complex in all affected and unaffected screened subjects. Five of 8 subjects have undergone pituitary surgery to date, and paraffin-embedded pituitary blocks were available for analysis. Loss of heterozygosity on chromosome 11q13 was studied by comparing microsatellite polymorphisms of leukocyte and tumor DNA using PYGM (centromeric) and D11S527 (telomeric), markers closely linked to the MEN-1 tumor suppressor gene. All tumors exhibited a loss of heterozygosity at both markers. Sequencing of the MEN-1 gene revealed no germline mutations in either family, nor was a somatic mutation found in tumor DNA from one subject in family A. The integrity of the MEN-1 gene in this subject was further supported by demonstration of the presence of MEN-1 messenger ribonucleic acid, as assessed by RT-PCR. These data indicate that loss of heterozygosity in these affected family members appears independent of MEN-1 gene changes and suggest that a novel (tissue-specific?) tumor suppressor gene(s) linked to the PYGM marker and expressed in the pituitary is essential for regulation of somatotrope proliferation.
Acromegaly↗
[Complications of pituitary surgery. Analysis of 120 operations at HUCFF-UFRJ].
We evaluated 120 pituitary operations performed at Hospital Universitario Clementino Fraga Filho of the Universidade Federal do Rio de Janeiro from 1979 to July 1998 with the aim of analysing the immediate post operative morbidity and mortality. The ages ranged from 15 to 70 years and the clinical diagnoses were: nonsecreting adenomas, 46 (38.34%); acromegaly, 30 (25%); prolactinomas, 29 (24.16%) and Cushing's disease 15 (12.5%). The main endocrine complications were: panhypopituitarism, 16 (13.34%); diabetes insipidus, 15 (12.5%) and adrenocortical insufficiency, 4 (3.34%). Neurological complications: infection, 13 (10.84%); and cerebrospinal fluid leakage, 6 (5%). Two patients died. Our results agree with those of the international literature. We identified a progressive decrease of morbidity and mortality due to surgeon's skill increase and to the uniformity of the clinical team which managed those patients.
Adenoma↗
Skeletal muscle function and body composition of patients with hyperthyroidism.
The purpose of this study was to determine whether the improvement in muscle performance after treatment of hyperthyroidism is only a result of an increased muscle mass or if it also depends on the improvement of intrinsic contractile function. Nine patients with Graves' disease were evaluated 1) at the time of diagnosis, 2) after 1 wk of monotherapy with propranolol, and 3) after the euthyroid state had been achieved with antithyroid drugs. At each evaluation the patients were submitted, on the dominant side, to anthropometric measurements and to skeletal muscle function tests to determine the maximal static voluntary contraction (MAX) and endurance (END); "endurance" is defined as the time limit at maintaining 30% of MAX. Three movements were tested: hip flexion, ankle dorsiflexion, and handgrip. Body weight changed from 53.4 +/- 3.2 to 58.2 +/- 2.9 kg (P = 0.004) and the sum of skinfold-corrected limb circumferences changed from 90.7 +/- 3.1 to 94.4 +/- 3.1 cm (P = 0.017). MAX and END of all movements increased at the end of the study even if adjusted for the sum of skinfold-corrected limb circumferences: Hip flexion: MAX 20.60 +/- 3.32 to 31.26 +/- 5.07 g.cm-1, END 0.43 +/- 0.18 to 1.18 +/- 0.42 kg.s-1.cm-1. Ankle dorsiflexion: MAX 12.34 +/- 1.97 to 26.88 +/- 2.46 g.cm-1, END 0.97 +/- 0.28 to 2.50 +/- 0.58 kg.s-1.cm-1; Handgrip: MAX: 2.20 +/- 0.23 to 2.9 +/- 0.2 g.cm-1, END 0.13 +/- 0.01 to 0.20 +/- 0.02 kg.s-1.cm-1. In conclusion, improved muscle performance resulting from the treatment of hyperthyroidism is a consequence of an enhanced intrinsic muscle function as well as a greater muscle mass.
Adult↗
[Acromegaly. Diagnostic and therapeutic aspects. Analysis of 18 cases].
The authors present a retrospective study of a series of eighteen patients with acromegaly diagnosed, treated and followed by the Endocrinology and Neurosurgery Services of the Hospital Universitário Clementino Fraga Filho of the Federal University of Rio de Janeiro. The average age of the patients was 43.2% years (varying between 15 and 63). Initial complaints were mainly due to somatic alterations in 83.33%; half the cases had manifestations secondary to tumor compression and 53.33% had neuro-ophtalmological alterations. Hypersecretion of growth hormone was demonstrated by basal hormone determinations and dynamic tests. Neuroradiological assessment showed supraselar expansion in 61.11% of cases. Surgical approach was transsphenoidal in all cases. The main objective of this study was to establish diagnostic criteria, discuss the therapeutic conduct and evaluate the results obtained, comparing them with other series of literature.
Acromegaly↗
Electroneuromyography and neuromuscular findings in 16 primary hypothyroidism patients.
There has been few reports on electroneuromyography (ENMG) changes in hypothyroidism. The objectives of the present study were to investigate the frequency of ENMG abnormalities in hypothyroidism and correlate them with neurological signs and symptoms and muscle enzyme levels; and to compare latency, amplitude and nerve conduction velocity from selected nerves with controls. Sixteen patients suffering from primary hypothyroidism were submitted to ENMG before treatment. ENMG abnormalities were found in 87.5% of the patients; 46.6% had myopathy and 43.7% had carpal tunnel syndrome. There was no case of polyneuropathy. A clear-cut clinical, laboratorial and ENMG correlation was observed in patients with myopathy and carpal tunnel syndrome. The patients showed a significant tendency of nerve conduction slowness as compared with controls. The findings are in accordance with the well-known nerve and muscle damage in hypothyroidism.
Adult↗
Abnormal proteins in the cerebrospinal fluid of a patient with Creutzfeldt-Jakob disease following administration of human pituitary growth hormone.
A Brazilian case of Creutzfeldt-Jakob disease in a hypopituitary patient who had received cadaver-derived human pituitary growth hormone between 1968 and 1977 is reported. The clinical diagnosis was confirmed during his lifetime by the demonstration of two abnormal 30-kDa proteins in the cerebrospinal fluid by two-dimensional gel electrophoresis. These proteins, characteristic of Creutzfeldt-Jakob disease, present isoelectric points of 5.1 and 5.2. Furthermore, both proteins migrate as doublets, each one displaying a molecular weight variant of about 29-kDa. This is one of 16 cases of the disease associated to therapy with cadaver-derived human growth hormone and one of the few examples among such cases of confirmation of the clinical diagnosis by biochemical characterization of abnormal proteins in the cerebrospinal fluid.
Adult↗
Pituitary growth hormone and Creutzfeldt-Jakob disease.
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Cerebrospinal Fluid Proteins↗
Computed tomography and ultrasonography of the adrenal glands in paracoccidioidomycosis. Comparison with cortisol and aldosterone responses to ACTH stimulation.
Fifteen patients with proven disseminated paracoccidioidomycosis (PCM) had computed tomography (CT) and ultrasonography (US) performed to evaluate the form, shape, density and size of their adrenal glands. Plasma and urinary cortisol were determined and adrenal reserve assessed by measuring the cortisol and aldosterone responses to synthetic ACTH. The adrenal CT showed unilateral lesions in two cases and bilateral in another four. The US study showed more frequent alterations, unilateral in seven and bilateral in three subjects. Combining both methods increased the sensitivity to 85% of the cases. All patients had normal plasma cortisol concentrations and normal or increased urinary cortisol excretion. Plasma aldosterone concentration was also normal except in one patient with hypokalemia. Seven patients showed diminished cortisol responses, five had subnormal aldosterone responses and in five plasma aldosterone concentration increased more than normally after stimulation by ACTH. There was an incidence of limited adrenal reserve in 53% of the patients on ACTH stimulation. No correlation was evident between the disorders in adrenal steroid responses to ACTH and changes in morphology revealed by CT and/or US.
Adrenal Glands↗
Treatment of symptomatic retinal breaks.
Forty-three patients with symptomatic retinal breaks were treated with photocoagulation and a comparable group of 43 patients were treated with cryopexy. All patients had either a vitreous hemorrhage, or photopsia and floaters. Most of the breaks were of the horseshoe type. Of the patient eyes, 14% (six patients) in both groups developed new retinal tears without detachment during the long term postoperative observation. The new breaks were treated with the method used for the original breaks, and no scleral surgery was necessary. The incidence of retinal detachment was 7% in patients treated with photocoagulation and 11.6% in patients with cryocoagulation, but two cases that developed retinal detachment arising from new tears years after the initial procedure were included.
Cryosurgery↗
[Thyroid function tests in viral chronic hepatitis].
BACKGROUND: One hundred and twenty five patients with virus B or C chronic active hepatitis and postnecrotic cirrhosis and different degrees of liver dysfunction were studied. AIM: 1) To determine a thyroid hormonal profile; 2) to evaluate the prognostic value of these tests in relation to the progression of the disease and mortality; 3) compare these findings with Child-Pugh classification. PATIENTS AND METHODS: The patients were divided in four groups: a) 31 with chronic active hepatitis; b) 41 with postnecrotic cirrhosis Child A; c) 35 with postnecrotic cirrhosis Child B and d) 18 with postnecrotic cirrhosis Child C. The protocol comprised serum measurements of albumin and bilirrubin, estimates of prothrombin time and clinical evaluation of ascites and encephalopathy, measurement of total serum triiodothyronine, thyroxine, thyroid-stimulating hormone, free thyroxine, reverse triiosothyronine, calculated rT3/T3 index (IrT3) and thyrotropin-releasing hormone test. RESULTS: Total serum triiodothyromnine showed the most significant difference among the groups, gradually lower as the disease became more advanced (CAH: 149.2 +/- 42.3 ng/dL; PNC-A: 137.4 +/- 37.2 ng/dL; PNC-B: 88.0 +/- 28.4 ng/dL and PNC-C: 41.8 +/- 21.9 ng/dL). Low levels of T4 (4.5 +/- 2.0 micrograms/dL) and FT4 (0.7 +/- 0.4 ng/dL) and elevated levels of thyroid-stimulating hormone (7.2 +/- 11.5 microIU/mL), reverse triiosothyronine (60.8 +/- 52.1 ng/dL) and calculated rT3/T3 index (2.2 +/- 2.6) were more frequent in patients with postnecrotic cirrhosis Child C. Thyrotropin-releasing hormone test was normal in the majority of the patients. CONCLUSION: The present study shows a positive relationship between the low serum levels of T3 and elevated serum levels of rT3 and IrT3/T3 with the degree of hepatic dysfunction according to the Child-Pugh classification.
Hepatitis B, Chronic↗
Orbital lymphoma misdiagnosed as Graves' ophthalmopathy.
OBJECTIVE: To describe a case of bilateral orbital lymphoma mistakenly diagnosed as Graves' ophthalmopathy. METHODS: We present a case report, with laboratory data and photographic documentation, and discuss the differential diagnosis in patients with orbital masses. RESULTS: A 65-year-old man with bilateral exophthalmos and substantial weight loss was referred to the Endocrine Clinic for evaluation of possible Graves' disease. A 6-cm mass was detected in the left axilla. Biopsy of this mass revealed the histopathologic diagnosis of anaplastic B-cell lymphoma. Treatment with intrathecally administered methotrexate and orally administered dexamethasone promptly resulted in decreased proptosis. CONCLUSION: The most frequent cause of bilateral proptosis is Graves' ophthalmopathy, and when it is associated with weight loss in an elderly patient, the initial diagnostic consideration is thyrotoxic Graves' disease. This case should remind physicians that bilateral orbital lymphoma, although uncommon, may mimic Graves' ophthalmopathy.
Aged↗