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THE ENDOCRINE SYSTEM. Purpose : Communication Nature : Slow, not specific Regulates : growth, metabolism, reproduction, autonomic functions. hormone. Cell A. Cell A. Cell A. Cell B. hormone receptor. blood. DEFINITIONS. HORMONE. Cell B. PARACRINE AGENT. AUTOCRINE AGENT.

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The endocrine system

THE ENDOCRINE SYSTEM

Purpose: Communication

Nature: Slow, not specific

Regulates: growth, metabolism, reproduction, autonomic functions


The endocrine system

hormone

Cell A

Cell A

Cell A

Cell B

hormone receptor

blood

DEFINITIONS

HORMONE

Cell B

PARACRINE AGENT

AUTOCRINE AGENT


The endocrine system

CHEMICAL NATURE OF HORMONES

Amines: epinephrine, norepinephrine, dopamine, T3, T4

Peptides and proteins: insulin, glucagon, TSH, TRH, (many others)

Steroids: testosterone, estrogen, progesterone, cortisol, aldosterone


The endocrine system

  • Amines, proteins and peptides (except T3, T4):

  • Water soluble

  • Can’t cross cell membranes

  • Bind to receptors on cell surface

  • Effects usually rapid and transient

  • Not effective when ingested

  • Steroids and T3, T4:

  • Not water soluble (need a carrier in blood)

  • Can cross cell membranes

  • Bind to receptors in the cytoplasm or on DNA

  • Act primarily by initiating gene transcription

  • Effects usually slow and sustained

  • Effective when ingested, can also be applied topically


The endocrine system

Regulation of Thyroid

Hormone release


The endocrine system

  • TSH causes:

  • Uptake of iodine

  • Synthesis of thyroglobulin

  • Iodination of thyroglobulin

  • Uptake of colloid into thyroid cell

  • Secretion of T3/T4 from thyroid cell

  • Increase in the size and number of thyroid cells


The endocrine system

T3

Cell membrane

T3

cytoplasm

Nuclear membrane

gene

T3 receptor


The endocrine system

EFFECTS OF THYROID HORMONES

  • Increased O2 consumption/metabolic rate

  • -Increased size of mitocondria

  • - Increased expression of respiratory enzymes

  • - Increase Na+/K+ ATPase

  • - Increased proteins for growth and maturation

  • Increased expression of b-adrenergic receptors

  • Required for brain development



The endocrine system

IODINE REQUIREMENTS (mg/kg/day)

Infants (10-12 mo) 15

Children (1-6 yr) 6

School children (6-12 yr) 4

Adults (12+ yr) 2

Pregnant and 3.5

lactating women


The endocrine system

DIETARY SOURCES OF IODINE (ug/g)

Fish (fresh water) 17-40

Fish (marine) 163-3180

Shellfish 308-1300

Meat 27-97

Milk 35-56

Eggs 93

Grain 22-72

Fruits 10-29

Legumes 23-36

Vegetables 12-201


The endocrine system

  • IODINE DEFICIENCY

  • Leading cause of brain damage worldwide (13% of world

  • population)

  • Another 39% at risk

  • 130 developing countries affected

  • particularly problematic in pregnant women (iodine

  • required for fetal development)

  • even mild cases with no symptoms can result in a

  • decrement of 15 IQ points



The endocrine system


The endocrine system

Regulation of Thyroid

Hormone release


The endocrine system

Insufficient dietary iodine

Inability of thyroid to make T3/T4

Reduced serum T3/T4

Less T3/T4 inhibition of anterior pituitary TSH synthesis

Increased serum TSH

Increased thyroid growth (goiter)

Increases efficiency of the thyroid for T3/T4 production


The endocrine system

CONSEQUENCES OF IODINE DEFICIENCY

Fetus Abortions/stillbirths

Congenital abnormalities

Increased perinatal mortality

Neurological deficits (cretinism)

Mental and growth retardation

Psychomotor defects

Neonates Goiter

Hypothyroidism

Children Goiter

Hypothyroidism

Impaired mental function

Retarded growth

Adults Goiter

Hypothyroidism

Impaired mental function


The endocrine system

A Public Health Story

Early 1900’s goiter was highly prevalent in the Great Lakes

and Northwest regions of the US

1924: Michigan department of Health does survey in 4 counties.

39% of children have goiter. Begins campaign for iodized salt.

1928: Same counties resurveyed. Goiter down by 75%

1951: Goiter prevalence less than 0.5%

1993: Universal Salt Iodization Program started (WHO).

Global rates of goiter, cretinism and mental retardation are

declining rapidly.


The endocrine system

  • Why salt?

  • Cheap (0.05 US$ per person per year)

  • Widely available

  • Consumed throughout the year


Hyperthyroidism grave s disease
Hyperthyroidism – Grave’s Disease

  • most common cause of hyperthyroidism

  • autoimmune disorder

    • Antibodies that stimulate TSH receptor

  • increased T3/T4 levels

  • goiter (enlargement of the thyroid)


The endocrine system

Regulation of Thyroid

Hormone release

Antibodies that stimulate TSH receptor


Grave s disease symptoms
Grave’s Disease - Symptoms

  • Hypermetabolic state

  • Excess sympathetic nervous activity

  • Psychological symptoms

  • Overactivity of muscles retracting eyelids: increased staring, decreased blinking

  • Exopthalmus (protruding eyes)

  • Increased gut motility (diarrhea)


Grave s disease treatment
Grave’s Disease - Treatment

  • Destroy gland

    • Surgery

    • Radioactive Iodine

  • Block T3/T4 synthesis

    • Thiouricil: inhibits peroxidation of thyroglobulin

    • Lithium (blocks TSH signal transduction pathway)


Hypothyroidism
Hypothyroidism

  • inadequate production of thyroid hormone

  • Primary

    • Ablation of thyroid by surgery/radioisotopes

    • Hashimoto’s thyroiditis

      • Autoimmune

    • idiopathic

  • Secondary

    • Lack of TSH


Hypothyroidism symptoms adult onset
Hypothyroidism – Symptoms (adult onset)

  • Decreased metabolic state

    • Cold intolerance, fatigue, hypothermia, weight gain

  • Decreased sympathetic activation

    • bradycardia

  • Slowing of intellectual and motor activity

    • Forgetfulness, apathy, even dementia

  • Decreased gut motility (constipation)

  • Myxedema


The endocrine system

  • Myxedema

    • Accumulation of mucopolysaccharides and fluid in tissues

    • Facial puffiness

    • Edema

    • Hoarseness

    • Joint stiffness

    • Nerve compressions/parathesias

    • Pleural, cardiac, and peritoneal effusions


The endocrine system

Hypothyroidism – Symptoms (childhood onset)

  • Cretinism (lack of T3/T4 in childhood)

    • impaired development of skeletal, nervous system

    • mental retardation

    • historically, dietary; iodine supplementation eliminates



The endocrine system

  • Results in:

  • Decreased adiposity

  • Increased lean body mass

  • Increased organ size and mass

  • Increased plasma glucose concentrations


The endocrine system


The endocrine system

  • Acromegaly

  • Caused by increased growth hormone secretion

  • Usual cause is a tumor of the GH secreting cells

  • of the anterior pituitary


The endocrine system

  • Alterations in GH secretion

  • Oral glucose challenge usually decreases GH levels to

  • undetectable, but not in acromegaly (used in diagnosis)

  • Response to GHRH is increased

  • Hypoglycemia and arginine both increase GH (same as normal)

  • Somatostatin lowers GH but not to normal


The endocrine system

  • Effects

  • Increased bone muscle and connective tissue growth

  • Increased incidence of diabetes

  • Effects of tumor mass

    • Headaches

    • Vision impairment, particularly peripheral vision

    • (optic nerve runs near the anterior pituitary)

  • Effects resulting from loss of anterior pituitary

  • hormones due to compression of the pituitary

  • by tumor mass (loss of FSH and LH: amennorhea in women,

  • impotence in men and reduced secondary sex characteristics in men)


The endocrine system

  • Effects on bone and tissue mass

  • Increased size of hands and feet (first sign may be increase in shoe

  • size)

  • Changes in facial features

  • orbital ridging

  • underbite

  • coarsening of features

  • Spaces between teeth due to enlargement of mandible

  • Thickening of vocal cords deepens voice

  • Thickening of skin

  • Increased sweating and decreased heat tolerance

  • Increased size of internal organs

  • Increased sleep problems (obstructive sleep apnea)

  • Muscle weakness, pain, loss of sensation (compression of nerves by

  • soft tissue)

  • Congestive heart failure





The endocrine system

  • Treatment:

  • Surgery to remove tumor (replacement therapy for other

  • hormones may be required)

  • Long acting analog of somatostatin

  • GH receptor antagonist, pegvisomant


The endocrine system

Gigantism

Etiology is the same as acromegaly, but the tumor occurs

before epiphyseal plate fusion


The endocrine system

  • GH deficiency, GH insensitivity, or IGF-1 deficiency, results in

  • Dwarfism, a condition of short stature, but otherwise normal

  • development in children

  • Achondroplasia:

  • short stature with disproportionally short arms and legs

  • and an enlarged head

  • autosomal dominant defect caused by mutations in the FGFR3