1

Under the guidance of: Dr. Sandeep Tandon Professor and Head of Dept. of Pedodontics Dr. Ambika Singh Rathore Dr. Rinku Mathur Dr .Shantanu Jain

Dr. Tripti Sharma Ra

2

CONTENT: Introduction Evolution of Endocrine system Chemical characteristics of

Hormones Regulation of Hormone Release Hypothalamus & its Hormone Various glands and their importance Disorders of Endocrine system

common in Children References

3

INTRODUCTION: Constant internal environment (i.e., homeostasis) should be maintained. Two systems help ensure communication:

Rapid transmission Long-lasting regulatory action Both systems interact: Stimuli from the

nervous system can influence the release of certain hormones and vice versa.

NERVOUS SYSTEM

HORMONAL Neuroendocrin

e

4

EVOLUTION OF ENDOCRINE SYSTEM The nervous system coordinates rapid and precise

responses to stimuli using action potentials.

The endocrine system maintains homeostasis and long-term control using chemical signals.

The most primitive endocrine systems seem to be those of the neurosecretory type, in which the nervous system either secretes neurohormones directly into the circulation or stores them in neurohemal organs (neurons whose endings directly contact blood vessels, allowing neurohormones to be secreted into the circulation), from which they are released in large amounts as needed.

True endocrine glands probably evolved later in the evolutionary history of the animal kingdom as separate, hormone-secreting structures.

5

CONVERGENT EVOLUTION: Similarities among the endocrine systems of

crustaceans, arthropods, and vertebrates.

The vertebrate endocrine system consistsof glands (pituitary, thyroid, adrenal), anddiffuse cell groups scattered in epithelial tissues.

Endocrine glands arise during development for all three embryologic tissue layers (endoderm, mesoderm, ectoderm).

The type of endocrine product is determined by which tissue layer a gland originated in.

Glands of ectodermal and endodermal origin: peptide and amine hormones;

Mesodermal-origin glands: hormones based on lipids.

6

WHAT ARE HORMONES????? ( “TO SPUR ON”)

Hormones are molecules that are produced by endocrine glands:

i. The hypothalamus,

ii. Pituitary gland,

iii. Adrenal glands,

iv. Gonads, (i.e., testes and ovaries),

v. Thyroid gland,

vi. Parathyroid glands, and

vii. Pancreas

7

The term “endocrine” implies that in response to specific stimuli, the products of those glands are released into the bloodstream.

The hormones then are carried via the blood to their target cells.

The target cells for each hormone are characterized by the presence of docking molecules (i.e., receptors) for the hormone that are located either on the cell surface or inside the cell.

The interaction between the hormone and its receptor triggers a cascade of biochemical reactions in the target cell that eventually modify the cell’s function or activity.

8

CHEMICAL CHARACTERISTICS OF HORMONES

Amines (from tyrosine)I. hydroxylation - catecholaminesII. iodination - thyroid hormones

Peptides/proteins Steroids (from cholesterol)

I. adrenocorticoidsII. sex hormonesIII. active metabolites of vitamin D

Their mechanisms of action (e.g., whether they can enter their target cells and how they modulate the activity of those cells) also differ.

9

MECHANISM OF ACTION:

STEROIDS: produced by gonads; structure similar to cholesterol.

Enter their target cells and interact with the cytoplasm or in the cell nucleus

Hormone-receptor complexes bind to certain regions of the cell’s genetic material (i.e., the DNA)

Regulating the activity of specific hormone-responsive genes

10

MECHANISM OF ACTION:

11

Amino acid derivatives: are modified versions of building blocks of proteins. thyroid gland & adrenal glands (i.e., the adrenal

medulla) Enter the cell, where they interact with receptor

proteins that are already associated with specific DNA regions. The interaction modifies the activity of the affected genes.

Polypeptide and protein hormones:found primarily in the hypothalamus, pituitary gland,

and pancreas Because of their chemical structure, the

polypeptide and protein hormones cannot enter cells. Instead, they interact with receptors on the cell surface.

12

REGULATION OF HORMONE RELEASE

Constant feedback from the target glands to the hypothalamus and pituitary gland ensures that the activity of the hormone system involved remains within appropriate boundaries.

To maintain the body’s homeostasis Negative feedback mechanism Short-loop feedback Positive-feedback mechanisms

13

Negative Feedback Loop

14

Positive Feedback Loop

15

THE HYPOTHALAMUS AND ITS HORMONES

Why is the Hypothalamus so Important?

Eating and drinking,Sexual functions and behaviors,Blood pressure and heart rate, Body temperature maintenance,The sleep-wake cycle, and

Emotional states (e.g., fear, pain, anger, and pleasure)

16

Neurosecretory cells

17

THE HYPOTHALAMIC-HYPOPHYSEALPORTAL SYSTEM

18

hypothalamic nuclei

superiorhypophysealartery superficial

capillary plexustrabecular artery deep

capillary plexus

inferiorhypophysealartery

long portal veins

superficialcapillary plexus

19

hypothalamic nuclei

superiorhypophysealartery superficial

capillary plexustrabecular artery deep

capillary plexuslong portal veins

short portal veins

inferiorhypophysealartery

20

hypothalamic nuclei

superiorhypophysealartery superficial

capillary plexustrabecular artery deep

capillary plexuslong portal veins

short portal veinssecondarycapillaryplexus

adeno-hypophysealcapillaryplexus inferior

hypophysealartery

21

superiorhypophysealartery superficial

capillary plexusdeepcapillary plexuslong portal veins

short portal veins

hypothalamic nuclei

trabecular artery

adeno-hypophysealcapillaryplexus

hypophyseal vein

inferiorhypophysealartery

22

Corticotrophin (CRH) Somatostanin ACTH

Gonadotropin (GnRH) Dopamine LH & FSH

Thyrotropin (TRH) TSH

Growth-Hormone (GHRH) GH

HYPOTHALAMIC HORMONES

RELEASING INHIBITING

23

24

THE PITUITARY AND ITS MAJOR HORMONES

25

There is also an intermediate lobe in many animals, but is rudimentary in humans.

For instance, in fish, it is believed to control physiological color change.

In adult humans, it is just a thin layer of cells between the anterior and posterior pituitary. The intermediate lobe produces melanocyte-stimulating hormone (MSH), although this function is often (imprecisely) attributed to the anterior pituitary.

INTERMEDIATE LOBE

26

GROWTH HORMONE Most abundant of the pituitary hormones Pivotal role in controlling the body’s growth and development.

1. Stimulates the linear growth of the bones; 2. Promotes the growth of internal organs, fat (i.e.,

adipose) tissue, connective tissue, endocrine glands, and muscle; and

3. Controls the development of the reproductive organs.

4. GH affects carbohydrate, protein, and fat (i.e., lipid) metabolism.

GH levels in the blood are highest during early childhood and puberty and decline thereafter.

27

28

INDIRECT ACTION OF GROWTH HORMONE

29

Two hypothalamic hormones control GH release: (1) GHRH: stimulates GH release, (2) Somatostatin: inhibits GH release.

Short-loop feedback component:GH acts on the hypothalamus to stimulate

somatostatin release.

In addition, GH release is enhanced by Stress, such as low blood sugar levels (i.e.,

hypoglycemia) or severe exercise, and by the onset of deep sleep.

Acute and chronic alcohol consumption have been shown to reduce the levels of GH and IGF-1 in the blood.

30

PROLACTIN. Central role in the development of the female

breast and in the initiation and maintenance of lactation after childbirth.

Factors control Prolactin release:

1. Response to the rise in estrogen levels in the blood that occurs during pregnancy.

2. In nursing women, Prolactin is released in response to suckling by the infant.

3. Dopamine, which has an inhibitory effect.4. Alcohol consumption by nursing women can

influence lactation both through its effects on the release of prolactin and oxytocin.

31

POSTERIOR PITUITARY:

32

VASOPRESSIN Vasopressin (arginine vasopressin, AVP; anti-

diuretic hormone, ADH) is a peptide hormone formed in the hypothalamus, then transported via axons to, and released from, the posterior pituitary.

Two principles site of action: KIDNEY & BLOOD VESSEL

33

MECHANISMS REGULATING THE RELEASE OF AVP Hypovolemia: decreased central venous

pressure, the decreased firing of atrial stretch receptors leads to an increase in AVP release.

Hypotension, which decreases arterial baroreceptor firing and leads to enhanced sympathetic activity, increases AVP release.

Angiotensin II receptors located in a region of the hypothalamus regulate AVP release – an increase in angiotensin II simulates AVP release.

Increased sympathetic activation stimulates AVP release

34

OXYTOCIN HORMONE

I. Stimulates the contractions of the uterus during childbirth.

II. In nursing women, the hormone activates milk ejection in response to suckling by the infant

(i.e., the so-called let-down reflex).

35

THE ADRENAL GLANDS AND THEIR HORMONES

36

Action of Cortisol:1. Cortisol increases glucose levels in the blood by

stimulating gluconeogenesis in the liver and promotes the formation of glycogen in the liver.

2. Reduces glucose uptake into muscle and adipose tissue,

3. Promotes protein and lipid breakdown into products (i.e., amino acids and glycerol, respectively) that can be used for gluconeogenesis.

4. Protect the body against the deleterious effects of various stress factors.

5. Suppress tissue inflammation in response to injuries and to reduce the immune response to foreign molecules.

37

ACTION OF ALDOSTERONE:

Regulate the body’s water and electrolyte balance.

Conserve sodium and to excrete potassium from the body.

Reducing water excretion and increasing blood volume.

Decreases the ratio of sodium to potassium concentrations in sweat and saliva, thereby preventing sodium loss via those routes.

Controlled primarily by another hormone system, the reninangiotensin system, which also controls kidney function.

38

THE THYROID AND ITS HORMONES

39

THYROID HORMONE PRODUCTION

40

THYROID HORMONE PRODUCTION

41

ACTION OF THYROID HORMONE Stimulates the production of certain proteins

involved in heat generation in the body, a function that is essential for maintaining body temperature in cold climates.

Promotes other metabolic processes involving carbohydrates, proteins, and lipids that help generate the energy required for the body’s functions.

Plays an essential role in the development of the central nervous system during late fetal and early postnatal developmental stages.

Required for the normal development of teeth, skin, and hair follicles as well as for the functioning of the nervous, cardiovascular, and gastrointestinal systems

42

Parafollicular C cells) in the thyroid gland produce calcitonin, a hormone that helps maintain normal calcium levels in the blood.

Specifically, calcitonin lowers calcium levels in the blood by reducing the release of calcium from the bones; inhibiting the constant erosion of bones (i.e., bone resorption), which also releases calcium; and inhibiting the reabsorption of calcium in the kidneys.

43

THE PARATHYROID GLANDSAND THEIR HORMONES

44

ROLE OF PARATHYROID HORMONE Increases calcium levels in the blood, helping

to maintain bone quality and an adequate supply of calcium.

Causes re-absorption of calcium from and excretion of phosphate in the urine.

Promotes the release of stored calcium from the bones as well as bone resorption.

PTH stimulates the absorption of calcium from the food in the gastrointestinal tract.

Functions facilitated by a substance called 1,25-dihydroxycholecalciferol, a derivative of vitamin D.

45

CALCIUM HOMEOSTASIS

46

THE PANCREAS AND ITS HORMONES

47

TWO DISTINCTLY DIFFERENT FUNCTIONS

EXOCRINE ENDOCRINE

Digestive Enzymes Islets of

Langerhans

PANCREAS

INSULIN GLUCAGON

48

INSULIN & GLUCAGON

Beta cells of Islet Alpha cells of Islet

Blood sugar-lowering Increases blood glucose levels

hormone Actions opposite to insulin

Effect of Insulin:1. Inhibits gluco-neogenesis

2. Insulin promotes the formation of storage forms of energy (e.g., glycogen, proteins, and lipids) and suppresses the breakdown of those stored nutrients.

49

REGULATION OF BLOOD GLUCOSE LEVELS

50

THE GONADS AND THEIR HORMONES

OVARIES AND TESTES They produce the germ cells. Synthesize steroid sex hormones that are

necessary for the development and function of both female and male reproductive organs and secondary sex characteristics.

Affect the metabolism of carbohydrates and lipids, the cardiovascular system, and bone growth and development.ESTROGEN

PROGESTERONE

ANDROGEN

51

DISORDER OF ENDOCRINE SYSTEM

52

DIABETES ''Type 1 diabetes is growing by 5% per year

among pre-school children in India. It is estimated that 70,000 children, who are

under 15 years, develop juvenile type 1 diabetes each year (almost 200 children a day!).“

Symptoms of Diabetes in Children: Stomach pains, Headaches Behaviour problems Weight loss, thirst, tiredness and frequent

urination. Detected through the presence of ketoacidosis

53

CAUSES:

Type I (Juvenile Diabetes): body’s inability to produce insulin

Genetic factors; environmental factors

Increased Type 2 Diabetes: linked overwhelmingly to lifestyle changes that have contributed to increased weight problems and lack of activity in children.

54

TREATMENT: INSULIN: The advent of insulin pumps for

administration has allowed many children added flexibility in their daily lives.

Monitoring blood sugar levels Crucial factor

Diet: reduced consumption of fats and sugars,

intake fibers, vegetables and fruits.

Exercise: helps in lowering blood glucose levels of the body

55

COMPLICATIONS Sudden hypoglycemia & hyperglycemia

Immediately giving the child a glucose tablet or glucose beverage

LONG-TERM COMPLICATIONS

Problems of the kidney, heart, lungs, eyes, feet and nerves.

High blood sugar or high cholesterol levels

56

GIGANTISM Gigantism refers to

abnormally high linear growth due to excessive action of insulin-like growth factor-I (IGF-I) while the epiphyseal growth plates are open during childhood.

Acromegaly is the same disorder of IGF-I excess when it occurs after the growth plate cartilage fuses in adulthood.

Robert Wadlow, called the Alton giant, who stood 8 feet 11 inches tall at the time of his death in his mid-20s

57

CAUSES Causes of excess IGF-I action may be

divided into 3 categories:

Those originating from primary GH excess released from the pituitary;

Those caused by increased GH-releasing hormone (GHRH) secretion or hypothalamic dysregulation; and

Hypothetically, those related to the excessive production of IGF-binding protein, which prolongs the half-life of circulating IGF-I.

58

Most people with giantism have GH-secreting pituitary adenomas or hyperplasia.

TREATMENTMedical Carei. Surgery clearly fails to cure a notable

number of patients with IGF-I excessii. Long-acting somatostatin analogs and

dopamine agonists improve adherence and efficacy.

iii. Octreotide are the most effective medical therapies for GH excess. Bromocriptine are best used as adjuvant treatments.

59

PITUITARY DWARFISM

The achondroplastic dwarf has an orthopedic reason for having short limbs and a short spinal colum.  The pituitary dwarf lacks growth hormone (an endocrine reason).

SYMPTOMS: GH Deficiency Low blood sugar 

60

RISK FACTORS: Disease of the hypothalamus of the brain

Disease of the front of the pituitary gland in the brain

Newborns who had some type of serious medical event (such as a lack of oxygen) happen in the perinatal period, are at risk for the type of growth hormone deficiency caused by damage to the hypothalamus.

TREATMENT:Treatment with human growth hormone

theoretically corrects the deficiency, but is most successful when the child is young.  It must be given by injection. 

61

PRECOCIOUS PUBERTY Precocious puberty

describes puberty occurring at an unusually early age.

CAUSES:Central: damage to the

inhibitory system of the brain

hypothalamic hamartoma produces pulsatile gonadotropin-releasing hormone (GnRH)

Langerhans cell histiocytosis

62

PERIPHERAL CAUSES Secondary sexual development induced by

sex steroids from other abnormal sources is referred to as peripheral precocious puberty.

Causes can include: Endogenous sources

gonadal tumors (such as arrhenoblastoma) adrenal tumors germ cell tumor congenital adrenal hyperplasia McCune–Albright syndrome

Exogenous hormones Environmental As treatment for another condition

63

TREATMENT GnRH agonists stimulate the pituitary to

release Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH).

One possible treatment is with anastrozole. Histrelin acetate.

64

PEDIATRIC CUSHING’S SYNDROME (CS)

Rare in childhood and adolescence. Caused by prolonged exposure to excessive

glucocorticoids which can be secreted endogenously or administered exogenously.

Supra-physiological doses of exogenous gluco-corticoids in the form of topical, inhaled or oral corticosteroids.

Eczema and asthma are common conditions in childhood often requiring treatment with corticosteroids.

65

66

67

TREATMENTPrimary adrenal lesions Surgical excision is the first-line therapy for a

cortical-secreting ACT. Mitotane therapy appears to be the

treatment of choice

Cushing’s disease Medical therapies such as Metyrapone and

Ketoconazole to lower serum cortisol levels can be used as a short-term measure, but cannot be recommended as long-term therapy.

68

THYROID DISORDERS

Thyroid disease occurs less frequently in children than in adults, the signs and symptoms can be similar.

Congenital hypothyroidismAffects infants at birth, and occurs in about 1

in 4000 live-born babies.Loss of thyroid function, due to the thyroid

gland failing to develop normally. Enzyme defect leading to deficient hormone

production, iodine deficiency and a brain pituitary gland abnormality.

69

Within the first week of life, a heelprick blood sample is taken to assess an infant's thyroid hormone level.

Infant is immediately given thyroid hormone replacement therapy (T4 — thyroxine). Normal growth and development should then continue, with no adverse effects on the child's mental capacity.

Subtle symptoms: Severe:1. Poor feeding Poor growth and development2. Constipation Dry skin & hair3. Low body temperature Slow tendon reflex4. Slow pulse Enlarged tongue5. Prolonged jaundice, Umbilical hernia6. Increased sleepiness Puffiness & swelling7. Decreased crying.

70

HYPERTHYROIDISM IN NEWBORNS Overactive thyroid gland:

referred to as NEONATAL

HYPERTHYROIDISM.

If the mother has Graves' disease, the thyroid-stimulating antibodies in her blood can cross the placenta and stimulate the unborn child's thyroid gland, thus producing too much thyroid hormone.

Some newborns may hardly be affected if the levels of antibodies are low.

No treatment may be necessary as the mother's antibodies will soon clear from the baby's bloodstream, usually within 2 to 3 months.

71

NEWBORNS WITH ADVANCED HYPERTHYROIDISM

TREATMENT

Anti-thyroid drugs is safe and effective, and will only be needed for a short period of time, until the stimulating antibodies pass from the baby's bloodstream.

If the mother is on a high dose of anti-thyroid medication, the diagnosis can be delayed by about a week until the infant clears the anti-thyroid medication.

EXTREMELY FAST PULSE

IRRITABILITY

FLUSHED MOIST SKIN• I

NFANT TENDS TO BE THIN & LONG

72

HASHIMOTO'S THYROIDITIS The most common cause

of hypothyroidism in children and adolescents is Hashimoto's thyroiditis, an autoimmune disease.

As the thyroid gland becomes increasingly underactive, physical and mental changes will become more obvious.

Symptoms of hypothyroidism develop very slowly

73

SIGNS AND SYMPTOMS The first sign is that the child's growth

rate decreases unexpectedly and skeletal development is delayed.

GOITREDecreased

EnergyLethargy

Dry Itchy Skin &

Constipation

WEIGHT GAIN

Poor Concentrati

on

74

TREATMENT Thyroid hormone replacement is taken daily for life. The dosage of thyroid hormone needs to be age-

appropriate, as the body's demands for thyroid hormone vary with age.

SIDE-EFFECTS:In children who have had long-standing

hypothyroidism, ultimate height potential may be partly lost.

As the child regains normal thyroid function, behavioural problems may arise as their physical and mental processes speed up

75

GRAVES' DISEASE The most common cause

of hyperthyroidism in children and adolescents is an autoimmune condition called Graves' disease.

In Graves' disease the body produces antibodies that stimulate the thyroid gland uncontrollably, to make too much thyroid hormone.

76

SIGNS AND SYMPTOMS

Increased Energy, hyperactive, restless, Easily

distracted

Enlarged Thyroid Gland, fast pulse, nervousness, heat intolerance, weight loss

Accelerated growth rate, Shaky hands

Muscle weakness, diarrhoea, and Sleep & behavioural disturbances.

77

TREATMENT Propylthiouracil (PTU) or Carbimazole.

Period of 'block and replace therapy' (anti-thyroid drugs as well as thyroxine) is useful.

Throughout a child's treatment, thyroid hormone levels will need to be monitored regularly, along with their clinical symptoms.

SIDE EFFECTS Anti-thyroid drugs can, however, occasionally stop the

production of white blood cells or platelets.

Sore throats, mouth ulcers, excessive bruising or skin rashes can indicate this.

The only safe action is to stop the medication until after the result of the blood test.

78

REFERENCES: Susanne Hiller-Sturmhöfel and Andrzej Bartke. The

Endocrine Syste An Overview. Alcohol Health & Research World; Vol. 22(3):1998; 153-64

Ashley B. Grossman, Martin O. Savage.Pediatric Cushing’s Syndrome: Clinical Features, Diagnosis, and Treatment. Arq Bras Endocrinol Metab 2007;51/8:1261-1271)

Kim E. Barrett, Susan M. Barman. Ganong’s Review of Medical Physiology;Vol.23:451-568

Arthur C. Guyton. Textbook of Medical Physiology 10th edi;993-1019

K. Sembulingham. Essentials Of Medical Physiology;3rd edi;667-714

79

Presented by: Dr. Ruby Kharkwal 1st year postgraduate student Department of Pedodontics