Secreting Pituitary Adenomas Research Articles

Associations of Ki-67 Labeling Index with Clinical and Paraclinical Features of Growth Hormone-Secreting Pituitary Adenomas: A Single Center Report from Iran.

BackgroundAcromegaly is a rare disorder resulting from benign growth hormone (GH)-secreting pituitary adenomas in 90% of the cases. In recent years, many researchers have studied the Ki-67 index level of pituitary tumors and its relationship with demographics, biochemical parameters, clinical behavior, and recurrence rate.ObjectivesThis study aimed to evaluate the correlation of Ki-67 index level with clinicoradiological and endocrinological parameters in confirmed GH-secreting pituitary adenomas, as well as with the surgical response and medical treatment after surgery.MethodsWe collected the medical and pathologic records of 49 patients with GH-secreting pituitary adenoma who underwent surgeries from 2008 to 2017 in Shariati hospital affiliated to Tehran University of Medical Sciences.ResultsAccording to MRI reports, 94% of the tumors were macroadenomas. The MRI findings also revealed the median maximal adenoma diameter of 18.5 mm. About 40% of the patients achieved remission three months after the surgery. Younger patients had a significantly higher Ki-67 index level (P = 0.036). We did not observe any significant difference in the Ki-67 index level regarding gender, tumor type, maximal tumor diameter, tumor invasiveness, tumor secretory type, and remission. Interestingly, the Ki-67 index level was negatively correlated with the insulin-like growth factor-1 (IGF-1) level at the last follow-up (P = 0.02). In logistic regression analysis, patients with higher preoperative GH serum levels had a better outcome.ConclusionsOur results indicated a negative correlation between age and Ki-67 index level. However, there was no association between the Ki-67 index level and some tumor behaviors, as well as short- and long-term remission.

Benzene affects the response to octreotide treatment of growth hormone secreting pituitary adenoma cells

Growth hormone (GH) secreting pituitary adenomas are the main cause of acromegaly. Somatostatin analogs are the gold standard of medical therapy; however, resistance represents a big drawback in acromegaly management. We recently demonstrated that benzene (BZ) modifies the aggressiveness of GH-secreting rat pituitary adenoma cells (GH3), increasing GH secretion and altering the synthesis of molecules involved in the somatostatin signaling pathway. Based on these pieces of evidence, this study aimed to evaluate the effects of BZ on octreotide (OCT) efficacy in GH-secreting adenoma cells. In GH3 cells, BZ counteracted the anti-proliferative action of OCT. GH gene expression, unmodified by OCT, remained high in BZ-treated cells as well as after treatment with the association of both. GH secretion, reduced by OCT, was increased after treatment with BZ alone or when the pollutant was used with OCT. The combination of BZ and OCT greatly reduced the gene expression of ZAC1 and SSTR2; and this reduction was also present at a protein level. BZ caused an increase in the protein level of the transcription factor STAT3 and in its phosphorylated form. In the presence of BZ, OCT lost the ability to reduce the phosphorylated protein levels. Finally, in primary cultures of human pituitary adenoma cells, BZ caused an increase in GH secretion. OCT decreased GH secretion, but the addition of BZ reversed the OCT effect. In conclusion, our results suggest that BZ may have an important role in the resistance of pituitary adenomas to the pharmacological treatment with somatostatin analogs.

Stereotactic Radiosurgery for Acromegaly: An International Multicenter Retrospective Cohort Study.

Stereotactic radiosurgery (SRS) is a treatment option for persistent or recurrent acromegaly secondary to a growth hormone secreting pituitary adenoma, but its efficacy is inadequately defined. To assess, in a multicenter, retrospective cohort study, the outcomes of SRS for acromegaly and determine predictors. We pooled and analyzed data from 10 participating institutions of the International Gamma Knife Research Foundation for patients with acromegaly who underwent SRS with endocrine follow-up of ≥6 mo. The study cohort comprised 371 patients with a mean endocrine follow-up of 79 mo. IGF-1 lowering medications were held in 56% of patients who were on pre-SRS medical therapy. The mean SRS treatment volume and margin dose were 3.0 cm3 and 24.2 Gy, respectively. The actuarial rates of initial and durable endocrine remission at 10 yr were 69% and 59%, respectively. The mean time to durable remission after SRS was 38 mo. Biochemical relapse after initial remission occurred in 9%, with a mean time to recurrence of 17 mo. Cessation of IGF-1 lowering medication prior to SRS was the only independent predictor of durable remission (P = .01). Adverse radiation effects included the development of ≥1 new endocrinopathy in 26% and ≥1 cranial neuropathy in 4%. SRS is a definitive treatment option for patients with persistent or recurrent acromegaly after surgical resection. There appears to be a statistical association between the cessation of IGF-1 lowering medications prior to SRS and durable remission.

Diagnosing Thyroid-Stimulating Hormone (TSH)-Secreting Pituitary Adenomas by Short-Term Somatostatin Analogue Test

Background: Diagnosis of thyroid-stimulating hormone (TSH)-secreting pituitary adenomas (TSHoma) before surgery remains a challenge, especially microadenomas. We aimed to establish a short-term somatostatin analogues (SSA) test to differentiate TSHoma from resistance of thyroid hormone (RTH). Methods: We first evaluated the sensitivity and specificity of SSA test in a retrospective cohort (TSHoma, N=32; RTH, N=20). We then applied the SSA test in a perspective SITSH cohort without THRB gene mutation (pituitary microadenoma, N=10; negative pituitary imaging, N=7). Findings: In the retrospective cohort, both TSHoma and RTH patients showed a decrease of TSH at the start of the SSA test, but the velocity of TSH slowly decreased in RTH patients after 2 h. The suppression ratio of TSH at 24 h versus 2 h and 0 h in TSHoma patients was remarkably greater than in RTH patients. The 24 h versus 2 h suppression ratio showed the best diagnostic accuracy at a cut-point of 44·46%, with sensitivity as 95·00%, specificity as 93·75%. In the perspective cohort, 10/17 patients diagnosed as TSHoma with mean TSH suppression ratio of 68·91%, in which seven patients with microadenoma received pituitary surgery and achieved euthyroid with positive TSH staining in the resected tissues. Interestingly, two patients with negative pituitary imaging showed TSH suppression ratio greater than 44·46% and developed microadenomas at follow-up. Interpretation: A short-term SSA test provides an alternative diagnostic approach for TSHoma, especially microadenoma. It may also diagnose TSHoma in very early stage before positive findings in pituitary imaging. Funding Statement: This study was sponsored by the grants from National Science Foundation of China (81570702, 81400772, 81700686). Foundation of Health and Family planning Commission of Shanghai (20174Y0204). National International Science Cooperation Foundation (2015DFA30560). The National Key Research and Development Program of China (2016YFC0901503). Declaration of Interests: The authors state: No conflicts of interest to declare. Ethics Approval Statement: The board of medical ethics of Ruijin Hospital approved the study, and all patients provided informed written consent.

Quality of life is significantly impaired in both secretory and non-functioning pituitary adenomas.

To evaluate the quality of life (QoL) in patients with pituitary adenomas in comparison with healthy Mexican population QoL scores. Cross-sectional study using the short form 36 questionnaire (SF-36) in 175 patients with pituitary adenomas grouped by adenoma subtype and disease activity, and compared them with the healthy Mexican population normative QoL scores. A total of 44 patients with non-functioning pituitary adenomas (NFPA), 48 with acromegaly, 53 with prolactinomas and 30 with Cushing disease (CD) were enrolled in this study. Mental and physical components scores (MCS & PCS) of SF-36 questionnaire were lower in patients with active disease in all adenoma subtypes (P<0.03). A significant negative relationship between prolactin levels and MCS (r=-0.30, P<0.01) and PCS (r=-0.41, P<0.01) were found in prolactinomas. Patients with CD showed 24hours urine-free cortisol levels negatively correlated with MCS (r=-0.43, P<0.01) but not with PCS. No significant correlation was found between IGF-1 ULN and QoL scores in acromegaly. NFPA patients had lower QoL scores than patients with controlled CD, acromegaly or prolactinoma (P<0.02). Active CD and prolactinoma have lower QoL scores in comparison of NFPA (P<0.05). Having an adenoma, secretory or non-functioning, decrease QoL scores in comparison of results in the healthy Mexican population register. Using an adjusted-multivariate model, we confirmed that disease activity in all secretory adenomas is an independent risk factor, reducing SF-36 scores significantly. Activity in all secretory pituitary adenomas' patients decrease mental and physical QoL. However, independently of disease activity, secretory and NFPA significantly decrease QoL in comparison with healthy Mexican population QoL register.

Effect of lncRNA HULC knockdown on rat secreting pituitary adenoma GH3 cells.

Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.

Surgical Results and Predictors of Initial and Delayed Remission for Growth Hormone-Secreting Pituitary Adenomas Using the 2010 Consensus Criteria in 162 Patients from a Single Center

The factors associated with initial and delayed remission after growth hormone (GH)-secreting pituitary adenoma excision have not been completely elucidated. We recruited 185 consecutive patients who had undergone resection of GH-secreting pituitary adenomas from January 2013 to December 2014 and assessed their tumor characteristics and surgical outcomes. The criteria for initial or delayed remission (using the 2010 consensus criteria) were normalized insulin-like growth factor 1 (IGF-1) levels, GH levels <0.4 μg/L with an oral glucose tolerance test, and/or random GH levels <1.0 μg/L at or after the postoperative 3-month (PO3M) follow-up, without adjuvant therapy. Remission was achieved in 92 of 162 patients (56.8%) after surgery alone and was associated with a lower Knosp grade of 0-2 and lower postoperative day 1 GH level on multivariate regression analysis. A baseline IGF-1 index (IGF-1 level/upper limit of normal) of <2.835 predicted for initial remission at the PO3M follow-up (positive predictive value, 95.3%; negative predictive value, 36.6%; P < 0.001). The PO3M IGF-1 index was significantly lower in the delayed remission group than in the nonremission group. Furthermore, the former had had fewer invasive tumors (1.23 ± 0.21 vs. 1.77 ± 0.37 [9.52% vs. 76.47%]; P < 0.001). A PO3M IGF-1 index of <1.485 predicted for delayed remission during subsequent follow-up (positive predictive value, 84.6%; negative predictive value, 92.3%; P < 0.001). A lower Knosp grade of 0-2 and lower postoperative day 1 GH level were independent predictors of surgical remission. The baseline IGF-1 and PO3M IGF-1 indexes might predict for initial and delayed remission, respectively.

Delayed Remission of Growth Hormone-Secreting Pituitary Adenoma After Transsphenoidal Adenectomy

To investigate the clinical characteristics of delayed remission (DR) of growth hormone (GH)-secreting pituitary adenoma after transsphenoidal adenectomy and inform follow-up treatments. We retrospectively reviewed 87 patients who had undergone transsphenoidal surgery for acromegaly. Demographic, radiological, and endocrinological data were reviewed before, immediately after, 3 months after, and in the long term (2.4 ± 1.1 years) after surgery. The definition of DR was that patients did not achieve GH remission immediately, 3 months, or later after surgery, but did so in the long term without any additional postoperative treatment. Fifty-one patients (58.6%) achieved long-term GH remission. There were 24 (27.6%) DR patients immediately postoperatively and 9 (10.3%) DR patients 3 months postoperatively. On average, the 24 DR patients achieved remission at 10.2 (range, 3-32) months. Immediate postoperative random and nadir GH after an oral glucose load were significantly lower in the DR group than in the nonremission group (2.73 ± 3.17 and 2.03 ± 2.59 vs. 8.05 ± 10.35 and 5.55 ± 5.91 μg/L, respectively). Three-month postoperative nadir GH was significantly lower in the DR group than in the nonremission group (1.63 ± 2.82 vs. 3.48 ± 4.25 μg/L, P= 0.007). Immediate postoperative random GHeffectively predicted long-term remission (Spearman's ρ= 0.513, area under the curve= 0.905 > 0.90). However, the best predictor of long-term remission was 3-month postoperative nadir GH (Spearman's ρ= 0.728, area under the curve= 0.944 > 0.90), with 76.5% sensitivity and 97.2% specificity. For certain groups of patients likely to achieve DR, additional treatments should not be performed early after surgery. Prolonged follow-up and close observation could help determine the therapeutic effect of surgery and guide postoperative treatments.

Carney Complex.

Carney complex is a rare, autosomal dominant, multiple endocrine neoplasia and lentiginosis syndrome, caused in most patients by defects in the PRKAR1A gene, which encodes the regulatory subunit type 1α of protein kinase A. Inactivating defects of PRKAR1A lead to aberrant cyclic-AMP-protein kinase A signaling. Patients may develop multiple skin abnormalities and a variety of endocrine and non-endocrine tumors. Endocrine manifestations include primary pigmented nodular adrenocortical disease, that may cause Cushing syndrome, growth-hormone secreting pituitary adenoma or pituitary somatotropic hyperplasia which can result in acromegaly, as well as gonadal and thyroid tumors. Non-endocrine tumors associated with Carney complex include myxomas of the heart, breast, and other sites, psamommatous melanotic schwannomas, breast ductal adenomas, osteochondromyxomas, and a predisposition to a number of malignancies from adrenal to pancreatic and liver cancer.

Endocrine Remission after Pituitary Stereotactic Radiosurgery: Differences in Rates of Response for Matched Cohorts of Cushing’s Disease and Acromegaly Patients

To compare and describe the time to endocrine remission and new hypopituitarism among patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH) secreting pituitary adenomas after radiosurgery after controlling for several known prognostic factors. An institutional review board approved, institutional retrospective analysis of patients with GH- and ACTH-secreting pituitary adenomas was performed, with matching based on patient gender, age at radiosurgery, time interval between the last resection and radiosurgery, use of previous radiotherapy, whole sella treatment, suprasellar extension, cavernous sinus invasion, and margin dose. Endocrine remission was defined, off of suppressive medications, as a normal serum IGF-1 (GH-secreting) or a normal 24-hour urine free-cortisol (ACTH-secreting). Endocrine remission and the incidence of new hypopituitarism after single fraction radiosurgery were described and compared between groups. Two-hundred and forty-two (242) patients were evaluated, 121 with GH-secreting tumors and 121 with ACTH-secreting tumors. A total of 75% of patients had cavernous sinus invasion and 10% had suprasellar extension at the time of radiosurgery. The median radiosurgical marginal dose was 25 Gy to the 50% isodose line between each group. After multivariable adjustment, factors associated with increased time to endocrine remission included patient age (HR 1.016, p = 0.023), cavernous sinus invasion (HR 1.793, p = 0.004), and patients with acromegaly (HR 2.912, p < 0.001). The incidence of a new hypopituitarism developing after SRS was 29% and did not appreciably differ by adenoma subtype (p = 0.180). After radiosurgery, patients with ACTH-secreting tumors achieve endocrine remission sooner than those with GH-secreting tumors. These results provide insight into the relative tumor biology and post-radiosurgical disease course that will serve to further improve clinical outcomes and patient management in the future.

Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas.

somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been described in patients with Cushing's disease (CD). The aim of the study is to verify whether USP8 mutation may predict early and late outcome of pituitary surgery in patients with CD operated at a single institution. We performed a retrospective genetic analysis of 92 adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Specimens were screened for USP8 hotspot mutations in the exon 14 with Sanger sequencing. Hormonal and surgical data were compared between USP8 variant carriers and wild-type tumors. USP8 variants were detected in 22 adenomas (23.9%) with higher prevalence in women (28.9% vs. 5.3% in men; p < 0.05). No significant difference in hormonal levels and tumoral features in relation to USP8 status was observed. Interestingly, USP8-variant carriers were more likely to achieve surgical remission than wild-type adenomas (100% vs. 75.7%; p = 0.01). Conversely, recurrence of CD occurred in 23% of USP8-mutated patients and in 13% of patients with wild-type adenoma. The recurrence-free survival did not differ significantly between the two groups (p = 0.42). ACTH-secreting pituitary adenomas carrying somatic USP8 mutations are associated with a greater likelihood of surgical remission in patients operated by a single neurosurgeon. Recurrence rates are not related with USP8-variant status.

Association between KISS1 rs5780218 promoter polymorphism and onset of growth hormone secreting pituitary adenoma

ObjectivesThis study analyzed the KISS1 c.-145delA (rs5780218) promoter polymorphism in a cohort of patients with growth hormone secreting pituitary adenoma (somatotropinoma) and controls, to investigate its role in the incidence of acromegaly and to assess patient/tumor characteristics.Material and methods rs5780218 allelic and genotypic distributions were compared between 49 somatotropinoma patients and 167 healthy controls. rs5780218 was also assessed in relation to patient characteristics and tumor aggressiveness, as characterized by tumor invasion and resistance to conventional therapy. The relationship between KISS1 mRNA expression and the rs5780218 genotype was also assessed in available pituitary tumor samples. ResultsThe homozygous -/- variant genotype was associated with high rates of somatotropinoma (P<0.01), but not with tumor invasiveness, patient characteristics or hormonal remission. KISS1 mRNA expression was much lower in somatotropinomas carrying the deleted allele than in homozygous wild type AA. ConclusionsIn this pilot study, the rs5780218 promoter polymorphism was evaluated in pituitary adenoma, and showed a possible association with the incidence of somatotropinoma but not with tumor progression.

Imatinib Inhibits GH Secretion From Somatotropinomas

Background: Imatinib, a tyrosine kinase inhibitor, causes growth failure in children with chronic myeloid leukemia probably by targeting the growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis. We aim to explore the imatinib targets expression in pituitary adenomas and study the effect of imatinib on GH secretion in somatotropinoma cells and GH3 cell line.Materials and Methods: The expression pattern of imatinib's targets (c-kit, VEGF, and PDGFR-α/β) was studied using immunohistochemistry and immunoblotting 157 giant (≥4 cm) pituitary adenomas (121 non-functioning pituitary adenomas, 32 somatotropinomas, and four prolactinomas) and compared to normal pituitary (n = 4) obtained at autopsy. The effect imatinib on GH secretion, cell viability, immunohistochemistry, electron microscopy, and apoptosis was studied in primary culture of human somatotropinomas (n = 20) and in rat somato-mammotroph GH3 cell-line. A receptor tyrosine kinase array was applied to human samples to identify altered pathways.Results: Somatotropinomas showed significantly higher immunopositivity for c-kit and platelet-derived growth factor receptor-β (PDGFR-β; P < 0.009 and P < 0.001, respectively), while staining for platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor (VEGF) revealed a weaker expression (P < 0.001) compared to normal pituitary. Imatinib inhibited GH secretion from both primary culture (P < 0.01) and GH3 cells (P < 0.001), while it did not affect cell viability and apoptosis. The receptor tyrosine kinase array showed that imatinib inhibits GH signaling via PDGFR-β pathway.Conclusion: Imatinib inhibits GH secretion in somatotropinoma cells without affecting cell viability and may be used as an adjunct therapy for treating GH secreting pituitary adenomas.

Gene expression profiling in human corticotroph tumours reveals distinct, neuroendocrine profiles.

Adrenocorticotrophic hormone (ACTH)‐secreting pituitary adenomas give rise to a severe endocrinological disorder, comprising Cushing's disease, with multifaceted clinical presentation and treatment outcomes. Experimental studies suggest that the disease variability is inherent to the pituitary tumour, thus indicating the need for further studies into tumour biology. The present study evaluated transcriptome expression pattern in a large series of ACTH‐secreting pituitary adenoma specimens in order to identify molecular signatures of these tumours. Gene expression profiling of formalin‐fixed, paraffin‐embedded specimens from 40 human ACTH‐secreting pituitary adenomas revealed the significant expression of genes involved in protein biosynthesis and ribosomal function, in keeping with the neuroendocrine cell profile. Unsupervised cluster analysis identified 3 distinct gene profile clusters and several genes were uniquely overexpressed in a given cluster, accounting for different molecular signatures. Of note, gene expression profiles were associated with clinical features, such as the age and size of the tumour. Altogether, the findings of the present study show that corticotroph tumours are characterised by a neuroendocrine gene expression profile and present subgroup‐specific molecular features.

Outcomes of Aggressive Surgical Resection in Growth Hormone–Secreting Pituitary Adenomas with Cavernous Sinus Invasion

Cavernous sinus (CS) invasion is an unfavorable factor hindering the remission of growth hormone (GH)-secreting pituitary adenomas. Little data exist on aggressive surgical resection, however. We investigated the role of CS exploration for GH-secreting pituitary adenomas with CS invasion. We classified 132 patients with GH-secreting pituitary adenomas invading CS into 4 groups. The patients underwent surgery using a microsurgical transsphenoidal approach (TSA) with endoscopic assistance. Adenomas with CS invasion confined to the medial compartment of the internal carotid artery (ICA) were classified as type A (without radiologic evidence) or type B (with radiologic evidence). Adenomas with ICA encasement were classified according to the surgical approach as type C (standard TSA) or type D (far-lateral TSA). Surgical and endocrinologic outcomes were compared across groups. For type A, B, C, and D tumors, the rates of gross total resection were 100%, 73.6%, 14.7%, and 0%, respectively, and the rates of endocrinologic remission by surgery alone were 100%, 62.3%, 26.5%, and 0%, respectively. There was no endocrinologic remission by surgery alone for type D tumors; nevertheless, compared with type C tumors, type D tumors showed marked reductions in the postoperative nadir of GH at 1 week, 6 months, and 1 year and of insulin-like growth factor I at 1 year. For tumors with CS invasion confined to the medial compartment of the ICA, total resection should be attempted by direct visualization of the entire medial wall of the CS. Even for tumors with ICA encasement, aggressive tumor resection by far-lateral TSA can increase the chance of remission with the help of adjuvant treatment.

Endoscopic Endonasal Approach to the Growth Hormone–Secreting Pituitary Adenomas: Endocrinologic Outcome in 68 Patients

The endoscopic endonasal approach has recently become an acceptable option for resection of all pituitary adenomas. We assessed biochemical outcome of endoscopic endonasal surgery in growth hormone (GH)-secreting adenomas, including remission rate, predictors of remission, and associated complications. Sixty-eight consecutive patients with acromegaly who underwent endoscopic endonasal surgery were analyzed prospectively. Tumors were classified according to size, Knosp grade, and Hardy-Wilson classification. Biochemical remission was defined as normal serum insulin-like growth factor 1 level and either a suppressed GH serum level less than 0.4 μg/L during an oral glucose tolerance test or a random GH level less than 1.0 μg/L at least 3 months after surgery. Total biochemical remission rate was 64.7%. Gross total resection was achieved in 61 of the 68 patients (89.7%). Remission was achieved in 12 of 16 microadenomas (75%) and 32 of 52 macroadenomas (61.5%). Based on univariate logistic regression analysis, preoperative variables predictive of remission were age (P=0.004), Knosp grade (P= 0.023), and preoperative GH levels (P= 0.042). Three patients (4.4%) experienced postoperative panhypopituitarism, and permanent diabetes insipidus was seen in 4 patients (5.9%). Two patients (2.9%) developed cerebrospinal fluid leaks, which were treated by lumbar puncture in one case and early surgical repair in the other case. Endoscopic endonasal adenoma resection leads to a high rate of endocrinologic remission in GH-secreting adenomas with a low complication rate. Patients with older age, higher preoperative GH levels, and higher Knosp grades are less likely to achieve remission.

Quantification of specific growth patterns and frequency of the empty sella phenomenon in growth hormone-secreting pituitary adenomas

PurposeTo assess and quantify the prevalence and co-occurence of a sellar floor lowering and empty sella phenomenon in patients with GH (growth hormone)-secreting pituitary adenoma. MethodsA total number of 159 acromegalic patients were included in this study, as well as two control groups (150 patients with non-GH-secreting adenomas and 50 patients without pituitary adenomas). Magnetic resonance images of all patients were evaluated for presence of an empty sella, downward and lateral tumor extension, and maximum superoinferior diameter of the mass. Additionally, these values were correlated with growth hormone and IGF-1 levels. ResultsThe empty sella phenomenon was detected significantly more often in patients with a GH-secreting adenoma with a prevalence of 22% vs. 5.3% in non-GH-secreting adenomas (p < 0.001) or 8% in the healthy control group (p = .036). Moreover, GH-secreting adenomas presented with a significant rate of downward tumor extension (74.8% vs. 35.5%; p < 0.001), whose extent correlated inversely but weakly with the GH hormone level (r = − 0.17; p = .036). It was also found that a decreased superoinferior diameter and higher ratio of intrasellar to suprasellar extension are predictive quantitative values for the presence of a GH-secreting adenoma (area under curve, 0.712). ConclusionsGH-secreting pituitary adenomas are frequently associated with an empty sella phenomenon. Moreover, GH-secreting adenomas are frequently accompanied by an enhanced, quantitatively measurable impression of the sellar floor. Hypothetically, this is caused by tumor-induced local bone remodeling processes.

Time trends of mortality in patients with GH secreting and non-functioning pituitary adenoma

Time trends of mortality in patients with GH secreting and non-functioning pituitary adenoma

Protein expression of somatostatin receptor 2, somatostatin receptor 5 and dopamine D2 receptor in normal pituitary gland and ACTH-secreting pituitary adenoma in dogs

PurposeTo evaluate the protein expression of somatostatin receptor (SSTR) 2, SSTR5 and dopamine D2 receptor (DA2R)—targets of somatostatin analogs and dopamine agonists—in normal canine pituitary and canine adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. MethodsSix normal canine pituitary glands and 14 canine ACTH-secreting pituitary adenoma cases were included in this study. The protein expression of SSTR2, SSTR5 and DA2R was determined by double-label immunofluorescence staining of these receptors and ACTH. ResultsSSTR2, SSTR5, and DA2R proteins were expressed in the anterior and intermediate lobes of normal canine pituitary glands. In the anterior pituitary lobes, the percentages of SSTR2-, SSTR5-, and DA2R-positive cells among the ACTH-positive population were 27.0 ± 8.6%, 27.9 ± 5.9%, and 34.0 ± 9.4%, respectively. In contrast, the corresponding percentages in the intermediate pituitary lobes were 97.8 ± 1.5%, 94.1 ± 4.4%, and 96.1 ± 6.6%, respectively. Of the 14 ACTH-secreting pituitary adenoma cases, 11, 12, and 6 cases expressed SSTR2, SSTR5, and DA2R, respectively. Additionally, four cases showed strong positive staining for both SSTR2 and SSTR5. Two of these were ACTH-secreting pituitary adenomas likely derived from the intermediate pituitary lobe, because these are α-Melanocyte-stimulation hormone (α-MSH)-positive stains. ConclusionImmunohistological detection and characterization of SSTR2, SSTR5 and DA2R may provide useful additional information for determining treatment options when an ACTH-secreting pituitary adenoma cannot be completely resected, or in the case of recurrence.

Erratum. Value of pituitary gland MRI at 7 T in Cushing's disease and relationship to inferior petrosal sinus sampling: case report.

Cushing's disease is caused by adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas, which are often difficult to identify on standard 1.5-T or 3-T MRI, including dynamic contrast imaging. Inferior petrosal and cavernous sinus sampling remains the gold standard for MRI-negative Cushing's disease.The authors report on a 27-year-old woman with Cushing's disease in whom the results of standard 1.5-T and 3-T MRI, including 1.5-T dynamic contrast imaging, were negative. Inferior petrosal sinus sampling showed a high central-to-peripheral ACTH ratio (148:1) as well as a right-to-left ACTH gradient (19:1), suggesting a right-sided pituitary microadenoma. The patient underwent 7-T MRI, which showed evidence of a right-sided pituitary lesion with focal hypoenhancement not visualized on 1.5-T or 3-T MRI. The patient underwent an endoscopic endonasal transsphenoidal operation, with resection of a right-sided pituitary mass. Postoperatively, she developed clinical symptoms suggestive of adrenal insufficiency and a nadir cortisol level of 1.6 μg/dl on postoperative day 3, and hydrocortisone therapy was initiated. Permanent histopathology specimens showed Crooke's hyaline change and ACTH-positive cells suggestive of an adenoma.MRI at 7 T may be beneficial in identifying pituitary microadenoma location in cases of standard 1.5-T and 3-T MRI-negative Cushing's disease. In the future, 7-T MRI may preempt inferior petrosal sinus sampling and help in cases of standard and dynamic contrast 1.5-T and 3-T MRI-negative Cushing's disease.