GH Adenomas Research Articles

GH and Prolactin co-secreting Adenomas: It Is Time for a Definition

GH and Prolactin co-secreting Adenomas: It Is Time for a Definition

Type 2 Diabetes Revealing a Mixed GH (Acromegaly) and Prolactin Adenoma: A Case Report of the Internal Medicine Department of the Gabriel Touré University Hospital, Bamako, Mali

Type 2 Diabetes Revealing a Mixed GH (Acromegaly) and Prolactin Adenoma: A Case Report of the Internal Medicine Department of the Gabriel Touré University Hospital, Bamako, Mali

Type 2 Diabetes Revealing a Mixed GH (Acromegaly) and Prolactin Adenoma: A Case Report of the Internal Medicine Department of the Gabriel Touré University Hospital, Bamako, Mali

Introduction: Pituitary adenomas are benign, well-differentiated tumours that usually grow slowly over several years and are developed monoclonally from anteropituitary endocrine cells. We report a case of mixed GH and prolactin adenoma diagnosed in the Internal Medicine Department of the Gabriel Touré University Hospital, Bamako, Mali. Observation: The patient was a 36-year-old man with a 4-year history of type 2 diabetes mellitus who had consulted a specialist for headache, polyuro-polydipsic syndrome, decreased libido and erectile dysfunction. On clinical examination, a tumour syndrome was noted with headache and visual blur. The biology revealed a GH hypersecretion syndrome (IGF1) which was elevated to 561.9 µg/ml (VN=116-353) and prolactin elevated to 463.3 µIU/ml (VN: 24-324) and diabetes. Pituitary MRI revealed a pituitary macroadenoma. Our patient was treated with Dostinex 0.5mg/week with a gradual increase in dose and insulin. He was also referred to neurosurgery, where he is awaiting removal of the adenoma after glycaemic control and hormone normalisation. The evolution was marked by the disappearance of headaches, improvement in vision, GH and prolactin hypersecretion syndrome and glycaemic control. Conclusion: In sub-Saharan Africa, the problems posed by pituitary adenomatous pathologies are complex, due to the limited biological and morphological investigation facilities and the rarity of specialised surgical facilities.

P-47 Rare case of acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome

Abstract Introduction The concurrence of acromegaly and Cushing syndrome is infrequent. Pituitary adenomas are responsible for acromegaly and for Cushing syndrome in about 95% and 80% of cases respectively. Except adrenal adenoma, the other causes of Cushing syndrome remain rare. We here describe a case of a Tunisian patient with acromegaly due to plurihormonal pituitary adenoma and ACTH-independent Cushing syndrome with bilateral macronodules. Clinical Case A 35-year-old male patient was diagnosed with acromegaly by acrofacial dysmorphia. He had a family history of type 2 diabetes mellitus and hypertension but no endocrine diseases. He has diabetes mellitus for 15 years, hypertension and obstructive sleep apnea. Physical examination showed multiple blue nevi in the trunk. IGF-1 was elevated (1680ng/mL) and GH levels were not suppressed after an oral glucose load (nadir 78ng/mL). He had hypogonadotropic hypogonadism with normal prolactin (9,66ng/mL). Basal cortisol, FT4 and TSH levels were in the normal ranges. Pituitary MRI showed pituitary macroadenoma of 25×20.7 mm, invading both cavernous sinuses and compression of optic chiasma. He underwent transsphenoidal resection with histology confirming a prolactin, GH and LH co-secretory pituitary adenoma. He received postoperatively somatostatin analogue and cabergoline, in addition to external radiotherapy. Ultrasonography found infracentimetric EU-TIRADS 2 left nodule and multiple colloid cysts of the thyroid, testicles microlithiasis and no cardiac myxomas. Nine years after the diagnosis of acromegaly, bilateral adrenal adenomas (left:14 mm, right: 9 mm) were incidentally discovered by CT-scan done for abdominal pain. Low dose dexamethasone suppression test was carried out showing no suppression of cortisol and the low ACTH level confirmed ACTH-independent Cushing syndrome. Conclusion In our patient, at least two endocrine syndromes deserve to be mentioned. The first syndrome is Multiple Endocrine Neoplasia Type 1 but calcium and PTH levels were normal and there was no sign for neuroendocrine tumors. The second one is Carney's complex since our patient has acromegaly and multiple blue nevi which are two major criteria confirming the diagnosis. Cushing syndrome in Carney's complex is related to primary pigmented nodular adrenal disease characterized by micronodular hyperplasia. However, bilateral macronodules could be found in up to 30% of cases.

Abstract #1407996: Co-secreting Pituitary Tumors: A Clinical Challenge

Co-secreting pituitary adenomas are rare, with complex clinical presentation and challenging long-term management. We present a small case series of co-secreting pituitary tumors, highlighting the importance of evaluating all pituitary hormones in the setting of a pituitary adenoma. Case 1: Active acromegaly with a functioning pituitary FSHoma A 46-year-old married male, presented with bilateral vision loss, headache, and weight gain for the last 18 months. He had also noticed enlarging hands and decreased libido. He was obese (BMI of 32.2 Kg/m2). Red reflex was present in the right eye, while temporal hemianopia was noted in the left eye. He had phenotypic features of acromegaly, had enlarged testicles measuring more than 25mls bilaterally. Acromegaly and FSHoma were confirmed with raised IGF-1 levels (733.70 ng/ml) and FSH levels, checked twice (108.9 & 107 mIU/ml respectively) with low LH (2.40 mIU/ml) and T (1.27 pg/ml); PRL, ACTH, and TSH were normal. MRI pituitary revealed a large mass measuring ∼ 2.9 x 3.6 x 4.7 cm. He was referred for pituitary surgery but was lost to follow-up thereafter. Case 2, 3, 4, 5: Acromegaly with co-secretion of prolactin Two single females, aged 18, and 33; one married, aged 33, and a 23-year-old single male presented with enlarging hands and feet and weight gain. All females had secondary amenorrhoea and galactorrhoea. A male patient and two of the females also had headaches and visual disturbances. The youngest of them did not have any classical signs of acromegaly but had bitemporal hemianopia. The male patient had right-sided temporal hemianopia. They all had raised IGF-1 levels (1195.0, 701.0, 1136.0, & 516.7ng/mL). PRL levels were 458.1, 303.0, 53.0, and 1825 ng/ml. Their LH, FSH, and FT4 levels were low. All had normal ACTH and Cortisol levels. MRI pituitary revealed pituitary macroadenomas. All were started with cabergoline and referred for surgery. Only the youngest patient underwent surgery. The other three declined surgery for the time being and were started on monthly long-acting Octreotide. Case 6: Prolactinoma with late co-secretion of growth hormone A 40-year-old female, with a history of micro prolactinoma diagnosed in 2004, recently presented in 2021 with complaints of enlarging hands and feet. There was no history of headache or visual symptoms. She presented, 16 years ago with secondary amenorrhoea with isolated hyperprolactinemia. Her MRI showed a pituitary mass measuring 1.2 x1.6 cm. Since that time, she was on cabergoline. She also had subtle signs of acromegaly. Showed raised IGF-1 (410.0) and GH nadir of 3.12mcg/L after a 75 g oral glucose challenge. Her FSH, LH, Estradiol, FT4, and cortisol were normal, while PRL was raised (49.6 ng/ml). Her cabergoline dose was increased and was referred for Trans-sphenoidal surgery. The literature review revealed a very rare synchronous presentation of acromegaly and FSH-secreting pituitary adenoma. FSH and FSHoma is specified in the etiology of macroorchidism, as present in our case. Up to 25% of GH adenomas co-secrete prolactin. The Third Type occurs due to Primitive acidophilic stem cell adenomas with dual hormone secretion from a single cell.

Giant Pituitary Adenoma Presenting With Disinhibition: A Case Report of a 25-Year-Old Male

Background: Giant growth hormone secreting pituitary adenomas (defined by a diameter >4cm) are rare and difficult to treat (1). These typically invade surrounding structures, making surgery challenging or impossible (1). This report highlights a giant mammosomatotrophinoma with an unusual clinical presentation. Clinical Case: A 25-year-old male presented with personality changes, disinhibition and executive dysfunction progressing over a 3 to 4-year period. Further enquiry elicited a history of increasing headaches and significant visual loss, on the background of unilateral childhood visual loss in the contralateral eye. He was noted to have clinical features of acromegaly and complete temporal visual field loss in the left eye. On initial testing plasma IGF-1 was 137 nmol/L (reference interval [RI] 13-43nmol/L), GH >100 ug/L and prolactin 23,900 mIU/L (RI 0-400mIU/L). GH remained >100ug/L at 120 minutes after a 75g oral glucose load. He has hypogonadotropic hypogonadism, however thyrotropic and corticotropic function remained normal. MRI of the brain with contrast revealed an 8.0 x 7.1 x 7.4 cm mass arising from the pituitary fossa, extending into the suprasellar region and displacing both frontal lobes. The mass encased the basilar and right internal carotid arteries. It was deemed inoperable due to its exceptionally large size and encasement of vascular structures. Medical treatment was initiated with cabergoline (3.5mg per week in divided doses) and octreotide LAR, initially 30mg then increased to 60mg 4-weekly. A weaning course of steroids was initiated for oedema of his optic nerve. Within one month of treatment there was improvement of clinical symptoms of headaches, sweating, irritable mood and disinhibition with associated modest biochemical improvement (reduction of IGF-1 to 129 nmol/L and prolactin reduction to 2119 mIU/L). MRI of the brain revealed a reduction in the size of the adenoma to 7.8 x 7.1 x 6.3 cm, with a reduction in the mass effect on the frontal lobes. The patient continues medical management and close clinical monitoring with the aim of ongoing tumour shrinkage to allow reassessment for possible surgical debulking. Conclusion: This unique case of a GH and prolactin co-secreting giant pituitary adenoma posed a therapeutic challenge due to the significant surgical risk, limiting treatment to aggressive medical therapy. The cognitive and behavioral changes experienced due to tumour size and location added to the management complexity. Although early on in the treatment course, there is improvement of symptoms and tumour size on cabergoline and octreotide LAR injections. (1) Iglesias P, Rodríguez Berrocal V, Díez JJ. Giant pituitary adenoma: histological types, clinical features and therapeutic approaches. Endocrine. 2018 Sep;61(3):407-421.

Exceptional Localization of a Prolactinoma as Part of Familial Isolated Pituitary Adenomas

The syndrome of familial isolated pituitary adenomas (FIPA) or predisposition to pituitary adenomas (PAP) is characterized by the presence within the same family of at least two isolated pituitary adenomas without any other type of associated endocrine tumor. These pituitary tumors may present as homogenous with the same tumor phenotype or heterogeneous with different patterns of pituitary tumor phenotypes (GH, Prolactine, ACTH secretion or non-functioning pituitary adenomas) within the same kindred. Patients with FIPA are significantly younger at diagnosis and have significantly larger pituitary adenomas than matched sporadic pituitary adenoma counterparts. We report the case of a prolactinoma attached to the pituitary stalk as part of FIPA, revealed by erectile dysfunction.

Long-term facial changes and clinical correlations in patients with treated acromegaly: a cohort study.

Facial abnormality is the most significant feature in acromegaly patients. However, it is unclear whether and how patient facial appearance improves after treatment. This study aimed to identify 3D facial changes in acromegaly patients after surgical treatment. This study included 30 acromegaly patients who underwent resection of a pituitary GH adenoma. The location and extent of facial changes were identified by comparing baseline and 2-year follow-up 3D images of the face. Relationships between facial changes and GH and IGF-1 were evaluated with simple or multivariable linear regression models. Significant soft tissue improvements were observed in acromegaly patients with complete remission, especially in the nose and lip region. Significant reductions in nasal width (3.46 mm, P < 0.001), tip protrusion (1.18 mm, P = 0.003), face curve length (3.89 mm, P = 0.004) and vermilion area (1.42 cm3, P = 0.001) were observed at the 2-year follow-up. Further, changes in nasal width were associated with decreases in GH (β = 4.440, P = 0.017), the GH nadir (β = 4.393, P = 0.011) and IGF-1 (β = 5.263, P = 0.002). The associations were maintained after adjusting for confounders. Acromegaly patients achieved considerable facial improvements after surgical treatment. The change in nose width was associated with GH and IGF-1 decrease. Better control of patient hormone levels after surgery improves patient facial recovery.

Clinical Evaluation on Non-Functional Invasive Hypophysis Adenomas

Background&#x0D; There are ongoing studies to predetermine non-functional invasive pituitary adenomas which may show aggressive behavior. Our aim is to discuss whether there is a relationship between the immunohistochemical presence of GH, FSH, LH, PRL, ACTH, TSH and their aggressive clinical course in non-functional pituitary adenomas.&#x0D; Materials and Methods &#x0D; In this study, we evaluated retrospectively the files of the patients who were diagnosed with thesellar or parasellar tumor in our endocrinology clinic between the years of 2004-2014.The patients were divided into two groups as non-invasive pituitary adenomas and non-functional invasive pituitary adenomas. The immunohistochemical staining characteristics were compared between the two groups.&#x0D; Results &#x0D; In this study, we scanned the data of 70 patients who were followed for non-functional sellar or parasellar mass. 47.1% of the patients were female and 52.9% of the patients were male.39 patients had a non-functional pituitary adenoma.The rate of non-functional invasive adenoma was found to be 20.5%. There was a significant relationship between the immunohistochemical positivity of GH, FSH, LH andaggressive behavior of non-functional invasive adenomas. There was no a significant relationship between the immunohistochemicalpositivityof PRL, ACTH, TSH and aggressive behavior of non-functional invasive adenomas.&#x0D; Conclusion &#x0D; We found silent GH and gonadotropin adenomas as non-functional aggressive pituitary adenoma. More aggressive treatment and close clinical monitoring should be performed because atypical pituitary adenomas are characterized by invasive growth and aggressive clinical course.

DAPT, a γ-Secretase Inhibitor, Suppresses Tumorigenesis, and Progression of Growth Hormone-Producing Adenomas by Targeting Notch Signaling.

Advances in the understanding of growth hormone-producing adenomas (GHomas) are ongoing, but current therapy is limited by moderate and variable efficacy and in need of life-long treatment. In this study, the molecular signaling pathway related to GHoma was investigated by proteomics and transcriptomics. The differentially expressed proteins and genes were significantly enriched in Extracellular Matrix-Receptor Interactions, Notch Signaling, Basal Cell Carcinoma Signaling, JAK-STAT3, Wnt Signaling, and Glioblastoma Multiforme Signaling by Ingenuity Pathway Analysis. Furthermore, the Notch2/Delta-like canonical Notch ligand (DLL) signaling pathway was identified to be associated with tumorigenesis and invasiveness of GHoma. In 76 patients, Notch2 and DLL3 were upregulated in invasive compared to those in non-invasive GHoma (p < 0.05). Disease-free survival was significantly longer in patients with low, compared with high, DLL3 expression (p = 0.027). Notch 2 knockdown inhibited cell migration in both GH3 cells and primary GHoma cells, along with downregulation of the mRNA expression of related genes. DAPT, a γ-secretase inhibitor, inhibited tumor growth and invasion in vivo and in vitro and suppressed the release of growth hormone in primary GHoma cells. The involvement of Notch2/DLL3 signaling in GHoma progression warrants additional study of Notch inhibitor, DAPT, as a potential GHoma treatment.Importance of the StudyCurrent treatments of GH adenomas (GHomas) are limited by their moderate and variable efficacy and in need of life-long treatment. We found that the Notch2/Delta-like Notch ligand 3 (DLL3) signaling pathway was active in GHoma tumorigenesis, progression, and invasion.The γ-secretase inhibitor DAPT is of potential use in GHoma treatment targeting Notch signaling.

MON-LB100 Worse Clinical Characteristics and More Unsatisfactory Therapeutic Outcomes in Coexisting Thyrotropin Pituitary Adenomas

: TSH-secreting adenoma (TSHoma) occupies less than 1% of pituitary adenomas and coexisting TSHoma is the rarer type(1). Few reports are available on the characteristics of coexisting TSHomas. To summarize the clinical, histological features and therapeutic outcomes of coexisting TSHomas, we retrospectively analyzed 51 patients (16 and 35 cases of coexisting TSHomas and pure TSHomas) diagnosed from January 2012 to April 2018 in a single center. A rate of mixed GH (68.8%) , GH+PRL (18.7%) and PRL adenomas (12.5%) were involved in our coexisting TSHoma population. Coexisting TSHomas had significantly longer median disease duration (84.0 vs 24.0 months, P=0.023), a larger rate of male patients (75.0% vs 40.0%, P=0.020), thyroid volume (41.8±17.3 cm3 vs 19.6±8.4cm3, P=0.003), tumor maximum diameter (28.2± 14.7 mm vs 15.8±9.3 mm, P=0.009), tumor volume (6.9 cm3 vs 1.0 cm3, P=0.002) and a higher ratio of cavernous sinus invasion (defined as Knosp≥3, 56.3% vs 6.5%, P=0.001). The effects of preoperative medical and surgical treatment were assessed. In preoperative medical treatment, coexisting TSHomas patients achieved a similar ratio of thyroid function normalization and tumor shrinkage≥20% with a longer course of treatment with somatostatin analogs (4.8 times vs 3.0 times, P=0.006) when compared with pure TSHomas. Coexisting TSHomas patients yielded a lower percentage of euthyroid remission (50.0% vs 92.9%, P=0.039) and complete remission (12.5% vs 92.9%, P=0.000) than pure TSHomas on the first day after the operation and a lower complete remission rate within six postoperative months (0% vs 69.2% , P=0.011). The univariate analysis showed that higher TSH levels at diagnosis may be an unfavorable factor affecting tumor shrinkage, and coexisting tumors were significantly correlated with poor euthyroid and complete remission rates on the first day after surgery. We speculate that coexisting tumors may require a longer period of preoperative pharmacotherapy and attain a high recurrence rate in the short term. Reference: (1) Molitch et al., Jama, 2017Feb, 317(5):516-524. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Pituitary adenomas in children and young adults.

Pituitary adenomas are rare in the pediatric population. We present a recent cohort of children operated transsphenoidally on pituitary adenoma from a single center. Inclusion criteria were age < 21years and histopathological diagnosis of adenoma after transsphenoidal surgery. The electronic file was used for prospective and retrospective data collection on symptoms, pituitary function before/after surgical intervention, and surgical complications. Surgical reports were used for assessment of resection grade. Follow-up data were collected from outpatient clinical visit and/or correspondence concerning pituitary function and MRI. Among 962 consecutive patients who underwent transsphenoidal surgery at the University Medical Center Hamburg-Eppendorf (Germany) between April 2013-December 2016, 50 patients (5.2%) were 21years old or younger (range 6-21years, mean 16.5). Twenty-five (50%) patients had pituitary adenomas; M:F = 13:12. Eight were macroadenomas (> 1cm3). Time from onset of symptoms to first operation had a range of 0-48months (mean 18.5months). Nine (36%) patients overall complained of headaches preoperatively. One patient had objective (hemianopsia) and four subjective visual disturbances preoperatively. Histopathological diagnosis revealed 13 (52%) ACTH adenomas, 5 (20%) prolactinomas, 3 (12%) mixed GH-prolactinoma, 1 (4%) GH adenoma, 2 (8%) TSH-producing adenomas, and 1 (4%) non-functioning adenoma. There were no surgical complications. On clinical follow-up (range 1-34.5months, mean 11.7months), 21/24 (88%) patients with hormonally active tumors were in biochemical remission by surgery alone; 2 patients with Cushing disease and 1 with GH-hypersecretion required further treatment. Our recent series confirms the effectiveness and safety of transsphenoidal surgery, especially in the pediatric patient population.

X-LAG: How did they grow so tall?

X-linked acrogigantism (XLAG) is a new, pediatric-onset genetic syndrome, due to Xq26.3 microduplications encompassing the GPR101 gene. XLAG has a remarkably distinct phenotype with disease onset occurring before the age of 5 in all cases described to date, which is significantly younger than in other forms of pituitary gigantism. These patients have mixed GH and prolactin positive adenomas and/or mixed-cell hyperplasia and highly elevated levels of GH/IGF-1 and prolactin. Given their particularly young age of onset, the significant GH hypersecretion can lead to a phenotype of severe gigantism with very advanced age-specific height Z-scores. If not adequately treated in childhood, this condition results in extreme final adult height. XLAG has a clinical course that is highly similar to some of the tallest people with gigantism in history.

Surgical treatment of pituitary adenomas in childhood and adolescence

Objective: To investigate the clinical characteristics and treatment of pituitary adenomas of childhood and adolescence. Methods: Thisarticle was a retrospective study of 140 pituitary adenomas of childhood and adolescence that was admitted into Peking Union Medical College Hospital from December 1987 to December 2014, whose clinical manifestations, hormone secretions, images, pathological types, surgical complications and follow-ups were studied. Results: A total of 58 (41.4%) males and 82 females (58.6%) were included, whose mean age was 12.5 years old (age range from 7 to 18). As for the type of tumors, ACTH adenoma, PRL adenoma, GH adenoma, non-functional adenoma and multiple-secreting adenoma accounted for 35.7%, 25.7%, 12.2%, 25.7% and 0.7%, respectively. Microadenoma accounted for 33.6% of total patients, while macroadenoma and giant adenoma accounted for 60.0% and 6.4% respectively. 19.3% of adenomas in our study wereinvasive. Transsphenoidal approach surgery was commonly used and accounted for 97.9% of cases in our study, 2 of which used intraoperative navigation assistance. Total resection was achieved in 93.6% of patients, and the rest achieved subtotal resection. 108 (77.1%) patients got full term follow-up until 1 year after surgery, and tumor recurred in 14 patients (13.0%). Conclusions: ACTH-secreting adenoma is the most common pituitary adenoma in childhood and adolescence which need surgical treatment. Transsphenoidal approach surgery is the most commonly used surgical procedure. The recurrence rate is about 13%, and the patients need regular examination of pituitary hormones and image study to confirm the recurrence.

Immune Cell Infiltrates in Pituitary Adenomas: More Macrophages in Larger Adenomas and More T Cells in Growth Hormone Adenomas.

Tumor immune microenvironment has been gradually recognized as a key contributor to tumor development, progression, and control. Immune cell infiltrates in brain tumors have been increasingly studied, but few have published on immune cell infiltrates in pituitary adenomas. We quantitatively assessed the infiltration of macrophages and lymphocytes in 35 pituitary adenomas, including 9 densely granulated growth hormone (DG-GH), 9 sparsely granulated growth hormone (SG-GH), 9 null cell (NC), and 8 adrenocorticotropic hormone (ACTH) adenomas. All the adenomas showed varying degrees of CD68+ macrophage infiltration. While SG-GH adenomas were significantly larger in size than DG-GH and ACTH adenomas, the infiltration of CD68+ macrophages was significantly greater in SG-GH than in DG-GH and ACTH adenomas. Similarly, NC adenomas that were significantly larger than DG-GH and ACTH adenomas had significantly greater infiltration of CD68+ macrophages than DG-GH and ACTH adenomas. The numbers of CD68+ macrophages were positively correlated with the tumor sizes and Knosp classification grades for tumor invasiveness. The infiltration of CD4+ and CD8+ T cells was relatively scant in these adenomas, but GH adenomas exhibited significantly more CD4+ and CD8+ T cells than non-GH adenomas. Both DG-GH and SG-GH adenomas had significantly more CD4+ cells than ACTH adenomas and significantly more CD8+ cells than NC adenomas. These results suggest an association of CD68+ macrophage infiltration with an increase in the pituitary adenoma size and invasiveness. Our observation contributes to understanding the growth environment of pituitary adenomas, for which adjuvant immunotherapy may help to constrain the tumor enlargement and invasiveness.

Clinical value of 68Ga-DOTATATE PET/CT in pituitary adenoma: a pilot study

Objective To investigate the correlation between the uptake of 68Ga-DOTATATE in pituitary adenoma and clinical parameters such as hormonal hypersecretion, and to evaluate the curative effect with 68Ga-DOTATATE imaging after octreotide therapy in patients with growth hormone-secreting adenoma (GH adenoma). Methods A total of 34 patients (15 males, 19 females) with pituitary adenoma were recruited, including 5 adrenocorticotropic hormone-secreting adenoma (ACTH adenoma), 17 GH adenoma, and 12 non-functioning adenoma (NF adenoma). In the 17 patients with GH adenoma, there were 13 patients treated by octreotide intramuscular injection 3 times with a total dose of 60 mg for 3 months. The finial diagnosis was based on histology. 68Ga-DOTATATE imaging was performed, and SUVmean, tumor volume and density index (DI) were recorded in all patients. The DI was the ratio of tumor SUVmean to tumor volume. The effective therapy was defined as more than 50% of hormonal suppression or more than 20% of tumor shrinkage. Non-parametric Mann-Whitney u test was used. Results NF adenoma showed greater tumor volume than secretory adenoma, ((9.10±7.00) cm3vs (2.92±1.60) cm3,u=43.0, P<0.05), whereas DI of secretory adenoma was higher than that of NF adenoma (7.16±4.52 vs 1.08±1.40, u=48.5, P<0.05). Additionally, DI was significantly higher(3.55±0.91 vs 1.38±0.69, u=2.0, P<0.05) in patients (n=8) with effective treatment than that in patients without effective treatment (n=5). Conclusion 68Ga-DOTATATE may be a useful probe for PET imaging in patients with pituitary adenoma, and may be valuable for predicting the therapeutic effect of somatostatin analog treatment. Key words: Pituitary neoplasms; Gallium radioisotopes; Tomography, emission-computed; Tomography, X-ray computed; DOTATATE

Endocrinological outcomes following endoscopic and microscopic transsphenoidal surgery in 113 patients with acromegaly

BackgroundTo describe outcomes and complications in patients undergoing transsphenoidal surgery for acromegaly using the 2010 consensus criteria for biochemical remission. MethodsRetrospective review of 113 treatment naïve patients who underwent transsphenoidal surgery with the endoscopic (n=66) and the endonasal microscopic technique (n=47). Cure was defined if the age and sex-adjusted IGF-1 level was normal and either the basal GH was <1ng/ml or the nadir GH was <0.4ng/ml following oral glucose suppression at last follow-up. ResultsThe mean age at presentation was 38.1±7.1 years and 86% of tumors were macroadenomas. Adenoma sizes averaged 21.1±9.7mm, but 56% of all tumors were ≥2cm in size and 43.4% were invasive. Remission rates between endoscopic and microscopic transsphenoidal surgery did not differ significantly overall (28.8% versus 36.2%). On univariate analysis, a preoperative GH level <40ng/ml, adenoma size <20mm and non-invasiveness were predictors of remission at follow-up. Although there were no statistically significant differences in remission rates between the endoscopic and microsurgical groups, surgically induced hypopituitarism was less frequent with the former. ConclusionsWe report our surgical experience with predominantly large, invasive GH adenomas using the 2010 criteria for cure. Patients with smaller, non-invasive tumors with lower preoperative GH levels are most likely to achieve remission. Outcomes with either the microscopic or endoscopic approach do not differ significantly, although the rate of surgically induced hypopituitarism may be higher with the former. Transsphenoidal surgery remains the first line of treatment for patients with acromegaly, but invasive adenomas will frequently require adjuvant therapy.

MiR-23b and miR-130b expression is downregulated in pituitary adenomas

MicroRNA (miRNA) deregulation plays a critical role in tumorigenesis. miR-23b and miR-130b are induced by thyrotropin in thyroid cells in a cAMP-dependent manner.The aim of our work has been to investigate the possible role of miR-23b and miR-130b in pituitary tumorigenesis. We have analyzed their expression in a panel of pituitary adenomas (PAs) including GH and NFPA adenomas.We report that miR-23b and miR-130b are drastically reduced in GH, gonadotroph and NFPA adenomas in comparison with normal pituitary gland. Interestingly, the overexpression of miR-23b and miR-130b inhibits cell proliferation arresting the cells in the G1 and G2 phase of the cell cycle, respectively. Moreover, we demonstrate that miR-23b and miR-130b target HMGA2 and cyclin A2 (CCNA2) genes, respectively. Finally, downregulation of miR-23b and miR-130b expression is associated with increased levels of their respective targets in human PAs.These findings suggest that miR-23b and miR-130b downregulation may contribute to pituitary tumorigenesis.

Aggressive Silent GH Pituitary Tumor Resistant to Multiple Treatments, Including Temozolomide

Temozolomide (TMZ) has been proposed as a therapeutic option in aggressive pituitary tumors. Among the published cases, GH expressing tumors were rare. We describe a patient with initially benign silent GH adenoma that transformed into an aggressive GH secreting tumor resistant to usual therapy. MGMT expression was high and the MGMT promoter was unmethylated. Before this aggressive course, patient received three cycles of TMZ; no response was observed. Four cases of GH aggressive tumor treated by TMZ have been reported. Response to TMZ was observed in one of these four patients. Predictive factors of failure of TMZ remain unclear.

Clinicopathological Features of Growth Hormone-Producing Pituitary Adenomas in 242 Acromegaly Patients: Classification according to Hormone Production and Cytokeratin Distribution

The aim of this study was to clarify the relationship between the histological features of GH-producing adenomas surgically resected at the Toranomon Hospital and the clinical features of the patients. Histological examinations, including immunohistochemistry for anterior pituitary hormones and cytokeratin (CK), were performed on 242 consecutively excised GH-producing pituitary adenomas. Immunohistochemistry showed 45% of the adenomas to be monohormonal and 55% to be plurihormonal, producing GH-PRL (77%), GH-TSH (13%), and GH-PRL-TSH (10%). One-fourth of the monohormonal GH adenomas had a dot-like pattern of CK immunoreactivity in the majority of the tumor cells (>80%); they were significantly more common in female or younger patients and usually tended to be larger and more invasive than monohormonal GH adenomas with perinuclear CK. Interestingly, CK-immunonegative adenomas were found in only 5% of the patients; they also showed a tendency to be larger, suggesting that they are a distinct type of GH adenoma with clinically aggressive features. Serum hormone levels correlated well with tumor size only in GH-producing adenomas with a perinuclear pattern of CK immunoreactivity. Each histological subtype of adenoma, classified according to the pattern of CK immunoreactivity, was associated with distinct clinical characteristics. This information is useful for understanding the pathophysiology of acromegaly-causing GH-producing adenomas.