Endocrine DisordersEndocrine Disorders

Harliansyah,Ph.DHarliansyah,Ph.DDept Biochemistry, FK-UYDept Biochemistry, FK-UY

Abnormalities of endocrine glands Abnormalities of endocrine glands generally fall into one of the generally fall into one of the

several categories;several categories; 1. Hypersecretion1. Hypersecretion - Excess activity of a specific hormone- Excess activity of a specific hormone - May be due to overproduction of a hormone due to - May be due to overproduction of a hormone due to

abnormal abnormal glandular function, glandular hypertrophy/ glandular function, glandular hypertrophy/

hyperplasia or thehyperplasia or the presence of tumors that secrete hormone.presence of tumors that secrete hormone.

2. Hyposecretion2. Hyposecretion - Reduced activity of a specific hormone- Reduced activity of a specific hormone - May be due to atrophy of glandular tissue or damage - May be due to atrophy of glandular tissue or damage

from autoimmune attack, infection or neeoplasia. from autoimmune attack, infection or neeoplasia.

3. Altered responsiveness of a tissue to a specific hormone

-. Tissue no longer responds to a specific hormone -. May involve down regulation of receptors or altered receptor/ secondary messenger function -. Circulating levels of hormone may be normal or even elevated ( Type II DM)

Metabolic syndromeMetabolic syndrome

The metabolic syndrome is identified by The metabolic syndrome is identified by the presence of three or more of these the presence of three or more of these

components:components: Central obesity as measured by waist Central obesity as measured by waist

circumference:circumference:Men — Greater than 40 inches (102 cm)Men — Greater than 40 inches (102 cm)

Women — Greater than 35 inches (88 cm)Women — Greater than 35 inches (88 cm) Fasting blood triglycerides greater than or equal to Fasting blood triglycerides greater than or equal to

1.7 mmol/L1.7 mmol/L Blood HDL cholesterol:Blood HDL cholesterol:

Men — Less than 1.03 mmol/LMen — Less than 1.03 mmol/LWomen — Less than 1.2 mmol/LWomen — Less than 1.2 mmol/L

Blood pressure greater than or equal to 130/85 Blood pressure greater than or equal to 130/85 mmHgmmHg

Fasting glucose greater than or equal to 6.1 mmol/LFasting glucose greater than or equal to 6.1 mmol/L

The Metabolic Syndrome:The Metabolic Syndrome:SignificanceSignificance

Body SizeBody Size BMIBMI

Central AdiposityCentral Adiposity

GlucoseGlucoseMetabolismMetabolism

Uric AcidUric AcidMetabolismMetabolism DyslipidemiaDyslipidemia Hemodynamic Novel Risk

Factors

CORONARY HEART DISEASECORONARY HEART DISEASE

Insulin ResistanceInsulin Resistance

HyperinsulinemiaHyperinsulinemia++

TGTG PP lipemiaPP lipemia HDL-CHDL-C

Small, dense LDLSmall, dense LDL

± ± GlucoseGlucoseintoleranceintolerance

Uric acidUric acid Urinary Urinary

uricuricacid clearanceacid clearance

SNS activitySNS activity Na retentionNa retentionHypertensionHypertension

CRPCRP PAI-1PAI-1

FibrinogenFibrinogen

There are three types of hormonal control pathways

Pathway Example

Stimulus Low bloodglucose

Receptorprotein

Pancreassecretesglucagon ( )

Endocrinecell Blood

vessel

LiverTarget

effectors

Response

Pathway Example

Stimulus Suckling

Sensoryneuron

Hypothalamus/posterior pituitary

Neurosecretorycell

Bloodvessel

Posterior pituitarysecretes oxytocin( )

Targeteffectors

Smooth musclein breast

Response Milk release

Pathway Example

Stimulus Hypothalamicneurohormonereleased inresponse toneural andhormonalsignals

Sensoryneuron

Hypothalamussecretes prolactin-releasinghormone ( )

Neurosecretorycell

Bloodvessel

Anteriorpituitarysecretesprolactin ( )Endocrine

cellBloodvessel

Targeteffectors

Response

Mammary glands

Milk production

(c) Simple neuroendocrine pathway

(b) Simple neurohormone pathway

(a) Simple endocrine pathway

Hypothalamus

Glycogenbreakdown,glucose releaseinto blood

Glucos

e Ra

TG

Normal Insulin Normal Insulin FunctionFunction

Insulin InsulinInsulin

Glucose

InsulinInsulin

Insulin

InsulinInsulin

Insulin

Insulin InsulinInsulin

GlucoseGlucose

GlucoseGlucose

GlucoseGlucoseGlucose

Glucose

Normal Insulin ActionNormal Insulin Action

Increase in glucose uptake by Increase in glucose uptake by muscle, liver, and fatmuscle, liver, and fat

Decrease glucose output by the Decrease glucose output by the liverliver

Increase TG storage, decreased Increase TG storage, decreased TG breakdownTG breakdown

Net Result:

Insulin ResistanceInsulin Resistance

Increased insulin production to Increased insulin production to force glucose uptakeforce glucose uptake

Decreased inhibition of glucose Decreased inhibition of glucose rate of appearance from the liverrate of appearance from the liver

Decreased inhibition of TG Decreased inhibition of TG breakdown FFA in blood.breakdown FFA in blood.

Net Result:

TGTGCholesterolCholesterolLDLLDLHDLHDLInsulin (hyperinsulinemia)Insulin (hyperinsulinemia)Post-prandial glucosePost-prandial glucose

Consequences of Prolonged Consequences of Prolonged HyperinsulinemiaHyperinsulinemia

Consequences of Prolonged Consequences of Prolonged Hyperinsulinemia….Hyperinsulinemia….

Prolonged high levels of insulin:Prolonged high levels of insulin: glucose continues to enter cells, but glucose continues to enter cells, but

stored in liver and fat cells and less stored in liver and fat cells and less glucose for immediate fuelglucose for immediate fuel

hunger returns quickly and eating hunger returns quickly and eating increases resulting in weight gain increases resulting in weight gain

Thanks you