Hormone-secreting Pituitary Adenoma Research Articles

Management of growth hormone-secreting pituitary adenomas causing acromegaly: a practical review of surgical and multimodal management strategies for neurosurgeons.

This review aimed to highlight the history, diagnostic criteria, preoperative prognostic factors, surgical management, and multimodal adjuvant therapies recommended to provide a comprehensive and multifaceted understanding of and clinical approach to treating growth hormone-secreting pituitary adenomas (GHPAs) in patients with acromegaly. The authors collated and reviewed published studies, many written by skull base neurosurgeons, endocrinologists, and radiation oncologists with expertise in pituitary adenoma management, to produce a practical and contemporary update pertaining to the optimal management of acromegaly for neurosurgeons. Acromegaly is a debilitating disease for which surgery can be curative in more than two-thirds of patients. Recent rates of hormonal remission by the authors' group and others following the resection of GHPAs are on the order of 70%-80%, and these increase to more than 85% with the addition of medical therapy in a minority of patients who do not achieve remission with surgery alone. Most tumors are accessible via a direct endoscopic endonasal transsphenoidal approach, which can be augmented with a variety of extended approaches to gain access to suprasellar, clival, and parasellar compartments as needed. Preoperative growth hormone levels, cavernous sinus invasion, and pituitary adenoma consistency are important factors in determining the extent of resection. In most patients with residual or recurrent disease, medical therapy (e.g., somatostatin analogs and dopamine agonists) can be used to help achieve hormonal remission. Repeat surgery can be safely performed in most cases if needed, whereas stereotactic radiosurgery is usually reserved for medically resistant tumors in surgically inaccessible compartments. The neurosurgeon has a primary and often definitive role in the management of acromegaly. The involvement of an integrated and multidisciplinary team consisting of experts from neurosurgery, otolaryngology, endocrinology, and radiation oncology optimizes the chances for a biochemical cure, even in large and aggressive GHPAs.

Lysine Methyltransferase 5A Promotes the Progression of Growth hormone Pituitary Neuroendocrine Tumors Through the Wnt/β-catenin Signaling Pathway.

Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine Methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. Immunohistochemistry, qRT-PCR and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, Flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation and FCM assays. Additionally, WB analysis identified the Wnt/β-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/β-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs.

A challenging case of a pituitary macroadenoma and toxic thyroid adenoma with inappropriate TSH secretion.

Thyroid-stimulating hormone-secreting pituitary adenomas (TSHomas) are rare, accounting for less than 1% of all pituitary adenomas. We present a case of hyperthyroidism secondary to a likely TSHoma and coexisting functional thyroid adenoma. Laboratory errors and familial abnormalities in thyroid function tests were ruled out, and a diagnosis of the toxic thyroid adenoma was confirmed on a thyroid uptake scan. However, the triiodothyronine suppression test was contraindicated due to the patient's cardiovascular disease, and the thyrotropin-releasing hormone stimulation test, measurement of glycoprotein hormone alpha-subunit, and genetic testing were unavailable. Magnetic resonance imaging of the brain revealed a suprasellar pituitary macroadenoma measuring 40 mm × 20.3 mm × 17 mm. The patient was initiated on carbimazole; however, thyroid stimulating hormone and thyroxine levels remained elevated. The patient declined trans-sphenoidal surgery and was treated with radioactive iodine to manage the toxic thyroid adenoma, leading to reduced thyroxine levels and symptom improvement. Unfortunately, the patient passed away before long-acting somatostatin analogs became available. This case highlights the diagnostic and therapeutic challenges involved in managing thyrotoxicosis with dual etiology. Hyperthyroidism can have multiple etiologies, which can coexist in the same patient. Persistent discordant thyroid function tests warrant further investigation. The gold standard for diagnosis of TSHomas remains immunohistochemical analysis of the tumor tissue.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

Growth hormone-secreting pituitary adenoma combined with Graves' disease: retrospective case series and literature review.

The coexistence of growth hormone-secreting pituitary adenoma (GHPA) and Graves' disease (GD) is rare. This study aimed to investigate the relationship between growth hormone (GH)/insulin-like growth factor 1 (IGF-1) levels and thyroid function in patients with GHPA combined with GD and to explore the underlying mechanisms. Eleven patients with GHPA combined with GD during 2015-2022 were collected by searching the medical record system of Beijing Tiantan Hospital, Capital Medical University. Changes in GH/IGF-1 levels and thyroid function were compared before and after the application of antithyroid drugs (ATD) and before and after transsphenoidal surgery (TSS) or somatostatin analog (SSA) treatment, respectively. After the application of ATD, with the decrease of thyroid hormone levels, GH/IGF-1 levels also decreased gradually. In patients without ATD application, after surgery or SSA treatment, thyroid hormone levels decreased as GH/IGF-1 decreased. Hyperthyroidism due to GD promotes the secretion of GH/IGF-1, and when thyroid hormone levels were decreased by the use of ATD, GH and IGF-1 levels were also decreased, suggesting that thyroid hormones may influence the synthesis and secretion of GH/IGF-1. The use of ATD to control thyrotoxicosis before TSS is not only beneficial in reducing the risk of anesthesia but may help to promote biochemical control of GHPA. On the other hand, high levels of GH/IGF-1 in patients with GHPA also exacerbate GD hyperthyroidism, which is ameliorated by a decrease in GH/IGF-1 levels by TSS or SSA treatment, suggesting that the GH-IGF-1 axis promotes growth, thyroid function, and thyroid hormone metabolism.

Surgical and non-surgical interventions for primary and salvage treatment of growth hormone-secreting pituitary adenomas in adults.

Surgical and non-surgical interventions for primary and salvage treatment of growth hormone-secreting pituitary adenomas in adults.

Diverse presentations of Cushing's syndrome during pregnancy - A case series.

Cushing's syndrome (CS) encompasses various causes of hypercortisolism including adrenocorticotropic hormone (ACTH) secreting pituitary adenoma with or without bilateral adrenal hyperplasia, an adrenal adenoma or carcinoma, ectopic ACTH or corticotrophin-releasing hormone (CRH) secretion by a neoplasm or exogenous corticosteroid therapy. The diagnosis of CS in pregnancy presents a challenge due to overlapping clinical features of pregnancy (weight gain, striae, acne). If untreated, CS in pregnancy is associated with increased risk of maternal and fetal complications. With fewer than 250 cases currently published, we aim to review the clinical presentations, diagnostic methods, management, and outcomes of patients with CS in pregnancy to help optimise our clinical practice. This is a single-centre, retrospective review of woman with documented hypercortisolism receiving antenatal care at a tertiary maternity hospital in Perth between 2006 to 2022. Data were collated from electronic and chart reviews. OMNI calculator was used for birthweight calculations. Local ethics and patient consent were obtained. Five women and seven pregnancies were identified. Four women had a pituitary source of ACTH-dependent CS as confirmed by brain magnetic resonance imaging. One woman had an ectopic source of ACTH. Two women were diagnosed during pregnancy. All pregnancies occurring prior to treatment of the Cushing's disease were complicated by secondary hypertension and diabetes. CS represents a rare and difficult to diagnose condition in pregnancy. When untreated, maternal and fetal outcomes are compromised. Close monitoring of the associated complications with involvement of a multidisciplinary team are recommended.

Evaluation of Beta-Arrestin Levels in Acromegaly Patients: A Comparison of Patients with and Without Obstructive Sleep Apnea

Background: Acromegaly is a rare endocrine disorder; it has an incidence of 4 per million annually and a prevalence of 40 per million. It is due to a growth hormone-secreting pituitary adenoma. Objective: To evaluate the levels of β-arrestin in patients with acromegaly with and without obstructive sleep apnea (OSA). Methods: One hundred and five registered patients with acromegaly at the National Diabetes Center, Mustansiriyah University, were enrolled in the study. Of the 105 patients with acromegaly, 81 have OSA, while the remaining 24 have no OSA. Obstructive sleep apnea affects 81.8% of males and 72% of females. All recruited patients have given oral consent to participate in the study, which was conducted from January to October 2023. Results: Males with OSA had a mean age of 52 years, while those without OSA had a mean age of 46 years. The Epworth sleepiness scale is higher among those with OSA. β-arrestin is higher in males with OSA (6.309 pg/ml), while in females with OSA, it is 6.278 pg/ml. In no OSA group, the β-arrestin level was 3.067 pg/ml, while in those with OSA, it jumped to 6.29 pg/ml. Conclusions: The results showed that β-arrestin was elevated in patients with acromegaly and obstructive sleep apnea versus those without obstructive sleep apnea. OSA is more common in males, particularly when they get older.

The role of hormonal status, morphological subtypes and proliferative marker Ki-67 labeling index on long-term outcomes in patients with acromegaly: a single tertiary center’s experience

Aims: Acromegaly is a rare disorder resulting from benign growth hormone secreting pituitary adenomas. Many factors affect long-term outcomes in acromegaly. In this study we aimed to investigate effects of hormonal status, morphological subtypes, immunohistochemical expression of pituitary hormones and Ki-67 labeling index on long-term outcomes in patients with acromegaly.&#x0D; Methods:. We collected the medical and pathological records of sixty-four patients who underwent surgery for growth hormone (GH) secreting somatotroph tumors between 2005-2017.&#x0D; Results: The remission rate after surgery was 48% (31/64) in all patients (33% for macroadenomas, 94% for microadenomas; p

Сytotoxic T lymphocyte-associated protein 4 (CTLA4) is overexpressed in a subset of prolactin- and growth hormone-secreting pituitary adenomas.

Cytotoxic T lymphocyte-associated protein 4 (CTLA4), a negative regulator typically expressed on the surface of T lymphocytes, is targeted by immunotherapy in patients with an ever-expanding spectrum of cancers. Characterizing the expression of CTLA4 in the pituitary gland could provide additional rationale for using immune checkpoint inhibitors in pituitary adenoma patients who do not respond to conventional treatments. We assessed the expression of CTLA4 mRNA and protein in a panel of 157 human pituitary glands, 45 collected at autopsy and 112 at surgery. These specimens included 50 normal glands and 107 adenomas: 41 nonsecreting, 25 PRL-, 24 ACTH-, 11 GH-, 2 TSH-, 1 FSH-secreting, and 3 atypical. Specimens were stained for CTLA4 and adenohypophyseal hormones using RNAscope in situ hybridization, immunohistochemistry, and RNAscope Multiplex Fluorescent Assay. CTLA4 mRNA was detectable in most normal pituitary glands (48 of 50, 96%) but varied in expression, with a histological score (H-score) ranging from 0.6 to 20. The variation did not depend upon the patient's gender and age and was not significantly affected by the archival storage time. CTLA4 expression was higher (P = 0.022) in pituitary adenomas than normal glands, with the greatest levels seen in PRL- and GH-secreting adenomas (P = 0.009 and 0.023 versus normal, respectively). Eight of 25 (32%) prolactinomas and 3 of 11 (27%) GH-adenomas had an H-score greater than 20, while no differences were seen for the other types. These novel data highlight the expression of an immune checkpoint such as CTLA4 on pituitary endocrine cells, a finding that could be exploited for therapeutical applications.

Clinical characteristics and therapeutic outcomes of acromegalic patients with giant growth hormone-secreting pituitary adenomas: a single-center study of 67 cases.

Acromegalic patients with giant growth hormone-secreting pituitary adenomas (GHPAs) (≥ 40mm) are relatively rare, and their clinical characteristics and treatment outcome data are limited. This study aims to analyze the clinical practice experience of giant GHPAs. Sixty-seven acromegalic patients with giant GHPAs and 67 patients with macro GHPAs (10-39mm), matched for age and gender from the same hospital during the same period, were retrospectively recruited. The clinical characteristics, treatment, and outcomes were analyzed. Enlargement of the extremities and facial features were the most common symptoms in most patients (92.5%). Compared with the macroadenoma group, more frequent visual impairment (86.6% vs. 25.4%, P < 0.001) and gonadal axis dysfunction (49.3% vs. 34.3%, P = 0.008), higher preoperative fasting GH, nadir GH after OGTT and IGF-1 levels, and a higher proportion of extrasellar tumor invasion were seen in the giant adenoma group. As the adenoma size increases, the total resection rate decreases, and postoperative complications and multimodal treatment strategies increase significantly. Fasting and nadir GH levels remained higher at 1week postoperatively, and there were more surgical complications and cases of anterior hypopituitarism in the giant group. After a median follow-up of 36months, 12 patients (36.4%) in the giant GHPA group and 17 (36.2%) in the macro GHPA group achieved biochemical remission. Other factors such as age of onset, age of diagnosis, delayed diagnosis time, metabolic complications, p53 positive rate, and Ki-67 index showed no significant difference between the two groups. With aggressive multimodal therapy, the biochemical remission rate of acromegalic patients with giant GHPAs is comparable to that of patients with macro adenoma. However, postoperative complications and hypopituitarism need to be closely monitored.

FRI318 A Case Of Mixed Growth Hormone And Prolactin-secreting Giant Pituitary Macroadenoma

Abstract Disclosure: A. Khan: None. I. Alpertunga: None. V. Kantorovich: None. Introduction Co-secretion of prolactin (PRL) and growth hormone (GH) from a single pituitary adenoma is an established entity in the medical literature and present in about 5% of the cases. Guidelines recommend to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the time of initial diagnosis. Our case describes the management of a giant pituitary macroadenoma co-secreting PRL and GH. Case A 20-year-old male with history significant for schizophrenia presented with visual disturbances and discharge from his left nipple. His prolactin level (PRL) was noted to be elevated at 12,396 (4.0-15.2) ng/ml on work-up during recent prior investigation. On physical exam, he had bilateral temporal visual field deficit as well as dysfunction in upward gaze of left eye. Head imaging showed a 7.5 x 6.2 x 5 cm associated with remodeling of the sella turcica and expanding into the suprasellar space and significant mass-effect on the adjacent frontal lobes bilaterally, mild mass-effect on the adjacent optic chiasm with significant surrounding vasogenic edema and compressing the bilateral anterior cerebral arteries. Patient was started on low dose cabergoline in caution of prevention of possibility of rapid response-related significant volume contraction of the tumor with possibility of reactive edema. The dose of cabergoline was rapidly titrated up to 3 mg bi-weekly with minimal prolactin fluctuation of PRL between 12,000 and 16,000 ng/ml. Because of mild atypical acromegalic facial features, patient had GH axis assessment. IGF-1 level came back elevated at 529 (83-456) ng/ml with a high IGF Binding Protein- 3 of 8.9 (2.9-7.2) mg/l. He was started on octreotide titrated up to a dose of 150 mcg three times daily. Repeat MRI brain did not show tumor shrinkage. Subsequently, patient underwent bifrontal craniotomy for resection/debulking of parasellar tumor. PRL dropped to 931 ng/ml immediately after surgery. At the time of writing, pathology of the tumor and repeat IGF-1 level is pending. Patient was monitored closely in the ICU with a steroid taper postoperatively. Discussion Dopamine agonists are the first-line therapy for medical treatment of hyperprolactinemia but can also suppress GH and IGF-1 levels. However, in acromegaly, cabergoline is utilized mostly for small adenomas with mild elevation of IGF-1. In our case, we decided to use a combination of cabergoline and somatostatin receptor analog, octreotide. However, given the giant adenoma with very high PRL and IGF-1 levels, patient showed a poor response to medical therapy, and given the impending threat to patient’s vision, he underwent surgical debulking. Our case highlights the management of a giant, mixed hormone-secreting pituitary adenoma. Presentation: Friday, June 16, 2023

Uric acid levels correlate with disease activity in growth hormone-secreting pituitary adenoma patients.

Few studies reported the effects of growth hormone-secreting pituitary adenoma (GHPA) on uric acid (UA) metabolism and the relationship between growth hormone (GH)/insulin-like growth factor-1 (IGF-1) levels and UA are controversial. This study aimed to evaluate the relationship between IGF-1 and UA in patients with GHPA and to further clarify whether UA levels are associated with GHPA disease activity by follow-up. A longitudinal study of 424 GHPA patients presenting to Beijing Tiantan Hospital, Capital Medical University between January 2015 and January 2023 was conducted. Spearman's correlation tests were performed to examine the relationship between IGF-1 and UA at baseline. Univariate and multivariate linear regression analysis was conducted to investigate the independent association between UA and IGF-1. Changes in postoperative IGF-1 and UA levels were followed prospectively, and the differences in UA levels between the biochemical remission and nonremission groups were compared. At baseline, male patients, the lower the age, the higher the IGF-1 and body mass index (BMI), and the higher the UA levels. IGF-1 was significantly associated with UA after controlling for sex, age, and BMI (r = 0.122, P = 0.012). In adjusted multiple linear regression analysis, IGF-1 was independently associated with UA, and UA levels increased significantly with increasing IGF-1. During postoperative follow-up, UA decreased gradually as IGF-1 levels decreased. At 12 months postoperatively, UA levels were significantly lower in the biochemical remission group than in the nonremission group (P = 0.038). In patients with GHPA, UA levels are associated with disease activity. Changes in UA levels should be taken into account in the comprehensive treatment of GHPA, patients presenting with HUA should be given lifestyle guidance and appropriate urate-lowering treatment according to their condition to better improve their prognosis.

Long-term control of acromegaly after pituitary surgery in South-Eastern Norway

PurposeSustained cure of acromegaly can only be achieved by surgery. Most growth hormone (GH) secreting pituitary adenomas are macroadenomas (≥ 10 mm) at diagnosis, with reported surgical cure rates of approximately 50%. Long-term data on disease control rates after surgery are limited. Our aim was to estimate short- and long-term rates of biochemical control after pituitary surgery in acromegaly and identify predictive factors.MethodsPatients operated for GH-secreting pituitary adenomas between 2005–2020 were included from the local pituitary registry (n = 178). Disease activity and treatment data were recorded at one-year (short-term) and five-year (long-term) postoperative follow-up. Biochemical control was defined as insulin-like growth factor 1 (IGF-1) ≤ 1.2 × upper limit of normal value. Multivariate regression models were used to identify factors potentially predicting biochemical control.ResultsA total of 178 patients with acromegaly (median age at diagnosis 49 (IQR: 38–59) years, 46% women) were operated for a pituitary adenoma. Biochemical control was achieved by surgery in 53% at short-term and 41% at long-term follow-up, without additional treatment for acromegaly. Biochemical control rates by surgery were of same magnitude in paired samples (45% vs. 41%, p = 0.213) for short- and long-term follow-up, respectively. At short-term, 62% of patients with microadenomas and 51% with macroadenomas, achieved biochemical control. At long-term, the biochemical control rate was 58% for microadenomas and 37% for macroadenomas (p = 0.058). With adjunctive treatment, 82% achieved biochemical control at long-term. Baseline IGF-1 levels significantly predicted biochemical control by surgery at short-term (OR: 0.98 (95% CI: 0.96–0.99), p = 0.011), but not at long-term (OR: 0.76 (95% CI: 0.57–1.00), p = 0.053).ConclusionIn unselected patients with acromegaly, the long-term biochemical control rate remains modest. Our findings indicate a need to identify patients at an earlier stage and improve therapeutic methods and surgical outcomes.

Endocrinologic Outcome Following Endonasal Transphenoidal Excision of Growth Hormone Secreting Pituitary Adenomas

Background: Endonasal Transphenoidal Approach for excision of pituitary adenomas has been gaining popularity over the traditional microsurgical approach. The objective of this study is to assess the rate of hormonal recovery following endonasal transphenoidal excision of growth hormone secreting pituitary macroadenoma in out center. Methods: In this prospective observational study all cases subjected to endonasal transphenoidal excision of growth hormone secreting pituitary adenoma, during the study period from January 2019 to December 2020 at National Neurosurgical Referral Center, Bir Hospital, Kathmandu were included in this study. Preoperative and postoperative patient characteristics were recorded. Hormonal remission was defined as normal insulin-like growth factor-1 level at 3 months follow-up. Results: A total of 24 cases were included. The mean age of acromegaly cases was 39.42±10.41 years (24-56 years), with male to female ratio of 0.71:1. Majority (9) of cases had a Knosp grade 1.Thirteen cases had a Wilson-Hardy Extension Grade 0. Majority (11) of cases had a Wilson-Hardy Invasion Grade I. Three cases developed post-operative CSF leak, which recovered after lumbar drainage with no sequel. Five cases developed epistaxis which resolved with nasal packing. Sixty three percent (15 cases) had normal IGF-1 levels at 3 months follow up. Conclusion: Endoscopic endonasal transphenoidal approach to excision of growth hormone secreting pituitary adenomas is a safe and effective modality at achieving hormonal control in our setting.

Correlation analysis of anterior pituitary hormone and tumor size in patients with pituitary adenomas

Objective: To summarize the correlation between anterior pituitary function and tumor size in patients with different hormone-secreting pituitary adenomas. Methods: This was a retrospective case series study. The clinical data of 1 946 patients with pituitary adenoma hospitalized in the First Medical Center of Chinese PLA General Hospital from January 1, 2005, to December 31, 2020, were collected. The correlation between tumor size and anterior pituitary hormone levels was analyzed using Spearman rank correlation analysis in different types of pituitary adenomas. Results: The median age of the 1 946 patients was 45.1 years, of which 857 (44.0%) were men. The maximum tumor diameter of the patients [M (Q1, Q3)] was 22 (14, 30) mm. Tumor size in nonfunctioning adenomas (n=1 191) was negatively correlated with adrenocorticotropic hormone (ACTH) (r=-0.11, P<0.001), growth hormone (r=-0.13, P<0.001), and luteinizing hormone (men: r=-0.26, P<0.001, women: r=-0.31, all P<0.001). The tumor size of somatotropic adenomas (n=297) was positively correlated with growth hormone (r=0.46, P<0.001), but negatively correlated with male testosterone (r=-0.41, P<0.001). The tumor size of ACTH-secreting pituitary adenomas (n=155) was positively correlated with the ACTH level at 8∶00 AM (r=0.25, P<0.001); however, no correlation was found with cortisol at 8∶00 AM (P>0.05). The tumor size of prolactinomas (n=303) was positively correlated with the prolactin level (men: r=0.34, P=0.001; women: r=0.13, P=0.070). Conclusions: The correlation between the function of the anterior pituitary and size of the tumor depends on the cellular origin of the pituitary adenoma and specific type of hormone secretion. In somatotroph adenomas, ACTH-secreting pituitary adenomas, and prolactinomas, there is a positive correlation between tumor size and level of hormones secreted by the corresponding tumors. In patients with nonfunctioning adenomas, the tumor size was negatively correlated with the hormone levels of the pituitary-adrenal and pituitary-growth hormone axes.

P.142 Characteristics of a large cohort of patients with acromegaly with surgical outcome by geographic living location

Background: Acromegaly is a rare disease caused by a growth hormone-secreting pituitary adenoma which results in potentially debilitating skeletal, cardiac and gastrointestinal disease. Surgical resection can be curative, but in Southern Alberta, skull base surgeons and multi-disciplinary pituitary teams work at a single centre, raising the question of whether rurally-dwelling patients experience worse outcomes. We aim to characterize post-surgical remission rates by living location in acromegaly patients at our institution. Methods: A retrospective chart review supplemented a single surgeon database of patients with acromegaly treated at our centre (February 2011-April 2022) with demographic, endocrinological, and surgical variables. Statistical analysis was performed using Stata Version 17. Results: Our cohort included 47 cases of acromegaly (53% male), all treated with endoscopic transsphenoidal surgery. The average age at first operation was 46.7 years (20-69 years), 77% were macroadenomas, and the average adenoma size at initial MRI was 16mm. 54.55% of the urban cohort achieved immediate post-surgical remission, versus 28.57% of the rural cohort (OR:3.0(95%CI:0.67,15.51)). Conclusions: The characteristics of our cohort agree with the literature. The odds of immediate post-surgical remission in urban-dwelling patients was 3.0 times that of rurally-dwelling patients. Our results failed to meet statistical significance likely due to lack of power secondary to sample size.

The Effect and Potential Mechanism Analysis of Growth Hormone–Secreting Pituitary Adenomas on Thyroid Function

ObjectiveCurrent studies on the effect of high growth hormone (GH)/insulin-like growth factor (IGF)-1 on thyroid function are inconsistent. The aim was to explore the effect and potential mechanism of high GH/IGF-1 on thyroid function by analyzing the changes of thyroid function in patients with growth hormone–secreting pituitary adenoma (GHPA). MethodsThis was a retrospective cross-sectional study. Demographic and clinical data of 351 patients with GHPA who were first admitted to Beijing Tiantan Hospital, Capital Medical University, from 2015 to 2022 were collected to analyze the relationship between high GH/IGF-1 levels and thyroid function. ResultsGH was negatively correlated with total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH). IGF-1 was positively correlated with total triiodothyronine (TT3), free triiodothyronine (FT3), and FT4 and negatively correlated with TSH. Insulin-like growth factor–binding protein (IGFBP)-3 was positively correlated with TT3, FT3, and FT3:FT4 ratio. The FT3, TT3, TSH, and FT3:FT4 ratio of patients with GHPA and diabetes mellitus (DM) were significantly lower than those with GHPA but without DM. With the increase of tumor volume, thyroid function gradually decreased. GH and IGF-1 were correlated negatively with age in patients with GHPA. ConclusionThe study emphasized the complex interaction between the GH and the thyroid axes in patients with GHPA and highlighted the potential effect of glycemic status and tumor volume on thyroid function.

Abstract #1400950: Chiari I Malformation with Concomitant Nonfunctioning Pituitary and Adrenal Tumors

Chiari I malformation (CM1) is a rare finding with an incidence ranging from 3.3 to 8.2 per 100000. CM1 has been described with growth hormone secreting pituitary adenomas, and with EPAS1 gain-of-function mutation syndrome with multiple paragangliomas/pheochromocytomas, somatostatinoma, and polycythemia. There is only one case report in the literature describing a nonfunctional pituitary adenoma with CM1. We describe the first reported case of a patient with CM1 with concomitant nonfunctional pituitary and adrenal incidentalomas. A 45-year-old female with history of diet-controlled diabetes and HTN presented with a two-week history of bilateral upper extremity weakness and paresthesia, along with gait instability. She had reduced motor power in the upper extremities on physical exam. MRI cervical spine demonstrated a cervicothoracic syrinx, cerebellar tonsillar ectopia consistent with CM1. MRI brain showed diffuse enlargement of the pituitary gland measuring 16 x 14 x 13 mm bulging into the suprasellar cistern and minimally abutting the inferior aspect of the optic chiasm. MRI lumbar spine revealed a left adrenal gland nodule measuring 1.5 x 2.0 cm. Endocrine hormonal evaluation showed normal prolactin, follicle stimulating and luteinizing hormone, estradiol, free T3, free T4, and IGF-I levels. Aldosterone level was high in supine position with normal plasma renin activity initially with normal levels on repeat testing. Plasma free metanephrine, normetanephrine, testosterone levels were also normal. Patient was started on dexamethasone in anticipation of surgery. Patient underwent suboccipital craniectomy, C1 laminectomy, coagulation of cerebellar tonsils and expansile duraplasty for CM1. Patient did well postoperatively and dexamethasone was tapered off. Postoperative follow up after patient had been off steroids for three weeks showed normal levels of all pituitary and adrenal hormones, including normal dexamethasone suppression test. While CM1 is a rare finding, pituitary adenomas are relatively common. In cases of concomitant occurrence of CM1 and growth hormone secreting pituitary adenoma, over-secretion of growth hormone has been proposed as a mechanism to precipitate symptoms of CM1 by causing hypertrophy of connective and ligamentous tissue in the skull base and of the cranio-cervical canal. Our patient had normal IGF-1 levels with a nonfunctional pituitary adenoma raising the question whether there is some other underlying mechanism, possibly a genetic predisposition, that contributed to the concomitant occurrence of CM1 with pituitary and adrenal tumors. Whether these tumors become functional in the future remains to be seen.

Validation of Myc-Associated Protein X (MAX) regulation in growth hormone secreting and nonfunctional pituitary adenoma.

Many patients with growth hormone-secreting pituitary adenoma (GHPA) fail to achieve biochemical remission, warranting investigation into epigenetic and molecular signatures associated with tumorigenesis and hormonal secretion. Prior work exploring the DNA methylome showed Myc-Associated Protein X (MAX), a transcription factor involved in cell cycle regulation, was differentially methylated between GHPA and nonfunctional pituitary adenoma (NFPA). We aimed to validate the differential DNA methylation and related MAX protein expression profiles between NFPA and GHPA. DNA methylation levels were measured in 52 surgically resected tumors (37 NFPA, 15 GHPA) at ~100,000 known MAX binding sites derived using ChIP-seq analysis from ENCODE. Findings were correlated with MAX protein expression using a constructed tissue microarray (TMA). Gene ontology analysis was performed to explore downstream genetic and signaling pathways regulated by MAX. GHPA had more hypomethylation events across all known MAX binding sites. Of binding sites defined using ChIP-seq analysis, 1,551 sites had significantly different methylation patterns between the two cohorts; 432 occurred near promoter regions potentially regulated by MAX, including promoters of TNF and MMP9. Gene ontology analysis suggested enrichment in genes involved in oxygen response, immune system regulation, and cell proliferation. Thirteen MAX binding sites were within coding regions of genes. GHPA demonstrated significantly increased expression of MAX protein compared to NFPA. GHPA have significantly different DNA methylation and downstream protein expression levels of MAX compared to NFPA. These differences may influence mechanisms involved with cellular proliferation, tumor invasion and hormonal secretion.