Update: GH secreting pituitary adenoma

75 % are > 10 mm at time of diagnosis.

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⁾.

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⁾.

Giant GH-secreting adenomas are invasive, uncontrolled by surgery, and respond poorly to medical treatment. Aggressive multimodal therapy is critical for their management, enhancing control rate and biochemical remission ⁴⁾.

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 ⁵⁾.

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

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

The enhancement was significantly lower in GH secreting pituitary adenoma than in non-secreting ones. ⁶⁾.

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 ⁷⁾.

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 ⁸⁾.

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 ⁹⁾.

see Growth hormone secreting pituitary adenoma treatment

Surgery is the first-line therapy.

The resection via a transsphenoidal approach is able to induce a long-term remission of acromegaly, with low risk of recurrence and complications. Endoscopic endonasal transsphenoidal approach is more suitable than microscopic technique in macroadenomas and adenomas with suprasellar extension ¹⁰⁾.

The cost of treatment including medications and the possibility of major side effects represent important limitations of the medical therapy ^11) 12).

The most widely used criteria for neurosurgical outcome assessment were combined measurements of IGF-1 and GH levels after oral glucose tolerance test (OGTT) 3 months after surgery. Ninety-eight percent of respondents stated that primary treatment with somatostatin receptor ligands (SRLs) was indicated at least sometime during the management of acromegaly patients. In nearly all centers (96%), the use of pegvisomant monotherapy was restricted to patients who had failed to achieve biochemical control with SRL therapy. The observation that most centers followed consensus statement recommendations encourages the future utility of these workshops aimed to create uniform management standards for acromegaly ¹³⁾

Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4-6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits ¹⁴⁾.

Somatostatin treatment can induce extensive fibrosis in GH secreting pituitary adenoma ¹⁵⁾.

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 ¹⁶⁾¹⁷⁾.

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 ¹⁸⁾.

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 ¹⁹⁾.

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. ²⁰⁾.

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 ²¹⁾.