Evaluation of Betatrophin, Chemerin, and Kisspeptin Levels in Acromegaly Patients.

Titration of growth hormone dose using insulin-like growth factor-1 measurements: Is it feasible in children?

Objective To observe the effectiveness of long-acting octreotide in the treatment of acromegaly patients who did not achieve biochemical control after neurosurgery or gamma knife therapy of growth hormone-secreting pituitary adenoma. Methods Six acromegaly patients who received long-acting octreotide treatment regularly were included. Five patients had received prior trans-sphenoidal surgery and 1 patient had received prior gamma knife therapy before admission. All patients were admitted monthly for evaluation of pituitary-target gland function and octreotide therapy. Data of treatment with octreotide for 6 months were retrospectively summarized. Results Symptoms were reported to be alleviated. Two patients achieved biochemical control of the disease. Two patients had fasting growth hormone level less than 2.5 μg/L, but insulin-like growth factor-1 (IGF-1) level was still higher than the age-adjusted normal range. Another 2 patients had decreased growth hormone and IGF-1 level, but both still higher than the normal range. Compared with baseline, IGF-1 level was decreased after treatment: (371.83 ± 217.46) μg/L vs. (713.33 ± 198.29) μg/L, and there was statistical difference (P= 0.017). There were no statistical differences in glycated hemoglobin and fasting plasma glucose before and after octreotide treatment (P > 0.05). Conclusions For acromegaly patients who do not achieve biochemical control after neurosurgery or gamma knife therapy, long-acting octreotide can effectively control IGF-1 level and increase the biochemical control rate of the disease. Key words: Acromegaly; Growth hormone-secreting pituitary adenoma; Octreotide; Insulin-like growth factor Ⅰ

Objective:Acromegaly is a chronic disease that causes high concentrations of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). GH and IGF-1 levels have important effects on bone homeostasis, bone turnover, and bone remodeling. The results of studies investigating the relationship between acromegaly and bone mineral density (BMD) are controversial. The aim of the current study was to evaluate BMD in newly diagnosed acromegaly patients and to determine the relationship between GH and IGF-1 levels with BMD.Materials and Methods:This cross-sectional study was conducted on 36 newly diagnosed acromegaly patients without a history of hypogonadism, whose BMD values can be obtained from the records of University of Health Sciences Turkey, Dışkapı Yıldırım Beyazıt Training and Research Hospital. The relationship between GH and IGF-1 levels and BMD measured from the femur and lumbar regions was examined separately.Results:The mean age of the patients was 46.2±12.5 years. Median IGF-1 and BH levels were 551 ng/mL and 8.2 ng/mL, respectively. While 58.3% of the patients had osteopenia, no osteoporosis was found in any patient. A positive correlation was found between the BMD value measured from the femoral neck and IGF-1 (r=0.484, p=0.036) and GH (r=0.595, p=0.007) levels. There was no significant correlation between BMD measurements evaluated from lumbar vertebrae and GH and IGF-1 levels.Conclusion:It was found that the increase in GH and IGF-1 levels in newly diagnosed eugonadal acromegaly patients increased BMD measured from the femur. There was no significant relationship between BMD measured from the lumbar region and GH and IGF-1 levels.

Serum phosphate: Does it more closely reflect the true state of acromegaly?

Discordance Between Gh and Igf-1 Levels in Turkish Acromegalic Patients

Evaluation of the insulin-like growth factors (IGF) IGF-I and IGF binding protein 3 in patients at high risk for breast cancer

Background: Acromegaly is a rare, chronic, systemic, and progressive disease characterized by an excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations, typically due to a macroadenoma in the pituitary gland. Both GH and IGF-1 are implicated in cancer promotion based on experimental and epidemiological data, but research findings remain conflicting and population-based data are scarce. Although there is a high mortality rate among acromegalic patients due to cardiovascular diseases, cancer is the third leading cause of death. Aim: The aim of the present study was to assess the risk of different types of cancer in acromegaly and the impact of changes in disease control and patient outcomes over time. Methods: Patients diagnosed with acromegaly at the Ankara University Ibn-i Sina Hospital Endocrinology and Metabolic Diseases Department between 2015 and 2019 were included in this study. Data including demographic data, history of cancer, size of adenoma (micro or macro), serum IGF-1 and GH levels at the time of diagnosis, serum prostate-specific antigen (PSA), thyroid ultrasonography, and, if needed, thyroid fine needle aspiration cytology (TFAC), colonoscopy, and mammography results were collected from patient records retrospectively. Results: We screened 83 patients, and 78 patients with the compensatory data (female/male: 39/39, 50%/50%) were included. The mean age of patients was 49.4 ± 11.9 years and 41.7 ± 12.1 years at the time of diagnosis. The median duration of follow-up was 72 (12-420) months. Periodic thyroid ultrasonography was performed in 65/78 (83.3%) of the patients, and a colonoscopy and mammography were also conducted in 27/78 (34.6%) and 32/39 (82%) of the patients at least once over the course of the disease, respectively. Cancer was detected in 17/78 (21.7%) of the patients; 11/78 (14.1%) of them had well-differentiated thyroid cancer and 2/39 (5.1%) had breast cancer. Prostate cancer, renal cell carcinoma, pancreatic cancer, malignant chordoma, schwannoma, and colon cancer were detected in one patient each. The increased cancer risk in acromegalic patients did not correlate with age, sex, age at diagnosis, time to diagnosing acromegaly, duration of acromegaly, GH and IGF-1 levels at diagnosis, pituitary adenoma size, or Ki-67 levels. Conclusions: Cancer was detected in 21.7% of the acromegaly patients, 14.1% of whom had well-differentiated thyroid cancer. In this study, we demonstrated that thyroid cancer is the most common malignancy in Turkish acromegalic patients, consistent with the results of previous studies. The increased cancer risk in acromegalic patients did not correlate with age, sex, age at diagnosis, time to diagnosing acromegaly, duration of acromegaly, or GH and IGF-1 levels at diagnosis.

Information about a real patient is presented in stages (boldface type) to expert clinicians (Dr Beckman), who respond to the information, sharing their reasoning with the reader (regular type). A discussion by the authors follows . Patient presentation: An 89-year-old woman presents to cardiology clinic with the concern of recurrent shortness of breath and dyspnea on exertion during the previous 6 months. Her symptoms are progressive such that she can no longer walk > 10 feet before becoming symptomatic. Previously, she was independent at home and able to climb stairs with groceries or laundry without difficulty. The patient reports dependent lower extremity edema, orthopnea, and paroxysmal nocturnal dyspnea, but neither chest pain, palpitations, diaphoresis, nor lightheadedness. Her medical history is significant for diabetes mellitus, hypertension, hyperlipidemia, and glaucoma. Her medications include insulin, lisinopril, losartan, furosemide, and pravastatin. She has no known medication allergies. The patient’s most recent medical history is notable for a new diagnosis of aortic stenosis now repaired by transcatheter valve replacement (TAVR). She underwent successful valve replacement; however, her hospital and immediate outpatient course were complicated by profound hyperglycemia requiring escalating doses of insulin and readmission to a local hospital. Furthermore, the patient’s dyspnea did not change appreciably after valve replacement, and she was hospitalized twice more with acute on chronic heart failure requiring intravenous diuresis. Before discharge, she was started on high doses of oral furosemide. Ongoing symptoms of heart failure despite TAVR prompted her primary care physician to refer her to a cardiologist at a tertiary care center. The patient’s initial examination showed an elderly appearing woman, sitting comfortably in a wheelchair with her son at her side. Her vitals in the office revealed a heart rate of 91 and blood pressure of 135/77. The patient’s head and neck examination showed a jugular venous pressure …

A Long-Term Follow-Up of 2 Cases of Subclinical Acromegaly.

Doses of the GH receptor (GHR) antagonist pegvisomant (PEGV) that normalize insulin-like growth factor 1 (IGF1) levels vary widely among acromegaly patients. Predictors for PEGV response are baseline IGF1 levels, sex, body weight and previous radiotherapy. A GHR polymorphism lacking exon 3 (d3-GHR) is frequent in the general population. The influence of d3-GHR on PEGV responsiveness in acromegaly is unclear. To assess the influence of d3-GHR on IGF1 levels and PEGV responsiveness in acromegaly patients using combined PEGV and long-acting somatostatin receptor ligand (LA-SRIF) treatment. Data were collected at the Rotterdam Pituitary Centre between 2004 and 2013. Patients with elevated IGF1 levels (>1.2 upper limit of normal; n=112) and over 6 months of high-dose LA-SRIF treatment were co-treated with PEGV. GHR genotype was assessed using genomic DNA in 104 patients. D3-GHR was observed in 51 (49.0%) of the patients (7.7% homozygous, 41.3% heterozygous) and was in Hardy-Weinberg equilibrium (P=0.859). Baseline characteristics were similar in d3-GHR and full-length (fl)-GHR genotypes. During PEGV/LA-SRIF treatment IGF1 levels were not different between d3-carriers and non-carriers. Similarly, no difference in PEGV dose required to normalize IGF1 (P=0.337) or PEGV serum levels (P=0.433) was observed between the two groups. However, adenoma size decreased significantly (>20% of largest diameter) in 25.6% of the fl-GHR genotype but only in 7.5% of d3-carriers (P=0.034, OR: 4.6 (CI: 1.1-18.9)). GHR genotype does not predict the IGF1 normalizing dose of PEGV in acromegaly patients using combination PEGV/LA-SRIF treatment. However, fewer d3-carriers showed significant reductions in adenoma size.

The aim of this work was to investigate the correlation between dynamic changes of serum insulin-like growth factor 1 (IGF-1), growth hormone (GH), neuroglobin (NGB), and neonatal behavioral neurological assessment (NBNA) scores in different periods in neonates with hypoxic ischemic encephalopathy (HIE). Sixty HIE patients in the Neonatal Department of our hospital were selected. They were divided into the mild group (35 cases), moderate group (19 cases), and severe group (six cases) according to the diagnostic criteria. During the same period, 18 neonatal patients born at term in our hospital were chosen as the control group. Data were analyzed by SPSS19.0 statistical software (SPSS Inc., Chicago, IL, USA). The dynamic changes of IGF-1, GH, and NGB in different periods, as well as NBNA scores in HIE patients and in the control group, were analyzed. Furthermore, we analyzed the degree of correlation of IGF-1, GH, and NGB in different periods as well as NBNA scores in HIE patients and in the control group. 1- IGF-1 levels between the three groups of HIE patients and control group had significant differences (p<0.05); 2- Comparing GH levels between the HIE experimental groups and control group, there was no statistical significance; 3-Comparing serum NGB levels between the three HIE experimental groups and control group, there were significant differences (p<0.05); 4- Comparing NBNA scores of the three groups of HIE patients and control group, there was a significant difference between the mild group and control group; 5- Serum IGF-1 and NBNA scores were positively correlated in the acute and recovery phase, while NGB level and NBNA scores were negatively correlated in the acute and recovery phase (p<0.05), which had statistical significance. In neonatal HIE, serum IGF-1, GH, and NGB levels change. IGF-1 and NGB levels correlate with the prognosis of HIE.

Body mass index and insulin-like growth factor 1 as risk factors for discordant growth hormone and insulin-like growth factor 1 levels following pituitary surgery in acromegaly

Background/Aim: Despite combined therapy consisting of surgery, external X-ray, and medical therapy, a significant number of acromegaly patients continue to have uncontrolled growth hormone (GH) secretion and active disease. These patients, particularly those with large or invasive tumors, require additional therapy to decrease their GH levels. Our aim was to investigate whether patients with documented GH-secreting pituitary adenomas leading to acromegaly would respond with attenuation of GH and insulin-like growth factor-1 (IGF-1) levels after treatment with a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist. Methods: We conducted prospective analyses in the Endocrinology Clinic of the Pamukkale University. Acromegaly patients who had active disease participated in two admissions: before and after 6 weeks of daily treatment with 8 mg of oral rosiglitazone. Four male and 3 female patients have completed the study. Basal and nadir GH levels during an oral glucose tolerance test were determined, and the IGF-1 and IGF-binding protein-3 levels were also measured both before and 6 weeks after the rosiglitazone treatment. Results: Treatment with rosigitazone did not reduce basal and nadir GH levels during the oral glucose tolerance test and the IGF-1 levels in the patient population as a whole (p > 0.05). Conclusions: The PPAR-γ activator rosiglitazone, used at maximum approved dosage, did not reduce plasma GH and IGF-1 levels in patients with acromegaly. Further studies with higher doses and longer duration of PPAR-γ agonist administration would be required to determine its usefulness in the treatment in this group of patients.

Despite improved supportive care, the mortality of sepsis and septic shock is still high. Multiple changes in the neuroendocrine systems, at least in part, are responsible for the high morbidity and mortality. A reduced circulating level of insulin-like growth factor and an elevated level of growth hormone are the reported characteristic findings early in the course of sepsis and septic shock in adults. The aim of this study was to evaluate the changes of growth hormone/insulin-like growth factor 1 axis in sepsis and septic shock and investigate the relationship between these hormones and survival. Fifty-one children with sepsis (S), 21 children with septic shock (SS) and 30 healthy, age- and sex-matched children (C) were enrolled in this study. Growth hormone, insulin-like growth factor 1 and cortisol levels of the sepsis and septic shock groups were obtained before administration of any inotropic agent. Growth hormone levels were 32.3 +/- 1.5 microIU/mL (range 4-56), 15.9 +/- 0.6 microIU/mL (range 11-28) and 55.7 +/- 2.7 microIU/mL (range 20-70) in S, C and SS groups, respectively. The difference between the growth hormone levels of the S and C groups, S and SS groups, and C and SS groups were significant (P < 0.001). Non-survivors (54.7 +/- 1.6 microIU/mL) had significantly higher growth hormone levels than survivors (29.4 +/- 1.5 microIU/mL) (P < 0.001). Insulin-like growth factor 1 levels were 38.1 +/- 2.1 ng/mL (range 19-100), 122.9 +/- 9.6 ng/mL (range 48-250) and 22.2 +/- 1.9 ng/mL (range 10-46) in the S, C and SS groups, respectively, and the difference between the insulin-like growth factor 1 levels of the S and C, S and SS, and C and SS groups were significant (P < 0.001). Non-survivors (8.8 +/- 1.1 micro g/dL) had significantly lower cortisol levels than survivors (40.9 +/- 2.1 microg/dL) (P < 0.001). We detected a significant difference between the levels of cortisol in non-survivors (19.7 +/- 1.8 microg/dL) and survivors (33.9 +/- 0.9 microg/dL) (P < 0.01). There were elevated levels of growth hormone with decreased levels of insulin-like growth factor 1 in children during sepsis and septic shock compared to healthy subjects. In addition, there were even higher levels of growth hormone and lower levels of insulin-like growth factor 1 in non-survivors than in survivors. We think that both growth hormone and insulin-like growth factor 1 may have potential prognostic value to serve as a marker in bacterial sepsis and septic shock in children. As there is insufficient data in the paediatric age group, more studies including large numbers of patients and additionally evaluating cytokines and insulin-like growth factor binding proteins are needed.

Role of the Growth Hormone/Insulin-like Growth Factor-1 Paracrine Axis in Rheumatic Diseases