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- Integral Indicator of Oxidative Stress in Human Blood. [JOURNAL ARTICLE]
- Bull Exp Biol Med 2014 Oct 24.
Here we performed individual evaluation of the oxidative stress index that serves as an integral criterion for the balance of LPO-antioxidant defense system in women with endocrine pathology (type 1 diabetes mellitus and infertility with hyperprolactinemia). The state of the LPO-antioxidant defense system was estimated from blood levels of LPO substrates with conjugated double bonds, conjugated dienes, ketodienes, conjugated trienes, thiobarbituric acid-reactive substances, retinol, α-tocopherol, reduced and oxidized glutathione, and SOD activity. The use of this oxidative stress index allowed us to diagnose oxidative stress in female patients with endocrine pathology.
- Reports of Pathological Gambling, Hypersexuality, and Compulsive Shopping Associated With Dopamine Receptor Agonist Drugs. [JOURNAL ARTICLE]
- JAMA Intern Med 2014 Oct 20.
Severe impulse control disorders involving pathological gambling, hypersexuality, and compulsive shopping have been reported in association with the use of dopamine receptor agonist drugs in case series and retrospective patient surveys. These agents are used to treat Parkinson disease, restless leg syndrome, and hyperprolactinemia.To analyze serious adverse drug event reports about these impulse control disorders received by the US Food and Drug Administration (FDA) and to assess the relationship of these case reports with the 6 FDA-approved dopamine receptor agonist drugs.We conducted a retrospective disproportionality analysis based on the 2.7 million serious domestic and foreign adverse drug event reports from 2003 to 2012 extracted from the FDA Adverse Event Reporting System.Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs.We identified 1580 events indicating impulse control disorders from the United States and 21 other countries:710 fordopamine receptor agonist drugs and 870 for other drugs. The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders (n = 710; PRR = 277.6, P < .001). The association was strongest for the dopamine agonists pramipexole (n = 410; PRR = 455.9, P < .001) and ropinirole (n = 188; PRR = 152.5, P < .001), with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D3 receptor (n = 37; PRR = 8.6, P < .001).Our findings confirm and extend the evidence that dopamine receptor agonist drugs are associated with these specific impulse control disorders. At present, none of the dopamine receptor agonist drugs approved by the FDA have boxed warnings as part of their prescribing information. Our data, and data from prior studies, show the need for more prominent warnings.
- Using Growth Hormone Levels to Detect Macroadenoma in Patients with Acromegaly. [JOURNAL ARTICLE]
- Endocrinol Metab (Seoul) 2014 May 27.
The aim of this study was to assess the clinical differences between acromegalic patients with microadenoma and patients with macroadenoma, and to evaluate the predictive value of growth hormone (GH) levels for early detection of macroadenoma.We performed a retrospective analysis of 215 patients diagnosed with a GH-secreting pituitary adenoma. The patients were divided into two groups: the microadenoma group and the macroadenoma group, and the clinical parameters were compared between these two groups. The most sensitive and specific GH values for predicting macroadenoma were selected using receiver operating characteristic (ROC) curves.Compared with the microadenoma group, the macroadenoma group had a significantly younger age, higher body mass index, higher prevalence of hyperprolactinemia and hypogonadism, and a lower proportion of positive suppression to octreotide. However, there were no significant differences in the gender or in the prevalence of diabetes between the two groups. The tumor diameter was positively correlated with all GH values during the oral glucose tolerance test (OGTT). All GH values were significantly higher in the macroadenoma group than the microadenoma group. Cut-off values for GH levels at 0, 30, 60, 90, and 120 minutes for optimal discrimination between macroadenoma and microadenoma were 5.6, 5.7, 6.3, 6.0, and 5.8 ng/mL, respectively. ROC curve analysis revealed that the GH value at 30 minutes had the highest area under the curve.The GH level of 5.7 ng/mL or higher at 30 minutes during OGTT could provide sufficient information to detect macroadenoma at the time of diagnosis.
- Recurrence of hyperprolactinemia and continuation of ovarian acyclicity in captive African elephants (Loxodonta africana) treated with cabergoline. [Journal Article]
- J Zoo Wildl Med 2014 Sep; 45(3):569-76.
Hyperprolactinemia is associated with reproductive acyclicity in zoo African elephants (Loxodonta africana) and may contribute to the non-self-sustainability of the captive population in North America. It is a common cause of infertility in women and other mammals and can be treated with the dopamine agonist cabergoline. The objectives of this study were to assess prolactin responses to cabergoline treatment in hyperprolactinemic, acyclic African elephants and to determine the subsequent impact on ovarian cyclic activity. Five elephants, diagnosed as hyperprolactinemic (>11 ng/ml prolactin) and acyclic (maintenance of baseline progestagens for at least 1 yr), were treated with 1-2 mg cabergoline orally twice weekly for 16-82 wk. Cabergoline reduced (P < 0.05) serum prolactin concentrations during the treatment period compared to pretreatment levels in four of five elephants (11.5 +/- 3.2 vs. 9.1 +/- 3.4 ng/ml; 20.3 +/- 16.7 vs. 7.9 +/- 9.8 ng/ml; 26.4 +/- 15.0 vs. 6.8 +/- 1.5 ng/ml; 42.2 +/- 22.6 vs. 18.6 +/- 8.9 ng/ml). However, none of the females resumed ovarian cyclicity based on serum progestagen analyses up to 1 yr posttreatment. In addition, within 1 to 6 wk after cessation of oral cabergoline, serum prolactin concentrations returned to concentrations that were as high as or higher than before treatment (P < 0.05). One elephant that exhibited the highest pretreatment prolactin concentration (75.2 +/- 10.5 ng/ml) did not respond to cabergoline and maintained elevated levels throughout the study. Thus, oral cabergoline administration reduced prolactin concentrations in elephants with hyperprolactinemia, but there was no resumption of ovarian cyclicity, and a significant prolactin rebound effect was observed. It is possible that higher doses or longer treatment intervals may be required for cabergoline treatment to result in permanent suppression of prolactin secretion and to mitigate associated ovarian cycle problems.
- Pituitary image: pituicytoma. [JOURNAL ARTICLE]
- Pituitary 2014 Oct 14.
Pituicytoma is a rare tumor arising from the neurohypophysis or pars intermedia of the adenohypophysis.A 36 year old male came to our observation presenting polydipsia, polyuria, polyphagia, decreased libido and altered sleep-wake rhythm. The biochemical tests showed hypotonic urine, mild hyperprolactinemia, hypogonadotropic hypogonadism, central hypothyroidism. Magnetic resonance revealed an expansive lesion of the suprasellar region (slightly isointense on T1, hyperintense on T2, impregnating contrast medium), that was partially removed by trans-cranial neurosurgical approach. The histopathological diagnosis was pituicytoma. After surgery, in addition to endocrine disorders, the patient presented severe neurological sequelae and hyperthermia, likely due to damage of the hypothalamus, followed by a progressive metabolic syndrome. The residual tumor was monitored by MRI, and, due to the early gradual increase in volume, was treated by stereotactic radiosurgery.Pituicytomas are often difficult to distinguish from other hypothalamic or pituitary lesions. However, their identification would be preferable in a pre-operative setting in order to optimize the work-up and to initiate a proactive management of the expected complications.
- Early prediction of long-term response to cabergoline in patients with macroprolactinomas. [Journal Article]
- Endocrinol Metab (Seoul) 2014 Sep; 29(3):280-92.
Cabergoline is typically effective for treating prolactinomas; however, some patients display cabergoline resistance, and the early characteristics of these patients remain unclear. We analyzed early indicators predicting long-term response to cabergoline.We retrospectively reviewed the cases of 44 patients with macroprolactinomas who received cabergoline as first-line treatment; the patients were followed for a median of 16 months. The influence of various clinical parameters on outcomes was evaluated.Forty patients (90.9%) were treated medically and displayed tumor volume reduction (TVR) of 74.7%, a prolactin normalization (NP) rate of 81.8%, and a complete response (CR; TVR >50% with NP, without surgery) rate of 70.5%. Most patients (93.1%) with TVR ≥25% and NP at 3 months eventually achieved CR, whereas only 50% of patients with TVR ≥25% without NP and no patients with TVR <25% achieved CR. TVR at 3 months was strongly correlated with final TVR (R=0.785). Patients with large macroadenomas exhibited a low NP rate at 3 months, but eventually achieved TVR and NP rates similar to those of patients with smaller tumors. Surgery independently reduced the final dose of cabergoline (β=-1.181 mg/week), and two of four patients who underwent surgery were able to discontinue cabergoline.Determining cabergoline response using TVR and NP 3 months after treatment is useful for predicting later outcomes. However, further cabergoline administration should be considered for patients with TVR >25% at 3 months without NP, particularly those with huge prolactinomas, because a delayed response may be achieved. As surgery can reduce the cabergoline dose necessary for successful disease control, it should be considered for cabergoline-resistant patients.
- The progesterone and estrogen modify the uterine prolactin and prolactin receptor expression of hyperprolactinemic mice. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2014 Oct 9.:1-4.
Abstract The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and PRL receptor's expression in the uterus of mice. For this purpose, 49 Swiss mice were divided into the following groups: GrSS (non-ovariectomized mice given vehicle); GrMET (non-ovariectomized mice treated with metoclopramide); OvSS (ovariectomized mice given vehicle); OvMET (ovariectomized mice treated with metoclopramide); OvMET+17βE (ovariectomized mice treated with metoclopramide and 17β estradiol); OvMET+MP (ovariectomized mice treated with metoclopramide and micronized progesterone); OvMET+17βE+MP (ovariectomized mice treated with metoclopramide and a solution of 17β estradiol and micronized progesterone). Immunohistochemical analyzes were evaluated semi-quantitatively. Our results showed that GrMET, OvMET+MP, and OvMET+17βE+MP presented strong PRL expression. OvMET and OvMET+17βE presented mild reaction, while GrSS and OvSS presented weak reaction. Concerning PRL receptor, OvMET+MP and OvMET+17βE+MP showed strong reaction; GrMET, OvSS, and OvMET+17βE showed mild reaction; and GrSS and OvMET showed weak reaction. These findings suggest that progesterone alone or in combination with estrogen may increase the expression of uterine PRL and PRL receptor.
- Insulin resistance and androgen levels in eugonadic and hypogonadic women with prolactinoma. [JOURNAL ARTICLE]
- Minerva Endocrinol 2014 Oct 7.
Hyperprolactinemia is the most common endocrinologic disorder in causing menstrual irregularities. Although the correlation between hyperprolactinemia and menstrual dysfunction is widely known, the etiology of menstrual cycle disorders is not profoundly understood in patients with prolactinoma. We aimed to investigate the correlation between prolactin levels and insulin resistance and hyperandrogenism in patients with prolactinoma.Sixty--four patients with microprolactinoma and 33 healthy women were enrolled. Thirty--six of these patients with prolactinoma (Group 1) had an estradiol (E2) level under 30 pg/ml, and 28 (Group 2) had an E2 level greater than 30 pg/ml. Blood samples were drawn to measure the levels of the following hormones: Follicle stimulating hormone (FSH), Luteinizing hormone (LH), E2, Prolactin (PRL), total testosterone (TT), Androstenedione (AS) and Dehydroepiandrostenedione sulphate (DHEAS). Body mass index (BMI of ≥30 kg/m2) was excluded from the study. Insulin resistance (IR) was calculated by the HOMA--IR.Body mass index was higher in patients with prolactinoma than the control group (p=0.02, p=0.025, respectively). IR and glucose intolerance existence were higher in patients with prolactinoma (p=0.007, p=0.097, respectively, figure 1) than the healthy women, but these differences did not exist between eugonadic and hypogonadic women with prolactinoma (p=0.020, p=0.032, respectively, Bonferroni correction). TT and AS were higher in eugonadic women with prolactinoma than the control group (p=0.004, p=0.003, Bonferroni correction, respectively).Our study revealed that the relationship between hyperprolactinemia and IR/glucose intolerance is irrespective of gonadal status in women with prolactinoma. Also, the study concluded that hyperandrogenism may be a cause of menstrual dysfunction in eugonadic women with prolactinoma.
- Primary non-necrotizing granulomatous hypophysitis mimicking pituitary adenomas. [Journal Article]
- Turk Neurosurg 2014; 24(5):688-94.
The authors review their experience in the endoscopic endonasal transsphenoidal treatment of 5 patients, finally diagnosed as primary hypophysitis but initially assumed to be pituitary adenomas.A retrospective study was undertaken to review 5 cases of primary non-necrotizing granulomatous hypophysitis (1.61%) through 310 endoscopic transsphenoidally operated cases with the diagnosis of pituitary adenoma between 2009 and 2013. All 5 cases were female without any background of autoimmunity or recent pregnancy. The initial presumptive diagnosis was pituitary adenoma for all patients. The endocrinological diagnoses of the patients were suspected Cushing's Disease, anterior pituitary deficiency with hyponatremia, hyperprolactinemia, and acromegaly. One of the patients had normal hormonal levels. All patients had macroadenomas including one invasive adenoma with skull base involvement. One of the patients (20%) had visual field defects. All patients underwent endoscopic endonasal transsphenoidal surgery (EETS).All patients had improvement of hormonal levels postoperatively except the one with anterior pituitary deficiency who required long term hormone replacement after the surgery. Mean follow-up duration was 14.8 months.Primary granulomatous hypophysitis without any known etiological factors is very rare in the literature. It can mimic pituitary adenomas in radiological and endocrinological aspects. EETS is an effective and safe treatment especially for visual and compression symptoms.
- Water Extract of Fructus Hordei Germinatus Shows Antihyperprolactinemia Activity via Dopamine D2 Receptor. [Journal Article]
- Evid Based Complement Alternat Med 2014.:579054.