Hepatic Steatosis Index in Acromegaly: Correlation with Insulin Resistance Regardless of the Disease Control

Abstract

Objective In acromegaly, both lipotoxicity secondary to GH excess and insulin resistance have a significant impact on the liver. Ultrasonography has shown poor sensitivity in detecting hepatic steatosis and noninvasive methods have been proposed. We evaluated the hepatic steatosis index (HSI), a validated surrogate index of hepatic steatosis, and we correlated it with disease activity and insulin resistance. Design Thirty-one patients with newly diagnosed acromegaly were studied at diagnosis and after 12 months of treatment with somatostatin receptor ligands. Methods Glucose and insulin levels, surrogate estimates of insulin sensitivity, and hepatic steatosis through ultrasonography and HSI were evaluated. Results At diagnosis, ultrasonography documented steatosis in 19 patients (61.2%) while 26 (83.8%) showed high HSI. After 12 months, both GH (p = 0.033) and IGF-1 (p < 0.001) significantly decreased and, overall, 58% of patients were classified as controlled. Ultrasonography documented steatosis in all the same initial 19 patients, while only 14 patients (45.1%) showed high HSI (p < 0.001). A significant reduction in HOMA-IR (p = 0.002) and HSI (p < 0.001) and increased ISI Matsuda (p < 0.001), was documented. The change of HSI from baseline to 12 months was found to be directly correlated with the change of ISI (Rho -0.611; p = 0.004) while no correlation was found with the change of GH or IGF-1 levels and other parameters. Conclusions In acromegaly, HSI is mainly related with insulin resistance and the reduction of GH and IGF-1 levels, and above all the improvement in insulin sensitivity leads to an improvement of this surrogate index of hepatic steatosis.

Acromegaly and ultrasound: how, when and why?

“…It is unknown whether acromegaly predisposes or prevents hepatic accumulation of fat since the pathophysiological network regulation is complex and not fully understood [48,49]. Among a sample of 19 newly diagnosed ACRO, Ciresi et al reported that 61.0% had hepatic steatosis, with no improvement after 12 months of therapy with octreotide (control of the disease was reached in 58%) [50]. Conversely, they reported a significant improvement in the hepatic steatosis index with therapy (p < 0.001) [50].…”

Hepatic steatosis in patients with acromegaly

“…23,24 Moreover, low serum IGF-1 concentrations have also been associated with NAFLD and it has been suggested that hepatic insulin resistance modulates hepatic GH production and thus IGF-1 concentrations. 20 The observed risk with GH and IGF-1 deficiencies would imply that treated patients with acromegaly might be prone to develop NAFLD, because treatment does, in some cases, lead to the development of GH deficiency, as illustrated in a recently published case study. 20 The observed risk with GH and IGF-1 deficiencies would imply that treated patients with acromegaly might be prone to develop NAFLD, because treatment does, in some cases, lead to the development of GH deficiency, as illustrated in a recently published case study.…”

“…25,26 A recent study showed hepatic steatosis (as assessed by a surrogate marker, the hepatic steatosis index) to be related to insulin resistance and the reduction of IGF-1 and GH levels; after 12 months of follow-up, improvements to insulin sensitivity paralleled reductions of hepatic steatosis. 20 The observed risk with GH and IGF-1 deficiencies would imply that treated patients with acromegaly might be prone to develop NAFLD, because treatment does, in some cases, lead to the development of GH deficiency, as illustrated in a recently published case study. 27 Moreover, an intervention study and another case study both report histological NASH resolution upon GH correction in patients with GH deficiency.…”

“…F I G U R E 2 Individual patient CAP scores (as well as mean ± SD) based on genotype for the following single nucleotide polymorphisms: patatin-like phospholipase domain-containing 3 (PNPLA3) p.I48M; membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) p.G17E; and transmembrane 6 superfamily member 2 (TM6SF2) p.E167K. 20 Detrimental consequences on glucose metabolism, insulin signalling and adipose tissue have been documented in patients with acromegaly and GH excess. No significant differences in CAP were demonstrated between the three MBOAT7 genotypes, where the lowest mean CAP value was observed in carriers of the wild-type genotype (GG) and the highest in patients homozygous for the risk allele (EE).…”

“…Specifically, growth hormone (GH) stimulates insulin resistance via its induction of gluconeogenesis and glycogenolysis, and indeed, hepatic lipid accumulation has been associated not only with GH deficiency but also with GH excess. 20 Detrimental consequences on glucose metabolism, insulin signalling and adipose tissue have been documented in patients with acromegaly and GH excess.…”