Untreated Acromegaly Research Articles

8442 Successful Pregnancy in the Setting of Medically Untreated Acromegaly

8442 Successful Pregnancy in the Setting of Medically Untreated Acromegaly

Risk of Depression in Patients with Acromegaly in Korea (2006-2016): A Nationwide Population-Based Study.

An increased prevalence of depression has been reported in patients with acromegaly. However, most studies included a relatively small sample size owing to the rarity of acromegaly. We aimed to investigate the risk of depression in patients with acromegaly using the Korean National Health Information Database (NHID). The data of patients with acromegaly in 2006-2016 were collected from the rare incurable disease registry of the NHID. Patients with acromegaly were matched with control participants without acromegaly for age and sex in a 1:5 ratio. Patients who did not receive treatment for acromegaly had a significantly increased risk of depression [hazard ratio (HR): 1.43, 95% confidence interval (CI): 1.12-1.82]. However, the risk of depression did not increase in patients who received treatment for acromegaly. The multiple Cox regression analysis showed that the risk of depression was significantly higher in the untreated group than in the control group during the first three years of observation (HR: 1.829; 95% CI: 1.305-2.563). However, after a time lag of over 3 years, the risk of depression decreased in the untreated group, which is similar to that in the control group. Our nationwide study suggests that patients who did not receive treatment for acromegaly have a higher risk of depression compared with controls. The untreated acromegaly patients should be monitored for the development of depression, especially in the early years after diagnosis. These results could serve as a basis for developing screening strategies to mitigate depression in acromegaly patients.

PMON101 Fluctuating Insulin Requirements in Untreated Acromegaly: From 200-to-0

Abstract Introduction Acromegaly is a clinical disorder that occurs from autonomous production of growth hormone (GH). Diabetic ketoacidosis (DKA) is an uncommon and late complication of acromegaly. Acromegaly presenting in DKA prognosticates glycemic management with insulin-based regimens. Cessation of insulin therapy, however, can be achieved in patients with acromegaly after proper medical and/or surgical interventions. Our case highlights a unique outcome in a patient with newly-diagnosed acromegaly that initially presented in DKA with very high insulin requirements and was ultimately de-escalated off all anti-hyperglycemic therapy with significant glycemic improvement prior to any treatment for acromegaly. Clinical Case A 32 year-old male with a past medical history of colorectal cancer and no known history of diabetes presented to the emergency department for evaluation of generalized weakness, epigastric pain, nausea, and vomiting and was admitted for DKA. Hemoglobin A1c was 11.6% (reference range < 5.7%), confirming the diagnosis of newly-diagnosed diabetes. C-peptide was 1.4 ng/mL (reference range 0.5-3.3 ng/mL) and anti-glutamic acid decarboxylase, anti-islet cell, and anti-zinc transporter 8 antibodies were all negative. He was initiated on intravenous insulin infusion, with rates achieving > 200 units of insulin per day. Given severe insulin resistance in conjunction with acromegalic features on physical exam and a unique history of colorectal cancer at a young age without any family history, evaluation for acromegaly was initiated. Human GH level was 68.60 ng/mL (reference range 0.05-3.00 ng/mL) and insulin-like growth factor-1 (IGF-1) level was 1,036 ng/mL (reference range 82-242 ng/mL). MRI brain revealed a hypoenhancing 1.3 cm lesion enlarging the left lateral pituitary gland. Diagnosis of acromegaly due to a GH-secreting macroadenoma was established. The patient was discharged on a high-dose insulin regimen in addition to metformin therapy with de-escalation off of all anti-glycemic therapy within a few weeks of diagnosis; at his 3 month follow-up visit, his repeat hemoglobin A1c was 6.1 with repeat GH level of 28.8 ng/mL and IGF-1 level of 1602 ng/mL, despite not yet undergoing any treatment for the underlying condition. Conclusion DKA as an initial presentation of acromegaly has been previously reported in literature, however, not with a concomitant history of colon cancer. Moreover, no previous cases of acromegaly have reported glycemic normalization off of anti-hyperglycemic therapy prior to any treatment for acromegaly. Our case highlights that evaluation for secondary causes, including acromegaly, should be considered in patients with severe insulin resistance and emphasizes the dramatic range of insulin requirements that patients with acromegaly may have. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

The evaluation of changes in maxillofacial bones using cone beam tomography in acromegaly.

Background The aim of the study was to evaluate the changes in craniofacial dimensions of newly diagnosed and untreated acromegaly patients, patients with non-functional pituitary adenoma and healthy individuals on Cone Beam Computed Tomography (CBCT).Material and Methods 50 newly diagnosed acromegaly patients who did not receive any treatment for acromegaly were included in the study (Group A). Twenty patients with nonfunctional pituitary adenoma (Group B) and 30 healthy individuals were included (Group C). Linear, angular and volumetric measurements were performed.Results Mandibular length showed significant difference in acromegaly patients, and maxillar length statistically significant difference was found between the A-B and B-C (p> 0,05), no difference was found between the A-C (p<0,05). SNB and ANB angle was statistically different in all groups, while SNA angle was statistically different between group A-C and B-C. In volumetric measurements, a statistically significant difference was found between groups a-c and groups A-B (p< 0,05), no difference was found between groups B-C (p>0,05).Conclusions CBCT measurements showed that mandibular volume and length were increased in the acromegaly group compared to the group B-C. Present study is the first research that compares acromegaly patients in respect to changes in maxillofacial dimensions. Key words:Acromegaly, pituitary adenoma, maxillofacial bones, cone beam computed tomography.

The Beta-Cell Function and Glucose Profile of Newly Diagnosed Acromegalic Patients with Normal Glucose Tolerance.

Objectives Untreated acromegaly is a nature model for unveiling the diabetogenic effects of GH. CGMS can uncover more glucose profile of acromegaly. This study aimed to evaluate the insulin resistance (IR), β-cell function, and glycemic spectrum of patients with newly diagnosed acromegaly with normal glucose tolerance (NGT). Methods This study was conducted in Huashan Hospital from January 2015 to February 2019. Eight newly diagnosed acromegalic patients without history of diabetes and eight age- and gender-matched healthy subjects were enrolled. All participants underwent oral glucose tolerance test (OGTT) and 72 h continuous glucose monitoring (CGM). Parameters on β-cell function and IR were calculated. Mean blood glucose (MBG) in 24 hours was adopted for the evaluation of the glycemic level, and standard deviation of blood glucose (SDBG) and mean amplitude of glycemic excursion (MAGE) were used for glucose fluctuation. Results HbA1c in the acromegaly group was significantly higher than in the control. During OGTT, glucose peaked at 60 min in acromegaly and at 30 min in controls. After glucose load, the acromegaly group had significantly higher insulin levels than controls, especially in 120 min and 180 min. Both insulin sensitivity index and disposal index after glucose load of acromegaly were significantly lower than those of controls. Moreover, acromegalic subjects had significantly higher MBG than controls. Conclusions The newly diagnosed acromegalic patients with NGT were characterized by IR and impaired β-cell function after glucose load. CGM showed that MBG of NGT acromegaly patients was higher than that of normal people.

Prevalence of Abnormal Glucose Metabolism in Acromegaly &amp; Impact of Treatment Modalities on Glucose Metabolism

Objective: To determine the frequency of diabetes mellitus impaired glucose tolerance and impaired fasting glucose in Pakistani patients with acromegaly and to establish the impact of the intervention (surgery/ medical) on glucose metabolism.Methods: Eighty-nine patients fulfilling the endocrine society criteria for acromegaly diagnosis were included. A data of baseline, growth hormone (GH), Insulin-like growth factor-1 (IGF-1) level, Hemoglobin A1C (HbA1C), fasting blood glucose (FBG), and random blood glucose (RBS) levels were reviewed before and after the intervention (surgery/medical therapy). Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were defined based on the 2003 ADA criteria. Patients were grouped into normoglycemic (NGT) and dysglycemic (IFG, IGT, and DM) based on FBS, RBS, and HbA1C. Results: Major risk factors for dysglycemia included age (15-45 years), male sex (33.70%), obesity (45.7%), and macroadenoma (76%). Both mean GH levels (58.29 vs. 54.36 ng/dl) and IGF-1 levels (862.98 vs. 824.32 ng/dl) were higher among the normoglycemic than dysglycemia. Pre-surgery, NGT, IFG, IGT, IFG, and IGT combined and DM were found in 48.31, 5.61, 1.1, 5.61, and 39.32 % of the subjects, respectively. Post-surgery, HbA1C improved in 79.5%, deteriorated in 6.8%, and remained the same in 13.6%. Similarly, it improved in 67.4.7% post-medical therapy. Both FBS and RBS improved post-surgery and medical therapy. Further, the number of anti-diabetic drugs used also decreased post-surgery. Conclusion: Dysglycemia is more common among patients with acromegaly as compared to the general population and tends to be poorly controlled in untreated acromegaly. Glycemic control improves significantly after the surgery and medical therapy.Keywords: Acromegaly, Diabetes Mellitus, Transsphenoidal surgery

The association between treatment and systemic inflammation in acromegaly

ObjectiveAcromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. DesignEx vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. ResultsCirculating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. ConclusionsAcromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

Patterns of Abnormal Glucose Metabolism in Acromegaly and Impact of Treatment Modalities on Glucose Metabolism

Background: Chronic exposure to high levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) leads to metabolic complications, most importantly dysglycemia in the form of diabetes mellitus and pre-diabetes. Dysglycemia if diagnosed early in the course of the disease can decrease complications. Treatment modalities in the form of surgery and medical therapy have varied impacts on glucose metabolism.Objective: To determine the frequency of diabetes mellitus, impaired glucose tolerance, and impaired fasting glucose in Pakistani patients with acromegaly and to establish the impact of the intervention (surgery/medical) on glucose metabolism.Methods: This study was a retrospective review of patient records. Eighty-nine patients fulfilling the Endocrine Society criteria for acromegaly diagnosis were included. A data of baseline, GH, IGF-1 level, hemoglobin A1C (HbA1C), fasting blood glucose (FBG), and random blood glucose (RBS) levels were reviewed before and after the intervention (surgery/medical therapy). Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were defined based on the American Diabetes Association (ADA) criteria. Patients were grouped into normoglycemic (NGT) and dysglycemic (IFG, IGT, and DM) based on FBG, RBS, and HbA1C.Results: Major risk factors for dysglycemia included age (15-45 years), male sex (33.70%), obesity (45.7%), and macroadenoma (77.52%). Both mean GH levels (58.29 vs. 54.36 ng/dl) and IGF-1 levels (862.98 vs. 824.32 ng/dl) were higher among the normoglycemic than dysglycemia. Pre-surgery NGT, IFG, IGT, IFG, and IGT/DM combined were found in 48.31%, 5.61%, 1.1%, 5.61%, and 39.32% of the subjects respectively. Post-surgery, HbA1C improved in 79.5%, deteriorated in 6.8%, and remained the same in 13.6%. Similarly, it improved in 67% post-medical therapy. Both FBG and RBS improved post-surgery and medical therapy. Further, the number of anti-diabetic drugs used also decreased post-surgery.Conclusion: Dysglycemia is more common among patients with acromegaly as compared to the general population and tends to be poorly controlled in untreated acromegaly. Glycemic control improves significantly after surgery and medical therapy.

Neuromuscular Blockade Correlates with Hormones and Body Composition in Acromegaly.

Tumor resection is the first-line therapy for acromegaly patients. In some cases, unsatisfactory intraoperative neuromuscular blockades (NMBs) lead to failed operations. The purpose of this study was to investigate and quantify the NMB status of acromegaly patients and explore the relationship between NMB status and hormone levels and body composition. Twenty patients with untreated acromegaly and seventeen patients with nonfunctioning pituitary adenomas as controls were enrolled in this study. NMB was assessed using the train-of-four (TOF) technique with TOF-Watch® SX. The onset time of NMB, deep neuromuscular blockade duration (DNMBD), and clinical neuromuscular blockade duration (CNMBD) were monitored. We found a significantly longer onset time (110.25 ± 54.90 vs. 75.00 ± 27.56, s, p=0.017), shorter DNMBD (21.99 ± 5.67 vs. 34.96 ± 11.04, min, p < 0.001), and shorter CNMBD (33.26 ± 8.09 vs. 46.21 ± 10.89, min, p < 0.001) in acromegaly patients compared with the controls. DNMBD and CNMBD decreased in patients with decreasing body fat percentage and increasing growth hormone (GH) level, insulin-like growth factor 1 (IGF-1) level, and GH and IGF-1 burden. The onset time increased with increasing IGF-1 level and GH and IGF-1 burden. Taken together, a unique NMB status was identified in acromegaly patients with the following characteristics: prolonged onset time and shortened DNMBD and CNMBD. Changes in the levels and burdens of GH and IGF-1 and body composition were linearly correlated with intraoperative NMB in acromegaly patients.

Reversibility of Cardiac Involvement in Acromegaly Patients After Surgery: 12-Month Follow-up Using Cardiovascular Magnetic Resonance.

PurposeCardiac comorbidity is one of the leading causes of death among acromegaly patients. We aimed to investigate the reversibility of acromegalic cardiac involvement after surgical treatment using the gold standard method, cardiovascular magnetic resonance, and to explore the effects of endocrine remission and gender on reversibility.MethodsIn this single-center, prospective cohort study, fifty untreated acromegaly patients were enrolled. Comprehensive cardiac assessments were performed using a 3.0 T magnetic resonance scanner before and 3 and 12 months after transsphenoidal adenomectomy.ResultsPreoperatively, left ventricular (LV) enlargement (13.0%), LV systolic dysfunction (6.5%), right ventricular (RV) enlargement (4.3%), RV systolic dysfunction (2.2%) and myocardial fibrosis (12.0%) were identified. On average, the LV and RV ejection fractions of acromegaly patients were higher than the healthy reference values. Male patients had thicker LV myocardia, wider ventricular diameters and more dilated pulmonary artery roots than female patients. After surgery, LV myocardial hypertrophy was reversed, the left atrium was remodeled, and ventricular systolic dysfunction recovered to normal. Cardiac alterations were detected early in the 3rd postoperative month and persisted until the 12th month. The interventricular septum was initially thickened in the 3rd postoperative month and then recovered at the 12th month. Notable postoperative cardiac reversibility was observed in male patients but did not occur in all female patients. Patients achieving endocrine remission with normalized hormone levels had thinner LV myocardia than patients without normalized hormone levels.ConclusionOur findings demonstrated that some of the cardiac involvement in acromegaly patients is reversible after surgical treatment which lowers hormone levels. Endocrine remission and gender significantly impacted postoperative cardiac reversibility.

MANAGEMENT OF ENDOCRINE DISEASE: Does gender matter in the management of acromegaly?

Gonadal steroids modulate the effects of GH, with oestrogens attenuating and androgens augmenting GH action. Whether these divergent effects influence the clinical manifestation, management and prognosis of acromegaly have not been carefully reviewed. This review examines whether there is a gender difference in epidemiology, presentation, quality of life (QoL), morbidity, treatments and mortality of acromegaly. Acromegaly is more common in women who present at an older age with longer diagnostic delay. At presentation, women have a higher GH relative to IGF-1 level than men. QoL is more adversely affected in women both before and after treatment. Prevalence of hypertension and diabetes are greater in women than in men with acromegaly. Treatment outcomes with SSAs are comparable between sexes, but women may require a higher dose of pegvisomant for equivalent response. Mortality in untreated acromegaly is more profoundly affected in women; however, improved treatments in recent decades have resulted in normalisation of standard mortality ratios in both sexes. We conclude that gender does matter in the management of acromegaly, with women presenting later in life, with greater diagnostic delay, higher prevalence of comorbidities and experiencing worse QoL.

Changes in metabolic parameters and cardiovascular risk factors after therapeutic control of acromegaly vary with the treatment modality. Data from the Bicêtre cohort, and review of the literature.

Untreated acromegaly is associated with increased morbidity and mortality due to malignant, cardiovascular, and cerebrovascular disorders. Effective treatment of acromegaly reduces excess mortality, but its impact on cardiovascular risk factors and metabolic parameters are poorly documented. We analyzed changes in cardiovascular risk factors and metabolic parameters in patients receiving various treatment modalities. We retrospectively studied 96 patients with acromegaly, both at diagnosis and after IGF-I normalization following surgery alone (n = 51) or medical therapy with first generation somatostatin analogues (SSA, n = 23), or pegvisomant (n = 22). Duration of follow-up was 77 (42-161) months, 75 (42-112) months, and 62 (31-93) months, in patients treated with surgery alone, SSA, and pegvisomant, respectively. In all the cases except four, patients treated medically had underwent previous unsuccessful surgery. IGF-I normalization was associated with increased body weight, decreased systolic blood pressure (SBP) in hypertensive patients, decreased fasting plasma glucose (FPG) and HOMA-IR and HOMA-B levels, increased HDL cholesterol (HDLc); whereas, LDL cholesterol (LDLc) was not significantly different. Plasma PCSK9 levels were unchanged in patients with available values. Cardiovascular and metabolic changes varied with the treatment modality: surgery, but not pegvisomant, had a beneficial effect on SBP; FPG decreased after surgery but increased after SSA; the decline in HOMA-IR was only significant after surgery; pegvisomant significantly increased LDLc and total cholesterol; whereas SA increased HDLc and had no effect on LDLc levels. Treatments used to normalize IGF-I levels in patients with acromegaly could have differential effects on cardiovascular risk factors and metabolic parameters.

The posterior pharyngeal wall thickness is associated with OSAHS in patients with acromegaly and correlates with IGF-1 levels.

To evaluate the incidence of obstructive sleep apnea-hypopnea syndrome (OSAHS), explore the structural changes in pharyngeal soft tissue underlying OSAHS development and analyze the correlation between hormone levels and pharyngeal soft tissue changes in patients with untreated acromegaly. Twenty-five patients with untreated acromegaly were prospectively enrolled. Pituitary hormones were tested, sellar magnetic resonance imaging was confirmed, overnight polysomnography was conducted, and upper airway computed tomography was performed on these patients. Patients with untreated acromegaly had a high incidence of OSAHS (52.0%, 13/25). The average age of the patients with OSAHS was 12 years older than that of patients without OSAHS (47.0 ± 8.5 years vs. 35.1 ± 9.5 years, p = 0.003). The posterior pharyngeal soft tissues were thicker in four different planes, including the planes of the soft palate, uvula, tongue and epiglottis (p = 0.003, 0.008, 0.027, and 0.003, respectively), and the soft palate (p = 0.024) was more hypertrophic in patients with acromegaly presenting with OSAHS than patients without OSAHS. The posterior pharyngeal wall thickness (cm) positively correlated with the serum insulin-like growth factor 1 (IGF-1) level (ng/ml) in the planes of the soft palate (slope = 0.001, p = 0.006) and epiglottis (slope = 0.002, p = 0.039). OSAHS is a common complication in patients with untreated acromegaly, and advanced age is a risk factor. Posterior pharyngeal soft tissue thickening and soft palate hypertrophy are structural changes underlying OSAHS development in patients with acromegaly. Higher IGF-1 levels predict an increase in the posterior pharyngeal soft tissue thickness in patients with acromegaly.

Elevated serum IGF-1 level enhances retinal and choroidal thickness in untreated acromegaly patients.

1) To compare the retinal, choroidal, Haller's layer, and Sattler's/choriocapillaris thicknesses of untreated acromegaly patients without chiasm compression or diabetes mellitus and healthy controls. 2) To evaluate the correlations of retinal and choroidal thicknesses with serum growth hormone (GH) and insulin-like growth factor 1 (IGF) burden. This prospective, case-control study included 27 untreated acromegaly patients and 27 sex-matched and age-matched controls. Subfoveal choroidal, Haller's layer and Sattler's/choriocapillaris thicknesses were determined by enhanced-depth imaging optical coherence tomography (EDI-OCT). Foveal and macular retinal thicknesses were determined with SD-OCT. GH and IGF-1 burdens were defined as the product of disease duration and treatment-naïve serum GH and IGF-1 levels. Compared with healthy controls, patients with acromegaly exhibited significantly increased foveal retinal (p = 0.003), subfoveal choroidal (p < 0.001), and Haller's layer (p < 0.001) thicknesses, with no differences in Sattler's/choriocapillaris layer thickness. Multiple point measurements in the posterior pole area showed equally increased nasal and temporal parts of the choroid. The retinal thickness maps of the two groups did not significantly differ. Correlation analysis indicated that choroidal thickness was significantly correlated with disease duration (p = 0.01), serum IGF-1 level (p = 0.03) and IGF-1 burden (p = 0.009). No significant correlations were detected between choroidal thickness and GH burden (p = 0.44). Retinal thickness was not significantly correlated with any factor. The choroidal thickness of acromegaly patients was greater than that of healthy controls and was significantly correlated with disease duration, IGF-1 level and IGF-1 burden, indicating that excessive serum IGF-1 and its exposure time have a combined effect on choroidal thickness.

Pre- and Postoperative Body Composition and Metabolic Characteristics in Patients with Acromegaly: A Prospective Study.

Objective To investigate the preoperative body composition, metabolic characteristics, and postoperative changes in patients with active acromegaly and analyze the effects of gender and age. Methods We included 36 patients with untreated acromegaly and 37 patients with nonfunctional pituitary adenomas. Adipose tissue (AT), the visceral fat index (VFI), sclerotin, protein, skeletal muscle, total body water (TBW), intracellular water (ICW), and extracellular water (ECW) were measured using bioelectrical impedance analysis (BIA). Total energy expenditure (TEE) and basal metabolism (BM) were measured with a cardiopulmonary and metabolic analyzer (CMA). Tricep skinfold thickness (TST), bicep circumference, waistline, hipline, and calf circumference were measured with a skinfold caliper and tape. These indices were measured before surgery and 3 months and 1 year after surgery. Results Overall, AT, VFI, and TST were lower, whereas sclerotin, protein, skeletal muscle, TBW, ICW, ECW, TEE, and BM were higher in acromegaly patients. Postoperatively, TST rose initially and then decreased, the waistline increased, and sclerotin, skeletal muscle, TEE, and BM decreased. Changes in these indices differed with gender and age in unique patterns. Conclusions Body composition and metabolism in acromegaly patients changed after surgery, and gender and age influenced these changes.

High levels of IGF-1 predict difficult intubation of patients with acromegaly

PurposeTo investigate the characteristics of difficult intubation and identify novel efficient predictors in patients with acromegaly.MethodsPatients with either untreated acromegaly or non-functional pituitary adenomas were enrolled. Patients with acromegaly underwent hormone assays, upper airway computed tomography and magnetic resonance imaging examinations and preoperative overnight polysomnography. The modified Mallampati classification, mouth opening, neck circumference, and neck extension were assessed, and the Cormack-Lehane grades and the time of tracheal intubation were recorded.ResultsPatients with acromegaly had a higher incidence of difficult intubation (62.5%). The time of tracheal intubation was prolonged, the neck circumference was enlarged, and the neck extension was confined. In patients with acromegaly and difficult intubation, the insulin-like growth factor 1 levels and apnea/hypoxia index were significantly higher compared to patients without difficult intubation (1115.40 ± 253.73 vs. 791.67 ± 206.62 ng/ml, P = 0.020; 22.17 ± 23.25 vs. 2.47 ± 2.84, P = 0.026, respectively). The bilateral regression analysis revealed that high levels of insulin-like growth factor 1 were an independent risk factor for developing difficult intubation (p = 0.042, Exp B = 1.006). The modified Mallampati classification was positively correlated with apnea/hypoxia index and could be calculated using the following logarithmic equation: MMC = 0.2982 * ln (AHI) + 2.1836.ConclusionsIn patients with acromegaly, neck movement is confined, the time of tracheal intubation is prolonged, and the neck circumference is enlarged, and these patients suffer from an increased incidence of difficult intubation (62.5%) during anesthesia induction. The apnea/hypoxia index and insulin-like growth factor 1 levels are both increased in acromegalic patients with difficult intubation, and elevated insulin-like growth factor 1 levels are an independent risk factor of difficult intubation in acromegalic patients.

Muscle strength in patients with acromegaly at diagnosis and during long-term follow-up.

Patients with acromegaly have decreased body fat (BF) and increased extracellular water (ECW) and muscle mass. Although there is a lack of systematic studies on muscle function, it is believed that patients with acromegaly may suffer from proximal muscle weakness despite their increased muscle mass. We studied body composition and muscle function in untreated acromegaly and after biochemical remission. Prospective observational study. Patients with acromegaly underwent measurements of muscle strength (dynamometers) and body composition (four-compartment model) at diagnosis (n = 48), 1 year after surgery (n = 29) and after long-term follow-up (median 11 years) (n = 24). Results were compared to healthy subjects. Untreated patients had increased body cell mass (113 ± 9% of predicted) and ECW (110 ± 20%) and decreased BF (67 ± 7.6%). At one-year follow-up, serum concentration of IGF-I was reduced and body composition had normalized. At baseline, isometric muscle strength in knee flexors and extensors was normal and concentric strength was modestly increased whereas grip strength and endurance was reduced. After one year, muscle strength was normal in both patients with still active disease and patients in remission. At long-term follow-up, all patients were in remission. Most muscle function tests remained normal, but isometric flexion and the fatigue index were increased to 153 ± 42% and 139 ± 28% of predicted values, respectively. Patients with untreated acromegaly had increased body cell mass and normal or modestly increased proximal muscle strength, whereas their grip strength was reduced. After biochemical improvement and remission, body composition was normalized, hand grip strength was increased, whereas proximal muscle fatigue increased.

Gender dependence of serum soluble Klotho in acromegaly

In acromegaly, disease activity is biochemically assessed by growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. However, they are often discrepant, as several factors including gender influence their relationship. We recently found excessively high serum levels of soluble Klotho (sKl) in acromegalic patients, which depended on GH to a comparable extent as IGF-1. To further elucidate the relationship between GH and sKl, we examined the effect of gender on sKl in patients with untreated acromegaly. We determined GH, IGF-1 and sKl in sera of 62 consecutive patients with newly diagnosed acromegaly (31 females/31 males, aged 20-85 years). For their given GH excess at presentation with acromegaly, females had lower IGF-1 (490 ± 33 vs 604 ± 33 ng/ml, P = 0·02), but higher sKl [5171 ± 590 vs 3439 ± 431 pg/ml (mean ± SE), P = 0·02] levels than males. In multiple regression analysis, IGF-1 was closely associated with logGH (estimate 139, SE 47, P = 0·005) and BMI (estimate 14·2, SE 4·8, P = 0·005). sKl was closely associated with logGH (estimate 3088, SE 652, P = 0·0001) and gender (estimate 2034, SE 612, P = 0·002), and to a lesser extent with BMI (estimate 174, SE 66, P = 0·01). For a given GH status, sKl concentrations are higher and IGF-1 concentrations are lower in women than in men. GH is the strongest predictor for both sKl and IGF-1, but gender needs to be considered when using these parameters for monitoring acromegalic patients.

Complex Rhythmicity and Age Dependence of Growth Hormone Secretion Are Preserved in Patients With Acromegaly: Further Evidence for a Present Hypothalamic Control of Pituitary Somatotropinomas

Traditionally, acromegaly is viewed as a disease resulting from GH hypersecretion from an autonomous pituitary somatotropinoma. To test the hypothesis that GH secretion in acromegaly is still subjected to normal hypothalamic control, we studied the daily rhythmicity of GH secretion in normal controls and patients with newly diagnosed, untreated acromegaly. This was an observational inpatient study in the General Clinical Research Center at the University of Michigan. One hundred four normal controls and 67 acromegalic patients were included in the study. The intervention consisted of frequent blood sampling over 24 hours. We hypothesized that acromegalic patients would show rhythmicity, sexual dimorphism, and age-related decline of GH secretion similar to normal controls. Both normal controls and the patients exhibited 3 major GH waves with the highest values at 12:00 pm, 5:00 pm, and 1:00 am (P < .001 for all). Both controls and patients exhibited a clear appearance of the nocturnal GH waves, irrespective of the gender (P < .001 for all). The amplitude of the maximal (nocturnal) GH secretory wave (1:00 am) as compared with the nadir GH secretion (9:00 am) was clearly different between the 2 groups, with a significantly smaller magnitude in acromegaly (P < .001). A subsequent subanalysis of both groups was performed separately for both genders. Similar to the entire groups, both controls and patients exhibited a clear appearance of the nocturnal GH waves, irrespective of the gender (P < .001 for all). Patients with clearly elevated GH values have shown an age-related decline of GH secretion (r = -0.35, P < .001), similar to controls. The analysis of GH profiles in multiple patients with untreated acromegaly discloses the persistence of the hallmarks of the central control of GH regulation, ie, nictohemeral rhythmicity, sexual dimorphism, and an age-related decline of GH output.

Neurocognitive Function in Acromegaly after Surgical Resection of GH-Secreting Adenoma versus Naïve Acromegaly

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions.