The association between hypopituitarism and metabolic dysfunction-associated steatotic liver disease is increasingly recognized, although data about therapies targeting recurrence posttransplant is limited. An 8-year-old with hypopituitarism-associated metabolic dysfunction-associated steatotic liver disease underwent a liver transplant due to rapid progression of metabolic dysfunction-associated steatohepatitis. Hepatosteatosis recurred within weeks. Her therapeutic plan included a glucagon-like peptide-1 agonist and growth hormone replacement. Her transaminases normalized in 2.5 months, and her macrosteatosis significantly improved on the 1-year surveillance biopsy. This case highlights one of the youngest reported children with hypopituitarism to have undergone transplantation for rapidly progressing metabolic dysfunction-associated steatohepatitis and its recurrence post-operatively. We observed that steatosis improved with growth hormone replacement and glucagon-like peptide-1 agonist therapy. If started early, this combination could help delay recurrence of steatosis post-transplantation. Further research is needed to determine long-term effects and establish protocols.

Adult growth hormone deficiency (AGHD) is often accompanied with metabolic dysfunction-associated steatotic liver disease (MASLD). Although some studies reported that MASLD is ameliorated by growth hormone replacement therapy (GHRT), the characteristics of AGHD that are associated with an improvement of hepatic steatosis by GHRT remain unknown. We aimed to investigate whether GHRT affects hepatic lipid accumulation as well as biochemical parameters, and investigated the association between these parameters (UMIN000044989). Thirty people with AGHD were recruited, and assigned to either the GHRT group or the non-GHRT group. Serum laboratory data were analyzed before and after GHRT. Hepatic lipid content was evaluated using magnetic resonance imaging-proton density fat fraction (MRI-PDFF). Correlations between MRI-PDFF and other clinical parameters were investigated. Twenty-nine people completed this study (19 in the GHRT group and 10 in the non-GHRT group). In the GHRT group, significant decreases in MRI-PDFF and serum levels of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase were observed after the treatment. The decrease in MRI-PDFF levels after GHRT significantly correlated with initial MRI-PDFF, triglyceride (TG), lactate dehydrogenase, and ALT levels, and age. Multiple regression analysis demonstrated that younger age and high serum TG levels were independent predictors of a decrease in MRI-PDFF levels. GHRT in people with AGHD significantly reduced lipid accumulation in the liver on MRI, and improved serum liver parameters. Age and serum TG levels were found to be associated with the effectiveness of GHRT.

Metabolic health is tightly regulated by neuro-hormonal control, and systemic metabolic dysfunction may arise from altered function of the hypothalamic-anterior pituitary axis (HAPA). Ancient experimental observations of hypothalamic obesity (HO) and liver cirrhosis occurring among animals subjected to hypothalamic injury can now be explained using the more recent concepts of lipotoxicity and metabolic dysfunction-associated steatotic liver disease (MASLD). Lipotoxicity, the range of abnormalities resulting from the harmful effects of fatty acids accumulated in organs outside of adipose tissue, is the common pathogenic factor underlying closely related conditions like hypothalamic syndrome, HO, and MASLD. The hormonal deficits and the array of metabolic and metabolomic disturbances that occur in cases of HO are discussed, along with the cellular and molecular mechanisms that lead, within the MASLD spectrum, from uncomplicated steatotic liver disease to steatohepatitis and cirrhosis. Emphasis is placed on knowledge gaps and how they can be addressed through novel studies. Future investigations should adopt precision medicine approaches by precisely defining the hormonal imbalances and metabolic dysfunctions involved in each individual patient with HO, thus paving the way for tailored management of MASLD that develops in the context of altered HAPA.

Pituitary stalk interruption syndrome (PSIS) is a congenital disease commonly found in patients with combined pituitary hormone deficiency (CPHD). Most PSIS patients manifest growth retardation and delayed puberty. We report a rare case of PSIS with tall stature, liver cirrhosis and diabetes, possibly caused by an inactivating KCNJ11 gene mutation.

A 37-year-old female patient initially presented with liver cirrhosis and diabetes, without any secondary sexual characteristics. Endocrine investigation indicated CPHD. Small anterior pituitary, invisible pituitary stalk and no eutopic posterior lobe hypersignal in the sella turcica viewed in magnetic resonance imaging (MRI) confirmed the diagnosis of PSIS. Despite receiving no growth hormone or sex hormone therapy, she reached a final height of 186 cm. Liver histopathology revealed nonalcoholic fatty cirrhosis. Genetic testing identified a heterozygous p.Arg301Cys mutation in the KCNJ11 gene.

This is a rare case of PSIS with liver cirrhosis and diabetes associated with an inactivating KCNJ11 gene mutation. It's supposed that early hyperinsulinism caused by the KCNJ11 gene mutation, as well as delayed epiphyseal closure due to estrogen deficiency, contributed to the patient's exceptionally tall stature. Untreated growth hormone deficiency (GHD) resulted in increased visceral fat, leading to nonalcoholic fatty liver disease (NAFLD) and cirrhosis. The decline in β cell function with age, combined with NAFLD, may have played a role in the development of diabetes.

Growth hormone (GH) plays an essential role not only in promoting growth in children, but also in many important metabolic processes in adults. One of the major metabolic functions of GH is its stimulatory effects on the liver in generating approximately 80% of circulating insulin-like growth factor 1 (IGF-1). Adult growth hormone deficiency (GHD) is an established clinical entity defined as a defect in endogenous GH secretion that is frequently associated with central obesity, loss of muscle mass, decreased bone mass, and impaired quality of life. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are conditions that are often under-recognized in adults with GHD, and accordingly some studies have shown that GH and IGF-1 levels are decreased in patients with NAFLD. Furthermore, it has been reported that it can progress to end-stage liver cirrhosis in some adults and children with GHD. Due to their underlying mechanisms of action, GH and IGF-1 can act on hepatocytes, macrophages, and hepatic stellate cells to mitigate progression to steatosis and fibrosis. It is, thus, important to recognize NAFLD/NASH as important complications in adult and childhood GHD. Therefore, careful and thorough evaluation of NAFLD/NASH in adults with GHD and the consideration for GH replacement therapy is crucial in these patients, together with management of other metabolic risk factors, such as obesity and dyslipidemia. This review will focus on recent reports on the role of GH and IGF-1 in the liver and its clinical significance in the regulation of hepatic function.

Overweight and obesity are associated with relative growth hormone (GH) deficiency, which has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD is a progressive disease without effective treatments.

We hypothesized that GH administration would reduce hepatic steatosis in individuals with overweight/obesity and NAFLD.

In this 6-month randomized, double-blind, placebo-controlled trial of low-dose GH administration, 53 adults aged 18 to 65 years with BMI ≥25 kg/m2 and NAFLD without diabetes were randomized to daily subcutaneous GH or placebo, targeting insulin-like growth factor 1 (IGF-1) to the upper normal quartile. The primary endpoint was intrahepatic lipid content (IHL) by proton magnetic resonance spectroscopy (1H-MRS) assessed before treatment and at 6 months.

Subjects were randomly assigned to a treatment group (27 GH; 26 placebo), with 41 completers (20 GH and 21 placebo) at 6 months. Reduction in absolute % IHL by 1H-MRS was significantly greater in the GH vs placebo group (mean ± SD: -5.2 ± 10.5% vs 3.8 ± 6.9%; P = .009), resulting in a net mean treatment effect of -8.9% (95% CI, -14.5 to -3.3%). All side effects were similar between groups, except for non-clinically significant lower extremity edema, which was more frequent in the GH vs placebo group (21% vs 0%, P = .02). There were no study discontinuations due to worsening of glycemic status, and there were no significant differences in change in glycemic measures or insulin resistance between the GH and placebo groups.

GH administration reduces hepatic steatosis in adults with overweight/obesity and NAFLD without worsening glycemic measures. The GH/IGF-1 axis may lead to future therapeutic targets for NAFLD.

Insulin resistance is associated with ectopic lipid deposition. Growth hormone (GH) status also modulates ectopic lipid accumulation, but how this associates with insulin resistance in patients with GH disorders is not well established.

Twenty-one patients diagnosed with acromegaly and 12 patients with adult GH deficiency (GHD) were studied at diagnosis and after treatment. A reference group of 12 subjects was included. Each study day comprised assessment of body composition with dual-energy X-ray absorptiometry, ectopic lipid deposition in the liver by MR spectroscopy, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).

Disease control of acromegaly decreased lean body mass (LBM) (P < .000) and increased the percentage of total body fat (TBF) (P < .000). GH replacement increased LBM in the GHD patients (P = .007) and decreased the percentage of TBF (P = .010). The intrahepatic lipid (IHL) content increased after disease control in acromegaly (P = .004), whereas IHL did not change significantly after GH replacement in GHD (P = .34). Insulin resistance (HOMA-IR) improved after disease control of acromegaly (P < .000) and remained unaltered after GH replacement in the GHD patients (P = .829).

GH status is a significant modulator of body composition and insulin sensitivity.GH excess reduces total fat mass and intrahepatic lipid content together with induction of insulin resistance.The data support the notion that GH-induced insulin resistance is unassociated with hepatic lipid accumulation.

Non-alcoholic fatty liver disease (NAFLD) is characterized by growth hormone deficiency (GHd). We investigated the association between NAFLD and GHd in patients with nonfunctioning pituitary adenomas (NFPA).

We recruited patients with NFPA who underwent transsphenoidal adenectomy between January 2005 and December 2018. Pituitary function was determined by the insulin tolerance test, thyroid hormone assay, and gonadal hormone levels. NAFLD was defined as a hepatic steatosis index greater than 36.

Among 278 patients (mean age, 44.2 years; 58.6% [n=163] female), 103 (37.0%) had GHd, 139 (50.0%) had hypogonadism, and 75 (27.0%) had NAFLD. The prevalence of NAFLD was significantly higher in patients with GHd than in those without (36.9% vs. 21.1%, p=0.01). Even after adjusting for age, total cholesterol level, gonadal function, and prolactin level, patients with GHd had approximately two-fold higher prevalence of NALFD than those without GHd (adjusted odds ratio [OR]=1.85, 95% confidence interval [CI]=1.05-3.28, p=0.03). Among female patients, the prevalence of NALFD was significantly higher in those with GHd than in those without (adjusted OR=2.39, 95% CI=1.03-5.55, p=0.04); whereas, among male patients, the prevalence of NAFLD was statistically similar between those with and without GHd (p>0.05). In addition, gonadal function did not affect the prevalence of NAFLD in patients with NFPA (29.3% with eugonadism vs. 47.8% with hypogonadism, p=0.14).

Among patients with NFPA, the prevalence of NAFLD was two-fold higher in patients with GHd than that in those without GHd. Thus, screening for NAFLD might be required in NFPA patients with GHd.

Over the past decades, adapted lifestyle and dietary habits in industrialized countries have led to a progress of obesity and associated metabolic disorders. Concomitant insulin resistance and derangements in lipid metabolism foster the deposition of excess lipids in organs and tissues with limited capacity of physiologic lipid storage. In organs pivotal for systemic metabolic homeostasis, this ectopic lipid content disturbs metabolic action, thereby promotes the progression of metabolic disease, and inherits a risk for cardiometabolic complications. Pituitary hormone syndromes are commonly associated with metabolic diseases. However, the impact on subcutaneous, visceral, and ectopic fat stores between disorders and their underlying hormonal axes is rather different, and the underlying pathophysiological pathways remain largely unknown. Pituitary disorders might influence ectopic lipid deposition indirectly by modulating lipid metabolism and insulin sensitivity, but also directly by organ specific hormonal effects on energy metabolism. In this review, we aim to I) provide information about the impact of pituitary disorders on ectopic fat stores, II) and to present up-to-date knowledge on potential pathophysiological mechanisms of hormone action in ectopic lipid metabolism.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most frequent chronic liver disease globally. NAFLD is strongly associated with metabolic syndrome and it has been recently suggested that to rename NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD). NAFLD has been studied in different endocrine axes and accumulating body of clinical and experimental studies have suggested that NAFLD is associated with polycystic ovarian syndrome (PCOS), hypopituitarism, growth hormone deficiency (GHD), hypogonadism and other endocrine disorders. In fact, endocrine dysfunction may be considered as the major contributor for the development, progression, and severity of NAFLD. In the present comprehensive review, we discussed the epidemiological and clinical evidence on the epidemiology, pathophysiology, and management of NAFLD in endocrine disorders, with an emphasis on the effects of sex-specific hormones/conditions as well as molecular basis of NAFLD development in these endocrine diseases.

Pituitary stalk interruption syndrome (PSIS), characterized by thinning or disappearance of the pituitary stalk, hypoplasia of the anterior pituitary, and an ectopic posterior pituitary, can lead to congenital combined pituitary hormone deficiency. There is a high prevalence of various metabolic disorders, including nonalcoholic fatty liver disease (NAFLD), in this population.

To investigate the characteristics of NAFLD in Chinese adult patients with PSIS and its association with growth hormone deficiency.

Retrospective cross-sectional study in a tertiary referral center of China.

Adult patients with PSIS diagnosed, followed up between September 2019 and August 2021, were consecutively enrolled.

Abdominal ultrasonography images were evaluated and noninvasive fibrosis scores were determined to assess the severity of NAFLD. Anthropometric, clinical, and biochemical parameters were compared between patients with and without NAFLD. Logistic regression was performed to assess the independent effects of insulin-like growth factor-1 (IGF-1) on NAFLD.

A total of 93 patients (77 men, 16 women, mean age: 29.6 ± 7.1 years) were included. The prevalence of NAFLD and advanced fibrosis/cirrhosis was 50.5% and 4.3%, respectively. Insufficient hormone therapy and prominent metabolic disorders, including central obesity, dyslipidemia, insulin resistance, and metabolic syndrome, were more common in the NAFLD (+) group. After adjusting for multiple variables, IGF-1 &lt;-2 standard deviation score (SDS) was found to be associated with an increased prevalence of NAFLD (odds ratio [OR]: 4.92, 95% confidence interval [CI]: 1.21-24.55, p = .035). Per 1 SDS increase in IGF-1 was associated with a 27% lower risk of NAFLD (OR: 0.73, 95% CI: 0.52-0.97, p = .042).

NAFLD is a frequent comorbidity among Chinese adult patients with PSIS and is strongly associated with lower IGF-1 levels. Timely and appropriate hormone replacement, particularly growth hormone may contribute to decreasing the risk of NAFLD in these patients.

Patients with obesity have a high prevalence of nonalcoholic fatty liver disease (NAFLD), representing a spectrum of simple steatosis to nonalcoholic steatohepatitis (NASH), without and with fibrosis. Understanding the etiology of NAFLD is clinically relevant since NAFLD is an independent risk factor for diabetes and cardiovascular disease. In addition, NASH predisposes patients to the development of cirrhosis and hepatocellular carcinoma, and NASH cirrhosis represents the fastest growing indication for liver transplantation in the United States. It is appreciated that multiple factors are involved in the development and progression of NAFLD. Growth hormone (GH) and insulin-like growth factor 1 (IGF1) regulate metabolic, immune, and hepatic stellate cell function, and alterations in the production and function of GH is associated with obesity and NAFLD/NASH. Therefore, this review will focus on the potential role of GH and IGF1 in the regulation of hepatic steatosis, inflammation, and fibrosis.

To investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) in adolescents and young adults with hypopituitarism and to examine the associations of growth hormone (GH) deficiency with the occurrence of NAFLD.

A cross-sectional study for the determination of NAFLD prevalence included 76 patients with childhood-onset hypopituitarism and 74 controls matched by age and body mass index (BMI). We investigated the prevalence of NAFLD in adolescent and young adult patients with hypopituitarism as well as the age- and BMI-matched controls. Among patients with hypopituitarism, anthropometric, clinical, and biochemical assessments using transient elastography and magnetic resonance imaging were performed. Logistic regression was used to identify the factors associated with NAFLD.

The adolescents and young adults with hypopituitarism exhibited higher prevalence of NAFLD than the age- and BMI-matched controls. Among patients with hypopituitarism, obesity and obesity-related metabolic derangements were significantly associated with liver steatosis and fibrosis, whereas lower insulin-like growth factor (IGF)-I standard deviation score (SDS) and IGF-I/IGF-binding protein 3 molar ratios were associated with steatosis. In regression analyses adjusted for BMI SDS, steatosis was found to be associated with a lower IGF-I SDS and IGF-I/IGF-binding protein 3 molar ratios, whereas liver fibrosis was found to be associated with a lower IGF-I SDS.

Our results suggest that GH deficiency contributes to the occurrence of NAFLD, along with obesity and obesity-related metabolic changes. Because NAFLD occurs early in patients with hypopituitarism, the surveillance, weight control, and timely replacement of deficit hormones, including GH, are essential.

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPG). Methods: Recommendations are based on diligent reviews of clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. Results: The Executive Summary of this 2019 updated guideline contains 58 numbered recommendations: 12 are Grade A (21%), 19 are Grade B (33%), 21 are Grade C (36%), and 6 are Grade D (10%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 357 citations of which 51 (14%) are evidence level (EL) 1 (strong), 168 (47%) are EL 2 (intermediate), 61 (17%) are EL 3 (weak), and 77 (22%) are EL 4 (no clinical evidence). Conclusion: This CPG is a practical tool that practicing endocrinologists and regulatory bodies can refer to regarding the identification, diagnosis, and treatment of adults and patients transitioning from pediatric to adult-care services with growth hormone deficiency (GHD). It provides guidelines on assessment, screening, diagnostic testing, and treatment recommendations for a range of individuals with various causes of adult GHD. The recommendations emphasize the importance of considering testing patients with a reasonable level of clinical suspicion of GHD using appropriate growth hormone (GH) cut-points for various GH-stimulation tests to accurately diagnose adult GHD, and to exercise caution interpreting serum GH and insulin-like growth factor-1 (IGF-1) levels, as various GH and IGF-1 assays are used to support treatment decisions. The intention to treat often requires sound clinical judgment and careful assessment of the benefits and risks specific to each individual patient. Unapproved uses of GH, long-term safety, and the current status of long-acting GH preparations are also discussed in this document. LAY ABSTRACT This updated guideline provides evidence-based recommendations regarding the identification, screening, assessment, diagnosis, and treatment for a range of individuals with various causes of adult growth-hormone deficiency (GHD) and patients with childhood-onset GHD transitioning to adult care. The update summarizes the most current knowledge about the accuracy of available GH-stimulation tests, safety of recombinant human GH (rhGH) replacement, unapproved uses of rhGH related to sports and aging, and new developments such as long-acting GH preparations that use a variety of technologies to prolong GH action. Recommendations offer a framework for physicians to manage patients with GHD effectively during transition to adult care and adulthood. Establishing a correct diagnosis is essential before consideration of replacement therapy with rhGH. Since the diagnosis of GHD in adults can be challenging, GH-stimulation tests are recommended based on individual patient circumstances and use of appropriate GH cut-points. Available GH-stimulation tests are discussed regarding variability, accuracy, reproducibility, safety, and contraindications, among other factors. The regimen for starting and maintaining rhGH treatment now uses individualized dose adjustments, which has improved effectiveness and reduced reported side effects, dependent on age, gender, body mass index, and various other individual characteristics. With careful dosing of rhGH replacement, many features of adult GHD are reversible and side effects of therapy can be minimized. Scientific studies have consistently shown rhGH therapy to be beneficial for adults with GHD, including improvements in body composition and quality of life, and have demonstrated the safety of short- and long-term rhGH replacement. Abbreviations: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; AHSG = alpha-2-HS-glycoprotein; AO-GHD = adult-onset growth hormone deficiency; ARG = arginine; BEL = best evidence level; BMD = bone mineral density; BMI = body mass index; CI = confidence interval; CO-GHD = childhood-onset growth hormone deficiency; CPG = clinical practice guideline; CRP = C-reactive protein; DM = diabetes mellitus; DXA = dual-energy X-ray absorptiometry; EL = evidence level; FDA = Food and Drug Administration; FD-GST = fixed-dose glucagon stimulation test; GeNeSIS = Genetics and Neuroendocrinology of Short Stature International Study; GH = growth hormone; GHD = growth hormone deficiency; GHRH = growth hormone-releasing hormone; GST = glucagon stimulation test; HDL = high-density lipoprotein; HypoCCS = Hypopituitary Control and Complications Study; IGF-1 = insulin-like growth factor-1; IGFBP = insulin-like growth factor-binding protein; IGHD = isolated growth hormone deficiency; ITT = insulin tolerance test; KIMS = Kabi International Metabolic Surveillance; LAGH = long-acting growth hormone; LDL = low-density lipoprotein; LIF = leukemia inhibitory factor; MPHD = multiple pituitary hormone deficiencies; MRI = magnetic resonance imaging; P-III-NP = procollagen type-III amino-terminal pro-peptide; PHD = pituitary hormone deficiencies; QoL = quality of life; rhGH = recombinant human growth hormone; ROC = receiver operating characteristic; RR = relative risk; SAH = subarachnoid hemorrhage; SDS = standard deviation score; SIR = standardized incidence ratio; SN = secondary neoplasms; T3 = triiodothyronine; TBI = traumatic brain injury; VDBP = vitamin D-binding protein; WADA = World Anti-Doping Agency; WB-GST = weight-based glucagon stimulation test.

Secondary nonalcoholic fatty liver disease (NAFLD) defines those complex pathophysiological and clinical consequences that ensue when the liver becomes an ectopic site of lipid storage owing to reasons other than its mutual association with the metabolic syndrome. Disorders affecting gonadal hormones, thyroid hormones, or growth hormones (GH) may cause secondary forms of NAFLD, which exhibit specific pathophysiologic features and, in theory, the possibility to receive an effective treatment. Here, we critically discuss epidemiological and pathophysiological features, as well as principles of diagnosis and management of some common endocrine diseases, such as polycystic ovary syndrome (PCOS), hypothyroidism, hypogonadism, and GH deficiency. Collectively, these forms of NAFLD secondary to specific endocrine derangements may be envisaged as a naturally occurring disease model of NAFLD in humans. Improved understanding of such endocrine secondary forms of NAFLD promises to disclose novel clinical associations and innovative therapeutic approaches, which may potentially be applied also to selected cases of primary NAFLD.

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.

Conventional glucocorticoid treatment has a significant impact on liver in patients with adrenal insufficiency. Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement in anthropometric and metabolic parameters. We aimed to evaluate the effects of 12-month DR-HC treatment on the hepatic steatosis index (HSI), a validated surrogate index of hepatic steatosis, in patients with secondary adrenal insufficiency (SAI).

A total of 45 patients with hypopituitarism, 22 with hypogonadism, hypothyroidism, ACTH, and GH deficiencies, and 23 with hypogonadism, hypothyroidism, and ACTH deficiency, on replacement therapy for all the pituitary deficiencies, were switched from conventional hydrocortisone to DR-HC. At baseline and after 12 months, glucose and insulin levels, surrogate estimates of insulin sensitivity, and hepatic steatosis were evaluated through ultrasonography and HSI.

At diagnosis, ultrasonography documented steatosis in 31 patients (68.8%) while 33 (73.3%) showed high HSI. Hydrocortisone (HC) dose (β = 1.231, p = 0.010), insulin resistance index (HOMA-IR) (β = 1.431, p = 0.002), and insulin sensitivity index (ISI)-Matsuda (β = -1.389, p = 0.034) were predictors of HSI at baseline. After 12 months of DR-HC, a significant decrease in body mass index (BMI) (p = 0.008), waist circumference (WC) (p = 0.010), fasting insulin (p = 0.041), HOMA-IR (p = 0.047), HSI (p < 0.001) and number of patients with HSI ⩾36 (p = 0.003), and a significant increase in sodium (p < 0.001) and ISI-Matsuda (p = 0.031) were observed. HOMA-IR (β = 1.431, p = 0.002) and ISI-Matsuda (β = -9.489, p < 0.001) were identified as independent predictors of HSI at 12 months.

In adults with SAI, DR-HC is associated with an improvement in HSI, regardless of the dose used, mainly related to an improvement in insulin sensitivity.