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Pituitary Jun 2024Copeptin efficiently predicts post-neurosurgical central diabetes insipidus (CDI) in patients with hypothalamic-pituitary lesions, but its role in characterizing changes...
PURPOSE
Copeptin efficiently predicts post-neurosurgical central diabetes insipidus (CDI) in patients with hypothalamic-pituitary lesions, but its role in characterizing changes in diuresis in individuals with acromegaly undergoing neurosurgery remains unexplored. Our study aimed to assess changes in postoperative fluid balance in acromegaly patients and correlate them with both copeptin and growth hormone (GH) levels.
METHODS
This was a secondary analysis of a prospective study involving 15 acromegaly patients undergoing endoscopic endonasal resection at our University Hospital. Fluid balance was assessed daily, and copeptin and GH levels were evaluated preoperatively (T0), and serially on the morning of the first (T2) and second (T3) postoperative day, with an additional measurement of copeptin one hour post-extubation (T1). Patients with pre-existing or post-neurosurgical CDI were excluded from the analysis.
RESULTS
Most patients (11/15) exhibited a negative fluid balance on the second postoperative day, with 4 developing polyuria. Postoperative GH levels did not differ significantly between polyuric and non-polyuric patients, but GH measured at T2 correlated significantly with negative total balance (r = -0.519, p = 0.048). Copeptin levels at T1 were significantly higher in those who developed polyuria (p = 0.013), and a copeptin value > 39.9 pmol/L at T1 showed excellent ability (Sensitivity 100%, Specificity 90.9%, p < 0.001) in predicting postoperative polyuria. Additionally, polyuric patients exhibited a higher T1 / T3 copeptin ratio (p = 0.013) and a negative fluid balance was associated with the remission of acromegaly at 12 months (p = 0.046).
CONCLUSION
The early assessment of copeptin, in addition to facilitating the rapid identification of individuals at increased risk of developing CDI, could also allow the recognition of subjects with a tendency towards non-pathological polyuria in the postoperative setting, at least in individuals affected by acromegaly.
PubMed: 38847919
DOI: 10.1007/s11102-024-01407-x -
Pituitary Jun 2024Cardiac abnormalities are common in patients with acromegaly, contributing to the increased morbidity and mortality. Cardiac magnetic resonance (CMR) is the gold...
PURPOSE
Cardiac abnormalities are common in patients with acromegaly, contributing to the increased morbidity and mortality. Cardiac magnetic resonance (CMR) is the gold standard for measuring cardiac morpho-functional changes. This study aims to detect cardiac alterations in acromegaly through CMR, even when the disease is adequately controlled.
METHODS
In this, multicentre, case-control study, we compared consecutive patients with acromegaly, cured after surgery or requiring medical treatment, with matched controls recruited among patients harbouring non-functioning adrenal incidentalomas.
RESULTS
We included 20 patients with acromegaly (7 females, mean age 50 years) and 17 controls. Indexed left ventricular-end-diastolic volume (LV-EDVi) and LV-end-systolic volume (LV-ESVi) were higher in patients than in controls (p < 0.001), as were left ventricular mass (LVMi) (p = 0.001) and LV-stroke volume (LV-SVi) (p = 0.028). Right ventricle (RV) EDVi and ESVi were higher, whereas RV-ejection fraction (RV-EF) was lower (p = 0.002) in patients than in controls (p < 0.001). No significant differences were observed in the prevalence of cardiometabolic comorbidities, including hypertension, glucose and lipid metabolism impairment, obstructive sleep apnoea syndrome, and obesity. IGF1 x upper limit of normal significantly predicted LVMi (b = 0.575; p = 0.008). Subgroup analysis showed higher LVMi (p = 0.025) and interventricular septum thickness (p = 0.003) in male than female patients, even after adjusting cardiac parameters for confounding factors.
CONCLUSIONS
The CMR analysis reveals a cluster of biventricular structural and functional impairment in acromegaly, even when the biochemical control if achieved. These findings appear specifically triggered by the exposure to GH-IGF1 excess and show sex-related differences advocating a possible interaction with sex hormones in cardiac disease progression.
PubMed: 38847918
DOI: 10.1007/s11102-024-01403-1 -
Best Practice & Research. Clinical... May 2024Injectable first-generation somatostatin receptor ligands (fg-SRLs) are the standard of care of medical treatment for acromegaly. While fg-SRLs control acromegaly in up... (Review)
Review
Injectable first-generation somatostatin receptor ligands (fg-SRLs) are the standard of care of medical treatment for acromegaly. While fg-SRLs control acromegaly in up to 50 % of patients, they may lead to bothersome injection pain and site reactions. Paltusotine is an investigational, highly selective somatostatin receptor subtype 2 agonist, which is administered orally once a day. To date, phase 2 and 3 clinical trials suggest paltusotine treatment can achieve biochemical and symptom control in acromegaly, with a safety profile comparable to those of the fg-SRLs. Since paltusotine is a once-daily oral drug, it may represent a future treatment option for addressing patient preference or improving quality of life.
PubMed: 38845246
DOI: 10.1016/j.beem.2024.101906 -
Nature Reviews. Endocrinology Jun 2024Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common... (Review)
Review
Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications.
PubMed: 38844688
DOI: 10.1038/s41574-024-00993-x -
The Journal of Clinical Endocrinology... Jun 2024
PubMed: 38843034
DOI: 10.1210/clinem/dgae386 -
Expert Review of Endocrinology &... Jul 2024Acromegaly is a rare endocrine disorder usually caused by a benign growth hormone‒secreting pituitary adenoma. Surgical adenoma resection is typically the first line... (Review)
Review
INTRODUCTION
Acromegaly is a rare endocrine disorder usually caused by a benign growth hormone‒secreting pituitary adenoma. Surgical adenoma resection is typically the first line of treatment, and medical therapy is used for patients with persistent disease following surgery, for adenoma recurrence, or for patients ineligible for, or declining, surgery. Approved somatostatin receptor ligands (SRLs) have been limited to injectable options, until recently. Oral octreotide capsules (OOC) are the first approved oral SRL for patients with acromegaly.
AREAS COVERED
We review published reports and provide case study examples demonstrating practical considerations on the use of OOC. Using two hypothetical case scenarios, we discuss current treatment patterns, breakthrough symptoms and quality of life (QoL), efficacy of SRLs, OOC dose titration, evaluation of OOC treatment response, and incidence and management of adverse events.
EXPERT OPINION
OOC are an option for patients with acromegaly including those who experience breakthrough symptoms, who have preference for oral therapies, or other reasons for declining injectable SRLs. OOC have been associated with improved patient-reported QoL measures compared with those reported for lanreotide and octreotide. Continued real-world experience will determine whether OOC, alone or in combination with other therapies, provides further advantages over current injectable acromegaly treatments.
Topics: Humans; Acromegaly; Octreotide; Administration, Oral; Antineoplastic Agents, Hormonal; Quality of Life; Capsules; Adenoma; Growth Hormone-Secreting Pituitary Adenoma; Clinical Trials as Topic; Treatment Outcome
PubMed: 38842362
DOI: 10.1080/17446651.2024.2363540 -
Growth Hormone & IGF Research :... Jun 2024This study aims to investigate whether the middle ear resonance frequency (RF) is affected in acromegaly, which causes growth in the skull bone.
OBJECTIVES
This study aims to investigate whether the middle ear resonance frequency (RF) is affected in acromegaly, which causes growth in the skull bone.
METHODS
Thirty acromegaly patients and 38 volunteers were included in the study. Pure tone average scores and middle ear RF values of the groups that underwent pure tone audiometry, tympanometry, and multifrequency tympanometry tests were compared.
RESULTS
The pure tone mean was 14.95 ± 12.13 in acromegaly patients and 5.70 ± 8.52 in the control group (p:0.18). Sensorineural hearing loss(SNHL) was observed in 16.6% of the patients. The average middle ear RF was calculated as 815 ± 179.05 Hz in patients with acromegaly and 773 ± 127.15 in the control group. (p = 0.0001).
CONCLUSION
This study is the first to evaluate middle-ear RF in acromegaly patients. Acromegaly-induced changes in soft tissues and bone structures impact middle ear functions. In this patient group, we found an increase in middle ear RF without conductive-type hearing loss and a 16.6% rate of SNHL.
Topics: Humans; Acromegaly; Female; Ear, Middle; Male; Adult; Skull; Middle Aged; Case-Control Studies; Hearing Loss, Sensorineural; Acoustic Impedance Tests; Audiometry, Pure-Tone; Prognosis
PubMed: 38833815
DOI: 10.1016/j.ghir.2024.101594 -
Pituitary Jun 2024A series of consensus guidelines on medical treatment of acromegaly have been produced in the last two decades. However, little information is available on their...
PURPOSE
A series of consensus guidelines on medical treatment of acromegaly have been produced in the last two decades. However, little information is available on their application in clinical practice. Furthermore, international standards of acromegaly care have not been published. The aim of our study was to report current standards of care for medical therapy of acromegaly, using results collected through an audit performed to validate criteria for definition of Pituitary Tumor Centers of Excellence (PTCOE).
METHODS
Details of medical treatment approaches to acromegaly were voluntarily provided by nine renowned international centers that participated in this audit. For the period 2018-2020, we assessed overall number of acromegaly patients under medical treatment, distribution of patients on different treatment modalities, overall biochemical control rate with medical therapy, and specific control rates for different medical treatment options.
RESULTS
Median number of total patients and median number of new patients with acromegaly managed annually in the endocrinology units of the centers were 206 and 16.3, respectively. Median percentage of acromegaly patients on medical treatment was 48.9%. Among the patients on medical treatment, first-generation somatostatin receptor ligand (SRL) monotherapy was used with a median rate of 48.7%, followed by combination therapies with a median rate of 29.3%. Cabergoline monotherapy was used in 6.9% of patients. Pegvisomant monotherapy was used in 7 centers and pasireotide monotherapy in 5 centers, with median rates of 7.9% and 6.3%, respectively.
CONCLUSIONS
Current standards of care in PTCOEs include use of first-generation SRLs as the first medical option in about 50% of patients, as recommended by consensus guidelines. However, some patients are kept on this treatment despite inadequate control suggesting that cost-effectiveness, availability, patient preference, side effects, and therapeutic inertia may play a possible role also in PTCOE. Moreover, at odds with consensus guidelines, other monotherapies for acromegaly appear to have a marginal role as compared to combination therapies as extrapolated from PTCOE practice data. Presence of uncontrolled patients in each treatment category suggest that further optimization of medical therapy, as well as use of other therapeutic tools such as radiosurgery may be needed.
PubMed: 38833044
DOI: 10.1007/s11102-024-01397-w -
Domestic Animal Endocrinology May 2024Feline hypersomatotropism (HST) is typically associated with diabetes mellitus (DM), whereas HST without concurrent DM has only been reported in a few cases. Weight gain...
Feline hypersomatotropism (HST) is typically associated with diabetes mellitus (DM), whereas HST without concurrent DM has only been reported in a few cases. Weight gain may be observed in cats with HST. The aims of this study were to evaluate circulating insulin-like growth factor-1 (IGF-1) in non-diabetic cats with overweight/obesity, to screen this population for the presence of HST, and to assess whether there is a correlation between body weight/body condition score (BCS) and serum IGF-1 concentration in overweight/obese cats. In this prospective study, 80 overweight/obese cats from referral centers in Buenos Aires (Argentina) were evaluated. Serum IGF-1 was measured as part of the routine tests for overweight/obesity. Non-diabetic cats were included in the study if they had a BCS>6/9. Twenty-nine cats were classified as overweight (BCS 7/9), whereas 51 were classified as obese (BCS 8-9/9). Median serum IGF-1 concentrations of cats with BCS 7/9, 8/9, and 9/9 were 570 ng/ml (range 123-1456 ng/ml), 634 ng/ml (range 151-1500 ng/ml), and 598 ng/ml (range 284-2450 ng/ml), respectively. There was a positive linear correlation between serum IGF-1 concentrations and body weight (r= 0.24, 95% CI 0.01-0.44 P=0.03), and between IGF-1 and BCS (r= 0.27, 95% CI 0.08-0.44 P=0.004). In total, 8.75% (95% confidence interval 3.6-17.2%) of the cats with overweight/obesity had IGF-1 concentrations >1000 ng/ml. Pituitary enlargement was detected on computed tomography in 4/7 cases. These seven cats showed varying degrees of phenotypic changes consistent with acromegaly. A proportion of 8.75 % of overweight/obese non-diabetic cats from referral centers in Buenos Aires had serum IGF-1 concentration in a range consistent with HST in diabetic cats. Likewise, 5% of overweight/obese cats were likely to be diagnosed with HST, supported by evidence of pituitary enlargement. Serum IGF-1 concentrations were positively correlated with body weight and BCS in this population of cats. This study highlights the relevance of screening different populations of non-diabetic cats to increase the detection of HST/acromegaly.
PubMed: 38830275
DOI: 10.1016/j.domaniend.2024.106858 -
The Journal of Clinical Endocrinology... Jun 2024Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly.
CONTEXT
Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly.
OBJECTIVE
To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs).
METHODS
This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had insulin-like growth factor I (IGF-I) ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0×ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary (ASD) score, and maintenance of mean 5-sample growth hormone (GH) <1.0 ng/mL.
RESULTS
The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0×ULN (odds ratio: 126.53; 95% CI: 13.73, >999.99; P<.0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (±SE) change in IGF-I of 0.04±0.09×ULN versus 0.83±0.1×ULN (P<.0001); mean (±SE) change in ASD score of -0.6±1.5 versus 4.6±1.6 (P=.02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) versus 5/18 (27.8%) patients (odds ratio: 16.61; 95% CI: 2.86, 181.36; P=.0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs.
CONCLUSION
Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated.
PubMed: 38828555
DOI: 10.1210/clinem/dgae385