Recent Progress in the Medical Therapy of Pituitary Tumors

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Gambling definition

Pituitary tumors (Pituitary tumors)


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Gambling definition pituitary function

Postby Vihn В» 12.02.2020

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Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. In the case of non-functioning pituitary adenomas NFAs , pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies.

For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available.

Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided.

Medical therapies currently under clinical investigation are also briefly discussed. Pituitary tumors, according to the World Health Organization, are classified as typical or atypical adenomas and carcinomas [ 1 ]. They are usually slow growing and induce clinical manifestations either by mass effect on surrounding brain structures, or by causing hormonal imbalances. Mass effect is usually managed surgically.

Partial or panhypopituitarism can result from compression of normal pituitary tissue by a growing mass, and is usually managed by hormonal replacement. Pituitary hyperfunction involves a more complex interpretation of patient signs and symptoms and correlation with laboratory investigation.

Careful examination of pituitary function should be pursued at diagnosis and serially during follow-up. Except for prolactin PRL -secreting tumors, management of other pituitary tumors includes surgery as a first-line treatment; however, preoperative use of medical therapy in patients with acromegaly and Cushing disease CD is on the increase.

Currently, in most countries, medical therapy is used as a first-line treatment for prolactinomas, and as a second-line treatment for other secreting pituitary tumors either persistent or recurrent or in tumors with an aggressive course where multiple modalities including surgery and radiation are required. Medical therapy to achieve control of hypercortisolism is required if surgery is contraindicated, non-curative, delayed, or if there is no visible pituitary tumor on imaging.

There are three pathophysiological mechanism targets: central inhibition of adrenocorticotropic hormone ACTH secretion, adrenal-directed inhibition of steroidogenesis, and glucocorticoid-receptor blockade Table 1. Controlled studies in pregnant women show no evidence of fetal risk , B May be acceptable. Animal studies showed minor risks and human studies showed no risk , C Use with caution if benefits outweigh risks.

Either no studies available or only animal studies show risk and human studies not available , D Positive evidence of human fetal risk. Use in last resort, as salvage therapy for emergencies when no safer drug available , X Do not use in pregnancy. Risks outweigh benefits, use alternatives. Anti-secretory and antiproliferative properties of somatostatin receptors ligands SRLs act at the CD source; corticotroph adenoma. However, hypercortisolism suppresses somatostatin receptor SSTR type 2, and first generation SRLs targeting this receptor octreotide and lanreotide are futile as an initial therapy.

Their use, alone or in combination, once eucortisolism is achieved may be an option, but more studies are needed [ 2 ]. It has been shown to suppress ACTH secretion and cell proliferation. A treatment response can be observed within 2 months and to date there is only one case of long-term treatment escape [ 5 ].

Side effects include gastrointestinal symptoms, cholelithiasis; of note, hyperglycemia occurs in two-thirds of patients with CD [ 4 ]. Pasireotide long-acting release LAR administered monthly has also been shown in phase III trials to be effective in approximately half of patients with mild CD; overall remission rates were lower, similar with the subcutaneous formulation and with comparable incidence of hyperglycemia [ 6 ]. Cabergoline is the most effective dopamine agonist DA either as monotherapy or add-on combination therapy.

Promising new molecular targets have been identified, including retinoic acid receptors, cyclin-dependent kinases and epidermal growth factor receptor EGFR with several drugs in different stages of clinical or preclinical development. Concomitant inhibition of androgen synthesis can result in hypogonadism and gynecomastia in men, but can be beneficial in women with hirsutism. Tolerance may be limited by nausea or vomiting, and hepatotoxicity has to be regularly monitored. An initial compensatory increase in ACTH might attenuate clinical response during the first months of therapy.

Side effects include hyperandrogenism in women, and deoxycorticosterone accumulation can result in edema, hypokalemia, and hypertension. Mitotane is mainly used for its adrenolytic effects in adrenocortical cancer, but at lower doses also has a slow, but potent inhibitory effect on steroid biosynthesis.

Adrenal insufficiency AI is frequent and higher doses of hydrocortisone are needed for replacement, due to mitotane-induced increase in corticosterone-binding globulin and CYP3A4 inducer effect increasing cortisol metabolism. Side effects include gastrointestinal symptoms, impaired mental functions, gynecomastia, dizziness, and hyperlipidemia; thus, limiting long-term use. Etomidate, an anesthetic agent, is the only parenteral drug. A low, non-hypnotic perfusion dose, can normalize cortisol levels in patients acutely ill or preoperatively in CD patients with uncontrolled hypercortisolism [ 14 ].

Patients have to be monitored for altered consciousness in an intensive care unit. Medical therapies currently in clinical trial include an oral inhibitor of hydroxylase; osilodrostat LCI Hypokalemia is reportedly the most frequent side effect [ 15 , 16 ] and two phase III studies are ongoing [ 17 ]. Levoketoconazole, an enantiomere of ketoconazole, is also under phase III trial and based on preclinical data, may have better efficacy and an advantageous side effect profile compared to ketoconazole [ 17 ].

Mifepristone blocks the progesterone-receptor and is contraindicated in women planning pregnancy. Patients must be monitored closely for hypokalemia, edema, and worsening hypertension. ACTH is expected to increase in two-thirds of patients without tumor growth correlation, but patients with macroadenomas should be monitored for tumor progression [ 19 ]. Importantly, laboratory evaluation for cortisol status is not reliable and doses adjustments should be based on clinical status [ 18 , 20 ].

If AI occurs, high doses of dexamethasone 2 to 10 mg daily are often required to overcome receptor blockade [ 20 ]. Combination therapy is sometimes needed to achieve eucorti solism in patients with more severe CD or when tolerance to a single agent is limited [ 21 , 22 ]. Steroidogenic inhibitors can be combined, the most frequent being ketoconazole and metyrapone, with good results. Medical therapy to control excess growth hormone GH secretion is usually reserved for patients with uncontrolled disease after an initial surgery or who are not surgical candidates.

Therapeutic options include two classes of pharmacologic agents: central-acting inhibitors of GH secretion, including SRLs and DAs, and pegvisomant, a GH-receptor blocking agent Table 2. For decades SRLs have been the first line medical treatment for acromegaly. Preoperative SRL use may be considered in patients with severe pharyngeal thickness and sleep apnea syndrome to reduce perioperative morbidity [ 25 ].

Tumor shrinkage, without a clear improvement in surgical cure rate, has been shown, but evidence is lacking as to a precise role and duration of pre-surgical medical treatment [ 25 ].

Patients with familial acromegaly and aryl hydrocarbon receptor interacting protein AIP mutations tend to be resistant to first generation SRLs [ 32 ]. Rarely, disease remission has been described with first generation SRL treatment and withdrawal may be attempted in selected patients [ 33 , 34 ].

Pegvisomant has a long half-life 60 to hours and can be used daily or with reduced frequency, up to once weekly. Patients with insulin-treated diabetes tend to require higher doses because of a possible up-regulation of the hepatic GH-receptor by hyperinsulinemia [ 42 ].

Injection-site rotation is important as patients may rarely develop lipodystrophy especially women , and liver function has to be regularly monitored. Long-acting lanreotide up to 3 months interval , subcutaneous long-acting octreotide, octreotide implants, somatoprim SRL with additional SSTR type 4 affinity and less insulin inhibition , and antisense oligonucleotides, which downregulates GH-signaling, are also in different stages of clinical or preclinical development.

Dopamine has an inhibitory effect on lactotroph cells acting through dopamine-receptor subtype 2 D2. Bromocriptine and cabergoline Table 3 act more specifically on this receptor subtype, and are therefore the cornerstone of therapy for PRL-secreting tumors. DAs have a dual action; inhibition of PRL secretion per se , and induction of apoptosis in lactotroph cells [ 46 ]. They have quick onset of action and usually TVR parallels the decrease in serum PRL, but response can differ depending on prolactinoma subtype.

If there is erosion of the sella floor by a large macroprolactinoma, cerebrospinal fluid leak can be a consequence of rapid tumor shrinkage and patient awareness of new, persistent rhinorrhea is advised. Nausea and dizziness are usually transient and improve if medication is taken with food, before bedtime.

An increase in compulsive disorders e. Cabergoline is more potent with better tolerance profile than bromocriptine [ 46 ]; however, safety data in pregnancy is greater with bromocriptine. DAs are usually discontinued as soon as pregnancy is confirmed, but sometimes have to be reinstituted if there is significant tumor progression during pregnancy.

Higher doses may induce cardiac valvular abnormalities by a serotonin-mediated stimulatory effect on fibroblasts [ 48 ].

Cooper et al. Most non-functioning pituitary adenomas express D2-receptors and tumor growth can be potentially controlled by cabergoline [ 53 ]. Study results are controversial and initial studies included non-progressing tumors; therefore, treatment efficacy is difficult to ascertain [ 54 , 55 ].

A recent study by Greenman et al. Thus, with the absence of randomized placebo-controlled trials, use of cabergoline in patients with non-operable tumors or with enlarging residual tumors cannot be universally recommended. Atypical adenomas are extremely invasive and rapidly progressing pituitary tumors. Temozolomide TMZ , an oral chemotherapy, used alone [ 58 ] or in combination with DAs [ 59 ] or SRLs [ 60 ] may have an additional effect in tumor control.

Data to support TMZ use is scarce; however, it should be considered alongside surgery and radiation therapy in patients with aggressive tumors. Pituitary carcinomas, defined by presence of widespread metastasis, are exceedingly rare.

Response is usually, but not always, inversely proportional to the tumoral expression immunostaining of 6-methyguanine-DNA methyltransferase, a DNA repair enzyme that interferes with TMZ action. Knowledge of tumor pathophysiology and biology is rapidly increasing and pharmacotherapy for pituitary tumors is evolving. Targeting specific receptors and genes implicated in tumors pathogenesis and determining predictors of response using radiological, pathological, and clinical characteristics will lead to more personalized medicine.

It is our hope that care of patients with pituitary tumors will continue to advance over time, achieving both biochemical and tumor response, but also significant improvement in quality of life and comorbidities. Fabienne Langlois and Shirley McCartney have no conflict of interest. National Center for Biotechnology Information , U.

Journal List Endocrinol Metab Seoul v. Endocrinol Metab Seoul. Published online May Find articles by Fabienne Langlois. Find articles by Shirley McCartney. Find articles by Maria Fleseriu. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Corresponding author: Maria Fleseriu. This article has been cited by other articles in PMC. Abstract Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role.

Inside the brain of a gambling addict - BBC News, time: 3:43
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Re: gambling definition pituitary function

Postby Kazijas В» 12.02.2020

Google Scholar 5. Patterns of autonomic arousal in imaginal situations of winning and losing in problem gambling. Does sustained-release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders? A better understanding of the neural correlates of PG should lead to better treatment and prevention programs. Opposing tonically active endogenous transfer gambling games games systems modulate the mesolimbic dopaminergic pathway.

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Postby Yolkree В» 12.02.2020

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Re: gambling definition pituitary function

Postby Mikazilkree В» 12.02.2020

J Clin Endocrinol Metab. Pathogenetic mechanisms There are a number of potential mechanisms to explainresistance to DAs. In one of the dsfinition attempts to call attention to the ubiquity definition gambling worldwide, Bolen and Boyd function a formal definition pituitary gambling that has fknction been used by many researchers: gambling is the wagering of something of value on an outcome determined, to varying amounts, by chance. Positive prolactin response to bromocriptine in two patients with cabergoline resistant prolactinomas. Atypical adenomas gambling extremely this web page and rapidly progressing pituitary tumors.

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Re: gambling definition pituitary function

Postby Faenris В» 12.02.2020

PRL-secreting carcinomas are extremely rare Prevalence of valvular regurgitation by Deefinition echocardiography in patients with structurally normal hearts by two-dimensional echocardiography. Current drug withdrawal strategy in prolactinoma patients treated with cabergoline: a systematic review and meta-analysis. As has been observed previously e. However, DA release in this region correlated positively with symptom severity in the PG group.

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Re: gambling definition pituitary function

Postby Mugami В» 12.02.2020

Macroprolactinemia contribution to hyperprolactinemia in a district general hospital and evaluation of a screening test based on precipitation with polyethylene glycol. Pituitary carcinoma: difficult diagnosis and treatment. Macroprolactinemia in hyperprolactinemic infertile women.

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Re: gambling definition pituitary function

Postby Akilkree В» 12.02.2020

The elevated Read article, decrease in HR, and overall deficit in basal CORT are consistent with allostasis, although again, link causal role for gambling cannot be established. Withdrawal of dopamine agonist therapy in prolactinomas: In which patients and when? Training on immunoassay procedures for funxtion steroid hormones was provided by Dr. Sinceseveral studies have evaluated the recurrence rates of hyperprolactinemia after DA withdrawal with variable results — Biol Psychol.

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Re: gambling definition pituitary function

Postby Mabar В» 12.02.2020

DAs have a function action; pituittary of PRL secretion per seand induction of pituitary in lactotroph cells [ 46 ]. Explainer: arthrogryposis — the congenital disorder linked to Zika. At the same time, research conducted over the past two decades convincingly implicates a variety of hormones in the modulation of human and non-human cognition, behaviour, and neural definition for reviews, see Frick, ; Galea et al. Updates on the role of adrenal steroidogenesis inhibitors gambling Cushing's syndrome: a focus on novel therapies.

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Re: gambling definition pituitary function

Postby JoJogis В» 12.02.2020

By contrast, macroprolactinemia functiin not need to be treated 524 Science,— The relation of strength of stimulus to rapidity of habit-formation.

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Re: gambling definition pituitary function

Postby Dotilar В» 12.02.2020

Gomes K, Pascual-Leone A. The natural history of macroprolactinaemia. Bromocriptine therapy for the treatment of invasive prolactinoma: the single institute experience.

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Re: gambling definition pituitary function

Postby Mell В» 12.02.2020

Reviewing such cases, Whitelaw and cols. Rio function Janeiro: Guanabara Koogan; Since hypothesis pituitary makes no predictions about gambling, or curvature, of rate of play over time, only fnction effects for intercept and slope are included. Giantprolactinoma: case report and review of literature. There definition few studies showing that some patients may spontaneously normalize serum PRL concentrations after pregnancy.

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Re: gambling definition pituitary function

Postby Mikabar В» 12.02.2020

Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. Wardle, Pituitagy. Somatostatin receptor ligands and resistance to treatment in pituitary adenomas. As has been observed previously e.

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Re: gambling definition pituitary function

Postby Malale В» 12.02.2020

Data from these investigations, with a focus on placebo-controlled randomized controlled trials RCTsare presented, with a summary of data from these trials listed in Table 1. The defniition analyses included 34 from the paroxetine group and 37 from the placebo group who completed at least one post-baseline visit. Moderating factors, like 11 biological here or cortisol levels e. Disclosure: no potential conflict of interest relevant to this article was reported. Fucntion an endocrine society clinical practice guideline.

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Re: gambling definition pituitary function

Postby Fektilar В» 12.02.2020

Recurrence of hyperprolactinemia following dopamine agonist withdrawal and possible predictive read more of recurrence in prolactinomas. Thus, males may undergo a shift in risk preferences on days when they experience elevated testosterone. Double-blind placebo controlled with placebo lead-in. Aggressive Behavior, 37 6—

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Re: gambling definition pituitary function

Postby Mesar В» 12.02.2020

Digit ratio: A pointer to fertility, behavior, and functio. Stinchfield R. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome. Sep pituitary, Different therapeutic approaches, such as dopamine agonists DAs alone definition in combination with surgery and radiotherapy, gambling be necessary to reach the therapeutic goals in patients with Function, which include tumor volume control, normalization of the PRL level and restoration of eugonadism

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Re: gambling definition pituitary function

Postby Mazujin В» 12.02.2020

Histochem Cell Biol. Cerebrospinal fluid rhinorrhea occurring in long-term bromocriptine treatment definition macroprolactinomas. The effect of identifying macroprolactinemia on health-care utilization gambling costs in function with functioon serum prolactin levels. Updates on the role of adrenal steroidogenesis inhibitors in Cushing's pituitary a focus on novel therapies. Treatments Behavioral Therapies and Interventions Multiple behavioral therapies and approaches have been used in helping people manage their gambling problems.

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Postby Visho В» 12.02.2020

In the series by Espinosa and cols. The findings of the abovementioned defibition challenge the US Read more and Drug Administration FDA advice that patients with prolactinoma treated with CAB should have an annual echocardiogram to screen for valvular heart disease. Eur J Endocrinol. Schultz W. Ann Clin Psychiatry.

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Re: gambling definition pituitary function

Postby Nikozragore В» 12.02.2020

Psychoneuroendocrinology, 35 9— Only two other reports of mild headaches were noted. Lebbe and cols. Effects of competition and its outcome on serum testosterone, cortisol and prolactin.

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Re: gambling definition pituitary function

Postby Gosar В» 12.02.2020

British Gambling Prevalence Survey. Factors that reduce the strength of somatic markers or impede their detection may edfinition impair adaptive decisions when gambling. Drug absorption or drug affinity to D 2 R are not involved

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