- Inhibition of neuronal nitric oxide synthase activity does not alter vasopressin secretion in septic rats. [Journal Article]
- PPituitary 2017 Jan 16
- CONCLUSIONS: We concluded that nNOS does not have a substantial role in vasopressin secretion during experimental sepsis.
- New medical therapies on the horizon: oral octreotide. [Review]
- PPituitary 2017 Jan 16
- Somatostatin analog treatment is first line medical treatment in patients with acromegaly. This drug is currently mainly administered by monthly depot preparations of octreotide and lanreotide. With ...
Somatostatin analog treatment is first line medical treatment in patients with acromegaly. This drug is currently mainly administered by monthly depot preparations of octreotide and lanreotide. With the innovative transient permeability enhancer, a technology enabling the absorption of drug molecules via transient opening of the tight junctions of the gut epithelium, it is possible to achieve therapeutic octreotide levels after oral ingestion. The present review summarized the preclinical work and the recently reported phase I and III study on oral octreotide capsules in patients with acromegaly. Maintenance of control in 155 participating patients was achieved in 65% at the end of core period. Once controlled on oral octreotide, the response was maintained to the end of the extension phase in 85%. Side effects were comparable to currently available preparations. There was a profound suppression of growth hormone levels, and significant symptom reduction. Currently available parental somatostatin analogs are generally well tolerated and are able to achieve longstanding biochemical control in patients with somatostatin sensitive tumors. Potential advantages of an oral alternative is the lack injection-related side effects, but there will be an ongoing need for a very strict compliance with the 2 daily dose regimen and fasting around drug administrations. A second phase III study is currently being conducted. The potential place in the treatment of acromegaly is discussed.
- Adipsic diabetes insipidus in adult patients. [Review]
- PPituitary 2017 Jan 10
- CONCLUSIONS: The management of ADI is challenging and is associated with significant morbidity and mortality. Prognosis is variable; hypothalamic complications lead to early death in some patients, but recent reports highlight the possibility of recovery of thirst.
- Cabergoline in acromegaly. [Review]
- PPituitary 2016 Dec 26
- Acromegaly, a rare disease due to growth hormone (GH) hypersecretion by a pituitary adenoma, is associated with severe comorbidity and premature death if not adequately treated. The usual first-line ...
Acromegaly, a rare disease due to growth hormone (GH) hypersecretion by a pituitary adenoma, is associated with severe comorbidity and premature death if not adequately treated. The usual first-line treatment is surgery. Various drugs, including somatostatin receptor ligands, dopamine agonists and GH receptor antagonists, are now available for use if surgery fails to suppress GH/IGF-I hypersecretion. Cabergoline, now the preferred dopamine agonist for treating hyperprolactinemia, is also used off-label for treating acromegaly. Cabergoline monotherapy is reported to normalize IGF-I levels in more than one-third of patients with acromegaly. When a somatostatin receptor ligand proves ineffective, cabergoline add-on therapy normalizes the IGF-I level in 40-50% of patients. Finally, when combined with the GH receptor antagonist pegvisomant in patients with mild uncontrolled disease, cabergoline helps to achieve normal IGF-I levels while avoiding the need for high-dose pegvisomant. Cabergoline is also inexpensive and well tolerated; in particular, it does not appear to promote heart valve disease.
- Management of aggressive growth hormone secreting pituitary adenomas. [Review]
- PPituitary 2016 Dec 16
- Aggressive GH-secreting pituitary adenomas (GHPAs) represent an important clinical problem in patients with acromegaly. Surgical therapy, although often the mainstay of treatment for GHPAs, is less e...
Aggressive GH-secreting pituitary adenomas (GHPAs) represent an important clinical problem in patients with acromegaly. Surgical therapy, although often the mainstay of treatment for GHPAs, is less effective in aggressive GHPAs due to their invasive and destructive growth patterns, and their proclivity for infrasellar invasion. Medical therapies for GHPAs, including somatostatin analogues and GH receptor antagonists, are becoming increasingly important adjuncts to surgical intervention. Stereotactic radiosurgery serves as an important fallback therapy for tumors that cannot be cured with surgery and medications. Data suggests that patients with aggressive and refractory GHPAs are best treated at dedicated tertiary pituitary centers with multidisciplinary teams of neuroendocrinologists, neurosurgeons, radiation oncologists and other specialists who routinely provide advanced care to GHPA patients. Future research will help clarify the defining features of "aggressive" and "atypical" PAs, likely based on tumor behavior, preoperative imaging characteristics, histopathological characteristics, and molecular markers.
- Somatostatin and dopamine receptor regulation of pituitary somatotroph adenomas. [Review]
- PPituitary 2016 Nov 29
- Somatostatin and dopamine receptors are expressed in normal and tumoral somatotroph cells. Upon receptor stimulation, somatostatin and the somatostatin receptor ligands octreotide, lanreotide, and pa...
Somatostatin and dopamine receptors are expressed in normal and tumoral somatotroph cells. Upon receptor stimulation, somatostatin and the somatostatin receptor ligands octreotide, lanreotide, and pasireotide, and to a lesser extent, dopamine and the dopamine analogs bromocriptine and cabergoline, suppress growth hormone (GH) secretion from a GH-secreting pituitary somatotroph adenoma. Somatostatin and dopamine receptors are Gαi-protein coupled that inhibit adenylate cyclase activity and cAMP production and reduce intracellular calcium concentration and calcium flux oscillations. Although their main action on somatotroph cells is acute inhibition of GH secretion, they also may inhibit GH production and possibly somatotroph proliferation. These receptors have been reported to create complexes that exhibit functions distinct from that of receptor monomers. Somatostatin suppression of GH is mediated mainly by somatostatin receptor subtype 2 and to a lesser extent by SST5. Human somatostatin receptor subtype 5 has also been shown to harbor mutations associated with GH levels, somatotroph tumor behavior, and somatostatin receptor ligand (SRL) responsiveness. Reviewing current knowledge of somatostatin and dopamine receptor expression and signaling in normal and tumoral somatotroph cells offers insights into mechanisms underlying SRL and dopamine agonist effectiveness in patients with acromegaly.
- SOCS2 polymorphisms are not associated with clinical and biochemical phenotypes in acromegalic patients. [Journal Article]
- PPituitary 2016 Nov 29
- CONCLUSIONS: Despite of the key role of SOCS2 in the regulation of GH receptor signaling, we did not find any significant association between SOCS2 polymorphisms and acromegaly.
- Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis. [Journal Article]
- PPituitary 2016 Nov 28
- CONCLUSIONS: Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.
- Erratum to: Predictive role of dynamic contrast enhanced T1-weighted MR sequences in pre-surgical evaluation of macroadenomas consistency. [Published Erratum]
- PPituitary 2016 Nov 21
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- Benzene and 2-ethyl-phthalate induce proliferation in normal rat pituitary cells. [Journal Article]
- PPituitary 2016 Nov 16
- CONCLUSIONS: Our findings indicate that benzene and 2-ethyl-phthalate activate AhR/AIP expression and stimulate proliferation in normal rat pituitary cells. This study is the first demonstration that pollutants can induce normal pituitary cells to proliferate and provides a link between epidemiological and genomic findings in pituitary tumors.