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Annales D'endocrinologie Dec 2023Acromegaly is a rare disease with prevalence of approximately 60 cases per million, slight female predominance and peak onset in adults in the fourth decade. Clinical... (Review)
Review
Acromegaly is a rare disease with prevalence of approximately 60 cases per million, slight female predominance and peak onset in adults in the fourth decade. Clinical diagnosis is often delayed by several years due to the slowly progressive onset of symptoms. There are multiple clinical criteria that define acromegaly: dysmorphic syndrome of insidious onset, symptoms related to the pituitary tumor (headaches, visual disorders), general signs (sweating, carpal tunnel syndrome, joint pain, etc.), complications of the disease (musculoskeletal, cardiovascular, pneumological, dental, metabolic comorbidities, thyroid nodules, colonic polyps, etc.) or sometimes clinical signs of associated prolactin hypersecretion (erectile dysfunction in men or cycle disorder in women) or concomitant mass-induced hypopituitarism (fatigue and other symptoms related to pituitary hormone deficiencies). Biological confirmation is based initially on elevated IGF-I and lack of GH suppression on oral glucose tolerance test or an elevated mean GH on repeated measurements. In confirmed cases, imaging by pituitary MRI identifies the causal tumor, to best determine management. In a minority of cases, acromegaly can be linked to a genetic predisposition, especially when it occurs at a young age or in a familial context. The first-line treatment is most often surgical removal of the somatotroph pituitary tumor, either immediately or after transient medical treatment. Medical treatments are most often proposed in patients not controlled by surgical removal. Conformal or stereotactic radiotherapy may be discussed on a case-by-case basis, especially in case of drug inefficacy or poor tolerance. Acromegaly should be managed by a multidisciplinary team, preferably within an expert center such as a reference or skill center for rare pituitary diseases.
Topics: Male; Adult; Humans; Female; Acromegaly; Human Growth Hormone; Pituitary Neoplasms; Glucose Tolerance Test; Clinical Protocols
PubMed: 37579837
DOI: 10.1016/j.ando.2023.08.003 -
Deutsches Arzteblatt International Feb 20243% of all children are unusually short, and 3% are unusually tall. New approaches have broadened the range of therapeutic options in treating growth disorders. (Review)
Review
BACKGROUND
3% of all children are unusually short, and 3% are unusually tall. New approaches have broadened the range of therapeutic options in treating growth disorders.
METHODS
This review is based on publications retrieved by a selective review of the literature and on the authors' clinical experience.
RESULTS
Pituitary growth hormone deficiency is treated with recombinant growth hormone. Long-acting preparations of this type became available recently, but their long-term safety and efficacy are still unknown. Vosoritide, a CNP analogue, has also been approved for the treatment of achondroplasia, and severe primary deficiency of insulin-like growth factor 1 (IGF-1) can be treated with recombinant IGF-1. In the treatment of excessively tall stature, new information on the safety of growth-attenuating treatment and an altered perception of above-average height in society have led to a change in management.
CONCLUSION
There are new options for the treatment of rare causes of short stature, while new information on the safety of treatment strategies for excessive tallness have led to a reconsideration of surgical intervention. There is insufficient evidence on the benefits and risks of supraphysiological GH therapy and of newer treatment options for which there are as yet no robust data on adult height. Therefore, before any treatment is provided, physicians should give patients and their families detailed information and discuss their expectations from treatment and the goals that treatment can be expected to achieve.
Topics: Child; Adult; Humans; Adolescent; Insulin-Like Growth Factor I; Human Growth Hormone; Growth Disorders; Dwarfism, Pituitary; Physicians
PubMed: 38051162
DOI: 10.3238/arztebl.m2023.0247 -
The Science of the Total Environment Feb 2024Tetrachlorobisphenol A (TCBPA) is the chlorinated derivative of bisphenol A (BPA). Several studies have found that BPA adversely affects the reproductive activity...
Tetrachlorobisphenol A (TCBPA) is the chlorinated derivative of bisphenol A (BPA). Several studies have found that BPA adversely affects the reproductive activity largely through binding to estrogen receptors and the critical period of BPA exposure advances the vaginal opening time in the female offspring via the kisspeptin/G protein-coupled receptor 54 (KGG) system. However, whether TCBPA can affect puberty initiation via KGG and the roles of estrogen receptors in this process remain unknown. Therefore, this study investigated the influence of TCBPA on the onset time of puberty in Wistar rats and the related molecular mechanisms by combing in vitro GT1-7 cells and molecular docking. In female Wistar rats, TCBPA at ≥100 mg/kg bw/day (49.2 μmol/L in rat body) markedly advanced vaginal opening time and increased serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropin-releasing hormone (GnRH). It also increased the relative gene expression of LH receptor (LHR), GnRH1, and FSH receptor (FSHR) in hypothalamic-pituitary-gonadal (HPG) axis tissues. In GT1-7 cells, TCBPA increased genes and proteins associated with KGG pathway and activated the extracellular-regulated protein kinase 1/2 (Erk1/2) and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) pathways via G protein-coupled estrogen membrane receptor 1 (GPER1) and estrogen receptor alpha (ERα). Docking analyses supported its interactions with GPER1 and ERα, and treatment with specific inhibitors of ERα- and GPER1-modulated PI3K/Akt and Erk1/2 signaling suppressed its effects. Taken together, TCBPA-induced advancement of puberty initiation in Wistar rats thus results primarily from increased LH, GnRH, and FSH secretion together with GnRH1, FSHR, and LHR upregulation driven by ERα- and GPER1-modulated Erk1/2 and PI3K/Akt signaling. Our results provide new molecular insights into the reproductive toxicity of EDCs.
Topics: Rats; Female; Animals; Receptors, Estrogen; Rats, Wistar; Estrogen Receptor alpha; Proto-Oncogene Proteins c-akt; Molecular Docking Simulation; Phosphatidylinositol 3-Kinases; Sexual Maturation; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Follicle Stimulating Hormone
PubMed: 37992829
DOI: 10.1016/j.scitotenv.2023.168643 -
PloS One 2023General anesthesia can disturb the hormone levels in surgical patients. Hormone deficiency is one of the major symptoms of craniopharyngioma (CP) in pediatric patients.... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
General anesthesia can disturb the hormone levels in surgical patients. Hormone deficiency is one of the major symptoms of craniopharyngioma (CP) in pediatric patients. The aim of this prospective randomized controlled clinical study is to evaluate whether propofol and sevoflurane influence the perioperative hormone levels in these patients and to determine which anesthesia technique causes less impact on hormone levels.
MATERIALS
Sixty-four ASA I and II pediatric patients with CP undergoing elective neurosurgery were randomly divided into the sevoflurane group (S group, n = 32) and the propofol group (P group, n = 32). Anesthesia was maintained with sevoflurane and propofol until the end of the operation. Demographic information, operation information and hemodynamic variables were recorded. The levels of hormones were evaluated preoperatively as the baseline (T0), 1h after the beginning of the operation (T1), immediately at the end of the operation (T2) and 72 h postoperatively (T3).
RESULTS
There were no significant differences in the two groups in terms of patients' demographics and intraoperative information, such as operation duration, blood loss and transfusion volumes, and fluid infusion volume (P>0.05). In both groups, compared to those at T0, the levels of TSH, FT3, TT3 and ACTH at T1, T2 and T3 were significantly lower. The levels of FSH, PRL and GH at T3 were also significantly lower (P<0.05). The FT3 and TT3 levels of both groups at T2 and T3 were significantly lower than those at T1, but the ACTH level was significantly increased (P<0.05). Compared to the levels at T2, the TSH, FT3, FT4 and ACTH levels of the two groups at T3 were significantly reduced (P<0.05). The baseline hormone levels of both groups were similar (P>0.05). At T1, the FT3, TT3, FT4, TT4 and ACTH levels in the P group were significantly lower than those in the S group (P<0.05). At T2, the TT3 and ACTH levels of the P group were significantly lower than those of the S group (P<0.05) At T3, the TT4 level in the P group was significantly lower than that of the S group (P<0.05).
CONCLUSION
Propofol and sevoflurane could reduce the levels of hormones intraoperatively and postoperatively in pediatric patients with craniopharyngioma. However, propofol reduced hormone levels more intensively, mainly intraoperatively. Postoperatively, propofol and sevoflurane had similar inhibition effects on the shift in hormone levels. Therefore, in pediatric patients with craniopharyngioma undergoing neurosurgery, sevoflurane might be the preferred anesthetic because it causes less interruption of hormone levels. However, because of their similar postoperative effects, which long-term effects of sevoflurane or propofol could produce optimal clinical situations? Thus more extensive clinical studies are needed.
TRIAL REGISTRATION
Clinical trial registration. This trail was registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn, Jun Xiong) on 28/12/2021, registration number was ChiCTR2100054885.
Topics: Humans; Child; Propofol; Sevoflurane; Craniopharyngioma; Anesthesia, General; Pituitary Neoplasms; Adrenocorticotropic Hormone; Thyrotropin; Methyl Ethers; Anesthetics, Inhalation
PubMed: 37506116
DOI: 10.1371/journal.pone.0288863 -
European Journal of Applied Physiology Sep 2023Heavy resistance exercise (HRE) is the most effective method for inducing muscular hypertrophy and stimulating anabolic hormones, including growth hormone, into the... (Review)
Review
Heavy resistance exercise (HRE) is the most effective method for inducing muscular hypertrophy and stimulating anabolic hormones, including growth hormone, into the blood. In this review, we explore possible mechanisms within the GH secretory pathway of the pituitary somatotroph, which are likely to modulate the flow of hormone synthesis and packaging as it is processed prior to exocytosis. Special emphasis is placed on the secretory granule and its possible role as a signaling hub. We also review data that summarize how HRE affects the quality and quantity of the secreted hormone. Finally, these pathway mechanisms are considered in the context of heterogeneity of the somatotroph population in the anterior pituitary.
Topics: Humans; Growth Hormone; Somatotrophs; Resistance Training; Human Growth Hormone; Signal Transduction
PubMed: 37421488
DOI: 10.1007/s00421-023-05263-8 -
Endocrine-related Cancer Mar 2024Radiotherapy is one of the major options currently for cancer treatment. Radiotherapy causes cellular damage inducing cell death, which is expected to be selective for... (Review)
Review
Radiotherapy is one of the major options currently for cancer treatment. Radiotherapy causes cellular damage inducing cell death, which is expected to be selective for tumor cells. However, side effects that alter the surrounding normal tissue are often hard to be avoided. When radiation involves the hypothalamic-pituitary axis, growth hormone deficiency (GHD) is frequently induced, causing developmental and metabolic-related diseases in childhood cancer survivors. Growth hormone (GH) replacement therapy has been used for these patients and has been shown to be safe in general. However, there are some debating for its long-term safety due to the known roles of GH in inducing cell growth, which could be related to cancer recurrence. In addition, studies have shown that GH is involved in the development of resistance to chemotherapy and radiotherapy through various mechanisms. In this review, we will first discuss the effects of GHD induced after radiotherapy and the safety of the GH replacement treatment. Then, we will discuss the role of the GH-IGF-1 axis in radioresistance via a mechanism of improving DNA repair.
Topics: Humans; Growth Hormone; Human Growth Hormone; Hypopituitarism; Insulin-Like Growth Factor I; Hormone Replacement Therapy
PubMed: 38174978
DOI: 10.1530/ERC-22-0371 -
Medicina (Kaunas, Lithuania) Nov 2023: The Marquette Method (MM) has been used for many years to track the postpartum return of fertility using the ClearBlue Fertility Monitor (CBFM). A new quantitative... (Observational Study)
Observational Study
: The Marquette Method (MM) has been used for many years to track the postpartum return of fertility using the ClearBlue Fertility Monitor (CBFM). A new quantitative urine hormone monitor (the Mira Analyzer) was compared to the CBFM in one previous study, and using this pilot data, several women have started to use the Mira Analyzer in the postpartum transition to fertility. : This study was a retrospective, observational case series that analyzed hormone data on the Mira Analyzer during the postpartum period. Participants were invited to share their postpartum cycle and hormone observations. Quantitative hormones in the urine included estrone-3-glucuronide (E3G), luteinizing hormone (LH), and pregnanediol glucuronide (PDG). Data were collected using an electronic survey and an online portal for hormone data. Data collected included participant demographics, menstrual cycle characteristics, and reproductive health history. Hormone range values were calculated, and thresholds were identified that would best predict the first ovulation that led to the first postpartum menstrual period, as well as in transition cycles. Hormone patterns were identified in the context of previous studies. : Twenty participants contributed data for the analysis. Triggering ovulation before the first period postpartum (Cycle 0) usually required higher LH thresholds than for regularly cycling women. Three different patterns were observed in the return of fertility postpartum: minimal ovarian activity, follicular activity without ovulation, and the early return of fertility. Abstinence rates for avoiding pregnancy with experimental thresholds were calculated. : Higher LH thresholds in Cycle 0 suggest a decreased responsiveness of the ovaries to LH stimulation from the pituitary. This study replicates postpartum hormone patterns from a previous study. Larger studies are planned to evaluate the effectiveness for avoiding pregnancy using the Mira Analyzer in the postpartum return of fertility.
Topics: Pregnancy; Female; Humans; Retrospective Studies; Luteinizing Hormone; Menstrual Cycle; Postpartum Period; Fertility
PubMed: 38004057
DOI: 10.3390/medicina59112008 -
Endocrine Oct 2023Non-functioning pituitary macroadenomas (NFPMs) may present with hypopituitarism. Pituitary surgery and radiotherapy pose an additional risk to pituitary function.
BACKGROUND
Non-functioning pituitary macroadenomas (NFPMs) may present with hypopituitarism. Pituitary surgery and radiotherapy pose an additional risk to pituitary function.
OBJECTIVES
To assess the incidence of hypopituitarism at presentation, the impact of treatment, and the likelihood of endocrine recovery during follow-up.
METHODS
All patients treated surgically with and without radiotherapy for NFPMs between 1987 and 2018 who had longer than six months follow-up were identified. Demographics, presentation, investigation, treatment, and outcomes were collected.
RESULTS
In total, 383 patients were identified. The median age was 57 years, with a median follow-up of 8 years. Preoperatively, 227 patients (227/375; 61%) had evidence of at least one pituitary deficiency. Anterior panhypopituitarism was more common in men (p = 0.001) and older patients (p = 0.005). Multiple hormone deficiencies were associated with large tumours (p = 0.03). Patients treated with surgery and radiotherapy had a higher incidence of all individual pituitary hormone deficiency, anterior panhypopituitarism, and significantly lower GH, ACTH, and TSH deficiencies free survival probability than those treated with surgery alone. Recovery of central hypogonadism, hypothyroidism, and anterior panhypopituitarism was also less likely to be reported in those treated with surgery and radiotherapy. Those with preoperative hypopituitarism had a higher risk of pituitary impairment at latest review than those presented with normal pituitary function (p = 0.001).
CONCLUSION
NFPMs are associated with a significant degree of hypopituitarism at time of diagnosis and post-therapy. The combination of surgery and radiotherapy is associated with a higher risk of pituitary dysfunction. Recovery of pituitary hormone deficit may occur after treatment. Patients should have regular ongoing endocrine evaluation post-treatment to assess changes in pituitary function and the need for long-term replacement therapy.
Topics: Male; Humans; Middle Aged; Retrospective Studies; Hypopituitarism; Pituitary Gland; Pituitary Neoplasms; Pituitary Hormones; Hypothyroidism
PubMed: 37389717
DOI: 10.1007/s12020-023-03434-3 -
Reviews in Endocrine & Metabolic... Jun 2024Growth hormone (GH) is secreted by somatotropic cells of the anterior pituitary gland. The classical effects of GH comprise the stimulation of cell proliferation, tissue... (Review)
Review
Growth hormone (GH) is secreted by somatotropic cells of the anterior pituitary gland. The classical effects of GH comprise the stimulation of cell proliferation, tissue and body growth, lipolysis, and insulin resistance. The GH receptor (GHR) is expressed in numerous brain regions. Notably, a growing body of evidence indicates that GH-induced GHR signaling in specific neuronal populations regulates multiple physiological functions, including energy balance, glucose homeostasis, stress response, behavior, and several neurological/cognitive aspects. The importance of central GHR signaling is particularly evident when the organism is under metabolic stress, such as pregnancy, chronic food deprivation, hypoglycemia, and prolonged exercise. These particular situations are associated with elevated GH secretion. Thus, central GH action represents an internal signal that coordinates metabolic, neurological, neuroendocrine, and behavioral adaptations that are evolutionarily advantageous to increase the chances of survival. This review summarizes and discusses recent findings indicating that the brain is an important target of GH, and GHR signaling in different neuronal populations regulates essential physiological functions.
Topics: Humans; Brain; Animals; Receptors, Somatotropin; Growth Hormone; Signal Transduction; Human Growth Hormone
PubMed: 38060062
DOI: 10.1007/s11154-023-09861-x -
Archives of Medical Research Dec 2023Acromegaly is a chronic disease resulting from constantly elevated concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I). If not adequately... (Review)
Review
Acromegaly is a chronic disease resulting from constantly elevated concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I). If not adequately treated, GH and IGF-I excess is associated with various cardiovascular risk factors. These symptoms mainly include hypertension and impaired glucose metabolism, which can be observed in approximately one-third of patients. Other comorbidities are dyslipidemia and the presence of obstructive sleep apnea syndrome. However, even in the absence of conventional cardiovascular risk factors, myocardial hypertrophy can occur, which reflects the impact of GH and IGF-I excess itself on the myocardium and is defined as acromegalic cardiomyopathy. Whereas previous echocardiography-based studies reported a high prevalence of cardiomyopathy, this prevalence is much lower in cardiac magnetic resonance imaging-based studies. Myocardial hypertrophy in acromegaly is due to a homogeneous increase in the intracellular myocardial mass and extracellular myocardial matrix and improves following successful treatment through intracellular changes. Intramyocardial water retention or ectopic lipid accumulation might not be of relevant concern. Successful treatment significantly improves myocardial morphology, as well as cardiovascular risk factors. In addition to GH/IGF-I-lowering therapy, the diagnosis and treatment of cardiovascular complications is crucial for the successful management of acromegaly.
Topics: Humans; Growth Hormone; Acromegaly; Cardiovascular Diseases; Insulin-Like Growth Factor I; Risk Factors; Human Growth Hormone; Cardiomyopathies; Heart Disease Risk Factors; Hypertrophy
PubMed: 38040526
DOI: 10.1016/j.arcmed.2023.102921