From liver to hormones: The endocrine consequences of cirrhosis

Abstract

Hepatocrinology explores the intricate relationship between liver function and the endocrine system. Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption. Despite its importance, assessing endocrine issues in cirrhotic patients is frequently neglected. This article provides a comprehensive review of the epidemiology, pathophysiology, diagnosis, and treatment of endocrine disturbances in liver cirrhosis. The review was conducted using the PubMed/Medline, EMBASE, and Scielo databases, encompassing 172 articles. Liver cirrhosis is associated with endocrine disturbances, including diabetes, hypoglycemia, sarcopenia, thyroid dysfunction, hypogonadotropic hypogonadism, bone disease, adrenal insufficiency, growth hormone dysfunction, and secondary hyperaldosteronism. The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system, respectively. Sarcopenia can be assessed through imaging and functional tests, while other endocrine disorders are evaluated using hormonal assays and imaging studies. Treatment options include metformin, glucagon-like peptide-1 analogs, sodium-glucose co-transporter-2 inhibitors, and insulin, which are effective and safe for diabetes control. Established standards are followed for managing hypoglycemia, and hormone replacement therapy is often necessary for other endocrine dysfunctions. Liver transplantation can address some of these problems.

Keywords: Diabetes mellitus; Hypoglycemia; Hypogonadism; Liver cirrhosis; Metabolic bone diseases; Thyroid diseases.

Figure 1

Pathophysiology of liver cirrhosis and associated endocrinopathies. A: Pathophysiology of liver cirrhosis (LC); B: Pathophysiology of the endocrinopathies associated to LC. AD: Antidiabetic drug; AVP: Arginine vasopressin; BCAA: Branched-chain amino acid; BP: Blood pressure; GH: Growth hormone; IGF-1: Insulin-like growth factor 1; IGFBP: Insulin-like growth factor binding protein; RAAS: Renin-angiotensin-aldosterone system; SHBG: Sex hormone-binding globulin; SNS: Sympathetic nervous system; T3: Triiodothyronine; T4: Thyroxine.

Figure 2

Summary of diagnostic tests used in the approach to endocrinopathies associated with liver cirrhosis. The asterisk (*) represents that adrenal insufficiency should be evaluated if there is refractory hypotension, sodium less than 125 mmol/L, and high-density lipoproteins less than 0.39 mmol/L. BMD: Bone mineral density; BMI: Body mass index; CGM: Continuous glucose monitoring; CT: Computed tomography; DXA: Dual-energy X-ray absorptiometry; FIB-4 index: Fibrosis-4 index; FSFI: Female Sexual Function Index; FSH: Follicle-stimulating hormone; FT: Free testosterone; GH: Growth hormone; HbA1c: Hemoglobin A1c; IGF-1: Insulin-like growth factor 1; IIEF: International Index of Erectile Function; IV: Intravenous; L3: 3^rd lumbar vertebrae; LH: Luteinizing hormone; LLN: Lower limit of normality; MRI: Magnetic resonance imaging; OGGT: Oral glucose tolerance test; PA: Primary aldosteronism; PAC: Plasma aldosterone concentration; POI: Primary ovarian insufficiency; PRA: Plasma renin activity; PRC: Plasma renin concentration; PRL: Prolactin; SHBG: Sex hormone-binding globulin; TSH: Thyroid-stimulating hormone; TT: Total testosterone.