This survey confirms that TMZ is established as first-line chemotherapeutic treatment of APT/PC. Clinically functioning tumours, low MGMT and concurrent radiotherapy were associated with a better response. The limited long-term effect of TMZ and the poor efficacy of other drugs highlight the need to identify additional effective therapies.
This study shows that TMZ is a valuable treatment option for patients with uncontrolled pituitary tumors. The data suggest that tumoral MGMT staining below 50% is associated with a high likelihood of treatment response.
Hyperprolactinemia has been associated with impaired metabolism, including insulin resistance. However, the metabolic effects of elevated prolactin (PRL) levels are not completely clarified. The aim of this study was to obtain more insights of metabolic consequences in hyperprolactinemia patients. Fourteen consecutive patients, eight women and six men, aged 39.7 (±13.7) years with prolactinomas (median PRL 72 [49-131] μg/L in women and 1,260 [123-9,600] μg/L in men) were included. Anthropometric data and metabolic values were studied before and after 2 and 6 months on DA agonists (Bromocriptine [5.7 (±3.9) mg/day, n = 13] or Cabergoline [0.5 mg/week, n = 1]). Euglycemic hyperinsulinemic clamps were studied in six patients before and after 6 months of treatment. PRL normalized in all patients. Anthropometric data changed only in males with a significant decrease of median body weight (95.6 [80.7-110.1] to 83.4 [77.8-99.1] kg, P = 0.046), waist circumference and fat percentage after 6 months. LDL cholesterol was positively correlated to PRL at diagnosis (r = 0.62, P = 0.025) and decreased within 2 months (3.4 [±0.9] to 2.9 [±0.6] mmol/L, P = 0.003). Insulin, IGFBP-1 and total adiponectin levels did not change. Insulin sensitivity tended to improve after 6 months; M-value from 5.7 (±1.8) to 7.8 (±2.6) mg/kg/min, P = 0.083 and per cent improvement in M-value was correlated to per cent reduction in PRL levels (r = -0.85, P = 0.034). In conclusion, beneficial metabolic changes were seen in prolactinoma patients after treatment with DA agonists, underscoring the importance of an active treatment approach and to consider the metabolic profile in the clinical management of hyperprolactinemia patients.
Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.
This is the first estimate of a national incidence of TSHoma. Additional epidemiological studies are needed to compare these results with other geographical areas. This study suggests an increased incidence of TSHomas, in agreement with reports on other pituitary adenomas.
ObjectiveHepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia.Research design and methodsWe used a sensitive and specific dual–monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist.ResultsIn response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels.ConclusionsIn humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency.
Context
Aggressive pituitary tumours (APTs) are characterised by unusually rapid growth and lack of response to standard treatment. About 1-2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumours are overrepresented amongst APTs and PCs. Mutations in the ATRX gene, regulating chromatin remodelling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumours.
Objective
To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs.
Design
We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumours lacking ATRX immunolabeling, mutational status of the ATRX gene was explored.
Results
Nine of the 48 tumours (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18 - 28%) than in those with APTs (4/30 – 13%). Lack of ATRX was most common in the corticotroph tumours, 7/22 (32%), vs 2/24 (8%) in the tumours of the Pit-1 lineage. Loss-of-function ATRX mutations were found in all the nine ATRX immuno-negative cases: nonsense mutations (n=4), frameshift deletions (n=4) and large deletions affecting 22-28 of the 36 exons (n=3). More than one ATRX gene defect was identified in two PCs.
Conclusion
ATRX mutations occur in a subset of aggressive pituitary tumours and are more common in corticotroph tumours. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumours.
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