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Pituitary Jun 2024
PubMed: 38916827
DOI: 10.1007/s11102-024-01416-w -
European Journal of Endocrinology Jun 2024Serum insulin-like growth factor (IGF-I) is the primary biochemical measure of disease activity in patients with acromegaly, and 2014 Endocrine Society guidelines...
Serum insulin-like growth factor (IGF-I) is the primary biochemical measure of disease activity in patients with acromegaly, and 2014 Endocrine Society guidelines recommended normal age-adjusted serum IGF-I as the biochemical target of treatment. However, quantification and interpretation of IGF-I levels are subject to limitations that may affect therapeutic decisions. Techniques for measuring IGF-I have evolved greatly over the past 40 years and continue to do so. Results can vary substantially for different assays, procedures, and laboratories. For any assay, interpretation of IGF-I values requires robust reference ranges. Using currently available large normative databases, the upper limit of normal (ULN) for IGF-I in middle-aged and elderly individuals is lower than historical reference ranges. Thus, the goal of achieving IGF-I <1× ULN is more demanding than in the past, and some patients with acromegaly who were classified as "normal" (IGF-I <1× ULN) in previous studies would be reclassified as above the ULN based on newer normative data. In addition, substantial intra-individual, week-to-week variation in serum IGF-I levels (unrelated to assay performance) has been observed. With changes over time in the measurement of IGF-I and the advent of updated reference ranges derived from large normative databases, it is difficult to justify rigid adherence to the goal of maintaining IGF-I below the ULN for all patients with acromegaly. Instead, symptoms, comorbidities, and quality of life should be considered, along with growth hormone and IGF-I levels, when evaluating the need for further treatment.
PubMed: 38916798
DOI: 10.1093/ejendo/lvae065 -
Molecular and Cellular Endocrinology Jun 2024AMPK (AMP-activated protein kinase) is an enzyme that acts as a metabolic sensor and regulates multiple pathways via phosphorylating proteins in metabolic and...
INTRODUCTION
AMPK (AMP-activated protein kinase) is an enzyme that acts as a metabolic sensor and regulates multiple pathways via phosphorylating proteins in metabolic and proliferative pathways. The aim of this work was to study the activated cellular AMPK (phosphorylated-AMPK at Thr172, pAMPK) levels in pituitary tumor samples from patients with sporadic and familial acromegaly, as well as in samples from normal human pituitary gland.
METHODS
We studied pituitary adenoma tissue from patients with sporadic somatotroph adenomas, familial acromegaly with heterozygote germline variants in the aryl hydrocarbon receptor interacting protein (AIP) gene (p.Q164*, p.R304* and p.F269_H275dup) and autopsy from normal pituitary glands without structural alterations.
RESULTS
Cellular levels of pAMPK were significantly higher in patients with sporadic acromegaly compared to normal pituitary glands (p < 0.0001). Tissues samples from patients with germline AIP mutations also showed higher cellular levels of pAMPK compared to normal pituitary glands. We did not observe a significant difference in cellular levels of pAMPK according to the cytokeratin (CAM5.2) pattern (sparsely or densely granulated) for tumor samples of sporadic acromegaly.
CONCLUSION
Our data show, for the first time in human cells, an increase of cellular levels of pAMPK in sporadic somatotropinomas, regardless of cytokeratin pattern, as well as in GH-secreting adenomas from patients with germline AIP mutations.
PubMed: 38908427
DOI: 10.1016/j.mce.2024.112318 -
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 -
The Journal of Clinical Endocrinology... Jun 2024a paradoxical growth hormone (GH) response to oral glucose load (OGTT) in acromegaly is associated with a milder phenotype.
CONTEXT
a paradoxical growth hormone (GH) response to oral glucose load (OGTT) in acromegaly is associated with a milder phenotype.
OBJECTIVE
To study whether the GH response to OGTT predicts the risk of recurrence after initial surgical cure.
DESIGN
Retrospective, observational study.
SETTING
Two tertiary care centers.
PATIENTS
We investigated 254 patients with acromegaly who were cured by surgery.
INTERVENTION
All patients underwent OGTT at diagnosis before pituitary surgery. A peak-to-basal GH ratio ≥ 120% within 90 minutes was used to distinguish paradoxical (GH-Par) from non-paradoxical acromegalic patients (GH-NPar).
MAIN OUTCOME MEASURE
Cox analysis was used to investigate whether the paradoxical GH response to OGTT was associated with the risk of disease recurrence.
RESULTS
A paradoxical GH response to OGTT occurred in 87 patients (34.3%, termed GH-Par group). Recurrence of acromegaly occurred in three patients of the GH-Par group (3.4%) and in 20 patients in the GH-NPar group (12.0%). In the multivariate analysis, the paradoxical GH response to OGTT was significantly associated with the risk of recurrence (HR 0.18, 95% CI, 0.05-0.63; P = 0.007). Basal GH level at diagnosis was the only other variable associated with the risk of disease recurrence (HR 1.58, 95% CI, 1.01-2.47; P = 0.04).
CONCLUSIONS
our study demonstrates that a paradoxical GH response to OGTT in the preoperative setting predicts a lower risk of disease recurrence after initial surgical cure. The pattern of GH responsiveness to OGTT is, therefore, useful to predict the long-term outcome of patients with acromegaly.
PubMed: 38878276
DOI: 10.1210/clinem/dgae410 -
Innere Medizin (Heidelberg, Germany) Jul 2024The widespread use of diagnostic imaging has led to an increase in the incidence of pituitary tumors. The majority of incidentalomas are hormone-inactive (HI) pituitary... (Review)
Review
The widespread use of diagnostic imaging has led to an increase in the incidence of pituitary tumors. The majority of incidentalomas are hormone-inactive (HI) pituitary microadenomas. The most common clinically relevant pituitary adenomas are prolactin-secreting, followed by HI, and far less common are growth hormone (GH)-, adrenocorticotropic hormone (ACTH)- and thyroid-stimulating hormone (TSH)-secreting adenomas. Pituitary adenomas are usually benign, although aggressive growth and invasion occurs in individual cases. Very rarely, they give rise to metastases and are then termed pituitary carcinomas. All pituitary tumors require endocrine testing for pituitary hormone excess. In addition to the medical history and clinical examination, laboratory diagnostics are very important. Symptoms such as irregular menstruation, loss of libido or galactorrhea often lead to the timely diagnosis of prolactinomas, and hyperprolactinemia can easily confirm the diagnosis (considering the differential diagnoses). Diagnosis is more difficult for all other hormone-secreting pituitary adenomas (acromegaly, Cushing's disease, TSHoma), as the symptoms are often non-specific (i.e., headaches, weight gain, fatigue, joint pain). Furthermore, comorbidities such as hypertension, diabetes, and depression are such widespread diseases that pituitary adenomas are rarely considered as the underlying cause. Timely diagnosis and appropriate treatment have a significant impact on morbidity, mortality, and quality of life. Therefore, the role of primary care physicians is very important for achieving an early diagnosis. In addition, patients with pituitary adenomas should always be referred to endocrinologists to ensure optimal diagnosis as well as treatment.
Topics: Humans; Pituitary Neoplasms; Diagnosis, Differential; Adenoma; Prolactinoma
PubMed: 38869654
DOI: 10.1007/s00108-024-01729-9 -
Clinical Endocrinology Jun 2024Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several...
OBJECTIVE
Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.
METHODS
A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.
RESULTS
Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.
CONCLUSION
This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
PubMed: 38865284
DOI: 10.1111/cen.15095 -
Zhonghua Jie He He Hu Xi Za Zhi =... Jun 2024Obstructive sleep apnea (OSA) shows sex differences in the pathophysiology, epidemiology, and clinical presentation. Women have different characteristics of OSA at...
Obstructive sleep apnea (OSA) shows sex differences in the pathophysiology, epidemiology, and clinical presentation. Women have different characteristics of OSA at different life stages. Based on 26 guidelines and consensus, 121 English literatures, and 24 Chinese literatures, the Sleep Disorder Group of Chinese Thoracic Society has drafted a consensus with multidisciplinary experts to summarize the epidemiology, clinical characteristics, diagnosis, treatment, and follow-up of OSA in women at different life stages, particularly issues related to OSA during pregnancy. The consensus is divided into four parts: epidemiology, diagnosis, treatment, and issues for pregnant women with OSA, with 34 recommendations covering 13 clinical issues. The aim was to improve the understanding and managements of OSA in women. What is the prevalence of OSA in women at different life stages?The prevalence of OSA varies among women at different life stages. Sex differences are not significant in childhood and adolescence. The prevalence of OSA in women of childbearing age is significantly lower than that in men. The prevalence of OSA increases during pregnancy due to changes in hormone levels and the influence of pregnancy physiology, as well as with gestational weeks. In postmenopausal women, the prevalence of OSA increases significantly, and the sex differences are no longer significant. What are the risk factors for OSA in women at different life stages?The risk factors for OSA in women at different life stages are not identical. (1) Childhood and adolescence: Tonsillar and adenoid hypertrophy, obesity, and craniofacial structural anomalies increase the risk of OSA; (2) Childbearing age: The prevalence of OSA in women is lower than in men. However, obesity, hypothyroidism, acromegaly, and polycystic ovary syndrome increase the risk of OSA, and these patients should be screened for OSA; (3) Pregnancy: hormonal effects, uterine enlargement, and weight changes increase the risk of OSA, especially in those with a history of snoring or OSA before pregnancy; (4) Perimenopausal and post-menopausal periods: Decreased levels of estrogen/progesterone reduce the protective effects on the upper airways, and increase the risk of OSA. Menopause is an important risk factor for OSA in women. What are the harms of OSA in women?OSA is an independent risk factor for diseases such as hypertension, cardiovascular and cerebrovascular diseases, metabolic disorders, emotional and cognitive impairments, and malignant tumors in women. OSA during pregnancy has several adverse effects on maternal and infant health, and is associated with increased risks of preeclampsia, hypertensive disorders complicating pregnancy (HDP), gestational diabetes mellitus (HDM), premature birth, neonatal asphyxia, fetal growth restriction, . What are the clinical symptoms and physical signs of OSA in women?The symptoms of OSA in women are different from those in men. Attention should be paid to whether women snore and the frequency of snoring, especially among postmenopausal and obese women. The atypical symptoms of OSA, including insomnia, daytime fatigue, morning headache, anxiety and nightmares, should not be ignored, especially in postmenopausal, obese, and pregnant women. When should women be screened for OSA?(1) Postmenopausal and pregnant women, as well as women with a first-degree relative with OSA. It should be noted that the clinical symptoms of OSA in women are not typical; (2) Women with polycystic ovary syndrome, hypothyroidism, and acromegaly; (3) Women engaged in various occupations, including driving and working at heights. How to screen OSA in women?Many screening tools and questionnaires can be used to screen for OSA, but should not be used to diagnose OSA in the absence of objective sleep tests. (1) Questionnaires and screening tools: The STOP-Bang questionnaire targeting the general population has higher sensitivity than Berlin Questionnaire (BQ), Epworth Sleepiness Scale (ESS), and others. STOP Bang≥3 points combined with ESS can further improve its specificity and can be used for OSA screening in women. However, the questionnaire has poor sensitivity for female OSA. Type Ⅳ monitoring devices can be used for OSA screening in women with a weak recommendation; (2) PSG is the gold standard for diagnosis. Type Ⅱ or Ⅲ portable monitoring (PM) devices are recommended for the diagnosis of OSA in women in the following conditions: 1) Diagnosis of high-risk OSA patients without complex comorbidities; 2) OSA patients who are immobile or critically ill and unable to undergo PSG monitoring in a sleep center; 3) Diagnosis of perioperative OSA patients; 4) Pregnant women with high suspicion of OSA. How to diagnose OSA in women?The diagnostic and grading criteria for adult non-pregnant women with OSA are the same as the diagnostic criteria for adult OSA; for diagnosis and grading of OSA in pregnant women, see "Section 4: OSA in Pregnancy". How to treat OSA in women?For all the OSA patients with varying degrees of severity in women, the general treatment can be applied: weight loss, dietary control, exercise, position therapy, reduction of alcohol intake, and cautious use of sedative and hypnotic drugs. Medical costs and the risk of comorbidities with OSA in women are higher than those in men. Therefore, OSA patients in women should be promptly evaluated and treated. How to optimize non-invasive positive pressure ventilation (NPPV) treatment and improve compliance for OSA patients in women?(1) NPPV is the first-line treatment for moderate to severe OSA in women. It can relieve upper airway obstruction, eliminate sleep hypoxia, improve sleep quality and quality of life, and reduce the incidence of related complications and mortality; (2) To improve compliance with NPPV treatment, behavioral interventions and patient education are recommended. Selecting an appropriate human-machine interface, improving the humidification effect, promptly handling adverse reactions, and applying remote medical models may improve the compliance. What are the other options for OSA treatment in women?Other treatment methods include oral appliances, upper airway surgery, and sublingual nerve stimulation therapy, which have moderate therapeutic effects in women. Postmenopausal hormone therapy (MHT) in women has a certain therapeutic effect on OSA, but its safety needs further evaluation. What is follow-up evaluation for OSA in women?(1) Follow-up every 6 months or 1 year after receiving NPPV treatment; (2) PSG should be rechecked at the 3rd and 6th months after surgical treatment to evaluate the therapeutic effects. For patients with poor therapeutic effects after surgery, it is recommended to use treatments such as NPPV; (3) PSG should be rechecked at the 3rd and 6th months after oral appliance treatment. Oral appliances should be adjusted as needed to consolidate long-term efficacy, or switched to a treatment such as NPPV; (4) During follow-up, attention should be paid to the improvement of apnea hypopnea index(AHI), symptoms, and side effects; (5) It is recommended that NPPV treatment be remotely managed via the internet, which can provide high-quality and comprehensive sleep care; (6) Follow-up of OSA during pregnancy can be found in "Section 4: OSA in Pregnancy ". How to diagnose and evaluate OSA during pregnancy?OSA during pregnancy has adverse effects on maternal and infant outcomes. It is recommended that high-risk pregnant women be screened and diagnosed for OSA during pregnancy management and healthcare.(1) Screening of the high-risk population: Individuals who meet any of the following criteria are considered at high risk for OSA during pregnancy. 1) Symptoms: snoring during sleep, arousal, headache in the morning, insomnia, depression, excessive daytime sleepiness, and fatigue; 2) Pregnant women over 35 years old; 3) Physical signs: weight exceeding standard body weight by 20% or more, BMI≥28 kg/m, and neck circumference>40 cm; anatomical abnormalities of the upper airways, such as nasal obstruction, tonsil hypertrophy, and mandibular retrognathia, .; 4) Combined internal medicine diseases, such as refractory hypertension, unknown arrhythmia, chronic congestive heart failure, refractory diabetes and insulin resistance, refractory asthma, hypothyroidism, primary aldosteronism; 5) Those with obstetric related diseases, such as preeclampsia, HDP, GDM, and intrauterine growth restriction of the fetus, and with symptoms of chest tightness and apnea that cannot be explained by other factors, and with previous history of gestational OSA or family history.(2) Screening time: There is currently no strong evidence to support the recommendation for optimal screening time. Given the adverse effects of OSA on mothers and infants, it is recommended that high-risk individuals of OSA be screened for OSA between12 and 18 weeks of pregnancy.(3) Screening tools: The main manifestations of OSA in pregnant women are insomnia and poor sleep quality, whereas daytime drowsiness is often not severe. Various sleep questionnaires and models for OSA in pregnancy have poor sensitivity and specificity. Type Ⅳ and consumer-level monitoring devices are lack of sufficient clinical validation. It is recommended that the results of the above screening tools should only have an indicative role in the diagnosis of OSA during pregnancy.(4) Diagnostic tools: PSG is the gold standard for the diagnosis of OSA in pregnancy. PM may be the first choice diagnostic technique for OSA in pregnancy, and Type Ⅲ monitoring devices are the most commonly used devices.(5) Diagnostic criteria: Diagnosis of OSA during pregnancy should be based on symptoms, signs, and PSG or PM monitoring results. Diagnostic criteria for OSA during pregnancy are as follows: 1) PSG or PM monitoring shows AHI≥5 times/h with symptoms or signs of OSA in women, or with related complications (such as diagnosed hypertension, emotional disorders, unexplained arrhythmias, chronic congestive heart failure, HDP, HDM, intrauterine growth restriction that cannot be explained by other factors, chest tightness and apnea excluding other reasons), or with previous history of OSA or family history of OSA; 2) PSG or PM monitoring shows AHI≥10 times/h in those with less daytime drowsiness (ESS≤9 points). How to manage OSA during pregnancy?(1) Once OSA is diagnosed during pregnancy, personalized treatment plans from pregnancy to birth should be developed through collaborative discussions between sleep center professionals, obstetricians, pregnant women, and their families. Multidisciplinary collaboration among anaesthesia, neonatology, and critical care medicine may be required in some cases. A comprehensive management approach should be adopted based on the patient's condition, which includes strengthening weight management, positioning treatment, NPPV treatment, oral appliances, and management of maternal and infant complications; (2) Considering the Regarding continuous weight gain during pregnancy, APAP treatment is more appropriate mode for pregnant women with OSA; (3) Oral appliances are suitable for patients with snoring or mild to moderate OSA, especially those with combined mandibular retraction or NPPV intolerance. However, oral appliances are not recommended as the first-line treatment; (4) It is not recommended to use surgical methods to treat OSA during pregnancy; (5) Follow-up and evaluation: Patients' conditions should be re-evaluated and treatment plans should be adjusted at around 24 weeks of pregnancy. Postpartum PSG or PM monitoring should be repeated to assess the need for continued treatment after delivery.
Topics: Humans; Sleep Apnea, Obstructive; Female; Pregnancy; Pregnancy Complications; Consensus
PubMed: 38858201
DOI: 10.3760/cma.j.cn112147-20240206-00072 -
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