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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 -
Endocrine May 2024Studies on intestinal microbiota in acromegaly are scant. This study aimed to characterize the gut microbiome in patients with acromegaly.
PURPOSE
Studies on intestinal microbiota in acromegaly are scant. This study aimed to characterize the gut microbiome in patients with acromegaly.
METHOD
Stool samples were collected from 11 patients newly diagnosed with acromegaly and 12 healthy controls matched for body mass index (BMI) and age after three days on a standard diet. Clinical and gut microbial composition assessments were performed for the two participant groups using 16S rRNA gene amplicon sequencing.
RESULTS
There was no difference in the alpha diversity of the microbiota between the samples from patients with acromegaly and those from the healthy controls. Based on beta diversity measurements, differences in microbial community structures were found to be significant only when compared using the Jaccard similarity index. The corresponding Firmicutes/Bacteroidota ratio tended to be higher in individuals with acromegaly than in healthy controls. The mean relative abundance of Actinobacteriota was 2.3 times higher in the acromegaly patient group than in the control group. Eggerthellaceae, Christensenellaceae, and Bacteroidaceae were among the significantly abundant bacterial families in the samples from the acromegaly patient group, while Butyricicoccaceae and Tannerellaceae were decreased. At the level of the genus, the most discriminative features were the abundance of Prevotella 7, Bacteroides, Senegalimassilia, Enterohabdus, the Family XIII AD3011 group, Howardella, and Hungatella in the samples from the acromegaly patient group. In contrast, the Butyrivibrio and the Eubacterium eligens group were the most discriminative genera for the healthy controls and were significantly less abundant in patients with acromegaly. While there were no significantly differentiated taxa between the diabetic and non-diabetic subgroups, Prevotella_7 was significantly enriched in the osteoarthritis (OA) subgroup. No significant association was found between individual genera and growth hormone (GH) levels and insulin-like growth factor-1 (IGF-1) levels as well as the upper limit of normal (ULN).
CONCLUSION
Although alpha and beta diversity were mainly similar between the two groups, significant differences were observed between the acromegaly group and the control group at the family and genus levels. These results suggest that the differences between the microbial communities in patients with acromegaly and those in healthy individuals consist primarily of compositional differences independent of abundance. Prospective studies are needed to further explore the clinical implications of gut microbiome dysbiosis in patients with acromegaly.
PubMed: 38822184
DOI: 10.1007/s12020-024-03892-3 -
Pituitary May 2024Given the increased cardio-metabolic risk in patients with acromegaly, this study compared cardiovascular outcomes, mortality, and in-hospital outcomes between patients...
PURPOSE
Given the increased cardio-metabolic risk in patients with acromegaly, this study compared cardiovascular outcomes, mortality, and in-hospital outcomes between patients with acromegaly and non-functioning pituitary adenoma (NFPA) following pituitary surgery.
METHODS
This was a nationwide cohort study using data from hospitalized patients with acromegaly or NFPA undergoing pituitary surgery in Switzerland between January 2012 and December 2021. Using 1:3 propensity score matching, eligible acromegaly patients were paired with NFPA patients who underwent pituitary surgery, respectively. The primary outcome comprised a composite of cardiovascular events (myocardial infarction, cardiac arrest, ischemic stroke, hospitalization for heart failure, unstable angina pectoris, cardiac arrhythmias, intracranial hemorrhage, hospitalization for hypertensive crisis) and all-cause mortality. Secondary outcomes included individual components of the primary outcome, surgical re-operation, and various hospital-associated outcomes.
RESULTS
Among 231 propensity score-matched patients with acromegaly and 491 with NFPA, the incidence rate of the primary outcome was 8.18 versus 12.73 per 1,000 person-years (hazard ratio [HR], 0.64; [95% confidence interval [CI], 0.31-1.32]). Mortality rates were numerically lower in acromegaly patients (2.43 vs. 7.05 deaths per 1,000 person-years; HR, 0.34; [95% CI, 0.10-1.17]). Individual components of the primary outcome and in-hospital outcomes showed no significant differences between the groups.
CONCLUSION
This cohort study did not find an increased risk of cardiovascular outcomes and mortality in patients with acromegaly undergoing pituitary surgery compared to surgically treated NFPA patients. These findings suggest that there is no legacy effect regarding higher cardio-metabolic risk in individuals with acromegaly once they receive surgical treatment.
PubMed: 38819619
DOI: 10.1007/s11102-024-01405-z -
Pituitary May 2024The COVID-19 pandemic created challenges in effective management of patients with acromegaly. Specifically, with regards to timely diagnosis, delays in surgeries, and... (Review)
Review
The COVID-19 pandemic created challenges in effective management of patients with acromegaly. Specifically, with regards to timely diagnosis, delays in surgeries, and disruption(s) to routine patient care. A transition to telemedicine did help to overcome safety restrictions that were placed on in-person care. Creation of surgical safety protocols in conjunction with widespread testing for COVID-19 has also helped with the resumption of pituitary surgery cases. However, acromegaly related comorbidities including cardiovascular disease, diabetes mellitus, sleep apnea and respiratory disease, vertebral fractures, and hypopituitarism, may increase the risk of a more severe COVID-19 infection course. Of note and to date, no negative trends in COVID-19 related outcomes have been reported in patients with acromegaly. Nevertheless, anxiety and depression rates in patients with acromegaly are higher than those in the general population. More studies are needed to assess the true impact of the COVID-19 pandemic on morbidity, mortality, and neuropsychiatric health of patients with acromegaly.
PubMed: 38819618
DOI: 10.1007/s11102-024-01404-0 -
Clinical Endocrinology May 2024To report our experience with F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI)...
OBJECTIVE
To report our experience with F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRI) in the care trajectory for persistent acromegaly.
DESIGN
Prospective case series.
PATIENTS
Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options.
MEASUREMENTS
FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery.
RESULTS
FET-PET/MRI showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRI was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRI identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRI findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients.
CONCLUSIONS
In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRI is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team.
PubMed: 38818709
DOI: 10.1111/cen.15079 -
Drugs in Context 2024Pasireotide-LAR is recommended as a second-line treatment for patients with acromegaly. Although the effects of pasireotide-LAR have been well characterized in clinical...
Pasireotide-LAR is recommended as a second-line treatment for patients with acromegaly. Although the effects of pasireotide-LAR have been well characterized in clinical studies, real-practice evidence is scant, especially in the long term and within the individualization of therapy in patients with comorbidities. To provide additional insight on the individualized approach to acromegaly management, six clinical cases of complex acromegaly treated with pasireotide-LAR for more than 5 years were reported. Pasireotide-LAR allowed the normalization of insulin-like growth factor 1 (IGF1) values in all patients and reduced tumour residue volume where present. A good safety profile and long-term tolerability were also reported.
PubMed: 38817802
DOI: 10.7573/dic.2024-1-2 -
TouchREVIEWS in Endocrinology Apr 2024Injectable somatostatin receptor ligands (iSRL) are the most frequently utilized medical therapy in patients with acromegaly; however, satisfaction rates are suboptimal.... (Review)
Review
Injectable somatostatin receptor ligands (iSRL) are the most frequently utilized medical therapy in patients with acromegaly; however, satisfaction rates are suboptimal. Injections can result in local erythema, discomfort and subcutaneous nodule formation, encompassed with the inconvenience of attending either primary or secondary care medical facilities for injections every 4 weeks. Some patients also note breakthrough of acromegaly-related symptoms towards the end of the injection cycle. To improve acceptance and ultimately improve wellbeing of these individuals, two oral SRLs, oral octreotide capsules (OOC) and paltusotine, have been developed. The OOC combines an enteric coating to allow delivery to the small intestines and a transient permeability enhancer to enable oral bioavailability. Comparable octreotide levels are obtained with twice-daily OOC and subcutaneous octreotide 100 µg. Phase III studies show OOC to maintain equivalent biochemical control in at least 60% of patients previously receiving a stable dose of iSRL. In longer-term studies, the response to OOC was durable up to 3 years. Paltusotine is a novel potent orally available non-peptidyl somatostatin receptor subtype-2 ligand. Studies in healthy volunteers show dose-dependent suppression of growth hormone-releasing hormone-induced growth hormone secretion and suppression of insulin-like growth factor-I (IGF-I) with repeat doses. In the recent phase II study, patients with acromegaly who were partial responders (IGF-I 1.0 - 2.5 x upper limit of normal) to monotherapy with iSRL when switched to once-daily paltusotine maintained control of IGF-I within 20% of baseline or lower in 87% after 13 weeks. Adverse events with both OOC and paltusotine were reflective of those recognized with iSRL and occurred at a similar frequency. OOC and paltusotine are well-received additions to the therapeutic armamentarium in medical therapy for the management of acromegaly; however, further data on efficacy, tumour control and shrinkage are required to allow positioning of this medication within the management algorithm for acromegaly.
PubMed: 38812672
DOI: 10.17925/EE.2023.20.1.3 -
TouchREVIEWS in Endocrinology Apr 2024The primary goal of acromegaly treatment is to normalize biochemical parameters as it significantly reduces the risks of complications and comorbidities associated with... (Review)
Review
The primary goal of acromegaly treatment is to normalize biochemical parameters as it significantly reduces the risks of complications and comorbidities associated with the disease. First-line medical treatment is commonly represented by injectable somatostatin analogues (SRLs) after surgery. In June 2020, with the integration of Transient Permeation Enhancer® technology, oral octreotide capsules (OOCs) received regulatory approval from the US Food and Drug Administration for long-term maintenance treatment in patients with acromegaly who have responded to and tolerated treatment with octreotide or lanreotide. We reviewed the clinical pharmacological data on the development and clinical use of OOCs. The pharmacokinetic and pharmacodynamic data on OOCs showed a dose-dependent increase in octreotide levels and remarkable suppression of growth hormone secretion. The efficacy and safety of OOCs were investigated in four clinical trials conducted on patients with complete or partially controlled acromegaly. The trials resulted in the maintenance of biochemical control after switching from injectable SRLs to OOCs, with a comparable side-effect profile. Moreover, the acromegaly symptoms improved in patients on OOC. The data showed a patient preference to continue in the OOC arm for the extension phase of the trials. From the clinical pharmacological perspective, oral formulation of octreotide has the advantage of efficacy and safety with respect to injectable octreotide.
PubMed: 38812667
DOI: 10.17925/EE.2024.20.1.9 -
Growth Hormone & IGF Research :... Jun 2024Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to... (Review)
Review
OBJECTIVE
Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species.
DESIGN
A comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed.
RESULTS
Acromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats. Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine.
CONCLUSION
Acromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found.
Topics: Acromegaly; Cats; Humans; Animals; Insulin-Like Growth Factor I; Cat Diseases
PubMed: 38810595
DOI: 10.1016/j.ghir.2024.101595