Liver and endocrine system

liver and endocrine system interaction in health and disease

1. Liver and endocrine system By: Alaa El- Deen Mostafa Assistant lecturer of internal medicine – minia university

2. The liver as an endocrine organ

3. The liver is involved with the synthesis of carrier proteins and metabolism of various hormones; therefore, liver diseases may be associated with various endocrine disturbances.

4. Liver and thyroid

5. The liver synthesize thyroxine binding proteins Thyroid function is dependent on a normally functioning liver axis.

6. Liver in thyroid disease

7. Thyroid function in liver diseases In acute hepatitis _ elavated serum levels of T4 due to increased thyroid-binding globulin, which is synthesized as an acute-phase reactant ; however, there are normal levels of free T4. In more severe cases with impending liver failure, the data is variable, and low T4 levels may reflect reduced hepatocellular synthesis of thyroid-binding globulin. Serum T3 levels are extremely variable. free T3:T4 ratio correlates negatively with severity of liver

8. I n cirrhosis The most consistent thyroid hormone profile in patients with cirrhosis is low total and free T3 and elevated rT3 levels, similar to changes in patients with euthyroid sick syndrome. This results in an increase in conversion of T4 to T3 and an increase in the rT3:T3 ratio. T3:rT3 ratio binds to the same plasma proteins; the T3:rT3 ratio provides a parameter of liver function . low T4 levels may be related with decreased short- and long-term survival of patients with liver cirrhosis . Low T3 levels are a good indicator of disease severity in cirrhosis [13 ]. A negative correlation was found between Child-Pugh scores and total serum T3 levels. Low T3 levels may be considered an adaptive hypothyroid condition that contributes to reducing the basal metabolic rate within hepatocytes to preserve liver function.

9. non-thyroidal systemic illness causing decreased serum levels of thyroid hormone without a concomitant rise in serum TSH normal total T4, normal-high freeT4, low free T3, and elevated rT3 levels . Serum T3 further decrease as the severity of disease progresses. It can occure in acute and chronic liver disease and It is associated with the severity and prognosis of disease

10. NAFLD and Thyroid Thyroid hormones play a fundamental role in lipid metabolism. Hypothyroidism causes hypercholesterolemia and play an essential role in the pathogenesis of NAFLD . Moreover, a recent study has shown the importance of thyroid hormones for the intrahepatic metabolism via autophagy, including fatty acid β-oxidation and delivery of fatty acids to the mitochondria. NAFLD

11. Autoimmune conditions:

12. Antithyroid drugs and liver PTU > Methemazole Dose related Can cause increased transaminases up to fulminant hepatitis

13. Liver and Thyroid Dysfunction Owing to Systemic Condition

14. Liver and parathyroid

15. Vitamin D deficiency is commonly associated with NAFLD and has even been correlated with disease severity. The metabolic, anti-inflammatory and anti-fibrotic properties of vitamin D provide plausible mechanisms by which vitamin D may impact on the various steps of disease progression and severity. 

16. The term hepatic osteodystrophy refers to bone disorders related to chronic liver disease and cirrhosis. The most prevalent bone disease is osteoporosis, however osteomalacia may also be seen (rarely) in cirrhosis . Reduced levels of IGF-1 in cirrhosis may contribute to reduced bone mass and osteoporosis Osteoprotegerin (OPG) is a member of tumor necrosis factor receptor superfamily that is secreted from osteoblasts and has an inhibitory effect on osteoclast differentiation Recent studies in patients with cirrhosis have illustrated the protective effect of OPG not only in bone loss56 but also in progression of liver disease. and the precise role of OPG remained to be clarify in future studies. The receptor activator of NF kappa beta (RANK) on osteoblasts and receptor activator of NF kappa beta ligand (RANKL) on osteoclasts are involved in bone resorption . Low serum level of RANKL has been reported in patients with PBC but the exact role of RANK/RANKL in pathophysiology of bone disease in cirrhosis is not clear

17. Liver and Adrenal gland

18. Adrenal dysfunction in liver disease Adrenal insufficiency is frequent with sepsis and septic shock in cirrosis , but it is reported in patients with stable cirrhosis for unclear cause. Pseuo-cushing is reported in Alcoholic liver diseases. Hyperaldosteronism occur in advanced liver disease with ascites, Aldosterone antagonist is also used to relieve edema state.

19. Liver affection in adrenal disease Addisson’s --- increased transaminases Cushing’s syndrome ---- insulin resistance and NAFLD

20. Liver and Growth hormone

21. Growth Hormone and Liver Disease Hepatomegaly, increased aminotransferase, insulin resistance is common with acromegaly

22. AGHD patients have a metabolic syndrome-like phenotype that is also associated with the development of NASH The metabolic changes that accompany hypopituitarism are central obesity,hyperlipidemia , and insulin resistance, which are thought to be caused primarily by GH deficiency . Moreover , adult patients with anterior pituitary deficiency and associated GH deficiency experience fatty infiltration of the liver more frequently than patients with anterior pituitary hormone deficiency than in those without GH deficiency . Few reports have demonstrated that GH replacement therapy reversed nonalcoholic steatohepatitis (NASH) in AGHD

23. Liver and sex hormones

24. Use of exogenous hormones

25. Hormonal changes in cirrhosis

26. PCOS and Liver Disease PCOS is considered a risk factor for the development of NAFLD in women. Conversely, NAFLD may also be a risk factor for PCOS [ 73 ]. Insulin resitance and androgen excess in PCOS patients may contribute to NAFLD. The prevalence of NAFLD in the PCOS population is estimated to be between 15 and 55 %. As the prevalence of NAFLD is higher in women with PCOS compared with the general population, early recognition is important. PCOS and NAFLD share a common attribute with regard to the pathogenesis of insulin resistance. Both PCOS and NAFLD are frequently accompanied by metabolic syndrome, and these two diseases can coexist and may respond to similar therapeutic strategies.

27. LIVER AND DIABETES

28. Metabolic syndorme ≥ 3

29. The high incidence of diabetes in patients with liver cirrhosis has been known from years ago. On the other hand patients with diabetes are more susceptible to chronic liver disease and HCC. Metabolic syndrome and diabetes are not only prevalent among patients with chronic liver diseases but also can occur after liver transplantation . The terms non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are hepatic manifestations of insulin resistance and metabolic syndrome. In patients with NAFLD, the incidence of type II diabetes is increased independent of insulin resistance and type II diabetes have been suggested by some authors .

30. Elevated liver chemistries have been observed in 10%-20% of patients with DM, more frequently in patients with type 2 than type 1 DM. One study reported that 16.5%, 9%, 11% and 6% of these patients had elevations in serum GGT, ALP, ALT and AST, respectively. Non-alcoholic fatty liver disease is a complication in 32% to 78% of patients with type 2 DM, and 50% of these patients may have non-alcoholic steatohepatitis (NASH ). NASH in DM patients may lead to liver cirrhosis and eventually to hepatocellular carcinoma.

31. We have recently shown that a pattern of sick euthyroid syndrome is prevalent in patients with NAFLD and the model of NAFLD

32. The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone defi ciency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing’s syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis . Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines ( leptin , acylation stimulating protein, adiponectin ) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

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