Growth hormone/insulin-like growth factor I axis in health and disease states: an update on the role of intra-portal insulin.

Growth hormone (GH) is the key regulator of insulin-like growth factor I (IGF-I) generation in healthy states. However, portal insulin delivery is also an essential co-player in the regulation of the GH/IGF-I axis by affecting and regulating hepatic GH receptor synthesis, and subsequently altering hepatic GH sensitivity and IGF-I generation. Disease states of GH excess (e.

IGF-I assay methods and biologic variability: evaluation of acromegaly treatment response.

Serum insulin-like growth factor (IGF-I) is the primary biochemical measure of disease activity in patients with acromegaly, and the 2014 Endocrine Society guidelines recommended normal age-adjusted serum IGF-I as the biochemical target of treatment. However, quantification and interpretation of IGF-I levels are subject to limitations that may affect therapeutic decisions. Techniques for measuring IGF-I have evolved greatly over the past 40 years and continue to do so.

Medical Costs Associated with High/Moderate/Low Likelihood of Adult Growth Hormone Deficiency: A Healthcare Claims Database Analysis.

Purpose: Adult growth hormone deficiency (AGHD) is often underdiagnosed and undertreated, leading to costly comorbidities. Previously, we developed an algorithm to identify individuals in a commercially insured US population with high, moderate, or low likelihood of having AGHD. Here, we estimate and compare direct medical costs by likelihood level.

Development of a Novel Algorithm to Identify People with High Likelihood of Adult Growth Hormone Deficiency in a US Healthcare Claims Database.

Objective: Adult growth hormone deficiency (AGHD) is an underdiagnosed disease associated with increased morbidity and mortality. Identifying people who may benefit from growth hormone (GH) therapy can be challenging, as many AGHD symptoms resemble those of aging. We developed an algorithm to potentially help providers stratify people by their likelihood of having AGHD.

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

The designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic.

Estrogen Stimulation of Pleiotrophin Enhances Osteoblast Differentiation and Maintains Bone Mass in IGFBP-2 Null Mice.

Insulin-like growth factor binding protein-2 (IGFBP-2) stimulates osteoblast differentiation but only male Igfbp2 null mice have a skeletal phenotype. The trophic actions of IGFBP-2 in bone are mediated through its binding to receptor tyrosine phosphatase beta (RPTPβ). Another important ligand for RPTPβ is pleiotrophin (PTN), which also stimulates osteoblast differentiation.

THYROID DYSFUNCTION, RECOVERY, AND PROGNOSIS IN MELANOMA PATIENTS TREATED WITH IMMUNE CHECKPOINT INHIBITORS: A RETROSPECTIVE REVIEW.

To describe thyroid dysfunction, factors associated with thyroid recovery, and survival in melanoma patients treated with immune checkpoint inhibitors that developed thyroid immune-related adverse events (irAEs). This was a retrospective study in a tertiary center from 2010-2017. We reviewed the charts of patients with melanoma that developed thyroid dysfunction after checkpoint inhibitor therapy.

IGFBP-2 stimulates calcium/calmodulin-dependent protein kinase kinase 2 activation leading to AMP-activated protein kinase induction which is required for osteoblast differentiation.

Insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins-2 (IGFBP-2) function coordinately to stimulate osteoblast differentiation. Induction of AMP-activated protein kinase (AMPK) is required for differentiation and is stimulated by these two factors. These studies were undertaken to determine how these two peptides lead to activation of AMPK.

Hyperglycemia induces vascular smooth muscle cell dedifferentiation by suppressing insulin receptor substrate-1-mediated p53/KLF4 complex stabilization.

Hyperglycemia and insulin resistance accelerate atherosclerosis by an unclear mechanism. The two factors down-regulate insulin receptor substrate-1 (IRS-1), an intermediary of the insulin/IGF-I signaling system. We previously reported that IRS-1 down-regulation leads to vascular smooth muscle cell (VSMC) dedifferentiation and that IRS-1 deletion from VSMCs in normoglycemic mice replicates this response.

A peptide containing the receptor binding site of insulin-like growth factor binding protein-2 enhances bone mass in ovariectomized rats.

Male -- mice have a significant reduction in bone mass and administration of a peptide that contains the insulin-like growth factor binding protein-2(IGFBP-2) receptor-binding domain stimulates bone formation in these animals. Female -/- mice do not have this phenotype but following ovariectomy (OVX) lose more bone than OVX wild-type mice. This suggests that in the absence of estrogen, IGFBP-2 is required to maintain bone mass.

A Consensus Statement on acromegaly therapeutic outcomes.

The 11th Acromegaly Consensus Conference in April 2017 was convened to update recommendations on therapeutic outcomes for patients with acromegaly. Consensus guidelines on the medical management of acromegaly were last published in 2014; since then, new pharmacological agents have been developed and new approaches to treatment sequencing have been considered. Thirty-seven experts in the management of patients with acromegaly reviewed the current literature and assessed changes in drug approvals, clinical practice standards and clinical opinion.

Role of IGF-binding proteins in regulating IGF responses to changes in metabolism.

The IGF-binding protein family contains six members that share significant structural homology. Their principal function is to regulate the actions of IGF1 and IGF2. These proteins are present in plasma and extracellular fluids and regulate access of both IGF1 and II to the type I IGF receptor.

DIAGNOSING AND MONITORING ENDOCRINE DYSFUNCTION, DIABETES, AND OBESITY IN A COHORT OF ADULT SURVIVORS OF CHILDHOOD CANCER.

Objective: The 5-year survival rate for childhood cancer has increased to 80%, resulting in a growing population of adult survivors of childhood cancer (ASOCC). Long-term endocrine dysfunction is as high as 63% when screened in research protocols. The purpose of this study was to evaluate the prevalence of endocrine testing, endocrine dysfunction, diabetes, obesity, and endocrinologist visits outside of a research screening protocol.

Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial.

Objective: Use of growth hormone is associated with side effects, including insulin resistance. The objective of this study was to determine whether tesamorelin, a stabilized growth hormone-releasing hormone analogue, would alter insulin sensitivity or control of diabetes.

Design: A 12-week randomized, placebo-controlled study of 53 patients with type 2 diabetes.

Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation.

Diabetes is a major risk factor for the development of atherosclerosis, but the mechanism by which hyperglycemia accelerates lesion development is not well defined. Insulin and insulin-like growth factor I (IGF-I) signal through the scaffold protein insulin receptor substrate 1 (IRS-1). In diabetes, IRS-1 is down-regulated, and cells become resistant to insulin.

Role of IGF Binding Proteins in Regulating Metabolism.

Insulin-like growth factors (IGFs) circulate in extracellular fluids bound to a family of binding proteins. Although they function in a classical manner to limit the access of the IGFs to their receptors they also have a multiplicity of actions that are independent of this property; they bind to their own receptors or are transported to intracellular and intranuclear sites to influence cellular functions that may directly or indirectly modify IGF actions. The availability of genetically modified animals has helped to determine their functions in a physiological context.

IRS-1 Functions as a Molecular Scaffold to Coordinate IGF-I/IGFBP-2 Signaling During Osteoblast Differentiation.

Insulin like growth factor I (IGF-I) and insulin like growth factor binding protein-2 (IGFBP-2) function coordinately to stimulate AKT and osteoblast differentiation. IGFBP-2 binding to receptor protein tyrosine phosphatase β (RPTPβ) stimulates polymerization and inactivation of phosphatase activity. Because phosphatase and tensin homolog (PTEN) is the primary target of RPTPβ, this leads to enhanced PTEN tyrosine phosphorylation and inactivation.

IGF-I and IGFBP-2 Stimulate AMPK Activation and Autophagy, Which Are Required for Osteoblast Differentiation.

IGF-I/insulin-like growth factor binding protein 2 (IGFBP-2) coordinately stimulate osteoblast differentiation but the mechanisms by which they function have not been determined. AMP-activated protein kinase (AMPK) is induced during differentiation and AMPK knockout mice have reduced bone mass. IGF-I modulates AMPK in other cell types; therefore, these studies determined whether IGF-I/IGFBP-2 stimulate AMPK activation and the mechanism by which AMPK modulates differentiation.