Liver and Endocrine System

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Liver and Endocrine System Clinical Aspects
By Ahmed Abdel Samie MD Head of GIT Unit, Egypt
Air Hospital Cairo, Egypt
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Endocrinal Function of the liver

• -Interacts with the hypothalamo-pituitary-endocrin
  e axis for hormonal homeostasis.
• -Inactivation and modification of several
  hormones e.g. insulin, glucagon, T3, T4, steroids
  and sex hormones.
• Somatomedins Synthesis SMc or insulin-like GFI
  are the mediators of GH action , they are kept at
  constant level while GH level is fluctuating.

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Endocrinal unbalance in liver cirrhosis

• - Diminished metabolism of hormones due to
• Decrease in hepatic blood flow.
• P.S. shunts.
• Increase in binding proteins leading to
  decrease in free active hormones.
• - Affection of the Hypothalamo-pituitary -
  endocrine axis.

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Liver and Glucose metabolism

• Liver is the glucostat of the body
• - With decrease in glucose levels
• Decrease in glucose uptake.
• Gluconeogenesis.
• Glycogenolysis.
• - With increase in glucose levels
• Increase in glucose uptake.
• Glycogenesis.
• Glycolysis.

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Clinical Aspects
1- Hypoglycemia -Only significant with
acute and fluminant hepatitis. 2- Glucose
intolerance - In cirrhotics.
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Hypoglycemia
- One of the correctable morbid or even mortal
factors in F.H. - Blood glucose must be
monitored every 2-4 hours. - 300 gm/day. - In
acute hepatitis high carbohydrate diet with
balanced diet. - High carbohydrate diet in
cirrhotics specially with H.E.
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Glucose Intolerance

• - With cirrhosis.
• - Normal or even decrease in fasting glucose and
  increase in P.P. glucose.
• - Insulin resistance
• Decrease in both number and affinity of insulin
  receptors.
• High glucagon level.
• - Increase in insulin level like all hormones.

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Liver and DM

• - In type I DM
• Increase in glucagon deposition vacoulization.
• - In type II DM
• Increase in fat deposition macro-vesicular.
• Fatty liver and steatosis.
• Insulin resistance in type II DM is the first hit
  in NASH.

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Clinical Aspects
Hypoglycemia - Cirrhotics are more liable for
hypoglycemia with hypoglycemic drugs. - So,
rules of tight control can not be applied. - And
short acting drugs are preferred. - Hypoglycemic
coma can mimic, aggravate and be masked by H.E. ,
so blood glucose must be monitored.
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Clinical Case
- Male patient 52 years old known to be cirrhotic
and diabetic presented with disturbed
consciousness, marked irritability and
tachycardia. - We must test blood glucose before
starting anti-H.E. measures and monitor the level
until recovery. - Both hypoglycemia and H.E.
cause irritability and aggression.
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Hypoglycemic drugs

• - Insulin
• is suitable for all stages of liver disease.
• - Insulin analogues
• advantage of less hypoglycemia.
• - Sulfonylurea
• are metabolized in liver so short acting ones are
  better.
• Rarely may cause cholestatic or granulomatous
  hepato-toxicity.
• - Metformin
• Avoided in cirrhosis as it may induce lactic
  acidosis.
• Can be used in chronic hepatitis.
• Beneficial for NASH.

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Hypoglycemic drugs

• - New insulin sensitizers Thiazolidines
• May increase liver enzymes (2).
• ALT and AST must be monitored.
• Beneficial for NASH to improve insulin
  resistance.
• - Benzoic acid derivatives
• Short acting, with each meal.
• Less hypoglycemia.
• - Alpha-glucosidase inhibitor Acarbose
• Safe.

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Association of D.M. and liver disorders

• - Auto immune hepatitis
• May be due to shared genetic predisposition
  HLA-B8 , DR3.
• Hemochromatosis
• HCV patients have higher incidence rate of D.M.
• - Association ?!!
• - Causal relation ?!!
• HCV alters antigenecity of B-cells or insulin
  receptors.
• Direct cytopathic effect on B-cells.

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Gall bladder disorders

• - Higher incidence of gall stones in D.M. may be
  due to associated obesity or hypercholesterolemia.
  
• - Emphysematous cholecystitis
• Specific relation to D.M.
• Clostridia organism.
• More in males.
• Gas in the G.B. wall in X-rays.
• Higher rate of perforation and mortality.

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Contraceptive pills

• - Intra-hepatic cholestasis
• Onset after weeks to months.
• Synergetic effect of estrogen and progesterone ,
  but mainly estrogen.
• More in families with benign cholestaisis of
  pregnancy, so must not be used.
• Peliosis hepatis
• Thin walled hepatic cysts filled with blood.
• May rupture and cause internal hemorrhage and
  sever abdominal pain.
• - Benign and rarely malignant neoplasma.

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Liver and Thyroid
- Liver is important for transportation, storage,
activation and metabolism of T3 and T4 hormones.
- No significant thyroid disease in liver
cirrhosis except for mild increase in T3, T4
while free T3, T4 are normal. - Auto-immune
thyroiditis may exist with AIH, HCV and INF
therapy.
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Thyrotoxicosis
- Mild increase in liver enzymes. - Rarely
cholestaisis even without H.F.. - May
aggravate Gilbert syndrome.
Myxoedema
- Ascites. - May be not evident clinically.
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Thyroid and HCV
- Thyroiditis may occur even without INF therapy.
- With INF, autoimmune thyroiditis occurs after
4 - 6 months ( like other auto-immune phenomena
) - Pre-existing anti-microsomal Ab is a risk
factor for INF therapy. - When to stop INF ? !!
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Anti thyroid drugs

• - Propyl-thiouracil
• Increase in liver enzymes transient for 2 months.
  
• - Neomercazole
• May cause cholestaisis.

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Liver and steroids

• - Prednisone is metabolized in liver to the more
  active prednisolone, so in liver cirrhosis
  prednisolone is preferred.
• - In TB addison disease
• Rifampicin is an inducer drug, so we must
  increase steroid dose to avoid addisonian crisis.