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Journal of Cellular and Molecular... Dec 2023Ghrelin is a brain-gut peptide, and the first 28-peptide that was found in the gastric mucosa. It has a growth hormone (GH)-releasing hormone-like effect and can... (Review)
Review
Ghrelin is a brain-gut peptide, and the first 28-peptide that was found in the gastric mucosa. It has a growth hormone (GH)-releasing hormone-like effect and can potently promote the release of GH from pituitary GH cells; however, it is unable to stimulate GH synthesis. Therefore, ghrelin is believed to play a role in promoting bone growth and development. The correlation between ghrelin and some degenerative diseases of the musculoskeletal system has been reported recently, and ghrelin may be one of the factors influencing degenerative pathologies, such as osteoporosis, osteoarthritis, sarcopenia and intervertebral disc degeneration. With population ageing, the risk of health problems caused by degenerative diseases of the musculoskeletal system gradually increases. In this article, the roles of ghrelin in musculoskeletal disorders are summarized to reveal the potential effects of ghrelin as a key target in the treatment of related bone and muscle diseases and the need for further research.
Topics: Ghrelin; Growth Hormone; Human Growth Hormone
PubMed: 37661635
DOI: 10.1111/jcmm.17944 -
The Journal of Clinical Endocrinology... Nov 2023Somapacitan is a long-acting GH derivative for treatment of GH deficiency (GHD). (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Somapacitan is a long-acting GH derivative for treatment of GH deficiency (GHD).
OBJECTIVE
Evaluate the efficacy and tolerability of somapacitan in children with GHD after 2 years of treatment and after the switch from daily GH.
DESIGN
A randomized, multinational, open-labelled, controlled parallel group phase 3 trial, comprising a 52-week main phase and 3-year safety extension (NCT03811535).
SETTING
Eighty-five sites across 20 countries.
PATIENTS
A total of 200 treatment-naïve prepubertal patients were randomized and exposed; 194 completed the 2-year period.
INTERVENTIONS
Patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (0.034 mg/kg/d) during the first year, after which all patients received somapacitan 0.16 mg/kg/wk.
MAIN OUTCOME MEASURES
Height velocity (HV; cm/year) at week 104. Additional assessments included HV SD score (SDS), height SDS, IGF-I SDS, and observer-reported outcomes.
RESULTS
HV was sustained in both groups between 52 and 104 weeks. At week 104, mean (SD) for HV between weeks 52 and 104 was 8.4 (1.5) cm/year after continuous somapacitan treatment and 8.7 (1.8) cm/year after 1 year of somapacitan treatment following switch from daily GH. Secondary height-related endpoints also supported sustained growth. Mean IGF-I SDS during year 2 was similar between groups and within normal range (-2 to +2). Somapacitan was well tolerated, with no safety or tolerability issues identified. GH patient preference questionnaire results show that most patients and their caregivers (90%) who switched treatment at year 2 preferred once-weekly somapacitan over daily GH treatment.
CONCLUSIONS
Somapacitan in children with GHD showed sustained efficacy and tolerability for 2 years, and after switching from daily GH. Patients/caregivers switching from daily GH expressed a preference for somapacitan.
CLINICAL TRIAL REGISTRATION
NCT03811535.
Topics: Humans; Child; Insulin-Like Growth Factor I; Human Growth Hormone; Growth Hormone; Growth Disorders; Dwarfism, Pituitary; Body Height
PubMed: 37406251
DOI: 10.1210/clinem/dgad394 -
Reviews in Endocrine & Metabolic... Jun 2024Hypopituitarism, or the failure to secrete hormones produced by the anterior pituitary (adenohypophysis) and/or to release hormones from the posterior pituitary... (Review)
Review
Hypopituitarism, or the failure to secrete hormones produced by the anterior pituitary (adenohypophysis) and/or to release hormones from the posterior pituitary (neurohypophysis), can be congenital or acquired. When more than one pituitary hormone axis is impaired, the condition is known as combined pituitary hormone deficiency (CPHD). The deficiency may be primarily due to a hypothalamic or to a pituitary disorder, or concomitantly both, and has a negative impact on target organ function. This review focuses on the pathophysiology, diagnosis and management of anterior pituitary hormone deficiency in the pediatric age. Congenital hypopituitarism is generally due to genetic disorders and requires early medical attention. Exposure to toxicants or intrauterine infections should also be considered as potential etiologies. The molecular mechanisms underlying the fetal development of the hypothalamus and the pituitary are well characterized, and variants in the genes involved therein may explain the pathophysiology of congenital hypopituitarism: mutations in the genes expressed in the earliest stages are usually associated with syndromic forms whereas variants in genes involved in later stages of pituitary development result in non-syndromic forms with more specific hormone deficiencies. Tumors or lesions of the (peri)sellar region, cranial radiation therapy, traumatic brain injury and, more rarely, other inflammatory or infectious lesions represent the etiologies of acquired hypopituitarism. Hormone replacement is the general strategy, with critical periods of postnatal life requiring specific attention.
Topics: Humans; Hypopituitarism; Child; Pituitary Hormones, Anterior
PubMed: 38112850
DOI: 10.1007/s11154-023-09868-4 -
Archives of Medical Research Dec 2023Pituitary tumors (PT) are highly heterogeneous neoplasms, comprising functioning and nonfunctioning lesions. Functioning PT include prolactinomas, causing... (Review)
Review
Pituitary tumors (PT) are highly heterogeneous neoplasms, comprising functioning and nonfunctioning lesions. Functioning PT include prolactinomas, causing amenorrhea-galactorrhea in women and sexual dysfunction in men; GH-secreting adenomas causing acromegaly-gigantism; ACTH-secreting corticotrophinomas causing Cushing disease (CD); and the rare TSH-secreting thyrotrophinomas that result in central hyperthyroidism. Nonfunctioning PT do not result in a hormonal hypersecretion syndrome and most of them are of gonadotrope differentiation; other non-functioning PT include null cell adenomas and silent ACTH-, GH- and PRL-adenomas. Less than 5% of PT occur in a familial or syndromic context whereby germline mutations of specific genes account for their molecular pathogenesis. In contrast, the more common sporadic PT do not result from a single molecular abnormality but rather emerge from several oncogenic events that culminate in an increased proliferation of pituitary cells, and in the case of functioning tumors, in a non-regulated hormonal hypersecretion. In recent years, important advances in the understanding of the molecular pathogenesis of PT have been made, including the genomic, transcriptomic, epigenetic, and proteomic characterization of these neoplasms. In this review, we summarize the available molecular information pertaining the oncogenesis of PT.
Topics: Male; Pregnancy; Humans; Female; Pituitary Neoplasms; Proteomics; Adenoma; Genomics; Adrenocorticotropic Hormone; Gene Expression Profiling; Epigenesis, Genetic
PubMed: 37981525
DOI: 10.1016/j.arcmed.2023.102915 -
Thyroid : Official Journal of the... Jul 2023Many members of the American Thyroid Association played prominent roles in discovering the various aspects of the hypothalamic-pituitary-thyroid axis. This axis is...
Many members of the American Thyroid Association played prominent roles in discovering the various aspects of the hypothalamic-pituitary-thyroid axis. This axis is fundamental for maintaining the normal serum levels of circulating thyroid hormones (THs) and thus the euthyroid state. The pituitary glycoprotein hormone, thyrotropin (TSH), controls the activity of the thyroid gland. Thyrotropin-releasing hormone and the negative feedback mechanism of circulating TH regulate the synthesis and the secretion of TSH. The dynamic interplay of these two dominant mechanisms has essential effects on TSH release. Therefore, the finding of abnormal serum levels of TSH often indicates the presence of a disorder of thyroid gland function. A summary of key historical discoveries in the understanding of the hypothalamic-pituitary axis is presented.
Topics: Humans; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroid Hormones; Pituitary Gland
PubMed: 36716249
DOI: 10.1089/thy.2022.0258 -
Reviews in Endocrine & Metabolic... Jun 2024Hypopituitarism is a rare endocrine disorder characterized by insufficient hormone secretion from the pituitary gland. This condition leads to deficient production of... (Review)
Review
Hypopituitarism is a rare endocrine disorder characterized by insufficient hormone secretion from the pituitary gland. This condition leads to deficient production of one or more pituitary hormones, including growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), and antidiuretic hormone (ADH), also called arginine vasopressin (AVP). Symptoms vary widely and are often not, late recognized.Diagnosis typically involves a thorough clinical evaluation, hormone level assessments, and neuroimaging studies to identify underlying causes. Treatment aims to replace deficient hormones and address the underlying cause and related complications when possible. In this special issue we address diagnosis, comorbidities, and management of hypopituitarism. We hope that it will help healthcare professionals to manage their patients.
Topics: Humans; Hypopituitarism
PubMed: 38801648
DOI: 10.1007/s11154-024-09889-7 -
Stem Cell Reports Aug 2023Pituitary organoids are promising graft sources for transplantation in treatment of hypopituitarism. Building on development of self-organizing culture to generate...
Pituitary organoids are promising graft sources for transplantation in treatment of hypopituitarism. Building on development of self-organizing culture to generate pituitary-hypothalamic organoids (PHOs) using human pluripotent stem cells (hPSCs), we established techniques to generate PHOs using feeder-free hPSCs and to purify pituitary cells. The PHOs were uniformly and reliably generated through preconditioning of undifferentiated hPSCs and modulation of Wnt and TGF-β signaling after differentiation. Cell sorting using EpCAM, a pituitary cell-surface marker, successfully purified pituitary cells, reducing off-target cell numbers. EpCAM-expressing purified pituitary cells reaggregated to form three-dimensional pituitary spheres (3D-pituitaries). These exhibited high adrenocorticotropic hormone (ACTH) secretory capacity and responded to both positive and negative regulators. When transplanted into hypopituitary mice, the 3D-pituitaries engrafted, improved ACTH levels, and responded to in vivo stimuli. This method of generating purified pituitary tissue opens new avenues of research for pituitary regenerative medicine.
Topics: Mice; Animals; Humans; Adrenocorticotropic Hormone; Epithelial Cell Adhesion Molecule; Cell Culture Techniques; Cell Differentiation; Pluripotent Stem Cells
PubMed: 37295423
DOI: 10.1016/j.stemcr.2023.05.002 -
Indian Journal of Pediatrics Oct 2023Acquired hypothyroidism is generally also referred to as juvenile hypothyroidism. Hypothyroidism is due to the deficient secretion of thyroid hormones causing metabolic... (Review)
Review
Acquired hypothyroidism is generally also referred to as juvenile hypothyroidism. Hypothyroidism is due to the deficient secretion of thyroid hormones causing metabolic and neurological sequelae at the cellular level. It can present as overt hypothyroidism wherein the thyroid hormones (T4 and T3) secretion fall and thyrotropin (TSH) rises. Acquired hypothyroidism frequently presents between 9 and 11 y of age and is rarely seen before 4 y of age. Approximately 80% of the children and adolescents are asymptomatic at the time of diagnosis. Children with moderate to severe hypothyroidism often present for evaluation of poor growth, constipation, lethargy and/or dry skin. A detailed history and examination will provide us with enough clues for diagnosing hypothyroidism. Primary hypothyroidism can be diagnosed with raised TSH with subnormal levels of T3 and T4. Titres of thyroid antibodies - Anti-thyroperoxidase (TPO) and anti-thyroglobulin (ATG) antibodies, will be high in autoimmune hypothyroidism. Subclinical hypothyroidism is diagnosed with mildly elevated or high normal levels of TSH with free T4 being in the normal range. Insufficient secretion of thyrotropin from the pituitary causes central hypothyroidism. Acquired hypothyroidism is treated by replacement with levothyroxine. Regular monitoring of thyroid profile is necessary for adjusting doses of levothyroxine. Close monitoring and individualization of levothyroxine therapy is essential for normal growth and development of the child.
Topics: Adolescent; Child; Humans; Thyroxine; Hypothyroidism; Thyroid Hormones; Thyrotropin
PubMed: 37256446
DOI: 10.1007/s12098-023-04578-w -
The Journal of Endocrinology Jul 2024The pituitary gland orchestrates multiple endocrine organs by secreting tropic hormones, and therefore plays a significant role in a myriad of physiological processes,... (Review)
Review
The pituitary gland orchestrates multiple endocrine organs by secreting tropic hormones, and therefore plays a significant role in a myriad of physiological processes, including skeletal modeling and remodeling, fat and glucose metabolism, and cognition. Expression of receptors for each pituitary hormone and the hormone itself in the skeleton, fat, immune cells, and the brain suggest that their role is much broader than the traditionally attributed functions. FSH, believed solely to regulate gonadal function is also involved in fat and bone metabolism, as well as in cognition. Our emerging understanding of nonreproductive functions of FSH, thus, opens potential therapeutic opportunities to address detrimental health consequences during and after menopause, namely, osteoporosis, obesity, and dementia. In this review, we outline current understanding of the cross-talk between the pituitary, bone, adipose tissue, and brain through FSH. Preclinical evidence from genetic and pharmacologic interventions in rodent models, and human data from population-based observations, genetic studies, and a small number of interventional studies provide compelling evidence for independent functions of FSH in bone loss, fat gain, and congnitive impairment.
Topics: Humans; Brain; Animals; Follicle Stimulating Hormone; Bone and Bones; Adipose Tissue; Pituitary Gland; Osteoporosis
PubMed: 38579764
DOI: 10.1530/JOE-23-0377 -
Head & Neck Oct 2023There are limited studies and no surveillance protocols on pituitary dysfunction for adults who underwent anterior skull base radiation.
BACKGROUND
There are limited studies and no surveillance protocols on pituitary dysfunction for adults who underwent anterior skull base radiation.
METHODS
Cross-sectional study of 50 consecutive patients with sinonasal or nasopharyngeal cancer who underwent definitive radiotherapy. The mean radiation doses, prevalence of pituitary dysfunction, and associated factors were calculated.
RESULTS
Pituitary hormone levels were abnormal in 23 (46%) patients, including 6 (12%) with symptomatic abnormalities requiring treatment. The most common hormonal abnormality was hyperprolactinemia (30%), central hypothyroidism (8%) and central hypogonadism (6%). Patients with abnormal pituitary hormone values received higher mean radiation doses to the pituitary gland (1143 cGy, P = 0.04), pituitary stalk (1129 cGy, P = 0.02), optic chiasm (1094 cGy, P = 0.01), and hypothalamus (900 cGy, P = 0.01).
CONCLUSIONS
Nearly half of the patients had abnormal pituitary function, including over a tenth requiring treatment. There may be a dose-dependent association between hormonal dysfunction and radiation.
Topics: Adult; Humans; Nasopharyngeal Neoplasms; Prevalence; Cross-Sectional Studies; Pituitary Gland; Pituitary Hormones; Nasopharyngeal Carcinoma
PubMed: 37534890
DOI: 10.1002/hed.27476