ergoline and Insulin-Resistance

Hyperprolactinaemia is suggested to be associated with metabolic and hormonal complications. No previous study has compared the effect of different dopamine agonists on plasma lipids, carbohydrate metabolism markers and cardiovascular risk factors in patients with elevated prolactin levels. The study included eight bromocriptine-resistant women with prolactinoma (group 1) and twelve matched women with hyperprolactinaemia unrelated to prolactinoma (group 2). Group 1 was then treated with cabergoline, while group 2 with bromocriptine. Plasma lipids, glucose homeostasis markers and plasma levels of prolactin, insulin-like growth factor-1 (IGF-1) and cardiovascular risk factors were assessed before and after 6 months of therapy. Both treatments normalized plasma prolactin levels. Cabergoline reduced triglycerides, 2-hr post-challenge plasma glucose, the homeostatic model assessment of insulin resistance (HOMA-IR), and circulating levels of IGF-1, free fatty acids (FFA), uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen, as well as increased HDL cholesterol and 25-hydroxyvitamin D. With the exception of a reduction in HOMA-IR, bromocriptine treatment produced no significant effect on the investigated biomarkers. Cabergoline was superior to bromocriptine in affecting 2-hr post-challenge plasma glucose levels, HOMA-IR, as well as circulating levels of IGF-1, FFA, uric acid, hsCRP, homocysteine, fibrinogen and 25-hydroxyvitamin D. Our results may suggest that cabergoline is superior to bromocriptine when it comes to affecting atherogenic dyslipidaemia, insulin sensitivity and circulating levels of cardiovascular risk factors in hyperprolactinaemic patients. These findings seem to support previous observations that cabergoline may be a better treatment for patients with elevated prolactin levels than bromocriptine.

Topics: Adult; Blood Glucose; Bromocriptine; Cabergoline; Cardiovascular Diseases; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Insulin Resistance; Insulin-Like Growth Factor I; Lipids; Middle Aged; Prolactin; Risk Factors

The aim of this study was to evaluate the effect of Cabergoline on insulin sensitivity, inflammatory markers, and carotid intima media thickness in prolactinoma patients. Twenty-one female, newly diagnosed patients with prolactinoma were included in the study. None of the patients were treated previously. Cabergoline was given as treatment, starting with 0.5 mg/day and tapered necessarily. Blood samples were taken for prolactin, highly sensitive C-reactive protein, homocysteine, total cholesterol, low density lipoprotein (LDL) cholesterol, fasting glucose, insulin, and HOMA (homeostasis model assessment of insulin resistance) score was calculated, prior to and 6 months after starting treatment. The body mass index (BMI) was measured and carotid intima media thickness (CIMT) was evaluated for each patient prior to and 6 months after the treatment. The prolactin levels and LDL decreased significantly after cabergoline treatment. Insulin sensitivity improved independently from the decrease in prolactin levels and BMI. The significant decrease in homocysteine and hs-CRP was not related with the decrease in prolactin levels. The significant decrease in CIMT was independent from the decrease in prolactin levels, HOMA score, and BMI. Our data suggest that cabergoline treatment causes an improvement in insulin sensitivity and inflammatory markers and causes a decrease in CIMT independent from the decrease in prolactin, LDL cholesterol, and BMI. We conclude that short term cabergoline treatment can improve endothelial function independently from the changes in metabolic disturbances and inflammatory markers.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Biomarkers; Cabergoline; Carotid Intima-Media Thickness; Ergolines; Female; Glucose Tolerance Test; Humans; Inflammation; Insulin Resistance; Middle Aged; Pituitary Neoplasms; Prolactinoma; Young Adult

In view of the association of hyperprolactinaemia with insulin resistance, we hypothesized that patients with hyperprolactinaemia may present increased cardiovascular risk markers.. Descriptive clinical trial.. Serum glucose, insulin, insulin resistance, lipids, high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and soluble E-selectin (sELAM-1) serum levels were determined in 15 patients with hyperprolactinaemia at baseline (compared with 20 healthy subjects) and after 12 weeks of cabergoline therapy (0.5-1 mg twice per week). We also measured mononuclear cell NF-kappaB activation and TNF-alpha production in a subset of subjects.. Serum levels of prolactin (PRL), insulin, insulin resistance (HOMA-IR) index and hsCRP were significantly higher in patients than in control subjects. Markers of mononuclear cell activation did not differ between the groups. Hyperprolactinaemia, BMI and age were predictors of hsCRP. BMI was the only predictor of HOMA-IR. Cabergoline therapy significantly reduced serum PRL, insulin, hsCRP and sELAM-1 levels.. These data suggest that hyperprolactinaemia is associated with insulin resistance related to increased BMI and low-grade inflammation independently of BMI. Short-term cabergoline therapy can reduce the inflammatory markers.

Topics: Adult; Biomarkers; Blood Glucose; C-Reactive Protein; Cabergoline; Cardiovascular Diseases; E-Selectin; Enzyme-Linked Immunosorbent Assay; Ergolines; Female; Humans; Hyperprolactinemia; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Linear Models; Lipids; Male; Middle Aged; Obesity; Risk Factors; Tumor Necrosis Factor-alpha

Acromegaly is characterized by growth hormone (GH) and insulinlike growth factor-1 (IGF-1) hypersecretion, and GH and IGF-1 play important roles in regulating body composition and glucose homeostasis.. The purpose of our study was to investigate body composition including ectopic lipids, measures of glucose homeostasis, and gonadal steroids in patients with active acromegaly compared with age-, body mass index (BMI)-, and sex-matched controls and to determine changes in these parameters after biochemical control of acromegaly.. Cross-sectional study of 20 patients with active acromegaly and 20 healthy matched controls. Prospective study of 16 patients before and after biochemical control of acromegaly.. Body composition including ectopic lipids by magnetic resonance imaging/proton magnetic resonance spectroscopy; measures of glucose homeostasis by an oral glucose tolerance test; gonadal steroids.. Patients with active acromegaly had lower mean intrahepatic lipid (IHL) and higher mean fasting insulin and insulin area under the curve (AUC) values than controls. Men with acromegaly had lower mean total testosterone, sex hormone-binding globulin, and estradiol values than male controls. After therapy, homeostasis model assessment of insulin resistance, fasting insulin level, and insulin AUC decreased despite an increase in IHL and abdominal and thigh adipose tissues and a decrease in muscle mass.. Patients with acromegaly were characterized by insulin resistance and hyperinsulinemia but lower IHL compared with age-, BMI-, and sex-matched healthy controls. Biochemical control of acromegaly improved insulin resistance but led to a less favorable anthropometric phenotype with increased IHL and abdominal adiposity and decreased muscle mass.

Topics: Acromegaly; Adipose Tissue; Adult; Aged; Blood Glucose; Body Composition; Cabergoline; Case-Control Studies; Cross-Sectional Studies; Ergolines; Female; Gonadal Steroid Hormones; Human Growth Hormone; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Lipid Metabolism Disorders; Lipodystrophy; Male; Middle Aged; Peptides, Cyclic; Prednisone; Somatostatin

The metabolic syndrome is a growing epidemic; it increases the risk for diabetes, cardiovascular disease, fatty liver, and several cancers. Several reports have indicated a link between hormonal imbalances and insulin resistance or obesity. Transgenic (TG) female mice overexpressing the human chorionic gonadotropin β-subunit (hCGβ+ mice) exhibit constitutively elevated levels of hCG, increased production of testosterone, progesterone and prolactin, and obesity. The objective of this study was to investigate the influence of hCG hypersecretion on possible alterations in the glucose and lipid metabolism of adult TG females. We evaluated fasting serum insulin, glucose, and triglyceride levels in adult hCGβ+ females and conducted intraperitoneal glucose and insulin tolerance tests at different ages. TG female mice showed hyperinsulinemia, hypertriglyceridemia, and dyslipidemia, as well as glucose intolerance and insulin resistance at 6 months of age. A 1-week treatment with the dopamine agonist cabergoline applied on 5-week-old hCGβ+ mice, which corrected hyperprolactinemia, hyperandrogenism, and hyperprogesteronemia, effectively prevented the metabolic alterations. These data indicate a key role of the hyperprolactinemia-induced gonadal dysfunction in the metabolic disturbances of hCGβ+ female mice. The findings prompt further studies on the involvement of gonadotropins and prolactin on metabolic disorders and might pave the way for the development of new therapeutic strategies.

Topics: Animals; Blood Glucose; Cabergoline; Chorionic Gonadotropin, beta Subunit, Human; Ergolines; Female; Glucose Intolerance; Hyperinsulinism; Hyperprolactinemia; Hypertriglyceridemia; Insulin; Insulin Resistance; Mice; Mice, Transgenic; Prolactin; Triglycerides

Pseudoacromegaly is a extremely rare condition previously described and characterized by acromegaloid changes, tissue overgrowth, without elevations in insulin-like growth factor or growth hormone as seen in Acromegaly. We present the case of a young female seen initially with acromegaloid features and a pituitary microadenoma. After work-up the patient was diagnosed as insulin-mediated pseudoacromegaly. Only a few cases of pseudoacromegaly has been reported and should always be considered when evaluating patients for acromegaloid features with negative biochemical and hormonal levels.

Topics: Acanthosis Nigricans; Acromegaly; Adult; Bromocriptine; Cabergoline; Diagnosis, Differential; Ergolines; Female; Gastrointestinal Diseases; Hirsutism; Human Growth Hormone; Humans; Hyperprolactinemia; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Complications, Neoplastic; Prognathism; Prolactinoma

Currently available studies that fully analyse the metabolic parameters in patients with prolactinoma are scarce and discordant. The aim of this study was to evaluate the metabolic effects of cabergoline (CAB) treatment in patients with newly diagnosed prolactinoma in relation to disease control and CAB dosage.. This is a retrospective clinical-based therapy analysis.. Forty-three patients with prolactinoma (eight men, 35 women), aged 33·65 ± 11·23 years, were evaluated metabolically at baseline and after 12 months of CAB treatment.. Body mass index (BMI), systolic and diastolic blood pressure, waist circumference (WC), lipid profile, haemoglobinA1c (HbA1c), glucose and insulin levels (and their areas under the curve, AUC) after an oral glucose tolerance test, homoeostasis model assessment of insulin resistance (Homa-IR) index, insulin sensitivity index (ISI) Matsuda, oral disposition index (DIo) and visceral adiposity index (VAI) were measured at baseline and after 12 months of treatment.. Twelve months of CAB reduced WC (P < 0·001), total (P = 0·001) and low-density lipoprotein \\terol (P < 0·001), triglycerides (P = 0·024), fasting insulin (P < 0·001), AUCINSULIN (P < 0·001), HbA1c (P = 0·022), Homa-IR (P < 0·001) and VAI (P < 0·001), with a concomitant increase in high-density lipoprotein cholesterol (P < 0·001) and in ISI Matsuda (P < 0·001), regardless of the degree of reduction in prolactin levels. The patients receiving higher doses (>0·50 mg/week) of CAB showed lower BMI (P = 0·009), fasting insulin (P = 0·001), Homa-IR (P < 0·001) and VAI (P = 0·018) and higher ISI Matsuda (P = 0·002) and DIo (P = 0·011), compared with those on lower doses.. A significant metabolic improvement was observed in patients with prolactinoma after 12 months of CAB treatment, especially when higher doses were used, highlighting the importance of considering the metabolic profile in these patients and the role of active treatment with high CAB doses.

Topics: Adiposity; Adult; Blood Glucose; Body Mass Index; Cabergoline; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Insulin Resistance; Lipids; Male; Metabolome; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Waist Circumference; Young Adult

Topics: Antineoplastic Agents, Hormonal; Biomarkers; Carotid Intima-Media Thickness; Ergolines; Female; Humans; Inflammation; Insulin Resistance; Pituitary Neoplasms; Prolactinoma

Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas.. 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuous CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria.. Compared to baseline, CAB induced a significant decrease in PRL with complete normalization in 93% of patients after the 60-month treatment. At baseline, MetS prevalence was significantly higher in patients with PRL above (34.5%) than in those with PRL lower (12.5%) than the median (129 μg/l, p = 0.03). MetS prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p = 0.001) months compared to baseline (28.0%). At both evaluations the lipid profile significantly improved compared to baseline. Fasting insulin and homeostatic model assessment of insulin resistance significantly decreased after 1 year of CAB (p = 0.012 and p = 0.002, respectively) and further improved after 60 months (p = 0.000). The visceral adiposity index significantly decreased after the 60-month treatment (p = 0.000) compared to baseline. At the 5-year evaluation CAB dose was the best predictor of percent decrease in fasting insulin (t = 2.35, p = 0.022).. CAB significantly reduces MetS prevalence and improves the adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and other metabolic parameters might reflect the direct effect of CAB.

Topics: Adiposity; Adult; Antineoplastic Agents; Cabergoline; Dose-Response Relationship, Drug; Ergolines; Fasting; Female; Humans; Hyperprolactinemia; Insulin; Insulin Resistance; Male; Metabolic Diseases; Metabolic Syndrome; Pituitary Neoplasms; Prevalence; Prognosis; Prolactin; Prolactinoma; Prospective Studies; Time Factors; Treatment Outcome

Hyperprolactinemia might be related to weight gain, metabolic syndrome (MS), and insulin resistance (IR). Treatment with dopamine agonist (DA) has been shown to reduce body weight and improve metabolic parameters. The objectives of this study were to determine the prevalence of obesity, overweight, MS, and IR in patients with prolactinoma before and after therapy with DA and to evaluate the relation between prolactin (PRL), body weight, fat distribution, leptin levels, IR, and lipid profile before treatment. In addition, we investigated the correlation of the reduction in PRL levels with weight loss and metabolic profile improvement. Twenty-two patients with prolactinoma completed 6 months of treatment with DA. These patients were submitted to clinical (BMI, waist circumference, blood pressure (BP)), laboratory evaluation (leptin, glucose, low-density lipoprotein (LDL)-cholesterol, and triglyceride (TG) levels) and abdominal computed tomography (CT) before and after treatment. The statistical analyses were done by nonparametric tests. At the beginning of the study, the prevalence of obesity, overweight, MS, and IR was 45, 27, 27, and 18%, respectively. After 6 months of treatment with DA, PRL levels normalized, but no significant difference in BMI was observed. However, there was a significant decrease on homeostasis model assessment of insulin resistance (HOMA(IR)) index, glucose, LDL-cholesterol, and TG levels. This study suggests a possible involvement of prolactinoma on the prevalence of obesity. We should consider that DA may be effective on improving metabolic parameters, and we speculate that a period longer than 6 months of treatment is necessary to conclude whether this drug can interfere in the body weight of patients with prolactinoma.

Topics: Adult; Aftercare; Aged; Blood Glucose; Body Composition; Body Mass Index; Body Weight; Bromocriptine; Cabergoline; Cholesterol, HDL; Cholesterol, LDL; Dopamine Agonists; Ergolines; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Metabolome; Middle Aged; Obesity; Prevalence; Prolactinoma; Waist Circumference; Weight Gain; Young Adult

The role of dopamine agonists in the treatment of Cushing's disease (CD) has been previously debated.. The aim of this study was to evaluate the effectiveness of short-term (3 months) and long-term (12-24 months) treatment with cabergoline in patients with CD.. 20 patients with CD unsuccessfully treated by surgery entered the study. Cabergoline was administered at an initial dose of 1 mg/wk, with a monthly increase of 1 mg, until urinary cortisol levels normalized or the maximal dose of 7 mg/wk was achieved. The responsiveness to treatment was evaluated according to changes in urinary cortisol excretion. A decrease greater than 25% was considered as a partial response, whereas complete normalization was considered as a full response at short-term evaluation; persistence of normal cortisol excretion was the only criterion to evaluate the response at long-term evaluation.. After short-term treatment, 15 (75%) patients were responsive to cabergoline treatment. Among these, normalization of cortisol excretion was maintained in 10, whereas treatment escape was observed in five patients after 6-18 months. Among the 10 long-term responsive patients, eight were followed for 24 months, whereas the remaining two were followed for 12-18 months, due to cabergoline withdrawal for intolerance. A sustained control of cortisol secretion for 24 month cabergoline treatment at the maximal dose ranging from 1-7 mg/wk (median: 3.5) without significant side effects, was obtained in eight of 20 (40%) patients.. The results of this study demonstrated that cabergoline treatment is effective in controlling cortisol secretion for at least 1-2 yr in more than one third of a limited population of patients with CD. If this evidence is confirmed by additional studies, this agent may be considered as a useful treatment option in patients with CD who are unsuccessfully treated by neurosurgery.

Topics: Adrenocorticotropic Hormone; Adult; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hydrocortisone; Insulin Resistance; Male; Middle Aged; Pituitary ACTH Hypersecretion

Topics: Adolescent; Cabergoline; Conduct Disorder; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Menarche; Pioglitazone; Polycystic Ovary Syndrome; Psychiatric Status Rating Scales; Thiazolidinediones; Violence

Limited data are available on clinical presentation and treatment strategy in patients with GH-secreting adenomas with onset in adolescence.. To report results of diagnosis and treatment in adolescents with GH and IGF-I excess.. Analytical, observational, retrospective.. Thirteen patients (five females and eight males, age 15-20 years) all with macroadenoma (two extrasellar, 11 invasive).. Height, body mass index (BMI), GH and IGF-I levels, tumour volume at diagnosis and after treatment.. Transsphenoidal surgery, octreotide subcutaneous (OCT, 0.3-0.8 mg/day), octreotide-LAR i.m. (LAR, 20-30 mg/q28 days), lanreotide i.m. (LAN, 60-90 mg/q28 days), bromocriptine (BRC, 5 mg/day), cabergoline (CAB, 1-2 mg/week).. Concomitant hyperprolactinaemia was found in eight patients (61.5%). All girls presented with amenorrhoea, which was associated with galactorrhoea in two patients; all boys presented with symptoms of tumour mass compression such as visual disturbance or headache; two girls also had these symptoms. Height at diagnosis was above the 97th centile in four of five girls and in six of eight boys. None of the patients had altered lipid profile while homeostasis model assessment of insulin resistance (HOMA-IR; 2.8 +/- 0.9) and beta-cell function (HOMA-beta, 207.6 +/- 98.1%) were higher than predicted (1% and 100%, respectively). First-line treatment was surgery in two patients and somatostatin analogues associated with dopaminergic drugs in 11 patients. None of the patients operated on were cured while six of 11 patients receiving pharmacotherapy (6-24 months) were controlled. In these six, tumour volume was reduced by 51.0 +/- 25.2% (median 51.5%). As second-line treatment, all the 11 patients treated with somatostatin analogues underwent surgical removal of their tumours. Surgery was successful in four patients and second-line pharmacotherapy in six patients. One patient was lost at follow-up and two patients maintained active acromegaly despite different treatment schedules; both patients were then treated with radiotherapy. At the last follow-up, there was a significant decrease in insulin levels, HOMA-IR and HOMA-beta without any change in lipid profile.. The clinical presentation of GH-secreting adenomas in adolescent girls is associated with menstrual disturbances and in boys with symptoms of mass effects; tall stature is characteristic in both. First-line treatment with depot somatostatin analogues followed by surgery and then by a second course of somatostatin analogues was successful and safe in 11 of 13 patients.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Body Height; Body Mass Index; Bromocriptine; Cabergoline; Combined Modality Therapy; Ergolines; Female; Growth Hormone; Growth Hormone-Secreting Pituitary Adenoma; Headache; Hormone Antagonists; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Male; Menstruation Disturbances; Octreotide; Peptides, Cyclic; Pituitary Neoplasms; Retrospective Studies; Somatostatin; Treatment Outcome

Topics: Cabergoline; Cardiovascular Diseases; Dopamine Agonists; Ergolines; Humans; Hyperprolactinemia; Insulin Resistance; Obesity; Risk Factors

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women in reproductive age. As for the treatment of this disease the lack of a clear etiology for PCOS has led to a symptom-orientated treatment. However, the overall aims of treatment are to induce ovulation for women desiring conception, to reduce androgen levels, to reduce body weight and to reduce long-term health risks of diabetes mellitus and cardiovascular disease. Clomiphene citrate (CC) is recommended as first line treatment for induction of ovulation in patients with PCOS by virtue of its efficacy, safety, and ease of administration. Alternatives for CC-resistant patients include gonadotrophin therapy (better with low-dose step-up protocol) and laparoscopic ovarian diathermy. Recently, recombinant FSH (rFSH) has been introduced in clinical practice and it seems more effective than urinary FSH as demonstrated by a significantly higher number of follicles recruited and embryos obtained with a shorter treatment period. The addition of GnRH-agonist to the stimulation protocol for women affected by PCOS could reduce premature luteinization and increase cycle fecundity. Other drugs under investigation are metformin and cabergoline. Hirsutism is the manifestation of hyperandrogenemia in PCOS. The primary goal of the treatment of hirsutim is central or peripheral androgen suppression using 3 groups of drugs: inhibitors of androgen production (oral contraceptives, GnRH analogues), peripheral androgen blockers (cyproterone acetate, flutamide, finasteride and spironolactone), and insulin-sensitizing agents (metformin). Weight reduction and exercise could also improve not only menstrual disturbances and infertility, but also insulin resistance and its adverse metabolic con-sequences.

Topics: Adult; Androgen Antagonists; Cabergoline; Cardiovascular Diseases; Clomiphene; Cyproterone Acetate; Diabetes Complications; Dopamine Agonists; Ergolines; Female; Finasteride; Flutamide; Follicle Stimulating Hormone; Gonadotropins; Hirsutism; Humans; Hypoglycemic Agents; Infertility, Female; Insulin Resistance; Metformin; Mineralocorticoid Receptor Antagonists; Obesity; Ovulation Induction; Polycystic Ovary Syndrome; Risk Factors; Spironolactone; Weight Loss