Genetics of Acromegaly and Gigantism

Bogusławska, Anna; Korbonits, Márta

doi:10.3390/jcm10071377

Cited by 32 publications

(33 citation statements)

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“…Thick bones and enlarged and prognathic mandible of OL-23/77 might also indicate acromegaly. However, without genetic studies on gene mutations (e.g., AIP, PRKAR1A, GPR101, GNAS, MEN1, CDKN1B, SDHx, MAX ( 57 ), it is difficult to assess whether OL-23/77 was affected by gigantism and acromegaly or just one of these diseases. Especially, since some anatomical features such as elongated bones and high body stature, typical of gigantism, may also occur in individuals with acromegaly ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

The Internal Cranial Anatomy of a Female With Endocrine Disorders From a Mediaeval Population

Kubicka¹,

Charlier²,

Balzeau³

2022

Front. Endocrinol.

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Gigantism and acromegaly have been observed in past populations; however, analyses usually focus on the morphological features of the post-cranial skeleton. The aim of this study is to characterize the internal anatomical features of the skull (brain endocast anatomy and asymmetry, frontal pneumatization, cranial thickness, sella turcica size) of an adult individual from the 11-14th centuries with these two diseases, in comparison with non-pathological individuals from the same population. The material consisted of 33 adult skulls from a mediaeval population, one of them belonging to an adult female with endocrine disorders (OL-23/77). Based on the CT scans, the internal cranial anatomy was analysed. The sella turcica of OL-23/77 is much larger than in the comparative sample. The endocast of the individual OL-23/77 shows a left frontal/left occipital petalia, while the comparative population mostly had right frontal/left occipital petalias. The asymmetry in petalia location in OL-23/77 comes within the range of variation observed in the comparative population. The individual has high values for cranial thickness. The frontal sinuses of the specimen analysed are similar in size and shape to the comparative sample only for data scaled to the skull length. Enlarged sella turcica is typical for individuals with acromegaly/gigantism. The pattern of the left frontal/left occipital petalia in the specimen OL-23/77 is quite rare. The position of the endocranial petalias has not influenced the degree of asymmetry in the specimen. Despite the large bone thickness values, skull of OL-23/77 does not show any abnormal features. The skull/endocast relationship in this individual shows some peculiarities in relation to its large size, while other internal anatomical features are within the normal range of variation of the comparative sample.

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Section: Discussionmentioning

confidence: 99%

The Internal Cranial Anatomy of a Female With Endocrine Disorders From a Mediaeval Population

Kubicka¹,

Charlier²,

Balzeau³

2022

Front. Endocrinol.

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“…14 However, familial or syndromic acromegaly occurs in a small minority of patients (Table 1). 15 These include familial isolated pituitary adenoma, multiple endocrine neoplasia 1 and 4, X-linked acrogigantism, hereditary paragangliomapheochromocytoma syndrome, Carney complex, and neurofibromatosis 1. 15 Exogenous GH, administered in excess, will recapitulate the phenotype of patients with acromegaly.…”

Section: Pathogenesis Of Acromegalymentioning

confidence: 99%

“…15 These include familial isolated pituitary adenoma, multiple endocrine neoplasia 1 and 4, X-linked acrogigantism, hereditary paragangliomapheochromocytoma syndrome, Carney complex, and neurofibromatosis 1. 15 Exogenous GH, administered in excess, will recapitulate the phenotype of patients with acromegaly. 16 Very uncommonly, GHRH secretion from an ectopic neuroendocrine tumor or sellar gangliocytoma may drive GH excess from pituitary somatotrophs.…”

Section: Pathogenesis Of Acromegalymentioning

confidence: 99%

“…60,63 Germline genetic abnormalities are present in a minority of patients with acromegaly and may influence the response to first-generation SRL therapy. 15 Patients with inactivating mutations in the aryl hydrocarbon receptoreinteracting protein (AIP) gene who develop acromegaly have been reported to exhibit lower GH and IGF-1 decrements after SRL administration and are less likely to show tumor shrinkage on such therapy. 64 In patients with AIPmutated somatotroph adenomas, miR-34a is up-regulated and appears to promote resistance to SRL therapy.…”

Section: Medical Therapymentioning

confidence: 99%

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Diagnosis and Treatment of Acromegaly: An Update

Ershadinia

Tritos

2022

Mayo Clinic Proceedings

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Acromegaly is typically caused by a growth hormoneesecreting pituitary adenoma, driving excess secretion of insulin-like growth factor 1. Acromegaly may result in a variety of cardiovascular, respiratory, endocrine, metabolic, musculoskeletal, and neoplastic comorbidities. Early diagnosis and adequate treatment are essential to mitigate excess mortality associated with acromegaly.PubMed searches were conducted using the keywords growth hormone, acromegaly, pituitary adenoma, diagnosis, treatment, pituitary surgery, medical therapy, and radiation therapy (between 1981 and 2021).The diagnosis of acromegaly is confirmed on biochemical grounds, including elevated serum insulin-like growth factor 1 and lack of growth hormone suppression after glucose administration. Pituitary magnetic resonance imaging is advised in patients with acromegaly to identify an underlying pituitary adenoma.Transsphenoidal pituitary surgery is generally first-line therapy for patients with acromegaly. However, patients with larger and invasive tumors (macroadenomas) are often not in remission postoperatively. Medical therapies, including somatostatin receptor ligands, cabergoline, and pegvisomant, can be recommended to patients with persistent disease after surgery. Select patients may also be candidates for preoperative medical therapy. In addition, primary medical therapy has a role for patients without mass effect on the optic chiasm who are unlikely to be cured by surgery. Clinical, endocrine, imaging, histologic, and molecular markers may help predict the response to medical therapy; however, confirmation in prospective studies is needed. Radiation therapy is usually a third-line option and is increasingly administered by a variety of stereotactic techniques. An improved understanding of the pathogenesis of acromegaly may ultimately lead to the design of novel, efficacious therapies for this serious condition.

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“…AIP -mutated somatotropinomas seem to be larger, more hidden and invasive, and to respond poorly to treatment with fg-SRL ( 60 ). Mutations in the MEN1 gene are also associated with somatotropinomas, requiring neurosurgery more often and multimodal approaches ( 61 ). However, a series comparing patients with isolated acromegaly with acromegaly associated with MEN1 found similar IGF-I control ( 62 ).…”

Section: Future Perspectives For Currently Available Injectable Srlsmentioning

confidence: 99%

The Future of Somatostatin Receptor Ligands in Acromegaly

Gadelha

Wildemberg

2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Currently, first-generation somatostatin receptor ligands (fg-SRLs), octreotide LAR and lanreotide autogel, are the mainstays of acromegaly treatment and achieve biochemical control in approximately 40% of patients and tumor shrinkage in over 60% of patients. Pasireotide, a second-generation SRL, shows higher efficacy with respect to both biochemical control and tumor shrinkage but has a worse safety profile. In this review, we discuss the future perspectives of currently available SRLs, focusing on the use of biomarkers of response and precision medicine, new formulations of these SRLs and new drugs, which are under development. Precision medicine, which is based on biomarkers of response to treatment, will help guide the decision-making process by allowing physicians to choose the appropriate drug for each patient and improving response rates. New formulations of available SRLs, such as oral, subcutaneous depot and nasal octreotide, may improve patients’ adherence to treatment and quality of life since there will be more options available that better suit each patient. Finally, new drugs, such as paltusotine, somatropin, ONO-5788 and ONO-ST-468, may improve treatment adherence and present higher efficacy than currently available drugs.

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Genetics of Acromegaly and Gigantism

Cited by 32 publications

References 192 publications

The Internal Cranial Anatomy of a Female With Endocrine Disorders From a Mediaeval Population

The Internal Cranial Anatomy of a Female With Endocrine Disorders From a Mediaeval Population

Diagnosis and Treatment of Acromegaly: An Update

The Future of Somatostatin Receptor Ligands in Acromegaly

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