Changes in acromegaly comorbidities, treatment, and outcome over three decades: a nationwide cohort study.

Objective: To study the time-dependent changes in disease features of Danish patients with acromegaly, including treatment modalities, biochemical outcome, and comorbidities, with a particular focus on cancer and mortality. Methods: Pertinent acromegaly-related variables were collected from 739 patients diagnosed since 1990. Data are presented across three decades (1990-1999, 2000-2009, and 2010-2021) based on the year of diagnosis or treatment initiation. Results: Adenoma size and insulin-like growth factor I (IGF-I) levels at diagnosis did not differ significantly between study periods. The risk of being diagnosed with diabetes, heart disease, sleep apnea, joint disease, and osteoporosis increased from the 1990s to the later decades, while the mortality risk declined to nearly half. The risk of cancer did not significantly change. Treatment changed toward the use of more medical therapy, and fewer patients underwent repeat surgeries or pituitary irradiation. A statistically significant increase in the proportion of patients achieving IGF-I normalization within 3-5 years was observed over time (69%, 83%, and 88%). The proportion of patients with three or more deficient pituitary hormones decreased significantly over time. Conclusion: Modern medical treatment regimens of acromegaly as well as increased awareness and improved diagnostics for its comorbidities have led to better disease control, fewer patients with severe hypopituitarism, and declining mortality in the Danish cohort of acromegaly patients. The risk of cancer did not increase over the study period.

The changing landscape of acromegaly - an epidemiological perspective.

Acromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an epidemiological perspective and describe the temporal evolution of the disease pertaining to epidemiological variables, clinical presentation and mortality. We present updated epidemiological data from the population-based Danish cohort of patients with acromegaly (AcroDEN), along with meta-analyses of existing estimates from around the world.Based on this, we conclude that the incidence, prevalence and age at acromegaly diagnosis are all steadily increasing, but with considerable variation between studies. An increased number of incidental cases may contribute to the increase in incidence and age at diagnosis, respectively. The clinical features at presentation are trending toward a milder disease phenotype at diagnosis, and advances in therapeutic options have reduced the mortality of patients with acromegaly to a level similar to that of the general population. Moreover, the underlying cause of death has shifted from cardiovascular to malignant neoplastic diseases.

The TRH test provides valuable information in the diagnosis of central hypothyroidism in patients with known pituitary disease and low T4 levels.

Objective: To evaluate the value of the thyrotropin-releasing hormone (TRH) test in the diagnosis of central hypothyroidism (CH) in patients with pituitary disease. Methods: Systematic evaluation of 359 TRH tests in patients with pituitary disease including measurements of thyroxine (T4), TBG-corrected T4 (T4corr), baseline TSH (TSH0) and relative or absolute TSH increase (TSHfold, TSHabsolute). Results: Patients diagnosed with CH (n=39) show comparable TSH0 (p-value 0.824) but lower T4corr (p-value <0.001) and lower TSH increase (p-value <0.001) compared to patients without CH. In 54% (42 of 78 cases) of patients with low T4corr, the CH diagnosis was rejected based on a high TSHfold. In these cases, a spontaneous increase and mean normalization in T4corr (from 62 to 73 nmol/L, p-value <0.001) was observed during the follow-up period (7.6 ± 5.0 years). Three of the 42 patients (7%) were started on replacement therapy due to spontaneous deterioration of thyroid function after 2.8 years. Patients diagnosed with CH reported significantly more symptoms of hypothyroidism (p-value 0.005), although, symptoms were reported in most patients with pituitary disease. The TRH test did not provide clinical relevant information in patients with normal T4 or patients awaiting pituitary surgery (78%, 281 of 359). There were only mild and reversible adverse effects related to the TRH test except for possibly one case (0.3%) experiencing a pituitary apoplexy. Conclusion: The TRH test could be reserved to patients with pituitary disease, low T4 levels without convincing signs of CH. Approximately 50% of patients with a slightly decreased T4 were considered to have normal pituitary thyroid function based on the TRH test results.

Sex difference in patients with controlled acromegaly-A multicentre survey.

OBJECTIVE: Active acromegaly is subject to sex differences in growth hormone (GH) and Insulin like growth factor 1 (IGF-I) patterns as well as clinical features but whether this also pertains to controlled disease is unclear. DESIGN: In a cross-sectional, multi-centre study, 84 patients with acromegaly (F = 43, M = 41), who were considered controlled after surgery alone (n = 23) or during continued somatostatin receptor ligand (SRL) treatment (n = 61), were examined. METHODS: Serum concentrations of GH, insulin, glucose and free fatty acid (FFA) were measured during an oral glucose tolerance test (OGTT) together with baseline serum IGF-I and completion of two HR-Qol questionnaires (acromegaly quality of life questionnaire [AcroQol] and Patient-assessed Acromegaly Symptom Questionnaire [PASQ]). RESULTS: The mean age at the time of the study was 57 (±1.1) years and the majority of females (were postmenopausal. Females had significantly higher fasting GH but comparable IGF-I standard deviation scores (SDS). Using fasting GH < 1.0 µg/L as cut off, disease control was less prevalent in females (F: 56% vs. M: 83%, p = .007) whereas a comparable figure was observed using IGF-I SDS < 2 (F:79% vs. M:76%, p = .71). Compared with males, female patients showed impaired AcroQol physical score (p = .05), higher fasting FFA (p = .03) and insulin concentrations during the OGTT (p = .04). CONCLUSION: In patients with acromegaly considered controlled, postmenopausal females exhibited higher GH levels than males despite comparable IGF-I levels, which also translated into impaired metabolic health and well-being. Our findings point to the relevance of including GH measurements in the assessment of disease control and suggest that disease-specific sex differences prevail after treatment.

The prevalence of acromegaly is higher than previously reported: Changes over a three-decade period.

OBJECTIVE: To study time-related changes in the prevalence and patient characteristics of acromegaly, as well as to assess the impact of changes in treatment on disease control. METHODS: A total of 107 patients with acromegaly were identified by healthcare registries and subsequently validated by patient chart review over a three-decade period (1992-2021). A systematic literature review focusing on the incidence and prevalence of acromegaly was performed identifying 31 studies. RESULTS: The prevalence of acromegaly significantly increased throughout the study period (R2 = 0.94, p < .001) and was 122 cases/106 persons in 2021 whereas the annual incidence remained constant at 4.6 cases/106 persons. The age at the first sign of acromegaly and the age at diagnosis significantly increased during the study period, whereas growth hormone and insulin-like growth factor I decreased. Incidentalomas constituted 32% of all cases diagnosed with acromegaly in the last decade. Primary surgery was used in 93% of all cases, and repeated surgery decreased from 24% to 10% during the three decades. The use of first-generation somatostatin analogues (21%-48%) and second-line medical treatment (4%-20%) increased with a concomitant improvement of biochemical disease control (58%-91%). CONCLUSION: The prevalence of acromegaly is higher than previously reported and the clinical presentation has shifted towards a milder phenotype. Modern treatment of acromegaly enables individualized treatment and disease control in the majority of patients.

Agreement between arterial and non-arterialised fingertip capillary blood gas and acid-base values.

Background: Arterial puncture is considered the gold standard for obtaining blood gas and acid-base values and facilitates the assessment of acutely and critically ill patients, as well as control of patients in long-term oxygen therapy (LTOT). Substitutional capillary sampling has been proposed, as researchers cite lower complication rates, physician independence, lower degree of invasiveness and higher degree of patient comfort. An arterialised earlobe is considered the method of choice to obtain capillary blood sampling, but in an acute setting, the need for vasodilating pastes may be time-consuming and impractical. The aim of this study is to examine whether accurate blood gas and acid-base measurements can be obtained using non-arterialised fingertip blood. Materials and methods: Consecutive arterial punctures and non-arterialised capillary blood samples were drawn from 62 patients with stable-phase chronic obstructive pulmonary disease (COPD), and subsequently analysed. Agreement between arterial and capillary blood gas values was compared using the method recommended by Bland and Altman. Results: Results show that limits of agreement (LoA) regarding PO2 (LoA: -1.27-4.45 kPa); Base Excess (LoA: -1.35-0.55); lactate (LoA: -0.77-0.20 mmol/l) and SO2 (LoA: -0.02-0.06) are wider than what would be applicable for clinical use. However, clinically acceptable LoA were obtained regarding PCO2 (LoA: -0.64-0.38 kPa); pH (LoA: -0.02-0.03), and HCO3 - (LoA: -1.06-0.55 mmol/l). Conclusion: LoA for PCO2, pH and HCO3 - indicate that measurement of these parameters in non-arterialised capillary blood may be useful in clinical practice/an acute setting. What this paper adds: Capillary blood sampling provides a fast, non-invasive means of obtaining blood gas-values;Traditionally, capillary blood sampling for blood gas analysis is obtained from the earlobe using arterialisation;The present study presents accurate measurements of PCO2, HCO3 - and pH using non-arterialised fingertip capillary blood;The present study is the first to show this in a population of stable-phase COPD patients.

Cardiac and hemodynamic consequences during capnoperitoneum and steep Trendelenburg positioning: lessons learned from robot-assisted laparoscopic prostatectomy.

STUDY OBJECTIVE: To determine and interpret the changes in preload, afterload, and cardiac function in the different phases of robot-assisted laparoscopic prostatectomy. DESIGN: Prospective, observational monocenter study. SETTING: Operating room at a university hospital. PATIENTS: 31 consecutive, ASA physical status 1, 2, and 3 patients. INTERVENTIONS: Observations were made at 5 distinct time points: baseline after induction of anesthesia, after initiation of capnoperitoneum, immediately after a 45° head-down tilt, 15 minutes after the 45° head-down tilt was established, after the release of the capnoperitoneum, and 5 minutes after the patient was returned to a horizontal position (end). MEASUREMENTS: Transpulmonary thermodilution and pulse contour analysis were used to record hemodynamic changes in preload, afterload, and cardiac function. MAIN RESULTS: While central venous pressure increased threefold from baseline, none of the other preload parameters showed excessive fluid overload or demand. There was no significant change in cardiac contractility over time. Afterload increased significantly during the capnoperitoneum and significantly decreased compared with baseline after the release of abdominal pressure at the end of the procedure. Heart rate and cardiac index increased significantly during robot-assisted laparoscopic prostatectomy. CONCLUSIONS: Selective arterial vasodilation at the time of capnoperitoneum may normalize afterload and myocardial oxygen demand.

Image quality influences the assessment of left ventricular function: an intraoperative comparison of five 2-dimensional echocardiographic methods with real-time 3-dimensional echocardiography as a reference.

OBJECTIVES: Transesophageal echocardiography has become a standard tool for evaluating left ventricular function during cardiac surgery. However, the image quality varies widely between patients and examinations. The aim of this study was to investigate the influence of the image quality on 5 commonly used 2-dimensional methods. METHODS: Transesophageal real-time 3-dimensional echocardiography (3DE) served as a reference. Left ventricular function was evaluated in 63 patients with sufficient real-time 3DE image quality. The image quality was rated using the ratio of the visualized border divided by the total endocardial border. These ratings were used to generate groups of poor (0%-40%), fair (41%-70%), and good (71%-100%) image quality. The ejection fraction (EF), end-diastolic volume, and end-systolic volume were analyzed by the Simpson method of disks (biplane and monoplane), eyeball method, Teichholz method, and speckle-tracking method. Furthermore, the fractional area change was determined. Each correlation with real-time 3DE was evaluated. RESULTS: Correlations of the EF and volumes, respectively, as determined by long-axis view methods increased with improving image quality: the Simpson biplane method was found to be the most accurate method, with good image quality for the EF (r = 0.946) and volumes (end-diastolic volume, r = 0.962; end-systolic volume, r = 0.989). Correlations of the EF and fractional area change by short-axis view methods decreased with improving image quality, with the Teichholz EF found to be most accurate with poor (r = 0.928) in contrast to good (r = 0.699) image quality. CONCLUSIONS: With good image quality, the Simpson biplane method is the most accurate 2-dimensional method for assessing the left ventricular EF. Short-axis view methods, especially the Teichholz method yield better correlations with poor image quality. The eyeball method was unaffected by image quality.

Entanglement of a circular mapping catheter in the mitral valve with persistent iatrogenic atrial septal defect after attempted pulmonary vein isolation: a word of caution.

A 34-year-old man presented with pulmonary vein isolation due to paroxysmal atrial fibrillation. During the standard procedure, the circular mapping catheter became dislocated and was caught in the mitral valve apparatus. Following multiple failed attempts to remove the catheter in the catheterization laboratory, the patient needed an emergency operation using the heart-lung machine.

Reproducibility in echocardiographic two- and three-dimensional mitral valve assessment.

BACKGROUND: Three-dimensional transesophageal echocardiography (3DTEE) has been demonstrated to provide more accurate information than two-dimensional transesophageal echocardiography (2DTEE) in the localization of mitral valve prolapse (MVP). However, most studies have been single-rater studies. Few results were tested for inter-observer variability with a single second rater. This multicenter study aimed to determine reliability of 2D and 3DTEE mitral valve evaluations by calculating inter-observer agreement between various echocardiographers. METHODS: Fifteen observers from 4 institutions in Germany and Switzerland interpreted 2D and 3DTEE images from 6 patients selected to represent a large spectrum of MVP diversity. Surgical findings served as reference. Individual assessments of MVP and ruptured chordae tendineae (ChR) pathology were compared by calculating Randolph's free-marginal multirater kappa coefficient. RESULTS: Accuracy of MVP evaluation with 3DTEE was 83.9%, CI [81.0%; 86.8%] and 78.7% CI [76.6% 80.8%] with 2DTEE. Flail leaflets with chordal ruptures were described correctly in 91.1%, CI [85.8, 96.4] with 3D compared to 71.1%, CI [65.0, 77.2] with 2DTEE. The multirater kappa coefficient of inter-observer agreement among all 15 observers was κ = 0.65/0.58 for 3D/2D evaluation of MVP and κ = 0.70/0.54 for detection of ChR. CONCLUSION: Three-dimensional assessment of MVP was superior to 2DTEE, although the accuracy of both 3DTEE and 2DTEE was found to be lower than previously published. 3D MVP assessment is less operator dependent than 2DTEE evaluation. Although validity has been demonstrated before, we provide evidence that 3DTEE is reproducible among 15 observers and is a reliable method for MVP evaluation.

Experts and beginners benefit from three-dimensional echocardiography: a multicenter study on the assessment of mitral valve prolapse.

BACKGROUND: Three-dimensional (3D) transesophageal echocardiography (TEE) has been claimed to provide more information than two-dimensional (2D) TEE in the localization of mitral valve prolapse (MVP). However, most studies have been performed by experts in echocardiography, without accounting for differences in training or expertise. This multicenter study was designed to assess the differences between experts and inexperienced echocardiographers in localizing MVP and ruptured chordae tendineae using 2D and real-time 3D TEE. METHODS: Thirty-six observers from 10 institutions in Germany and Switzerland interpreted 2D and 3D transesophageal echocardiographic images from six patients selected to represent a large spectrum of MVP diversity. Surgical findings served as a reference. Individual performance in the prediction of pathology was scored. Differences between 15 experts and 21 beginners in TEE were assessed, and the benefits conferred by 3D TEE were compared. RESULTS: Both study groups scored significantly higher when interpreting 3D transesophageal echocardiographic images (P ≤ .001). The experts were superior in 2D MVP localization (14.8%; P ≤ .001), a difference that diminished with 3D TEE (1.4%; P = .41). The benefit of access to 3D information for MVP localization was greater for inexperienced echocardiographers compared with experts (P < .001). CONCLUSIONS: The reported diagnostic advantage of 3D TEE over 2D TEE in MVP assessment for expert echocardiographers can be transferred to inexperienced echocardiographers. Inexperienced echocardiographers benefit from the technology to a greater extent than their expert colleagues.

Assessment of left ventricular size and function during cardiac surgery. An intraoperative evaluation of six two-dimensional echocardiographic methods with real time three-dimensional echocardiography as a reference.

Transesophageal echocardiography is recommended to monitor left ventricular (LV) size and function in various operations. Generally, two-dimensional (2D) methods are applied intraoperatively. The aim of this study was to compare the accuracy and feasibility of 6 commonly used 2D methods to assess LV function during surgery. LV function in 120 consecutive patients was evaluated. Real time three-dimensional transesophageal echocardiograpy (3DTEE) served as reference. End-diastolic and end-systolic volumes and ejection fraction (EF) were analyzed with Simpson's method of discs (monoplane [MP] and biplane [BP]), eyeball method, Teichholz' method, and speckle tracking (ST) methods. Furthermore, fractional area change (FAC) and peak systolic pressure rise (dP/dt) were determined. Each 2D method was evaluated regarding correlation and agreement with 3DE, intra- and interobserver variability and the time required for evaluation. Simpson BP showed the strongest correlation and best agreement with 3DE for EF (limits of agreement 3.7 ± 11.6%) and volumes. Simpson MP showed similar agreement with 3DE compared to ST (2.8 ± 14.5% vs. 2.0 ± 15.3% and 3.8 ± 14.4% vs. 1.9 ± 15.6%, respectively). Both the eyeball method and Teichholz' method showed wide limits of agreement (-1.5 ± 18.2% and 5.2 ± 22.1%, respectively). DP/dt did not correlate with 3DE. FAC and ST FAC showed similar agreement. Application of 3DE (429 ± 108 seconds) took the longest time, and the eyeball method took the shortest time (8 ± 5 seconds) for analysis. Simpson BP is the most accurate intraoperative 2D method to evaluate LV function, followed by long-axis MP evaluations. Short-axis views were less accurate but may be suited for monitoring. We do not recommend using dP/dt.

Real-time three-dimensional transesophageal echocardiography: improvements in intraoperative mitral valve imaging.

BACKGROUND: Successful surgical repair of a regurgitant mitral valve (MV) is dependent on a comprehensive assessment of its complex anatomy. Although there is limited evidence of the feasibility and accuracy of intraoperative real-time 3-dimensional transesophageal echocardiography (RT3DTEE) in MV surgery, its use is increasing worldwide. We designed this prospective observational study of patients with mitral regurgitation to test initial findings on the accuracy of RT3DTEE images in the diagnosis of MV prolapse and chordal rupture relative to 2D imaging and to assess the potential of RT3DTEE for visualizing leaflet clefts. METHODS: TEE-certified anesthesiologists examined 62 consecutive patients undergoing MV surgery by acquiring a full standard set of 2D TEE sections and 3D zoom recordings. Offline, 2D and 3D images were presented independently and in randomized order to 2 expert interpreters. Accuracy was determined using the surgical findings as the "gold standard." RESULTS: Surgical inspection identified 52 cases of MV prolapse (MVP). RT3DTEE correlated stronger with the surgical findings than 2D TEE for detection and localization of MVP (difference in proportions=33.9%, P<0.001) and chordal rupture (difference in proportions=25.8%, P<0.001). The superiority of RT3DTEE was significant for scallops A2, P1, P2 in MVP and A2, P2 in chordal rupture (all P<0.05). In 22 patients, leaflet clefts were also surgically repaired, and RT3DTEE was feasible in accessing them (κ=0.65, confidence interval [0.44, 0.81]). CONCLUSION: Although 2D TEE is currently the standard tool for intraoperative imaging in MV surgery, RT3DTEE improves the visualization of MV pathology and increases the accuracy of interpretation by facilitating spatial orientation. Further investigations, particularly those aimed at establishing its cost effectiveness, are indicated.

Surgical management of subaortic stenosis.

A 63-year-old male patient with subaortic stenosis (Pmax 105 mmHg, Pmean 55 mmHg) and an aneurysm of the ascending aorta was referred to our hospital due to progressive angina pectoris. Transesophageal echocardiography demonstrated high and turbulent subaortic flow velocities. A calcified subaortic membrane was identified. The membrane was removed and the aneurysm was treated with a Bentall procedure. The patient recovered smoothly from surgery and was doing well 6 months after discharge.

Thromboembolus crossing patent foramen ovale: appearance in multislice computed tomography and echocardiography.

A 31-year-old woman was referred to our hospital due to progressive dyspnea and a family history of pulmonary embolism. Multislice computed tomography depicted massive bilateral pulmonary embolism, and transesophageal echocardiography demonstrated a serpentine structure in both atria with the appearance of a thrombus. Furthermore, a highly mobile mass trapped in her patent foramen ovale was identified. She underwent emergency cardiac embolectomy and was discharged from our hospital with conventional anticoagulant therapy.

Comparison of intraoperative three-dimensional Doppler color flow mapping to assess mitral regurgitation.

BACKGROUND: Three-dimensional (3D) transesophageal echocardiography (TEE) enables the determination of the vena contracta area (VCA), which is an approved parameter to quantify mitral regurgitation (MR). The aim of this study was to determine the VCA in the operative setting and to compare it to alternative 3D and standard 2D methods, with respect to different etiologies of MR. METHODS: MR in 56 consecutive patients undergoing cardiac surgery was evaluated using 2D and 3D TEE. VCA, vena contracta (VC), and effective regurgitation orifice area (EROA) by 3D and 2D flow convergence methods were determined. The correlations among the methods and the determined areas were evaluated. RESULTS: EROA determination using 3D flow convergence areas correlated strongly with VCA (r = 0.653), however the resulting areas were considerably smaller. VC measurements in the 3D data set correlated slightly less (r = 0.629). EROA, which was determined using 2D flow convergence areas, showed the strongest correlation among the 2D methods (r = 0.406). 2D VC measurements showed weak to no correlation with VCA. Although a correlation was detected when using the biplane method or the midesophageal long-axis view to measure VC, statistical significance was only reached in functional MR and MR due to simple prolapse. CONCLUSIONS: Intraoperative 3D methods to determine MR were feasible and showed improved correlation with VCA compared to 2D measurements. The agreement of 2D methods with VCA declined from functional MR to MR due to prolapse. We recommend the utilization of 3D color Doppler for intraoperative evaluation of MR, especially in patients with complex mitral valve prolapses.

Right ventricular function during orthotopic liver transplantation: three-dimensional transesophageal echocardiography and thermodilution.

BACKGROUND: Right ventricular (RV) function is an important aspect of anesthesia management during orthotopic liver transplantation (OLT). Because of its geometrical complexity, assessment of RV dimensions with transesophageal echocardiography (TEE) is a difficult task. The aim of this prospective single-site study was to investigate the feasibility of intraoperative assessment of RV parameters based on reconstructive three-dimensional (3D) TEE and to compare the measurements to thermodilution-derived values acquired with a modified pulmonary artery catheter. MATERIAL/METHODS: Measurements were performed at four different time points during 30 OLT with 3D-TEE. At the same time comparative values of RV parameters were acquired with a fast-response thermistor pulmonary artery catheter. RESULTS: 3D reconstruction was feasible in all patients. RV dimensions measured with 3D-TEE averaged 119.4 ml (± 38.5 ml) for enddiastolic and 68.9 ml (± 27.7 ml) for endsystolic volumes. The RV ejection fraction was 42.2% (± 9.3%). The volumes obtained by thermodilution were 263.7 ml (± 64.5 ml) enddiastolic and 159.3 ml (± 47.5 ml) endsystolic, both significantly greater than by 3D-TEE, and the ejection fraction was found to be 39.5% (± 8.4%). No correlation was found between the volumes or the function determined by either method. CONCLUSIONS: Reconstructive 3D-TEE is a viable technique during OLT and leads to plausible RV parameters. However, no correlation was found with simultaneous measurements or parameters performed with thermodilution. However, based on our data cardiac output measurements by thermodilution appear reasonable. Due to both lack of agreement with 3D-TEE and extraordinary high RV volumes the question about the most valuable monitoring technique of RV dimensions and function during OLT can not finally be answered.

Tricuspid valve endocarditis with septic pulmonary emboli in a drug addict.

Presented is a case of a young, polytoxicomaniac male with a history of intravenous drug abuse. He arrived at our department in a septic state with fever and showed signs of right-sided decompensated cardiac insufficiency. The patient tested positive for hepatitis C, and blood cultures were positive for Staphylococcus aureus. A thoracic computed tomographic scan revealed bilateral, multiple septic pulmonary emboli. Transesophageal echocardiography disclosed large mobile vegetations on the tricuspid valve associated with severe regurgitation. The infected tricuspid valve was replaced with a mechanical heart valve, and the patient recovered uneventfully from surgery.