Arq Bras Endocrinol Metabol
· 2014 Mar · PMID 24830587
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The onset of puberty is first detected as an increase in the amplitude and frequency of pulses of gonadotropin-releasing hormone (GnRH) after a quiescent period during childhood. The reemergence of pulsatile GnRH secreti...The onset of puberty is first detected as an increase in the amplitude and frequency of pulses of gonadotropin-releasing hormone (GnRH) after a quiescent period during childhood. The reemergence of pulsatile GnRH secretion leads to increases in the secretion of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by the pituitary gland, and the consequent activation of gonadal function. Early activation of the hypothalamic-pituitary-gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty (CPP), which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. CPP is diagnosed on the basis of clinical signs of progressive pubertal development before the age of 8 years in girls and 9 years in boys, pubertal basal and/or GnRH-stimulated LH levels, and advanced bone age. Magnetic resonance imaging of the central nervous system is essential for establishing the CPP form as organic or idiopathic. Depot GnRH-analogues represent the first-line of therapy in CPP. Very recently, the genetic component of CPP was demonstrated by the evidence that the deficiency of the MKRN3 gene, located on long arm of chromosome 15, causes familial CPP in humans. In this current review, clinical and therapeutic aspects of the CPP will be discussed, contributing to adequate diagnosis and criterious approach of this relevant condition of pediatric endocrinology.
Arq Bras Endocrinol Metabol
· 2014 Mar · PMID 24830586
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Hirsutism is defined as excessive terminal hair growth in androgen-dependent areas of the body in women, which grows in a typical male distribution pattern. Hirsutism is a common clinical problem in women, and the treatm...Hirsutism is defined as excessive terminal hair growth in androgen-dependent areas of the body in women, which grows in a typical male distribution pattern. Hirsutism is a common clinical problem in women, and the treatment depends on the cause. The condition is often associated with a loss of self-esteem. Hirsutism reflects the interaction between circulating androgen concentrations, local androgen concentrations, and the sensitivity of the hair follicle to androgens. Polycystic ovary syndrome and idiopathic hirsutism are the most common causes of the condition. A woman's history and, physical examination are particularly important in evaluating excess hair growth. The vast majority of women with hirsutism have the idiopathic variety, and the diagnosis is made by exclusion. Serum testosterone level>200 ng/dL is highly suggestive of adrenal or ovarian tumor. Treatment of hirsutism should be based on the degree of excess hair growth presented by the patient and in the pathophysiology of the disorder. Treatment includes lifestyle therapies, androgen suppression, peripheral androgen blockage, and cosmetic treatments. The current review discusses definition, pathogenesis, physiopathology, differential diagnosis, diagnostic strategies, and treatment.
Arq Bras Endocrinol Metabol
· 2014 Mar · PMID 24830585
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The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity...The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.
Villar-Taibo R, Ballesteros-Pomar MD, Vidal-Casariego A
… +3 more, Alvarez-San Martín RM, Kyriakos G, Cano-Rodríguez I
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728169
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Pituitary apoplexy is a rare but potentially life-threatening clinical syndrome characterized by ischemic infarction or hemorrhage into a pituitary tumor. The diagnosis of pituitary tumor apoplexy is frequently complicat...Pituitary apoplexy is a rare but potentially life-threatening clinical syndrome characterized by ischemic infarction or hemorrhage into a pituitary tumor. The diagnosis of pituitary tumor apoplexy is frequently complicated because of the nonspecific nature of its signs and symptoms, which can mimic different neurological processes, including meningitis. Several factors have been associated with apoplexy, such as dopamine agonists, radiotherapy, or head trauma, but meningitis is a rarely reported cause. We describe the case of a 51-year-old woman with acromegaly due to a pituitary macroadenoma. Before surgical treatment, she arrived at Emergency with fever, nausea, vomiting and meningismus. Symptoms and laboratory tests suggested bacterial meningitis, and antibiotic therapy was initiated, with quick improvement. A computerized tomography (CT) scan at admission did not reveal any change in pituitary adenoma, but a few weeks later, magnetic resonance imaging (MRI) showed data of pituitary apoplexy with complete disappearance of the adenoma. Currently, her acromegaly is cured, but she developed hypopituitarism and diabetes insipidus following apoplexy. We question whether she really experienced meningitis leading to apoplexy or whether apoplexy was misinterpreted as meningitis. In conclusion, the relationship between meningitis and pituitary apoplexy may be bidirectional. Apoplexy can mimic viral or bacterial meningitis, but meningitis might cause apoplexy, as well. This fact highlights the importance of differential diagnosis when evaluating patients with pituitary adenomas and acute neurological symptoms.
Gonçalves AP, Baptista F, Nobre E
… +1 more, Carmo Id
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728168
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Hypoglycemia in apparently healthy adults is a rare finding in clinical practice requiring a thorough investigation of the cause. During the investigation, identification of hypoglycemia associated with inappropriately h...Hypoglycemia in apparently healthy adults is a rare finding in clinical practice requiring a thorough investigation of the cause. During the investigation, identification of hypoglycemia associated with inappropriately high levels of insulin and C-peptide should prompt the exclusion of rare causes of hypoglycemia, including pancreatic islet-cells disease and autoimmune hypoglycemia. In this paper, we describe two cases of hypoglycemia associated with endogenous hyperinsulinism, whose causes are uncommon in clinical practice, and review important aspects of the diagnosis and treatment of hyperinsulinemic hypoglycemia.
Souto SB, Baptista PV, Braga DC
… +1 more, Carvalho D
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728167
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Leydig cell tumors are rare ovarian steroid cell neoplasms. More than 75% of patients show signs of virilization due to overproduction of testosterone. We report a case of an 81-year-old woman with progressive signs of v...Leydig cell tumors are rare ovarian steroid cell neoplasms. More than 75% of patients show signs of virilization due to overproduction of testosterone. We report a case of an 81-year-old woman with progressive signs of virilization, and presenting vaginal bleeding. Clinical analyses revealed high levels of serum testosterone, delta 4-androstenedione and estradiol, and also inappropriate low levels of gonadotrophins for a post-menopausal woman. Transvaginal ultrasound showed no evidence of ovarian tumor, but pelvic and abdominal computerized axial tomography imaging revealed a left ovarian solid nodule, and no evidence of alteration in the adrenal glands. Total hysterectomy and bilateral salpingoophorectomy were performed. Histopathology and immunohistochemistry confirmed the diagnosis of Leydig cell tumor. After surgery, androgen levels returned to normal, and there was regression of the signs of virilization.
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728166
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OBJECTIVES: Phenylketonuria (PKU) was the first inherited metabolic disease known to cause mental retardation for which a newborn screening program (NBS) was developed. The objective of this study was to evaluate the eff...OBJECTIVES: Phenylketonuria (PKU) was the first inherited metabolic disease known to cause mental retardation for which a newborn screening program (NBS) was developed. The objective of this study was to evaluate the effectiveness of PKU NBS and the management of cases in the northeastern Brazilian state of Sergipe (SE). MATERIALS AND METHODS: We reviewed the phenylalanine concentrations in filter-paper collected from the heel (PKUneo) of 43,449 newborns; blood concentrations obtained by venipuncture in the subjects with abnormal PKUneo; the children's age at several phases of the program, the incidence of the disease from January 2007 to June 2008; and metabolic control of the patients. RESULTS: The coverage of NBS/SE was 78.93%. The children's age was 10 ± 7 days at PKUneo collection. Twelve children were recalled based on the PKUneo cutoff value at 28 ± 13 days. From these, the concentrations of phenylalanine collected by venipuncture were normal in five children. The incidence of hyperphenylalaninemia was 1/43,449, and of PKU was 1/8,690 (5 cases). One suspected subject died. Another death occurred in the cohort, in a confirmed PKU case. PKU treatment began within 51 ± 12 days of life. In the four patients under dietary phenylalanine restriction, metabolic control was often difficult. CONCLUSIONS: PKU NBS/SE has satisfactory coverage and adequate cutoff for recalling patients and diagnosis, but the onset of treatment is delayed, and follow-up metabolic control is frequently inadequate.
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728165
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OBJECTIVE: The Brazilian population has heterogeneous ethnicity. No previous study evaluated NR3C1 polymorphisms in a Brazilian healthy population. MATERIALS AND METHODS: We assessed NR3C1 polymorphisms in Brazilians of...OBJECTIVE: The Brazilian population has heterogeneous ethnicity. No previous study evaluated NR3C1 polymorphisms in a Brazilian healthy population. MATERIALS AND METHODS: We assessed NR3C1 polymorphisms in Brazilians of Caucasian, African and Asian ancestry (n = 380). In a subgroup (n = 40), we compared the genotypes to glucocorticoid (GC) sensitivity, which was previously evaluated by plasma (PF) and salivary (SF) cortisol after dexamethasone (DEX) suppression tests, GC receptor binding affinity (K d ), and DEX-50% inhibition (IC 50 ) of concanavalin-A-stimulated mononuclear cell proliferation. p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) allelic discrimination was performed by Real-Time PCR (Polymerase Chain Reaction). Exons 3 to 9 and exon/intron boundaries were amplified by PCR and sequenced. RESULTS: Genotypic frequencies (%) were: rs6195 (n = 380; AA:96.6/AG:3.14/GG:0.26), rs6189-6190 (n = 264; GG:99.6/GA:0.4), rs41423247 (n = 264; CC:57.9/CG:34.1/GG:8.0), rs6188 (n = 155; GG:69.6/GT:25.7/TT:4.7), rs258751 (n = 150; CC:88.0/CT:10.7/TT:1.3), rs6196 (n = 176; TT:77.2/TC:20.4/CC:2.4), rs67300719 (n = 137; CC:99.3/CT:0.7), and rs72542757 (n = 137; CC:99.3/CG:0.7). The rs67300719 and rs72542757 were found only in Asian descendants, in whom p.N363S and p.ER22/23EK were absent. The p.ER22/23EK was observed exclusively in Caucasian descendants. Hardy-Weinberg equilibrium was observed, except in the Asian for rs6188 and rs258751, and in the African for p.N363S. The K d , IC 50 , baseline and after DEX PF or SF did not differ between genotype groups. However, the mean DEX dose that suppressed PF or SF differed among the BclI genotypes (P = 0.03). DEX dose was higher in GG- (0.7 ± 0.2 mg) compared to GC- (0.47 ± 0.2 mg) and CC-carriers (0.47 ± 0.1 mg). CONCLUSION: The genotypic frequencies of NR3C1 polymorphisms in Brazilians are similar to worldwide populations. Additionally, the BclI polymorphism was associated with altered pituitary-adrenal axis GC sensitivity.
Onal ED, Saglam F, Sacikara M
… +2 more, Ersoy R, Cakir B
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728164
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OBJECTIVE: To establish whether there is a relationship between hyperprolactinemia and primary thyroid disorders, focusing on patients with autoimmune features. MATERIALS AND METHODS: The medical records of 100 patients...OBJECTIVE: To establish whether there is a relationship between hyperprolactinemia and primary thyroid disorders, focusing on patients with autoimmune features. MATERIALS AND METHODS: The medical records of 100 patients with hyperprolactinemia (HPRL) were retrospectively examined. Records of thyroid ultrasonography (USG), basal serum levels of thyroid stimulating hormone, circulating free thyroxine, free triiodothyronine, antithyroglobulin (anti-Tg), and antithyroperoxidase (anti-TPO) antibodies were analyzed. In 100 control subjects, matched by age and gender with HPRL patients, thyroid USG, thyroid function tests (TFTs), and autoantibody panel were obtained. RESULTS: The median PRL in patients was 93 ng/mL (range: 37-470). Twenty-five patients (25%) and 22 controls (22%) had positive anti-Tg and/or anti-TPO titers (P = 0.739). The median serum PRL was 98 (37-470) ng/mL in patients with positive thyroid autoantibodies, and 92 (40-470) ng/mL in patients who were negative (P = 0.975). Among the individuals with autoantibody positivity TFTs abnormalities were more frequent in HPRL patients (60%, out of 25 patients, 14 with subclinical hypothyroidism and one with hyperthyroidism) than in controls (9.1%, out of 22 patients, 2 with subclinical hyperthyroidism) (P < 0.001). Twenty-seven patients with HPRL and 31 controls had goiter (27 vs. 31%, P = 0.437). Forty-six patients (46%) and 50 (50%) controls had one or more of the features of thyroid disorder, which were goiter, positive thyroid autoantibody, and thyroid function abnormality (P = 0.888). CONCLUSION: HPRL may be associated with more severe thyroid dysfunction in patients with thyroid autoimmunity.
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728163
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OBJECTIVE: Visfatin is a recently discovered adipocytokine that contributes to glucose and obesity-related conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unkno...OBJECTIVE: Visfatin is a recently discovered adipocytokine that contributes to glucose and obesity-related conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unknown. We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats. MATERIALS AND METHODS: Sprague-Dawley rats were fed a normal diet or a high-fat diet for 16 weeks to develop obesity model. The high-fat-induced obesity model rats were then randomized to metformin (MET), swimming exercise (SWI), or adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat obesity control group and a normal control group, all with 10 rats per group. Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT and SM were determined by Western Blot. RESULTS: Metformin and swimming exercise improved lipid profile, and increased insulin sensitivity and body weight reduction were observed. Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM. CONCLUSION: Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity.
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728162
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OBJECTIVE: To investigate the efficacy of sorafenib in progressive radioiodine resistant metastatic thyroid carcinoma. SUBJECTS AND METHODS: Off-label observational study. Sorafenib 400 mg twice daily was evaluated. Ther...OBJECTIVE: To investigate the efficacy of sorafenib in progressive radioiodine resistant metastatic thyroid carcinoma. SUBJECTS AND METHODS: Off-label observational study. Sorafenib 400 mg twice daily was evaluated. Therapy duration was 12 ± 3 months (range 6-16 months). RESULTS: Eight patients were included (seven papillary, one insular variant). The eight patients meeting study criteria received sorafenib 400 mg orally twice a day until disease progression or unacceptable toxicity developed. One patient showed a partial response with tumor regression of -35%, six months after the beginning of the treatment; five patients exhibited stable disease and two patients had progressive disease and died. Thyroglobulin decreased within 4 weeks in all patients by 50% ± 23%. Adverse events: one patient had heart failure, and recovered after sorafenib withdrawal. However, she died five months later of sudden death. CONCLUSION: These data suggest a possible role for sorafenib in the treatment of progressive metastatic DTC. Adverse event are usually manageable, but severe ones may appear and these patients should be strictly controlled.
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728161
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OBJECTIVE: Therefore, we evaluated the relationship between the subclinical hypothyroidism and red cell distribution width (RDW) levels in a healthy population. SUBJECTS AND METHODS: The medical records of 23,343 consecu...OBJECTIVE: Therefore, we evaluated the relationship between the subclinical hypothyroidism and red cell distribution width (RDW) levels in a healthy population. SUBJECTS AND METHODS: The medical records of 23,343 consecutive health subjects were reviewed. Subjects were classified into four thyroid stimulating hormone (TSH) groups to determine the correlation between TSH and other variables in detail (0.3 to < 2.5 mU/L, 2.5 to < 5 mU/L, 5 to < 7.5 mU/L, and ≥ 7.5 mU/L). RESULTS: In the multivariate linear regression analysis, RDW was associated with TSH levels, and e-GFR was inversely associated with TSH levels, respectively (standardized beta coefficient = 0.102, -0.019; p < 0.001, p < 0.001). After adjusting for age and sex, in the four groups, TSH levels were significantly correlated with RDW, estimated glomerular filtration rate (e-GFR), and free thyroxine (fT4) levels in all groups. Furthermore in the 4 th group, RDW levels were more strongly associated with TSH levels than in the other groups (p = 0.006). CONCLUSIONS: RDW levels are correlated with euthyroid and subclinical thyroid status. Notably, RDW is more correlated with subclinical hypothyroidism than the euthyroid status. This study presents the relationship between the RDW levels and thyroid function using TSH level in a large healthy population.
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728160
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OBJECTIVES: GH therapy is still controversial, except in severe GH deficiency (SGHD). The objective of this study was to compare the response to growth hormone (GH) therapy in children with partial GH insensitivity (PGHI...OBJECTIVES: GH therapy is still controversial, except in severe GH deficiency (SGHD). The objective of this study was to compare the response to growth hormone (GH) therapy in children with partial GH insensitivity (PGHIS) and mild GH deficiency (MGHD) with those with SGHD. SUBJECTS AND METHODS: Fifteen PGHIS, 11 MGHD, and 19 SGHD subjects, followed up for more than one year in the Brazilian public care service, were evaluated regarding anthropometric and laboratory data at the beginning of treatment, after one year (1st year) on treatment, and at the last assessment (up to ten years in SGHD, up to four years in MGHD, and up to eight years in PGHIS). RESULTS: Initial height standard deviation score (SDS) in SGHD was lower than in MGHD and PGHIS. Although the increase in 1 st year height SDS in comparison to initial height SDS was not different among the groups, height-SDS after the first year of treatment remained lower in SGHD than in MGHD. There was no difference in height-SDS at the last assessment of the children among the three groups. GH therapy, in the entire period of observation, caused a trend towards lower increase in height SDS in PGHIS than SGHD but similar increases were observed in MGHD and SGHD. CONCLUSION: GH therapy increases height in PGHIS and produces similar height effects in MGHD and SGHD.
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728159
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The definition of the etiology of hyperprolactinemia often represents a great challenge and an accurate diagnosis is paramount before treatment. Although prolactin levels > 200-250 ng/mL are highly suggestive of prolacti...The definition of the etiology of hyperprolactinemia often represents a great challenge and an accurate diagnosis is paramount before treatment. Although prolactin levels > 200-250 ng/mL are highly suggestive of prolactinomas, they can occasionally be found in other conditions. Moreover, as much as 25% of patients with microprolactinomas may present prolactin levels < 100 ng/mL, which are found in most patients with pseudoprolactinomas, drug-induced hyperprolactinemia, or systemic diseases. On the other hand, some conditions may lead to falsely low PRL levels, particularly the so-called hook effect, that is an assay artifact caused by an extremely high level of PRL, and can be confirmed by repeating assay after a 1:100 serum sample dilution. The hook effect must be considered in all patients with large pituitary adenomas and PRL levels within the normal range or only modestly elevated (e.g., < 200 ng/mL). An overlooked hook effect may lead to incorrect diagnosis and unnecessary surgical intervention in patients with prolactinomas. Another important challenge is macroprolactinemia, a common finding that needs to be identified, as it usually requires no treatment. Although most macroprolactinemic patients are asymptomatic, many of them may present galactorrhea or menstrual disorders, as well as neuroradiological abnormalities, due to the concomitance of other diseases. Finally, physicians should be aware that pituitary incidentalomas are found in at least 10% of adult population.
Griz LH, Bandeira F, Gabbay MA
… +2 more, Dib SA, Carvalho EF
Arq Bras Endocrinol Metabol
· 2014 Feb · PMID 24728158
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Vitamin D deficiency and diabetes mellitus are two common conditions and they are widely prevalent across all ages, races, geographical regions, and socioeconomic conditions. Epidemiologic studies have shown association...Vitamin D deficiency and diabetes mellitus are two common conditions and they are widely prevalent across all ages, races, geographical regions, and socioeconomic conditions. Epidemiologic studies have shown association of vitamin D deficiency and increased risk of chronic diseases, such as cancer, cardiovascular disease, type 2 diabetes, and autoimmune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The identification of 1,25(OH)2D receptors and 1-α-hydroxilase expression in pancreatic beta cells, in cells of the immune system, and in various others tissues, besides the bone system support the role of vitamin D in the pathogenesis of type 2 diabetes. Observational studies have revealed an association between 25(OH) D deficiency and the prevalence of type 1 diabetes in children and adolescents. This review will focus on the concept of vitamin D deficiency, its prevalence, and its role in the pathogenesis and risk of diabetes mellitus and cardiovascular diseases.