Postoperative GH Levels Research Articles

Cystic versus non-cystic silent corticotrophic adenomas: clinical and histological analysis of 62 cases after microscopic transsphenoidal surgery—a retrospective, single-center study

Silent corticotrophic adenomas (SCAs) represent a rare group of non-functioning adenomas with a potentially aggressive clinical course. Cystic component is a very common finding among SCAs, but its clinical relevance has not yet been investigated. The aim of this study was to analyze clinical features of cystic and non-cystic SCAs, perioperative complications after microscopic transsphenoidal surgery, clinical outcome after first and repeat surgery along with risk factors for recurrence. We conducted a retrospective analysis of 62 silent corticotrophic adenomas treated at our university medical center via microscopic transsphenoidal surgery between January 2008 and July 2019. Parameters investigated included histology, invasiveness, intratumoral haemorrhage or cystic component on MRI, perioperative alteration of visual field, tumor size, pre- and postoperative ACTH, FSH, GH, LH, TSH, prolactin, cortisol, free T4, free T3, IGF-1, estrogen and testosterone levels, perioperative complications, neoadjuvant and adjuvant therapy along with clinical outcomes. A total of 62 patients were analyzed. The mean follow up was 28.3 months. Tumors with a cystic component occur statistically significant more often among male than non-cystic (80.6% vs. 44.4%, p = 0.02) and display lower rates of cavernous sinus invasion and sphenoid sinus invasion were significantly lower for cystic lesions comparing to non-cystic tumors (42.3% vs. 69.4%, p = 0.04 and 3.8% vs. 47.2%, p < 0.001). GTR after MTS was not statistically significant higher by cystic SCAs (80% vs. 57.1%, p = 0.09). Cystic lesions were also associated with higher risk of hyperprolactinemia (19.4% vs. 2.8%, p = 0.02) and only densely granulated cystic SCAs presented with preoperative intratumoral hemorrhage (19.2% vs. 0%, p = 0.01). Mean duration of first surgery was significantly shorter for cystic SCAs (71.6(± 18.7) vs. 94.8(± 31.1) minutes, p = 0.01). Preoperative pituitary insufficiency (25% vs. 16.7%, p = 0.49), intraoperative CSF space opening (21.1% vs. 37.5%, p = 0.32), along with postoperative new pituitary insufficiency (15% vs. 10%, p = 0.67) or diabetes insipidus/SIADH (10% vs. 13.3%, p > 0.99) with histological markers such as Ki67 (21.1% vs. 13.8%, p = 0.70) and p53 expression (6.3% vs. 0%, p = 0.39) as well as mitotic rate (5.3% vs. 10.3%, p > 0.99) were comparable between both groups. The presence of cystic component did not affect the tumor recurrence (10% vs. 16%, p = 0.68). Mean duration of surgery was first surgeries was not statistically shorter than repeat surgeries (85.4 ± 29.1 vs. 93.8 ± 28 min, p = 0.15). Patients undergoing first surgery had a higher probability of gross total resection (74.4% vs. 30%, p = 0.01) and lower probability of intraoperative CSF space opening (26% vs. 58.3%, p = 0.04) as well as a lower rate of preoperative anterior pituitary insufficiency (20% vs. 58.3%, p = 0.01). The incidence of new postoperative anterior pituitary insufficiency (10% vs. 0%, p = 0.57) and transient diabetes insipidus/SIADH (12% vs. 8.3%, p > 0.99) between those groups were comparable. No statistical difference was observed between patients with remission and with recurrent tumor regarding cortisol and ACTH levels, incidence of different histological subgroups, invasively growing tumors and lesions with cystic components as well as the percentage of cases with increased Ki67 proliferation index, p53 expression and mitotic indices. Our study presents one of the largest available cohorts of SCAs after microscopic transsphenoidal surgery and first clinical analysis of cystic versus non-cystic SCAs so far. We also performed the first comparison of index and repeat surgeries for this tumor entity. Cystic tumors presented with characteristic clinical aspects like male predominance, higher risk of hyperprolactinemia as well as lower rates of cavernous sinus and sphenoid sinus invasion comparing to non-cystic lesions. Mean duration of first surgery was significantly shorter for cystic SCAs. Moreover preoperative intratumoral hemorrhage had 100% specificity and 60% sensitivity for densely granulated cystic SCAs. All these clinical hallmarks may suggest a novel subgroup of SCAs with distinct clinical and biological features, however further clinical and molecular investigations are required. Second surgeries are associated with a higher incidence of preoperative pituitary insufficiency, and a higher risk of subtotal resection, and a higher probability of CSF space opening intraoperatively compared to first surgeries. On the other hand, the risk of new postoperative pituitary insufficiency was higher after first surgeries. In our cohort of patients, no prognostic factor for recurrence among histological diagnosis, Ki67-proliferation index, p53 expression, number of mitoses, invasive growth or cystic lesions for SCAs could be detected.

Pure Endoscopic Endonasal Treatment of Acromegaly; Classification, Remission Rates, Factors Affecting Remission, and Complications

Aim This study aims to evaluate the effectiveness of the pure endoscopic endonasal transsphenoidal (PEET) approach in treating acromegaly, focusing on remission criteria set by the 2002 and 2010 consensus guidelines. It also seeks to identify variables that affect remission and to analyze early postoperative IGF-1 levels 24 hours after surgery to determine their predictive value for remission. Material and Methods The study retrospectively reviewed the medical records of 129 acromegaly patients who underwent the PEET (Pure Endoscopic Endonasal Transsphenoidal) surgical approach between November 2010 and March 2016 at Ankara Numune Training and Research Hospital. Out of these, 124 patients with complete follow-up and laboratory data were included in the analysis. The study evaluated a range of variables including patients' symptoms, pre- and postoperative GH and IGF-1 levels, imaging results, and remission statuses based on the 2002 and 2010 consensus guidelines. Inclusion criteria for the study required patients to have specific preoperative and postoperative data and a minimum follow-up duration of at least 6 months. Results The study found statistically significant differences between the remission rates based on the 2002 and 2010 consensus criteria for acromegaly, with a 73.4% remission rate under the 2002 criteria and a 65.3% remission rate under the 2010 criteria (p=0.002). Multivariate logistic regression analysis indicated that the atypical nature of the adenoma (p=0.018) and surgical intervention due to recurrence (p=0.028) were significant negative factors affecting cure rates. The study also identified that advanced stages in Hardy Wilson (p=0.008) and Knosp (p&lt;0.001) classifications had a statistically significant negative impact on achieving a cure. No statistically significant predictive value was found for early postoperative IGF-1 levels in relation to cure (p=0.612). Conclusion: PEET is currently the preferred treatment option for GH-secreting pituitary adenomas and has high remission rates.

ODP363 Growth hormone and prolactin co-secretion in acromegaly: a case study and review of the literature

Abstract Introduction Growth hormone (GH) and prolactin co-secreting pituitary adenoma is the most common type of pleuri-hormonal adenomas. We present a case of GH and prolactin co-secreting macroadenoma with somato-mammotroph (SMT) histopathology. Case A 48-year-old female presented with complaints of chronic headaches and coarsening of facial features for &amp;gt;5 years. Associated symptoms included chronic fatigue, joint pain, heat intolerance, diaphoresis, and 20 lbs weight gain. She noted acral enlargement and ill-fitting dentures. She also reported snoring and witnessed apneic spells. She denied peripheral vision loss, galactorrhea, or breast tenderness. Past medical history included prediabetes, bilateral carpal tunnel surgery, and uterine ablation. On examination, her weight was 269 lbs, height 5'8", and BP 148/92 mmHg. She had acromegalic features including frontal bossing with coarse facial features, prominent jaw, and large hands with sausage-like fingers and sweaty palms. Her oropharynx was crowded with Mallampati grade 4. Laboratory data showed elevated IGF-1 level of 981 ng/mL (77- 220) and prolactin level – 189 ng/mL (4.8–23.3). The fasting GH level was 5.1 ng/mL (&amp;lt;7.1). Fasting blood sugar was 145 mg/ dl with an HbA1C of 6.4%. Repeat testing confirmed elevated IGF-1–803 ng/mL with a Z score of 4.5 and prolactin– 130.2 ng/mL. Prolactin levels were higher than expected for stalk effect, hence GH and prolactin co-secretion was suspected. The patient had secondary hypogonadism with normal cortisol and thyroid axes. MRI pituitary showed a 2.6×1.8×1.9 cm pituitary macroadenoma with erosion of sellar floor, extension into the right sphenoid sinus, and possible involvement of the left cavernous sinus. The patient underwent transsphenoidal hypophysectomy, which was complicated by transient diabetes insipidus. Postoperative GH levels remained elevated &amp;gt; 3ng/ mL (goal for remission &amp;lt; 1 ng/ ml). Surgical pathology showed SMT type pituitary adenoma, with tumor cells staining both for GH and prolactin. The patient will have repeat pituitary MRI and biochemical testing 2 months following surgery to assess the presence and extent of residual disease. Discussion The WHO's 2017 classification divides GH and prolactin co-secreting tumors to 1) SMT cell adenomas where monomorphous cells co-secrete both GH and prolactin; 2) mixed GH cell and prolactin cell adenomas, bimorphous tumors where 2 different cell types secrete GH and prolactin; and 3) acidophil cell tumors. SMT adenomas are morphologically similar to densely granulated adenomas. These are usually slow growing and rarely invade surrounding structures. They have low intensity on T2-weighted MR imaging. In a study of 94 acromegaly cases, SMT adenomas were the smallest in size, with minimal cavernous sinus invasion, and had a higher chance of complete tumor resection. In contrast, our patient had a relatively large and invasive SMT adenoma. Presentation: No date and time listed

Predictors of postoperative biochemical remission in lower Knosp grade growth hormone-secreting pituitary adenomas: a large single center study.

Growth hormone-secreting pituitary adenomas (GH-PAs) with a low Knosp grade are typically associated with a good postoperative biochemical remission (BR) rate. However, a proportion of patients do not achieve remission. In this study, we aimed to investigate predictive factors of postoperative remission for lower Knosp GH-PAs. In this retrospective study, we enrolled 140 patients who were diagnosed with lower Knosp (0-2) GH-PAs and received trans-sphenoidal surgery between December 2016 and June 2021 from the largest pituitary tumor surgery center in southern China. The univariate, binary Logistic regression, and receiver operating characteristic curve (ROC) analyses were employed to determine independent predictors and cutoff values of remission. The postoperative outcome was defined as remission using the 2010 consensus criteria of acromegaly. One hundred and thirty six patients (97.1%) achieved gross total resection. The postoperative long-term BR was 68.6%. Empty sella, tumor maximum diameter and postoperative GH levels were independent factors predicting remission. ROC revealed that postoperative 24h GH ≤ 1.3ng/mL and ≤ 1.23ng/mL were valuable predictors for 3-month and long-term remission respectively, and that postoperative 3-month GH ≤ 1.6ng/mL and tumor maximum diameter ≤ 17mm were predictors for delayed remission. Early postoperative GH levels can be used as predictors of remission. However, BR was not associated with preoperative somatostatin analogs therapy or Knosp grade (0-2). For patients without residual tumor or recurrence and whose GH levels are slightly elevated within 1year after surgery, adjuvant treatments may not be necessary.

Age, GH/IGF-1 levels, tumor volume, T2 hypointensity, and tumor subtype rather than proliferation and invasion are all reliable predictors of biochemical response to somatostatin analogue therapy in patients with acromegaly: A clinicopathological study

PurposeTo determine whether biochemical responses to long-acting forms of first-generation somatostatin analogue (SSA) therapy in patients with acromegaly could be predicted from baseline and postoperative hormone concentrations, and tumor radiological and histopathological characteristics. MethodsA total of 68 patients with acromegaly for whom postoperative SSA therapy was started were categorized according to their responses to treatment (SSA-responders vs. non-responders). The patients were compared based on their demographic characteristics, hormone levels, magnetic resonance imaging (MRI), and histopathological findings. Receiver-operating-characteristic (ROC) curves were constructed using the predictive factors that were significant in the univariate analysis to determinate the optimal cut-off values. ResultsThe SSA-responders were significantly older (p = 0.041). Lower GH at diagnosis (p = 0.036), the postoperative 1st-week GH level (p = 0.027), baseline GH, insulin-like growth factor-1 (IGF-1) and IGF-1% upper limit of normal (ULN) (p = 0.001, p = 0.006, p = 0.023, respectively) were associated with biochemical response. T2-hypointensity and lower tumor volume were more common in the SSA-responders (p = 0.018, p = 0.03, respectively). Compared to sparsely granulated somatotroph tumors, densely granulated somatotroph tumors and other PitNETs causing GH excess including mammosomatotroph and mixed somatotroph and lactotroph tumors were more likely to respond to SSA therapy (p = 0.026, p = 0.03, respectively). The cut-off values generated by ROC curve analysis were GH at diagnosis of ≤8.8 ng/mL, GH at baseline of ≤2.69 ng/mL, IGF-1 at baseline ≤461.5 ng/mL, IGF-1% ULN at baseline ≤180.4%, and tumor volume of ≤1.11 cm3 (all p < 0.05). There were no differences between the groups in terms of tumor invasiveness, proliferative activity (mitotic count per 2 mm2 and Ki-67 labeling index) and quantitative analyses of T2-weighted MRI. ConclusionThis study underscores that advanced age, low baseline GH and IGF-1 at diagnosis, low tumor volume, densely granulated tumor subtype, and T2 hypointensity may help predict biochemical response to SSA therapy in cases of acromegaly. These variables should be assessed with utmost attention for all patients prior to SSA treatment. In cases of possible resistance to SSA therapy, therapeutic activity should be monitored more closely and other therapies should be administered immediately in the event of poor response.

A single-center experience of transsphenoidal endoscopic surgery for acromegaly in 73 patients: results and predictive factors for remission

Background Transsphenoidal endoscopic surgery is the first-line treatment for growth hormone-secreting adenomas. Objective To analyse the results of the transsphenoidal endoscopic approach for acromegaly and to determine the predictive factors of remission. Methods A single-centre retrospective review was performed in patients who underwent endoscopic transsphenoidal surgery for acromegaly between January 2009 and January 2019. Demographic features, clinical presentation, histopathology records, complications and pre- and postoperative radiologic and endocrinological assessments were evaluated. The factors that influenced the remission rates were investigated. Results A total of 73 patients underwent surgery via the transsphenoidal endoscopic approach. Cavernous sinus invasion was detected in 32 patients (43.8%); and macroadenoma, in 57 (78%). The pathology specimens of the 27 patients (36.9%) showed dual-staining adenomas with prolactin. A total of 51 patients (69.8%) attained biochemical remission 1 year after surgery. A second operation was performed in 10 patients (13.6%) with residual tumours without biochemical remission in the first year. Six (60%) of the patients attained remission at the last follow-up. Transient diabetes insipidus was observed in 18 patients (24.6%); and rhinorrhoea, which was resolved with conservative treatment, in 4 (5.4%). None of the patients developed panhypopituitarism. The presence of cavernous sinus invasion and preoperative IGF-1, immediate postoperative GH and third-month IGF-1 levels were predictive of remission. Conclusion Transsphenoidal endoscopic surgery is a safe and effective treatment for acromegaly. Reoperation should be considered in patients with residual tumours without remission.

A Rare Case of a Plurihormonal Pituitary Adenoma

Background: Pituitary adenomas are usually benign tumors that arise from adenophypophyseal cells and produce one or two types of hormones. Plurihormonal adenomas are a rare subtype that produce two or more hormones and represent less than 1% of all pituitary adenomas. Clinical Presentation: A 76-year-old female presented for evaluation of abnormal thyroid function test results. She was found to have an elevated free T4 of 1.92 ng/dL and total T4 of 14.4 ug/dL with an inappropriately normal TSH of 2.11 uIU/mL. Physical examination was significant for tachycardia, tremors, diaphoresis, coarse facial features, and enlarged hands. Further biochemical evaluation of her pituitary hormone levels demonstrated an elevated prolactin (PRL) of 237.2 ng/mL, elevated insulin-like growth factor 1 (IGF-1) of 787 ng/mL, normal morning ACTH of 47 pg/mL, normal morning cortisol of 17.0 ug/dL, an inappropriately suppressed FSH of <5.0 mIU/mL, an elevated alpha subunit of pituitary glycoprotein hormones (PGH) of 6.9 ng/mL, and an elevated free T4 of 3.5 ng/dL by equilibrium dialysis. She underwent an MRI of the pituitary and brain which demonstrated a pituitary adenoma measuring 1.2 x 1.3 x 1.8 cm with a portion herniating into the sella turcica with no mass effect of the optic chiasm. A formal visual field examination was normal. The patient underwent workup for Cushing’s Disease with a low dose overnight dexamethasone suppression test, resulting in an appropriate response with an 8 AM cortisol of <1.0 ug/dL. Glucose suppression test confirmed the diagnosis of acromegaly with growth hormone at 120 minutes of 19.90 ng/mL. Neurosurgery performed a trans-sphenoidal pituitary adenoma resection. Thyroid function tests on post-operative day 4 demonstrated a suppressed TSH of 0.01 uIU/mL and an elevated free T4 of 2.30 ng/dL. Histological evaluation revealed dual expression of transcription factors pituitary-specific positive transcription factor 1 (PIT1) and steroidogenic factor 1 (SF1) as well as PRL, GH, TSH and FSH expression. Immunostaining for LH and ACTH were negative. Post-operative IGF-1 and GH levels were 106 ng/mL and 0.51 ng/mL at 17 weeks, respectively. Post-operative TSH normalized to 0.82 uIU/mL, free T4 normalized to 1.04 ng/dL, and PRL normalized to 8.1 ng/mL at 12 weeks. The patient remained symptom free after successful surgical resection. Discussion: Our case demonstrates the clinical course of a unique patient with clinical and biochemical manifestations of thyroid dysfunction and acromegaly with a pituitary adenoma immunoreactive for GH, TSH, FSH, and PRL. The co-secretion of GH, TSH, PRL, and FSH as well as positivity for the alpha-subunit is extremely unusual. This case emphasizes the importance of considering pituitary abnormalities as a cause for abnormal thyroid function tests.

MON-307 Prospective, Longitudinal Study of Glucose-Suppressed GH Levels in 87 Acromegaly Patients with IGF-1 Normalization After Surgical Therapy: Prognostic Value of Nadir GH Levels for Long-Term Remission or Recurrence

Surgical removal of the GH-secreting tumor is the initial treatment of choice for acromegaly. Outcome of surgery is assessed by measuring IGF-1 and glucose-suppressed GH levels. IGF-1 normalization is an essential biochemical criterion for remission. The cut-off for nadir GH after oral glucose that signifies remission, however, is debated. It also remains unclear whether GH levels provide additional prognostic or clinically relevant information when IGF-1 results are definitive. To address this question, we examined how initial postoperative glucose-suppressed GH levels change over time on serial testing in patients who achieve initial remission as defined by IGF-1 normalization. We studied 87 acromegaly patients (48M, 39F) who achieved a normal IGF-1 level after surgery alone longitudinally from 1996 to 2019. All had GH measured before and 60, 90 and 120 minutes after 75 or 100 mg oral glucose (OGTT) at ≥ 3 months after surgery and GH and IGF-1 repeated ≥ 1 year later. GH was by measured by sensitive, 22KDa GH specific assays, either a IRMA (DSL, International Reference Standard (IRS) 88/624) or a chemiluminescence immunoassay (IDS-iSYS, IRS 98/574). OGTT Nadir GH levels were also measured in healthy subjects; n=46 (26 M, 20 F, ages 19-71 yr.) by DSL and n=46 (29 M, 17 F; ages 20-66 yr.) by IDS-iSYS. Nadir GH levels in acromegaly patients were compared to the 95%CI of healthy subjects’ mean and categorized relative to healthy subjects’ 97.5 percentile, which was 0.14 µg/L for both assays. IGF-1 levels were compared to age and gender adjusted normal ranges. Subjects were grouped based on initial nadir GH ≤ or > 0.14 µg/L and the patterns of change in nadir GH and IGF-1 at last follow up or until IGF-1 became elevated (i.e. recurrence). Follow up durations are given as median(range). In follow up, 73 patients remained in remission (normal IGF-1) and 14 had a recurrence (elevated IGF-1). Of the 73 in remission, 55 had initial nadir GH ≤ 0.14 µg/L that persisted to 10 yr.(1-22yr.) of follow up, 5 had initial GH ≤ 0.14 µg/L that rose to > 0.14 µg/L by 9(3-21)yr., 10 had GH > 0.14 µg/L that persisted at 5.5(2-22)yr., and 3 had GH > 0.14 µg/L that fell to ≤ 0.14 µg/L at 5(4-7)yr. of follow up. Of the 14 that recurred, 11 had an initial and persistent GH > 0.14 µg/L and developed an elevated IGF-1 level after 6(1-23) yr.. The 3 other patients that recurred had an initial GH ≤ 0.14 µg/L that rose to > 0.14 µg/L by 1-6 years later and subsequently developed an elevated IGF-1 level by 14-16 years of follow up. In summary, we found that the pattern of normal IGF-1 along with nadir GH > 0.14 µg/L on initial testing or developing with time, was associated with recurrence in 14/32 patients. We also found that initial nadir GH ≤ 0.14 µg/L was highly predictive of long-term persistent remission: 60/63 such patients remained in remission. In conclusion, glucose-suppressed GH levels are of prognostic value in acromegaly patients with normal IGF-1 after surgery.

Early postoperative GH level as biomarker for surgical outcome in patients with acromegaly

Early postoperative GH level as biomarker for surgical outcome in patients with acromegaly

Predictors of surgical outcome and early criteria of remission in acromegaly.

Transsphenoidal surgery (TSS) is the cornerstone of acromegaly treatment, however there are no robust predictors of surgical outcome and remission can only be defined three months after surgery. To analyze if biochemical, demographical, radiological, and immunohistochemical characteristics are predictors of surgical remission and investigate if immediate postoperative GH and IGF-I levels can help defining remission earlier. Consecutive acromegaly patients submitted to TSS between 2013-2016 were evaluated. Remission criteria was defined as normal IGF-I and GH <1 mcg/L three months after surgery. Data of age, sex, GH and IGF-I levels, tumor volume, cavernous sinus invasion, T2-weighted signal, Ki-67, and granulation pattern were correlated with remission status. GH and IGF-I levels at 24, 48 h, and one week postoperative were evaluated as early criteria of remission. Sixty-nine patients were included (84% macroadenomas) and surgical remission was achieved in 45%. No difference between cured and not cured patients concerning age, gender, preoperative GH or IGF-I levels, tumor volume, T2-weighted signal, Ki-67 and tumor granularity was observed. Remission was obtained in 20 of 36 (56%) of the non-invasive tumors, and in 3 of 16 (19%) of the invasive tumors (p = 0.017). A GH <1.57 mcg/L 48 h after surgery was able to predict remission with 93% sensitivity and 86% specificity and an IGF-I < 231% ULNR one week after surgery predicted remission with 86% sensitivity and 93% specificity. Cavernous sinus invasion is the only preoperative predictor of surgical remission. GH at 48 h and IGF-I one week after surgery can define earlier not cured patients.

Validity of Early Postoperative Random GH Level as a Predictor Factor of Long Term Control of GH- Producing Pituitary Adenoma

Objective: The aim of this study was to evaluate and to validate the relationship between the early postoperative basal GH level and the long- term surgical treatment outcome of GH-producing pituitary adenoma as well as to present our experience of treating such types of pituitary adenoma in our institute. Materials and Methods: We retrospectively analyzed 103 patients with GH-secreting pituitary adenoma who underwent a surgical treatment between the years 2002 and 2010 in the department of Neurosurgery, University hospital, Damascus. The basal GH level was measured in the first week after surgery. With respect to basal GH levels, the patients were assigned to one of three groups: Group 1:patients with postoperative basal GH levels < 1 ng/mL. Group 2:patients with postoperative basal GH levels between 1-2.25 ng/mL. Group 3:patients with postoperative basal GH levels > 2.25 ng/mL. In every group the hormone activity was monitored postoperatively on a regular basis, the mean follow up duration was approximately 49 months (range 32-96 months). Definitive long term remission of acromegaly was considered to have been achieved when GH levels were less than 1 ng/mL and there was no clinical or magnetic resonance imaging evidence of a persisting disease. Results: The cure rate in Group 1 was 93.75 %, and in Group 2 was 72.72%, whereas in Group 3 all patients presented evidence of tumor residual or recurrence. The overall rate of cure was 45.23%. There was a significant relationship between the early postoperative basal GH concentration and long- term postoperative outcome (p<0.05). Conclusion: The early postoperative basal GH level is a simple and reliable factor that may help with predicting long term surgical outcome of pituitary adenoma.

Clinical features and natural course of acromegaly in patients with discordance in the nadir GH level on the oral glucose test and the IGF-1 value at 3 months after adenomectomy.

Discordant GH and IGF-1 levels after adenomectomy are well recognized in acromegalics. The aim of this study was to evaluate the clinical features and natural course of postoperative acromegaly associated with discordant GH and IGF-1 levels over a postoperative period. A total of 69 acromegalics underwent surgery with at least 1 year of follow-up and received 75-g oral glucose tolerance tests (OGTTs) at 3 months postoperatively. The patients were categorized into four groups according to the postoperative nadir GH levels and IGF-1 levels: controlled group (normal GH and normal IGF-1), high-IGF-1 group (normal GH and high IGF-1), high-GH group (high GH and normal IGF-1), and uncontrolled group (high GH and high IGF-1). The incidence of discordant GH and IGF-1 levels was 27.5%: high-IGF-1 group = 10.1% (n = 7) and high-GH group = 17.4% (n = 12). All patients in the high-IGF-1 group exhibited a decline in the IGF-1 level after surgery, with normalization observed in 71.4% of the patients without additional treatment (median 23 months). These subjects had preoperatively high IGF-1 levels despite not demonstrating higher GH levels than the patients in the controlled group. On the other hand, four patients in the high-GH group exhibited an elevated nadir GH level higher than 1.0 μg/L on repeated OGTTs after 3 months, and one patient experienced a recurrence of acromegaly. Patients in the high-IGF-1 group require no additional treatments, and their IGF-1 levels are likely to normalize within a few years. However, patients in the high-GH group should be carefully followed due to the possibility of recurrence.

Resection of pituitary adenomas invading cavernous sinus through transsphenoidal approach

Objective To explore the characteristics,surgical indications,methods and outcomes of the resection of invasive pituitary adenomas through transsphenoidal approach.Methods The clinical data of patients with pituitary adenomas invading cavernous sinus underwent surgery through transsphenoidal approach wcrc analyzed retrospectively.The extent of tumor removal,the change of hormone levels and the postoperative complications were analyzed.Results In 23 cascs,total tumor removal was achieved in 7 cases,subtotal in 12,and partial in 4.There were 12 cases of non-functioning adenomas,10 prolactinomas and 1 growth hormone adenoma.The postoperative PRL levels were decreased to normal in 4 cases,≥80％ in 4,＜ 80％ in 2.The postoperative GH level was decreased to ＞ 50％ in 1 case.The postoperative complications included 3 cases of hypopituitarism,l cerebrospinal fluid fistulae,1 deterioration of vision,2 transient cranial nerve palsy,5 transient diabetes insipidus and 4 electrolyte unbalance.18 cases had been followed-up from 3 months to 2 years,5 cases of recurrence.Conclusions The pituitary adenomas invading cavernous sinus could be revealed and removed satisfactorily with fewer surgical complications through the transsphenoidal approach. Key words: Transsphenoidal approach ; Pituitary adenoma ; Invasion ; Cavernous sinus

Clinical predictors of GH deficiency in surgically cured acromegalic patients.

Even in patients with cured acromegaly, GH deficiency (GHD) after transsphenoidal adenomectomy (TSA) adversely affects body composition and inflammatory biomarkers of cardiovascular risk. In this study, clinical parameters for predicting GHD after TSA in 123 cured acromegalic patients were investigated. GH levels were measured at 6, 12, 18, 24, 48, and 72 h after TSA and serial insulin tolerance tests were conducted at 6 months, 2 years, and then every 2 years after TSA. GHD was found in 12 patients (9.8%) at 4.1 (range: 0.5-4.1) years after TSA. IGF1 levels were significantly lower at 6 months after TSA in GHD group than intact GH group (175.9 vs 316.8 μg/l, range: 32.0-425.0 and 96.9-547.3 respectively, P=0.008). Adenomas involving both sides of the pituitary gland were significantly more frequent in GHD patients (29.7 vs 83.3%; P=0.002). Furthermore, immediate postoperative 72-h GH levels after TSA were significantly lower (0.17 vs 0.45, range: 0.02-0.93 and 0.02-5.95 respectively, P=0.019) in GHD patients. In multiple logistic regression analysis, bilaterality of tumor involvement (odds ratio (OR)=10.678, P=0.003; 95% CI=2.248-50.728) and immediate postoperative 72-h GH level (OR=0.079, P=0.047; 95% CI=0.006-0.967) showed significant power for predicting GHD. These data suggest that bilateral involvement of a pituitary adenoma and severely decreased immediate postoperative serum GH levels at 72 h after TSA may be independent risks factor for accelerated GHD in acromegalic patients.

Endoscopic vs Microsurgical Transsphenoidal Surgery for Acromegaly: Outcomes in a Concurrent Series of Patients Using Modern Criteria For Remission

It is unclear whether endoscopic transsphenoidal surgery (ETSS) or microsurgical transsphenoidal surgery (MTS) is a superior surgical approach for pituitary adenomas. The objective of the study was to compare the outcome of surgery with ETSS and MTS by experienced pituitary surgeons using criteria of remission using current consensus criteria for acromegaly. This was a retrospective review of prospectively recorded outcomes. The study was conducted at a tertiary referral center. Patients, Interventions, and Outcome Measures: Remission was defined as a normal IGF-I level and either suppressed GH less than 0.4 ng/mL during an oral glucose tolerance test or random GH less than 1.0 ng/mL. The Youden indices were calculated to determine the optimal cutoffs for using immediate postoperative GH levels to predict the results of later testing for remission. Preoperative demographics and tumor characteristics were not significantly different between patients undergoing ETSS (72 patients) or MTS (41 patients). Overall, postoperative remission was achieved in 20 of 23 microadenomas (87%) and 59 of 90 macroadenomas (66%). Remission rates and perioperative complications were not significantly different between ETSS and MTS groups, except for self-reported sinusitis and alterations in taste or smell, which were significantly higher in patients treated with ETSS. Preoperative variables predicting remission in multivariate analysis included GH less than 45 ng/mL [odds ratio (OR) 6.4, P = .010)] and Knosp score of 0-2 (OR 6.8, P < .001). Postoperative in-hospital GH less than 1.15 ng/mL provided the best predictor of remission (OR 7.7, P < .001; sensitivity of 73%, specificity of 85%) defined by follow-up testing. Outcomes of transsphenoidal surgery for acromegaly by experienced pituitary surgeons do not differ between endoscopic and microscopic techniques. Regardless of the mode of resection, patients with high preoperative GH levels and Knosp scores are less likely to achieve remission. An immediate postoperative GH level of less than 1.15 ng/mL provides the best immediate predictor of remission, but long-term outcomes are indicated.

Repeat Endoscopic Transsphenoidal Surgery for Acromegaly: Remission and Complications

Reported biochemical remission rates following surgical intervention for acromegaly range from 38 to 83 %. In patients not achieving surgical remission, few options remain, mostly limited to medical management and radiation therapy. There is debate over whether or not to offer reoperation to patients in whom surgical remission is not achieved with initial resection. Retrospective chart review was undertaken to determine all patients having acromegaly with persistently elevated GH and/or IGF-1 levels after initial pituitary adenoma resection, and who underwent reoperation using endoscopic endonasal approach at a single institution. Biochemical remission was defined as a postoperative GH level <1 ng/mL and a normal postoperative IGF-1 level in the absence of any medical therapy. In total, 14 patients underwent repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach. Of the 14 patients, 8 (57 %) achieved biochemical remission following repeat surgical intervention. Lower preoperative GH levels were associated with greater chance of biochemical remission (P = 0.048). New endocrinopathies were seen in 2 patients (14 %), and both were transient diabetes insipidus. Meningitis occurred in 2 patients (14 %); both were aseptic meningitis with no sequelae. No mortality was encountered. Repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach appears safe and effective. With no mortality and minimal morbidity, repeat surgical intervention via endoscopic transsphenoidal approach appears a reasonable option for these hard-to-treat patients and should be considered for patients in whom surgical remission is not achieved with initial surgery.

Repeat endoscopic transsphenoidal surgery for acromegaly: remission and complications

Reported biochemical remission rates following surgical intervention for acromegaly range from 38 to 83%. In patients not achieving surgical remission, few options remain, mostly limited to medical management and radiation therapy. There is debate over whether or not to offer reoperation to patients in whom surgical remission is not achieved with initial resection. Retrospective chart review was undertaken to determine all patients having acromegaly with persistently elevated GH and/or IGF-1 levels after initial pituitary adenoma resection, and who underwent reoperation using endoscopic endonasal approach at a single institution. Biochemical remission was defined as a postoperative GH level <1 ng/mL and a normal postoperative IGF-1 level in the absence of any medical therapy. In total, 14 patients underwent repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach. Of the 14 patients, 8 (57%) achieved biochemical remission following repeat surgical intervention. Lower preoperative GH levels were associated with greater chance of biochemical remission (P = 0.048). New endocrinopathies were seen in 2 patients (14%), and both were transient diabetes insipidus. Meningitis occurred in 2 patients (14%); both were aseptic meningitis with no sequelae. No mortality was encountered. Repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach appears safe and effective. With no mortality and minimal morbidity, repeat surgical intervention via endoscopic transsphenoidal approach appears a reasonable option for these hard-to-treat patients and should be considered for patients in whom surgical remission is not achieved with initial surgery.

Endoscopic Transsphenoidal Surgery for Acromegaly: Remission Using Modern Criteria, Complications, and Predictors of Outcome

Despite the growing application of endoscopic transsphenoidal surgery (ETSS), outcomes for GH adenomas are not clearly defined. We reviewed our experience with ETSS with specific interest in remission rates using the 2010 consensus criteria, predictors of remission, and associated complications. This was a retrospective single institution study. PATIENTS, INTERVENTIONS, AND OUTCOME MEASURES: Sixty acromegalic patients who underwent ETSS were identified. Remission was defined as a normal IGF-I and either a suppressed GH less than 0.4 ng/ml during an oral glucose tolerance test or a random GH less than 1.0 ng/ml. Remission was achieved in all 14 microadenomas and 28 of 46 macroadenomas (61%). Tumor size, age, gender, and history of prior surgery were not predictive on multivariant analysis. In hospital postoperative morning GH levels less than 2.5 ng/ml provided the best prediction of remission (P < 0.001). Preoperative variables predictive of remission included Knosp score (P = 0.017), IGF-I (P = 0.030), and GH (P = 0.042) levels. New endocrinopathy consisted of diabetes insipidus in 5%, adrenal insufficiency in 5.4%, and new hypogonadism in 29% of men and 17% of women. However, 41% of hypogonadal men had normal postoperative testosterone levels and 83% of amenorrheic women regained menses. The most common complaints after surgery were sinonasal (36 of 60, 60%) resolving in all but two. ETSS for GH adenomas is associated with high rates of remission and a low incidence of new endocrinopathy. Despite the panoramic views offered by the endoscope, invasive tumors continue to have lower rates of remission.

Effect of presurgical long-acting octreotide treatment in acromegaly patients with invasive pituitary macroadenomas: a prospective randomized study

Therapeutic effects of presurgical long-acting octreotide treatment on tumor shrinkage, and short- and long-term postoperative GH and IGF-1 levels of acromegaly patients with invasive pituitary macroadenomas were investigated prospectively in Huashan Hospital, Shanghai, China. Thirty-nine untreated acromegaly patients, all with invasive pituitary macroadenomas, were randomly divided into two groups: experimental group (n=19), and control group (n=20). Patients in the experimental group received a three-month course of long-acting octreotide treatment before transsphenoidal surgery; the control group underwent surgery directly. Tumor shrinkage after drug treatment and short- and long-term postoperative GH and IGF-1 levels were analyzed in the two groups. Long-acting octreotide treatment reduced tumor size from 7893 ± 6450 to 4794 ± 4682 mm(3). Mean shrinkage rate was 37.4 ± 30.9%. GH and IGF-1 levels of the experimental group were lower than the control group at 3 months, 6 months after surgery, and after long-term follow-up. Remission rate (both GH and IGF-1 normal) of the experimental group was higher at 3 and 6 months follow-up, but exhibited no advantage in long-term follow-up. In the experimental group, the total resection rate was higher in patients whose Hardy-Knosp grading decreased to ≤ 2 than those whose Hardy-Knosp grading is still ≥ 3 after drug pretreatment. In conclusion, presurgical long-acting octreotide treatment effectively reduces tumor size and invasion, which helps enhance early remission rates of invasive macroadenomas by transsphenoidal surgery, but does not appear to improve the long-term cure rate.

Wide variation in surgical outcomes for acromegaly in the UK

Unsuccessful surgery for acromegaly has major consequences for the patient as well as financial consequences for the National Health Service (NHS). Surgical expertise affects the outcome. We have used the UK National Acromegaly Register to assess surgical outcomes in different centres to investigate whether these match the previously published case series. Retrospective and prospective observational study by analysis of anonymized national computer register records derived from individual clinical case records from 22 UK endocrine units and their associated pituitary surgical services. Cases of acromegaly, presenting in 1970-2004, with levels of GH or IGF-1 (785 and 430 cases, respectively) recorded prior to transsphenoidal adenomectomy and in the 12 months postsurgery, before any subsequent pituitary surgery or radiotherapy. GH-lowering pharmacological therapy was permitted only if suspended for biochemical testing. Percentage of cases with 'safe' mean postoperative GH levels (< 5 mU/l) and/or IGF-1 in the age- and sex-adjusted normal range. 'Safe' GH, normal IGF-1, or both was achieved for 26%, 29% and 20% of extrasellar macroadenomas (> 1 cm), respectively, 39%, 39% and 29% of intrasellar macroadenomas, 56%, 51% and 37% of microadenomas (< 1 cm) and 39%, 39% and 28% of cases overall. In centres contributing more than 10 patients' data, rates of safe GH levels ranged from 20% to 68% and IGF-1 from 19% to 55%. Success rates in attaining safe postsurgical levels of GH improved only slightly in the UK between 1974 and 1999 but markedly thereafter. Surgical outcomes for acromegaly in UK centres vary widely and historically have not, except in a few centres, matched those of large published series, which mostly have a success rate around 60%. Results have, however, improved substantially since 2000 and in the most successful units match those of the best published series. Experience is an important determinant of surgical success in acromegaly and the very recent improvement in surgical results in the UK coincides with a trend to concentrate pituitary surgery in the hands of a smaller number of specialists. Therefore, patients should be offered surgery by a dedicated pituitary surgeon with a caseload sufficient to offer the prospect of safe postsurgical GH and IGF-1 levels for the majority of cases.