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Frontiers in Endocrinology 2023Hypopituitarism is defined as a complete or partial deficiency in one or more pituitary hormones. Anterior hypopituitarism includes secondary adrenal insufficiency,... (Review)
Review
Hypopituitarism is defined as a complete or partial deficiency in one or more pituitary hormones. Anterior hypopituitarism includes secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency and prolactin deficiency. Patients with hypopituitarism suffer from an increased disability and sick days, resulting in lower health status, higher cost of care and an increased mortality. In particular during adulthood, isolated pituitary deficits are not an uncommon finding; their clinical picture is represented by vague symptoms and unclear signs, which can be difficult to properly diagnose. This often becomes a challenge for the physician. Aim of this narrative review is to analyse, for each anterior pituitary deficit, the main related etiologies, the characteristic signs and symptoms, how to properly diagnose them (suggesting an easy and reproducible step-based approach), and eventually the treatment. In adulthood, the vast majority of isolated pituitary deficits are due to pituitary tumours, head trauma, pituitary surgery and brain radiotherapy. Immune-related dysfunctions represent a growing cause of isolated pituitary deficiencies, above all secondary to use of oncological drugs such as immune checkpoint inhibitors. The diagnosis of isolated pituitary deficiencies should be based on baseline hormonal assessments and/or dynamic tests. Establishing a proper diagnosis can be quite challenging: in fact, even if the diagnostic methods are becoming increasingly refined, a considerable proportion of isolated pituitary deficits still remains without a certain cause. While isolated ACTH and TSH deficiencies always require a prompt replacement treatment, gonadal replacement therapy requires a benefit-risk evaluation based on the presence of comorbidities, age and gender of the patient; finally, the need of growth hormone replacement therapies is still a matter of debate. On the other side, prolactin replacement therapy is still not available. In conclusion, our purpose is to offer a broad evaluation from causes to therapies of isolated anterior pituitary deficits in adulthood. This review will also include the evaluation of uncommon symptoms and main etiologies, the elements of suspicion of a genetic cause and protocols for diagnosis, follow-up and treatment.
Topics: Humans; Prolactin; Pituitary Hormones, Anterior; Hypopituitarism; Pituitary Hormones; Pituitary Gland; Hypothalamic Diseases; Hypothyroidism
PubMed: 36967769
DOI: 10.3389/fendo.2023.1100007 -
Current Opinion in Neurobiology Jun 2017The melanin-concentrating hormone (MCH) is an essential neuromodulator involved with homeostatic regulation and motivated behaviors. The majority of MCH neurons are... (Review)
Review
The melanin-concentrating hormone (MCH) is an essential neuromodulator involved with homeostatic regulation and motivated behaviors. The majority of MCH neurons are localized within the zona incerta, lateral hypothalamic and incerto-hypothalamic areas but others regions, as the olfactory turbecle, the laterodorsal tegmental nucleus, the paramediam pontine reticular formation and the medial preoptic area, can also express the peptide depending on the gender and metabolic state of the animal. If the MCH on these novel sites of expression are also related with the control of wake-sleep cycle will be discuss in this review.
Topics: Animals; Humans; Hypothalamic Hormones; Melanins; Pituitary Hormones; Sex Factors; Sleep
PubMed: 28527391
DOI: 10.1016/j.conb.2017.04.008 -
The Journal of Clinical Endocrinology... Apr 2022Current GH therapy requires daily injections, which can be burdensome. Somapacitan is a long-acting GH derivative in development for treatment of GH deficiency (GHD). (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Current GH therapy requires daily injections, which can be burdensome. Somapacitan is a long-acting GH derivative in development for treatment of GH deficiency (GHD).
OBJECTIVE
Evaluate the efficacy, safety, and tolerability of once-weekly somapacitan after 3 years of treatment.
DESIGN
A multicenter, randomized, controlled, phase 2 study comparing somapacitan and once-daily GH for 156 weeks (NCT02616562).
SETTING
Twenty-nine sites in 11 countries.
PATIENTS
Fifty-nine children with GHD randomized (1:1:1:1) and exposed to treatment. Fifty-three children completed the 3-year period.
INTERVENTIONS
Patients received somapacitan (0.04 [n = 14], 0.08 [n = 15], or 0.16 [n = 14] mg/kg/wk) or daily GH (n = 14) (0.034 mg/kg/d, equivalent to 0.238 mg/kg/wk) subcutaneously during the first year, after which all patients on somapacitan received 0.16 mg/kg/wk.
MAIN OUTCOME MEASURES
Height velocity (HV) at year 3; changes from baseline in height SD score (HSDS), HVSDS, and IGF-I SDS.
RESULTS
The estimated treatment difference (95% CI) in HV for somapacitan 0.16/0.16 mg/kg/wk vs daily GH at year 3 was 0.8 cm/y (-0.4 to 2.1). Change in HVSDS from baseline to year 3 was comparable between somapacitan 0.16/0.16 mg/kg/wk, the pooled somapacitan groups, and daily GH. A gradual increase in HSDS from baseline was observed for all groups. At year 3, mean HSDS was similar for the pooled somapacitan groups and daily GH. Change from baseline to year 3 in mean IGF-I SDS was similar across treatments.
CONCLUSIONS
Once-weekly somapacitan in children with GHD showed sustained efficacy over 3 years in all assessed height-based outcomes with similar safety and tolerability to daily GH. A plain language summary (1) is available for this study.
CLINICAL TRIAL INFORMATION
This study has been registered at ClinicalTrials.gov, number NCT02616562 (REAL 3).
Topics: Body Height; Child; Dwarfism, Pituitary; Growth Hormone; Histidine; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Mannitol; Phenol; Pituitary Hormones, Anterior
PubMed: 34964458
DOI: 10.1210/clinem/dgab928 -
ELife Jan 2023The past decade has seen significant advances in our understanding of skeletal homeostasis and the mechanisms that mediate the loss of bone integrity in disease. Recent...
The past decade has seen significant advances in our understanding of skeletal homeostasis and the mechanisms that mediate the loss of bone integrity in disease. Recent breakthroughs have arisen mainly from identifying disease-causing mutations and modeling human bone disease in rodents, in essence, highlighting the integrative nature of skeletal physiology. It has become increasingly clear that bone cells, osteoblasts, osteoclasts, and osteocytes, communicate and regulate the fate of each other through RANK/RANKL/OPG, liver X receptors (LXRs), EphirinB2-EphB4 signaling, sphingolipids, and other membrane-associated proteins, such as semaphorins. Mounting evidence also showed that critical developmental pathways, namely, bone morphogenetic protein (BMP), NOTCH, and WNT, interact each other and play an important role in postnatal bone remodeling. The skeleton communicates not only with closely situated organs, such as bone marrow, muscle, and fat, but also with remote vital organs, such as the kidney, liver, and brain. The metabolic effect of bone-derived osteocalcin highlights a possible role of skeleton in energy homeostasis. Furthermore, studies using genetically modified rodent models disrupting the reciprocal relationship with tropic pituitary hormone and effector hormone have unraveled an independent role of pituitary hormone in skeletal remodeling beyond the role of regulating target endocrine glands. The cytokine-mediated skeletal actions and the evidence of local production of certain pituitary hormones by bone marrow-derived cells displays a unique endocrine-immune-skeletal connection. Here, we discuss recently elucidated mechanisms controlling the remodeling of bone, communication of bone cells with cells of other lineages, crosstalk between bone and vital organs, as well as opportunities for treating diseases of the skeleton.
Topics: Humans; Bone and Bones; Osteoblasts; Osteoclasts; Osteocytes; Pituitary Hormones
PubMed: 36656634
DOI: 10.7554/eLife.83142 -
Neuro-oncology Jun 2017Pituitary adenomas are one of the most common primary central nervous system tumors and have an estimated prevalence of 17%. Approximately half of pituitary adenomas... (Review)
Review
Pituitary adenomas are one of the most common primary central nervous system tumors and have an estimated prevalence of 17%. Approximately half of pituitary adenomas secrete distinct pituitary hormones (most often prolactin, growth hormone, or adrenocorticotropic hormone). While these tumors are histologically benign, they have potent endocrine effects that lead to significant morbidity and shortened lifespan. Because of their pathophysiologic endocrine secretion and anatomic location near critical neural/vascular structures, hormone-secreting pituitary adenomas require defined management paradigms that can include relief of mass effect and biochemical remission. Management of hormone-secreting pituitary adenomas involves a multidisciplinary approach that can incorporate surgical, medical, and/or radiation therapies. Early and effective treatment of hormone-secreting pituitary adenomas can reduce morbidity and mortality. Consequently, understanding clinical features as well as therapeutic options in the context of the specific biological features of each type of hormone-secreting pituitary adenoma is critical for optimal management.
Topics: Adenoma; Animals; Humans; Pituitary Hormones; Pituitary Neoplasms
PubMed: 27543627
DOI: 10.1093/neuonc/now130 -
Nature Reviews. Endocrinology Dec 2023Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone... (Review)
Review
Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone secretion from endocrine organs. However, the evolutionary biology of pituitary hormones and their receptors provides evidence for a broad range of functions in vertebrate physiology. Over the past decade, we and others have discovered that thyroid-stimulating hormone, follicle-stimulating hormone, adrenocorticotropic hormone, prolactin, oxytocin and arginine vasopressin act directly on somatic organs, including bone, adipose tissue and liver. New evidence also indicates that pituitary hormone receptors are expressed in brain regions, nuclei and subnuclei. These studies have prompted us to attribute the pathophysiology of certain human diseases, including osteoporosis, obesity and neurodegeneration, at least in part, to changes in pituitary hormone levels. This new information has identified actionable therapeutic targets for drug discovery.
Topics: Humans; Pituitary Hormones; Pituitary Gland; Prolactin; Adipose Tissue; Brain
PubMed: 37715028
DOI: 10.1038/s41574-023-00894-5 -
Hormones (Athens, Greece) Jun 2022Prolactin, a pituitary hormone that was discovered about 80 years ago and is primarily known for its functions in mammary gland development and lactation, is now known... (Review)
Review
Prolactin, a pituitary hormone that was discovered about 80 years ago and is primarily known for its functions in mammary gland development and lactation, is now known to participate in numerous functions across different phylogenetic groups. Fundamentally known for its secretion from lactotroph cells in adenohypophysis region of pituitary gland, newer studies have demonstrated a number of extrapituitary sites which secrete prolactin, where it acts in an autocrine, paracrine, and endocrine manner to regulate essential physiological and biochemical processes. These sites include lymphocytes, epithelial cells of lactating mammary glands, breast cancer cells of epithelial origin, and the placenta. The placenta is one of the most important organs secreting prolactin; however, its role in placental biology has not to date been reviewed comprehensively. This review elaborates upon the various facets of prolactin hormone, including prolactin production and its post-translational modifications and signaling. Major emphasis is placed on placental prolactin and its potential roles, ranging from the role of prolactin in angiogenesis, preeclampsia, maternal diabetes, and anti-apoptosis, among others.
Topics: Female; Humans; Lactation; Pituitary Gland; Placenta; Pregnancy; Prolactin; Signal Transduction
PubMed: 35545690
DOI: 10.1007/s42000-022-00373-y -
Endocrinology Dec 2022The discovery of hypothalamic hormones propelled exciting advances in pharmacotherapy and improved life quality worldwide. Growth hormone-releasing hormone (GHRH) is a... (Review)
Review
The discovery of hypothalamic hormones propelled exciting advances in pharmacotherapy and improved life quality worldwide. Growth hormone-releasing hormone (GHRH) is a crucial element in homeostasis maintenance, and regulates the release of growth hormone from the anterior pituitary gland. Accumulating evidence suggests that this neuropeptide can also promote malignancies, as well as inflammation. Our review is focused on the role of that 44 - amino acid peptide (GHRH) and its antagonists in inflammation and vascular function, summarizing recent findings in the corresponding field. Preclinical studies demonstrate the protective role of GHRH antagonists against endothelial barrier dysfunction, suggesting that the development of those peptides may lead to new therapies against pathologies related to vascular remodeling (eg, sepsis, acute respiratory distress syndrome). Targeted therapies for those diseases do not exist.
Topics: Humans; Growth Hormone-Releasing Hormone; Growth Hormone; Pituitary Gland, Anterior; Peptides; Inflammation; Receptors, Pituitary Hormone-Regulating Hormone
PubMed: 36503995
DOI: 10.1210/endocr/bqac209 -
Hormone Research in Paediatrics 2022People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in... (Review)
Review
BACKGROUND
People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in "shows." Serious medical evaluation began in the late 19th century with the description of acromegaly and its association with pituitary tumors. In the early 20th century, multiple investigators attempted to extract a growth-promoting factor from the anterior pituitary and then, over the decades, to purify it and distinguish it from other anterior pituitary hormones. With relatively pure growth hormone (GH), its biological activity in growth promotion and as a metabolic hormone were studied, and species specificity became apparent: primate GH was the only GH active in man. Human GH was prepared from cadaveric pituitaries and distributed by the NIH to treat children with GH deficiency, but there was never enough pituitary hGH for all of the children who required it. When Creutzfeldt-Jakob disease was found in some patients who received pituitary GH, the production and FDA approval of biosynthetic hGH dramatically accelerated. With a large supply, one could treat those who were GH deficient and test its efficacy in other causes of short stature; longer acting versions of hGH have now been developed, tested, and in a few instances received FDA approval.
SUMMARY
It has been a long journey from the description of over- and underproduction of GH in animals to the production and clinical use of the biosynthetic hormones.
KEY MESSAGES
The efforts of basic scientists led to the extraction and purification of GH. Clinical scientists have expanded the appropriate use of hGH for short children with conditions in addition to GH deficiency.
Topics: Animals; Humans; Acromegaly; Dwarfism; Endocrine System Diseases; Growth Hormone; Human Growth Hormone; Pituitary Hormones, Anterior
PubMed: 36446319
DOI: 10.1159/000526440 -
American Journal of Physiology.... Nov 2015The hormonal family of vasoinhibins, which derive from the anterior pituitary hormone prolactin, are known for their inhibiting effects on blood vessel growth,... (Review)
Review
The hormonal family of vasoinhibins, which derive from the anterior pituitary hormone prolactin, are known for their inhibiting effects on blood vessel growth, vasopermeability, and vasodilation. As pleiotropic hormones, vasoinhibins act in multiple target organs and tissues. The generation, secretion, and regulation of vasoinhibins are embedded into the organizational principle of an axis, which integrates the hypothalamus, the pituitary, and the target tissue microenvironment. This axis is designated as the prolactin/vasoinhibin axis. Disturbances of the prolactin/vasoinhibin axis are associated with the pathogenesis of retinal and cardiac diseases and with diseases occurring during pregnancy. New phylogenetical, physiological, and clinical implications are discussed.
Topics: Animals; Cell Cycle Proteins; Gene Expression Regulation; Humans; Neovascularization, Physiologic; Prolactin
PubMed: 26310939
DOI: 10.1152/ajpregu.00256.2015