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Current Biology : CB Oct 2022Sauropod dinosaurs include the largest land animals to have walked the earth, mostly weighing 10-70 tons (e.g., Sander et al. and Carballido et al.). Osteohistology... (Review)
Review
Sauropod dinosaurs include the largest land animals to have walked the earth, mostly weighing 10-70 tons (e.g., Sander et al. and Carballido et al.). Osteohistology suggests that derived physiological traits evolved near the origin of sauropod gigantism, including both rapid and uninterrupted growth from juvenile to adult with little developmental plasticity. This differs from the slower, seasonally interrupted growth of their direct ancestors, as evident in most non-sauropodan sauropodomorphs, which also show developmental plasticity in some groups. Accelerated but seasonally interrupted growth is present in Lessemsauridae, the sister clade to Sauropoda, which also attained giant adult body sizes (>10 tons). These observations suggest a correlation between giant size and accelerated growth. However, testing this evolutionary connection has been limited by the incomplete understanding of the growth patterns in some of the closest non-giant relatives of sauropods. We present the osteohistology of two such taxa, Aardonyx celestae and Sefapanosaurus zatronensis. Both exhibit highly vascularized woven-parallel complexes, with fibrolamellar complexes during early to mid-ontogeny, containing regular growth marks. These observations provide strong evidence for rapid but seasonally interrupted growth with limited developmental plasticity (indicated by the regular spacing of growth marks). Combined with our review of early branching sauropodomorph osteohistology, these results show that highly accelerated growth rates originated among smaller, non-sauropodan sauropodomorphs weighing 1 to 2 tons but preceded the origins of giant size (>10 tons). Therefore, the capacity for rapid bone tissue formation, a derived aspect of rapid growth seen in sauropods, did not evolve specifically to enable giant body sizes but may have been a prerequisite for them.
Topics: Animals; Fossils; Biological Evolution; Gigantism; Phylogeny; Dinosaurs
PubMed: 36084648
DOI: 10.1016/j.cub.2022.08.031 -
Atlanta Journal-record of Medicine Aug 1899
PubMed: 36019255
DOI: No ID Found -
Orphanet Journal of Rare Diseases May 2008McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP). It...
McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP). It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. FD can involve a single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and development of breast tissue in girls, testicular and penile enlargement and precocious sexual behavior in boys), other hyperfunctioning endocrinopathies may be involved including hyperthyroidism, growth hormone excess, Cushing syndrome, and renal phosphate wasting. Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention. Renal involvement is seen in approximately 50% of the patients with MAS. The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP regulating protein, Gs alpha. The extent of the disease is determined by the proliferation, migration and survival of the cell in which the mutation spontaneously occurs during embryonic development. Diagnosis of MAS is usually established on clinical grounds. Plain radiographs are often sufficient to make the diagnosis of FD and biopsy of FD lesions can confirm the diagnosis. The evaluation of patients with MAS should be guided by knowledge of the spectrum of tissues that may be involved, with specific testing for each. Genetic testing is possible, but is not routinely available. Genetic counseling, however, should be offered. Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm. Treatment is dictated by the tissues affected, and the extent to which they are affected. Generally, some form of surgical intervention is recommended. Bisphosphonates are frequently used in the treatment of FD. Strengthening exercises are recommended to help maintaining the musculature around the FD bone and minimize the risk for fracture. Treatment of all endocrinopathies is required. Malignancies associated with MAS are distinctly rare occurrences. Malignant transformation of FD lesions occurs in probably less than 1% of the cases of MAS.
Topics: Adolescent; Adult; Cafe-au-Lait Spots; Child; Child, Preschool; Endocrine System Diseases; Female; Fibrous Dysplasia, Polyostotic; Genetic Counseling; Gigantism; Humans; Hyperthyroidism; Male; Puberty, Precocious
PubMed: 18489744
DOI: 10.1186/1750-1172-3-12 -
Clinics (Sao Paulo, Brazil) 2012Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial... (Review)
Review
Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas.
Topics: Acromegaly; Gigantism; Growth Hormone-Secreting Pituitary Adenoma; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Multiple Endocrine Neoplasia Type 1; Mutation; Pituitary Neoplasms
PubMed: 22584702
DOI: 10.6061/clinics/2012(sup01)06 -
Proceedings of the National Academy of... Jul 2023The evolution of the extinct megatooth shark, , and its close phylogenetic relatives remains enigmatic. A central question persists regarding the thermophysiological...
The evolution of the extinct megatooth shark, , and its close phylogenetic relatives remains enigmatic. A central question persists regarding the thermophysiological origins of these large predatory sharks through geologic time, including whether was ectothermic or endothermic (including regional endothermy), and whether its thermophysiology could help to explain the iconic shark's gigantism and eventual demise during the Pliocene. To address these uncertainties, we present unique geochemical evidence for thermoregulation in from both clumped isotope paleothermometry and phosphate oxygen isotopes. Our results show that had an overall warmer body temperature compared with its ambient environment and other coexisting shark species, providing quantitative and experimental support for recent biophysical modeling studies that suggest endothermy was one of the key drivers for gigantism in and other lamniform sharks. The gigantic body size with high metabolic costs of having high body temperatures may have contributed to the vulnerability of species to extinction when compared to other sympatric sharks that survived the Pliocene epoch.
Topics: Animals; Sharks; Phylogeny; Gigantism; Body Temperature Regulation; Body Size
PubMed: 37364100
DOI: 10.1073/pnas.2218153120 -
Pituitary Feb 2023We present the results of transsphenoidal microsurgical treatment in 14 patients with gigantism. The influence on the prognosis of factors such as the tumor size and...
PURPOSE
We present the results of transsphenoidal microsurgical treatment in 14 patients with gigantism. The influence on the prognosis of factors such as the tumor size and preoperative levels of GH and IGF-1 is also quantified.
MATERIALS AND METHODS
The patients, operated between 1982 and 2004, were reviewed retrospectively in June 2022. All patients had complete endocrinological studies in the preoperative period and a postoperative control between 6 days and 3 weeks. Follow-up has been supported with annual check-ups between 3 and 31 years. We have compared the preoperative levels of GH and IGF-1 of these patients with the levels of a series of acromegalic patients operated on in the same Center.
RESULTS
In this series there were 4 women and 10 men. The age ranged between 14 and 21 years. In 6 patients, postoperative hormone levels achieved the disease control criteria (42.8%). The CT/MRI studies revealed the existence of invasive tumors in 10 of the patients (71.4%). Postoperative CT/MRI showed no tumor tissue in 3 patients but in 7 patients there were tumor remains. The remaining 4 patients had abnormal images although not considered as tumor. A statistical comparison of preoperative serum GH and IGF-1 levels in patients with gigantism and patients with acromegaly showed a significant elevation in the former.
CONCLUSION
Pituitary adenomas that cause gigantism are generally large and invasive, which makes them difficult to cure. High preoperative levels of GH and IGF-1 are also factors that decrease remission.
Topics: Male; Humans; Female; Adolescent; Young Adult; Adult; Gigantism; Acromegaly; Insulin-Like Growth Factor I; Prognosis; Retrospective Studies; Human Growth Hormone; Pituitary Neoplasms; Treatment Outcome
PubMed: 36335516
DOI: 10.1007/s11102-022-01286-0 -
Saudi Medical Journal Jun 2015
Topics: Adult; Foot Deformities, Congenital; Humans; Leg; Lipomatosis; Male
PubMed: 25987124
DOI: 10.15537/smj.2015.6.11344 -
The New England Journal of Medicine Dec 2014Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood.
BACKGROUND
Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood.
METHODS
We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly.
RESULTS
We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein-coupled receptor, was overexpressed in patients' pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone-producing cells.
CONCLUSIONS
We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).
Topics: Acromegaly; Adolescent; Adult; Age of Onset; Child; Child, Preschool; Chromosome Duplication; Chromosomes, Human, X; Female; Gigantism; Human Growth Hormone; Humans; Infant; Male; Mutation; Phenotype; Protein Conformation; Receptors, G-Protein-Coupled
PubMed: 25470569
DOI: 10.1056/NEJMoa1408028 -
Seminars in Cell & Developmental Biology Aug 2022Satellite DNAs are arrays of tandem repeats found in the eukaryotic genome. They are mainly found in pericentromeric heterochromatin and have been believed to be mostly... (Review)
Review
Satellite DNAs are arrays of tandem repeats found in the eukaryotic genome. They are mainly found in pericentromeric heterochromatin and have been believed to be mostly inert, leading satellite DNAs to be erroneously regarded as junk. Recent studies have started to elucidate the function of satellite DNA, yet little is known about the peculiar case where satellite DNA is found within the introns of protein coding genes, resulting in incredibly large introns, a phenomenon termed intron gigantism. Studies in Drosophila demonstrated that satellite DNA-containing introns are transcribed with the gene and require specialized mechanisms to overcome the burdens imposed by the extremely long stretches of repetitive DNA. Whether intron gigantism confers any benefit or serves any functional purpose for cells and/or organisms remains elusive. Here we review our current understanding of intron gigantism: where it is found, the challenges it imposes, how it is regulated and what purpose it may serve.
Topics: Animals; DNA, Satellite; Drosophila; Gigantism; Heterochromatin; Introns
PubMed: 35469677
DOI: 10.1016/j.semcdb.2022.04.010 -
Journal of Endocrinological... Apr 2024Tall stature is defined as height greater than the threshold of more than 2 standard deviations above the average population height for age, sex, and ethnicity. Many... (Review)
Review
PURPOSE
Tall stature is defined as height greater than the threshold of more than 2 standard deviations above the average population height for age, sex, and ethnicity. Many studies have described the main aspects of this condition during puberty, but an analysis of the characteristics that the physician should consider in the differential diagnosis of gigantism-tall stature secondary to a pituitary tumour-during the transition age (15-25 years) is still lacking.
METHODS
A comprehensive search of English-language original articles was conducted in the MEDLINE database (December 2021-March 2022). We selected all studies regarding epidemiology, genetic aspects, and the diagnosis of tall stature and gigantism during the transition age.
RESULTS
Generally, referrals for tall stature are not as frequent as expected because most cases are familial and are usually unreported by parents and patients to endocrinologists. For this reason, lacking such experience of tall stature, familiarity with many rarer overgrowth syndromes is essential. In the transition age, it is important but challenging to distinguish adolescents with high constitutional stature from those with gigantism. Pituitary gigantism is a rare disease in the transition age, but its systemic complications are very relevant for future health. Endocrine evaluation is crucial for identifying conditions that require hormonal treatment so that they can be treated early to improve the quality of life and prevent comorbidities of individual patient in this age range.
CONCLUSION
The aim of our review is to provide a practical clinical approach to recognise adolescents, potentially affected by gigantism, as early as possible.
Topics: Adolescent; Humans; Young Adult; Adult; Gigantism; Quality of Life; Syndrome; Diagnosis, Differential; Body Height
PubMed: 37891382
DOI: 10.1007/s40618-023-02223-z