1,720,977 research outputs found
Investigational therapies for acromegaly.
No full textINTRODUCTION:
The treatment of acromegaly aims at normalizing growth hormone (GH) and insulin-like growth factor (IGF-I) levels and controlling tumor growth. The approaches to therapy are essentially three: surgery and pharmacotherapy, alone or in combination, and radiotherapy, generally used in more aggressive tumors.
AREAS COVERED:
This review focuses on the novel drug formulations being developed for medical therapy of acromegaly. Even though many efficient treatments have been made available to manage acromegaly in the last two decades, a significant number of patients remain still uncontrolled. Medical therapy represents an important therapeutic option and can be used as the first-line treatment in many patients. However, roughly 25% of patients might be considered as poor responsive or resistant to conventional long-acting somatostatin analogs (SSA) treatment. Therefore, new longer-acting SSA, oral SSA formulations, new combined therapies with weekly doses of pegvisomant, combination therapy with pegvisomant (PEG) and cabergoline (CAB) or SSA and new approaches have been proposed. New molecules are currently under investigation in clinical trials, such as the SSA multi-receptor ligand, pasireotide, which represents a promising option therapy, especially in patients not adequately controlled with currently available SSA. Further, temozolomide has been suggested as an efficient drug for treating GH-aggressive pituitary tumors resistant to conventional therapy.
EXPERT OPINION:
All these novel SSA formulations and new molecules implement the available options in therapies of acromegaly to improve disease control. However, further studies are needed to define the exact role of these newer agents. The predicting factors for response to these new therapies should also be determined
Somatostatin analogs as a first-line treatment in acromegaly: when is it appropriate?
No full textPURPOSE OF REVIEW: To discuss the role of medical therapy of acromegaly as a first-line treatment, focusing on recent data on the use of somatostatin analogs (SSAs), the first-choice pharmacotherapy for treating acromegaly.
RECENT FINDINGS: Despite pituitary surgery and radiotherapy, a significant number of patients with acromegaly needed adjuvant medical therapy, and primary medical therapy nowadays is increasingly considered. According to a recent consensus statement on the management of acromegaly, primary pharmacological therapy with SSAs may be indicated in patients who are otherwise poor surgical candidates or refuse surgery, and in those in whom there is a low probability of a surgical cure. The long-acting SSAs have been found to be effective in improving symptoms and signs of acromegaly in a high percentage of patients and induce normalization of growth hormone and insulin-like growth factor-I levels approximately in 60-80% of patients, respectively. Evidence has suggested that SSAs induce a clinically significant tumor shrinkage when given as first-line, when this reduction of tumor volume could be helpful in improving the outcome of subsequent surgery or improving the clinical syndrome in patients with unacceptable surgical risk, whereas the tumor shrinkage was seen less frequently when the drug was used after surgical resection and/or radiotherapy.
SUMMARY: Pharmacological management plays a pivotal role in the treatment of acromegaly, and first-line medical therapy with SSAs is being widely used in clinical practice, either prior to surgery or in patients who are otherwise poor surgical candidates and in those in whom there is a low probability of a surgical cure
Therapy of aggressive pituitary tumors.
No full textINTRODUCTION: Aggressive tumors of the pituitary gland are classically defined as pituitary tumors with a massive invasion of the surrounding anatomical structures and rapid growth. They are notoriously difficult to manage and are associated with poor prognosis because the therapeutic options are limited and the tumors are generally unresponsive to therapy. AREAS COVERED: This review focuses on treatment options for aggressive pituitary tumors, including surgery, radiotherapy and medical treatment, as well as focusing on the promising therapeutic options for aggressive pituitary tumors, evaluating the literature of the last 15 years. With the exception of prolactinomas, surgery is the first-line option, but most aggressive pituitary tumors often require repeated surgery. Pharmacotherapies are useful when surgery is unlikely to improve symptoms, or as an adjunct therapy to surgery. In prolactinomas, dopamine agonists are the first-line treatment and normalize prolactin levels in most patients, even those with macroprolactinomas. Somatostatin analogs are effective agents for primary therapy, pre-operatively or post-operatively to control tumor re-expansion of pituitary adenomas. However, dopamine agonists and somatostatin analogs are not as effective as they are for the treatment of non-aggressive adenomas. When surgery and pharmacotherapy fail, radiotherapy is a useful third-line strategy. Conventional chemotherapy is poorly effective but recent case reports with the temozolomide, an alkylating agent, have provided better results in the short term. EXPERT OPINION: Aggressive pituitary tumors are associated with poor prognosis as therapeutic options are limited. Moreover, they tend to recur quickly after initial treatment, are generally unresponsive to therapy, and are difficult to manage. To improve the overall response rate, the early application of current therapeutic approaches with the incorporation of new therapeutic developments is mandatory
Growth hormone, prolactin, and sexuality.
No full textGH and PRL, although not considered as 'classical' sexual hormones, could play a role in the endocrine control of sexual function both in men and women. Physiologically, PRL seems to be involved in the central control of sexual behavior and activity, by modulating mainly the effects of dopaminergic and serotoninergic systems on sexual function. Indeed, circulating PRL levels increase after orgasm and may potentially play a role in the acute regulation of further sexual arousal following orgasm both in men and women. On the other hand, either short-term or long-term PRL increase can modulate central nervous system areas involved in the control of sexual function and, peripherally, can directly influence mechanisms of penile erection in men, and presently only as an hypothesis, mechanisms related to the sexual response of genitalia in women. Furthermore, chronic hyperprolactinemia is classically associated with hypogonadotropic hypogonadism and sexual dysfunction in both sexes. Successful treatment of chronic hyperprolactinemia generally restores normal sexual function both in men and women although this effect is not only related to relapse of gonadal function. Hypoprolactinemia is recently recognised as a possible risk factor of arteriogenic erectile dysfunction while a possible role on female sexual function is not known. The physiological role of GH on sexual function is not fully elucidated. GH is an important regulator of hypothalamuspituitary- gonadal axis and seems to participate in the regulation of the sexual response of genitalia in men, and potentially also in women. Sexual function in men and women with GH deficiency (GHD) and GH excess, particularly in acromegaly, is scantily studied and GH- or IGF-I-dependent effects are difficult to quantify. Nevertheless, a decrease of desire and arousability both in men and women, together with an impairment of erectile function in men, have been described both in patients with GHD and acromegaly, although it is not clear whether they are dependent directly on the hormone defect or excess or they are consequence of the hypogonadism or the different clinical complications or the physical disfigurement and psychological imbalance, which are associated with the diseases, and are potentially affecting sexual function. Data on beneficial effects of GH replacement therapy and specific surgical or pharmacological approach for acromegaly are far to be fully elucidated although restoring normal GH/IGF-I levels have been associated to improvement of sexual function
Glucose tolerance and somatostatin analog treatment in acromegaly: a 12-monthstudy.
No full textOBJECTIVE: The objective of the study was to investigate the impact of first-line
somatostatin analogs (SSAs) on glucose tolerance (GT) in acromegaly.
DESIGN: The design was open and prospective.
PATIENTS: One hundred twelve patients [63 with normal GT (56.2%), 24 with
impaired GT (21.4%), and 25 with diabetes (22.3%)] were treated with depot SSAs
for 12 months: 54 patients (48.2%) achieved mean fasting GH levels less than 2.5
microg/liter in presence of normal IGF-I levels (controlled) during SSA.
PRIMARY OUTCOME MEASURES: Fasting glucose and glycosylated hemoglobin levels were
measured.
RESULTS: At study end, 57 patients had normal GT (50.1% vs. baseline; P = 0.55),
30 had impaired fasting glucose or impaired GT (26.8%, P =0.43) and 25 had
diabetes (22.3%; P = 1.0). Twenty-eight patients (25.0%), modified their GT [11
improved (9.8%), 17 worsened (15.2%)]: 90% of the patients with GT improvement
achieved control of acromegaly and 89% of those having GT worsening did not (P <
0.0001). The major predictors of GT changing were disease control (t = -4.99; P <
0.0001), baseline GT (t = -2.84; P = 0.0054), and GH levels (t = 2.70; P =
0.008). Fasting glucose levels were predicted by patients' age (t = 2.74; P =
0.0071) and IGF-I levels (t = 2.14; P = 0.035). Glycosylated hemoglobin levels
were predicted by disease duration (t = 3.53; P = 0.0006), GH levels (t = 2.70; P
= 0.0071), and IGF-I levels (t = 2.11; P = 0.037).
CONCLUSIONS: This study showed a similar prevalence of deterioration and
improvement of GT 12 months after first-line SSA treatment. Uncontrolled
acromegaly during SSA treatment and abnormal GT at baseline were associated with
GT worsening
The cardiovascular system in growth hormone excess and growth hormone deficiency.
No full textThe clinical conditions associated with GH excess and GH deficiency (GHD) are known to be associated with an increased risk for the cardiovascular morbidity and mortality, suggesting that either an excess or a deficiency in GH and/or IGF-I is deleterious for cardiovascular system. In patients with acromegaly, chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction and, in later stages, with systolic dysfunction ending in heart failure if GH/IGF-I excess is not controlled. Abnormalities of cardiac rhythm and anomalies of cardiac valves can also occur. Moreover, the increased prevalence of cardiovascular risk factors, such as hypertension, diabetes mellitus, and insulin resistance, as well as dyslipidemia, confer an increased risk for vascular atherosclerosis. Successful control of the disease is accompanied by a decrease of the cardiac mass and improvement of cardiac function and an improvement in cardiovascular risk factors. In patients with hypopituitarism, GHD has been considered the underlying factor of the increased mortality when appropriate standard replacement of the pituitary hormones deficiencies is given. Either childhood-onset or adulthood-onset GHD are characterized by a cluster of abnormalities associated with an increased cardiovascular risk, including altered body composition, unfavorable lipid profile, insulin resistance, endothelial dysfunction and vascular atherosclerosis, a decrease in cardiac mass together with an impairment of systolic function mainly after exercise. Treatment with recombinant GH in patients with GHD is followed by an improvement of the cardiovascular risk factors and an increase in cardiac mass together with an improvement in cardiac performance. In conclusion, acromegaly and GHD are associated with an increased risk for cardiovascular morbidity and mortality, but the control of GH/IGF-I secretion reverses cardiovascular abnormalities and restores the normal life expectancy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
