Mean IGF-1 Levels Research Articles

Appraisal of skeletal maturity indicators with respect to non-invasive biomarkers

Non-invasive salivary biomarkers are being investigated as they may be helpful in predicting skeletal age. This study was conducted to evaluate the correlation between salivary insulin-like growth factor-1, salivary alkaline phosphatase, cervical vertebrae maturation stages and chronological age in the assessment of skeletal age during the growth period. This study also aims to find associations with mandibular base length and maxillary base length. Total 80 eligible subjects aged 7 to 21 years were selected and divided into two gender-specific groups (41 males, 39 females). A further subdivision was made on the basis of six cervical vertebral maturation stages from the lateral cephalogram. The chronological age was given for each subject, and The maxillary base length and the length of the mandibular base was calculated from the impressions on the lateral cephalogram. Saliva samples were collected from each subject to determine salivary IGF-1 and ALP levels using an enzyme-linked immunosorbent assay (ELISA). The data obtained was statistically analysed using SPSS (20.0) software. It was found that the mean IGF-1 activity in saliva was highest at CVMI stage 3 and the highest mean ALP levels in saliva occurred in males at CVMI stage 3 and in females at CVMI stage 4. Mean salivary ALP and IGF-1 levels correlate well with . Salivary ALP levels show a correlation with chronological age and could also be used as a diagnostic model to predict cervical stage. The diagnostic levels of certain biomarkers that appear in human saliva are representative of an individual's circumpubertal growth spurt. The collective pattern of increase and decrease in the sample during the circumpubertal stages is essential to study for orthodontic diagnosis and treatment planning.

Abstract P512: Associations of Serum Insulin-Like Growth Factor (IGF)-1 Levels With Cognitive Function and Atherosclerosis in a Japanese General Population: The Tanushimaru Study

Background: Insulin-like growth factor (IGF)-1 is a peptide hormone implicated in insulin sensitivity and anti-inflammatory. However, there is limited exploration of the association of serum IGF-1 levels with cognitive function and atherosclerosis. This study aimed to investigate the association between serum IGF-1 levels and cognitive function, as well as carotid atherosclerosis in a general population. Methods: In 1,345 participants (544 men; mean age, 68.7 (11.3) years) recruited from the Tanushimaru cohort, we measured their serum IGF-1 levels and evaluated cognitive function using mini-mental state examination (MMSE) and atherosclerosis through carotid intima-media thickness (IMT). Linear regression models were utilized to analyze the association between quartiles of serum IGF-1 levels and MMSE scores, as well as IMT, continuous dependent variables. We also visualized the continuous associations using restricted cubic spline models. Two-sided statistical significance was defined as p <0.05. All statistical analyses were performed using the SAS system (Release 9.4, SAS Institute, Cary, NC, USA). Results: The mean serum IGF-1 level was 96.6 (30.2) ng/ml. Multiple linear regression analysis revealed that the highest quartile of serum IGF-1 levels showed a statistically significant association with higher MMSE scores (p=0.0019), and the third quartile also reached statistical significance (p=0.0006) compared to the lowest. We observed a positive association between serum IGF-1 levels and MMSE scores, even when exploring the full spectrum of serum IGF-1 levels with their spline terms (Figure). In contrast, serum IGF-1 levels did not exhibit a significant association with IMT measurements. Conclusion: High serum IGF-1 levels were associated with higher cognitive function, while no significant association was observed with carotid atherosclerosis. Our findings suggest that IGF-1 levels may play a role in preserving cognitive function, potentially distinct from its role in atherosclerosis.

The Impact of Prenatal Alcohol Exposure on Longitudinal Growth, Nutritional Status, and Insulin-Like Growth Factor 1 in Early Childhood in Leyte, the Philippines

To assess the impact and potential mechanistic pathways of prenatal alcohol exposure (PAE) on longitudinal growth and nutritional status in early childhood. A cohort of 296 mother-infant dyads (32% with PAE vs 68% unexposed) were recruited in Leyte, the Philippines, and followed from early gestation through 24months of age. PAE was assessed using serum phosphatidylethanol (PEth) captured twice prenatally and in cord blood and supplemented with self-reported alcohol consumption. Linear mixed models were used to examine longitudinal effects of PAE on growth from birth through 2years including key potential mediating factors (placental histopathology, and infant serum leptin and Insulin-like Growth Factor 1 [IGF-1]). After adjusting for potential confounders, we found that PAE was significantly associated with a delayed blunting of linear growth trajectories (height-for-age z-score, body length) and weight (weight-for-age z-score, body weight) that manifested between 4 and 6months and continued through 12-24months. PAE was also associated with a decreased rate of mid-upper-arm circumference growth from birth to 12months, and a lower mean IGF-1 levels at birth and 6months. This study demonstrates a delayed impact of PAE on growth that manifested around 6months of age, underscoring the importance of routine clinical monitoring in early childhood. Furthermore, the findings supported prior animal model findings that suggest a mechanistic role for IGF-1 in PAE-induced growth delay.

Correlation between the middle phalanx of the third finger skeletal maturation staging system and insulin-like growth factor-1 levels among Indian children - A 3-year longitudinal study.

Tracking insulin-like growth factor-1 (IGF-1) level alongside the middle phalanx of the third finger (MP3) staging modification could provide valuable insights into the relationship between hormonal factors and skeletal maturation during different stages of growth. Longitudinal studies indeed play a crucial role in understanding these complex relationships over time, allowing for a more comprehensive assessment of how IGF-1 might serve as a marker for pubertal growth stages. The present longitudinal prospective cohort study was done among 26 boys and 26 girls. For each child, once in every 6 months for 3 years, blood samples (to estimate IGF-1 level) and X-rays of the left hand middle finger were taken. DRG IGF-1 600 Human Enzyme-Linked Immunosorbent Assay kit was used for the quantitative measurement of IGF1 from serum. The MP3 stages of the middle phalanx of the middle finger were evaluated using a modified MP3 system. The collected data were subjected to suitable descriptive and inferential statistics. The mean IGF1 levels were significantly higher in girls compared to boys across all the stages of MP3 skeletal maturity indicators. However, in both boys and girls, IGF-1 levels showed increasing trends from Stage F to H where it peaked and showed deceleration to Stage I (P < 0.05). The observed increase in serum IGF-1 levels during pubertal stages, followed by a decline in late puberty, aligning with the stages of skeletal maturation, suggests a close relationship between hormonal changes and bone development.

The efficacy of metformin as adjuvant to chemotherapy on IGF levels in non-diabetic female patients with progressive and non-progressive metastatic breast cancer.

Some studies have shown that metformin inhibits the proliferation of breast cancer (BC) cells via multiple ways. One of these mechanisms is through the indirect control of the IGF-route mediated via the activation of the AMPK-LKB1 pathway in the liver, which leads to a decrease in blood glucose and insulin levels. The objective of this study was to investigate the effects of metformin as adjuvant to chemotherapy on IGF levels in female patients with progressive and non-progressive metastatic BC. In this trial, 107 women receiving chemotherapy for metastatic breast cancer (MBC) were divided into two groups: the metformin group received 500 mg of metformin twice daily, whereas the control group did not receive any metformin. All patients received chemotherapy according to the South Egypt Cancer Institute's (SECI) established regimen. The level of IGF-1 was determined in the blood at the initiation of therapy (baseline) and at six months post treatment. No substantial differences were noted regarding IGF-1 levels in both groups at baseline (IGF-1 average level was 40.74 ± 36.16 vs. 32.06 ± 20.00 in the metformin and the placebo group, respectively, p = 0.462). While after six months, the mean IGF-1 level was 37.62 ± 31.35 vs. 39.12 ± 2 5.93 in the metformin and placebo groups, respectively, (p = 0.170). Metformin as an adjuvant to chemotherapy in MBC patients had no significant effect on reducing IGF-l levels which promotes the inhibition of the proliferation of BC cells in MBC patients.

The Effect of Infant Massage on Nutritional Status and IGf-1 of Malnourished Babies Aged 6-12 Months

Malnourished and poor nutrition are still a health center problem in Indonesia. A good nutritional intake can often not be fulfilled by a child, including due to various factors. Baby massage is a touch therapy that is carried out on baby so that it can provide assurance of ongoing body contact, maintain a feeling of security in the baby and strengthen the parent's love cord with the baby. The purpose of this study was to analyze the effectiveness of baby massage by mothers on improving the nutritional status of baby with malnutrition aged 6-12 months. This study used a quasi-randomized pre-test and post-test control group design. Samples were 48 babies aged 6-12 months with malnutrition divided into two groups (intervention and control group). This research was carried out for 3 months. Results showed that stimulation of baby massage is effective in increasing mean IGF-1 levels for malnourished baby aged 6-12 months, namely the average IGF-1 level in the pre-intervention group for baby massage by 1.37 ± 1.00, showed a significant increase (p = 0.003). Whereas in the control group showed a significant increase (p = 0.001) with the average IGF-1 pretreatment level was 3.37 ± 8.15. The results of the case and control group analysis showed significant differences in mean IGF-1 levels (p = 0.002) or (p &lt;0.05). Baby massage is effective in increasing nutritional status and IGF-1 in baby aged 6-12 months. Babies’ Mother and health provider are recommended to apply baby massage to improve nutritional status of malnourished babies.

Dysglycemia in patients with Acromegaly and Cushing’s syndrome

Introduction: Acromegaly and Cushing’s syndrome are endocrine disorders associated to frequent metabolic abnormalities. The aim of our study was to assess the prevalence of prediabetes and overt diabetes in patients presenting with acromegaly and Cushing’s syndrome and to find the association between glucose intolerance, age, gender, sex, body mass index, the level of activity of the disease and the duration of symptoms. Patients and methods: This is a retrospective and descriptive review of patient records presenting acromegaly and Cushing’s syndrome. Seventy-eight patients were included. Patients were grouped into normoglycemic and dysglycemic based on fasting blood glucose and hemoglobin A1C. Data of age, sex, gender, levels of fasting blood glucose and hemoglobin A1C were reviewed before and after treatment of acromegaly or Cushing’s syndrome. Results: Major risk factors for dysglycemia included: a mean age of 43 years in acromegaly and 28.6 years in Cushing’s syndrome patients, a male predominance in acromegalic patients and female predominance in Cushing’s syndrome ones, body mass index and duration of disease was higher in dysglycemic Cushing’s syndrome patients. Mean IGF-1 levels were higher among the dysglycemic than normoglycemic acromegalic patients. A decrease in mean HbA1c after surgical or medical treatment was also noted in both patients with Cushing’s syndrome and acromegaly. Conclusion: Dysglycemia in the form of prediabetes and diabetes are frequently observed in patients with acromegaly and hypercortisolism. Early diagnosis of glucose metabolism abnormalities in the course of the disease can decrease complications. Treatment modalities have varied impacts on glucose metabolism.

Real-world experience with pasireotide-LAR in resistant acromegaly: a single center 1-year observation

ContextPasireotide-LAR, a second-generation somatostatin receptor ligand (SRL), is recommended for patients with acromegaly as second-line treatment. Its efficacy and safety were assessed in clinical trials; however, the real-world evidence is still scarce.ObjectiveThe aim of this study was to evaluate the impact of 1-year treatment with pasireotide-LAR on disease control and glucose metabolism in acromegaly patients resistant to first-generation SRLs.DesignA single-center prospective study.MethodsTwenty-eight patients with active acromegaly or acrogigantism on first-generation SRLs following ineffective pituitary surgery were switched to treatment with pasireotide-LAR 40 or 60 mg i.m. every 28 days. To assess the efficacy of the treatment GH and IGF-1 levels were measured every 3 months. Safety of treatment was carefully evaluated, especially its impact on glucose metabolism.ResultsComplete biochemical control (GH ≤ 1 ng/mL and IGF-1 ≤ 1 × ULN) was achieved in 26.9% of patients and partial + complete response (GH ≤ 2.5 ng/mL and IGF-1 ≤ 1.3 × ULN) in 50.0% of patients. Mean GH level decrease was the largest within first 6 months (P = 0.0001) and mean IGF-1 level decreased rapidly within the first 3 months (P < 0.0001) and they remained reduced during the study. Blood glucose and HbA1c levels increased significantly within 3 months (P = 0.0001) and stayed on stable level thereafter. Otherwise, the treatment was well tolerated and clinical improvement was noticed in majority of patients.ConclusionsThis real-life study confirmed good effectiveness of pasireotide-LAR in patients resistant to first-generation SRLs. Pasireotide-LAR was overall safe and well tolerated, however significant glucose metabolism worsening was noted.

Real-World Experience With Pasireotide Lar in Acromegaly Resistant to First-Generation Somatostatin Analogs: A Single Center 1-Year Observation

Introduction: First generation somatostatin analogs (SSAs) are the treatment of choice in persistent acromegaly after transsphenoidal surgery. However, they are effective in 25% to 45 % of patients and a second generation SSA - pasireotide LAR may be a more effective alternative. Aim Our aim was to evaluate the impact of 1-year treatment with pasireotide LAR on disease control and on glucose metabolism in patients with acromegaly after debulking surgery resistant to first-generation SSAs. Material and methods In this single-center prospective study 29 consecutive patients with resistant acromegaly were treated with pasireotide LAR. The initial drug dose was 40 mg i.m. every 28 days. If patient did not achieve biochemical control (GH <2.5 ng/mL and IGF-1 ≤ULN for age and sex) at month 3, the dose was increased to 60 mg i.m. every 28 days. Assessment (GH, IGF-1, glucose, HbA1c) was performed at month 3, 6, 9 and 12. Results: In total, 22 patients (10 females, 12 males) completed a 1-year treatment. Mean age was 41.8±13.8 years. Twelve patients (54.5%) were ≤ 40 years old (including 6 (27.3%) patients of age ≤30 years). At baseline, mean IGF-1 level was 2.3 (SD 0.7) x ULN (age- and sex-specific) (583.9 ng/mL; SD 182.2) and mean GH concentration was 3.9 (SD 2.8) ng/mL. Both values decreased significantly after 1 year of treatment (P<0.001). Pasireotide LAR dose was increased to 60 mg in 16 (72.7%) patients and decreased to 20 mg in one patient patient due to worsening of diabetes control. The magnitude of mean GH level decrease was the largest within first 6 months (mean change from baseline: -1.75 ng/mL, 95% CI: -2.64, -0.85, P=0.0006). Mean IGF-1 level decreased rapidly within the first 3 months (mean change from baseline: -153.20 ng/mL, 95% CI: -203.20, -103.19, P<0.0001) and remained low during 12-month follow-up. GH level ≤ 1 ng/mL and ≤2.5 ng/mL was achieved by 7 (31.8%) and 17 (77.3%) patients, respectively. Six patients (27.3%) achieved normal IGF-1 level (IGF-1 ≤1 x ULN) (P=0.0275). IGF-1 ≤1.3 x ULN was observed in 11 (50.0%) of patients. Full biochemical control (GH ≤1 ng/mL and IGF-1 ≤1 x ULN) was achieved in 3 (13.6%) patients. Pasireotide LAR treatment resulted in significant increase of mean fasting glucose level: 119.2 (SD 17.3) vs. 107.5 (SD 13.9) mg/dL, P<0.001. The largest change was observed in first 3 months, and it remained stable until month 12. HbA1c level also increased significantly during first 3 months and stayed on similar level during follow-up (mean for month 12: 6.3 (SD 0.6) vs. 5.9 (SD 0.5) % at baseline, P<0.001). Conclusions: Pasireotide LAR is an effective treatment in most patients with persistent acromegaly after surgical debulking resistant to first generation SSAs. The largest increase of glycemia occurs during first 3 months of treatment and it remains stable afterwards.

Pegvisomant as Monotherapy or Combination Therapy in Somatostatin Refractory Acromegaly

Abstract Background: Pegvisomant, a growth hormone antagonist, has been widely used as monotherapy or combination therapy with somatostatin (SST) analogs and/or dopamine agonists in acromegaly poorly controlled by SST analogs. Limited information is available to compare pegvisomant monotherapy, combination with SST analogs or dopamine agonists, and combination of all three agents. Method: In this retrospective cohort study, we identified 23 patients with SST analog refractory acromegaly who received pegvisomant as monotherapy or in combination with SST analogs and/or dopamine agonists through the Research Patient Data Registry. We divided the patients into four groups: Group 1. pegvisomant alone (n=8); Group 2. pegvisomant plus a SST analog (pasireotide, octreotide or lanreotide) (n=8); Group 3. pegvisomant plus cabergoline (n=5) Group 4. Pegvisomant plus SST analog and dopamine agonist (n=2). We analyzed the changes in IGF-1, HbA1C, ALT and AST, blood pressure, and radiographic tumor size before and 6 months after treatment. Results: In 6 months, the mean IGF-1 level (ng/ml) changed from baseline 482 to 290 and decreased by 40% (P = 0.050) in group 1, changed from baseline 623 to 291 and decreased by 53% (P= 0.003) in group 2, changed from baseline 579 to 367 and decreased by 36% (p = 0.100) in group 3, and decreased 47% from 609 to 326 (P= 0.100) in group 4. The mean systolic blood pressure (mmHg) before and 6 months after treatment changed from 139 to 128 (p = 0.001) in group 1, changed from 130 to 126 (p = 0.553) in group 2, changed from 134 to 126 (p = 0.373) in group 3, and changed from 125 to 127 (p= 0.700) in group 4. Diastolic blood pressure (mmHg) changed from 82 to 76 (P = 0.110) in group 1, changed from 79 to 76 (p = 0.325) in group 2, changed from 80 to 74 (p=0.002) in group 3, and changed from 80 to 75 (p=0.126) in group 4. There were no significant changes in ALT and AST and A1C before and 6 months after treatment in all groups. In terms of radiographic tumor size change before and 6 months after the treatment, there was no change in tumor size in 5 of 5 patients in group 1. In group 2, the tumor size in 4 of 7 remained unchanged but 3 of 7 patients had increased tumor sizes. In group 3, there was no change in tumor size in 3 of 3 patients. In group 4, there was no change in tumor size in 2 of 2 patients. Conclusion: Our results suggest that in somatostain analog refractory acromegaly, combination pegvisomant and a SST analog significantly decreased IGF-1 level although decrease in IGF-1 in pegvisomant monotherapy almost reach statistical significance (P = 0.050). Although there was a trend in decrease of blood pressure in all groups, the decrease reached significant significance in systolic blood pressure in group 1 and diastolic blood pressure in group 3. Finally, except group 2, the tumor size remained unchanged.

Sodium glucose cotransporter 2 inhibitors treatment in acromegalic patients with diabetes-a case series and literature review.

Diabetes mellitus (DM) represents one of the most frequent comorbidities in patients with acromegaly. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent an important class for diabetes management. However, limited data is reported regarding the use of this class in patients with acromegaly and diabetes. Reporting data regarding patients with acromegaly and diabetes under treatment with SGLT2i. 29 acromegalic patients with diabetes were identified. Treatment with SGLT-2i was documented in nine patients, out of them 5 females and 4 males with a mean age (SD) of 61 ± 12 yr. The mean (SD) duration of treatment with SGLT2i was 27.5 ± 7.3 months. Mean HbA1c before and after SGLT-2i initiation was 8.1 ± 1.1 and 7.0 ± 0.9% respectively. Mean IGF-1 level (SD) before SGLT-2i initiation was 177 ± 68 ng/mL and the mean GH level (SD) was 0.7 ± 0.5 µg/L. All nine patients are still under treatment with SGLT2i and none of them had reported any adverse reaction related to SGLT2i. The present article provides us for the first time with new data regarding the use of SGLT2i among acromegalic patients with diabetes.

Insulin-like Growth Factor 1 and Prolactin Levels in Chimpanzees (Pan troglodytes) Across the Lifespan.

As human and chimpanzee genomes show high homology for IGF1 and PRL, we analyzed the sera of 367 healthy chimpanzees obtained during routine physical examinations in a single colony and measured chimpanzee insulin-like growth factor (IGF)-1 and prolactin (PRL) levels across the lifespan using standard human immunoassays. Assuming chimpanzee IGF-1 levels peak during puberty as in humans, we randomly defined puberty as the age at which most IGF-1 levels were equal to or above the 90th percentile for each sex (males, ages ≥7.00 but <9.20 years; females, ≥5.00 but <8.00 years). IGF-1 levels steadily increased at a similar rate in juvenile males and females and peaked in puberty, strongly correlating with age, then slowly decreased faster in adult males than in adult females. As a group, males had a higher mean IGF-1 level than did females, but comparison by age category showed similar mean IGF-1 levels in males and females. PRL levels increased with age in females more than in males and levels were twice as high in females than in males. One pubertal male reported to have short stature had lower IGF-1 and weight compared with other males in the age group, confirming suspected growth hormone deficiency; a second male of normal height but low IGF-1 may have had delayed puberty. Overall, results show that differences in IGF-1 levels over the lifespan in this cohort of chimpanzees largely mimic those seen in humans, while patterns of PRL changes are less similar.

The Relationship Of Insulin‑Like Growth Factor 1 With Bone Mass In Obese Female

This study aimed to analyze the relationship of insulin-like growth factor 1 with bone mass in obese female. This study used a cross sectional study method using 30 obese women aged 19-23 years, body mass index (BMI) 25-35 kg / m2, normal blood pressure, normal resting heart rate (RHR), normal hemoglobin (Hb). and fasting blood glucose (FBG) &lt;100 mg / dL. Measurement of IGF-1 levels used the Enzym Link Immunosorbent Assay (ELISA) method. Measurement of bone mass using TANITA (Body Composition Analyzer DC3607601 (2) -1604 FA, TANITA Corporation of America, Inc., USA). The data analysis technique used the Pearson product-moment test with Statistical Package for Social Science (SPSS). The results showed that mean levels of IGF-1 (1.17 ± 0.10) ng / mL and bone mass (2.49 ± 0.06) kg (r = 0.712, P ≤ 0.001). Our findings suggest that there was a positive correlation between IGF-1 levels and bone mass

An IGF-1 Levels Decrease in SOPK-RI Model Mice After A Low-Carb Diet

The aim of this study is to analyze the IGF-1 levels decrease in mice modeled by Polycystic Ovary Syndrome Insulin Resistance post carbohydrate high in protein. True Experimental Design with a Posttest Control Group Design research using 36 tails, female Wistar Rattus Norvegicus Strains, 3 months, 100-200 grams and randomly divided into 3 groups, namely K-(n =12, negative control group), K+(n=12, positive control group) and KP(n=12, treatment group). SOPK-IR modeling is done by mice in the injection of the hormone testosterone provionate at a dose of 100 mg/kg BW for 28 days, on the last day after injection a vaginal swab is performed to identify the condition of diestrus. The measurement of IGF-1 levels used the Enzyme-Linked Immunosorbent Assay method. Data analysis techniques used ANOVA test and LSD post hoc test. The results obtained mean levels of IGF-1 at K- (234.126±32.568) ng/mL, K+ (169.662±30.150) ng/mL, KP (146.528±29.562) ng/mL (p=0.000)

Serum DHEA-S levels could be used as a comparable diagnostic test to assess the pubertal growth spurt in dentofacial orthopedics

BackgroundPubertal growth spurt assessment guides the timing of intervention for correcting the skeletal discrepancies in dentofacial orthopedics. Serum hormones are being studied for the skeletal age assessment to avoid unnecessary radiographic exposure. The present study is to evaluate the relationship of serum hormones dehydroepiandrosterone-sulfate (DHEA-S), insulin-like growth factor (IGF-1), and cervical vertebral stages (CS stages) in the skeletal age assessment of orthodontics patients around the circumpubertal age.MethodsA total of ninety subjects with age ranging from 7 to 21 years were selected and divided into two groups based on the sex (45 males, 45 females). They were further distributed in each group based on the six CS stages determined from the lateral cephalogram. Blood samples from each subject were collected to evaluate the serum DHEA-S and IGF-1 levels by using the enzyme-linked immunosorbent assay (ELISA). Collected data were analyzed in SPSS software with a test of normalcy, unpaired t test, and one-way analysis of variance (ANOVA) followed by the least significant difference (LSD) post hoc comparison test and univariate regression analysis.ResultsThe highest mean serum hormone levels were found in CS 4 in group A (male) and CS 3 in group B (female). ANOVA results showed that there was a significant difference in the serum hormone levels among the different CS stages in both the groups for both the hormones. Statistically, a significant difference was found between each CS stages for both the hormones except in the DHEA-S levels between CS 5 and CS 6.ConclusionsThe mean serum DHEA-S levels followed a typical pattern from the CS 1 till CS 6 which was comparable and similar to the mean serum IGF-1 levels in respect to CS stages. Thus, serum DHEA-S levels could be used as a possible diagnostic test for the assessment of the skeletal pubertal growth spurt in dentofacial orthopedics.

MON-303 Giant Growth Hormone Secreting Pituitary Adenomas: A Single Institution Case Series

The prevalence of growth hormone (GH)-secreting pituitary adenoma is around 11-13% of all pituitary adenomas. Giant GH-secreting pituitary adenomas (≥ 4 cm) are rare tumors, and its prevalence of among acromegalic patients is <5%.This is a retrospective cohort study including patients with giant GH-secreting pituitary adenomas. The study population consisted of 10 patients (5 M/5 F). The mean age at diagnosis was 33.0±12.9 yrs (11-55 yrs). The mean delay between first symptom onset and diagnosis was 2.9 years. The most frequent symptoms were acral enlargement and facial changes (80%), followed by headache (70%) and visual deterioration (50%). One patient had epilepsy. Amenorrhea was presented in three females but obvious galactorrhea in two. The mean adenoma diameter was 42.6±4.7 mm (40-51 mm) at diagnosis. The vast majority of adenomas presented suprasellar extension (100%) or cavernous sinus invasion (80%). Cystic adenomas accounted for 50%. At presentation, mean GH and IGF-1 levels were 40.0±21.4 ng/mL (14.8-51.0) and 2.62±1.09 x ULN (1.08-3.96), respectively. Six patients presented with PRL cosecretion. At diagnosis maximal tumor diameter was not correlated with GH or IGF-1 levels.All patients underwent pituitary surgery as first-line treatment. Three cases were treated with an endoscopic approach and four cases with a microscopic approach. Transcranial approach was also employed in three cases. Postoperative mean GH and IGF-1 levels were 14.9±16.1 ng/mL (0.6-51.0) and 2.25.±0.82 x ULN (1.48-3.74), respectively. After first surgery, only one patient had more than 50% reduction in IGF-1 levels. Five patients (50%) underwent repeat surgery on two to three procedures because remission was not achieved. Postoperative somatostatin receptor ligands (SRLs) were used by all patients. Six patients were treated with dopamine agonist in combination with SRL. Six patients (60%) received postoperative radiotherapy.The mean follow-up period was 12.6±5.3 yrs (4-21 yrs). The mean GH and IGF-1 levels were 1.47±1.54 ng/mL (0.08-5.25) and 0.73±0.44 x ULN (0.08-1.56), respectively at the last visit. Residual adenoma was present at the last MRI in eight patients (mean diameter 9.0±3.6 mm). Panhypopituitarism rose from 10% at baseline to 30% at the last visit. During follow-up, one patient diagnosed breast cancer, while another diagnosed thyroid papillary cancer.Giant GH-secreting pituitary adenomas can have a clinically aggressive behavior with mass effect. Moreover, treatment in patients with giant GH-secreting pituitary adenoma is complex and multimodal therapy is necessary.

Gender differences and temporal trends over two decades in acromegaly: a single center study in 112 patients.

To evaluate the impact of gender and year at surgery on clinical presentation and postoperative outcomes in acromegaly. Retrospective review of patients operated between 1994 and 2016 to compare presentation and outcomes in groups defined by gender and year of surgery. Kaplan-Meier survival analyses with a composite endpoint (recurrence, reoperation, and radiation) were used for gender comparison and Youden indices for biochemical remission rates changes during study period. Primary indications for evaluation were phenotype, neurological symptoms, incidentaloma, hypogonadism, and galactorrhea. At surgery, men (N = 54) were younger (43.6 ± 12.7 years) than women (N = 58, 48.7 ± 12.3, P = 0.04). Male:female ratios before and after age 50 were 1.4 and 0.6 respectively. Men had higher mean IGF-1 levels (874 ± 328 vs 716 ± 296, P < 0.01) and smaller tumors (1.8 ± 1.3 cm vs 2.3 ± 1.5, P = 0.04). Postoperative remission rates were comparable (51% men, 56% women) and inversely associated with cavernous sinus invasion and GH levels. Women had longer mean follow-up (5.2 ± 3.4 years vs 3.6 ± 3.6 men, P = 0.02) and longer endpoint-free survival (P < 0.01). At last follow-up, 89.6% women and 70% men had normal IGF-1 levels (P = 0.03). Postoperative remission rates were higher in patients operated after February 15, 2011 (67.35 vs 43.5% previously, P = 0.01). In late vs early surgery group, physical changes as main indication for screening decreased (54 vs 30%, P < 0.01), while incidentaloma and hypogonadism increased. Median GH levels were lower in late vs early surgery group (P = 0.03). We demonstrate gender-specific characteristics and an evolving spectrum of clinical presentation with implications for earlier diagnosis and personalized management of acromegaly.

SUN-LB074 Racial Distribution, Presentation and Outcome in Acromegaly and Cushing's Disease: A Tertiary Referral Center Study in 220 Patients

Background: Transsphenoidal surgery (TSS) is the primary therapy for acromegaly (ACM) and Cushing’s disease (CD) with superior outcomes at high-volume centers. According to the U.S. Central Brain Tumor Registry, African Americans (AA) have higher incidence of pituitary adenomas than non-Hispanic white (W) patients, but race-specific data in ACM and CD are not available. Our aims are to evaluate racial distribution, presentation, and long-term outcomes of adult patients who underwent TSS for these conditions at our pituitary center by a single dedicated neurosurgeon. Methods: We reviewed all cases of TSS operated between 1994-2016 and compared presentation and postoperative events (biochemical remission, recurrence, reoperation, radiation, and death) across racial demographic groups. For patients living in Metropolitan Atlanta, we used U.S. Census data to compare patient racial distribution to the demographics. Results The ACM group consisted of 112 patients (54 men and 58 women), of whom 87 were W and 13 AA. Age and gender were similar in AA and W. Main reasons for referral were physical changes (23% AA vs 44% W), headaches (38% AA vs 17% W), and pituitary incidentaloma (31% AA vs 14% W). AA had higher rates of diabetes (54% vs 16%, p 0.005) and hypertension (69% vs 42% p 0.08), lower mean IGF-1 levels (662±324 ng/ml vs 823±321 ng/ml, p 0.06), and lower median GH levels (8.6. vs 45 ng/ml p 0.002). Mean tumor diameter and cavernous sinus invasion were similar. Biochemical remission at 3 months (46% AA and 55% W) and event-free survival during follow-up (median 3.8 years) were similar in AA and W. Normal IGF-1 at last follow-up was achieved by 92% AA and 80%W after multimodality therapy. The CD group consisted of 108 patients (15 men and 93 women) of whom 70 were W and 24 AA. Age, gender, and prevalence of diabetes and hypertension were similar in AA and W. Mean urinary cortisol and ACTH levels were similar. Mean tumor diameter was similar but AA had more macroadenomas (33% AA vs 14% W). During follow-up (median 4.3 years), event-free survival was similar although AA had fewer recurrences (4.35% vs 22.0% W, p 0.06). Of the total 220 operated patients, 88% lived in Georgia and 59% in Metropolitan Atlanta. In the latter group, W represented 75% of ACM and 62% of CD patients; AA 16% ACM and 28% CD; Hispanics (H) 0% ACM and 6.5% CD; Asian 8.2% ACM and 3% CD. Census racial distribution during study period was 58-67% W, 33-34% AA, 7-10% H, and 3-5% Asians. Conclusions To our knowledge, this is the first report of race-specific patient characteristics in CD and ACM. Proportion of AA and H with ACM operated at our tertiary referral center was lower than expected, while such disparity was not seen in CD. In addition AA with ACM exhibited different clinical presentations and milder biochemical activity. Notably, the long-term outcomes of patients with ACM and CD treated at our center were similar in AA and W. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SAT-451 Acromegaly and Thyroid Cancer

Introduction Acromegaly is associated with higher morbidity and mortality due to malignant neoplasms. However, data on the incidence and evolution of thyroid cancer in acromegaly is controversial. Objectives: To describe the clinical and biochemical characteristics of a group of acromegalic patients with differentiated thyroid carcinoma (DTC). Identify any predicting factor for DTC evolution. Analyze risk of recurrence (RR), initial response to treatment and response at the end of follow-up (RFU), comparing the outcomes with non-acromegalic patients with DTC. Patients and methodsRetrospective, multicenter study of 16 acromegalic patients with DTC. Acromegaly control or remission was defined with an IGF-1 ≤1 ULN with or without medical treatment (MT) respectively. AJCC Staging System 8th Edition was used for TNM staging, and the initial RR, initial response and RFU were defined according to ATA Guidelines 2015. As a control group, 56 patients with DTC without acromegaly were selected. Statistical analyses were done using SPSS Statistics 2.0. Results Median age of patients at the diagnosis of acromegaly was 44 years (range 12-69). Delay in diagnosis of acromegaly was a median of 2.5 years (range 0.5-10). Basal mean IGF-1 level was 3.2 ± 1.2 xULN. Surgery was performed in 85.7%. Post surgically, the best mean IGF-1 was 1.24 ± 0.34 xULN. Control with MT was achieved in 80%, with a median time to control since diagnosis of 21 months (6-132). Mean age at CDT diagnosis was 46.5 years (18-69). No patient had personal history of cervical irradiation. Most patients (86.7%) had normal thyroid function tests At the moment of diagnosis of DTC 62.5% of the patients had active acromegaly, IGF-1 of 2.5 ± 1.4 xULN. Median time from CDT diagnosis to acromegaly control was 1 year (0.5-7). Mean DTC tumor diameter of the bigger lesion was 13.7 ± 7.4 mm, being multifocal in 40% of the cases. All were papillary carcinoma, one case an aggressive variety. In 6/15 lymph node dissection was done, 50% with metastasis. One patient had distant metastasis. Radioiodine ablation was given to 87.5%, mean dose 115 ± 64.5 mCi. Twelve of the patients were stage I, 3 stage II and 1 IVb. Initial RR was low in 14/16, intermediate in 1 and high in 1 patient. RFU was: 13/15 with no evidence of disease, 1 patient with biochemical incomplete response and 1 with structural incomplete response, on average at 47.7 ± 33.3 months of FU. No statistically significant correlations were found between characteristics of the acromegalics and DTC outcomes. When comparing response on FU between acromegalics and controls no statistically significant differences were found. Conclusions The acromegalics with DTC had a low initial RR, that could be related to an early diagnosis of DTC (anticipated bias). We did not find any predisposing factor for unfavorable evolution. When comparing with the control group, we can conclude that DTC in acromegaly does not have a worse evolution.

Serum Insulin Like Growth Factor-1– A Skeletal Maturity Indicator for the Assessment of Orthopedic Treatment Timing of Skeletal Class II Malocclusion

Orthodontic treatment planning decisions are dependent on the assessment of growth status. Skeletal maturity could be assessed with various radiologic and non-radiologic biologic markers.The purpose of our study was to investigate the reliability of serum Insulin like Growth Factor – 1(IGF-1) as a skeletal maturity indicator in comparison to the stages in cervical vertebral maturation (CVM). Twenty five subjects with skeletal class II malocclusion in the age range of 11-19 years were recruited for the study. The cervical vertebrae staging was assessed by lateral cephalograms. Blood was collected aseptically and serum was separated. The serum levels of IGF- 1 were quantitatively assessed using a commercial ELISA kit, IGF-1 600 ELISA (DRG Instruments GmbH, Germany). There was a significant decline in the mean IGF-1 levels with increase in age in both the sexes. Statistically significant difference was observed in the concentration of IGF-1 among the different age groups. There was a significant decline in the mean IGF-1 levels with increase in CVM staging from stage 2 to stage 4. IGF-1 could be a more reliable biologic skeletal maturity indicator in comparison to cervical vertebral maturity indicator and thus could predict more accurately the growth status of the mandible to facilitate correction of skeletal class II jaw discrepancies.