Prevalence of type 2 diabetes among tribal population of india: a multi-centric cross-sectional study.

BACKGROUND: The perception among healthcare workers is that the Indian tribal (indigenous) population are less affected by diabetes. This paper reports the prevalence of type 2 diabetes and its associated factors among tribal populations from six districts across India. METHODOLOGY: Random blood glucose (RBG) and fasting blood glucose (FBG) were measured for 8486 and 3131 adults, respectively, with a glucose meter. FBG ≥ 126 mg/dL (7.0 mmol/L) and RBG ≥ 200 mg/dL (11.1 mmol/L) were used to diagnose diabetes. In addition, blood pressure, anthropometric (height, weight, waist and hip circumferences), socio-demographic (age, gender, education, type of tribe and type of village) and behavioural data (tobacco smoking, non-smoking tobacco use and alcohol consumption) were collected. RESULTS: The overall prevalence of type 2 diabetes, based on RBG, was 4.77% (95% CI: 4.33-5.25). The prevalence of type 2 diabetes and prediabetes, based on FBG, was 6.80% (95% CI: 5.95-7.74) and 8.69% (7.72-9.73), respectively. The prevalence of type 2 diabetes was significantly associated with age (p<0.001), smokeless tobacco use (p < 0.05), hypertension (p < 0.001) and obesity (p < 0.01). CONCLUSION: The prevalence of type 2 diabetes among the Indian tribal population reported in this study is less than the national average of 7.3% for the general population. Hypertension and obesity were the major risk factors. Due to changing behavioural patterns, including dietary behaviour, there is likely to be an increase in the prevalence of hypertension and obesity, which further leads to increased prevalence of type 2 diabetes. Hence, appropriate interventions are to be initiated by the primary healthcare system.

Normative Data on Dehydroepiandrosterone Sulphate (DHEAS) and its Attributes in Healthy Indian Children and Adolescents.

Dehydroepiandrosterone sulphate (DHEAS), the biochemical indicator of adrenarche and pubarche, is of paramount importance in the evaluation of puberty-related disorders. The reference range of DHEAS should be ethnicity, age, sex, pubarche and Tanner stage specific. Anthropometry, puberty assessment and hormonal parameters were estimated using electrochemiluminescence assay. Bone age was estimated using the BoneXpert software. Of 2191 healthy Indian children aged 5-18 y screened at Chandigarh, 1919 were included in the final analysis (994 boys). The median DHEAS levels at pubarche stage P2 were 82.10 (55.0-129.0) g/dl in girls and 132.50 (95.12-205.50) g/dl in boys. By ROC analysis, the level of DHEAS at pubarche was 63.7 g/dl (sensitivity 72.6%, specificity 64.4%) in girls and 82.2 g/dl (sensitivity 81.8%, specificity 68.8%) in boys. The median age at adrenarche was 9.5 y in both sexes. On multivariate regression analysis; bone age, body mass index (BMI), gonadal steroids, and insulin-like growth factor-1 (IGF-1) significantly correlated with serum DHEAS levels in either sex.

Hypertension Prevalence, Awareness, Treatment, Control and Risk Factors in Tribal Population of India: a Multi-Centric Cross-Sectional Study.

The prevalence of hypertension is increasing in the tribal population of India. Lifestyle modifications, including dietary changes and acculturation, are the main reasons for the high prevalence of hypertension among the Indian indigenous (tribal) population. This paper reports hypertension prevalence, awareness, treatment, control and risk factors among tribes in five districts of different geographical zones of India. A cross-sectional study was conducted among the adult tribal population of 7590 from these states. Data related to blood pressure, anthropometry, demographic and behavioural variables were collected with prior consent from the participants. The prevalence of hypertension is 34.0% and 28.3% among men and women, respectively. Of the total hypertensives, 27.5% were aware of their hypertension status; of them, 83.9% were receiving treatment, and blood pressure was in control among 33.5% of patients who were receiving treatment. Age, alcohol intake, sedentary lifestyle, Particularly Vulnerable Tribal Groups status and body mass index are found to be significantly associated with the prevalence of hypertension. The prevalence of hypertension is high among these tribal populations, which could be due to modernization and acculturation. Awareness and treatment-seeking behaviour are poor. Hence, early screening, awareness campaigns for seeking treatment, and health promotion are immediately required. Comprehensive health promotion programs need to promote lifestyle modification and re-orientation of the primary health care system to improve availability and accessibility to hypertension screening and treatment.

Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes.

BACKGROUND: Organic cation transporter 1 primarily governs the action of metformin in the liver. There are considerable inter-individual variations in metformin response. In light of this, it is crucial to obtain a greater understanding of the influence of OCT1 expression or polymorphism in the context of variable responses elicited by metformin treatment. RESULTS: We observed that the variable response to metformin in the responders and non-responders is independent of isoform variation and mRNA expression of OCT-1. We also observed an insignificant difference in the serum metformin levels of the patient groups. Further, molecular docking provided us with an insight into the hotspot regions of OCT-1 for metformin binding. Genotyping of these regions revealed SNPs 156T>C and 1222A>G in both the groups, while as 181C>T and 1201G>A were found only in non-responders. The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity. CONCLUSION: Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders.

Clinical Manifestations of Hyperandrogenism and Ovulatory Dysfunction Are Not Associated with His1058 C/T SNP (rs1799817) Polymorphism of Insulin Receptor Gene Tyrosine Kinase Domain in Kashmiri Women with PCOS.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder affecting premenopausal women. Besides primary features like anovulation, hyperandrogenism, and polycystic ovaries, women with PCOS present with multiple metabolic, cardiovascular, and psychological disorders. The etiology is multifactorial and the different genetic variants are suggested to play an important role in pathogenesis. Insulin resistance is a ubiquitous finding in PCOS and SNPs in genes involved in the insulin signaling pathway are possible candidates that can explain the development of clinical manifestations of PCOS. AIM: We aimed to investigate the association of INSR His1058 C/T (rs1799817) single nucleotide polymorphism with PCOS in Kashmiri women. The genotypic-phenotypic correlation of the tested SNP with hyperandrogenism, ovulatory dysfunction, and metabolic markers was evaluated. RESULTS: The allele frequency (OR = 1.00, 95% CI = 0.67-1.48, χ 2 = 0.01, P=0.99) and genotype distribution (χ 2 = 3.73, P=0.15) in INSR C/T polymorphism were comparable with controls. No significant association was found with PCOS in dominant (P=0.194), recessive (P=0.442), and homo vs. het. (P=0.5) genotype models. Genotype-phenotype correlation analysis revealed that variant TT genotype had significantly higher HOMA (P=0.029) and reduced insulin sensitivity QUICKI (P=0.037) values. There was no significant variation in the prevalence of hirsutism, acne, alopecia, menstrual disturbances, acanthosis nigricans, and obesity (all P > 0.05) in different INSR C/T genotypes. CONCLUSION: The INSR C/T SNP (rs1799817) does not increase the risk of PCOS in Kashmiri women. This SNP is unlikely to play a significant role in the development and manifestation of clinical symptoms of polycystic ovary syndrome.

Effect of steroid hormone receptor gene variants PROGINS (Alu insertion) and PGR C/T (rs1042839) as a risk factor for recurrent pregnancy loss in Kashmiri population (North India).

AIM: To unveil and evaluate the association and analyze the incidence and pattern of PGR gene polymorphisms (PROGINS insertion and PGR exon 5-C/T polymorphism) in recurrent pregnancy loss (RPL) couples of Kashmir. METHODS: In this study, analyses of PGR gene polymorphisms in RPL couples were genotyped by amplification-refractory mutation system polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. RESULTS: Molecular analysis of PGR gene polymorphisms indicated that the genotypic and allelic frequencies of PROGINS insertion and PGR exon 5 C/T polymorphisms of female group in cases and controls to be significantly different and poses risk in predisposition to RPL. Moreover, haplotype analysis in female group revealed that P1P2/CC and P1P2/CT genotype are significantly associated with RPL. CONCLUSION: Our data indicate that the PROGINS insertion and exon 5-C/T polymorphism can act as useful genetic markers in the female group, but needs to be replicated in further studies including various other single nucleotide polymorphisms of PGR gene relevant to pregnancy loss which may contribute to novel therapeutic targets with improved conclusions.

Impact of rs2414096 polymorphism of CYP19 gene on susceptibility of polycystic ovary syndrome and hyperandrogenism in Kashmiri women.

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in pre-menopausal women having complex pathophysiology. Several candidate genes have been shown to have association with PCOS. CYP19 gene encodes a key steroidogenic enzyme involved in conversion of androgens into estrogens. Previous studies have reported contradictory results with regard to association of SNP rs2414096 in CYP19 gene with PCOS and hyperandrogenism in different ethnic populations. Present study was aimed to investigate the impact of SNP rs2414096 polymorphism of CYP19 gene on susceptibility of PCOS and hyperandrogenism in Kashmiri women. Further we also studied the genotypic-phenotypic association for various clinical and biochemical parameters of this polymorphism. Case control study. 394 PCOS cases diagnosed on the basis of Rotterdam criteria and age matched 306 healthy women. We found a significant differences in genotypic frequency (χ2 = 18.91, p < 0.05) as well as allele frequency (OR 0.63, CI 0.51-0.78, χ2 = 17.66, p < 0.05) between PCOS women and controls. The genotype-phenotype correlation analysis showed a significant difference in FG score (p = 0.047) and alopecia (p = 0.045) between the three genotypes. Also, the androgen excess markers like DHEAS (p < 0.001), Androstenedione (p < 0.001), Testosterone (p < 0.001) and FAI (p = 0.005) were significantly elevated in GG genotype and showed a significant difference in additive model in PCOS women. rs2414096 polymorphism of CYP19 gene is associated with the risk of PCOS as well as with clinical and biochemical markers of hyperandrogenism, hence suggesting its role in clinical manifestations of PCOS in Kashmiri women.

RET/PTC Gene Rearrangements in Thyroid Carcinogenesis: Assessment and Clinico-Pathological Correlations.

Rearranged during transfection (RET) is a proto oncogene implicated in thyroid carcinogenesis of papillary type (PTC). The RET proto-oncogene in PTC is constitutively activated by fusion of its tyrosine kinase domain with the 5 ´region of another gene thereby generating chimeric products collectively named RET/PTCs. RET/PTC1 and RET/PTC3 are best characterized among all RET/PTC rearrangements. Kashmir valley has witnessed an alarming increase in thyroid cancer incidence in young women. Therefore, we investigated the occurrence of RET/PTC 1 & 3 rearrangements by semi quantitative and qPCR in thyroid cancer patients (n = 48) of Kashmiri population and interrelated results with various clinicopathological characteristics. We observed that all the RET/PTC rearrangements were confined to PTC cases (10/40). Presence of RET/PTC rearrangement significantly correlated with gender, elevated TSH levels and lymph node metastasis. Overall, our study advocates that RET/PTC3 rearrangement is a frequent event in the carcinogenesis of thyroid gland in Kashmiri population although a study with a larger sample size is needed to get a clear scenario.

Evaluation of serum anti-nuclear antibody among women with PCOS: a hospital based single center cross sectional study.

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8-12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.

Genetic variations in key inflammatory cytokines exacerbates the risk of diabetic nephropathy by influencing the gene expression.

BACKGROUND: Diabetic nephropathy is the single strongest predictor of mortality in patients with diabetes. The development of overt nephropathy involves important inter-individual variations, even after adjusting for potential confounding influences of modifiable and non-modifiable risk factors. Genome-wide transcriptome studies have reported the activation of inflammatory signaling pathways and there is mounting indication of the role of genetic factors. METHODS: We screened nine genetic variations in three cytokine genes (TNF-α, IL-6 and IL-ß) in 1326 unrelated subjects comprising of healthy controls (n = 464), type 2 diabetics with nephropathy (DN, n = 448) and type 2 diabetes without nephropathy (T2D, n = 414) by sequence-specific amplification. Functional implication of SNPs was elucidated by correlation studies and relative gene expression using Realtime-Quantitative PCR (RT-qPCR). RESULTS: Individual SNP analysis showed highest association of IL-1ß rs16944-TT genotype (OR = 3.51, 95%CI = 2.36-5.21, P = 0.001) and TNF-α rs1800629-AA genotype (OR = 2.75, 95% CI = 1.64-4.59, P = 0.001) with T2D and DN respectively. The haplotype frequency showed significant risk of seven combinations among T2D and four combinations among DN subjects. The highest risk of T2D and DN was associated with GGTGAGTTT (OR = 4.25, 95%CI = 3.3-14.20, P = 0.0016) and GACGACCTT (OR = 21.3, 95%CI = 15.1-28.33, P = 0.026) haplotypes respectively. Relative expression by RT-qPCR showed increased cytokine expression in cases as compared to controls. TNF-α expression was increased by more than four-folds (n-fold = 4.43 ±â€¯1.11) in DN. TNF-α, IL-6 and IL-1ß transcript levels were significantly modulated by promoter region SNPs. CONCLUSIONS: The present study implicates a strong association between cytokine TNF-α, IL-6 and IL-1ß gene promoter polymorphisms and modulation of transcript levels with susceptibility to nephropathy in diabetes subjects.

Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition.

Diabetes mellitus is increasing at an alarming rate and has become a global challenge. Insulin resistance in target tissues and a relative deficiency of insulin secretion from pancreatic ß-cells are the major features of type 2 diabetes (T2D). Chronic low-grade inflammation in T2D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and ß-cell dysfunction. Many factors advocate a causal link between metabolic stress and inflammation. Numerous cellular factors trigger inflammatory signalling cascades, and as a result T2D is at the moment considered an inflammatory disorder triggered by disordered metabolism. Cellular mechanisms like activation of Toll-like receptors, Endoplasmic Reticulum stress, and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2D with inflammation. This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2D by capturing relevant evidence from various sources. The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic ß-cells in T2D.

Significant association of TP53 Arg72Pro polymorphism in susceptibility to differentiated thyroid cancer.

BACKGROUND: Among various polymorphic variants of TP53 gene, codon 72 polymorphism (Arg72Pro) has been found to be associated with cancer susceptibility, but only few studies have investigated their effect on thyroid cancer risk. OBJECTIVE: A case control study was conducted to elucidate the possible role of this SNP as risk factor in thyroid cancer development and to examine its correlation with various clinicopathological variables. METHODS: In this study, we tested the genotype distribution by PCR-RFLP in 140 thyroid cancer patients and 200 cancer-free controls from Kashmir Valley. RESULTS: Genotype frequencies of Arg/Arg (GG), Arg/Pro (GC), and Pro/Pro (CC) genotypes among cases were 0.286, 0.343 and 0.371 while in controls 0.45, 0.37 and 0.18 respectively. Proline allele frequency was significantly higher than arginine frequency in patient group (OR = 2.06, 95% C.I = 1.5-2.8). Significant association was found between variant genotype of codon 72 of TP53 gene and young age group, female gender, urban dwellers, non-smokers and patients with elevated TSH levels (P < 0.05). CONCLUSION: It is evident from our study that Arg72Pro SNP of TP53 gene is connected with higher susceptibility to thyroid cancer especially in young age group, female gender, non-smokers and patients with elevated TSH levels, hence, implicated in thyroid carcinogenesis.

Epigenetic silencing of TSHR gene in thyroid cancer patients in relation to their BRAF V600E mutation status.

Promoter hypermethylation of multiple genes have been identified to play a role in thyroid cancers and most prominent among them is TSHR gene promoter hypermethylation in particular showing a close association with BRAF gene-altered status. Thus, the aim of this study was to analyze the TSHR gene promoter hypermethylation in a series of thyroid tumor tissues in the backdrop of their BRAF gene mutational status. Methylation-specific PCR (MS-PCR) was used for detection of promoter methylation while BRAF gene mutational status was analyzed by PCR followed by DNA sequencing in the same series of 60 thyroid tumor tissues. The promoter region of TSHR gene was found to be methylated in 25 % (15 of 60) of the thyroid cancer patients. Patients having elevated TSH levels showed strong association with methylation (OR = 4.0, P = 0.02). BRAF V600E mutation was found in 25 % (15 of 60) patients and among them TSHR promoter was methylated in 73.3 % (11 of 15) patients and only 26.7 % (4 of 15) patients with mutated BRAF showed the absence of TSHR promoter methylation. We found a significant association between the presence of methylation in TSHR with the BRAF V600E mutation-positive cases (P < 0.05). In conclusion, our study showed a high implication of TSHR gene methylation and its significant association with BRAF V600E mutation in thyroid tumors, depicting a positive connection between TSHR pathway and MAP Kinase pathway.

Impact of molecular alterations of BRAF in the pathogenesis of thyroid cancer.

BRAF alterations represent a novel indicator of the progression and aggressiveness of thyroid carcinogenesis. So, the main aim of the study was to elucidate the involvement of BRAF gene mutations and its expression in Kashmiri (North India) patients and investigate their association with clinico-pathological characteristics. Mutational analysis of BRAF gene was performed by polymerase chain reaction followed by DNA sequencing, whereas analysis of BRAF protein expression was done by western blotting. Overall mutations in BRAF was found to be 25% (15 of 60) and all of them were transversions (T>A) affecting codon 600 (valine to glutamine), restricted only to papillary thyroid cancer and well-differentiated grade. Patients with well-differentiated disease and in particular elevated thyroid-stimulating hormone levels were significantly associated with BRAF mutations (P < 0.05). Overall, 90% (54 of 60) of thyroid cancer cases showed increased expression of BRAF and non-smokers being significantly associated with BRAF over-expression. Totally, 86.7% (13 of 15) of BRAF mutation-positive patients were having over-expression of BRAF protein, whereas 91.2% (41 of 45) of patients with wild-type BRAF status were having over-expressed BRAF protein (P > 0.05). We conclude that both mutational events as well as over-expression of BRAF gene is highly implicated in pathogenesis of thyroid cancer and the BRAF protein over-expression is independent of the BRAF mutational status of thyroid cancer patients.

CTTTA Deletion/Insertion polymorphism in 3'-UTR of LEPR gene in type 2 diabetes subjects belonging to Kashmiri population.

BACKGROUND: Type 2 diabetes mellitus is a multi-factorial disease in which both genetic and non-genetic factors interact in order to precipitate the diabetic phenotype. Among various predisposing genetic loci, a pentanucleotide (CTTTA) Del/Ins variant in the 3'-UTR of the LEPR gene is associated with type 2 diabetes and its related traits. This study was done to explicate for the first time the association of this Del/Ins polymorphism of LEPR gene in type 2 diabetes patients belonging to the ethnic population of Kashmir valley. METHODS: 670 unrelated subjects comprising of 320 type 2 diabetes patients and 350 healthy controls were included in the study. Genotyping of the untranslated region of LEPR gene encompassing this Del/Ins variant was done by PCR-RFLP technique and results were validated by direct sequencing. RESULTS: Genotype frequencies for both type 2 diabetes cases and healthy controls were consistent with Hardy-Weinberg equilibrium (χ(2) = 3.09 and 2.37, P = NS). The Del/Del genotype was predominantly found in cases than controls (P = 0.003, OR: 0.62, CI: 0.45-0.85). Carriers of Ins/Ins genotype were relatively protected against the risk factors (P = 0.0004, OR: 0.31, 95% CI: 0.15-0.61). A positive association was observed between the Del allele and the risk factors of type 2 diabetes. CONCLUSION: The results elucidate that the CTTTA Del allele is a genotypic risk factor of type 2 diabetes in the Kashmiri population.

Trp homozygotes at codon 64 of ADRB3 gene are protected against the risk of type 2 diabetes in the Kashmiri population.

The prevalence of type 2 diabetes mellitus has reached epidemic proportions worldwide. Type 2 diabetes is a consequence of complex interactions among multiple genetic variants and environmental risk factors. Polymorphisms in various candidate genes confer susceptibility to diabetes. This study was undertaken to analyse a single nucleotide polymorphism Trp64Arg (C↔T) in the ADRB3 gene and elucidate its effects on type 2 diabetes and its associated risk factors. The study included 200 type 2 diabetes patients and 300 age and gender matched healthy controls belonging to the ethnic Kashmiri population. Polymerase chain reaction-restriction fragment length polymorphism technique was used for genotyping and the results were validated by direct sequencing assay. Genotypes for Trp64Arg polymorphism were in Hardy-Weinberg equilibrium (χ(2)=0.48, p=NS). Frequency of the Arg64 allele was 40% and 10.2% in cases and controls, respectively (p<0.05; odds ratio 5.89; 95% CI; 3.69-9.39). The Arg64 allele was directly related to higher body mass index, waist-to-hip ratio, dyslipidemia and uncontrolled disease status. The study signifies that the Arg64 allele of the ADRB3 gene is a genotypic risk factor and confers susceptibility to type 2 diabetes, whereas the homozygous Trp64 genotype exerted a protective effect in our population.

Lack of mutational events of RAS genes in sporadic thyroid cancer but high risk associated with HRAS T81C single nucleotide polymorphism (case-control study).

High incidence of thyroid cancer worldwide indicates the importance of studying genetic alterations that lead to its carcinogenesis. Specific acquired RAS mutations have been found to predominate in different cancers, and HRAS T81C polymorphism has been determined to contribute the risk of various cancers, including thyroid cancer. We screened the exons 1 and 2 of RAS genes (HRAS, KRAS, and NRAS) in 60 consecutive thyroid tissue (tumor and adjacent normal) samples, and a case-control study was also conducted for HRAS T81C polymorphism in HRAS codon 27 using the polymerase chain reaction-restriction fragment length polymorphism to test the genotype distribution of 140 thyroid cancer patients in comparison with 170 cancer-free controls from a Kashmiri population. No mutation was found in any of the thyroid tumor tissue samples, but we frequently detected polymorphism at nucleotide 81 (T > C) in exon 1 of HRAS gene. In HRAS T81C SNP, frequencies of TT, TC, and CC genotypes among cases were 41.4, 38.6, and 20.0 %, while in controls genotype frequencies were 84.1, 11.7, and 4.2 %, respectively. A significant difference was observed in variant allele frequencies (TC + CC) between the cases and controls (58.6 vs. 16 %) with odds ratio = 7.4; confidence interval (CI) = 4.3-12.7 (P < 0.05). Interestingly, combined TC and CC genotype abundantly presented in follicular thyroid tumor (P < 0.05). Moreover, a significant association of the variant allele (TC + CC) was found with nonsmokers (P < 0.05). This study shows that although thyroid cancer is highly prevalent in this region, the mutational events for RAS genes do not seem to be involved. Contrary to this HRAS T81C SNP of HRAS gene moderately increases thyroid cancer risk with rare allele as a predictive marker for follicular tumors.

Long-term efficacy of bromocriptine in macroprolactinomas and giant prolactinomas in men.

We prospectively analyzed presentations and long-term therapeutic responses to bromocriptine (BRC) in 29 newly diagnosed men with macroprolactinomas including 14 patients with 'giant prolactinoma'. Clinical symptoms, prolactin (PRL) levels and tumor size on MRI were measured before BRC and sequentially thereafter. The duration of follow-up were 6 to 96 (30.7 +/- 14.4) months. Pretreatment PRL ranged between 124 and 29200 ng/mL (1698 +/- 857.1) and tumor volume was between 2.81 and 132 cm(3) (21.1 +/- 24.3). Baseline PRL levels did not correlated with tumor volume (r = 0.45, P > 0.05). Significant decrease (P = 0.0003) in PRL, at least 96% of the pretreatment value from 1698 +/- 857.1 ng/mL to 42.4 +/- 30.6 ng/mL occurred in 26 patients. Persistent normalization of PRL levels (< 16 ng/mL) for at least 6 months was achieved in 12 patients (40.8%). Twenty-two patients (74.8%) achieved significant tumor shrinkage (P = 0.005) at study completion. An improvement in visual field defects (VFD) and restoration of libido and potency was observed in 40% and 33.3%, respectively. Trans-sphenoidal / trans-frontal pituitary surgery was performed in 9 patients (31%) for various reasons: pituitary apoplexy in 1, CSF rhinorrhea in 2, increasing prolactin in spite of BRC therapy in 3, and intolerant /resistant to BRC in 3 patients. These data suggest that, in male macro- and giant prolactinomas, dopamine agonists represent the first-line therapy effective in reducing PRL, restoration of libido and potency, improvement of VFD and determining tumor shrinkage.