Under the guidance of:

Dr. Sandeep Tandon Professor and Head of Dept. of Pedodontics

Dr. Ambika Singh
1

Rathore
Dr. Rinku Mathur Dr .Shantanu Jain Dr. Tripti Sharma Ra

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

INTRODUCTION:

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

NERVOUS SYSTEM

HORMONAL Neuroendocrine

Rapid transmission

Long-lasting regulatory action Both systems interact: Stimuli from the nervous system can influence the release of certain hormones and vice versa.

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.

CONVERGENT EVOLUTION: Similarities among the endocrine systems of crustaceans, arthropods, and vertebrates.
The vertebrate endocrine system consists of glands (pituitary, thyroid, adrenal), and diffuse 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.

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

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 cells function or activity.

CHEMICAL CHARACTERISTICS
OF HORMONES

Amines (from tyrosine)

I.
II.

Peptides/proteins Steroids (from cholesterol)

I. II. III.

hydroxylation - catecholamines iodination - thyroid hormones

adrenocorticoids sex hormones 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.

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 cells genetic material (i.e., the DNA) Regulating the activity of specific hormoneresponsive genes

MECHANISM OF ACTION:

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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.

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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 bodys homeostasis

Negative feedback mechanism Short-loop feedback Positive-feedback mechanisms

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Negative Feedback Loop

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Positive Feedback Loop

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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

pleasure)

states (e.g., fear, pain, anger, and

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Neurosecretory cells

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THE HYPOTHALAMIC-HYPOPHYSEAL PORTAL SYSTEM

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hypothalamic nuclei
superior hypophyseal artery trabecular artery long portal veins

superficial capillary plexus deep capillary plexus

inferior 18 hypophyseal artery

hypothalamic nuclei
superior hypophyseal artery trabecular artery long portal veins

superficial capillary plexus deep capillary plexus short portal veins

inferior 19 hypophyseal artery

hypothalamic nuclei
superior hypophyseal artery trabecular artery long portal veins adenosecondary capillary hypophyseal plexus capillary plexus

superficial capillary plexus deep capillary plexus short portal veins

inferior 20 hypophyseal artery

hypothalamic nuclei
superior hypophyseal artery trabecular artery long portal veins adenohypophyseal capillary plexus hypophyseal vein

superficial capillary plexus deep capillary plexus short portal veins

inferior 21 hypophyseal artery

HYPOTHALAMIC HORMONES

RELEASING

INHIBITING

Corticotrophin (CRH) ACTH

Somatostanin

Gonadotropin (GnRH) LH & FSH

Dopamine

Thyrotropin (TRH) TSH

Growth-Hormone (GHRH) GH
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THE PITUITARY AND ITS MAJOR HORMONES

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INTERMEDIATE LOBE

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 melanocytestimulating hormone (MSH), although this function is often (imprecisely) attributed to the anterior pituitary.

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GROWTH HORMONE

Most abundant of the pituitary hormones Pivotal role in controlling the bodys growth and development. Stimulates the linear growth of the bones; Promotes the growth of internal organs, fat (i.e., adipose) tissue, connective tissue, endocrine glands, and muscle; and Controls the development of the reproductive organs. 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.

1. 2.

3. 4.

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INDIRECT ACTION OF GROWTH HORMONE

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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.

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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.

2.

3. 4.

Response to the rise in estrogen levels in the blood that occurs during pregnancy. In nursing women, Prolactin is released in response to suckling by the infant. Dopamine, which has an inhibitory effect. Alcohol consumption by nursing women can influence lactation both through its effects on the release of prolactin and oxytocin.

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POSTERIOR PITUITARY:

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VASOPRESSIN

Vasopressin (arginine vasopressin, AVP; antidiuretic 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

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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
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OXYTOCIN HORMONE
I.

Stimulates the contractions of the uterus during childbirth.

In nursing women, the hormone activates milk ejection in response to suckling by the infant (i.e., the so-called let-down reflex).
I.

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THE ADRENAL GLANDS AND THEIR HORMONES

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 Action
1.

of Cortisol:

2. 3.

4. 5.

Cortisol increases glucose levels in the blood by stimulating gluconeogenesis in the liver and promotes the formation of glycogen in the liver. Reduces glucose uptake into muscle and adipose tissue, Promotes protein and lipid breakdown into products (i.e., amino acids and glycerol, respectively) that can be used for gluconeogenesis. Protect the body against the deleterious effects of various stress factors. Suppress tissue inflammation in response to injuries and to reduce the immune response to foreign molecules.

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ACTION OF ALDOSTERONE:

Regulate the bodys 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.

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THE THYROID AND ITS HORMONES

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THYROID HORMONE PRODUCTION

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THYROID HORMONE PRODUCTION

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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 bodys 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

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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.
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THE PARATHYROID GLANDS AND THEIR HORMONES

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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.

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CALCIUM HOMEOSTASIS

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THE PANCREAS AND ITS HORMONES

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TWO DISTINCTLY DIFFERENT FUNCTIONS

PANCREAS

EXOCRINE

ENDOCRINE

Digestive Enzymes Langerhans

INSULIN

GLUCAGON
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Islets of

INSULIN & GLUCAGON

Beta cells of Islet Blood sugar-lowering hormone Alpha cells of Islet Increases blood glucose levels Actions opposite to insulin

Effect of Insulin:
1. 2.

Inhibits gluco-neogenesis Insulin promotes the formation of storage forms of energy (e.g., glycogen, proteins, and lipids) and suppresses the breakdown of those stored 48 nutrients.

REGULATION OF BLOOD GLUCOSE LEVELS

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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.

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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

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CAUSES:
Type

to produce insulin Genetic factors; environmental factors

I (Juvenile Diabetes): bodys inability

Increased

overwhelmingly to lifestyle changes that have contributed to increased weight problems and lack of activity in children.

Type 2 Diabetes: linked

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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

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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

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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

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CAUSES
Causes

of excess IGF-I action may be divided into 3 categories:

released from the pituitary;

Those originating from primary GH excess Those caused by increased GH-releasing

hormone (GHRH) secretion or hypothalamic dysregulation; and production of IGF-binding protein, which prolongs the half-life of circulating IGF-I.

Hypothetically, those related to the excessive

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

TREATMENT
Medical
i. ii. iii.

Care

Surgery clearly fails to cure a notable number of patients with IGF-I excess Long-acting somatostatin analogs and dopamine agonists improve adherence and efficacy. Octreotide are the most effective medical therapies for GH excess. Bromocriptine are best used as adjuvant treatments.
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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

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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.
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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

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PERIPHERAL CAUSES

Secondary sexual development induced by sex steroids from other abnormal sources is referred to as peripheral precocious puberty. Endogenous sources

Causes can include:

gonadal tumors (such as arrhenoblastoma) adrenal tumors germ cell tumor congenital adrenal hyperplasia McCuneAlbright syndrome

Exogenous hormones
Environmental As treatment for another condition

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TREATMENT

GnRH agonists stimulate the pituitary to release Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). One possible treatment is with anastrozole. Histrelin acetate.

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PEDIATRIC CUSHINGS 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 glucocorticoids in the form of topical, inhaled or oral corticosteroids. Eczema and asthma are common conditions in childhood often requiring treatment with corticosteroids.

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TREATMENT
Primary

adrenal lesions

Surgical excision is the first-line therapy for a cortical-secreting ACT. Mitotane therapy appears to be the treatment of choice
Cushings

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.

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THYROID DISORDERS

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

Congenital hypothyroidism
Affects 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.

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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:
1.

2.
3. 4. 5.

6.
7.

Poor feeding Poor growth and development Constipation Dry skin & hair Low body temperature Slow tendon reflex Slow pulse Enlarged tongue Prolonged jaundice, Umbilical hernia Increased sleepiness Puffiness & swelling Decreased crying.
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Severe:

HYPERTHYROIDISM IN NEWBORNS

Overactive thyroid gland: referred to as NEONATAL HYPERTHYROIDISM.

If the mother has Graves' disease, the thyroidstimulating 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 70 bloodstream, usually within 2 to 3 months.

NEWBORNS WITH ADVANCED HYPERTHYROIDISM

EXTREMELY FAST PULSE IRRITABILITY
FLUSHED MOIST SKIN INFANT TENDS TO BE THIN & LONG

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.

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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
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SIGNS AND SYMPTOMS

The first sign is that the child's growth rate decreases unexpectedly and skeletal development is delayed.
GOITRE
Decreased Energy Lethargy

Dry Itchy Skin & Constipation

WEIGHT GAIN

Poor Concentration

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

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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.

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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.

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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.
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REFERENCES:

Susanne Hiller-Sturmhfel 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 Cushings Syndrome: Clinical Features, Diagnosis, and Treatment. Arq Bras Endocrinol Metab 2007;51/8:1261-1271)

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

Arthur C. Guyton. Textbook of Medical Physiology 10th edi;9931019 K. Sembulingham. Essentials Of Medical Physiology;3rd edi;667-714

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Presented by: Dr. Ruby Kharkwal 1st year postgraduate student Department of Pedodontics 79