[Show abstract][Hide abstract] ABSTRACT: Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa).
This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH).
This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups.
PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p < 0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p < 0.001) and at the inclusion in the study (p < 0.001) and IGFBP3 (0.016) among patients with Gleason < 7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason < 7 and ≥7.
Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients.
[Show abstract][Hide abstract] ABSTRACT: Acromegaly is frequently associated with thyroid diseases. In this study, we evaluated the frequency of thyroid disorders in a series of acromegalic patients.
We evaluated 106 acromegalic patients using thyroid ultrasonography (US) and measurements of GH, IGF-I, free T4, TSH and anti-thyroperoxidase antibody levels. IGF-I was expressed in mass units and age-related standard deviation scores (SD-scores). Fine-needle aspiration biopsy (FNAB) was performed on thyroid nodules with a diameter greater than one centimeter or with suspicious characteristics.
Thyroid disorders were found in 75 patients. Eleven patients had diffuse goiter, 42 patients had nodular goiter, and 22 patients had unspecific morphological abnormalities. Four patients (3.8%) had thyroid carcinoma. Considering the patients with diffuse or nodular goiter, thyroid volume was greater in patients with active acromegaly, and was positively correlated with GH, IGF-I, and IGF-I SD-score.
Our study confirmed that benign thyroid diseases are frequent in acromegalic patients. The prevalence of thyroid cancer was higher than in the overall population. We suggest that thyroid US should be routinely performed in patients with acromegaly.
Arquivos brasileiros de endocrinologia e metabologia 12/2013; 57(9):685-690. DOI:10.1590/S0004-27302013000900003 · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: Published data suggest that patients with acromegaly have an increased prevalence of prostate disorders. Objective: To evaluate prostatic disorders in acromegalic patients comparing these results after one year of treatment of acromegaly and with a group of healthy men. Materials and Methods: This study was composed of two parts: sectional study comparing patients with healthy controls (baseline) and prospective, longitudinal study (at baseline and after one year of treatment). Forty acromegalic patients were enrolled and evaluated at baseline and after one year with the application of international prostatic symptoms score (IPSS), digital rectal examination, measurements of growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein-3 (IGFBP-3), sex hormone-binding globulin (SHBG), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, total and free prostate-specific antigen (PSA) levels and prostate ultrasonography (US). Thirty healthy men were selected as control group. Results: We stratified patients and controls according to age, considering 40 years-old as cut off. Healthy controls under 40 had IPSS values lower than acromegalic patients. When considering only older patients and controls prostate hyperplasia and structural abnormalities were more frequent in acromegalics. After one year of treatment there was significant decrease in GH, IGF-I and prostate volume in acromegalics over 40 years-old. Conclusions: Acromegalics under 40 have more urinary symptoms according to IPSS and above 40 years-old higher frequency of structural changes and increased prostate volume than healthy men. Significant reduction of GH and IGF-I levels during treatment of acromegaly leads to decrease in the prostate volume.
International braz j urol: official journal of the Brazilian Society of Urology 06/2013; 39(3):393-401. DOI:10.1590/S1677-5538.IBJU.2013.03.13 · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer is the second most frequent malignancy diagnosed in adult men. Androgens are considered the primary growth factors for prostate normal and cancer cells. However, other non-androgenic growth factors are involved in the growth regulation of prostate cancer cells. The association between IGF-I and prostate cancer risk is well established. However, there is no evidence that the measurement of IGF-I enhances the specificity of prostate cancer detection beyond that achievable by serum prostate-specific antigen (PSA) levels. Until now, there is no consensus on the possible association between IGFBP-3 and prostate cancer risk. Although not well established, it seems that high insulin levels are particularly associated with risk of aggressive prostatic tumours. This review describes the physiopathological basis, epidemiological evidence, and animal models that support the association of the IGFs family and insulin with prostate cancer. It also describes the potential therapies targeting these growth factors that, in the future, can be used to treat patients with prostate cancer.
Arquivos brasileiros de endocrinologia e metabologia 11/2009; 53(8):969-75. DOI:10.1590/S0004-27302009000800010 · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acromegalic patients have an increased prevalence of prostatic disorders compared to age-matched healthy subjects. Increased size of the whole prostate or the transitional zone, together with an elevated incidence of other structural changes, such as nodules, cysts, and calcifications, have been reported. Prostate enlargement in young acromegalic patients with low testosterone levels due to central hypogonadism supports the hypothesis that chronic GH and IGF-I excess cause prostate hyperplasia. The relationship between prostatic carcinoma and acromegaly is, until now, only circumstantial. Long-term follow-up of these patients is necessary since epidemiologic studies showed association between serum IGF-I levels in the upper normal limit and prostate cancer in the general population. This review approaches prostate diseases in patients with acromegaly.
Arquivos brasileiros de endocrinologia e metabologia 11/2009; 53(8):963-8. DOI:10.1590/S0004-27302009000800009 · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acromegalic patients are considered "discordant" if their insulin-like growth factor type I (IGF-I) levels are increased for their age with "safe" growth hormone (GH) levels or if their IGF-I levels are normal for their age with "unsafe" GH levels. The prevalence of discordance in acromegalics has been described to vary from 9.4% to 39%, and it may be observed at diagnosis or during the follow up.
To evaluate the prevalence of discordant levels of IGF-I and GH in our acromegalic population.
Hormonal evaluation was made with an oral glucose tolerance test (OGTT) with the IGF-I being assessed in the basal sample at diagnosis and after 3 months of the adenomectomy. During treatment with octreotide LAR, a GH curve (for the calculation of mean GH) and IGF-I assessment were made every 3 months.
Among the 51 patients evaluated at diagnosis, the prevalence of discordance was 13.7% (7/51). Among the 58 patients evaluated after the surgical procedure, eight (13.8%) had discordant GH and IGF-I levels. Among the 42 patients evaluated during treatment with octreotide LAR, the prevalence of discordant GH and IGF-I levels was 33.3% (14/42). Using 1 microg/L as a cut off level for "safe" GH, the prevalence of discordance was 3.9%, 8.6% and 28.6% at diagnosis, after surgery and during treatment with octreotide LAR, respectively. No difference of sex, age or treatment modality was observed among discordant and concordant patients with any GH cut off level.
We observed a prevalence of discordance similar to that previously described in the literature. We believe that studies evaluating morbidity and mortality in discordant patients are also necessary and will enlighten the true impact of this condition in the follow up of acromegaly.
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence of sleep apnea (SA) and SA syndrome (SAS) in patients with acromegaly and correlate SA with clinical, laboratory, and cephalometric parameters.
Prospective and cross-sectional study of 24 patients with active acromegaly evaluated by clinical and laboratory (GH, IGF-I) parameters, polysomnography and magnetic resonance imaging (MRI) of the pharynx.
Out of 24 patients, 21 had SA (87.5%), of which 20 (95.3%) had the predominant obstructive type. Median age of these 21 patients was 54 years (range 23-75) and median estimated disease duration was 60 months (range 24-300). The frequency in SA patients of impaired glucose tolerance, diabetes mellitus (DM), and hypertension was 19, 33.3, and 71.4% respectively. Goiter was found in 10 patients (47.6%) and obesity in 18 (90%). Median GH level was 14 mug/l (1.4-198) and median %IGF-I (percentage above the upper limit of normal range of IGF-I) was 181% (-31.6 to 571.2). The prevalence of SAS was 52.4%. Apnea-hypopnea index (AHI) correlated significantly with age, waist circumference, body mass index, and hypopharynx area. The AHI was significantly higher in patients with hypertension and DM.
The prevalence of SA and SAS in acromegaly was similar to the one previously described in other series. Age was a significant risk factor, and hypertension and DM were significantly associated complications of SA. Obesity was also significantly related to SA, as a risk factor, a complication or both. Overall, cephalometric parameters by MRI did not correlate with SA.
European Journal of Endocrinology 05/2008; 158(4):459-65. DOI:10.1530/EJE-07-0753 · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the glucose metabolism in acromegalic patients before and after treatment with octreotide LAR.
This was a prospective and longitudinal study involving 30 patients from the acromegaly research outpatient clinic of the Endocrinology unit of the HUCFF/UFRJ. They underwent clinical and laboratorial evaluations, with measurements of growth hormone (GH), insulin-like growth factor type I (IGF-I), insulin, proinsulin, C peptide, glycosylated hemoglobin (HbA1c), IGF binding protein type 1 (IGFBP-1) and glucose, during oral glucose tolerance test (OGTT), before and after six months of treatment with octreotide LAR. The Wilcoxon signed-rank test was used and values of 5% were considered statistically significant.
We found 16 (54%) patients with normal glucose tolerance, 7 (23%) with impaired glucose tolerance and 7 (23%) diabetics. Twelve patients completed the six-month treatment, out of which three showed worsening of glucose tolerance and two (diabetics) had worse blood glucose control. Whereas there was an increase in waist circumference (p=0.03), there was a decrease in GH (p=0.04), with %IGF-I above the upper limit of reference values (% ULRV) [p=0.001], insulin (p=0.019), C peptide levels (p=0.002) and homeostatic model assessment (HOMA-IR) [p=0.039].
In this series, treatment with octreotide LAR led to a worsening of glucose tolerance in three non-diabetic patients and worsened glycemic control in two diabetics, in spite of reducing insulin resistance.
[Show abstract][Hide abstract] ABSTRACT: GH secretion, in acromegaly, is characterized by increased basal levels, as well as by increased frequency and amplitude of pulses. Evaluation of disease activity during follow-up of treated patients is frequently done with mean GH levels, although there is no established protocol for sample collection.
Determine mean GH value of 5 blood samples collected 30 min apart for 2 consecutive hours in the follow-up of acromegalic patients treated with octreotide LAR.
Ninety-one GH curves of 44 patients (25 women) were evaluated as were the respective IGF-I values (basal). Normal IGF-I for age and sex was considered standard for control of disease activity. Correlations between basal and mean GH were studied as were correlations between both values and %IGF-I above the upper limit of reference values (%ULRV).
Median age of the group was 45.5 years (range 28-73). Twenty-five patients (56.8%) had previous surgery and 7 (15.9%) had both surgery and radiotherapy. A positive correlation was found between mean and basal GH (r=0.953; p<0.001). Both basal and mean GH were correlated to %ULRV (r=0.645 and 0.661; p<0.001 for both). In only 3 of the 91 curves (3.3%) there were discordances between basal GH and IGF-I, however the latter was concordant with mean GH. In 3 other curves there was concordance between basal GH and IGF-I although the latter was discordant with mean GH.
There was no benefit to perform GH curves with the present protocol. It may be due to our established outpatient follow up protocol. The use of more complex protocols and the cost of multiple GH assays should be acknowledged, and probably reserved for patients with basal GH levels between 1 and 5 microg/L with discordant GH and IGF-I.
[Show abstract][Hide abstract] ABSTRACT: Ectopic growth hormone-releasing hormone (GHRH)-secreting tumors are rare and cause acromegaly with somatotroph hyperplasia. We report a case of acromegaly secondary to GHRH secretion by an incidentally discovered pheochromocytoma in a normotensive patient. A 23-year-old man presented with signs and symptoms of acromegaly. Laboratory evaluation confirmed the diagnosis and magnetic resonance imaging (MRI) revealed a sellar mass which was thought to be a macroadenoma and surgically resected. The patient was not cured and medical treatment was indicated. An abdominal ultrasound performed before initiation of medical treatment showed a solid/cystic lesion superiorly to the right kidney. An abdominal MRI confirmed an adrenal tumor. Hormonal workup of the adrenal incidentaloma revealed elevated urinary catecholamine and total metanephrines findings strongly suggestive of a pheochromocytoma. Acromegaly was then suspected to be due to ectopic secretion of GHRH by the tumor. Patient underwent surgical resection and histopathologic examination confirmed a pheochromocytoma which stained positively for GHRH. Also, review of the pituitary specimen confirmed somatotrophic hyperplasia. Genetic analysis of the ret proto-oncogene showed no mutation. Pituitary MRI was repeated 10 months after pheochromocytoma resection and revealed a slightly enlarged pituitary and partial empty sella. The diagnosis of acromegaly caused by ectopic production of GHRH is a challenging task. A careful histopathological examination of the surgically excised pituitary tissue has a key role to arouse the suspicion and guide the investigation of a secondary cause of acromegaly.
[Show abstract][Hide abstract] ABSTRACT: Acromegaly is a systemic disease with various etiologies. It can occur as a sporadic or, more rarely, as a familial disease. Numerous complications such as endocrine, cardiovascular, respiratory, metabolic, osteoarticular and neoplastic disturbances occur and must be taken into account when establishing a therapeutic strategy. For this reason, the decision as to a treatment modality of acromegaly must be followed by a thorough evaluation of the patient and once the diagnosis of complications is settled, adequate treatment should be instituted. Follow up of the patients requires periodical re-assessment of complications status.
[Show abstract][Hide abstract] ABSTRACT: Initially used to measure algic symptoms, visual analogue scales (VAS) can also be useful for the evaluation of satiety. The antiobesity agent sibutramine, unlike anorectic agents, decreases food intake mainly by stimulating satiety. To evaluate the effect of sibutramine on satiety, we used a VAS in obese adolescents participating in a double-blind, randomized trial comparing 10 mg of sibutramine to placebo. Each patient received 13 scales to be checked at hourly intervals, in a single day, from 9 am to 9 pm. A 500 kcal deficit diet was divided into 3 meals, with previously fixed times: 9:30 h, 12:30 h, 18:30 h. Using the scores obtained from each scale, a line graph was designed to represent the average satiety score throughout the day. Comparing the area under the curve for the 2 groups, we found 4.609 +/- 1.309 for the group treated with sibutramine and 4.141 +/- 1.432 for the placebo group, not reaching statistical significance (p= NS). Therefore, sibutramine does not seem do have an effect on satiety of obese adolescents, at least when satiety is evaluated by a VAS.