Complex Rhythmicity and Age Dependence of Growth Hormone Secretion Are Preserved in Patients With Acromegaly: Further Evidence for a Present Hypothalamic Control of Pituitary Somatotropinomas

Ribeiro‐Oliveira, Antônio; Abrantes, Marcelo Militão; Barkan, Ariel L.

doi:10.1210/jc.2013-1581

Cited by 24 publications

(14 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Acromegaly is classically characterized by an increased GH pulse frequency, higher basal GH secretion rates and higher ApEn values, suggesting more irregular GH concentration profiles than those in normal subjects (Hartman et al 1994). Nevertheless, in keeping with our studies of Aip +/− mice, recent data suggest that the complex rhythm and age dependency of GH secretion are both preserved in patients with acromegaly (Ribeiro-Oliveira et al 2013). However, the biological significance of this subtle increase in total GH secretion is questionable, as it does not result in elevated IGF1 plasma concentrations.…”

Section: Discussionsupporting

confidence: 87%

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice

Lecoq

Zizzari

Hage

et al. 2016

Journal of Endocrinology

View full text Add to dashboard Cite

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip +/− ) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip +/− mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip +/− mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip +/− mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip +/− mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip +/− mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip +/− mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model.

show abstract

Section: Discussionsupporting

confidence: 87%

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice

Lecoq

Zizzari

Hage

et al. 2016

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Older age, female sex, and lower IGF-1 levels were associated with an increased likelihood of achieving hormonal control defined as GH levels ≤ 2.5 µg/L and normalized IGF-1 levels at LVA. This may be related to the pattern of GH secretion in female patients with acromegaly, as well as the age-dependent decline in GH secretion in acromegaly [34]. Older patients were also more likely to achieve tight hormonal control (GH levels < 1.0 µg/L and normalized IGF-1 levels).…”

Section: Discussionmentioning

confidence: 99%

Predictive factors for responses to primary medical treatment with lanreotide autogel 120 mg in acromegaly: post hoc analyses from the PRIMARYS study

Petersenn¹,

Houchard

Sert

et al. 2019

Pituitary

View full text Add to dashboard Cite

Purpose PRIMARYS (NCT00690898) was a 48-week, open-label, phase 3b study, evaluating treatment with the somatostatin receptor ligand lanreotide autogel (stable dose: 120 mg/28 days) in treatment-naïve patients with growth hormone (GH)-secreting pituitary macroadenoma. This post hoc analysis aimed to evaluate factors predictive of long-term responses. Methods Potential predictive factors evaluated were: sex, age, and body mass index at baseline; and GH, insulin-like growth factor-1 (IGF-1), and tumor volume (TV) at baseline and week 12, using univariate regression analyses. Treatment responses were defined as hormonal control (GH ≤ 2.5 µg/L and age-and sex-normalized IGF-1), tight hormonal control (GH < 1.0 µg/L and normalized IGF-1), or ≥ 20% TV reduction (TVR). Receiver-operating-characteristic (ROC) curves were constructed using predictive factors significant in univariate analyses. Cut-off values for predicting treatment responses at 12 months were derived by maximizing the Youden index (J). Results At baseline, older age, female sex, and lower IGF-1 levels were associated with an increased probability of achieving long-term hormonal control. ROC area-under-the curve (AUC) values for hormonal control were high for week-12 GH and IGF-1 levels (0.87 and 0.93, respectively); associated cut-off values were 1.19 μg/L and 110% of the upper limit of normal (ULN), respectively. Results were similar for tight hormonal control (AUC values: 0.92 [GH] and 0.87 [IGF-1]; cut-off values: 1.11 μg/L and 125% ULN, respectively). AUC and J values associated with TVR were low. Conclusions The use of predictive factors at baseline and week 12 of treatment could inform clinical expectations of the long-term efficacy of lanreotide autogel.

show abstract

“…The OGTT was not standardized, as 50–100 g of oral glucose was administered and variable GH assays were used. Additionally, data on the reproducibility of the paradoxical GH response to oral glucose are lacking, as it may be influenced by the well-documented spontaneous GH fluctuations in acromegalic patients [95]. …”

Section: Ogtt In the Diagnosis Of Acromegalymentioning

confidence: 99%

Growth Hormone Response to Oral Glucose Load: From Normal to Pathological Conditions

Hage

Kamenický

Chanson³

2019

Neuroendocrinology

View full text Add to dashboard Cite

The exact physiological basis of acute growth hormone (GH) suppression by oral glucose is not fully understood. Glucose-mediated increase in hypothalamic somatostatin seems to be the most plausible explanation. Attempts to better understand its underlying mechanisms are compromised by species disparities in the response of GH to glucose load. While in humans, glucose inhibits GH release, the acute elevation of circulating glucose levels in rats has either no effect on GH secretion or may be stimulatory. Likewise, chronic hyperglycemia alters GH release in both humans and rats nonetheless in opposite directions. Several factors influence nadir GH concentrations including, age, gender, body mass index, pubertal age, and the type of assay used. Besides the classical suppressive effects of glucose on GH release, a paradoxical GH increase to oral glucose may be observed in around one third of patients with acromegaly as well as in various other disorders. Though its pathophysiology is poorly characterized, an altered interplay between somatostatin and GH-releasing hormone has been suggested and a link with pituitary ectopic expression of glucose-dependent insulinotropic polypeptide receptor has been recently demonstrated. A better understanding of the dynamics mediating GH response to glucose may allow a more optimal use of the OGTT as a diagnostic tool in various conditions, especially acromegaly.

show abstract

Complex Rhythmicity and Age Dependence of Growth Hormone Secretion Are Preserved in Patients With Acromegaly: Further Evidence for a Present Hypothalamic Control of Pituitary Somatotropinomas

Cited by 24 publications

References 31 publications

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice

Predictive factors for responses to primary medical treatment with lanreotide autogel 120 mg in acromegaly: post hoc analyses from the PRIMARYS study

Growth Hormone Response to Oral Glucose Load: From Normal to Pathological Conditions

Contact Info

Product

Resources

About