Nadir GH Levels Research Articles

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

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

Post-surgery Quality of Life in Patients with Acromegaly Using SF36 Quality of Life Questionnaire-prospective Study

Introduction: Acromegaly is chronic progressive disease with multisystem involvement characterised by an excess secretion of growth hormone and increased circulating insulin like growth factor 1 concentration.Aims and Objectives: To assess surgical outcome of acromegaly patients at tertiary care institute using SF 36 quality of life questionnaire. SF-36 scores comprise 3 components: the physical component summary (PCS), the mental component summary (MCS) and role-social component summary (RCS).30 acromegaly patients admitted in Guwahati medical college were enrolled in study and followed up post operatively for surgical remission. All participants completed the SF-36 preoperatively, 1 year and 2 years postoperatively.Material and Method: Out of 30 patients 6 patients had surgical remission post operatively on the basis of postoperative glucose suppressed GH Level done after 12 weeks. Preoperatively subscale scores (physical functioning, role physical, general health) which were below the set standards for the normal population show significant postoperative improvements along with mental health (MH) scores. Similarly, PCS, MCS and RCS scores changed significantly after surgery. We also compared the QOL of 6 patients whose peak GH level was &lt; 0.4 µg/L during postoperative oral glucose tolerance testing with those patients whose nadir GH level was ≥ 0.4 µg/L. There was significant difference between partial and complete remission group in subscale score role physical, social function and mental health. Similarly, PCS and RCS score significantly different in partial and complete remission group than MCS score.Conclusions: QOL is considerably reduced in patients with acromegaly compared to general population which improves significantly after surgical treatment. Patients achieving the new remission criteria had significant improvement in physical and social components than those who did not.

Prognostic value of nadir GH levels for long-term biochemical remission or recurrence in surgically treated acromegaly.

Outcome of acromegaly surgery is assessed by IGF-1 and glucose-suppressed GH, but whether the latter provides additional clinically relevant information when IGF-1 is normal is unclear. The role of GH suppression testing after surgery requires clarification. We studied 97 acromegaly patients with normal IGF-1 after surgery by measuring GH after oral glucose longitudinally, initially at ≥ 3months after surgery and repeated one or more times ≥ 1year later. Nadir GH was categorized as normal or abnormal relative to the 97.5th percentile of nadir GH in 100 healthy subjects, which were ≤ 0.14µg/L (DSL IRMA) or ≤ 0.15µg/L(IDS iSYS). Signs and symptoms scores and insulin resistance were followed longitudinally. Of 68 patients with initial normal GH suppression 63 (93%) remained in remission and of 29 with initial abnormal GH suppression, 9 (31%) recurred. Recurrence was more common in patients with abnormal suppression (P < 0.001). A total of 14 patients recurred, including 5 with normal GH suppression progressing to abnormal and then recurrence. Overall, serial signs and symptoms and insulin resistance assessments did not identify patients with abnormal suppression or recurrence. Risk of recurrence after surgery is increased for patients with a normal IGF-1 level, but abnormal GH suppression. We newly find, using both our and others' cut-offs, that while normal suppression predicts long-term remission in most patients, some can progress from normal to abnormal suppression and then recurrence after many years of follow up. Nadir GH levels are of prognostic value in acromegaly patients with normal IGF-1 levels after surgery.

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

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

SAT-436 Adjuvant Therapeutic Modalities in Acromegaly: Clinical Course and Factors Predicting Biochemical Controls

Background Although surgical resection is the first line therapy for acromegaly, many patients do not achieve biochemical remission after surgery and require the adjuvant therapy including medical treatment (somatostatin analogues; SSA, GH antagonist, and dopamine agonist), conventional radiotherapy, and gamma-knife surgery (GKS). Due to the limitations of rare disease, there are few studies evaluating the efficacy of each adjuvant treatment. In this study, we investigated clinical course and disease control after initiation of adjuvant treatment. Method We performed a single-center retrospective study including acromegalic patients treated with SSA at least for 6 months from January 1, 2005 to June 30, 2018. Age, gender, fasting GH, IGF-1 levels, 75 g oral glucose tolerance tests and tumor size were measured before/after operation, medical treatments, or radiotherapy. The patients were considered biochemically controlled/cured if fasting mean GH levels were less than 2.5ng/ml or nadir GH after oral glucose loading was less than 1 ng/ml together with age- and sex-matched normalized IGF-1. Result We analyzed 72 patients for median 62.9 months (40.0-111.5). The median age was 46 (37-53) years. The median duration of SSA use was 31.5 months (12.6-53.0). The median GH level was 30.5 (17.6-47.3) ng/ml, IGF-1 was 694.7 (600.0-862.8) ng/ml, initial tumor size was 24 (17.2-32.2) mm. Of 72 patients, 59 patients (81%) underwent surgical resection and 40 patients (55.6%) underwent GKS. Of the 40 patients who underwent GKS, 16 (40%) discontinued the medication after 26 (10.3-35.2) months. After treatment, 54 patients (75%) were biochemically controlled. Before initiation of SSA treatment, biochemically controlled group had significantly lower GH (3.63 vs 15.35ng/ml, p<0.001), IGF-1 (514.0 vs 641.9ng/ml, p=0.005), nadir GH after oral glucose loading (2.66 vs 7.9ng/ml, p<0.001) and basal glucose level (94.5 vs 104.5g/ml, p=0.098) than non-controlled group. There was no significant difference in tumor size and Hardy classification between biochemically controlled group and non-controlled group. Among the enrolled patients, 34 subjects (52.3%) had a size reduction of more than 10%. A group with a decrease in tumor size by more than 10% had a smaller initial tumor size (20.0 vs 29.5mm, p<0.001) and lower GH level (3.30 vs. 5.05 ng/ml, p=0.033). There was no significant difference in IGF-1, nadir GH, and basal glucose level. Conclusion In conclusion, basal GH level and presence of visible remnant tumor was correlated with biochemical response after adjuvant treatment. Appropriate adjuvant treatment should be decided according to the disease status of acromegalic patients.

Clinical Characteristics of Acromegalic Patients With Paradoxical GH Response to Oral Glucose Load.

A paradoxical GH response to oral glucose (OG) is often found in acromegaly. However, the clinical characteristics of patients with acromegaly and a paradoxical GH response to OG (OG responders) remain unclear. The aim of the present study was to define the clinical characteristics of OG responders with acromegaly. Retrospective study. Hospitalized care at Osaka University Hospital. Of 63 patients with acromegaly admitted to our hospital from January 2006 to January 2017, 19 were classified as OG responders and 44 as nonresponders. The clinical characteristics of these groups were compared. Before surgery, OG responders had substantially greater IGF-1 SD scores than nonresponders (P < 0.05), although no difference was found in basal GH levels between the two groups (P = 0.46). Regarding glucose metabolism, 120-minute plasma glucose and immunoreactive insulin after OG administration and hemoglobin A1c were significantly greater in OG responders than in nonresponders (P < 0.01, P < 0.05, P < 0.05, respectively). GH levels during octreotide or bromocriptine testing were decreased more significantly in OG responders than in nonresponders (P < 0.05, P < 0.05, respectively). The proportion of pituitary tumors with hypointensity on T2-weighted MRI was significantly greater in OG responders than in nonresponders (P < 0.05). The difference in IGF-1 and parameters of glucose metabolism described disappeared between the two groups after surgery. The paradoxical GH response reflected the clinical characteristics, especially IGF-I level, glucose metabolism, and drug efficacy in acromegaly. A paradoxical GH response, in addition to the nadir GH levels, to OG load is potentially useful for evaluation of the clinical characteristics of acromegaly.

Presurgical treatment with somatostatin analogues in growth hormone-secreting pituitary adenomas: A long-term single-center experience

ObjectiveAcromegalic patients with macro- or giant adenomas often had poor prognosis after surgery. Somatostatin analogues (SSAs) show high effectiveness in both tumor shrinkage and serum GH reduction. But the role of SSAs in pre-surgical treatment and the management among macro- and giant adenomas remains controversial. Patients and MethodsA total of 100 acromegalic patients with macro- or giant adenomas that underwent surgery in our institution between January 2010 and December 2016 were enrolled in the current retrospective study. The relationships between several potential parameters and surgical outcomes were further analyzed. ResultsThe overall long-term remission rate was 45% accompanied by gross total resection (GTR) rate of 44%. GTR (adjusted OR = 16.346; p = .001) and nadir GH level on OGTT 7 days after surgery (GH-7, adjusted OR = 0.660, p = .039) showed predictive significance for remission after surgery. Tumor size and invasiveness as well as cavernous sinus invasion were risk factors for residual tumor. For invasive macro- or giant adenomas, 6 of 15 patients achieved long-term remission with SSA pre-treatment whereas none of the 18 patients without any preoperative treatment was endocrine controlled. ConclusionsAcromegalic patients did not gain more benefits from SSAs pretreatment. But, pre-treatment with SSA could be recommended to patients with invasive macro- or giant adenomas for significant improvement in long-term remission. GTR and GH-7 could be significant predictors in postoperative management of macro- or giant adenomas.

Postoperative Gamma Knife Radiosurgery for Cavernous Sinus-Invading Growth Hormone-Secreting Pituitary Adenomas.

We aimed to determine the long-term effects of Gamma knife radiosurgery (GKS) on remnants in the cavernous sinus (CS) after transsphenoidal surgery (TSS) for acromegaly and to identify its possible adverse effects. Thirty patients who had remnant tumors only inside the CS after TSS and who consequently underwent GKS were included. They were followed for a median period of 47 months after GKS with regular hormonal and radiologic examinations. The mean tumor volume and margin dose irradiated by GKS was 3.7 cm3 and 26.2 Gy, respectively. Radiologic tumor control was identified in all patients, and no tumor regrowth or recurrent tumors were identified. For 14 patients who achieved endocrinologic remission, the median duration from GKS until remission was 35 months. The actuarial rates of remission at 2, 5, and 10 years were 7.1%, 43.6%, and 65.6%, respectively. The degree of decrease in the nadir GH level in the OGTT at 6 months after GKS was a statistically significant predictor of remission. Newly developed hypopituitarism frequently developed in a time-dependent manner. Radiation necrosis developed in 4 patients with relatively large remnant volumes. GKS is an effective adjuvant treatment option for remnant tumors inside the CS after TSS. Maximal surgical resection, leaving minimal volume of remnants only inside the CS, allows the safe and sufficient delivery of a radiation dose to tumors, thereby increasing the possibility of remission. However, the risk of new hypopituitarism and radiation necrosis should be considered when tumors inside the CS are treated with GKS.

Utility of baseline serum phosphorus levels for predicting remission in acromegaly patients.

High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively. Patients were classified into two groups according to their plasma P levels; P ≤ 4.5mg/dl (Group-1, n: 23, 45.1%), P>4.5mg/dl (Group-2, n: 28, 54.9%). Two groups were compared according to remission status; remission (n: 27) and non-remission (n: 24). Remission was defined with absence of clinical symptoms, normal plasma IGF-1 (adjusted for age and gender) and GH levels (<1 mcg/dl) at least 3 months after initial treatment. Serum P levels decreased significantly after treatment in both groups (p < 0.001). There was a significant correlation between baseline phosphorus levels and remission rates, nadir GH in OGTT, pituitary adenoma size and Ki-67 scores (p = 0.001, r: -0.51; p = 0.01, r: 0.44; p = 0.001, r: 0.52; p = 0.02, r: 0.71, respectively). Mean baseline P levels were significantly higher in patients with non-remission (4.8 vs 4.2, P < 0.001). Logistic regression analysis did not reveal an independent effect on remission with any of these risk factors. High serum P levels may be an indicator for a low likelihood of onset of remission in acromegaly patients. Further studies with wider spectrum are needed to make specific suggestions.

Changes in quality of life in patients with acromegaly after surgical remission &amp;mdash; A prospective study using SF-36 questionnaire

Patients with acromegaly have a compromised quality of life (QOL). Modern surgical techniques have improved the surgical cure rate. However, there are no prospective studies reporting postoperative changes in QOL among patients cured solely by surgery. The aim of the present study was to determine the effect of surgery on QOL using the 36-item short form health survey (SF-36) questionnaire. SF-36 scores comprise 3 components: the physical component summary (PCS), the mental component summary (MCS) and role-social component summary (RCS). Included in this prospective cohort were 41 patients with acromegaly who underwent surgery alone and achieved postoperative normalization of insulin-like growth factor-1. All participants completed the SF-36 preoperatively and 1 year postoperatively. Preoperatively, RCS and 4 subscale scores (role physical, social functioning, role emotional, mental health) were below the set standards for the normal population. Postoperatively, the PCS and RCS scores did not change significantly, but the MCS score improved significantly (from 48.1 ± 11.3 to 51.7 ± 8.9, p=0.03). Further we compared the QOL of 26 patients whose nadir GH level was < 0.4 μg/L during postoperative oral glucose tolerance testing (complete remission group) with that of 15 patients whose nadir GH level was ≥ 0.4 μg/L (partial remission group). There were no significant differences between these groups in terms of PCS, MCS, RCS, or any subscale scores. In conclusion, surgical remission mostly improved the participants' mental condition. There was no difference in QOL between patients who achieved the new remission criteria and those who did not.

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

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

Analysis of IGF(CA)19 and IGFBP3-202A/C gene polymorphisms in patients with acromegaly: association with clinical presentation and response to treatments.

IGF1 and IGFBP3 gene polymorphisms have been recently described. However, their potential role in the setting of acromegaly and its outcome is unknown. In this study, we analyze these polymorphisms in patients with acromegaly and investigate their association with clinical presentation and response to treatments. A retrospective observational study was conducted in patients with acromegaly to analyze IGF1 and IGFBP3 gene polymorphisms. A total of 124 patients with acromegaly (57.3% women, mean age 44.9±13.1 years old) were followed up for a period of 11.4±8.0 years in eight tertiary referral hospitals in Spain. Clinical and analytical data were evaluated at baseline and after treatment. IGF1 and IGFBP3 gene polymorphisms were analyzed using PCR and specific primers. Baseline laboratory test results were GH 19.3 (8.0-39.6) ng/ml, nadir GH 11.8 (4.1-21.5) ng/ml, and index IGF1 2.65±1.25 upper limit of normal. Regarding the IGF1 gene polymorphism, we did not find any association between the number of cyto-adenosine (CA) repeats and patients' baseline characteristics. Nevertheless, a trend for higher nadir GH values was observed in patients with <19 CA repeats. Regarding the IGFBP3 polymorphism, the absence of an A allele at the -202 position was associated with a higher baseline IGF1 and a higher prevalence of cancer and polyps. There were no differences in response to therapies according to the specific genotypes. Polymorphisms in the IGF1 and IGFBP3 genes may not be invariably determinant of treatment outcome in acromegalic patients, but they may be associated with higher nadir GH levels or baseline IGF1, and determine a higher rate of colorectal polyps and cancer.

Stereotactic Gamma Knife Radiosurgery is Effective for the Treatment of Acromegaly

Objective: To assess the effectiveness of Gamma Knife (Elekta, Stockholm, Sweden) radiosurgery for acromegaly. Study Design: Retrospective. Patients/material and Methods: Data was collected from 35 patients in eight regional centers, via the UK National Acromegaly Register. All patients had neurosurgery and a perfexion Gamma Knife was used for radiosurgery at one institution (Sheffield, United Kingdom). The mean peak dose was 53 Gy. Results Biochemical: Of 35 patients, 66% achieved a normal age and sex-adjusted IGF-1 at median follow-up of 65 months after Gamma Knife. Of 30 patients tested, 72% achieved controlled (<2.5 µg/L) nadir GH level, median follow-up of 60 months; of these patients 35% (n = 8) were also receiving medical therapy. The mean IGF-1 before and after Gamma Knife was 777 and 436 µg/L, respectively (p = 0.015). Mean GH level before Gamma Knife in 24 patients was 5.62 µg/L and after was 1.25 µg/L (p = 0.0051). The probability of control of IGF-1 and GH levels did not correlate with dose of radiation delivered. Radiological: Post Gamma Knife MRI demonstrated pituitary tumor size unchanged or reduced in 100% of 24 patients at median follow-up of 50.5 months. Endocrine Side Effects: A total of 17% (6/35) developed new endocrine disturbances. Of these three were being treated with medical therapy. Other Side Effects: No patient suffered visual disturbance on follow-up. Conclusions: Gamma Knife radiosurgery for acromegaly is a safe and effective long-term adjunctive treatment.

Cavernous sinus invasion and effect of immunohistochemical features over remission in growth hormone secreting pituitary adenomas

We examined the cavernous sinus invasion and tumor biological markers that influence the remission rate. Cavernous sinus (CS) invasion was evaluated radiologically. Tumor biological markers consisting of the tumor cell growth parameter Ki-67 and the cancer cell vasculature marker of vascular endothelial growth factor (VEGF) were evaluated. We examined 28 immunohistochemically proven GH secreting pituitary adenoma patients who had been operated via endoscopic transsphenoidal surgery at Department of Neurosurgery, Kocaeli University Hospital between 2003 and 2008. Pathology preparations were stained with Ki-67 and VEGF. We evaluated remission at the postoperative 6th week. The basal GH level, nadir GH level and IGF-1 levels were evaluated to determine remission. Remission was achieved in 6 of 18 patients (33%) who had cavernous sinus invasion. Remission was achieved in 7 of 10 patients (70%) who did not have cavernous sinus invasion. There was no correlation between the Ki-67 proliferation index and cavernous sinus invasion (p=0.593). There was a positive correlation between VEGF expression and cavernous sinus invasion (p=0.03). The remission rate found less in the cavernous sinus invasion group. No association was found between Ki 67 proliferation index and cavernous sinus invasion. We found that a positive correlation between VEGF expression and cavernous sinus invasion. VEGF expression can therefore indirectly affect remission via cavernous sinus invasion.

Unusual presentation of acromegaly and functioning pituitary gonadotrophinoma (FSHoma)

Investigations: Endocrine profiling confirmed acromegaly on OGTToral glucose tolerance test (non-suppressed nadir GH level of 1.2 ug/L with basal GH level of 1.5 ug/L). IGF 1 level was elevated at 64 (9.5-45) nmol/L. There was significantly elevated FSH level of 107.2 (1-10.1) U/l with LH 1.2 (1.5-6.3) U/l and testosterone 9.3 (8-29) nmol/l. The rest of pituitary profiling was normal: Prolactin 370 (45375) mU/L, TSH 0.65 (0.35 to 5.5) mU/L, FT4 12.3 (10-19.8) pmol/L, normal short syn cthen test. US testes confirmed bilateral testicular enlargement: left testis measuring 46cc and right testis measuring 50c with no neoplastic changes. MRI pituitary demonstrated a large pituitary macroadenoma 3.5x 2.8 cm, with the expansion of pituitary fossa, compressing optic chaism and extending into left cavernous sinus.

GH deficiency in patients after cure of acromegaly by surgery alone

The aim of this study was to determine the frequency and characteristics of severe GH deficiency (sGHD) in patients after treatment of acromegaly by surgery alone. One hundred and eighty-six patients fulfilling the criteria for cure of acromegaly were examined by GH-releasing peptide-2 stimulation test or arginine stimulation test as well as oral glucose tolerance test (GTT). In addition, the Japanese adult hypopituitarism questionnaire was completed to determine the quality of life (QoL). sGHD was found in 17 patients (9.1%; the GH-deficient group), and not found in 169 patients (90.9%; the GH-sufficient group). There were no significant differences in preoperative serum GH levels, IGF1 levels, incidence of hyperprolactinemia, tumor volumes, or incidence of microadenoma between the two groups. Upon follow-up examination, IGF1 levels and Z-scores of IGF1 levels were significantly lower in the GH-deficient group than in the GH-sufficient group, whereas neither basal GH levels nor nadir GH levels during 75 g GTT were significantly different between the two groups. Moreover, sGHD patients had a substantially higher incidence of multiple pituitary failures (17.6 vs 2.4%) and dyslipidemia (60 vs 16.2%). sGHD patients had a substantially poorer condition-related QoL. This is the first large-scale, single-center, clinical study to evaluate sGHD in patients after cure of acromegaly by surgery alone. This study found that sGHD occurred in ~9% of patients and assessment of GHD by stimulation tests is critical after successful treatment of acromegaly by surgery.

Assessment of biochemical control of acromegaly during treatment with somatostatin analogues by oral glucose load and insulin-like growth factor I.

The use of oral glucose tolerance test (OGTT) in evaluating biochemical control in acromegalic patients on somatostatin analogues (SSA) has recently been questioned. To gain further insights into this topic, we analyzed basal and nadir GH levels during OGTT in acromegalic patients on SSA. Basal IGF-I and GH values, as well as GH levels along the test, were analyzed in 115 standard OGTT performed in 33 acromegalic patients followed up between 1993 and 2009. All patients were on SSA at the time of the study; 22 of them had previously undergone unsuccessful surgery. No patient had undergone radiotherapy. GH suppression was considered normal when the hormonal value fell to <1 μg/l during OGTT. Diagnostic accuracy was analyzed by receiver operating characteristic (ROC) curves. ROC analysis showed that the GH basal value yielding the best specificity (100%) was 3.9 μg/l. All patients with basal GH>3.9 μg/l displayed lack of GH suppression after OGTT and 80% also displayed high IGF-I. Conversely, patients with basal GH<3.9 μg/l presented a variable biochemical pattern with half of them failing to suppress GH after OGTT and 36.6% displaying high IGF-I levels. Our results show that baseline GH levels >3.9 μg/l are predictive of absent OGTT-dependent GH suppression; however, 20% of these patients display partial biochemical control (normal IGF-I levels). On the other hand, basal GH values <3.9 μg/l are not predictive of GH suppressibility by glucose and are often discordant with IGF-I levels.

Effects of Long-acting Release Octreotide on Glucose Homeostasis in Acromegaly Patients after Trans-Sphenoidal Surgery

The present study was aimed to investigate glucose homeostasis and insulin secretion in acromegalic patients during octreotide-long acting release (LAR) therapy and designed as an observational prospective study. 18 acromegalic patients who had undergone trans-sphenoidal surgery with active disease were included. All patients were treated with octreotide-LAR injection for 1 year. These patients received oral glucose tolerance test (OGTT) before, 21 days after, and 1 year after octreotide-LAR treatment. Primary outcomes were changes in glucose levels and insulin secretion during an OGTT. We also determined the differences between subjects with normalized and uncontrolled IGF-1 levels. Of the 18 patients treated with octreotide-LAR for 1 year, 89% achieved fasting GH levels <2.5 μg/l, 85% reached the nadir GH concentration <1 μg/l, and 61% achieved normal age- and sex-matched IGF-1 values. 21 days after one dose of octreotide-LAR injection, insulin response during OGTT significantly decreased, and the Matsuda index increased significantly. One year after octreotide-LAR therapy, most parameters of glucose homeostasis returned to baseline levels. However, insulin response during OGTT at 30 and 60 min, and the insulinogenic index were still significantly decreased. Compared with the IGF-1-normalized group, the IGF-1 uncontrolled group had the same fasting GH and nadir GH levels and a higher insulin AUC and total insulin secretion. During octreotide-LAR treatment, the early-phase insulin response to OGTT is reduced and plasma glucose levels remained normal in most patients. The IGF-1 uncontrolled group had the same fasting GH and nadir GH levels during OGTT, but had better glucose homeostasis.

Acromegaly: recent progress in diagnostics and treatment

Acromegaly is a serious disease with different complications leads to reduced life expectancy and increase mortality. Only early diagnosis and modern methods of management of disease lead to remission. According to consensus on criteria for cure of acromegaly (2010) the measurement of GH and age-matched total IGF-I concentrations are the most important biochemical variables for the diagnosis of acromegaly and for monitoring progression or treatment response. The optimal disease control is now defined as IGF-I level in the age – adjusted normal range, random GH levels less than 1,0 µg/liter and nadir GH level during OGTT less than 0,4 µg/liter. MRI with use a contract substance is the best method of adenoma visualization. The trassphenoidal surgery with new technologies (endoscope, intraoperative blood sampling, neuronavigation, intraoperative MRI), radiosurgery, modern medical treatment (multiligand long-acting somatostatin analogs, GH receptor antagonist) are effective modalities for treatment of acromegaly, which elaborated last decades.

Growth hormone nadir during oral glucose load depends on waist circumference, gender and age: normative data in 231 healthy subjects

(i) To analyse the predictors of GH suppression after standard glucose load (oGTT) in the healthy population and (ii) to establish the 97th percentile of GH nadir post-oGTT according to these variables. Design Analytical, retrospective. GH nadir after oGTT. Two hundred and thirty-one healthy subjects (113 women, 118 men 15-80years) were studied. The GH nadir after glucose load ranged from 0·01 (<assay detection limit) to 0·65 μg/l was higher in women and was inversely correlated with age, BMI, waist circumference, waist/hip, total cholesterol, triglycerides, basal and maximal glucose and basal insulin levels and directly correlated with basal GH levels, IGF-I SDS and HDL-cholesterol (P values ranging 0·004-<0·0001). On multistep regression analysis, the best predictors of nadir GH levels were waist circumference (t = -9·64, P < 0·0001), gender (t = -3·86, P = 0·0001) and age (t = -3·63, P = 0·0003). The results of comparative analysis among subjects grouped according to these variable showed different results in GH nadir in premenopausal women with waist circumference ≤88 cm (97th percentile 0·65 μg/l), in premenopausal women with waist circumference ≤88 cm and in men of any age with waist circumference ≤102 cm (97th percentile 0·33 μg/l) and in subjects of either gender and any age with waist circumference >88 cm in women and 102 cm in men (97th percentile 0·16 μg/l). CONCLUSIONS The results of this study show that GH nadir after oGTT should be analysed according to gender, menopausal status and waist circumference. The GH cut-off should be limited to the assay used.