Uncontrolled Acromegaly Research Articles

An open-label long-term Phase 3 study of CAM2029 in patients with acromegaly (ACROINNOVA 2): interim analysis of the subgroup of patients 'new to CAM2029' with controlled or uncontrolled acromegaly on standard-of-care treatment

An open-label long-term Phase 3 study of CAM2029 in patients with acromegaly (ACROINNOVA 2): interim analysis of the subgroup of patients 'new to CAM2029' with controlled or uncontrolled acromegaly on standard-of-care treatment

Factors associated with disease control failure in acromegaly patients treated with pegvisomant: an ACROSTUDY analysis.

The aim of this study was to examine the probability of achieving acromegaly disease control according to several patient-, disease- and treatment-related factors longitudinally. We analyzed data from ACROSTUDY, an open-label, noninterventional, post-marketing safety surveillance study conducted in 15 countries. A total of 1546 patients with acromegaly and treated with pegvisomant, with available information on baseline IGF-1 level, were included. Factors influencing IGF-1 control were assessed up to 10 years of follow-up by mixed-effects logistic regression models, taking into account changing values of covariates at baseline and at yearly visits. Twenty-eight anthropometric, clinical and treatment-related covariates were examined through univariate and multivariate analyses. We tested whether the probability of non-control was different than 0.50 (50%) by computing effect sizes (ES) and the corresponding 95% CI. Univariate analysis showed that age <40 years, normal or overweight, baseline IGF-1 <300 µg/L or ranged between 300 and 500 µg/L, and all pegvisomant dose <20 mg/day were associated with a lower probability of acromegaly uncontrol. Consistently, in multivariate analyses, the probability of uncontrolled acromegaly was influenced by baseline IGF-1 value: patients with IGF-1 <300 µg/L had the lowest risk of un-controlled acromegaly (ES = 0.29, 95% CI: 0.23-0.36). The probability of acromegaly uncontrol was also lower for values 300-500 µg/L (ES = 0.37, 95% CI: 0.32-0.43), while it was higher for baseline IGF-1 values ≥700 µg/L (ES = 0.58, 95% CI: 0.53-0.64). Baseline IGF-l levels were a good predictor factor for long-term acromegaly control. On the contrary, our data did not support a role of age, sex, BMI and pegvisomant dose as predictors of long-term control of acromegaly. Among factors that could influence and predict the efficacy of pegvisomant therapy in controlling acromegaly, a central role of baseline IGF-1 values on the probability of achieving a biochemical control of acromegaly during the treatment with pegvisomant was identified, in a real-life setting.

The Relationship between the Burden of Acromegaly, Associated Comorbidities, Complications and Disease Status.

Uncontrolled acromegaly causes increased morbidity and mortality. The analysis of acromegaly comorbidities and complications is important when establishing a standard of care for the entire population of acromegaly patients. The aim of this study was to determine the frequency of comorbidities and complications of acromegaly and their dependence on the activity of the disease. A retrospective analysis of medical records from 124 patients with acromegaly was carried out, including 39 who were cured, 73 treated with somatostatin analogs and 12 newly diagnosed patients. The incidence of comorbidities and complications was very high, and those most frequently observed were arterial hypertension, multinodular goiter, lipid disorders, hypopituitarism and degenerative changes. At least one complication of acromegaly was observed in 92% of patients undergoing successful neurosurgery and in all pharmacologically treated patients. By contrast, two or more complications were observed in 77% of cured patients and in pharmacologically controlled and uncontrolled patients, 82% and 91%, respectively. Conclusions: Acromegaly is associated with a high prevalence of complications. Active acromegaly is associated with a higher incidence of complications than in treated groups. Untreated patients have more complications than treated patients. Successfully cured patients have significantly fewer complications than pharmacologically controlled patients and patients with active acromegaly.

Increased Risk of Arrhythmias in Active Acromegaly with Complications and Persistent Uncontrolled Active Acromegaly

Objective: Previous studies showed acromegaly have significant higher prevalence of ventricular arrhythmias and often complicated by diabetes mellitus (DM) and hypertension (HT). Both HT and DM are notoriously associated with the development of arrhythmias. However, the effect of complication (DM and/or HT) in acromegaly on ventricular arrhythmias and the risk of ventricular arrhythmias in acromegaly accept therapy but no control is largely unknown. Methods: A cross-sectional study with 307 acromegaly and 303 patients with non-functional pituitary adenoma as control group. All subjects divided into acromegaly with/without complication and controls with/without complication. In the longitudinal study, 30 persistent uncontrolled active acromegaly with at least three months follow-up. Electrocardiographic Measurements, laboratory examination, and clinical data collection performed in all subjects. QT interval corrected for heart rate (QTc) analysed among groups. Results: QTc in acromegaly population significantly increased compared to controls (p&lt;0.001). Factorial design twoway ANOVA correcting age revealed significant main effects of complication (p=0.016) and acromegaly (p&lt;0.0001), as well as positive interactions between complication and acromegaly (P&lt;0.038) on QTc. Persistent uncontrolled active acromegalic patients after therapy showed QTc significantly increase in follow-up relative to pre-treatment (p&lt;0.0001). The normalized GH level (r=0.11, p&lt;0.05) and complication (r=0.25, p&lt;0.0001) have a significant positive correlation with QTc in acromegaly. Conclusions: Acromegaly is an independent risk factor for ventricular arrhythmias and acromegaly with complication have an elevated risk for ventricular arrhythmia. Persistent uncontrolled acromegaly, who have significantly decreased in serum GH/IGF-1 levels relative to pre-treatment, also enhance the risk of ventricular arrhythmia.

Safety of pregnancy in acromegaly patients and maternal and infant outcomes after pregnancy: single-center experience from China and review of the literature

BackgroundPregnancy in acromegaly is uncommon and still in debate for fear of tumor progression or potential threat to both mother and fetus’s health. Besides, the data for pregnancy complications in uncontrolled acromegaly is limited. Thus, the objective of this study was to summarize pregnancy safety and disease courses after pregnancy in acromegalic patients and review their clinical characteristics based on disease activity in the literature.MethodsAn evaluation of eight acromegalic women from Peking Union Medical College Hospital (PUMCH) with 11 pregnancies was conducted. We also summarized a literature review of 82 disease-active pregnancies and 63 disease-controlled pregnancies with acromegaly. A second analysis was conducted to compare pregnancy courses and outcomes in different disease activities.ResultsBefore pregnancy, all patients had macroadenomas and underwent pituitary surgery. Pregnancy occurred at a median of 6 years (4–10) after the diagnosis of acromegaly. Assisted reproductive therapy was needed in 42.9% of participants. No cases had a premature birth or congenital malformations. Biochemical control was achieved in 50% of females before pregnancy and 75% at the last follow-up after delivery. Data analysis showed no differences in the prevalence of gestational diabetes mellitus (GDM) or pregnancy-induced hypertension (PIH) between acromegaly-active or acromegaly-controlled groups. The GDM prevalence in patients diagnosed during pregnancy (33.3%) was higher than that in patients diagnosed before pregnancy (4.8%) (p = 0.001).ConclusionPregnancy without biochemical control in acromegaly and receiving medical treatment during pregnancy are not rare and generally safe for the fetus. There could be a higher prevalence of PIH in acromegalic pregnancies. The treatment of acromegaly and related complications can be managed with regular follow-up after pregnancy.

Uncontrolled Acromegaly, Diabetes Mellitus and Metabolic Syndrome are the Main Risk Factors of Colon Polyposis Recurrence in Patients with Acromegaly

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1395486: Uncontrolled Acromegaly Resulting in the Need for LVAD as Bridge to Heart Transplant

Acromegaly is an uncommon pituitary disorder with an incidence of six per million persons. While hypertension is often encountered in these patients, heart failure rarely is seen with an incidence rate under 10%. We describe a case of an individual who was diagnosed with acromegaly after an acute exacerbation of heart failure with subsequent management requiring an LVAD to perform Transsphenoidal Surgery (TSS). 37-year-old male otherwise healthy initially presented to an emergency room and was found to be in acute heart failure exacerbation. Concerning acromegaly features included macrognathia, enlarged hands and feet, swollen phalanges, widened spacing of teeth, and frontal bossing. IGF-1 level was found 455 ng/mL. MRI showed a 10mm macroadenoma. A right heart catheterization showed elevated filling pressures. Cardiac MRI showed no defects or enhancement. Endomyocardial biopsy showed no inflammatory infiltrates or evidence of infiltrative diseases. Patient had an ejection fraction of 15% corroborated by cardiac MRI along with the presence of aortic root dilatation and mitral regurgitation. The patient started on 0.5mg of Cabergoline twice weekly and 120mg weekly Lanreotide injections. Patient stabilized with plans for further close monitoring and outpatient neurosurgical evaluation. The COVID-19 pandemic and insurance gaps led the patient to spend two years off his medicines and he was unable to be seen by his medical team. Patient was seen by our system after recurrent hospitalizations for heart failure at our sister hospital, AICD was unable to be placed due to the patient’s anatomy, he was placed on wearable cardiac defibrillator and required milrinone infusion for progression to end-stage heart failure with cardiac cachexia. At our institution, the patient was evaluated for Orthotopic Heart Transplant (OHT) but due to active GH secreting macroadenoma there was concern for OHT failure without TSS. Decision was made to utilize LVAD as Bridge-to-Transplant for OHT so the patient could be stabilized and safely undergo TSS. The patient tolerated surgeries well and is currently on the active transplant list. Heart failure is an uncommon presentation of severe acromegaly requiring multidisciplinary management. We describe a case of a patient who initially presented with heart failure too unstable for surgery. Due to the COVID-19 pandemic the patient’s disease progressed resulting in end-stage heart failure requiring LVAD placement for further treatment. We would like to draw attention to the use of LVAD placement in acromegalic patients who develop severe cardiovascular disease who are not candidates for OHT.

Associations between paraclinical parameters, symptoms and quality of life in patients with acromegaly: a cross sectional study

IntroductionAcromegaly is a rare chronic endocrine disorder that can lead to significant quality of life (QoL) impairment and persistent symptomatology in both biochemically uncontrolled as well as in cured or controlled patients. We aimed to conduct an observational cross-sectional study investigating the associations between biochemical disease control, associated comorbidities, and symptoms severity on QoL in a cohort of acromegalic patients.MethodsThirty-one patients with acromegaly were enrolled in our study. AcroQoL and PASQ (Pain assessed acromegaly symptoms questionnaire) questionnaires were applied to all patients. Information about disease status, associated comorbidities, and other relevant clinical and paraclinical data were gathered.ResultsPatients with uncontrolled acromegaly presented worse QoL and symptoms scores than controlled patients, but the difference was not statistically significant (AcroQoL 57.22 vs 64.04, p > 0.05; PASQ 12 vs 16.47, p > 0.05). Worse symptoms were significantly associated with impaired QoL (overall symptoms score on PASQ was negatively correlated with AcroQoL total score, r = − 0.61, p < 0.05). Cardiovascular complications were associated with lower QoL scores, but not with worse symptoms (AcroQoL total score in patients with- versus patients without cardiovascular complications: 54.89 vs 70.14, p < 0.05).ConclusionsAchieving biochemical control of acromegaly might not be enough to reverse the QoL impairment and improve symptomatology in acromegalic patients. While symptoms severity and the presence of cardiovascular complications seem to play an important role in reducing patients QoL, the roles of disease control, diabetes, and pituitary insufficiency are less clear.

OR27-4 Placebo-Controlled and Open-Label Extension Study of a Novel Hepatic-Targeted Antisense Cimdelirsen (IONIS-GHR-LRx) Under Investigation in Acromegaly Patients

Abstract Cimdelirsen (IONIS-GHR-LRx; ISIS 766720) is a novel, ligand-conjugated, hepatic-targeted investigative antisense molecule designed to reduce growth hormone receptor (GHr) synthesis, thereby inhibiting deleterious effects of growth hormone (GH) hypersecretion and reducing circulating insulin-like growth factor-1 (IGF-1) levels in acromegaly patients. Methods Cimdelirsen was evaluated in a 4-month double-blind, placebo-controlled phase 2 study (DBL) in uncontrolled acromegaly patients (IGF-1&amp;gt;1.3-&amp;lt;5xULN) treated with stable long-acting somatostatin receptor ligand (SRL) injections (NCT03548415). Due to COVID-19 pandemic, the study closed early resulting in smaller cohorts than planned. While no longer powered to assess Day 141 primary endpoint (PE), the study permitted placebo-controlled evaluation of safety and efficacy. The final analysis included 41 patients in the cimdelirsen low dose (60 and 80 mg; n=22), high dose (120 and 160 mg; n=7) or placebo (n=12) cohorts. 39 of these patients subsequently entered an open label extension (OLE) safety study where all patients were treated with cimdelirsen and at the time of interim analysis, 23 patients were treated for ≥ 1 year (NCT03967249).Patient reported outcomes were assessed using the validated ACROQoL and an acromegaly symptoms questionnaire. Results Cimdelirsen treatment resulted in a significant, dose dependent reduction in GH-binding protein (GHBP), a biomarker of hepatic GHR reduction: -2% placebo, -43% low dose, -64% high dose; p&amp;lt;0.001. Importantly, GHBP reductions were not associated with fasting GH increases. The GH mean change from baseline to PE was 1 ng/mL placebo, 0 ng/mL low dose and 1 ng/mL high dose (p&amp;gt;0.5). GHBP reductions without GH increases were maintained for up to 1 year of treatment in all patients.Integrated AUC for IGF-1 calculated after GHBP had reached near-maximal reductions (Day 57 to PE) demonstrated dose-dependent reductions that were significant at the high dose (+692%*day placebo, -460 low dose, and -1378 high dose; p=0.21 and 0.05 for the low dose and high dose groups, respectively). A greater reduction in IGF-1 AUC was observed in patients who had higher IGF-1 levels at baseline.Patients with higher IGF-1 levels showed significant improvements in ACROQoL at the PE; all patients demonstrated improvements after 1 year. Importantly, high-dose cimdelirsen improved sweating and headaches at PE.In both studies, there were no drug-related SAEs. The most frequently reported TEAE were UTI (16.1%) and COVID-19 (12.8%) in DBL and OLE, respectively. No safety signals were observed including no ALT elevation &amp;gt;3×ULN and no thrombocytopenia (&amp;lt;100 10^3/uL). Glycemic control remained stable and showed no worsening of HbA1c. Conclusion Once monthly SC cimdelirsen injections demonstrated long-term safety, were well-tolerated, and resulted in significant reductions in GHBP and IGF-1 AUC without increased GH levels. Cimdelirsen also improved PRO, collectively supporting further development of this novel, liver-directed potential therapy for uncontrolled acromegaly. Presentation: Tuesday, June 14, 2022 10:30 a.m. - 10:45 a.m.

Association of Epicardial Adipose Tissue Thickness with Cardiovascular Risk in Acromegaly

Objective:Acromegaly is a rare disease associated with increased mortality. Reports on coronary artery disease in acromegaly are controversial. This study aimed to investigate the possible association of epicardial adipose tissue thickness with cardiovascular risk in patients with acromegaly.Methods:The study included 38 patients followed up with the diagnosis of acromegaly and 29 healthy controls. Patients with acromegaly were divided into controlled and uncontrolled acromegaly groups based on insulin-like growth factor-1 levels. Epicardial adipose tissue thickness measurements were obtained from chest computed tomography, and laboratory data were extracted from patient files.Results:Twenty-nine patients (76.3%) had controlled acromegaly. Eleven patients with acromegaly had diabetes mellitus (28.9%), 18 (47.4%) had hypertension, and 27 (71%) had a concomitant chronic disease. Epicardial adipose tissue thickness was significantly increased in the acromegaly group (p<0.001). No significant difference was observed between the controlled and uncontrolled acromegaly groups in terms of the epicardial adipose tissue thickness. Age was the only parameter that was significantly correlated with the epicardial adipose tissue thickness. When the Framingham risk score was calculated, the 10-year cardiovascular risk of patients with acromegaly was 5.63%.Conclusions:The epicardial adipose tissue thickness is increased in acromegaly. However, this increase may not have clinical relevance in terms of cardiovascular risk.

Association between uncontrolled acromegaly and nasopharyngeal tumor-case presentation

Association between uncontrolled acromegaly and nasopharyngeal tumor-case presentation

Characterizing the burden of uncontrolled acromegaly – a description of real-world patient characteristics in Colombia

Objective: To describe the epidemiology and clinical characteristics, relative to biochemical and disease control after treatment initiation, in patients with acromegaly in Colombia. Methods: Retrospective chart review of newly diagnosed acromegaly patients who initiated medical treatment at referral health institutions in Colombia. Patients with controlled vs uncontrolled disease were analyzed, including comorbidities and treatment patterns. In addition, patients receiving somatostatin analogues (SSAs) as first-line treatment (SSA cohort) were compared with those receiving other medical therapy (non-SSA cohort). Results: Data obtained from medical records of 53 patients showed a mean age of 49 years (SD 13.31) and a female preponderance (33 [62.26%]). After 1 year of treatment, 10 (18.9%) patients from the SSA cohort achieved complete biochemical control, showing significantly lower levels of median growth hormone (GH) and insulin-like growth factor-1 (IGF-1) vs 43 (81.1%) patients from the uncontrolled group (p=0.0010 and p=0.0001, respectively). During follow-up, acromegaly-related comorbidities were higher in patients with uncontrolled disease and in the non-SSA group vs the controlled group. Similarly, the percentage of physician visits was lower in the controlled (n=4/10, 40.0%) vs uncontrolled (n=31/43, 72.0%) group and in the SSA (n=24/38, 63.2%) vs non-SSA (n=11/15, 73.3%) cohort. Conclusion: In patients with acromegaly receiving medical therapy, both GH and IGF-1 levels tended to decline over time with the use of SSAs. Lower frequency of comorbidities and use of healthcare resources were associated with controlled acromegaly. Optimizing disease control with adequate patient follow-up and drug treatment may improve clinical outcomes and promote efficient use of healthcare resources.

A prospective study on the efficacy of oral estrogen in female patients with acromegaly.

To evaluate the efficacy and safety of oral estrogen therapy in female patients of childbearing age with uncontrolled acromegaly and to verify the significance of the presence of estrogen receptor α (ER-α) in somatotropinomas. Prospective study in which biochemical and radiological evaluations were performed at baseline and after six months of treatment with an oral formulation of ethinyl-estradiol 0.03mg and levonorgestrel 0.15mg. ER-α was assessed by immunohistochemistry and immunopositivity was considered when it was present in ≥ 1% of cells. Eight patients with uncontrolled acromegaly were selected. All patients underwent surgery. Four patients were on octreotide LAR 30mg, two patients were on lanreotide autogel 120mg, and two patients had active disease after surgery. At the end of follow-up, IGF-I normalized in 3/8 (37%), 2/8 (25%) patients presented with mean IGF-I reduction of 25% but without IGF-I normalization, and 2/8 (25%) did not respond-one had a 13% increase in IGF-I and IGF-I level remained unchanged after treatment in the other. In one patient, treatment was discontinued after 3months due to side effects (headache), with an IGF-I reduction of 28% but without normalization. Tumor volume increase (41%) was observed in only one patient (the only tumor with positive ER-α expression). In uncontrolled patients with acromegaly, a trial with oral estrogen can be an option for young women. Oral estrogen was well tolerated, but the somatotropinoma that presented ER-α expression was the only somatotropinoma that presented growth during treatment.

GH Is a Component of SASP in Aging Tissue

Deficient GH signaling results in lifespan extension in murine and human models, while patients with uncontrolled acromegaly and transgenic mice overexpressing GH have a shorter lifespan. Colon polyp development increases with age, and also with GH excess in acromegaly. Aging is characterized by senescent cell accumulation with p53/p21 or p16 upregulation as well as cell cycle arrest and expression of a senescence-associated secretory phenotype (SASP). Senescence is reinforced by the SASP, which comprises pro-inflammatory cytokines, chemokines, growth modulators, angiogenic factors, and matrix metalloproteinases. SASP contributes to pro-aging phenotypes, and depletion or removal of senescent cells increases lifespan by partially protecting from age-related pathologies. Senescence, triggered by genotoxic insult with DNA damage, can be reversed by p53 inactivation; senescent cells with low p53 and unrepaired DNA damage can then re-enter the cell cycle (Beausejour et al, EMBO 2003), potentially resulting in chromosomal instability. We showed GH induction in non-pituitary senescent cells leading to suppressed p53/p21 (Chesnokova PNAS 2013). We now show that, in senescent human colon cells (hNCC) and in 3-dimensional human intestinal organoids, non-pituitary GH (npGH) is a component of SASP. In response to DNA damage, npGH is expressed and secreted locally as measured by RT-PCR, WB, and ELISA. High autocrine/paracrine GH further exacerbate DNA damage and reverses senescent in colon cells, enabling them to re-enter the cell cycle, as evidenced by p53 downregulation and increased Ki67 expression. Senescent colon cells expressing high intracellular GH form colonies in soft agar, indicative of cell transformation and proliferation, while GH deletion by shRNA results in Ki67 downregulation and decreased colony formation and size. The SASP protein CXCL1, a chemo-attractant that also functions to eliminate senescent cells, dose-dependently activates GH in hNCC and in intestinal organoids. GH, in turn, suppresses CXCL1 expression. Consistent with these findings, colon CXCL1 was induced in GHRKO mice, and also in hNCC with abrogated GH signaling by shRNA. Taken together with our finding that GH accumulates in aging normal human colon tissue and co-localizes in cells expressing senescence-associated β-galactosidase, these results suggest that GH, as a SASP component, initiates senescent cell proliferation and transformation. By inhibiting CXCL1, GH also functions to attenuate immune-mediated senescent cell elimination that protects aging tissue from deleterious effects of SASP. These mechanisms may underly an initial step in age-associated epithelial polyp development.

Use of Oral Concomitant Medications in Patients With Acromegaly

Background: Acromegaly is a rare condition characterized by excess GH and IGF-I levels.1 Injectable somatostatin analogs (SSAs) are recommended as first-line medical treatment.2 Comorbidities including diabetes, hypertension and hypopituitarism reduce quality of life in patients with acromegaly; 3,4 treatment for these includes oral medications. We assessed the most common oral medications used by patients with acromegaly during treatment with lanreotide autogel 120 mg (LAN). Methods: This post-hoc analysis reports data from the PRIMARYS5 (NCT00690898) and LEAD6 (NCT00701363) open-label trials in which adult patients with acromegaly received LAN. PRIMARYS patients were SSA/surgery-naïve with uncontrolled acromegaly, LEAD patients were previously treated with octreotide long-acting release with normal age-adjusted IGF-I levels for two consecutive measurements. Results: PRIMARYS included 90 patients: mean (standard deviation [SD]) age 49.5 (12.4) years; 47.8% male; mean (SD) baseline IGF-I 809.9 (300.0) µg/L, 97.8% had IGF-I >1.3xULN. LEAD included 124 patients: mean (SD) age 55.4 (10.9) years; 37.1% male. Median (range) time since diagnosis was 99.0 (27.0-1,261.0) days (PRIMARYS) and 7.1 (0.5-27.0) years (LEAD). 51.1%, 24.4% and 3.3% of participants in PRIMARYS had a history of cardiovascular disorders (including hypertension), diabetes/glucose intolerance, and hypopituitarism/hypothalamic disorders; the corresponding values in LEAD were 69.4%, 33.9% and 18.5%. 83.3% of participants in PRIMARYS and 86.3% in LEAD used ≥1 concomitant oral medication with LAN. Of these participants, >50% used >3 types (PRIMARYS: 53.3%; LEAD: 61.7%). Out of participants in both studies who used concomitant oral medication with LAN, this was commonly indicated for cardiovascular disorders including: renin-angiotensin agents (PRIMARYS: 33.3%; LEAD: 45.8%); antithrombotic agents (PRIMARYS: 10.7%; LEAD: 19.6%); beta-blocking agents (PRIMARYS: 22.7%; LEAD: 19.6%) and calcium channel blockers (PRIMARYS: 16.0%; LEAD: 22.4%). Diuretics (PRIMARYS: 16.0%; LEAD: 20.6%) and lipid modifying agents (PRIMARYS: 20.0%; LEAD: 39.3%) were also common concomitant oral medications, as were medications used in diabetes (PRIMARYS: 17.3%; LEAD: 20.6%) and for thyroid therapy (PRIMARYS: 28.0%; LEAD: 31.8%). Conclusions: In this analysis, most patients with acromegaly receiving LAN, regardless of prior therapy, used ≥1 concomitant oral medication. An awareness of the ongoing burden of comorbidities requiring oral medications should help physicians in managing acromegaly. Funding: This study was sponsored by Ipsen.1. Lavrentaki A Pituitary 2017;20:4-92. Melmed S Nat Rev Endocrinol. 2018;14:552-613. Lesén E Eur J Endocrinol. 2017:176:203-124. Vilar L Pituitary 2017;20:22-325. Caron PJ J Clin Endocrinol Metab. 2014;99:1282-906. Neggers SJ Eur J Endocrinol. 2015;173:313-23

Economic and clinical burden of comorbidities among patients with acromegaly

ObjectiveAcromegaly is a rare, pituitary hormonal disorder that requires improved awareness worldwide. The objective of this analysis was to quantify the clinical and economic burden of comorbidities for patients with acromegaly and examine the influence of biochemical control on these outcomes. Study designMarkov cohort decision analytic model consisting of two states, including alive (with and without comorbidity) and dead. MethodsA cohort of patients with acromegaly who had achieved biochemical control, a cohort of patients with acromegaly who had not achieved biochemical control, and a cohort of individuals from the general US population were tracked over a lifetime time horizon. The model tracked the proportion of the alive population that had each comorbidity based on age, sex, presence of acromegaly, and biochemical control status. The proportion of patients with each acromegaly-associated comorbidity were assigned comorbidity-associated costs, disutilities, and increased risk of mortality. ResultsCompared with the general population, controlled acromegaly resulted in $192,000 additional comorbidity-related costs, 0.7 fewer years of life, 2.9 fewer quality-adjusted life years, and 1.1 more comorbidities across the remaining lifespan. Compared with the general population, uncontrolled acromegaly resulted in $285,000 additional comorbidity-related costs, 0.9 fewer years of life, 4.2 fewer quality-adjusted life years, and 1.6 more comorbidities across the remaining lifespan. ConclusionsAchieving biochemical control is associated with improvements in cost, quality of life, and mortality, albeit not to the level of the general population. A multimodal treatment strategy including biochemical control and management of comorbidities is necessary to improve patient outcomes.

Quality of Life and its Determinants in Patients With Treated Acromegaly: A Cross-Sectional Nationwide Study in China.

Quality of life (QoL) continues to be impaired in acromegaly after treatment. We conducted the first nationwide survey assessing QoL status among Chinese patients with treated acromegaly and explored correlations with clinical parameters, treatment modalities, and outcomes. Cross-sectional study. Survey via Chinese Association of Patients with Acromegaly (CAPA) online platform. Treated patients from CAPA. QoL was assessed using acromegaly QoL questionnaire (AcroQoL), 5-level EuroQoL five-dimensional questionnaire (EQ-5D-5L), and 12-item short-form health survey questionnaire (SF-12). Complete, valid questionnaires from 327 patients (mean age: 39.2 years, 61.5% females) at a mean of 10 years after treatment were included. Biochemical control was satisfied in 52.9% of these patients. The controlled patients had significantly better QoL than the uncontrolled patients in all AcroQoL dimensions, most SF-12 dimensions, and pain/discomfort and anxiety/depression dimensions of the EQ-5D-5L. Patients with either controlled or uncontrolled acromegaly had significantly worse QoL than the age- and sex-adjusted population reference in most SF-12 dimensions except for physical functioning. More acromegaly-associated symptoms and comorbidities at follow-up were independent risk factors for decreased QoL across all questionnaires. Medical treatment, especially with somatostatin analogs (SSAs), and radiotherapy were predictors of worse QoL. Female patients had lower scores of physical-related QoL than male patients. Our study suggests that biochemical control improved but did not normalize QoL in acromegaly. Numbers of symptoms and comorbidities at follow-up, sex, radiotherapy, and medical treatment with SSAs were factors determining QoL of patients with treated acromegaly.

Growth hormone control and cardiovascular function in patients with acromegaly.

Acromegaly is associated with cardiovascular alterations. Up to 50% acromegalic patients suffered from treatment failure after multiple modalities. We investigated correlation between cardiovascular function and control of growth hormone (GH) in acromegalic patients following transsphenoidal adenomectomy (TSA). We recruited acromegalic patients who had undergone TSA between 2006 and 2014 in this cross-sectional study. Patients were assigned to group 1, controlled acromegaly (GH <1.0 ng/mL and normalized insulin-like growth factor-1 [IGF-1]); group 2, partially controlled acromegaly (either GH >1.0 ng/mL or non-normalized IGF-1); or group 3, uncontrolled acromegaly (GH >1.0 ng/mL and non-normalized IGF-1). Echocardiography evaluated the left ventricular mass index, left ventricular ejection fraction, and the early transmitral filling velocity (E)-to-late transmitral filling velocity (A) and the E-to-the early diastolic mitral annular velocity (E') ratios. Carotid tonometry evaluated the intima-media thickness of the carotid artery, carotid-femoral pulse wave velocity, augmentation index, aortic characteristic impedance (Zc), and pulse pressure amplification. Thirty-three patients participated in this study. Fourteen of the 33 patients were males (42%). Mean age at diagnosis was 50.33 years (SD 18.45). Compared to patients in group 1, patients in group 3 had younger age and shorter years after operation, without statistical significance. Cumulative GH levels were progressively higher from group 1 to group 3, without statistical significance. The groups did not differ with respect to cardiovascular structure and function evaluated by echocardiography and carotid tonometry. Only Zc value had a difference that was of borderline significance (group 1: 109.13 ± 32.99; group 2: 129.30 ± 32.27; group 3: 159.56 ± 77.4 dynes × s/cm5; ANOVA p = 0.088; p = 0.086 for group 1 vs group 3). In the patients with acromegaly who had undergone TSA, cardiac structure and vascular stiffness did not differ among the groups with different levels of GH control.

Acromegaly - dealing with an uncooperative patient

Introduction: Acromegaly is a chronic disease resulting from increased secretion of growth hormone. The main reason of elevated GH concentration is pituitary adenoma that originates from somatotropic cells. As a consequence, several changes in the organism appear such as progressive deformation of the skeleton with enlargement of the skull, hands and feet, growth of soft tissues, bones and internal organs as well as many other systemic complications which are responsible for increased mortality in untreated patients. Case report: A 60-year-old patient was diagnosed with acromegaly due to the pituitary macroadenoma and associated hypopituitarism in the thyroid and gonadotropic axis 4 years ago. The disease was suspected in April 2016 by a rheumatologist, and then confirmed on the basis of hormonal tests in the Endocrinology Clinic (IGF1 - 754.7 ng/ml, N: 77-224; GH - 2.51 ng/ml, no inhibition in OGTT). The imaging examination revealed a pituitary macroadenoma with dimensions of 17x15x19 mm. The medical history revealed the characteristic symptoms of acromegaly like enlargement and deformation of the fingers, enlarged nose, excessive sweating and headaches for the last 12 years. There have been several studies investigating the complications of acromegaly that found abnormalities in the cardiovascular system, metabolic disorders (dyslipidemia, abnormal fasting glycaemia), arthropathies, sigmoid polyps and nodular goiter. Due to the patient's lack of consent to the surgical intervention, treatment with a somatostatin analogue was introduced. During 2-year therapy, the normalization of IGF-1 concentration was not achieved. In October 2018 patient completely abandoned therapy with somatostatin analogue. In 2019 the lack of control of acromegaly was confirmed. During hospitalization in 2020 the uncontrolled acromegaly was stated once again. The patient still does not consent to the surgical procedure to remove pituitary macroadenoma, however, he agreed for systematic re-treatment with a somatostatin analogue. Conclusions: Isolated pharmacological treatment doesn’t always allow for sufficient control of an illness. Effective treatment of acromegaly should consist of surgery as well as conservative treatment. The introductinon of both 2nd generation analogues and GH receptor antagonists in therapeutic programs makes effective pharmacological treatment possible.

Depressive symptoms in acromegaly: factors that affect their incidence and severity?

Aim. The study aimed to evaluate the influence of acromegaly on the prevalence and the severity of depressive symptoms in patients with active and inactive disease. Material and Methods. The study group comprised 56 patients with acromegaly, which were divided into two groups based on growth hormone (GH) and insulin-like growth factor (IGF-1) levels, with controlled/cured and with uncontrolled acromegaly. The presence and severity of depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II). Results. The mean score of BDI-II in the whole group of patients was 13.43±10.41, with no significant difference in the severity of depressive symptoms between patients with cured/controlled and uncontrolled acromegaly (p=0.620). Similarly, the lack of statistically significant differences was confirmed in patients with micro- and macroadenomas, as well as with and without hypopituitarism. There were no significant correlations between BDI-II scores and GH or IGF-1 levels, patient age or duration of the illness. Conclusions. Depressive symptoms are common in acromegalic patients even if remission has been attained. They are most likely caused by psychological, non-organic causes. Patients diagnosed with acromegaly should undergo a screening BDI test as a part of comprehensive care, and in the event of elevated levels should be provided with a psychiatric consultation and psychological care.