PEDIATRICS

2A ENDOCRINE SYSTEM
PEDIA Dr.PALABRICA | December 14, 2018
Endocrine system- is made up of endocrine organs:
hypothalamus, pituitary gland, adrenal glands, pancreas, thyroid
gland, parathyroid and gonads Cells Hormones secreted
Somatotropes GH
HYPOTHALAMUS AND PITUITARY GLAND Lactotropes Prolactin
A.PITUITARY GLAND
Thyrotropes TSH
 Major regulator of an elaborate hormonal system
Corticotropes Propriomelanocortin
 receives signals from the hypothalamus and responds to
(precursor of ACTH)
these signals by sending pituitary hormones to target
Gonadotropes LH and FSH
glands
ANTERIOR PITUITARY GLANDS AND ITS HORMONES
 ***these target glands will then produce hormones that will
provide negative feedback at the level of both the
A.GROWTH HORMONES
hypothalamus and pituitary
 secreted in a pulsatile fashion under the regulation of the
 regulates itself
hypothalamic hormones
 Central role:
 alternating secretion of GHRH and somatostatin
- ability to interpret a variety of signals which leads to its
accounts for its secretion
name as master gland.
 GHRH /GrowthHormone ReleasingHormone
- located at the base of the skull, in a saddle shaped cavity
 stimulates GH release
of the sphenoid bone that we call the Sella turcica
 Somatostatin
***surrounds and protects the pituitary gland bilaterally
 inhibits GH release
and inferiorly
 peaks of GH:
 connected to the hypothalamus by the Pituitary stalk
 occurs when peaks of GHRH coincides
 composed of:
with low levels ofsomatostatin
1. Anterior Lobe (adenohypophysis)
 GHRELIN
- 80% of the gland
 peptide produced in the hypothalamus
2. Posterior Lobe (neurohypophysis)
and in much greater quantity in the
stomach STIMULATES growth
B.ARTERIAL BLOOD SUPPLY
hormone secretion
 originates from the ICA via the:
 Growth stimulants;
a. INFERIOR HYPOPHYSEAL ARTERY
o GHRH
b. MIDDLE HYPOPHYSEAL ARTERY
o Ghrelin
c. SUPERIOR HYPOPHYSEAL ARTERY
o Other factors that can stimulate GH secretion:
-its branches penetrate the pituitary stalk and form a
o Sleep
network of vessel that traverse the pituitary stalk and
o Exercise
terminate in a network of capillaries within the anterior
o Physical stress
lobe
o Trauma
**These network of vessels form a unique PORTAL
o Puberty
CIRCULATION connecting the hypothalamus
o Acute illness
and pituitary
o Fasting
**Hypothalamic hormones are delivered to anterior
o Hypoglycemia
pituitary by this portal system
 inhibit GH release;
o HYPERGLYCEMIA
C. 5 CELL TYPES IN APG AND THEIR PEPTIDE HORMONES
o HYPOTHYROIDISM
o GLUCOCORTICOIDS
BIOLOGIC EFFECT OF GROWTH HORMONE
-It will increase:

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1. Linear growth b.
TRH will go into the hypothalamic-pituitary portal
2. Bone thickness system
3. Soft tissue growth c. TRH stimulates TSH release from thyrotropes
4. Protein synthesis d. TSH stimulates release of T4 (Thyroxine) and T3
5. FA release from the adipose tissue (Triiodothyronine) from the thyroid gland
6. Insulin resistance e. T3 produces negative feedback inhibition in the
7. Blood glucose level release of both TRH and TSH together with
MITOGENIC EFFECTS: Dopamine, Glucocorticoids and Somatostatin w/c
- mediated through the synthesis of Insulin-like Growth also inhibit the release of TRH and TSH
Factor-1 DEFICIENCY OF TSH d/t the inactivity and
Insulin-like Growth Factor-1 atrophy of the thyroid
o formerly named as Somatomedin C gland
o Primarily synthesized in the liver and form locally
EXCESSIVE TSH d/t hypertrophy
in ectodermal and mesodermal cells
and hyperplasia of
o Circulating levels of IGF-1 is related to the levels the thyroid
of GHand nutritional status gland
o the higher the IGF-1, the higher the GH
secretion D. ACTH (ADENOCORTICOTROPIC HORMONE)
 Derived from the proteolytic cleavage of
B. PROLACTIN PROOPRIOMELANOCORTIN
 consistently secreted unless actively inhibited by **240 Amino acid precursor; glycoprotein
DOPAMINE (a peptide produced by the hypothalamus) product of the pituitary; also contains sequences
 Disruption of the hypothalamus/pituitary stalk results to for lipoproteins; Melanocyte stimulating hormone
INCREASED level of Prolactin (MSH) which is the principal pigmentary hormone
Dopamine antagonist in human; and Beta endorphin
INCREASE PROLACTIN Primary hypothyroidism  Secretion is regulated by
Administration of TRH Corticotrophin releasing hormone (CRH)
Pituitary tumors
 Secretion is in DIURNAL PATTERN
a. HIGHEST: morning upon awakening
Dopamine agonist
b. LOW: afternoon and evening
DECREASE PROLACTIN Destruction of Pituitary
gland c. LOWEST: 1-2h after beginning sleep
 Acts on adrenal cortex to stimulate cortisol synthesis
 PHYSIOLOGIC ROLE: initiation and maintenance of and secretion
lactation  PRODUCTS OF PROOPRIOMELANOCORTIN
 Prepares the breast for lactation and stimulates milk a.) ACTH
production postpartum b.) Lipoprotein
 Pregnancy: stimulates development of milk secretory c.) MSH
apparatus, however, lactation does not occur during d.) Beta endorphin
pregnancy because of high levels of Estrogen and E. FSH (Follicle Stimulating Hormone) and LH (Luteinizing
progesterone. Hormone)
 After Delivery: Estrogen and progesterone levels drop  Gonadotropic hormones
and physiologic stimuli such as suckling and nipple  Regulated by LHRH and GnRH
stimulation will signal prolactin release and initiate  Mechanism;
lactation or milk production a. Hypothalamus will release LHRH and gonadotropin
C. TSH (THYROID STIMULATING HORMONE) releasing hormone (GnRH)
 stored in secretory granules b. Release of LH and FSH from the pituitary
 released in the circulation in response to Thyrotropin c. LH and FSH will stimulate the release of Androgen and
Releasing Hormone (TRH) produced by the hypothalamus Estrogen
 Mechanism; d. Androgen and Estrogen produce negative feedback of
a. TRH released from the hypothalamus LH production INHIBIN from Sertoli cells inhibits
FSH
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FSH (Follicle stimulating FEMALES: Stimulates b. tPA
hormone) follicular development in the  V3 receptor mediates stimulation of ACTH secretion and
ovaries phosphatidyl inositol hydrolysishas short
 half-life and responds quickly to change in hydration
MALES: Stimulates
gametogenesis in  Stimuli for release;
the testes -Increased plasma osmolality (concentrated
serum) and decreased hydration
LH (luteinizing hormone) FEMALES: stimulates Perceived by OSMORECEPTORS in the hypothalamus
luteinization in the ovary **Osmoreceptors- detect increase in osmotic pressure
MALES: stimulates Leydig  Decreasedblood volume
cell function ofthe testes -perceived by BARORECEPTORS in the carotid sinus of the
Aortic arch
**Baroreceptors- detect decrease blood pressure
 Inhibits FSH: INHIBIN
 Effects of the Stimuli
 Inhibits LH: ANDROGEN and ESTROGEN
-production and release of ADH leading to:
HORMONES OF ANTERIOR PITUITARY GLAND
a. Increased Blood volume
a. GH b. Increase blood pressure
b. Prolactin c. Increase water reabsorption
c. TSH d. Oxytocin
d. LH e. Love Hormone
e. FSH
 stimulates uterine contraction at the time of labor and
f. ACTH
delivery in response to distention of the reproductive
tract
POSTERIOR PITUITARY GLAND (NEUROHYPOPHYSIS)
 stimulates smooth muscle contraction in the breast
 Only produces 2 hormones
during suckling and results in milk let down
a. ADH
(coordinates with prolactin)
b. Oxytocin
 Also plays a role in orgasm, social recognition, paired
 Part of a functional unit called the Neurohypophysis
bonding, anxiety, trust, love and maternal behavior
 consisting of:
 interacts with the receptors in the adipose tissue and
a.) neurons of the supraoptic and paraventricular nuclei
pancreas for appetite regulation, obesity and anorexia
of the hypothalamus
 Take note!!!
b.) neuronal axons that form the pituitary stalk
Prolactin= milk production
c.) Neuronal terminal in the median eminence of the
Oxytocin= milk let down/ejection
posterior lobe
A. Arginine Vasopressin (ADH)
THYROID GLAND
 regulates water conservation at the level of the kidneys by
increasing the permeability of the renal collecting duct to  Synthesizes T3 and T4
water  Only physiologic role of Iodide (ionized form of
 Mechanism: Iodine) is the synthesis of T3 and T4
a. (+) high ADH concentration  Thyroid tissue is always attracted to iodide making
b. Activation of the V1 receptors in the smooth it able to trapped, transport and concentrate
muscles and hepatocytes Iodide in the follicular lumen for synthesis of thyroid
c. Exerts pressor and glycogenolytic effect hormones
through mobilization of intracellular Calcium
stores
 ADH also stimulates translocation of water channels
through interaction with V2 receptors (Vasopressin 2
receptors)in the collecting duct
 Increase permeability of kidneys to water
 V2 receptor mediates
a. vWF

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SYNTHESIS OF THYROID HORMONE
Entry of Iodide from the circulation into
thyroid is carried out by Na-Iodide
symporter
Will go the follicular cells and then diffuses
across the cell to the apical membrane
Iodide is transported in the colloid via
Pendrin
Iodide is trapped
Iodide Oxidized into iodine by Thyroidal
peroxidase
Iodide will react with tyrosine present in the
thyroglobulin (a large globular glycoprotein
containing 120 tyrosine units)
Iodination of tyrosine
forms Monoiodotyrosine
(MIT) and Diiodotyrosine
(DIT)
Iodinated tyrosines are linked together to
form T3 and T4
T3= 1 MIT + 1 DIT
T4= 2 DIT
Once T4 and T3 are formed, they will be
stored as Thyroglobulin in the lumen of the
follicle until ready to be delivered to the
target
T4 and T3 are liberated from cells
the thyroglobulin colloid by the
activation of protease and peptides
T3 is 3-4x potent than T4; physiologically active thyroid
hormone
Adult: 100 µg T4, and only 20 µg T3 is produced
20% of circulated T3à secreted by thyroid
The rest of circulated T3 produced by the iodination of T4 in
the liver, kidney and other tissues (T4 is converted back into
T3)
FUNCTIONS OF THYROID HORMONES
1.) Increase oxygen consumption
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2.) Stimulate Protein synthesis
3.) Influence growth and differentiation
4.) Affect Carbohydrate, lipid and Vitamin
metabolism
HOW DO THYROID HORMONES DO THESE FUNCTIONS?
Specific thyroid hormone transporters facilitate the
entry of T3 and T4 in the cellà T4 conversion to T3 inside the cell à
intracellular T3 enters the nucleus and binds to thyroid hormone
receptors à binding of T3 activates thyroid receptor response
element à production of mRNAà stimulation of protein synthesis
specific for the target cell
T4- 70% of circulating T4 is bound to T4 binding globulin;
0.03% is free T4
T3- 50% of circulating T3 is bound to protein/albumin; 0.30%
is free T3
PARATHYROID GLAND
 Controls and regulates Calcium homeostasis by secreting
Parathyroid hormones (PTH)
 84 AA chain
 biologic activity resides in the first 32 AA only
 PreproPTH synthesis to proPTH
 Decrease serum calcium signal is transduced to the
Calcium Sensing Receptor increase PTH secretion
 Calcium Sensing Receptor- regulates PTH secretion
and reabsorption of calcium by the renal tubules in
response to alterations in serum calcium
concentrations
 PTH stimulates the activity 1-alpha hydroxylase in
kidney enhancing production of Vitamin D
 Increased Vitamin D induces synthesis of Calcium
binding protein in the intestinal mucosa leading to
increased absorption of Calcium
 FUNCTIONS OF PTH
a.) increased absorption of Calcium in the GIT
b.) Increased Calcium reabsorption in the kidney
c.) mobilizes Calcium by directly enhancing bone
resorption
HYPOCALCEMIA induce INCREASE PTH secretion
HYPERCALCEMIA induce DECREASE PTH secretion
ADRENAL GLAND
with 2 endocrine tissues:
A.) MEDULLA-center
B.) CORTEX- comprised of 3 zones
1.) Z. Glomerulosa- outer zone; just beneath the
capsule
2.) Z. Fasciculata- middle and largest zone;
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3.) Z. Reticularis-innermost; lie next to adrenal medulla
FUNCTIONS OFGLUCOCORTICOIDS
A.) Metabolic effect: Increase glucose production by
ZONE HORMONE SECRETED
increasing hepatic gluconeogenesis
GLOMERULOSA ALDOSTERONE (most B.) Increase cellular resistance to insulin
potent natural C.) Increase free fatty acid levels
mineralocorticoid in D.) Exerts catabolic effect or anti-anabolic effect in protein
human) metabolism
FASCICULATA CORTISOL (most potent E.) (+) inotropic influence on the heart F.) For
glucocorticoid in human) normal growth and development
G.) Immune regulation and diminishes inflammation
RETICULARIS ADRENAL ANDROGEN
H.) Inhibits fibroblast productionà easy bruising and
(sex hormones) poor wound healing
I.) Decrease calcium
ALDOSTERONE- Regulated mainly by RAAS and K+ levels J.) Decrease osteoblastic activity
K.) Decrease CNS edema and stimulates appetite,
insomnia, irritability and emotional labilityà because
Corticosteroids readily penetrates the BBB and has
direct effect on brain metabolism

FUNCTIONS OF ALDOSTERONE
A.) Maintain intravascular volume by conserving Na+ and
eliminating K+ and hydrogen ions
I in the liver
EXPANDED NEWBORN SCREENING
Angiotensin I is converted into Angiotensin II in the
NEWBORN SCREENING (NBS)

 A simple procedure to find out if a baby has a

pathological metabolic disorder that may lead to
mental retardation or even death if left untreated
which is a potent vasoconstrictor  Important because most babies may look normal
at birth and through NBS, these metabolic
Increased extracellular K disorders may be detected even before clinical
signs and symptoms are present
**Early treatment can prevent consequences of
untreated conditions
Increase K excretion
When is it done? 24 hours from birth
- Collected by a physician, a nurse, medical
technologist or trained midwife
How is it done?
- A few drops of blood are taken from the baby’s
heel and blotted in a special absorbent filter card
and then send to the NBS center.
What is the expanded NBS?
- Expanded NBS increases the panel of
metabolic disorders from the original 6 to 28
disorders.
- Same process of collection but lab methods applied
are different

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short AA, actetylcoA deficiencies,
ORIGINAL METABOLIC DISORDERS IN NBS - Organic acid deficiencies
1.) Congenital hypothyroidism
- Cystic fibrosis
2.) Congenital adrenal hyperplasia
3.) Galactosemia Metabolic disorder Effect if not screened
4.) PKU (phenylketonuria) Congenital Severe Growth
5.) G6PD deficiency hypothyroidism and
6.) Maple syrup disease mental retardation
CAH DEATH
CONGENITAL HYPOTHYROIDISM Galactosemia Death or cataracts
- results from lack or absence of thyroid hormone PKU Severe mental
which is important in physical and mental retardation
development G6PD Severe anemia
- if not treated in 2 weeks, baby may suffer from and
growth and mental retardation kernicterus
CONGENITAL ADRENALHYPERPLASIA MSUD Death/ mental
- causes severe salt loss, dehydration and retardation
abnormally high levels of male sex hormones in both
sexes
-
if not detected and treated early, babies may die
within 7-14 days
GALACTOSEMIA
- condition where in babies are unable to process
galactose which is the sugar present in milk
-accumulation of excessive galactose may cause
liver damage, brain damage and cataracts
PHENYLKETONURIA
- baby cannot properly use one of the building blocks
of protein called phenylalanine
- accumulation of excessive phenylalanine in the
blood causes brain damage
G6PD DEFICIENCY
- baby lacks the enzyme called Glucose 6
phosphate dehydrogenase
- babies may have hemolytic anemia resulting from
exposure to oxidative substances found in food,
chemicals and drugs
MAPLE SYRUP URINE DISEASE (MSUD)
- results from the defective activity of the enzyme
branched chain alpha ketoacid dehydrogenase
complex
- accumulation of this branched chain amino acid
are toxic to the brain
EXPANDED NBS (28 disorders)
- Endocrine disorders
- Amino acid disorders- homocystinuria,
tyrosinemia
- Fatty acid disorder- uptake deficiencies, medium
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