Random Growth Hormone Levels Research Articles

Predictors of Remission of Acromegaly following Surgical Treatment in Growth Hormone-Secreting Pituitary Adenoma.

Background and Objective Surgery is the treatment of choice for growth hormone (GH)-secreting pituitary adenoma. The remission of random GH depends on various factors. We aimed to evaluate the predictors related to remission of random GH following surgical treatment. Methods We collected the data retrospectively from the chart review from a single unit of neurosurgery. The diagnostic criteria for remission were a random GH < 1 ng/mL or nadir GH < 0.4 ng/mL after an oral glucose tolerance test. Results Data from a total of 110 (females 62 [56.4%]) patients were available for follow-up and were analyzed. The mean age was 36.5 years (14-69 years). Vision impairments were seen in 39 (35.5%) patients. The mean duration of symptoms before surgery was 34 months. The mean volume of the tumor was 7.2 mL (0.44-109.8 mL). Knosp grade 3 and 4 tumors were seen in 41.5% of cases. The mean preoperative random GH level was 68.9 ng/mL. Transsphenoidal surgery was done in 107 (97.3%) cases. The gross total resection could be done in 36 (32.7%) cases. At 3 months, 25 (26%) patients had a biochemical remission. In univariable analysis, lower Knosp grade, preoperative GH level < 40 ng/mL, gross total resection, and male gender were associated with remission at 3 months. In regression analysis, preoperative GH and male gender were related to remission at 3 months. Conclusion The preoperative GH level < 40 ng/mL is associated with higher chances of remission after surgery for GH-secreting pituitary adenoma.

PMON49 Checkpoint Inhibitor Induced Hypophysitis with Growth Hormone Deficiency and Implications for the Treatment of ACTH Deficiency

Abstract Background/Purpose Hypophysitis is a known complication of immune checkpoint inhibitor (ICI) therapies used in the treatment of malignant cancers. In general, central adrenal insufficiency (AI) and hypothyroidism are the most recognized deficiencies following a diagnosis of ICI induced hypophysitis. As a result, other hypothalamic-pituitary axes (HPAs) are either incompletely evaluated or are disregarded from a therapeutic standpoint. Of particular importance is the growth hormone axis which is well established to affect tissue level metabolism of cortisol and cortisone through its effect on 11 beta hydroxysteroid dehydrogenase in target tissues. Our hypothesis is that growth hormone deficiency is also present in ICI induced hypophysitis. Methods We queried current and legacy electronic medical records of patients who received ICI for clinical notes mentioning adrenal insufficiency and concern for hypophysitis using the EMERSE tool. Patients with ICI exposure were included if they had 2 of the following 3 criteria; new onset central AI as defined by a low ACTH and cortisol, pituitary imaging suggestive of hypophysitis, or clinical presentation concerning hypophysitis. Patients were excludedfrom the analysis if there was a history of brain irradiation or in whom the diagnosis was not clear due to high dose steroid exposure prior to biochemical evaluation. Results Twenty-nine patients met inclusion criteria. Out of 29 patients, 16 underwent testing of the growth hormone axis with IGF-1 (11) and/or random growth hormone level (5). Seventeen patients (59%) had biochemical evidence of deficiency of 3 or more HPAs. Twenty-six patients (90%) had biochemical evidence of 2 or more PHAs. Two patients only underwent evaluation of 2 pituitary axes so it is unknown if they indeed suffered from panhypopituitarism. Most patients (28/29) were prescribed hydrocortisone for AI with an average dose of 20 mg per day. Conclusions Our findings are suggestive that growth hormone deficiency may be present in ICI induced hypophysitis. This finding holds implications for cortisol replacement therapy for coexisting AI. When one considers the average adrenal cortisol production is 5.7–7.4 mg/m2/day or 9.5–9.9 mg/day, 20 mg of daily cortisol replacementmay be too high in the face of concomitant growth hormone deficiency. Practice changes may include lower doses ofhydrocortisone replacement or adjustment to cortisone acetate which has been shown to have more favorable effectson tissue level metabolic effects. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

The utility of a random growth hormone level in determining neonatal growth hormone sufficiency

Background Random growth hormone (GH) levels have been used in the neonate to investigate congenital growth hormone deficiency (GHD). The cut-off value for use in this diagnosis is yet to be established. Methods This is a retrospective chart review of all random GH levels obtained in neonates ≤28 days of age. Neonates were divided into three groups: those diagnosed with congenital GHD, those at risk for GHD (ARF-GHD) and a non-growth hormone deficient (non-GHD) group. Mean GH levels for each group were compared, and ROC analysis was used to identify a cut-off for the diagnosis of GHD. Results The study included 138 neonates with the mean age of 9.07 ± 6.6 days, and 65% of these were born at term gestation. Mean GH levels were lower in the GHD group (2.73 ± 1.19 ng/ml) as compared to the ARF-GHD (9.4 ± 7.96 ng/ml, p = .002) and non-GHD groups (14.86 ± 14.42 ng/ml, p = .027). GH values were not significantly different between non-GHD and ARF-GHD groups. ROC analysis identified a cut-off of serum random GH level of 4.5 ng/ml that achieved 100% sensitivity and 83% specificity for the diagnosis of congenital GHD. Conclusion This study demonstrates that random GH levels obtained in the first 28 days of life can be useful in diagnosing congenital GHD. Moreover, a diagnostic cut-off for congenital GHD using random GH levels was identified.

Prevalence and outcome of comorbidities associated with acromegaly.

Acromegaly is associated with various comorbidities, such as arterial hypertension (aHT), type 2 diabetes mellitus (DM2), obstructive sleep apnoea syndrome (OSAS), carpal tunnel syndrome (CTS) and polyposis coli. For therapeutic decisions, it is essential to know if, and to what extent, these associated morbidities are reversible or preventable. The aim of this study is to assess the prevalence and course of aHT, obesity, OSAS, CTS, DM2 and polyposis coli in acromegalic patients. The following criteria for inclusion in this database study were used: treatment for acromegaly at the authors' institutions; full endocrinological and radiological work- and follow-up; screening for aHT, DM2, CTS, OSAS, obesity and polyposis coli. All patients were followed-up for > 3months, and treatments were indicated with the intent of biochemical remission (normal IGF-1 and random growth hormone level). Sixty-three patients were included. Twelve (19%), 45 (71%) and 6 (10%) patients harboured micro-, macro- and giant adenomas, respectively. Nineteen tumours (30%) invaded the cavernous sinus. Mean tumour volume was 5.4 cm3. Mean follow-up time was 42months. Sixty-one (97%) patients had transsphenoidal surgery; two patients only had drug therapy. Surgery led to remission in 31 (51%) patients. Intracavernous growth and larger tumour volume were negative predictors for cure. Drug therapy lead to remission in 22 (73%) patients within a mean follow-up of 54months. The pretherapeutic prevalence of associated morbidities was as follows: aHT, 56%; DM2, 25%; OSAS, 29%; CTS, 29%; polyposis coli, 5%. There were neither age nor gender preferences for the respective prevalences. Surgery leads to remission of aHT and DM2 in 6% and 25%, respectively. Additional drug therapy resulted in remission of aHT, DM2 and CTS in 17%, 14% and 14%, respectively. Other associated morbidities persisted regardless of therapeutic efforts. Even if criteria for remission were not met, no new comorbidities of acromegaly developed during follow-up. Treating acromegaly may relieve threatening associated morbidities such as aHT and DM2; nevertheless, only few comorbidities are reversible, which highlights the importance of treating acromegaly as early as possible.

In patients with controlled acromegaly, indices of glucose homeostasis correlate with IGF-1 levels rather than with type of treatment.

Acromegaly is accompanied by abnormalities in glucose and lipid metabolism which improve upon treatment. Few studies have investigated whether these improvements differ between treatment modalities. This study aimed to compare glucose homeostasis, lipid profiles and postprandial gut hormone response in patients with controlled acromegaly according to actual treatment. Cross-sectional study at a tertiary care centre. Twenty-one patients with acromegaly under stable control (ie insulin growth factor 1 [IGF1] levels below sex- and age-specific thresholds and a random growth hormone level <1.0µg/L) after surgery (n=5), during treatment with long-acting somatostatin analogues (n=10) or long-acting somatostatin analogues+pegvisomant (n=6) were included. Glucose, insulin, total cholesterol and high-density lipoprotein-cholesterol were measured in fasting serum samples. Glucose, insulin, triglycerides, glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 were measured during a mixed meal test. Insulin sensitivity was evaluated by a hyperinsulinaemic-euglycaemic clamp. There were no significant differences in glucose tolerance, insulin sensitivity or postprandial gut hormone responses between the three groups. Positive correlations between IGF1 levels and HbA1c, fasting glucose and insulin levels and postprandial area under the curve (AUC) of glucose and insulin and also an inverse association between IGF1 and glucose disposal rate were found in the whole cohort (all p<.05, lowest p=.001 for postprandial AUC glucose with rs =0.660). In this cross-sectional study in patients with controlled acromegaly, there were no differences in glucose homeostasis or postprandial substrate metabolism according to treatment modality. However, a lower IGF1 level seems associated with a better metabolic profile.

The utility of a random growth hormone level in determining neonatal growth hormone sufficiency.

Random growth hormone (GH) levels have been used in the neonate to investigate congenital growth hormone deficiency (GHD). The cut-off value for use in this diagnosis is yet to be established. This is a retrospective chart review of all random GH levels obtained in neonates ≤28days of age. Neonates were divided into three groups: those diagnosed with congenital GHD, those at risk for GHD (ARF-GHD) and a non-growth hormone deficient (non-GHD) group. Mean GH levels for each group were compared, and ROC analysis was used to identify a cut-off for the diagnosis of GHD. The study included 138 neonates with the mean age of 9.07±6.6days, and 65% of these were born at term gestation. Mean GH levels were lower in the GHD group (2.73±1.19ng/ml) as compared to the ARF-GHD (9.4±7.96ng/ml, p=.002) and non-GHD groups (14.86±14.42ng/ml, p=.027). GH values were not significantly different between non-GHD and ARF-GHD groups. ROC analysis identified a cut-off of serum random GH level of 4.5ng/ml that achieved 100% sensitivity and 83% specificity for the diagnosis of congenital GHD. This study demonstrates that random GH levels obtained in the first 28days of life can be useful in diagnosing congenital GHD. Moreover, a diagnostic cut-off for congenital GHD using random GH levels was identified.

Reappraisal of microscopic microsurgical transsphenoidal surgery for GH-secreting pituitary macroadenoma in patients with acromegaly: Historical data from Vietnam (2010–2013)

ObjectiveIn Vietnam, microscopic transsphenoidal surgery has been implemented to treat acromegaly patients since 2000. However, no specific outcome studies have been conducted. We assess outcomes of this technique and factors associated with remission. MethodsThis prospective observational study was conducted in 43 patients with acromegaly resulting from Growth Hormone (GH)-secreting pituitary macroadenoma. The primary outcome of interest was remission status, as defined by random GH levels below 2.5 ng/mL and Insulin-like Growth Factor-1 (IGF-1) within the normal range three months post-operation. ResultsThe proportion of patients with remission three months after surgery was 69.8% with a 95% confidence interval (CI) = 53.9–82.8%. The proportions of residual tumors three months after surgery in the remission and non-remission groups were 10.0% (3/27) and 23.1% (3/10), respectively, but there was no significant difference between these proportions (Fisher's exact test, p = 0.35). In a multivariate logistic regression analysis adjusted for sex and age, remission was associated with the absence of cavernous sinus invasion, with an odds ratio (OR) = 5.2 (95% CI = 1.1–26.5). In addition, remission was also associated with a post-operative GH level < 2.5 ng/mL (OR = 7.4, 95% CI = 1.1–48.0). ConclusionWe report that the proportion of patients with disease remission three months after surgery was high, indicating that microscopic transsphenoidal surgery was efficacious. More studies should be conducted to assess outcomes of various acromegaly treatment methods in the current context of Vietnam.

MON-298 IGF-1 in the Early Post-operative Assessment of Acromegaly

Introduction: Transsphenoidal surgery is recommended as first line therapy in the vast majority of patients with acromegaly. Successful surgical intervention is determined by normalization of insulin like-growth factor (IGF) - 1 and adequate suppression of growth hormone (GH) during glucose GH suppression test or random GH levels <1.0 ng/mL. Given the long half-life of IGF-1, evolution of IGF-1 and GH assays and limitations of GH suppression test, clinicians remain reliant on IGF-1 results 3–6 months following surgery to assess disease remission following surgical intervention. This can lead to delayed treatment of patients with persistent disease and significantly increase patient anxiety. Aim: To determine if IGF-1 levels at 6 weeks were equally predictive of surgical outcomes when compared to IGF-1 levels at 3–6 months postoperative. Methods: Retrospective review of patients with newly diagnosed acromegaly who had surgery between 2010–2019 and had post-operative IGF-1 level measured at 6 weeks and 3–6 months. IGF-1 was measured using the Siemens Immulite assay until 2016 when it was replaced by a LC-MS/MS assay. IGF-1 measurements at 6 weeks are obtained based on clinician discretion. Results: 69 patients (mean age 49 ± 14.8, female 31/69, 44.9%) with acromegaly had surgery and IGF-1 follow-up measurements at 6 weeks and 3–6 months. Persistent acromegaly was noted in 45/69 at 3–6 months. The median IGF-1 pre-operative was 701 ng/ mL (289–1600), 6 weeks postoperative was 286 ng/ mL (109–1038) and at 3–6 months was 267 ng/ mL (77–996). The median pre-operative IGF-1 was significantly higher than the median IGF-1 level at 6 weeks and 3–6 months (P=<0.001). Although a statistically significant difference was seen between IGF-1 levels at 6 weeks and 3–6 months, the mean difference between these time points was small (20 ng/mL, P=<0.001). There was a greater percent reduction in IGF-1 at 6 weeks following surgery in those who had a normal IGF-1 at 3–6 months compared to those who did not (63% vs 35%, P=<0.01). Among patients who were deemed in remission at 3–6 months (24/69, 35%), 3/24 patients (all male with macroadenoma and no cavernous sinus invasion) had mildly elevated IGF-1 levels at 6 weeks (≤1.12 upper limit of normal) which subsequently normalized. In all of these patients, GH was <1 ng/mL post-op. In 1 male (macroadenoma and cavernous sinus invasion), IGF-1 levels increased from normal at 6 weeks to abnormal when measured at 3–6 months. Conclusion: In the vast majority of patients, 6 weeks post-operative IGF-1 can be used to assess response to surgery avoiding a delay in treatment. However, we would recommend repeating IGF-1 levels at 3–6 months in those who have marginally elevated IGF-1 above normal (≤ 1.12), without cavernous sinus invasion and a post-operative GH of <1 ng/mL prior to intervening if the IGF-1 is elevated 6 weeks as the IGF-1 may normalize.

Diagnosis, treatment and follow-up of patients with acromegaly in a clinical practice setting in Spain: the ACROPRAXIS program Delphi survey

AimThe ACROPRAXIS program aims to describe the management of acromegaly in Spain and provide guidance.MethodsNinety-three endocrinologists were organized into 13 panels to discuss the practical issues in managing acromegaly. Based on the key learnings, an online Delphi survey with 62 statements was performed, so those statements achieving consensus could be used as guidance. Statements were rated on a 9-point scale (9, full agreement; consensus > 66.6% of response in the same tertile).ResultsNinety-two endocrinologists (98.8%) answered two rounds of the survey (mean age 47.6 years; 59.8% women; median 18.5 years of experience). Consensus was achieved for 49 (79%) statements. Diagnosis: The levels of insulin-like growth factor I (IGFI) is the preferred screening test. If IGFI levels 1–1.3 ULN, the test is repeated and growth hormone (GH) after oral glucose tolerance test (OGTT) is assessed. A pituitary magnetic resonance is performed after biochemical diagnosis. Treatment: Surgery is the first treatment choice for patients with microadenoma or macroadenoma with/without optical pathway compression. Pre-surgical somatostatin analogues (SSA) are indicated when surgery is delayed and/or to reduce anaesthesia-associated risks. After unsuccessful surgery, reintervention is performed if the residual tumor is resectable, while if non-resectable, SSA are administered. Follow-up First biochemical and clinical controls are performed 1–3 months after surgery. Disease remission is considered if random GH levels are < 1 µg/L or OGTT is < 1 or ≤ 0.4 µg/L, depending on the assay’s sensitivity.ConclusionCurrent clinical management for acromegaly is homogeneous across Spain and generally follows clinical guidelines.

The argument for growth hormone day curve testing in acromegaly; significant discrepancy between mean growth hormone and random growth hormone levels

The argument for growth hormone day curve testing in acromegaly; significant discrepancy between mean growth hormone and random growth hormone levels

Current perspectives on the impact of clinical disease and biochemical control on comorbidities and quality of life in acromegaly.

Acromegaly is a rare chronic, systemic disorder caused by excessive growth hormone (GH) secretion from a somatotroph pituitary adenoma. GH hypersecretion leads to overproduction of insulin-like growth factor-1 (IGF-1), which contributes to the somatic overgrowth, physical disfigurement, onset of multiple systemic comorbidities, reduced quality of life (QoL) and premature mortality of uncontrolled patients. Somatostatin receptor ligands, dopamine agonists and a GH receptor antagonist are currently available for medical therapy of acromegaly. The main aim of treatment is biochemical normalisation, defined as age-normalised serum IGF-1 values and random GH levels <1.0μg/L. However, there is an increasing evidence suggesting that achieving biochemical control does not always decrease the burden of disease-related comorbidities and/or improve patients' QoL. This lack of correlation between biochemical and clinical control can be due to both disease duration (late diagnosis) or to the peculiarity of a given comorbidity. Herein we conducted ad hoc literature searches in order to find the most recent and relevant reports on biochemical and clinical disease control during medical treatment of acromegaly. Particularly, we analyse and describe the relationship between biochemical, as well as clinical disease control in patients with acromegaly receiving medical therapy, with a focus on comorbidities and QoL. In conclusion, we found that current literature data seem to indicate that clinical disease control (besides biochemical control), encompassing clinical signs and symptoms, comorbidities and QoL, emerge as a primary focus of acromegaly patient management.

SUN-287 Pituitary Gigantism Presenting as Anxiety

Overproduction of growth hormone in a young person with open epiphyses results in gigantism. Pituitary gigantism is rare and its cause is most often a pituitary adenoma. We present a 9 y.o. boy followed by his psychiatrist, referred for worsening anxiety and rapid growth. He had a history of mild anxiety in childhood with worsening of symptoms a year prior to the endocrine visit. He also had aggressive behavior, irritable mood and poor concentration. He was started on guanfacine with subsequent addition of escitalopram. He has been rapidly outgrowing his clothes and shoes (men’s size 9) and complains of heat intolerance. He was following along the 97th percentile for height with significant growth acceleration observed starting at age 7 y.o. Current height is at +2.8 SDS. Weight has increased from the 90th percentile to the 97th percentile since age 4 y.o. and currently at +2.3 SDS. His BMI was at the 95th percentile. Physical examination showed a prominent jaw, widely-spaced teeth, large hands and feet, Tanner I pubic hair, no axillary hair, testicular volume 3 ml bilateral. Initial bloodwork showed elevated IGF-1 at 925 ng/mL (+13.7 SDS). Random growth hormone level was elevated at 5.66 ng/mL. He had normal male karyotype, free T4 was 1.5 ng/dL, with TSH of 2.13 uIU/mL. Prolactin level was normal. Growth hormone level after an oral glucose load showed a nadir of 2.76 ng/mL. This confirms growth hormone excess. ACTH and cortisol levels were normal. FSH and testosterone levels were prepubertal. Intact PTH, calcium and phosphorus levels were all normal. Skeletal survey did not identify any fibrous dysplasia seen in McCune Albright syndrome. Echocardiogram did not show atrial myxoma associated with Carney complex. MRI of the brain and pituitary gland was obtained which showed 4mm x 5 mm pituitary microadenoma. He underwent transsphenoidal surgery. IGF-I level twelve weeks post-surgery had decreased to 384 ng/mL (+4.3 SDS) showing a good response to transsphenoidal surgery. Repeat growth hormone suppression test showed a nadir level of 0.66 ng/mL. Goal of treatment is to normalize IGF-I level based on age. On subsequent visit with his psychiatrist, behavior issues and anxiety have improved with plans to discontinue psychotropic medications. We report a case of growth-hormone secreting pituitary adenoma presenting with anxiety. Patients with pituitary adenomas show a distinct pattern of increased anxiety-related personality traits compared with the general population, proposed to be due to direct and indirect effects of the pituitary lesion or hormonal disturbance on neural circuits or neurotransmission. Symptoms of anxiety and depression are valuable targets for possible future treatment interventions.

A registry of acromegaly patients and one year following up in Taiwan

The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4±12.9 years. Their mean age at diagnosis was 41.8±12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7±9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9±8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and theinsulin-like growth factor 1 levels were 2.7±4.9μg/L, 2.4±6.1μg/L, and 291.5±162.4ng/mL, respectively. The remission rate assessed by random GH level (≦2μg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0±19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly.

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

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

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

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

Value of early postoperative random growth hormone levels and nadir growth hormone levels after oral glucose tolerance testing in acromegaly

ObjectiveThere is no ideal marker to identify residual tumor tissue after surgery in patients with acromegaly. The purpose was to elucidate if early postoperative hormone testing gives reliable information regarding complete resection of a GH-producing pituitary adenoma. DesignFourty-eight patients undergoing surgery for acromegaly from 04/2013-05/2014 were prospectively examined for random GH, IGF1, and GH levels after oral glucose tolerance testing (OGTT) in the early postoperative phase and on follow-up. Criterion for inclusion was a minimum follow-up of one year for each patient with respect to remission. ResultsThirty-three patients showed GH suppression below 1 μg/l after OGTT in the early postoperative phase. Follow-up GH, IGF1 and OGTT tests confirmed the initial findings in 30 patients. The three remaining patients showed biochemical signs of persisting acromegaly. In the remaining 15 patients early postoperative GH suppression was above 1 μg/l. Of those, six patients went into remission during follow-up, nine patients without postoperative GH suppression <1 μg/l remained acromegalic. ConclusionsGH suppression to <1 μg/l as well as random GH levels below 1 μg/l in the early postoperative phase seem to be of good positive predictive value for long-term remission. However, several patients without suppression of GH to <1 μg/l in the early postoperative OGTT went into delayed remission. These results have to be taken into account prior to initiation of further therapy.

Endoscopic Transsphenoidal Approach for Surgical Treatment of Growth Hormone Secreting Pituitary Adenoma: Endocrinological Outcome in 49 Patients Based on 2010 Consensus Criteria for Remission - Preliminary Result

Background: Nowadays, the endoscopic transsphenoidal approach is the initial option for resection of all pituitary adenomas. The current study reported the experience with endoscopic transsphenoidal surgery remission rates using the 2010 consensus criteria, predictors of remission, and the associated complications. Methods: A prospectively collected database of 49 patients with acromegaly who underwent endoscopic endonasal transsphenoidal surgery was analyzed. Tumors were classified according to size, as well as the Knosp and the Hardy-Wilson classifications. Endocrinological remission was defined as normal insulin-like growth factor (IGF)-I level and either a suppressed growth hormone (GH) level < 0.4 ng/mL during an oral glucose tolerance test, or a random GH level < 1.0 ng/mL at least 3 months after the surgery. The extent of resection was evaluated on postoperative contrast-enhanced magnetic resonance imaging (MRI). Results: Biochemical remission was achieved in 7 of 9 (77.8%) microadenoma and 28 of 40 (70%) macroadenoma. The total remission rate was 71.4% and gross total resection was achieved in 45 of 49 (91.8%) patients. Tumor size, age, gender, history of prior surgery, suprasellar extension, and sphenoid sinus invasion were not associated with remission rate. Preoperative variables predictive of remission included the Knosp score (P = 0.041) and GH levels (P = 0.047). Two patients (4.1%) experienced postoperative pan hypopituitarism, and permanent DI was observed in 3 (6.1%) patients. One patient (2%) had cerebrospinal fluid (CSF) leaks treated with serial lumbar punctures. The median follow-up period was 25.45 months; ranged from 3 to 49. Conclusions: Endoscopic transsphenoidal adenoma resection leads to a high rate of endocrinological remission in patients with low acromegaly complication. Patients with high preoperative GH levels and the Knosp scores are less likely to achieve remission.

Can Immediate Post-Operative Random Growth Hormone Levels Predict Long Term Cure in Patients with Acromegaly?

Background: Growth hormone (GH) levels following oral glucose tolerance (OGTT) have been accepted as the most reliable parameter for defining remission and/or cure in patients with acromegaly. However, the role of random GH for predicting remission in the immediate post- operative period using modern criteria is not known. To evaluate the role of random GH levels in first five post-operative days as an early predictive tool for long-term remission of patients with acromegaly following transsphenoidal pituitary surgery (TSS).

Can immediate postoperative random growth hormone levels predict long-term cure in patients with acromegaly?

Growth hormone (GH) levels following oral glucose tolerance test (OGTT) at 12 weeks or later after surgery have been accepted as the most reliable parameter for defining remission and/or cure in patients with acromegaly. However, the role of random GH in predicting remission in the immediate postoperative period using modern criteria is not known. This study was undertaken to evaluate the role of random GH levels in first 5 postoperative days as an early predictive tool for long-term remission of patients with acromegaly following transsphenoidal pituitary surgery (TSS). Seventy-five consecutive acromegaly patients with at least three postoperative OGTT values at 3, 6, and 12 months of follow-up were included in the study. GH levels were measured just before surgery, in the immediate postoperative period, at 6 h and on day 1 to day 5 after surgery. Remission was defined as normal age-specific insulin-like growth factor-1 and either basal fasting GH <1 ng/ml or a nadir GH following OGTT <0 .4 ng/ml at 3 months of surgery. Of the 75 patients with acromegaly who underwent TSS, long-term remission was achieved in 42 (56%) patients. GH values ≤1.55 ng/ml at 6 h of surgery showed the highest predictive power for long-term remission, with a sensitivity of 81.2% and a specificity of 83.3%. The duration of disease and tumor volume had no effect on the 6 h GH value-related prediction of cure. Early postoperative GH values may be used to predict long-term cure. A value of ≤1.5 ng/ml at 6 h following surgery may predict long-term cure in two-thirds of the patients with acromegaly who undergo TSS.

Growth hormone tumor histological subtypes predict response to surgical and medical therapy.

Growth hormone (GH) pituitary tumors are associated with significant morbidity and mortality. Current treatments, including surgery and medical therapy with somatostatin analogs (SSA), dopamine agonists and/or a GH receptor antagonist, result in disease remission in approximately half of patients. Predictors of GH tumor response to different therapies have been incompletely defined based on histologic subtype, particularly densely (DG) versus sparsely (SG) granulated adenomas. The aim of this study was to examine our own institutional experience with GH adenomas and correlate how subtype related to clinical parameters as well as response to surgery and medical therapies. A retrospective chart review of 101 acromegalic patients operated by a single neurosurgeon was performed. Clinical data were correlated with histologic subtype and disease control, as defined by IGF-1 levels, and random growth hormone levels in response to surgery and/or medical therapies. SG tumors, compared to DG, occurred in younger patients (p = 0.0010), were 3-fold larger (p = 0.0030) but showed no differences in tumor-invasion characteristics (p = 0.12). DG tumors had a higher rate of remission in response to surgery compared to SG, 65.7 vs. 14.3 % (p < 0.0001), as well as to medical therapy with SSAs (68.8 % for DG vs. 28.6 % for SG tumors; p = 0.028). SG tumors not controlled with SSAs consistently responded to a switch to, or addition of, a GH receptor antagonist. Histological GH tumor subtyping implicates a different clinical phenotype and biologic behavior, and provides prognostic significance for surgical success and response to medical therapies.