Claudio E Kater

MD, PhD
Chief, Adenal and Hypertension Unit
Universidade Federal de São Pa... · Department of Medicine, Div. of Endocrinology

Publications

  • [show abstract] [hide abstract]
    ABSTRACT: Germline mutations in p27kip1 are associated with increased susceptibility to multiple endocrine neoplasias both in rats and humans, however the potential role of common polymorphisms of this gene in endocrine tumor susceptibility and tumorigenesis remain mostly unrecognized. To assess the risk associated with polymorphism rs2066827 (p27 V109G), we genotyped a large cohort of Brazilian patients with sporadic endocrine tumors (pituitary adenomas [n=252]; pheochromocytomas [n=125]; medullary thyroid carcinoma [n=51] and parathyroid adenomas [n=19]) and 885 population-matched healthy controls and determined the odds ratios and 95% CIs. Significant associations were found for the group of patients with pituitary adenomas (p=0.01), particularly for those with ACTH-secreting pituitary adenomas (p=0.005). In contrast, no association was found with GH-secreting pituitary tumors alone or with MEN2-related tumors. Our in vitro analyses revealed increased colony formation and cell growth rate for an atT20 corticotropin mouse cell line over-expressing the p27 V109G variant compared to cells transfected with the wild-type p27. However, the genotypic effects in genetic and in vitro approaches were divergent. In accordance with our genetic data showing specificity for ACTH-secreting pituitary tissues, the over-expression of p27 V109G in a GH3 somatotropin rat cell line presented no difference compared to the wild type. Pituitary tumors are one of the major clinical components of syndromes associated with the p27 pathogenic mutations MENX and MEN4. Our genetic and in vitro data indicate that the common polymorphism rs2066827 may play a role in corticotropinoma susceptibility and tumorigenesis through a molecular mechanism not fully understood thus far.
    Endocrine Related Cancer 02/2014; · 5.26 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: PURPOSE: Percutaneous ablation of functioning adrenal adenomas has been an alternative to videolaparoscopic treatment. This study aimed to evaluate the feasibility, safety and efficacy of radiofrequency ablation (RFA) in the treatment of functioning adrenal tumors using a computed tomography (CT)-guided percutaneous technique as demonstrated by our experience and the literature. METHODS: Eleven adult patients (mean age 46 years) with a diagnosis of functioning adrenal adenoma underwent CT-guided RFA between October 2011 and August 2012. All RFA procedures were performed using a needle electrode with a single lateral filament and the RITA(®) 1500X radiofrequency generator. The RFA protocol consisted of two cycles of 5 min each with 1-min interval, with no additional ablation cycles. Contrast-enhanced CT scans were obtained and analyzed for immediate treatment success and possible complications. RESULTS: Maximum tumor dimension ranged from 1.2 to 3.4 cm. The mean procedure time was 74 min, and length of hospital stay ranged from 0.9 to 3.2 days (mean 1.8 days). One patient had residual pneumothorax and one patient had neuritis involving the T10 dermatome. Of 11 patients, 10 recovered from their condition. Only one patient remained with hyperaldosteronism, but with reduced anti-hypertensive medication. CONCLUSIONS: CT-guided percutaneous RFA was a safe and effective treatment for functioning adrenal adenomas, with short hospital length of stay and low complication rate.
    Abdominal Imaging 04/2013; · 1.91 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: The purpose of this study was to identify factors that might interfere with reaching the final height in patients with 21-hydroxylase deficiency (21-OHD). Thirty-one patients with classical 21-OHD who reached their FH in our Institution were eva-luated in order to compare the Z score for final height (FHZ) with: (1) the target height, (2) the standard height for the population, and (3) the hydrocortisone treatment schedule. The FHZ of -2.13 ± 1.11 had a significant negative correlation with the hydrocortisone doses used throughout the period of study. Patients who reached FH within the normal population range were those who received lower doses of hydrocortisone, as compared to those whose FH remained below -2 SDS. We conclude that careful treatment adjustments have a major influence on growth of children with CAH, and that the dose range for hydrocortisone replacement that does not lead to side effects is relatively narrow. The better height outcome was achieved in 21-OHD patients who received lower doses of hydrocortisone.
    Arquivos brasileiros de endocrinologia e metabologia 03/2013; 57(2):126-31. · 0.68 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Purpose. To assess glutamine/glutamate (Glx) and lactate (Lac) metabolism using proton magnetic resonance spectroscopic imaging (1H-MRS) in order to differentiate between adrenal gland nodules and masses (adenomas, pheochromocytomas, carcinomas, and metastases). Materials and Methods. Institutional review board approval and informed consent were obtained. A total of 130 patients (47 men) with 132 adrenal nodules/masses were prospectively assessed (54 ± 14.8 years). A multivoxel system was used with a two-dimensional point-resolved spectroscopy/chemical-shift imaging sequence. Spectroscopic data were interpreted by visual inspection and peak amplitudes of lipids (Lip), choline (Cho), creatine (Cr), Lac, and Glx. Lac/Cr and Glx/Cr were calculated. Glx/Cr was assessed in relation to lesion size. Results. Statistically significant differences were observed in Glx/Cr results between adenomas and pheochromocytomas (P < 0.05), however, with a low positive predictive value (PPV). Glx levels were directly proportional to lesion size in carcinomas. A cutoff point of 1.44 was established for the differentiation between carcinomas larger versus smaller than 4 cm, with 75% sensitivity, 100% specificity, 100% PPV, and 80% accuracy. Lac/Cr results showed no differences across lesions. A cutoff point of -6.5 for Lac/Cr was established for carcinoma diagnosis. Conclusion. Glx levels are directly proportional to lesion size in carcinomas. A cutoff point of -6.5 Lac/Cr differentiates carcinomas from noncarcinomas.
    BioMed research international. 01/2013; 2013:835385.
  • [show abstract] [hide abstract]
    ABSTRACT: Maternally-inherited diabetes with deafness (MIDD) is a rare form of monogenic diabetes that results, in most cases, from an A-to-G transition at position 3243 of mitochondrial DNA (m.3243A>G) in the mitochondrial-encoded tRNA leucine (UUA/G) gene. As the name suggests, this condition is characterized by maternally-inherited diabetes and bilateral neurosensory hearing impairment. A characteristic of mitochondrial cytopathies is the progressive multisystemic involvement with the development of more symptoms during the course of the disease. We report here the case of a patient with MIDD who developed hyporeninemic hypoaldosteronism. Arq Bras Endocrinol Metab. 2012;56(8):574-7.
    Arquivos brasileiros de endocrinologia e metabologia 11/2012; 56(8):574-7. · 0.68 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: (1) Characterize serum (S) and urinary (U) steroid metabolites in complete CYP17 deficiency (cCYP17D); (2) analyze the relative 17α-hydroxylase (17OH) and 17,20-lyase (17,20L) activities in vivo; and (3) comparedata from the two most prevalent mutations in Brazil. 20 genotyped cCYP17D patients from a previously reported cohort were homozygous for W406R or R362C; 11 controls were CYP17 wild types (WT). WT and cCYP17D patients had S and U samples drawn to measure: cortisol (F), corticosterone (B), deoxycorticosterone (DOC), 18OH-B, 18OH-DOC, and 17OHP; and tetrahydro (TH)-B, THA, THDOC, THF+5α-THF, TH-cortisone, androsterone, etiocholanolone, 5-pregnenediol, 17OH-pregnenolone and pregnanetriol. Compared to WT, cCYP17D patients had marked elevations of B, DOC, 18OH-B and 18OH-DOC, whereas 17OHP, F and adrenal androgens (AA) were reduced; U steroids parallel S findings. Metabolite ratios revealed that both 17OH and 17,20L activities were impaired in cCYP17D. There were nodifferences between W406R andR362C mutations. cCYP17D patients show parallel overproduction/overexcretion of 17-deoxysteroids, and marked reduction of F and AA. In addition to 17OH, 17,20-L activity was also impaired in cCYP17D. W406 and R362C mutations disclose similar Sand U patterns.
    Arquivos brasileiros de endocrinologia e metabologia 12/2010; 54(9):826-32. · 0.68 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. We sequenced the FP/TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction-based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. The frequency and type of FP/TMEM127 mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. We identified 19 potentially pathogenic FP/TMEM127 germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (P = 2.7 × 10(-4)) and/or with familial disease (5 of 20 samples; P = .005). The median age at disease onset in the FP/TMEM127 mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively; P = .54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel FP/TMEM127 mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. Germline mutations of FP/TMEM127 were associated with pheochromocytoma but not paraganglioma and occurred in an age group frequently excluded from genetic screening algorithms. Disease-associated mutations disrupt intracellular distribution of the FP/TMEM127 protein.
    JAMA The Journal of the American Medical Association 12/2010; 304(23):2611-9. · 29.98 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Congenital adrenal hyperplasia caused by classic 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder with a high prevalence of asymptomatic heterozygote carriers (HTZ) in the general population, making case detection desirable by routine methodology. HTZ for classic and nonclassic (NC) forms have basal and ACTH-stimulated values of 17-hydroxyprogesterone (17OHP) that fail to discriminate them from the general population. 21-Deoxycortisol (21DF), an 11-hydroxylated derivative of 17OHP, is an alternative approach to identify 21OHD HTZ. To determine the discriminating value of basal and ACTH-stimulated serum levels of 21DF in comparison with 17OHP in a population of HTZ for 21OHD (n = 60), as well as in NC patients (n = 16) and in genotypically normal control subjects (CS, n = 30), using fourth generation tandem mass spectrometry after HPLC separation (LC-MS/MS). Basal 21DF levels were not different between HTZ and CS, but stimulated values were increased in the former and virtually nonresponsive in CS. Only 17·7% of the ACTH-stimulated 21DF levels overlapped with CS, when compared to 46·8% for 17OHP. For 100% specificity, the sensitivities achieved for ACTH-stimulated 21DF, 17OHP and the quotient [(21DF + 17OHP)/F] were 82·3%, 53·2% and 87%, using cut-offs of 40, 300 ng/dl and 46 (unitless), respectively. Similar to 17OHP, ACTH-stimulated 21DF levels did not overlap between HTZ and NC patients. A positive and highly significant correlation (r = 0·846; P < 0·001) was observed between 21DF and 17OHP pairs of values from NC and HTZ. This study confirms the superiority of ACTH-stimulated 21DF, when compared to 17OHP, both measured by LC-MS/MS, in identifying carriers for 21OHD. Serum 21DF is a useful tool in genetic counselling to screen carriers among relatives in families with affected subjects, giving support to molecular results.
    Clinical Endocrinology 12/2010; 73(6):700-6. · 3.40 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Congenital adrenal hyperplasia (CAH) resulting from 17α-hydroxylase/17,20-lyase deficiency is a rare autosomal recessive disease and the second most common form of CAH in Brazil. We describe the case of a Brazilian patient with CYP17 deficiency (17α-hydroxylase/17,20-lyase deficiency) caused by a homozygous p.R96W mutation on exon 1 of the CYP17 gene, an unusual genotype in Brazilian patients with this form of CAH. The patient, raised as a normal female, sought medical care for lack of pubertal signs and primary amenorrhea at the age of 16 years. At evaluation, the presence of a 46,XY karyotype, hypertension and hypokalemia were observed. We emphasize the recognition of CYP17 deficiency in the differential diagnosis of cases of hypergonadotrophic hypogonadism and hypertension in young patients who need specific treatment for both situations.
    Arquivos brasileiros de endocrinologia e metabologia 11/2010; 54(8):744-8. · 0.68 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Although much is known about the increased levels of the 21-hydroxylase substrates 17-hydroxyprogesterone (17OHP) and 21-deoxycortisol (21DF) - the biochemical markers of all forms of 21-hydroxylase deficiency (21OHD), only limited information is available on the zona fasciculata (ZF) products distal to the enzymatic block: 11-deoxycortisol (S), 11-deoxycorticosterone (DOC), and corticosterone (B). To investigate whether basal and post-ACTH levels of S, DOC, and B and the 21-hydroxylase precursor-to-product ratios determined by tandem mass spectrometry preceded by high-performance liquid chromatography separation (liquid chromatography-tandem mass spectrometry) could disclose distinct profiles in genotypically confirmed classic (no.=14) and non-classic (NC) (no.=18) patients, heterozygote carriers (no.=61) and wildtypes (WT) (no.=27) for 21OHD. Salt wasting (SW) and simple virilizing (SV) had higher basal levels of DOC with no further increase in response to ACTH. Stimulated DOC was similar in 21OHD patients and carriers but was reduced as compared to WT. ACTH-stimulated B increased gradually from SW and SV through WT. The post-ACTH 21DF/B ratio was able to detect 92% of the carriers among WT. All NC patients could be detected by post-ACTH 17OHP/DOC and 21DF/B, with no overlap with 21OHD carriers. Although 21-hydroxylase is a key enzymatic step in both 17-hydroxy and 17-deoxy pathways of ZF, the reaction is mostly affected in the latter pathway, leading to a significant impairment of B production, which may further characterize the 21OHD subtypes. Also, the precursor-to-product ratios, particularly 21DF/B, can demonstrate the distinctive outline of 21OHD subtypes, including carriers and normal subjects.
    Journal of endocrinological investigation 10/2010; 34(8):587-92. · 1.65 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: To identify relevant questions related to sex definition and re-designation and reconstructive surgery in patients with congenital adrenal hyperplasia (CAH), and to understand the role of the psychologist in providing care for these patients. We selected 21 subjects: 7 pediatric endocrinologists from 5 Brazilian Public Health System institutions, 9 parents and 6 patients with CAH, according to a qualitative research model. In this paper, 3 of the studied categories are analyzed: 'sex definition and re-designation', 'reconstructive surgery/vaginal dilation', and 'psychology'. Parents' main anguish relates to the situation of an unnamed sex at birth, whereas sex re-designation was distressful to physicians. A sense of loneliness when dealing with the disease and treatment was a common anguish among patients; dilation procedures were the major complaint. In general, physicians recommend that genital reconstructive surgery be performed early on to avoid future trauma. In such a complex scenario, it is remarkable that not all the reference service staff have a psychologist on duty. Difficulties to deal with questions involving sexuality were evident and dilation procedures are an additional source of trauma for these patients.
    Arquivos brasileiros de endocrinologia e metabologia 12/2009; 53(9):1125-36. · 0.68 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: To understand the meanings/thoughts of a group of parents, patients and physicians regarding congenital adrenal hyperplasia (CAH), and to evaluate their anguishes, doubts and anxieties. We selected 21 subjects: 7 pediatric endocrinologists from five Brazilian Public Health System institutions, 9 parents and 6 patients with CAH, according to the qualitative research model. Three of the studied categories are presented: 'disease and treatment', 'doubts and anguishes' and 'relationships.' Parents' main anguishes relate to the situation of an unnamed sex at birth. A sense of loneliness when dealing with the disease is the major anguish among patients, whereas physicians show hopelessness with the passivity parents and patients. The apparent submissiveness of patients/parents during consultations must be evaluated cautiously. University Hospitals outpatient clinic dynamics have a direct effect on this behavior: physicians do not talk openly with parents who in turn do not talk with their children, whereas patients chose to protect their parents from additional suffering. Thus, some miscommunication is noticeable among these subjects. These observations suggest that a special mindful measure should be built for these patients.
    Arquivos brasileiros de endocrinologia e metabologia 12/2009; 53(9):1112-24. · 0.68 Impact Factor
  • Arquivos Brasileiros De Endocrinologia E Metabologia - ARQ BRAS ENDOCRINOL METABOL. 01/2009; 53(9).
  • Arquivos Brasileiros De Endocrinologia E Metabologia - ARQ BRAS ENDOCRINOL METABOL. 01/2009; 53(9).
  • [show abstract] [hide abstract]
    ABSTRACT: The question addressed in this study was the nature of the enzyme required to remove the side-chain of 17-hydroxycorticosteroids, leading in the case of cortisol to the excretion of 11beta-hydroxyandrosterone, 11-oxo-androsterone and the corresponding etiocholanolones. We questioned whether it could be CYP17, the 17-hydroxylase/17,20-lyase utilized in androgen synthesis. The conversion of exogenous cortisol to C(19) steroids in patients with complete 17-hydroxylase deficiency (17HD) was studied rationalizing that if CYP17 was involved no C(19) steroids would be formed. The urinary excretion of the four 11-oxy-C(19) steroids as well as many of the major C(21) cortisol metabolites were measured by GC/MS. Our results showed that the conversion of cortisol to C(19) steroids was normal in 17HD indicating that a currently unidentified enzyme must be responsible for this transformation. A secondary goal was to determine to what extent 11-oxy-C(19) steroids were metabolites of cortisol or adrenal synthesized 11beta-hydroxyandrostenedione. Since cortisol-treated 17HD patients cannot produce androstenedione, all C(19) 11-oxy-metabolites excreted must be derived from exogenous cortisol. The extent to which 17HD patients have lower relative excretion of C(19) steroids should reflect the absence of 11beta-hydroxyandrostenedione metabolites. Our results showed almost all of 11-oxo-etiocholanolone and 11beta-hydroxyetiocholanolone were cortisol metabolites, but in contrast the excretion of 11beta-hydroxyandrosterone was less than 10% that of normal individuals, indicating that in excess of 90% must be a metabolite of 11beta-hydroxyandrostenedione.
    Steroids 08/2008; 73(6):652-6. · 2.80 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: The activity of the hypothalamic-pituitary-adrenal axis is usually modulated by several stress factors, including exercise. Different responses are induced by physical training according to duration and intensity of exercise. During prolonged training, cortisol remains normal or decreased as a consequence of altered cortisol secretion, metabolism and excretion, and possibly by changes in glucocorticoid sensitivity. The aim of this study was to evaluate the impact of prolonged physical training on the glucocorticoid sensitivity. Eighteen cadets of the Air Force Academy, mean (SD) age: 18.7 (1.0) years, underwent an intensive 6-week preparatory training-period considered adequate by inducing significant changes on body composition measured by bioelectrical impedance. Measurement of individual's pituitary glucocorticoid sensitivity was done by an intravenous very low dose dexamethasone suppression test (20 microg/m (2)) that was performed before and after the training period. Cortisol levels were obtained at basal condition and 120 minutes after the dexamethasone infusion. Basal cortisol showed a significant decrease after prolonged training. The percent cortisol suppression after dexamethasone tended to be lower after the training period. Overall, our data suggest that prolonged physical training is able to reduce glucocorticoid sensitivity, which can have a beneficial impact in chronic stress conditions.
    Hormone and Metabolic Research 07/2008; 40(10):718-21. · 2.15 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: 21-Hydroxylase deficiency (21OHD) is the commonest form of congenital adrenal hyperplasia, while 11betaOHD represents 5% of cases. Although both result from mutations in distinct genes, cases of 'apparent' combined 21OHD and 11betaOHD (AC21,11OHD) have been occasionally reported. A 6 year-old girl, born with ambiguous genitalia and salt-loss, had serum elevations (ng/dl) of androstenedione (>1,000), 17-hydroxyprogesterone (17OHP; 38,483), 21-deoxycortisol (21DF; 23,338), and 11-deoxycortisol (S; 4,928), suggesting AC21,11OHD. CYP21A and CYP11B1 genotyping identified mutations only in the former. On follow-up, serum S became normal but 17OHP and 21DF were still elevated. ACTH stimulation disclosed elevated levels of 17OHP and 21DF, but unresponsive S and undetectable deoxycorticosterone. The hormonal pattern initially suggested AC21,11OHD, but subsequent normalization of S showed transient 11-hydroxylase inhibition. This may have occurred by enzyme or co-enzyme immaturity or functional discrepancy, but also by selective inhibition of 11betaOH by excess intra-adrenal concentration of androgens, acting as pseudo-substrates for this enzyme.
    Journal of pediatric endocrinology & metabolism: JPEM 05/2008; 21(5):487-94. · 0.75 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: To report and analyse cases of cystic phaeochromocytoma at our institution and in previous publications, as adrenal cystic masses are usually associated with nonfunctional lesions, but they can be phaeochromocytoma. The prospective adrenalectomy database at our institution was reviewed to identify patients with phaeochromocytoma and cystic lesions. The clinical, radiological and histological features of cystic phaeochromocytoma were evaluated. Other previously published data were identified and compared with the present series. In all, there were 107 adrenalectomies at our institution from November 2000 to March 2007; 31 of these patients had a confirmed diagnosis of phaeochromocytoma and six (19%) were cystic phaeochromocytomas. Three of the six cases were asymptomatic and had a negative biochemical evaluation (one male and five females, mean tumour size 6.6 cm); the imaging diagnosis was mainly based on computed tomography and magnetic resonance imaging, and the foremost feature was the enhancement of the tumour rim associated with a central cystic mass. Nine other previously published cases were reviewed. From the present large series and previous anecdotally reported cases, patients with cystic phaeochromocytomas are more likely to be asymptomatic, to complain of chronic abdominal pain, and to have a negative biochemical evaluation, which might deter physicians from conducting a full evaluation for phaeochromocytoma and mislead the final diagnosis. As such, there could be an even higher prevalence of this entity that is yet to be determined.
    BJU International 03/2008; 101(3):345-50. · 3.05 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: The wide variability of responses to corticotherapy suggests a role for individual recognition of steroid sensitivity in order to customize treatment. Oral dexamethasone (DEX) administration may be hindered by the rate of its intestinal absorption and the liver first-passage effect. In this study we suggest that an intravenous very low dose DEX suppression test (VLD IV-DST) can be used as an index for glucocorticoid (GC) sensitivity. We evaluated 87 normal subjects: 44 prepubertal children, 23 adolescents and 20 adults with a VLD IV-DST using 20 mug/m(2) of DEX (dose able to recognize GC sensitivity). Cortisol was initially measured at several time-points after DEX prompting us to establish its nadir and subsequent simplification of the test by measuring cortisol at baseline and after 120 min. Baseline cortisol was similar in adolescents and in adults, but lower in children. There was a spectrum of individual responses in all age groups. The percent reduction of cortisol after 120 min was different in these three age groups, with median values of 44.4% in children, 25.9% in adolescents and 61.6% in adults. This simplified VLD IV-DST using 20 mug/m(2) of DEX is useful to evaluate individual sensitivity to GC in different age groups.
    Hormone Research 02/2008; 69(6):357-62. · 2.48 Impact Factor
  • Journal of Urology - J UROL. 01/2008; 179(4):18-18.

46 Following View all

29 Followers View all