liver and endocrine system interaction in health and disease

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

4. • 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.

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

8. • 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

9. In 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.

10. • 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

11. • 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.

12. AIH
PSC
Grave’s
Hashimoto

13. • PTU > Methemazole
• Dose related
• Can cause increased transaminases up to fulminant
hepatitis

14. Diseases
• Malignancies,
• amyloidosis,
• secondary
hemochromatosis
Drugs
•amiodarone,
•mefloquine,
•carbamazepine
• antineoplastic.

18. • 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

20. • 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.

22. • Addisson’s --- increased transaminases
• Cushing’s syndrome ---- insulin resistance and NAFLD

25. • Hepatomegaly, increased aminotransferase, insulin
resistance is common with acromegaly

26. • 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 .

31. LC in
males
Feminie
distribution
of hair
Hypogonadism
Altered
levels of
sex
hormones
Test.
Atrophy
Decreased
lipido
Gynacomastia

32. LC in
females
ammenorhea
Hypogonadism
Altered
levels of
sex
hormones
Loss of
2ry
sexual
ch
Early
menopause

34. • 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.

35. PCO
insulin
resistance
Hypertension
Dyslipidemi
a
DM

36. NAFLDPCO

40. NAFLDDM-MS

42. Fasting glucose ≥100 mg/dL
Blood pressure ≥130/85 mm Hg
Triglycerides ≥150 mg/dL
HDL-C <40 mg/dL in men or <50 mg/dL in women
Waist circumference ≥102 cm in men or ≥88 cm in women

43. • 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.

44. • 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.

45. NAFLD
IR
Oxidative
stress

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

48. • 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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50. Thank you