The endocrine system
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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


Purpose: Communication

Nature: Slow, not specific

Regulates: growth, metabolism, reproduction, autonomic functions


Cell A

Cell A

Cell A

Cell B

hormone receptor




Cell B




Amines: epinephrine, norepinephrine, dopamine, T3, T4

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

Steroids: testosterone, estrogen, progesterone, cortisol, aldosterone

  • 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

Regulation of Thyroid

Hormone release

  • 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


Cell membrane



Nuclear membrane


T3 receptor


  • 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


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


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


  • 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

Regulation of Thyroid

Hormone release

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


Fetus Abortions/stillbirths

Congenital abnormalities

Increased perinatal mortality

Neurological deficits (cretinism)

Mental and growth retardation

Psychomotor defects

Neonates Goiter


Children Goiter


Impaired mental function

Retarded growth

Adults Goiter


Impaired mental function

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.

  • 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)

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)


  • 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

  • Myxedema

    • Accumulation of mucopolysaccharides and fluid in tissues

    • Facial puffiness

    • Edema

    • Hoarseness

    • Joint stiffness

    • Nerve compressions/parathesias

    • Pleural, cardiac, and peritoneal effusions

Hypothyroidism – Symptoms (childhood onset)

  • Cretinism (lack of T3/T4 in childhood)

    • impaired development of skeletal, nervous system

    • mental retardation

    • historically, dietary; iodine supplementation eliminates

  • Results in:

  • Decreased adiposity

  • Increased lean body mass

  • Increased organ size and mass

  • Increased plasma glucose concentrations

  • Acromegaly

  • Caused by increased growth hormone secretion

  • Usual cause is a tumor of the GH secreting cells

  • of the anterior pituitary

  • 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

  • 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)

  • 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

  • Treatment:

  • Surgery to remove tumor (replacement therapy for other

  • hormones may be required)

  • Long acting analog of somatostatin

  • GH receptor antagonist, pegvisomant


Etiology is the same as acromegaly, but the tumor occurs

before epiphyseal plate fusion

  • 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