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Growth Hormone & IGF Research :... 2016Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1... (Review)
Review
Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly.
Topics: Acromegaly; Adenoma; Carney Complex; Genetic Diseases, X-Linked; Gigantism; Growth Hormone-Secreting Pituitary Adenoma; Humans; Multiple Endocrine Neoplasia; Multiple Endocrine Neoplasia Type 1; Succinate Dehydrogenase
PubMed: 27657986
DOI: 10.1016/j.ghir.2016.08.002 -
Journal of Clinical Medicine Mar 2021Growth hormone (GH)-secreting pituitary tumours represent the most genetically determined pituitary tumour type. This is true both for germline and somatic mutations.... (Review)
Review
Growth hormone (GH)-secreting pituitary tumours represent the most genetically determined pituitary tumour type. This is true both for germline and somatic mutations. Germline mutations occur in several known genes (, , , , , , , ) as well as familial cases with currently unknown genes, while somatic mutations in are present in up to 40% of tumours. If the disease starts before the fusion of the epiphysis, then accelerated growth and increased final height, or gigantism, can develop, where a genetic background can be identified in half of the cases. Hereditary GH-secreting pituitary adenoma (PA) can manifest as isolated tumours, familial isolated pituitary adenoma (FIPA) including cases with mutations or duplications (X-linked acrogigantism, XLAG) or can be a part of systemic diseases like multiple endocrine neoplasia type 1 or type 4, McCune-Albright syndrome, Carney complex or phaeochromocytoma/paraganglioma-pituitary adenoma association. Family history and a search for associated syndromic manifestations can help to draw attention to genetic causes; many of these are now tested as part of gene panels. Identifying genetic mutations allows appropriate screening of associated comorbidities as well as finding affected family members before the clinical manifestation of the disease. This review focuses on germline and somatic mutations predisposing to acromegaly and gigantism.
PubMed: 33805450
DOI: 10.3390/jcm10071377 -
Expert Review of Endocrinology &... May 2020: Acromegaly and gigantism entail increased morbidity and mortality if left untreated, due to the systemic effects of chronic GH and IGF-1 excess. Guidelines for the... (Review)
Review
: Acromegaly and gigantism entail increased morbidity and mortality if left untreated, due to the systemic effects of chronic GH and IGF-1 excess. Guidelines for the diagnosis and treatment of patients with GH excess are well established; however, the presentation, clinical behavior and response to treatment greatly vary among patients. Numerous markers of disease behavior are routinely used in medical practice, but additional biomarkers have been recently identified as a result of basic and clinical research studies.: This review focuses on genetic, molecular and genomic features of patients with GH excess that have recently been linked to disease progression and response to treatment. A PubMed search was conducted to identify markers of disease behavior in acromegaly and gigantism. Markers already considered as part of routine studies in clinical care guidelines were excluded. Literature search was expanded for each marker identified. Novel markers not included or only partially covered in previously published reviews on the subject were prioritized.: Recognizing the most relevant markers of disease behavior may help the medical team tailoring the strategies for approaching each case of acromegaly and gigantism. This customized plan should make the evaluation, treatment and follow up process more efficient, greatly improving the patients' outcomes.
Topics: Acromegaly; Biomarkers; Gigantism; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Humans; Insulin-Like Growth Factor I
PubMed: 32372673
DOI: 10.1080/17446651.2020.1749048 -
Annales D'endocrinologie Jun 2017X-linked acrogigantism (XLAG) is a new, pediatric-onset genetic syndrome, due to Xq26.3 microduplications encompassing the GPR101 gene. XLAG has a remarkably distinct... (Review)
Review
X-linked acrogigantism (XLAG) is a new, pediatric-onset genetic syndrome, due to Xq26.3 microduplications encompassing the GPR101 gene. XLAG has a remarkably distinct phenotype with disease onset occurring before the age of 5 in all cases described to date, which is significantly younger than in other forms of pituitary gigantism. These patients have mixed GH and prolactin positive adenomas and/or mixed-cell hyperplasia and highly elevated levels of GH/IGF-1 and prolactin. Given their particularly young age of onset, the significant GH hypersecretion can lead to a phenotype of severe gigantism with very advanced age-specific height Z-scores. If not adequately treated in childhood, this condition results in extreme final adult height. XLAG has a clinical course that is highly similar to some of the tallest people with gigantism in history.
Topics: Age of Onset; Female; Gene Duplication; Gigantism; History, 19th Century; History, 20th Century; Humans; Male; Pituitary Hormones; Prolactinoma; Receptors, G-Protein-Coupled
PubMed: 28457479
DOI: 10.1016/j.ando.2017.04.013 -
Current Opinion in Endocrinology,... Feb 2016To provide an update on the mechanisms leading to pituitary gigantism, as well as to familiarize the practitioner with the implication of these genetic findings on... (Review)
Review
PURPOSE OF REVIEW
To provide an update on the mechanisms leading to pituitary gigantism, as well as to familiarize the practitioner with the implication of these genetic findings on treatment decisions.
RECENT FINDINGS
Prior studies have identified gigantism as a feature of a number of monogenic disorders, including mutations in the aryl hydrocarbon receptor interacting protein gene, multiple endocrine neoplasia types 1 and 4, McCune Albright syndrome, Carney complex, and the paraganglioma, pheochromocytoma, and pituitary adenoma association because of succinate dehydrogenase defects. We recently described a previously uncharacterized form of early-onset pediatric gigantism caused by microduplications on chromosome Xq26.3 and we termed it X-LAG (X-linked acrogigantism). The age of onset of increased growth in X-LAG is significantly younger than other pituitary gigantism cases, and control of growth hormone excess is particularly challenging.
SUMMARY
Knowledge of the molecular defects that underlie pituitary tumorigenesis is crucial for patient care as they guide early intervention, screening for associated conditions, genetic counseling, surgical approach, and choice of medical management. Recently described microduplications of Xq26.3 account for more than 80% of the cases of early-onset pediatric gigantism. Early recognition of X-LAG may improve outcomes, as successful control of growth hormone excess requires extensive anterior pituitary resection and are difficult to manage with medical therapy alone.
Topics: Gigantism; Humans
PubMed: 26574647
DOI: 10.1097/MED.0000000000000212 -
Ugeskrift For Laeger Mar 2023Splenic artery aneurysms are rare but can be fatal. The majority are asymptomatic and small (less-than 2cm). The diagnosis is often incidental on abdominal CT, but this...
Splenic artery aneurysms are rare but can be fatal. The majority are asymptomatic and small (less-than 2cm). The diagnosis is often incidental on abdominal CT, but this case report presents of a 78-year-old woman who was diagnosed with a splenic artery aneurysm through a gastroscopy. The posterior gastric wall in the fundus-corpus junction showed a 7 cm area that was bulging into the lumen. The subsequent CT showed a gigantic splenic artery aneurysm measuring 9 cm in diameter. EUS is recommended because it has a high precision in diagnosing subepithelial lesions compared to abdominal CT scan.
Topics: Female; Humans; Aged; Gastroscopy; Aneurysm; Stomach; Tomography, X-Ray Computed; Abdomen
PubMed: 36999282
DOI: No ID Found -
Orphanet Journal of Rare Diseases Sep 2007Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and... (Review)
Review
Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty, and associated with variable minor features. The exact prevalence remains unknown but hundreds of cases have been reported. The diagnosis is usually suspected after birth because of excessive height and occipitofrontal circumference (OFC), advanced bone age, neonatal complications including hypotonia and feeding difficulties, and facial gestalt. Other inconstant clinical abnormalities include scoliosis, cardiac and genitourinary anomalies, seizures and brisk deep tendon reflexes. Variable delays in cognitive and motor development are also observed. The syndrome may also be associated with an increased risk of tumors. Mutations and deletions of the NSD1 gene (located at chromosome 5q35 and coding for a histone methyltransferase implicated in transcriptional regulation) are responsible for more than 75% of cases. FISH analysis, MLPA or multiplex quantitative PCR allow the detection of total/partial NSD1 deletions, and direct sequencing allows detection of NSD1 mutations. The large majority of NSD1 abnormalities occur de novo and there are very few familial cases. Although most cases are sporadic, several reports of autosomal dominant inheritance have been described. Germline mosaicism has never been reported and the recurrence risk for normal parents is very low (<1%). The main differential diagnoses are Weaver syndrome, Beckwith-Wiedeman syndrome, Fragile X syndrome, Simpson-Golabi-Behmel syndrome and 22qter deletion syndrome. Management is multidisciplinary. During the neonatal period, therapies are mostly symptomatic, including phototherapy in case of jaundice, treatment of the feeding difficulties and gastroesophageal reflux, and detection and treatment of hypoglycemia. General pediatric follow-up is important during the first years of life to allow detection and management of clinical complications such as scoliosis and febrile seizures. An adequate psychological and educational program with speech therapy and motor stimulation plays an important role in the global development of the patients. Final body height is difficult to predict but growth tends to normalize after puberty.
Topics: Abnormalities, Multiple; Animals; Craniofacial Abnormalities; Gigantism; Humans; Mutation; Syndrome
PubMed: 17825104
DOI: 10.1186/1750-1172-2-36 -
American Journal of Medical Genetics.... Sep 2022Beckwith-Wiedemann spectrum, Simpson-Golabi-Behmel syndrome, familial adenomatous polyposis and trisomy 18 are the most common congenital conditions associated with an... (Review)
Review
Beckwith-Wiedemann spectrum, Simpson-Golabi-Behmel syndrome, familial adenomatous polyposis and trisomy 18 are the most common congenital conditions associated with an increased incidence of hepatoblastoma (HB). In patients with these genetic disorders, screening protocols for HB are proposed that include periodic abdominal ultrasound and measurement of alpha-fetoprotein levels. Surveillance in these children may contribute to the early detection of HB and possibly improve their chances of overall survival. Therefore, physicians must be aware of the high HB incidence in children with certain predisposing genetic diseases.
Topics: Beckwith-Wiedemann Syndrome; Child; Genetic Diseases, X-Linked; Gigantism; Hepatoblastoma; Humans; Liver Neoplasms
PubMed: 35478319
DOI: 10.1002/ajmg.a.62767 -
Italian Journal of Pediatrics Aug 2017Referral for an assessment of tall stature is less common than for short stature. Tall stature is defined as a height more than two standard deviations above the mean... (Review)
Review
Referral for an assessment of tall stature is less common than for short stature. Tall stature is defined as a height more than two standard deviations above the mean for age. The majority of subjects with tall stature show a familial tall stature or a constitutional advance of growth (CAG), which is a diagnosis of exclusion. After a careful physical evaluation, tall subjects may be divided into two groups: tall subjects with normal appearance and tall subjects with abnormal appearance. In the case of normal appearance, the paediatric endocrinologist will have to evaluate the growth rate. If it is normal for age and sex, the subject may be classified as having familial tall stature, CAG or obese subject, while if the growth rate is increased it is essential to evaluate pubertal status and thyroid status. Tall subjects with abnormal appearance and dysmorphisms can be classified into those with proportionate and disproportionate syndromes.A careful physical examination and an evaluation of growth pattern are required before starting further investigations. Physicians should always search for a pathological cause of tall stature, although the majority of children are healthy and they generally do not need treatment to cease growth progression.The most accepted and effective treatment for an excessive height prediction is inducing puberty early and leading to a complete fusion of the epiphyses and achievement of final height, using testosterone in males and oestrogens in females. Alternatively, the most common surgical procedure for reducing growth is bilateral percutaneous epiphysiodesis of the distal femur and proximal tibia and fibula.This review aims to provide up-to-date information and suggestions about the diagnosis and management of children with tall stature.
Topics: Acromegaly; Adolescent; Anthropometry; Body Height; Child; Diagnosis, Differential; Dimensional Measurement Accuracy; Female; Gigantism; Growth Hormone; Humans; Male; Physical Examination
PubMed: 28774346
DOI: 10.1186/s13052-017-0385-5