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gh_secreting_pituitary_adenoma

GH secreting pituitary adenoma

Growth hormone-secreting functioning pituitary adenoma (GHPA) is a rare, chronic, systemic disease that is associated with premature death and significant morbidity 1).

75 % are > 10 mm at time of diagnosis.

Epidemiology

An increased rate of acromegaly was reported in industrialized areas, suggesting an involvement of environmental pollutants in the pathogenesis and behavior of GH secreting pituitary adenomas 2).

Etiology

The aim of a study was to evaluate the effects of some widely diffused pollutants (i.e. benzene, BZ; bis(2-ethylhexyl) phthalate, DEHP and polychlorinated biphenyls, PCB) on growth hormone secretion, the somatostatin and estrogenic pathways, viability and proliferation of rat GH-producing pituitary adenoma (GH3) cells. All the pollutants induced a statistically significant increase in GH secretion and interfered with cell signaling. They all modulated the expression of SSTR2 and ZAC1, involved in the somatostatin signaling, and the expression of the transcription factor FOXA1, involved in the estrogen receptor signaling. Moreover, all the pollutants increased the expression of the CYP1A1, suggesting AHR pathway activation. None of the pollutants impacted on cell proliferation or viability. Present data demonstrate that exposure to different pollutants, used at in vivo relevant concentrations, plays an important role in the behavior of GH3 pituitary adenoma cells, by increasing GH secretion and modulating several cellular signaling pathways. These observations support a possible influence of different pollutants in vivo on the GH-adenoma aggressiveness and biological behavior 3).

Types

Patients with acromegaly usually harbor macroadenomas measuring between 10 and 30 mm in maximal diameter. Giant (adenoma size ≥40 mm) GH-secreting pituitary tumors are rarely encountered.

see Giant GH secreting pituitary adenomas or invasive.


Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done 4).

Clinical Features

Excessive growth hormone (GH) is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults.

Diagnosis

It is related to high levels of growth hormone (GH) and insulin-like growth factor-I (IGF-1).

MRI

The enhancement was significantly lower in GH secreting pituitary adenoma than in non-secreting ones. 5).

T2 weighted image differentiates GH secreting pituitary adenomas into subgroups with particular behaviors. This raises the question of whether T2-weighted signal could represent a factor in the classification of acromegaly in future studies 6).

In patients with acromegaly, T2 weighted image signal intensity at diagnosis correlates with histological features and predicts biochemical outcome of first-line somatostatin analogues (SA) treatment 7).

Biomarkers

Each of the biomarkers, Ki-67 and p53, along with patient's age and mixed GH-prolactin secretion showed a kind of correlation with each of aspects of the clinical, hormonal and radiologic outcome of GH-secreting pituitary adenomas 8).

Treatment

Outcome

The standardised mortality index (the ratio of observed mortality in the acromegalic population to expected mortality in the general population) ranged from 1.2 to 3.3. If left untreated, patients with acromegaly can die approximately 10 years earlier than the healthy subjects. According to prior studies, approximately 60, 25 and 15% of the patients die from cardiovascular disease, respiratory complications and cancer, respectively 9) 10).

Control of serum GH and insulin-like growth factor (IGF) 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity.

Remission rates for micro- and macroadenomas were 81.8% and 45.8%, respectively. Patients of older age, with a smaller tumor, lower Knosp grade, lower preoperative GH, and insulinlike growth factor 1 levels were more likely to achieve remission. Remission rate decreased significantly with repeat surgeries. Those patients with adenomas that stained positive for somatostatin receptor subtype 2A were less likely to experience tumor recurrence and more likely to respond to medical treatment with persistent or elevated GH hypersecretion 11).

A retrospective review of 53 patients who had follow up endocrinologic data at least 3 months post-surgery was performed among patients who were treated by EEA between 1998 and 2012. Data were analyzed for remission using GH and IGF-I levels based on 2010 consensus criteria. We also analyzed the outcomes using 2000 consensus criteria for ease in comparison to prior studies of outcomes of surgery for acromegaly. In this series of mostly large (88.2% macroadenomas), invasive (46.9% Hardy-Wilson C, D, E) adenomas, there were 27 patients (50.9%) who achieved remission after EEA only. For patients who had no remission with EEA alone, RS and/or medical therapy were used and 37 patients (69.8 %) achieved remission overall. Statistical analysis showed larger tumor size, Hardy Stages C, D, E and Knosp Scores 3, 4 to be predictive against remission for EEA only and EEA with other modalities. The volume of residual tumor after EEA was not found to be predictive of remission with additional therapies. We used stringent consensus criteria from 2010 in a series which included a high proportion of invasive GH secreting adenomas to show that EEA alone or combined with other modalities results in comparable remission rates to earlier studies which used less strict criteria, while retaining low complication rates 12).

Each of the biomarkers, Ki-67 and p53, along with patient's age and mixed GH-prolactin secretion showed a kind of correlation with each of aspects of the clinical, hormonal and radiologic outcome of GH-secreting pituitary adenomas in the series of Alimohamadi et al. 13).

Case reports

2015

A 37-year-old woman has presented with complaints of headache, amenorrhea and acromegaly.

Her laboratory studies showed markedly elevated levels of Insulin like Growth Factor 1 (IGF-1), and low levels of follicle stimulating hormone and luteinizing hormone. Computerized tomography has revealed a pituitary tumor without extra-sellar extension. The tumor has completely excised via Endoscopic transsphenoidal approach. Histologically, the tumor has diagnosed as a pituitary adenoma with GH positive cells. The serum IGF1 levels have gradually decreased to the normal range and the patient was symptom free for three and a half years when she has returned with complaint of visual impairment. The brain MRI that time has shown a supra-sellar mass growing independently into the remaining sellar part. Subsequently, surgical operation has performed via trans-nasal endoscopic approach. Histopathological and immunohistochemistry examination have revealed a rare case of growth hormone producing pituitary adenoma with brain invasion and lymphocytic infiltration.

The aim of this publication was to present a rare case of growth hormone producing pituitary adenoma with brain invasion and lymphocytic infiltration 14).

1)
Ayuk J, Clayton RN, Holder G, Sheppard MC, Stewart PM, Bates AS. Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J Clin Endocrinol Metab. 2004;89:1613–7.
2) , 3)
Fortunati N, Guaraldi F, Zunino V, Penner F, D'Angelo V, Zenga F, Pecori Giraldi F, Catalano MG, Arvat E. Effects of environmental pollutants on signaling pathways in rat pituitary GH3 adenoma cells. Environ Res. 2017 Jul 18;158:660-668. doi: 10.1016/j.envres.2017.07.015. [Epub ahead of print] PubMed PMID: 28732322.
4)
Manuylova E, Calvi LM, Hastings C, Vates GE, Johnson MD, Cave WT Jr, Shafiq I. Late presentation of acromegaly in medically controlled prolactinoma patients. Endocrinol Diabetes Metab Case Rep. 2016;2016. pii: 16-0069. PubMed PMID: 27855229.
5)
Lundin P, Bergström K. Gd-DTPA-enhanced MR imaging of pituitary macroadenomas. Acta Radiol. 1992 Jul;33(4):323-32. PubMed PMID: 1633042.
6)
Potorac I, Petrossians P, Daly AF, Schillo F, Ben Slama C, Nagi S, Sahnoun Fathallah M, Brue T, Girard N, Chanson P, Nasser G, Caron P, Bonneville F, Ravérot G, Lapras V, Cotton F, Delemer B, Higel B, Boulin A, Gaillard S, Luca F, Goichot B, Dietemann J, Beckers A, Bonneville J. Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences. Endocr Relat Cancer. 2015 Jan 2. pii: ERC-14-0305. [Epub ahead of print] PubMed PMID: 25556181.
7)
Heck A, Ringstad G, Fougner SL, Casar-Borota O, Nome T, Ramm-Pettersen J, Bollerslev J. Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly. Clin Endocrinol (Oxf). 2012 Jul;77(1):72-8. doi: 10.1111/j.1365-2265.2011.04286.x. PubMed PMID: 22066905.
8)
Alimohamadi M, Ownagh V, Mahouzi L, Ostovar A, Abbassioun K, Amirjmshidi A. The impact of immunohistochemical markers of Ki-67 and p53 on the long-term outcome of growth hormone-secreting pituitary adenomas: A cohort study. Asian J Neurosurg. 2014 Jul-Sep;9(3):130-6. doi: 10.4103/1793-5482.142732. PubMed PMID: 25685203; PubMed Central PMCID: PMC4323896.
9)
Chanson P, Salenave S, Kamenicky P, Cazabat L, Young J. Pituitary tumours: Acromegaly. Best Pract Res Clin Endocrinol Metab. 2009;23:555–74.
10)
Holdaway IM, Rajasoorya C. Epidemiology of acromegaly. Pituitary. 1999;2:29–41.
11)
Sun H, Brzana J, Yedinak CG, Gultekin SH, Delashaw JB, Fleseriu M. Factors associated with biochemical remission after microscopic transsphenoidal surgery for acromegaly. J Neurol Surg B Skull Base. 2014 Feb;75(1):47-52. doi: 10.1055/s-0033-1354578. Epub 2013 Sep 9. PubMed PMID: 24498589; PubMed Central PMCID: PMC3912146.
12)
Shin SS, Tormenti MJ, Paluzzi A, Rothfus WE, Chang YF, Zainah H, Fernandez-Miranda JC, Snyderman CH, Challinor SM, Gardner PA. Endoscopic endonasal approach for growth hormone secreting pituitary adenomas: outcomes in 53 patients using 2010 consensus criteria for remission. Pituitary. 2013 Dec;16(4):435-44. doi: 10.1007/s11102-012-0440-6. PubMed PMID: 23179961.
13)
Alimohamadi M, Ownagh V, Mahouzi L, Ostovar A, Abbassioun K, Amirjmshidi A. The impact of immunohistochemical markers of Ki-67 and p53 on the long-term outcome of growth hormone-secreting pituitary adenomas: A cohort study. Asian J Neurosurg. 2014 Jul-Sep;9(3):130-6. doi: 10.4103/1793-5482.142732. PubMed PMID: 25685203; PubMed Central PMCID: PMC4323896.
14)
Bidari-Zerehpoosh F, Sharifi G, Novin K, Mortazavi N. Invasive Growth Hormone Producing Pituitary Adenoma With Lymphocytic Infiltration: A Case Report and Literature Review. Iran J Cancer Prev. 2015 Dec;8(6):e3504. Epub 2015 Dec 23. PubMed PMID: 26855718.
gh_secreting_pituitary_adenoma.txt · Last modified: 2018/01/01 11:59 by administrador