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The Journal of Clinical Endocrinology... Sep 2023Congenital combined pituitary hormone deficiency (cCPHD) is the loss of ≥2 pituitary hormones caused by congenital factors. (Observational Study)
Observational Study
CONTEXT
Congenital combined pituitary hormone deficiency (cCPHD) is the loss of ≥2 pituitary hormones caused by congenital factors.
OBJECTIVE
We aimed to estimate the national incidence of cCPHD diagnosed before age 18 years and in subgroups.
METHODS
Patients with cCPHD were identified in the Danish National Patient Registry and Danish hospital registries in the period 1996-2020. Hospital files were reviewed and incidences calculated using background population data. Incidence was the main outcome measure.
RESULTS
We identified 128 patients with cCPHD; 88 (68.8%) were males. The median (range) age at diagnosis was 6.2 (0.01-19.0) years. The median (25th;75th percentile) number of hormone deficiencies at diagnosis was 3 (3; 4) at <1 year vs 2 (2; 2) at 1-17 years, P < .0001. Abnormal pituitary magnetic resonance imaging findings were seen in 70.3% (83/118). For those born in Denmark aged <18 years at diagnosis (n = 116/128) the estimated national incidence (95% CI) of cCPHD was 10.34 (7.79-13.72) per 100 000 births, with an annual incidence rate of 5.74 (4.33-7.62) per million. In subgroup analysis (diagnosis <1 vs 1-17 years), the incidence was highest in the 1-17 years subgroup, 7.97 (5.77-11.00) vs 1.98 (1.39-2.84) per 100 000 births, whereas the annual incidence rate was highest at <1 year, 19.8 (13.9-28.4) vs 4.69 (3.39-6.47) per million births.
CONCLUSION
cCPHD had the highest incidence rate and the most hormone deficiencies in those diagnosed at <1 year. The incidence was highest in the 1-17 years age group, underscoring the need for multiple pituitary hormone investigations throughout childhood and adolescence in children with only 1 hormone deficiency.
Topics: Male; Child; Female; Adolescent; Humans; Infant; Child, Preschool; Incidence; Hypopituitarism; Pituitary Hormones; Denmark
PubMed: 37043518
DOI: 10.1210/clinem/dgad198 -
Endocrinology and Metabolism (Seoul,... Oct 2022Over the past years, pituitary hormones and their receptors have been shown to have non-traditional actions that allow them to bypass the hypothalamus-pituitary-effector...
Over the past years, pituitary hormones and their receptors have been shown to have non-traditional actions that allow them to bypass the hypothalamus-pituitary-effector glands axis. Bone cells-osteoblasts and osteoclasts-express receptors for growth hormone, follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin, and vasopressin. Independent skeletal actions of pituitary hormones on bone have been studied using genetically modified mice with haploinsufficiency and by activating or inactivating the receptors pharmacologically, without altering systemic effector hormone levels. On another front, the discovery of a TSH variant (TSH-βv) in immune cells in the bone marrow and skeletal action of FSHβ through tumor necrosis factor α provides new insights underscoring the integrated physiology of bone-immune-endocrine axis. Here we discuss the interaction of each pituitary hormone with bone and the potential it holds in understanding bone physiology and as a therapeutic target.
Topics: Mice; Animals; Pituitary Hormones; Thyrotropin; Follicle Stimulating Hormone; Prolactin; Adrenocorticotropic Hormone
PubMed: 36168775
DOI: 10.3803/EnM.2022.1573 -
Journal of Clinical Research in... Nov 2023Recent reports have indicated the role of the prokineticin receptor 2 gene () in the etiology of pituitary hormone deficiencies, suggesting a potential role for the...
OBJECTIVE
Recent reports have indicated the role of the prokineticin receptor 2 gene () in the etiology of pituitary hormone deficiencies, suggesting a potential role for the PROK2 pathway in pituitary development, in addition to its role in gonadotropin releasing hormone-expressing neuron development. Here, we present the clinical and molecular findings of four patients with mutations.
METHODS
Next-generation targeted sequencing was used to screen 25 genes in 59 unrelated patients with multiple pituitary hormone deficiency (MPHD), isolated growth hormone (GH) deficiency, or idiopathic short stature.
RESULTS
Two different, very rare missense alterations classified as pathogenic (NM_144773.4:c.518T>G; NP_658986.1:p. (Leu173Arg)) and likely pathogenic (NM_144773.4:c.254G>A; NP_658986.1:p.(Arg85His)) were identified in four patients in heterozygous form. Patient 1 and Patient 2 presented with short stature and were diagnosed as GH deficiency. Patient 3 and Patient 4 presented with central hypothyroidism and cryptorchidism and were diagnosed as MPHD. No other pathogenic alterations were detected in the remaining 24 genes related to short stature, MPHD, and hypogonadotropic hypogonadism. Segregation analysis revealed asymptomatic or mildly affected carriers in the families.
CONCLUSION
dominance should be kept in mind as a very rare cause of GH deficiency and MPHD. Expressional variation or lack of penetrance may imply oligogenic inheritance or other environmental modifiers in individuals who are heterozygous carriers.
Topics: Growth Hormone; Pituitary Hormones; Dwarfism, Pituitary; Humans; Pedigree; Male; Female; Infant; Child; Receptors, G-Protein-Coupled; Consanguinity
PubMed: 37338295
DOI: 10.4274/jcrpe.galenos.2023.2023-4-4 -
Trends in Endocrinology and Metabolism:... Mar 2010Somatotropin-release inhibitory factor (SRIF) is a major regulator of pituitary function, mostly inhibiting hormone secretion and to a lesser extent pituitary cell... (Review)
Review
Somatotropin-release inhibitory factor (SRIF) is a major regulator of pituitary function, mostly inhibiting hormone secretion and to a lesser extent pituitary cell growth. Five SRIF receptor subtypes (SSTR1-5) are ubiquitously expressed G-protein coupled receptors. In the pituitary, SSTR1, 2, 3 and 5 are expressed, with SSTR2 and SSTR5 predominating. As new SRIF analogs have recently been introduced for treatment of pituitary disease, we evaluate the current knowledge of cell-specific pituitary SRIF receptor signaling and highlight areas of future research for comprehensive understanding of these mechanisms. Elucidating pituitary SRIF receptor signaling enables understanding of pituitary hormone secretion and cell growth, and also encourages future therapeutic development for pituitary disorders.
Topics: Animals; Humans; Models, Biological; Pituitary Diseases; Pituitary Hormones; Receptors, Somatostatin; Signal Transduction
PubMed: 20149677
DOI: 10.1016/j.tem.2009.12.003 -
Human Molecular Genetics Jan 2023Congenital hypopituitarism is a genetically heterogeneous condition that is part of a spectrum disorder that can include holoprosencephaly. Heterozygous mutations in...
Congenital hypopituitarism is a genetically heterogeneous condition that is part of a spectrum disorder that can include holoprosencephaly. Heterozygous mutations in SIX3 cause variable holoprosencephaly in humans and mice. We identified two children with neonatal hypopituitarism and thin pituitary stalk who were doubly heterozygous for rare, likely deleterious variants in the transcription factors SIX3 and POU1F1. We used genetically engineered mice to understand the disease pathophysiology. Pou1f1 loss-of-function heterozygotes are unaffected; Six3 heterozygotes have pituitary gland dysmorphology and incompletely ossified palate; and the Six3+/-; Pou1f1+/dw double heterozygote mice have a pronounced phenotype, including pituitary growth through the palate. The interaction of Pou1f1 and Six3 in mice supports the possibility of digenic pituitary disease in children. Disruption of Six3 expression in the oral ectoderm completely ablated anterior pituitary development, and deletion of Six3 in the neural ectoderm blocked the development of the pituitary stalk and both anterior and posterior pituitary lobes. Six3 is required in both oral and neural ectodermal tissues for the activation of signaling pathways and transcription factors necessary for pituitary cell fate. These studies clarify the mechanism of SIX3 action in pituitary development and provide support for a digenic basis for hypopituitarism.
Topics: Child; Humans; Heterozygote; Holoprosencephaly; Hypopituitarism; Transcription Factors; Mutation; Pituitary Hormones; Transcription Factor Pit-1
PubMed: 35951005
DOI: 10.1093/hmg/ddac192 -
Frontiers in Endocrinology 2023Over the past decades, adapted lifestyle and dietary habits in industrialized countries have led to a progress of obesity and associated metabolic disorders. Concomitant... (Review)
Review
Over the past decades, adapted lifestyle and dietary habits in industrialized countries have led to a progress of obesity and associated metabolic disorders. Concomitant insulin resistance and derangements in lipid metabolism foster the deposition of excess lipids in organs and tissues with limited capacity of physiologic lipid storage. In organs pivotal for systemic metabolic homeostasis, this ectopic lipid content disturbs metabolic action, thereby promotes the progression of metabolic disease, and inherits a risk for cardiometabolic complications. Pituitary hormone syndromes are commonly associated with metabolic diseases. However, the impact on subcutaneous, visceral, and ectopic fat stores between disorders and their underlying hormonal axes is rather different, and the underlying pathophysiological pathways remain largely unknown. Pituitary disorders might influence ectopic lipid deposition indirectly by modulating lipid metabolism and insulin sensitivity, but also directly by organ specific hormonal effects on energy metabolism. In this review, we aim to I) provide information about the impact of pituitary disorders on ectopic fat stores, II) and to present up-to-date knowledge on potential pathophysiological mechanisms of hormone action in ectopic lipid metabolism.
Topics: Humans; Lipid Metabolism; Pituitary Hormones, Anterior; Energy Metabolism; Homeostasis; Insulin Resistance; Lipids
PubMed: 36860364
DOI: 10.3389/fendo.2023.1075776 -
Minerva Endocrinologica Sep 2016Hypophysitis is generally accepted as an autoimmune disease which is characterized by inflammation and cellular infiltration of the pituitary gland. It can be either...
Hypophysitis is generally accepted as an autoimmune disease which is characterized by inflammation and cellular infiltration of the pituitary gland. It can be either primary or secondary. In this review, treatment of primary hypophysitis of various histological subtypes are discussed. Management of primary hypophysitis is usually symptomatic aiming to reduce the size of the pituitary mass and/or replace deficient pituitary hormones. Observation with replacement for deficient pituitary hormones can be applied in some group of patients. Keeping the complications of surgery in mind, surgical intervention should be limited to cases with severe and/or deteriorating compressive signs or cases with inconclusive findings of hypophysitis in whom treatment would be based on histopathological examination. The most commonly used drugs in the treatment of hypophysitis are glucocorticoids. They are able to reduce the size of the mass lesion with their anti-inflammatory effects and sometimes pituitary functions may also recover. However, there is no consensus about the optimal duration and dose of glucocorticoid use. When glucocorticoids and/or surgery fail, azathioprine, methotrexate, cyclosporin A and novel immunotherapies can be tried as third or forth line treatment. Radiotherapy and radiosurgery have been seldom used for treatment of hypophysitis in order to reduce the mass effect.
Topics: Autoimmune Hypophysitis; Combined Modality Therapy; Hormone Replacement Therapy; Humans; Immunotherapy; Pituitary Hormones
PubMed: 26963662
DOI: No ID Found -
The Journal of Endocrinology Dec 2015Central congenital hypothyroidism (CCH) may occur in isolation, or more frequently in combination with additional pituitary hormone deficits with or without associated... (Review)
Review
Central congenital hypothyroidism (CCH) may occur in isolation, or more frequently in combination with additional pituitary hormone deficits with or without associated extrapituitary abnormalities. Although uncommon, it may be more prevalent than previously thought, affecting up to 1:16 000 neonates in the Netherlands. Since TSH is not elevated, CCH will evade diagnosis in primary, TSH-based, CH screening programs and delayed detection may result in neurodevelopmental delay due to untreated neonatal hypothyroidism. Alternatively, coexisting growth hormones or ACTH deficiency may pose additional risks, such as life threatening hypoglycaemia. Genetic ascertainment is possible in a minority of cases and reveals mutations in genes controlling the TSH biosynthetic pathway (TSHB, TRHR, IGSF1) in isolated TSH deficiency, or early (HESX1, LHX3, LHX4, SOX3, OTX2) or late (PROP1, POU1F1) pituitary transcription factors in combined hormone deficits. Since TSH cannot be used as an indicator of euthyroidism, adequacy of treatment can be difficult to monitor due to a paucity of alternative biomarkers. This review will summarize the normal physiology of pituitary development and the hypothalamic-pituitary-thyroid axis, then describe known genetic causes of isolated central hypothyroidism and combined pituitary hormone deficits associated with TSH deficiency. Difficulties in diagnosis and management of these conditions will then be discussed.
Topics: Congenital Hypothyroidism; Humans; Infant, Newborn; Pituitary Gland; Pituitary Hormones
PubMed: 26416826
DOI: 10.1530/JOE-15-0341 -
American Journal of Physiology.... Sep 2015The somatotropic signaling pathway has been implicated in aging and longevity studies in mice and other species. The physiology and lifespans of a variety of mutant... (Review)
Review
The somatotropic signaling pathway has been implicated in aging and longevity studies in mice and other species. The physiology and lifespans of a variety of mutant mice, both spontaneous and genetically engineered, have contributed to our current understanding of the role of growth hormone and insulin-like growth factor I on aging-related processes. Several other mice discovered to live longer than their wild-type control counterparts also exhibit differences in growth factor levels; however, the complex nature of the phenotypic changes in these animals may also impact lifespan. The somatotropic axis impacts several pathways that dictate insulin sensitivity, nutrient sensing, mitochondrial function, and stress resistance as well as others that are thought to be involved in lifespan regulation.
Topics: Aging; Animals; Fibroblast Growth Factors; Growth Hormone; Insulin-Like Growth Factor I; Longevity; Mice; Mice, Knockout; Models, Animal; Pituitary Gland, Anterior; Pituitary Hormones, Anterior; Receptors, Somatomedin; Signal Transduction
PubMed: 26219867
DOI: 10.1152/ajpendo.00262.2015 -
Hormone Molecular Biology and Clinical... Nov 2016Pituitary hormones have traditionally been thought to exert specific, but limited function on target tissues. More recently, the discovery of these hormones and their... (Review)
Review
Pituitary hormones have traditionally been thought to exert specific, but limited function on target tissues. More recently, the discovery of these hormones and their receptors in organs such as the skeleton suggests that pituitary hormones have more ubiquitous functions. Here, we discuss the interaction of growth hormone (GH), follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin and arginine vasopressin (AVP) with bone. The direct skeletal action of pituitary hormones therefore provides new insights and therapeutic opportunities for metabolic bone diseases, prominently osteoporosis.
Topics: Animals; Bone Diseases, Metabolic; Bone and Bones; Humans; Pituitary Hormones
PubMed: 27508964
DOI: 10.1515/hmbci-2016-0015