PEDIATRIC ENDOCRINOLOGY PART 2 Pediatrics 2
Dr. Ruby Ann Punongbayan 4th Shifting
January 19, 2009
(Adrenals na dapat ang start ng trans namin pero isinama ko ulit ung
Calcium Homeostasis kasi may ilang slides na hindi naisama sa part na
un)
CALCIUM HOMEOSTASIS
 PTH & Vit.D are the principal regulators of calcium homeostasis
 Calcitonin & PTH-related peptide (PTHrP) – important primarily in
the fetus
 In the parathyroid gland, pre-pro-PTH & a proparathyroid hormone
are synthesized--- pre-pro-PTH converted to pro-PTH-
converted to PTH (rapidly cleaved in the liver & kidney into smaller
fragments)
 PTH has C-terminal, mid-region & N-terminal fragments
o N-terminal – assay most useful for detecting acute secretory
changes
o C-terminus & mid-region – inert & represent 80% of plasma
immunoreactive PTH
o C-terminal assay – detects hyperparathyroidism
 When serum Ca falls, secretion of PTH increases.
 PTH stimulates 1-a-hydroxylase in the kidney--enhances
production of 1,25-OH2D3-- induces synthesis of a Ca-binding
protein (calbindin-D) in the intestinal mucosa with Ca absorption
 PTH mobilizes Ca by directly enhancing bone resorption
 Hypocalcemia induces increased PTH secretion; hypercalcemia
depresses PTH secretion.
 Calcitonin – 32-AA polypeptide; secreted in parafollicular cells (C
cells) of the TG
o In the fetus, high levels augment bone metabolism & skeletal
growth stimulated by the normally high fetal Ca levels.
o Main biologic effect: inhibition of bone resorption by decreasing
the number & activity of bone-resorbing osteoclasts.
HYPOPARATHYROIDISM
 Hypocalcemia is common from 12-72 hrs of life esp.in premature
infants, in infants with asphyxia at birth & in infants of diabetic
mothers
 Clinical Manifestations
o Muscular pain and cramps – early
o Numbness, stiffness, tingling of the hands & feet
o (+)Chvostek or Trosseau sign or laryngeal & carpopedal spasm
o Convulsions with loss of consciousness
o Chronic: late teeth eruption, irregular enamel formation, soft
teeth
o Dry & scaly skin
o Horizontal lines in nails of the fingers & toes
o Mucocutaneous candidiasis
o Cataracts
o Permanent mental & physical deterioration occur if initiation of
treatment is delayed.
 Serum Calcium
o About 50% of calcium is ionized
o 40-45% is bound to albumin
o 5-10% is bound to other anions (sulfate, PO4, lactate, citrate)
o Only ionized fraction is physiologically active & can be rapidly
measured
o Blood pH should always be performed with ionized Ca
(increased in acidosis; decreased in alkalosis)
 Laboratory Findings
o Serum calcium <5-7 mg/dL
o Serum phosphorus >7-12 mg/dL
o Serum ionized calcium (45% of the total) is low
o Serum alkaline phosphatase is normal or low
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o Low level of 1,25 OH2D3
o Normal serum magnesium
o Low serum PTH
o X-ray of the bones: increased density limited to the
metaphyses
o X-ray and CT of the skull: calcifications in the basal ganglia
o ECG: prolonged QT interval
o EEG: widespread slow activity
 Management
o Emergency treatment for neonatal tetany: 5-10 ml of 10%
solution of calcium gluconate IV at a rate of 0.5-1 mL/min
while HR is monitored
o 1,25-dihydroxycholecalciferol (calcitriol) should be given –
initial dose 0.25 ug/day & MD 0.01-0.1 ug/kg/day; given in 2
equal divided doses
o Management
o Supplemental calcium gluconate or glubionate to provide 800
mg of elemental calcium daily
o Reduce high phosphorus content in diet such as milk, eggs &
cheese
o Frequent monitoring of serum calcium levels
HYPERPARATHYROIDISM
 Excessive production of PTH due to primary defect of the
parathyroid glands such as adenoma or hyperplasia; may also be
due to vitamin D excess
 Increased PTH production is compensatory aimed at correcting
hypocalcemic states of diverse origins
 Childhood occurrence is rare; usually due to a single benign
adenoma manifested after 10 yrs of age
 Some occur as part of multiple endocrine neoplasia (MEN)
syndrome (AD) characterized by hyperplasia or neoplasia of the
endocrine pancreas, the anterior pituitary & parathyroid glands
 Clinical Manifestations
o Muscular weakness, anorexia, nausea, vomiting, constipation,
polydipsia, polyuria, loss of weight, fever
o Progressively diminished renal function in chronic cases
o Osseous changes may produce pain in the back or extremities,
gait disturbances, fractures
o Abdominal pain
o Parathyroid crisis: serum calcium >15 mg/dL, progressive
oliguria, azotemia, stupor, coma
o Infants: failure to thrive, poor feeding, hypotonia
o Chronic cases: mental retardation, convulsions, blindness
 Laboratory Tests
o Serum calcium should always be measured at the same time
as PTH.
o Primary case: increased serum Ca; increased serum PTH;
increased serum chloride; decreased serum phosphorus in
50% of cases
o Serum & ionized calcium elevated
o Serum phosphorus is low <3 mg/dL
o Serum magnesium is low
o Low specific gravity of urine
o Serum nonprotein nitrogen & uric acid inc.
o Elevated serum PTH
o Most consistent X-ray finding is resorption of subperiosteal
bone best seen along the margins of the phalanges of the
hands
o Skull X-ray: gross trabeculation or a granular appearance due
to focal rarefaction
o Abdominal X-ray: renal calculi or nephrocalcinosis
 Management
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o Surgical exploration is indicated in all instances.
o All glands should be carefully inspected.
o Removal of the adenoma
o Total parathyroidectomy for infants with severe hypercalcemia
o Good prognosis if recognized early & there is appropriate
surgical treatment
ADRENAL GLANDS
 Adrenal gland: 2 endocrine systems: medullary gland &
cortical system
 Adrenal cortex:
1. Zona glomerulosa – aldosterone (15%)
2. Zona fasciculata – cortisol & androgens
3. Zona reticularis – androgens (10%)
Hypothalamic-Pituitary-Adrenal Axis
 Pulses of ACTH & cortisol occur every 30-120 minutes, are
highest at about the time of waking, are low in late afternoon
& evening, and reach their lowest point an hour or two after
sleep begins.
 In the hypothalamus (paraventricular nucleus): CRH is
synthesized which is the most important stimulator of ACTH
secretion.
 AVP augments CRH action--neural stimuli from the brain
cause the release of CRH & AVP-- pulsatile release in the
hypophyseal-portal circulation--pulsatile release of ACTH
Role of ACTH
 Acute effects of ACTH:
o Stimulates cholesterol release
o Transport of cholesterol into mitochondria
o Binds cholesterol to P450 cytochrome
o Releases newly synthesized pregnenolone
 Long-term effects of ACTH stimulation:
o increase the uptake of LDL cholesterol
o Formation of the steroidogenic enzymes
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Renin-Angiotensin-Aldosterone System
 Major regulators of aldosterone secretion are the R-A system
& potassium
 Renin produced by the JG apparatus reacts with renin
substrate --angiotensin I--angiotensin-converting
enzyme cleaves-- angiotensin II---angiotensin III (potent
stimulators of aldosterone secretion)
 Both angiotensin & K act by IC signal transduction
mechanisms to stimulate conversion of cholesterol to
pregnenolone.
Adrenal Steroids
 Glucocorticoids:
o Regulate RNA & protein synthesis
o Catabolic effect in muscles, skin, connective, adipose &
lymphoid tissues: increased degradation of protein
o Anabolic in the liver: increase protein & glycogen
content, enhances gluconeogenesis
o Effects of insulin & androgens are antagonistic to those
of glucocorticoids
 Mineralocorticoids
o Aldosterone maintains electrolyte balance-blood
volume & BP stabilization
o Controls Na & H20 reabsorption in the distal tubules
 Androgens
o inc. retention of N, K, P, S04
o Promote growth & have androgenic effects
o DHEAS levels begin to rise before the other hormonal
changes of puberty occur
ADRENAL MEDULLA
 Catecholamines: dopamine, norepinephrine, epinephrine
 Synthesis occur in the brain, sympathetic nerve endings & in
chromaffin cells
 Metabolites are excreted in the urine: VMA, metanephrine,
normetanephrine
 Both epi- & norepinephrine raise the mean arterial BP,
increase PVR-inc.systolic & diastolic BP
 Epinephrine increases the PR-dec.PVR
ACTH INSUFFICIENCY
 Addison’s disease
 Deficient production of cortisol or aldosterone due to
congenital or acquired lesions of the hypothalamus, pituitary
gland or adrenal cortex
 Etiology: congenital hypo- or aplasia of the pituitary
(abnormalities of skull & brain, craniopharyngioma), adrenal
hypoplasia congenita, inborn defects of steroidogenesis,
autoimmune destruction of the glands, CNS demyelination,
etc.
 Laboratory Tests
o Low serum Na & Cl, increased K
o Inc. urinary excretion of Na & Cl
o Nonprotein nitrogen plasma level is high, hypoglycemia
o Most definitive test: measurement of plasma or serum
level of cortisol before & after administration of ACTH
 Clinical Manifestations
o S/Sx begin shortly after birth (adrenal hypoplasia,
steroidogenesis defects): failure to thrive, vomiting,
lethargy, anorexia, dehydration
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o Older children: gradual, muscular weakness, lassitude,
anorexia, weight loss, general wasting, hypotension,
intense craving for salt
o Increased skin pigmentation on face & hands, most
intense around the genitals, umbilicus, axilla, nipples,
joints
o Failure of suntan to disappear may be the first clue
 Management
o D5 0.9 NSS IV – to correct hypoglycemia & the Na loss
o Hydrocortisone succinate IV (25 mg for infants & 75 mg
for children) every 6 hrs for the 1st 24 hrs
o After 48 hrs, may discontinue fluids & shift to oral
cortisol in 5-20 mg every 8 hrs
o Further reduction until maintenance levels & a stable
clinical situation are achieved.
o May add Florinef ( flurohydrocortisone) 0.05-0.3 mg
daily
C0NGENITAL ADRENAL HYPERPLASIA
 AR disorders of adrenal steroidogenesis leading to a
deficiency of cortisol-- inc. secretion of corticotropin--
adrenocortical hyperplasia & overproduction of intermediary
metabolites
 Deficiency of 21-hydroxylase accounts for 90% of affected
patients
 Clinical Manifestations
1. NON-SALT-LOSING CAH
o Normal at birth but signs of sexual & somatic precocity
appear within the 1st 6 months of life
o Well developed muscles & BA > CA
o Stunted adult stature
o Small testes and enlarged penis
o Usually normal mental development
o Females: pseudohermaphroditism; enlarged clitoris,
labial fusion; internal genital organs are those of a
normal female
o Masculinization progresses after birth
o Tall for age with advanced ossification
2. SALT-LOSING CAH
o Severity of virilization is generally greater in this type
o Symptoms begin shortly after birth: failure to regain
birthweight, progressive weight loss, dehydration,
prominent vomiting, anorexia
o Females: virilization of external genitals
o Males: genitals appear normal
 Laboratory Findings
o Salt-losing type: low serum Na & Cl; inc. K; low serum
cortisol
o Inc.plasma renin; serum aldosterone
o 21-hydroxylase deficiency: increased serum 17-OHP
o Pelvic ultrasound to visualize presence of uterus in
female pseudohermaphrodites
o Urinary 17-ketosteroid excretion & plasma levels of
DHEAS elevated with CAH & cortical tumors but very
high values favor the diagnosis of neoplasm
o Management
o Glucocorticoids inhibit excessive production of
androgens & prevents progressive virilization
o Hydrocortisone 10-20 mg/m2/day orally in 2-3 divided
doses
o Monitor growth & hormonal levels
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o Flurohydrocortisone (0.05-0.3 mg daily) & NaCl 1-3 gms
given to normalize plasma renin activity
o Hydrocortisone continued indefinitely in all patients with
classic forms of CAH
 Management
o Adequate indices of control: monitor serum 17-OHP,
androstenedione, testosterone, renin preferably
measured at 8-9 am prior to taking the morning
medication
o Surgical correction of enlarged clitoris at 6-12 months
old
o Outcome: short stature, disordered puberty, menstrual
irregularity, infertility
CUSHING SYNDROME
 Characteristic pattern of obesity with associated
hypertension which is the result of abnormally high blood
levels of cortisol resulting from hyperfunction of the adrenal
cortex; ACTH –dependent or independent
 Etiology: functioning adrenocortical tumor (infants); pituitary
adenomas; hyperplasia of adrenals
 Clinical Manifestations
o More severe in infants
o Rounded face, prominent cheeks, moon facies, buffalo
hump, generalized obesity, abnormal masculinization,
impaired growth, hypertension, inc. susceptibility to
infection
o Older children: purplish striae on hips, abdomen &
thighs, delayed puberty, emotional lability, weakness,
headache, renal stones
 Laboratory Findings
o Serum cortisol levels are normally elevated at 8 am &
decrease to <50% by 8pm--- diurnal rhythm is lost
o Urinary excretion of free cortisol & 17-
hydroxycorticosteroids are increased
 Management
o Unilateral adenalectomy for benign cortical adenomas
o Bilateral tumors: subtotal adenalectomy
o Trans-sphenoidal pituitary microsurgery for children
o Adequate preoperative & postoperative replacement
therapy
o Substantial catch-up growth; abnormal bone density
PHEOCHROMOCYTOMA
 Catecholamine-secreting tumor arising from the chromaffin
cells
 Most common site of origin is the adrenal medulla
 Tumors may develop anywhere along the abdominal
sympathetic chain, likely to be located near the aorta at the
level of the IMA or at its bifurcation.
 Periadrenal area, urinary bladder, ureteral walls, thoracic
cavity, cervical region
 Occur in children 6-14 yrs old
 Tumors found more often on the right side, about 1-10 cm in
diameter
 Bilateral in >20% affected children
 Inherited as AD trait
 May be associated with other syndromes such as
neurofibromatosis, part of MEN syndromes, tuberous
sclerosis, Sturge-Weber syndrome, ataxia-telangiectasia
Biosynthesis & Metabolism
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Phenylalanine Tyrosine in the ovary; supporting cells --- Sertoli cells in testes or
granulosa cells in ovaries
Dopamine Dihydroxyphenylalanine  In the absence of a testis-determining factor (SRY or sex-
determining region on the Y chromosome), the gonad
Norepinephrine Epinephrine develops into an ovary.
 46,XX – needed for the development of normal ovaries
3-Methoxy-dopamine Normetanephrine  Development of the testis requires a Y chromosome (short
Metanephrine arm of the Y is critical for sex determination)
Homovanillic acid 3-Methoxy-4-hydroxy Function of the Testes
mandelic acid (VMA)
 During the 1st trimester of pregnancy – levels of placental
chorionic gonadotropin peak (8-12 wks) & stimulate the fetal
 Clinical Manifestations
Leydig cells to secrete testosterone; critical period for normal
o S/Sy result from excessive secretion of epinephrine &
virilization of the XY fetus
norepinephrine
o May be symptom-free in between attacks of  Shortly after birth, transient increase of gonadotropins (LH)
hypertension occurs- sharp inc. in serum testosterone which peak at 1-3
o Headache, palpitations, abdominal pain, dizziness, months old-- 6 mos.old levels dec. to low prepubertal
pallor, vomiting, sweating, convulsions levels that persist until the beginning of puberty
o Severe: precordial pain radiate into the arms, pulmonary  Within specific target cells, 6-8% of testosterone is converted
edema, cardio- & hepatomegaly by 5-reductase to dihydrotestosterone & 0.3% is acted on by
o Good appetite but does not gain weight due to aromatase to produce estradiol
hypermetabolism  Half of circulating testosterone is bound to sex-hormone-
o Polyuria, polydipsia, growth failure, papilledema, binding globulin (SHBG) & half to albumin; only 2%
hemorrhages, exudates & arterial constriction on circulates in the free form
ophthalmoscopy  Mullerian-inhibiting substance (MIS) – earliest secreted
 Laboratory Findings product of the Sertoli cells of the fetal testis; causes
o Urine contains protein & few casts involution of the embryologic precursors of the cervix, uterus
o Gross hematuria suggests that the tumor is in the & fallopian tubes during sexual differentiation; secreted in
bladder wall males by Sertoli cells both during fetal & postnatal life’ in
o Dx: demonstration of elevated blood or urinary levels of females, it is secreted by granulosa cells only postnatally
catecholamines & their metabolites  Inhibin – glycoprotein secreted by the Sertoli cells of the
o Predominant catecholamine in children is testes & granulosa & theca cells of the ovary; inhibits FSH
norepinephrine derived from the adrenal gland & secretion
adrenergic nerve endings  Activin – stimulates pituitary FSH secretion
o Total urinary catecholamine excretion >300 ug/day
 Follistatin – protein produced by gonads that inhibits FSH
o Urinary excretion of vanillylmandelic acid (major secretion
metabolite of epi-, norepi- & metanephrine) is increased
o Vanilla-containing foods & fruits can produce falsely Function of the Ovaries
elevated levels of VMA
 Oocytes are present from the 4th mo of gestation; need
o Ultrasound, CT scan, MRI: tumors
granulosa cells to form primordial follicles
o I-metaiodobenzylguanidine taken up by chromaffin
tissue is useful for localizing small tumors  Most important estrogens produced by the ovary are:
 Management estradiol-17 (E2) & estrone (E1); estriol is a metabolic
o Surgical removal of tumors product of these two & all three may be found in the urine of
mature females
o Preoperative a- & B-adrenergic blockers
 Estrogens also arise from androgens in the adrenal glands &
o Thorough transabdominal exploration of all the usual
in the testis.
sites
o Accurate indicators of malignancy – presence of  Ovary also synthesizes progesterone, a progestational
metastatic disease or local invasiveness that precluded steroid; the adrenal cortex & testis synthesize progesterone
complete resection or both as a precursor for other adrenal & testicular hormones.
o Pediatric malignant tumors – rare  Estrogens, like androgens, inhibit secretion of LH & FSH.
o Prolonged follow-up is indicated because functioning  In females, estrogens also provoke the surge of LH secretion
tumors at other sites may become manifested many that occurs in midmenstruation.
years after the initial operation
Conversion of Androgens to Estrogens
DEVELOPMENT OF GONADS
 The undifferentiated, bipotential fetal gonad arises from a Androstenedione Testosterone
thickening of the urogenital ridge
P450 Aromatase
 6 wks of gestation – gonad contains germ cells & stromal
cells -- Leydig cells in testes; theca, interstitial or hilar cells
Estrone (E1) 17B-Estradiol (E2)
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PRIMARY HYPOGONADISM
 Hypergonadotropic hygonadism in the male
 Congenital anorchia occurs in 0.6% of boys with
nonpalpable testes (1/20,000 males)
 Have normal external genitals; noxious factor damaged the
fetal testes of the genetic male fetus after sexual
differentiation took place
 Chromosomal aberrations
Noonan Syndrome
 Boys & girls have normal karyotypes
 Occurs in ½,000 live births
 Autosomal dominant
 Short stature, webbing of the neck, pectus
carinatum/excavatum, cubitus valgus, right-sided CHD,
hypertelorism, downward slanted palpebral fissures, ptosis,
micrognathia, moderate MR in 25%, SNHL;
hepatosplenomegaly; delayed puberty, cryptorchidism
 Human growth hormone has been used.
KLINEFELTER SYNDROME
 1/500-1/1,000 newborn males have 47,XXY chromosome –
most common sex chromosomal aneuploidy in males
 Due to meiotic nondisjunction of an X chromosome during
parental gametogenesis; the extra X chromosome is
maternal in origin in 54% & paternal in 46% of patients.
 Clinical Manifestations
o Dx rarely made before puberty due to paucity of s/sy in
childhood
o Considered in all boys with MR & in children with
psychosocial, learning, or school adjustment problems
o Anxious, immature, excessively shy, aggressive,
antisocial acts
o Tall, slim, underweight, long legs, small testes & penis,
gynecomastia, azoospermia, associated with leukemia
& lymphoma (15-30 yrs old)
 Management
o Normal basal plasma levels of FSH & LH before 10 yrs
old.
o Midpuberty – testicular growth stops & testosterone
levels are low
o Replacement therapy with a long-acting testosterone
preparation at 11-12 yrs old
o Enanthate ester 25-50 mg IM every 3-4 wks with 50-mg
increments every 6-9 mos until a maintenance dose for
adults is achieved (200-250 mg every 3-4 wks)
TURNER SYNDROME
 45,X chromosomal complement
 Unknown mechanism of chromosome loss
 Risk does not increase with maternal age
 Recognizable at birth: edema of the dorsa of the hands &
feet, loose skin folds at the nape, LBW, decreased length,
webbed neck, low posterior hairline, small mandible,
prominent ears, epicanthal folds, high arched palate, widely
spaced nipples, hyperconvex fingernails, delayed sexual
maturation
 Short stature – cardinal finding in all girls
 Hypofunction Of The Ovaries
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o postnatal Caused by congenital failure of development,
destruction (primary hypogonadism), or lack of
stimulation by the pituitary (secondary hypogonadism)
o Hypergonadotropic hypogonadism in the female
o Diagnosis before puberty is difficult
o Nonstenotic bicuspid aortic valves, horseshoe kidney,
complete absence of one kidney, idiopathic
hypertension, IBD
o Ultrasound of the heart, kidneys & ovaries is indicated
after the dx is established
o Most common skeletal abnormalities: shortening of the
4th metatarsal & metacarpal bones, epiphyseal
dysgenesis in the joints of the knees & elbows
 Plasma level of gonadotropins (FSH) are elevated---
decrease from 2-8 yrs old--by 10-11 yrs old rise to adult
levels
 Tx: recombinant GH increases height velocity & ultimate
stature in most but not all children (starting dose 0.375
mg/kg/wk)
 Replacement therapy with estrogens is indicated (little
consensus re: initiation)
 Premarin (conjugated estrogen) 0.3-0.625 mg given daily for
3-6 mos – effective in inducing puberty
 Estrogen is then cycled (taken on days 1-23) & Provera
(progestin) is added taken on days 10-23 in a dose of 5-10
mg daily
 Withdrawal bleeding occurs in the remainder of the calendar
month
 Psychosocial support
47,XXX FEMALES
 Most frequent X chromosome abnormality occurring in about
1/1,000 liveborn girls
 Due to maternal meiotic nondisjunction
 Phenotype is of a normal female; normal sexual
development
 By 2 yrs old, delays in speech is evident, lack of
coordination, poor academic performance, immature
behavior
 Tall & gangly, well coordinated, academically superior,
socially outgoing
DIABETES MELLITUS
 Syndrome of metabolic disease characterized by
hyperglycemia due to deficiency of insulin secretion or
insulin action or both resulting in abnormal metabolism of
CHO, CHON & fat
 Most common endocrine-metabolic disorder of childhood &
adolescence
 Etiologic Classification
o Type I – B-cell destruction leading to absolute insulin
deficiency: immune-mediated or idiopathic
o Type II – insulin resistance with relative deficiency or a
secretory defect with insulin resistance
o Drug- or chemical-induced – glucocorticoids, thyroid
hormone, diazoxide, thiazides, dilantin, B-adrenergic
agonists
o Infections – congenital rubella, CMV
o Gestational DM
o Neonatal DM
Impaired Glucose Tolerance
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 Refers to a metabolic stage that is intermediate between

normal glucose homeostasis & diabetes
 Fasting glucose concentration of 109 mg/dL – upper limit of
“normal”
 Many individuals are euglycemic; manifest hyperglycemia
only when challenged with oral glucose load

Insulin
 Insulin is synthesized in the RER of the B cells of the
pancreas- transported to the Golgi apparatus ---
packaged in membrane-bound granules-- move to the
cell wall & their membranes fuse expelling the insulin to the
exterior-- insulin crosses the basal lamina of the B cell &
the fenestrated epithelium of the capillary to reach the
bloodstream
 Effects of Insulin
• Adipose tissue
o Increase glucose entry
o Increase FA synthesis
o Increase glycerol phosphate synthesis
o Increase triglyceride deposition
o Activation of lipoprotein lipase
o Increase K uptake
o Inhibition of hormone-sensitive lipase
• Muscle
o Increase glucose entry
o Increase glycogen synthesis
o Increase amino acid uptake
o Increase protein synthesis in ribosomes
o Decrease protein catabolism
o Decrease release of gluconeogenic amino acids
o Increase ketone uptake
o Increase K uptake
• Liver
o Decrease ketogenesis
o Increase protein synthesis
o Increase lipid synthesis
o Decrease glucose output due to decrease
gluconeogenesis & increase glycogen synthesis
• General
o Increase cell growth
TYPE I DM
 Girls=boys; peaks at 5-7 yrs old & puberty
 Basic cause of the initial clinical findings is the sharply
diminished insulin secretion
 Mechanisms that lead to failure of pancreatic B-cell function
point to the likelihood of autoimmune destruction of
pancreatic islets in predisposed individuals
 Associated with increased frequency of HLA-B8, -DR3,
-BW15, -DR4
 About 80-90% of newly diagnosed patients have islet –cell
antibodies (ICAs) directed at cell surface.
 Some evidence of abnormal T-cell function with an alteration
in the ratio of suppressor to killer T cells at the onset
 Tissue damage of pancreatic B cells is mediated by T
lymphocytes-- produce cytokines-- induce destruction of
islet cells
Effects of Insulin Deficiency
 With progressive deficiency--excessive glucose production
& impairment of its utilization--hyperglycemia w/
glucosuria---resultant osmotic diuresis produces polyuria,
urinary losses of electrolytes, dehydration, polydipsia-
hypersecretion of epinephrine, glucagon, cortisol & GH
which amplifies & perpetuates metabolic derangements &
accelerates metabolic decompensation
 Combination of insulin deficiency & inc. counterregulatory
hormones is responsible for accelerated lipolysis & impaired
lipid synthesis- inc.plasma total lipids, cholesterol, TG,
FFA ketone body formation w/c exceeds the capacity for
peripheral utilization & renal excretion--metabolic acidosis
& rapid deep breathing
 Clinical Manifestations
o Classic: polyuria, polydipsia, polyphagia, weight loss
(often in a less than a month)
o Clue to polyuria: onset of enuresis in a previously toilet-
trained child
o Pyogenic skin infections & monilial vaginitis in
adolescent females
o Lethargy & weakness
 Diagnosis
o Dependent on the demonstration of hyperglycemia in
association with glucosuria with or w/o ketonuria
o Postprandial determinations of blood glucose or
screening oral glucose tolerance tests yield low
detection rates in children
 Diagnostic Criteria
o Symptoms of diabetes plus a random plasma glucose
>200 mg/dL or fasting plasma glucose >126 mg/dL or a
2-hr plasma glucose during the OGTT >200 mg/dL
o Polyuria, polydipsia, & unexplained weight loss with
glucosuria & ketonuria
DIABETIC KETOACIDOSIS
 Glucose >300 mg/dL, ketonemia, acidosis (pH <7.3 & HCO3
<15 mEq/L), glucosuria, ketonuria
 Precipitating factors like trauma, infections, vomiting,
psychologic disturbances
NONKETOTIC HYPEROSMOLAR COMA
 Blood glucose >600 mg/dL, absence of or only slight ketosis,
nonketotic acidosis, severe dehydration, depressed
sensorium or coma, various neurologic signs
 Serum osmolarity is >350 mOsm/kg
 Pre-existing neurologic damage
 Management

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Pediatric Endocrinology Part 2
o 3 phases: ketoacidosis, postacidotic or transition period
for establishment of metabolic control, continuing phase
of guidance of the diabetic child
o Ketoacidosis: expansion of intravascular volume,
correction of deficits in fluid, electrolyte & acid-base
status; initiation of insulin therapy
o Blood pH & electrolytes; ECG; blood culture; monitoring
I&O
o Initial hydrating fluid is isotonic saline (hypotonic relative
to the patient’s serum osmolality)
o Rate of fluid replacement is adjusted to provide 50-60%
of the calculated deficit within the 1st 12 hrs; the
remainder is given during the next 24 hrs
o Administration of glucose (5% solution in 0.2 N saline) is
initiated when blood glucose approaches 300 mg/dL to
limit the decline of serum osmolality & reduce cerebral
edema
o Give potassium added after the initial 20 ml/kg if UO is
adequate.
o Bicarbonate only if pH <7.2 given slowly
o Anticipate cerebral edema – limit rate of fluid to 4
L/m2/day or less
o Insulin 0.1 U/kg of regular insulin followed by constant
infusion of 0.1 U/kg/hr
o When acidosis has been corrected, the continuous
infusion may be discontinued & insulin given
subcutaneously at 0.2-0.4 U/kg every 6-8 hrs while
maintaining the glucose infusion until the child can fully
tolerate food.
o Monitor blood glucose before & 2 hrs after each meal &
the insulin dose adjusted to maintain the blood glucose
in the range of 80-180 mg/dL.
 Nutritional Management
o CHO 55%, fat 30%, CHON 15%
o 70% of CHO content should be derived from complex
CHO & intake of sucrose & highly refined sugars should
be limited.
o Polyunsaturated:saturated fat ratio 1.2:1
o Total daily caloric intake divided to provide 20% at
breakfast, 20% at lunch, 30% at dinner with 10% for
each of the midmorning, midafternoon & evening
snacks.
 Monitoring
o Reliable index of long-term glycemic control – measure
glycosylated Hgb
o Glycohemoglobin (HbA1c) represents the fraction of
Hgb to which glucose has been nonenzymatically
attached in the bloodstream
o The higher the blood glucose & the longer the RBC’s
exposure to it, the higher will be the fraction of HbA1c--
 reflects the average blood glucose concentration of
the preceding 2-3 months
Glycohemoglobin
 Glucose combines with Hgb continuously & nearly
irreversibly during the life span of RBC (120 days)
 Glycated Hgb is proportional to the mean plasma glucose
level during the previous 6-12 weeks
 Glycated Hgb predicts risk of progression of diabetic
complications
 HbA1c measurements obtained 3-4x/yr to get a profile of
long-term glycemic control
Marias
 The more consistently lower the level, the better the
metabolic control, the more likely it is that microvascular
complications will be less severe, delayed in appearance or
avoided.
 Use: monitor diabetic patients’ compliance with therapeutic
regimen & long-term blood glucose level control
 In known diabetics: 7% indicates good diabetic control; 10%
indicates fair diabetic control; 13-20% indicates poor diabetic
control
Somogyi Phenomenon
 Hypoglycemic episodes manifest as late nocturnal or early
AM sweating, night terrors & headaches alternating rapidly
within 4-5 hrs with ketosis, hyperglycemia, ketonuria &
glucosuria suggest the possibility of Somogyi phenomenon.
 Due to an outpouring of counterregulatory hormones in
response to insulin-induced hypoglycemia.
Dawn Phenomenon
 Elevations of blood glucose occur between 5-9 am without
preceding hypoglycemia
 Normal event; reflects the waning effects of insulin probably
due to increased clearance of insulin & nocturnal surges of
GH that antagonize insulin’s metabolic effects
Brittle Diabetes
 Implies that control of blood glucose fluctuates widely &
rapidly despite frequent adjustment of insulin doses
 Somogyi & dawn phenomena are the most common cause
of “brittleness”.
 To distinguish: measure blood glucose at 3,4,7 am. If blood
glucose >80 mg/dL in the 1st 2 samples & markedly higher in
the last ---dawn (tx: inc. evening dose of intermediate insulin
10-15%)
 If the 3 or 4 am blood glucose level is 60 mg/dL or less
followed by rebound hyperglycemia at 7 am- Somogyi (tx:
reduction of the evening intermediate-acting insulin of 10-
15% or a delay in its injection until about 9 pm is indicated)
FILLER! FILLER!FILLER! FILLER!FILLER! FILLER! FILLER!
Here’s a poem by E. E. Cummings (cited in one of
Cameron Diaz’s films)… Para kay: Rej at Jen, Aiza at
Patrick…patience is a virtue... To real-life lovers: Dhess &
Pats, Sheng & Myron, Roche & Fluffy, Khaye & Pau…
more power to you guys! To my inspiration & bestfriend,
‘til we meet again… Para sa mga in-lurv jan!
i carry your heart with me (i carry it in
my heart) i am never without it
(anywhere
i go you go, my dear; and whatever is
done
by only me is your doing, my darling)
i fear no fate (for you are my fate, my
sweet) i want
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 PEDIATRICS 2
Pediatric Endocrinology Part 2

no world (for beautiful you are my

world, my true)
and it's you are whatever a moon has
always meant
and whatever a sun will always sing is
you

here is the deepest secret nobody

knows
(here is the root of the root and the
bud of the bud
and the sky of the sky of a tree called
life; which grows higher than soul can
hope or mind can hide)
and this is the wonder that's keeping
the stars apart

i carry your heart (i carry it in my

heart)

…owww… how sweet…

MOTTO OF THE WEEK:

“Ang point kasi dun ay…. “

“It’s not what you say that matters, it’s how you say it”

The End

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