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Frontiers in Endocrinology 2024Acromegaly is a rare endocrine disorder caused by hypersecretion of growth hormone (GH) from a pituitary adenoma. Elevated GH levels stimulate excess production of...
UNLABELLED
Acromegaly is a rare endocrine disorder caused by hypersecretion of growth hormone (GH) from a pituitary adenoma. Elevated GH levels stimulate excess production of insulin-like growth factor 1 (IGF-1) which leads to the insidious onset of clinical manifestations. The most common primary central nervous system (CNS) tumors, meningiomas originate from the arachnoid layer of the meninges and are typically benign and slow-growing. Meningiomas are over twice as common in women as in men, with age-adjusted incidence (per 100,000 individuals) of 10.66 and 4.75, respectively. Several reports describe co-occurrence of meningiomas and acromegaly. We aimed to determine whether patients with acromegaly are at elevated risk for meningioma. Investigation of the literature showed that co-occurrence of a pituitary adenoma and a meningioma is a rare phenomenon, and the majority of cases involve GH-secreting adenomas. To the best of our knowledge, a systematic review examining the association between meningiomas and elevated GH levels (due to GH-secreting adenomas in acromegaly or exposure to exogenous GH) has never been conducted. The nature of the observed coexistence between acromegaly and meningioma -whether it reflects causation or mere co-association -is unclear, as is the pathophysiologic etiology.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022376998.
Topics: Humans; Meningioma; Acromegaly; Meningeal Neoplasms; Human Growth Hormone; Risk Factors; Adenoma
PubMed: 38919490
DOI: 10.3389/fendo.2024.1407615 -
Endocrinology and Metabolism (Seoul,... Jun 2024To identify a screening tool for obstructive sleep apnea (OSA) and evaluate the effects of endoscopic transsphenoidal surgery on improving OSA in patients with...
BACKGROUND
To identify a screening tool for obstructive sleep apnea (OSA) and evaluate the effects of endoscopic transsphenoidal surgery on improving OSA in patients with acromegaly.
METHODS
We prospectively enrolled adults with acromegaly scheduled for endoscopic transsphenoidal surgery. All measurements were conducted when participants were admitted for a baseline work-up for acromegaly before surgery and surveillance approximately 3 to 6 months after surgery. Respiratory event index (REI) was used as a surrogate for apnea-hypopnea index (Trial Registration: NCT03526016).
RESULTS
Of the 35 patients with acromegaly (median age, 47 years; 40% men; median body mass index, 24.4 kg/m2), 24 (68.6%) had OSA (REI ≥5/hour), 15 (42.9%) had moderate-to-severe OSA (REI ≥15/hour). At baseline, serum insulin-like growth factor 1 (IGF-1) levels were positively correlated with the REI (ρ=0.53, P=0.001). The sensitivity and negative predictive value of a Snoring, Tiredness, Observed apnea, high blood Pressure-Body mass index, age, Neck circumference, and Gender (STOP-Bang) score ≥ 3 were 93.3% and 87.5%, respectively, detecting moderate-to-severe OSA. Biochemical acromegaly remission was achieved in 32 (91.4%) patients. The median difference in the REI was -9.5/hour (95% confidence interval, -13.3 to -5.3). Half of the 24 patients diagnosed with OSA preoperatively had REI <5/hour postoperatively. In a linear mixed-effects model, changes in the REI across surgery were related to changes in IGF-1 levels.
CONCLUSION
The STOP-Bang questionnaire is a reliable tool for OSA among patients with acromegaly. Improvement in OSA severity after surgery is related to decreased IGF-1 levels.
PubMed: 38918903
DOI: 10.3803/EnM.2024.1933 -
BMC Endocrine Disorders Jun 2024An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary...
PURPOSE
An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index.
METHODS
We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55).
RESULTS
IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04).
CONCLUSIONS
Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.
Topics: Humans; Prolactinoma; Insulin-Like Growth Factor I; Female; Male; Adult; Retrospective Studies; Dopamine Agonists; Pituitary Neoplasms; Middle Aged; Cabergoline; Body Weight; Follow-Up Studies; Prolactin; Body Mass Index; Prognosis
PubMed: 38902646
DOI: 10.1186/s12902-024-01622-4 -
Cureus May 2024Headache is a frequent symptom in patients with acromegaly; however, it has never been described as a cervicogenic-like headache. This paper reports on an 18-year-old...
Headache is a frequent symptom in patients with acromegaly; however, it has never been described as a cervicogenic-like headache. This paper reports on an 18-year-old Brazilian man with a four-year history of unilateral headaches characterized as a sensation of tightness or pressure in the right nuchal region spreading across the forehead. An MRI of the brain revealed a pituitary tumor and a transsphenoidal surgical resection of the macroadenoma was performed. During follow-up, he reported a complete relief of headaches after one week of surgery, persisting for six months. This paper shows a cervicogenic-like headache as the first symptom of acromegaly and the improvement of symptoms after surgery.
PubMed: 38894775
DOI: 10.7759/cureus.60599 -
Cureus Jun 2024Angle's class III malocclusions are characterized by the anterior positioning of the mandible in relation to the maxilla. The discrepancy can be caused by an anterior...
Angle's class III malocclusions are characterized by the anterior positioning of the mandible in relation to the maxilla. The discrepancy can be caused by an anterior deficiency of the maxilla, excessive mandibular prognathism, or a combination of both. Acromegaly is a dysfunction caused by the excessive production of growth hormone (GH), which leads to systemic changes and orofacial manifestations. In acromegaly caused by a pituitary adenoma, which secretes an excessive amount of GH, disproportionate mandibular growth may occur, leading to skeletal class III malocclusion in adulthood. Excessive growth stops when the tumor is removed, but the skeletal deformity persists, requiring orthognathic surgery to reposition the mandible. This article reports the case of a 31-year-old man referred to the maxillofacial surgery consultation due to severe Angle's class III malocclusion, with prognathism, mandibular asymmetry, and maxillary retrusion. He had a history of disproportionate soft tissue growth (hands and feet) up to 18 years old, less evident after that age. Considering the possibility of acromegaly due to a pituitary adenoma, imaging studies (CT scan and magnetic resonance imaging (MRI)) and directed analytical studies were requested. When the diagnosis was confirmed, the patient was referred to endocrinology and neurosurgery consultations. After undergoing endoscopic resection of the pituitary adenoma, the patient underwent surgery-first orthognathic surgery to correct the dental malocclusion.
PubMed: 38855491
DOI: 10.7759/cureus.61999 -
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