Transient Elastography and Controlled Attenuation Parameter (CAP) in the Assessment of Liver Steatosis in Severe Adult Growth Hormone Deficiency

Abstract

Non-alcoholic fatty liver disease (NAFLD) is common in patients with growth hormone deficiency (GHD). Some noninvasive techniques have been used to quantify liver fat, such as the controlled attenuation parameter (CAP). Objective: To evaluate CAP as a tool to identify liver steatosis and its relationship with different clinical and biochemical metabolic parameters in a group of patients with severe adult growth hormone deficiency (AGHD), and to compare the evolution of metabolic profiles after 6 months of human growth hormone (rhGH) replacement therapy in a subgroup of patients. Methods: Cross-sectional observational study at baseline of naive rhGH multiple pituitary hormonal deficiency (MPHD) hypopituitarism patients. A 6-month intervention clinical trial in a selected group of a non-randomized, non-controlled cohort was also applied. Results: Liver stiffness measurement (LSM) was normal in severe AGHD patients. CAP evaluation showed steatosis in 36.3% of baseline patients (8/22), associated with higher BMI, waist circumference, insulin, and alanine aminotransferase (ALT) levels. According to steatosis degree by CAP, child-onset growth hormone deficiency (CO-GHD) was graded as 68.75% (11/16) S0, 12.5% (2/16) S1, and 18.75% (3/16) S3, whereas AO-GHD was graded as 50% (3/6) S0, 16.66% (1/6) S2, and 33.33% S3. After 6 months of hrGH replacement, CAP measurements did not change significantly, neither on group without hepatic steatosis at baseline (194.4 ± 24.3 vs. 215.4 ± 51.3; p = 0.267) nor on the group with hepatic steatosis (297.2 ± 32.3 vs. 276.4 ± 27.8; p = 0.082). A significant improvement of body composition was observed only in the first group. Conclusions: We have demonstrated the importance of CAP as a non-invasive tool in the liver steatosis identification on hypopituitary patients. This method may be an important indicator of the severity of metabolic disorders in MPHD patients. In our study, no liver health modification in LSM at baseline or after 6 months of rhGH replacement was found. Longer studies can help to establish the potential repercussions of growth hormone replacement therapy on liver steatosis.

Growth hormone deficiency and NAFLD: An overlooked and underrecognized link

“…The data on effectiveness of GH therapy on NAFLD/NASH in this patient population are limited to a few studies that included a very small number of patients for a duration of treatment only for 6 months (Table 2 ). [ 14 , 15 , 16 , 17 , 18 ] In all studies, treatment was started with a low‐dose rhGH and titrated to normal IGF‐1 level per guidelines recommendations. One demonstrated significant improvement of steatosis and fibrosis in 5 patients with NASH who underwent paired liver biopsies after 6–12 months of treatment with GH.…”

“…[ 11 ] The role of GH therapy for reversal of NAFLD in patients with AGHD is still controversial, with some studies showing beneficial effect (including histologic improvement), [ 14 , 17 ] while others lacking improvement (via nonhistologic measures). [ 16 , 18 ] Interestingly, GH‐releasing hormone analogue had shown robust beneficial effect on NAFLD in patients with human immunodeficiency virus (HIV). [ 19 ]…”

Magnetic Resonance Spectroscopy of Hepatic Fat from Fundamental to Clinical Applications

“…Transient elastography (TE) is an ultrasound-based modality that simultaneously measures liver steatosis and fibrosis. TE transducer produces a low-frequency (50 Hz) shear wave that propagates through the liver tissue, followed by a pulse-echo ultrasound that measures its velocity, which reflects the degree of liver stiffness or liver stiffness measurement (LSM) [ 33 , 34 , 35 , 36 ]. The controlled attenuation parameter (CAP) estimates the degree of ultrasound attenuation by hepatic fat at the central frequency of transient elastography [ 37 ].…”

Classic Cardiovascular Risk Factors improve in Very Elderly Hypopituitary Patients Treated on Standard Hormone Replacement in Long Term Follow- Up.

“…11 It is known to be associated with an unfavorable lipid pro le, with increased triglycerides, cholesterol, body fat, and liver steatosis, all of which are associated with an increased incidence of vascular disease. 12 A recent study demonstrated that hypopituitary patients without GH replacement have more dyslipidemia, but lower homeostasis model assessment (HOMA-IR) and waist/height values and the occurrence of metabolic syndrome was similar to a control group, paired by age, gender, and Body Mass Index (BMI). 13 Clinical manifestations of Secondary Adrenal Insu ciency are nonspeci c, such as lassitude in the early stage, symptoms frequently attributed to disability related to aging.…”