Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
PEDIATRICS 2021
Endocrinology
CDC Percentiles - Birth to 36 months: Boys Chart
Growth Disorders
CDC Percentiles - Birth to 36 months: Girls Chart



If you measure a child lying down = LENGTH

Length is longer than the height (1-2 cm diff.)
If you measure a child standing up = HEIGHT
The old name for Centers for Disease Control and
Prevention (CDC) percentile growth charts was National
Center for Health Statistics (NCHS) percentile growth charts
CDC Percentiles - 2 to 20 years: Boys Chart
CDC Percentiles - 2 to 20 years: Girls Chart
1
PEDIATRICS 2021
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
Before, the NCHS percentile only focused for 2 to 18 years
old. Now, CDC extended it for 2 to 20 years old.

Percentile - rank of the child among 100 children

Ex. Baby X belongs to the 50th percentile
(median) for length

If Baby X is to be compared to 100
babies with the same age and sex,
Baby X’s length is in the middle

Out of 100 babies, there will be 50
babies who are longer than Baby X
and there will be 49 or 50 babies
shorter than Baby X

Ex. Baby A belongs to the 10th percentile for
length

Out of 100 babies, there will be 90
babies who are longer than Baby A
and there will be 9 or 10 babies
shorter than Baby A

In short, Baby A is short

Percentiles: 97th , 90th , 75th , 50th , 25th , 10th , 5th

Why should we measure the head circumference? To
check for brain development of the child indirectly

In the CDC chart, the height and weight is in one page

CDC interpretations:
Height percentile
Weight percentile
Interpretation
50
50
STHENIC
HYPOSTHENIC/
95
25
ASTHENIC
10
75
HYPERSTHENIC
HYPOSTHENIC/
95
10
ASTHENIC
10
95
HYPERSTHENIC

WHO Chart - Weight for age
WHO Chart - Length for age


CDC charts can be used for breastfed and formula fed
infants
WHO charts are used exclusively for breastfed infants for
the 1st 6 months
GROWTH RATE

Average birth length:

Newborns: 50 cm

1st year: 75 cm

2nd year: 88 cm

Estimated growth rate :

1st year of life: 25 cm

2nd year of life: 12.5 cm -15 cm

3rd year of life: 6.5 cm or 7 cm

4th year of life: 5 - 6 cm

Formula:
��� �� ����� × � + �� = ��

Child in a prepubertal period would only grow 5cm/ year

WHO growth charts come in Z-scores

+ 2 = 9th percentile

+ 1 = 85th percentile

0 = 50th percentile

-1 = 15th percentile

-2 = 3rd percentile
WEIGHT GAIN

1st week of life - may decrease by 5-10% of baby’s birth
weight

Expected weight gain thereafter is 30 grams or 1 oz per
day

After 3 months of age, weight gain is expected to slow
down - 1 pound per month

Formula (applicable for 3-12 months of life):
��� �� ������ + �� = ������ (���)

1 pound = 16 oz

A baby should gain at least 1 pound every 2 weeks (14
days)

There should a a weight gain of 1 kilo (2.2 lbs)
per month

This is acceptable during the first 3 or 4 months
of life

After 3 months, the weight gain slows down (1
pound per month)

Expected or allowable weight gain: 2 kg per year
2
PEDIATRICS 2021
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
Ex. A 2 year old child weighs 12 kilos; After a
year, his weight became 18 kilos

Weight he gained: 6 kilos

Is his weight normal or not?
ABNORMAL

Normal weight for this patient should
be (3 years old x 2 + 8) = 14 kilos

Ex. 6 years old child with a weight of 30 kilos.
What is your consideration?

Child may be chubby/ obese

Check for the patient’s
height first before you
conclude if pathologic or
nutritional obesity
Nutritional or physiologic obesity generally happens when
a child is tall (above 0 Z-score) but his weight is obese/
overweight

Problem: Increased calorie intake
Overweight and height is short differentials:

Pathologic obesity (growth hormone deficiency)
- hypersthenic

Congenital hyperthyroidism

Cushing’s syndrome (pathologic or iatrogenic
cause) - rare

Increased cortisol = causes gain
weight and retard the bones leading
to short height



HEAD CIRCUMFERENCE

Average head size in a full term newborn: 35 cm

1st year of life - increases by 12 cm

1.5 cm/ month on the 1st 4 months

1.0 cm/ month on the 2nd 4 months

0.5 cm/month on the 3rd 4 months

2nd year of life - increases by 2 cm

Determine if macrocephaly or microcephaly


When do you say it is SGA (small for gestational age) in full
term?

< 2500g
When the baby is SGA, you have to determine if there is:

IUGR (intrauterine growth restriction)

Assess if there is any abnormal
maternal condition

Environmental or placental problem

Fetal problem (e.g. dysmorphic syndrome,
chromosomal abnormalities)
SHORT STATURE



Short stature - height is less then -2 Z-score
Growth rate of a 1 year old: 25 cm
Familial Short Stature

Annual growth rate normal

Height at or below 3rd percentile





No systemic or endocrine disease
Pubertal growth spurt at normal age
Skeletal age (bone age or x-ray) equal to
chronological age
Ancestors relatively short
Estimates:
50th percentile / 0
15th percentile/ -1
3rd percentile/ -2
Height of male
5 feet 7 inches
or
5 feet 8 inches
5 feet 6 inches
5 feet 4 inches
(64 inches)
Height of female
5 feet 4 inches
5 feet
CONSTITUTIONAL DELAY IN GROWTH AND PUBERTY (CDGP):
PHYSIOLOGICAL FEATURES

Exaggerated “phase-change” growth deceleration

Transient deficiencies in GH secretion, particularly prior to
puberty

Severity of CDGP/ Bone age (BA) delay reflects duration of
periods of impaired GH secretion

Slowed tempo of growth → BA delay → eventual pubertal
delay

Prolonged school-age growth deceleration and enhanced
susceptibility to exogeneous growth suppression (e.g.
ADHD medications, ICS)
Table 7-10 Criteria for Presumptive Diagnosis of Constitutional
Delay of Growth and Maturation

No history of systemic illness

Normal nutrition

Normal physical examination, including body proportions

Normal thyroid and GH concentrations

Normal CBC, sedimentation rate, electrolytes, blood urea
nitrogen

Height at or below the 3rd percentile but with annual
growth rate >5th percentile for age

Delayed puberty:

Males: Failure to achieve Tanner G2 stage by
age 13.8 years or P2 by 15.6 years

Females: Failure to achieve Tanner B2 stage by
age 13.3 years

Delayed bone age

Normal predicted adult height:

Males: >163 cm (64 inches)

Females: >150 cm (59 inches)

Chronological age is the age that you base on date of
birth

If there is a visual problem, the diagnosis basing on the 1st
line (dotted line) of the growth chart on the left side?
Postnatal onset pathologic short stature

There might be a brain tumor (most common:
craniopharyngioma)
3
PEDIATRICS 2021






Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
Constitutional growth delay and puberty

Condition that describes children who growing
at a normal rate at the 1st 6 months and after
that, experiences growth deceleration

Children experience delayed puberty to their
peers of similar age associated with a delay in
pubertal growth spurt (late bloomers)

Have a short stature relative to their parent’s
heights, and a delayed bone age

These children will typically have an adult height
that is within range of what is expected for their
genetic potential
Growth deceleration on the 1st 3 years: Normal variant
(constitutional growth delay and puberty)
Growth deceleration beyond 3 years of life: Consider this
as pathologic
Familial short stature

Child is short because the parents are short

No pathological cause of short stature in the
parents or the child
Prenatal onset pathologic short stature

Started in utero but much smaller

Started at -3 Z-score
-3 Z-score or more babies need to be worked up to
determine any pathologic cause since this finding is usually
abnormal
NORMAL VARIANT GROWTH PATTERNS
NVSS
History
Unremarkable
General PE
Unremarkable
NVCD
Unremarkable
Delayed physical
development
Height
Short
Short
Growth rate
Normal
Normal
Laboratory
Normal
Normal
Bone Age
Normal
Delayed
Predicted adult height
Short*
Normal
*Less than 163 cm (64 in) for male and 151 cm (59 in) for females
CHARACTERISTICS OF AUTOSOMAL DOMINANT INHERITANCE

There is vertical transmission of the phenotype, with an
affected child usually having an affected parent (except
with reduced penetrance, new mutation, germline
mosaicism, or anticipation)

At conception, the chance of transmitting the phenotype
from affected parent to affected child is 1 in 2

An unaffected individual not inheriting the phenotype has
no risk of transmitting the phenotype to his or her own
children
(except
with
reduced
penetrance
or
anticipation). In other words, there is no carrier state.

Males and females are just as likely to transmit the
phenotype, unlike the case for sex-linked recessive
disorders where the phenotype is transmitted through
carrier females and there is no male-to-male transmission

New mutations are relatively common, sometimes
accounting for up to half or more of all patients, and
depends on the fitness of the syndrome
HYPOPHOSPHATEMIC RICKETS

5 and a 1/2 years old

Severe short stature (-7 score) - pathological

Disproportionate growth

Prominence of the carpal bones

Normally, in the 1st year of life, there is
ossification of 2 carpal bones

Normally, at 5 years old, you should have an
ossification of 6 carpal bones (out of the 8
carpal bones)

In the radiologic imaging, only 2 carpal bones
are ossified and the epiphyseal plate is funnelshaped

(+) Osteopenia
Bypassing GH and treating directly with IGF-1 could constitute a
reasonable alternative therapy. Studies of this mode of therapy
await sufficient supplies of these somatomedin peptides
DISORDERS
RHIZOMELIC DWARFISM

Rhizo = root; Milia = extremities

Type of dwarfism where the dominant feature is proximal
(femoral or humeral) limb shortening

Severely short

Disproportionate growth

Deep V formation = short arm

Normally, the antecubital crease is slightly
higher than the umbilicus


Upper segment - vertex of the head to the symphysis pubis
Lower segment - symphysis pubis up to the sole of the foot


Total calcium for this patient is normal; Phosphorus was low
Hydroxyapatite contains calcium and phosphorus
ACHONDROPLASIA

Most of these patients will not have a normal pregnancy
(narrow pelvis)

Increased distance between 3rd and 4th fingers if
radiographic imaging is done

Pathological disproportionate short stature
4
PEDIATRICS 2021

Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
Calcitriol - other name for 1,25-dihydroxy vitamin D3; active
form of vitamin D

Increase absorption of calcium and phosphorus
from the intestine → normal calcium and
phosphorus
4P MINUS SYNDROME (4P DELETION SYNDROME; WOLFHIRSCHHORN SYNDROME)

4 month old baby Caucasian

Length: -2 Z score; Weight: 2.3 kilos (borderline)

Abnormal due to presence of hypotelorism (abnormally
increased distance between 2 organs or body parts; for
this patient, the distance between the eyes and nasal
bridge)

Pathologic problem

Proportionate growth

Prenatal onset pathologic short stature

In this syndrome, there is a deletion of part of the short arm
of chromosome 4 (4p)

Distinctive facial features, including a broad, flat nasal
bridge and a high forehead = Greek warrior helmet
appearance

Other features: short philtrum, micrognathia, downturned
mouth, and poorly formed ears with small holes or flaps of
skin

Estrogen excess
CONGENITAL HYPOTHYROIDISM

22 months old; Female; unable to walk with developmental
delay

(+) palmar grasp; short; thyroid test: low T4; high TSH

Problem in her memory

Treatment: Levothyroxine

Most common cause: Thyroid dysgenesis
CONGENITAL HYPOTHYROIDISM

Frequent constipation was the main problem

Puffiness can also be seen; anemia

Speech delay
SECKEL SYNDROME

Born SGA; Developed seizure activity on the 1st 2 years of
life

P.E: Head is smaller than the trunk; short; developmental
delay; prominent beak-like protrusion of the nose

Other features: Abnormally large eyes; narrow face;
malformed ears; micrognathia; clinodactyly; dysplasia of
the hips; and radial dislocation

Prenatal onset pathologic short stature
TRISOMY 18 (EDWARDS SYNDROME)

Born at 2 kg; At birth, noted with heart murmur; Enamel
hyperplasia; 5th finger overlapping the 4th finger;
overlapping of the 2nd and the 3rd finger; Rockerbottom
foot; Prominent occiput; syndactyly

Poor prognosis on the 1st year
METHYLMALONIC ACIDEMIA

13 months old; female; CC: difficulty in breathing

Problem is more on the weight than length

ABG: metabolic acidosis; blood sugar: high; passed
ketones in the urine (ketonuria); vomiting

Primary diagnosis: TYPE 1 DIABETES MELLITUS
IN KETOACIDOSIS (DKA)

HbA1c: 5.2 (normal)

Diagnosis: METHYLMALONIC ACIDEMIA

Type of organic acidemia that
mimics DKA

Autosomal recessive

Rare disease

Poor weight gain
ORGANIC ACIDEMIA

Group of metabolic disorders which disrupt normal amino
acid metabolism, particularly branched-chain amino acids
(isoleucine, leucine, valine), causing a buildup of acids
which are usually not present

Prominent big ears; chromosome: del 22 short arm

Length: more than -3 Z score = pathological short stature
ENDOCRINE DISODERS FOR SHORT STATURE

Growth hormone deficiency

Hypothyroidism

Gonadal dysgenesis

Glucocorticoid excess

Pseudohypoparathyroidism

Premature epiphyseal fusion

Androgen excess
5
PEDIATRICS 2021
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
Features:
Large
(macrocephaly)
dolichocephalic head, prominent forehead and
jaw, hypertelorism, antimongoloid slant of the
palpebral fissures, high arched palate, and
large hands and feet with thickened
subcutaneous tissue

Clumsiness and awkward gait are noted

Great difficulty in sports or tasks that require
coordination
BECKWITH-WIEDEMANN SYNDROME (BWS)

An overgrowth malformation syndrome

Incidence: 1: 13,700 births

Caused by genetic or epigenetic abnormalities
(loss or gain of DNA methylation) of IC1 and IC2

Features: Hypoglycemia, large tongue, ear pits,
omphalocele
or
umbilical
hernia,
hemihyperplasia, organomegaly, high risk of
embryonal tumors til age 8

Hypoinsulinemic
EXOGENOUS OBESITY (NUTRITIONAL OBESITY)

Associated with rapid linear growth and
relatively early onset of puberty

Bone age is accelerated leading to relative tall
stature in childhood but adult height is normal

To diagnose:

Look at the growth chart

Identify BMI

Measure
height
and
weight


TALL STATURE
Equivalent Average Height Among Males and Females Based on
Z-score
Males
Females
-2
5 feet 4 inches
5 feet
0
5 feet 8 inches
5 feet 4 inches
+2
6 feet
5 feet 8 inches

DIAGNOSTIC ALGORITHM FOR DIFFERENTIAL DIAGNOSIS OF TALL
STATURE AND OVERGROWTH SYNDROMES
OVERGROWTH SYNDROMES

Group of disorders associated with excessive growth and
growth of specific organs

Caused by excess production and availability of insulin-like
growth factor 2 (IGF-2) encoded by gene Igf2

MATERAL DIABETES MELLITUS

Most common cause of infants being large for
gestational age

Baby is macrosomic

Hypoglycemia - ↑ insulin exposure

Ketonuric = insulin is shut off

Non-ketonuric = insulin is open

Ketone bodies = product of the breakdown of
glucose

SOTOS SYNDROME

Cerebral gigantism

They are above the 90th percentile for both
length and weight at birth

Growth is markedly rapid

By 1 year of age, affected infants are
taller than 97th percentile in height

Accelerated growth continues for
the 1st 4-5 year then returns to a
normal rate

Macrocrania
becomes
more
apparent
postnatally

Caused by the mutations in NSD1 (nuclear
receptor SET domain-containing protein 1) gene

Autosomal dominant

Incidence: 1 in 14,000 live births

Puberty usually occurs at the expected time but
may occur slightly early
Note:

Nutritional obesity = height is more than the 50th percentile
+ normal muscle development

Pathologic obesity/ endogenous obesity = height is short or
at 10th percentile + abnormal muscle development

Hypothyroidism → retard the bones →
decreased bone growth → short child

Prolactin-secreting pituitary adenomas - most common
pituitary tumors in adolescents

Increased cholesterol → overweight and short →
congenital hyperthyroidism → Cushing’s syndrome

Hypercortisolism due to asthma medications → retard the
bones → decreased growth rate → overweight → buffalo
hump

Excess GH → pituitary gigantism

PRECOCIOUS PUBERTY

Results in accelerated linear growth during
childhood, mimicking the pubertal growth spurt

Skeletal maturation is advanced thus, height is
often compromised

MARFAN SYNDROME

Autosomal dominant connective tissue disorder

Consist of tall stature, arachnodactyly, thin
extremities, increased arm span, and decreased
upper body: lower body segment ratio

Also include: ocular abnormalities (lens
dislocation), hypotonia, kyphoscoliosis, cardiac
valvular deformities, and aortic root dilation

Wrist sign; thumb sign; joint is so lax

Normal intelligence

A well-known person with this syndrome is
Abraham Lincoln
6
PEDIATRICS 2021



Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
HOMOCYSTINURIA

Autosomal recessive inborn error of amino acid
metabolism

Caused by a deficiency of the enzyme
cystathionine synthetase

Features: intellectual disability when untreated;
resemble Marfan syndrome, particularly ocular
manifestations (Marfanoid syndrome)
XXY SYNDROME

Associated with tall stature, severe acne in
adolescence, increased incidence of learning
disabilities,
and
behavioral
problems,
particularly impulsivity

Intelligence is usually in the normal range

Common in detention centers
ESTROGEN AND ANDROGEN DEFICIENCY
CHARACTERISTICS OF SEX-LINKED RECESSIVE INHERITANCE

Males are more commonly affected than females

The gene responsible is transmitted from an affected man
through his daughters, who are seldom affected. Each
daughter is an obligatory heterozygous carrier. Each of the
carrier daughter’s sons has a 50% chance of inheriting it

No male-to-male transmission occurs

The affected males in a pedigree are usually related
through females

Heterozygous female carriers are usually unaffected, but
infrequently may demonstrate variable severity of the
phenotype
C. During palpation, testes was felt on the area







A sexual hormone fuses with the sexual membrane through
the cytoplasm and attaches itself through a specific
receptor.
The sexual hormone and sexual membrane will form a
complex.
They will go inside the nucleus and stimulate the initiation of
transcription, translation, and then the steroid response.
If there are any problems in any of these steps, then the
child remains to be “female”

In other words, regardless if the baby is female
or male, if no hormonal influence will be done,
the baby will come out with a normal female
external genitalia.

This is because, for a baby to become male, it
needs the effect of testosterone

KLINEFELTER SYNDROME

XXY syndrome

Relatively common (1 in 500-1000 live births)

Chromosomal abnormality associated with tall
stature, learning disabilities, gynecomastia, and
decreased upper body: lower body segment
ratio

Affected
boys
can
have
hypotonia,
clinodactyly, and hypertelorism

Testes are invariably small

Sertoli cell function are defective →
infertility

Small phallus

Increased incidence of hypospadias,
and cryptochordism
GONADOTROPIN DEPENDENT PRECOCIOUS PUBERTY

Aka. Central precocious puberty

Results from premature activation of the
hypothalamic-pituitary-gonadal (HPG) axis
Others:




Simpson-Golabi-Behmel syndrome
Costello syndrome
Weaver syndrome
Perlman syndrome
ANDROGEN INSENSITIVITY SYNDROME (INCOMPLETE)

Aka. Testicular feminization

Sex hormone receptor problem

This will lead to ambigous genitalia
7
PEDIATRICS 2021
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
Gene Mapping of HLA Molecules
Diabetes Mellitus Type I


Insulin-dependent diabetes mellitus/ Juvenile diabetes
Characterized by low or absent levels of endogenously
produced insulin and by dependence on exogenous
insulin to prevent development of ketoacidosis
Some Perspectives of Diabetes

1000 BC

Sushruta and Charaka, Hindu physicians

Recognized 2 forms of diabetes

1683

Brunner

Described polydipsia and polyuria
pancreatectomy in dogs

1869

Langerhans

Described pancreatic islets

1921

Banting and Best

Extraction of insulin
after
Nomenclature for Diabetes Mellitus

Traditionally, based on the age of patient at the onset of
symptoms

1979, based on “therapeutic” classification

1997 - Diabetes Mellitus Type 1 and Diabetes Mellitus Type 2

Diabetes Mellitus Type 1 other names:

Juvenile diabetes

Insulin-dependent diabetes

Chronic
condition;
pancreas
produce little or no insulin

Diabetes Mellitus Type 2 other names:

Adult-onset diabetes

Insulin-resistant diabetes

There is high levels of glucose in the
blood
Incidence of Diabetes Mellitus Type I


HLA is located in the chromosome 6
Focus on the class II - DP, DQ, DR
HLA DR and DQ Phenotype Frequencies in IDDM Patients and
Healthy Control Subjects
Phenotype
Diabetic %
Non
Odds Ratio
diabetic %
DR (Serology)
DR 3/ DR 4
33
6
8.3
DR 3/ DR 3
7
1
9.8
DR 3/ DRX
7
14
0.05
DR 4/ DR 4
26
0
DR 4/ DRX
22
16
1.5
DRX/ DRX
4
23
0.02
DQ (molecular probes)
Non-Asp/
96
19
107.2
non-asp
Non-Asp/ Asp 4
46
0.04
Asp/ Asp
0
34
0


Heterozygous: 4% diabetic
At position 57 (Asp/Asp): 0% diabetic
Prevalence of Islet Cell Antibodies at the Time of Diagnosis

Islet cell cytoplasmic antibodies - 60-80%

Islet cell surface antibodies - 60-80%

Insulin autoantibodies - 30-50%
Proposed Scheme of Natural History of Beta-Cell Defect



It starts with genetic predisposition
Honeymoon period

This period is temporary thus, it is important to
monitor these patients

C-peptide - indicate the endogenous release of insulin
Philippines may be of similar incidence rates to Hongkong
in relation to DM Type I
Possible Etiologic Factors in Diabetes Mellitus Type I

VIRUS

Coxsackie

Mumps

Rubella

CHEMICAL

Alloxan

Streptozotocin

Pyrminil (Vacor)

PHARMACEUTICALS

Pentamidine

L-asparaginase
8
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
PEDIATRICS 2021
Endocrine Effects of Insulin

EFFECT ON LIVER

Reversal of catabolic features of insulin
deficiency

Inhibits glycogenolysis

Inhibits conversion of fatty acids and
amino acids to keto acids

Inhibits conversion of amino acids to
glucose

Anabolic action

Promotes
glucose
storage
as
glycogen

Increases triglyceride synthesis

EFFECT ON MUSCLE

EFFECT ON ADIPOSE TISSUE
Note:

Insulin is anabolic

Insulin deficiency → protein breakdown → muscle
deficiency

Anabolic causes weight gain

Adequate insulin → no formation ketone bodies

Ketone bodies are water-soluble molecules (acetoacetate,
beta-hydroxybutyrate, and acetone)

70-80% - beta-hydroxybutyrate
Diabetes Control and Complications Trial (DCCT)

1441 patients with type 1 diabetes mellitus were studies
over a 10 year period

“Near” normalization of blood glucose resulted in a delay
in the onset of established microvascular and neuropathic
complications
Insulin Treatment
Lipoatrophy Due to Insulin Injection

Do not inject insulin on one side only to avoid this
Clinical Case
History

F.M., 9 y.o., female came in due to dyspnea and body
malaise

Prenatal, natal, and postnatal were unremarkable

Immunization: BCG, DPT3, OPV3, AMV, MMR, Hep B3

(+) allergy to chicken and yellow colored foods

Non-asthamtic with history of wheezing

Maintained on Ketotifen for several months

Had UTI but 2 urinalysis exam was negative for glucose

No heredofamilial disease like hypertension or diabetes
mellitus

No history of previous hospitalization


4 hours prior to admission, she became dyspneic. Vomiting
and body malaise persisted thus, prompted admission
Physical Examination

Examined awake, not irritable, in distress, afebrile

HR: 120

RR: 40

T: 36.2C

Weight: 30.3 kg

Skin: dry, warm, fair turgor

HEENT: (+) alar flaring, dry lips

Chest and Lungs: Decreased BS on the R lung, (+) rales on
both LF, (-) wheezing

CVS: tachycardic, regular rhythm

Extremities: strong pulses, CRT < 2 seconds

CNS: within normal limits
Impression: Bronchopneumonia
Differential Diagnosis

Acute bronchitis

Acute gastritis with dehydration

Bronchial asthma

Urinary tract infection
Insulin Regimen (Split Coverage)


Insulin


MPH


Peak: 2-4 hours
Duration: 6 hours
2 peaks for 24 hours
Duration: 12 hours
Course in the Ward
On Admission

IVF started with D5 0.3% NaCl at 5% correction NPO

O2 inhalation at 2L/min via nasal prong

CBC: Hct of 49.9% and leukocytosis with segmenter
predominance

Chest x ray: Inflammatory process in the right lower lobe

Medications: Salbutamol p.o.; Cefuroxime IVTT
6th Hospital Hour

Tachypneic and diaphoretic with wheezing on both lung
fields

Hydrocortisone IVTT and Terbutaline nebulization were
given

Na: 133; K: 4.9; Cl: 103; CO2: 5

ABG result: severe metabolic acidosis

NaHCO3 at 2 meq/kg (60 meq) was given

Urine specimen was sent to the laboratory

Total IVF received: 0.6 L

Anion gap: 27.2 mmol/L
10th Hospital Hour

Restless, tachypneic, diaphoretic and polyuric

IVF was increased to 10% fluid correction

O2 inhalation was increased to 6L/min

Another NaHCO3 at 2 meq/kg (60 meq) was given

Total IV fluid received: 1.5 L
13thHospital Hour

Repeat ABG still showed severe metabolic acidosis

Another NaHCO3 at 2 meq/kg (60 meq) was given total IV
fluid received: 2.1 L
16th Hospital Hour

Became drowsy with the following vital signs: HR: 160; RR:
60s-70s; faint pulses

Referred to pediatric intensivist
9
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
PEDIATRICS 2021
Intubated and was transferred to ICU
TACS eventually grown S. pneumoniae
Mechanical ventilator was attached
Repeat chest x-ray showed inflammatory processes on the
right upper lobe

Sedation was started

Amikacin IVTT was added
24th Hospital Hour

Vital Signs did not improve

Dopamine at 8μgm/kg was started

Repeat ABG showed severe metabolic acidosis

Total IV fluid received: 4.5L

Urinalysis showed glucose +3 (glucosuria) with large
ketones

RBS was 766 mg/dl

Referred to pediatric endocrinologist

Insulin infusion was started

History reviewed revealed (+) history of weight loss and
polyuria a month prior to admission

CBS monitoring was done

Weaning from the mechanical ventilator started

Repeat ABG showed moderate metabolic acidosis

Dopamine was discontinuted

Hemoglobin A1c was 13.9%
2nd Hospital Day

Had stable vital signs

Repeat ABG showed normal result

She was extubated and was on O2 inhalation at 4L/min via
nasal prong

Insulin was shifted to subcutaneous (SQ) injection

Soft diet was started




CBS and SQ Insulin given
DATE
TIME
8/15/03
10am
2pm
6pm
10pm
8/16/03
2am
6am
11:30am
5:45pm
10pm
8/17/03
2am
CBS (mg/dl)
293
350
164
247
224
439
559
497
209
DATE
TIME
CBS (mg/dl)
8/17/03
7:30 am
141
12 nn
5:30 pm
303
530
7 am
244
11:30 am
5:30 pm
159
373
10 pm
5 am
274
221
8/18/03
8/19/03
HUMULIN R
4 units
5
7
4
6
5
8
12
8
5
64
HUMULIN R/
HUMULIN N
6 units/ 14
units
No coverage
8 units/ 5
units
6 units/ 14
units
No coverage
8 units/ 5
units
No coverage
7 units/ 14
units
6th Hospital Day

She was discharged improved

Home medication: Insulin SQ injection BID

CBS monitoring was continued QID

Instructions on dietary modification as well as SQ injection
of insulin were explained to the patient
Final Diagnosis:

Diabetic Ketoacidosis

Bronchopneumonia
Note:

Things to take note in management of diabetes: Hydration,
Electrolyte correction, Insulin, Monitor the patient

Catecholamines, Cortisol, Growth hormone, Glucagon stress hormones/ counter-regulatory hormones

When increased, there can be leukocytosis

CO2 or CO2 combining power is equivalent to the
bicarbonate levels in the arterial blood gas

Normal range: 22-28 mmHg

Causes: Metabolic Acidosis and Elevated Anion Gap
Mnemonic: MUD PILERS

Methanol, Metformin

Uremia

Diabetic ketoacidosis

Paraldehyde, Phenformin

Iron, Isopropyl alcohol, Isoniazid

Lactic acidosis

Ethylene glycol, Ethyl alcohol

Rhabdomyolysis

Salicylates
TYPE 1 DIABETES MELLITUS

Epidemiology

Incidence is highly variable among different
ethnic groups

0.7/100,000 per year in Pakistan

40/100,000 per year in Finland

US:

School-age children 1.9/1,000

Highly correlated with increasing age

5 years old - 1:1,430

16 years old - 1:360

Genetics

Cannot be classified according to a specific
model of inheritance

MHC class II region on chromosome 6p21

Account for about 60%

Contribution to the pathogenesis: unclear

HLA-DR3 or HLA-DR4: 2 - 3 fold risk

Both: 7 - 10 fold risk

Homozygous absence of aspartic acid at
position 57 of the HLA DQ beta chain: 100 fold

Presence of arginine at position of the DQ beta
chain: marked susceptibility

Concordance rate among identical twin: 3050%

Siblings

Both HLA - D haplotypes: 12-20%

1 haplotype: 5 - 7%

No haplotypes in common: 2-5%

Offspring of a diabetic parent: 2-5%

Higher risk of a diabetic father

Pathogenesis

Clinical Manifestations

Most symptoms are non-specific

Intermittent polyuria or nocturia →
polydipsia

Compensatory
hyperphagia
→
weight loss

Extremely low insulin levels → ketoacids
 Accumulate → child quickly deteriorates
10
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
PEDIATRICS 2021
Diabetic Ketoacidosis (DKA)

Pathophysiology

With the release of the counter-regulatory
hormones (glucagon, epinephrine, cortisol and
GH), there is INCREASE IN BLOOD SUGAR

In
diabetes,
there
is
production
of
autoantibodies → Destruction of islet of
Langerhans (Beta cell) → Insulin deficiency→
Decreased glucose utilization → Glucose will
remain in the blood (hyperglycemia)
Kidney threshold of sugar: 180 mg/dl
If the kidney threshold of sugar goes beyond 180
mg/dl, glucosuria happens → it will drive fluid
out of the cells to the tubules and excreted out
→ dehydration → stimulation of the thirst centers
→ patient will start drinking but will eventually go
into dehydration
Since there is also no energy in the cell, it is
undergoing cellular starvation
As an alternative fuel, the body will start to
breakdown fats causing the formation of ketone
bodies







Causes

Infection is the most frequent cause

Consider empiric antibiotic therapy

Poor compliance with existing insulin regimen in
diagnosed patient

Caregivers lack of competence
Clinical Manifestation

Polydipsia, polyuria, polyphagia, and weight loss

Nausea/ vomiting

Abdominal pain

Fatigue and body malaise

Fever

Often insidious

Often are absent in toddlers
Physical Examination

Altered mental status without evidence of head
trauma

Tachycardia

Tachypnea or hyperventilation (Kussmaul)

Normal or low blood pressure

Increased CRT/ poor perfusion

Lethargy and weakness

Acetone breath
Laboratory Workup

Serum glucose

Serum K+

ABG

Serum Na, Cl, BUN, creatinine, Mg, Ca, and
phosphates

Glycosylated hemoglobin, ECG

CBC, urinalysis, blood and urine cultures

Misleading Laboratories
SODIUM

Na depressed 1.6 mEq/L per 100 mg% glucose

Corrected Na+ = measured Na + [1.6 meq/L x (glucose100)/100]

Correction is only done if the blood Na is high

Na should be corrected because it depresses 1.6 meq/L
per 100 mg rise of glucose

Example:

Na = 133 meq/L and glucose = 766 mg/dl

766-100 = 666/100 = 6.66 x 1.6 = 10.6 meq/L

Corrected Na = 133 + 10.6 = 143.6 mEq/L
POTASSIUM

Dehydration and volume depletion

Increased aldosterone → Increased sodium absorption
and K wasting

Acidosis leads to flux of K out of cells as H enters cells to
buffer

Serum K usually normal or high, but cells, total body K is low

In a state of metabolic acidosis, K should be high
(hyperkalemic)
URINARY KETONES

Initially, false (-) in dipstick method

Uses
the
nitroprusside
reaction
that
measures
acetoacetate but not beta-hydroxybutyrate (elevated)
WBC

Elevated with shift to the left is just a stress response

Not helpful for diagnosing intercurrent infection since it can
be mistaken as infection

DIAGNOSIS

Combination of hyperglycemia (glucose >300 mg/dl),
ketonemia (ketones strongly positive at > 1:2 dilution of
serum), acidosis (pH <7.30 and HCO3 <15 meq/L),
glucosuria and ketonuria in addition to the clinical
manifestation
Note:

Methylmalonic acidemia (type of organic acidemia) can
be considered a differential diagnosis for diabetic
ketoacidosis

13 months old, F, hyperglycemic, blood sugar:
300 mg/dl), difficulty in breathing, ABG:
metabolic acidosis; bicarbonate: 4; pH: 7,
glucosuria, (+) ketones in the urine

Primary impression was DKA

Other important data: 2 times vomiting, no
diarrhea, no fever, suddenly experienced
Kussmaul breathing with metabolic acidosis,
anion gap: high

HBA1C: normal
TREATMENT

FLUID THERAPY

Generally assume 8.5% dehydration (Milwaukee
protocol)

Provide 20 ml/kg 0.9 NaCl in 1st 1-2 hours to
restore peripheral perfusion

Calculate remainder of replacement after the
loading dose based on 8.5% dehydration and
maintenance for the next 22-23 hours

After initial 0.9% NaCl bolus, continue
rehydration or maintenance with 0.45% NaCl

ELECTROLYTE THERAPY

If initial serum K is <6 mmol/L before rehydration
therapy, incorporate KPO4/K acetate 20-40
meq/L to IVF at initiation of therapy
11
PEDIATRICS 2021


INSULIN



Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
Bicarbonate is rarely indicated

Never
give
by
IV
push
→
hypokalemia

May give 1-2 meq/kg or 80 mmol/m2
body

Surface in 2 hours if severe metabolic
acidosis is present (if pH is <7.0)



0.1 “u”/kg/hr (regular insulin) as a continuous
infusion

How to calculate: 50 u of regular
insulin to 500 cc of normal saline

Then, let this run in patient weight

Example: If the patient is
50 kg, then you run at
50cc per hour

This will come out 2.1
u/kg/hr
Started immediately at the time of initial fluid
expansion
In the postacidotic phase, SQ injection of fast
acting insulin at 0.1-0.25 “u”/kg/q 6-8 hours
before meals with simultaneous monitoring of
blood glucose and adjustment of the insulin
dose for 1-2 days

Example: Serum CO2 is more than 15
and pH is more than 7.25 → switch
the patient to insulin subcutaneous
injection

Intermediate-acting (Humulin N and Humulin L) - 1½ to 2
hours after SQ injection; peak effect: less than Humalog
and Regular insulin; Intervals: 12 hours
Humalog mix 75/25 - pre-mixed; Humalog is 25% and the
rest is protaminized/ intermediate, which is 75%

10 units = 2.5 units of Humalog + 7.5 units of
intermediate
Humulin 70/30 - Regular insulin + intermediate insulin

10 units = 3 units regular insulin + 7 units
intermediate insulin
Humulin 50/50 - Regular insulin + intermediate insulin

10 units = 5 units regular insulin + 5 units
intermediate insulin
MONITORING

Vital signs

CBS, Serum K

Urine output

Neurologic statis (Glasgow coma score)

ECG monitoring

Nursing personnel must have a clear guideline when to
refer

Mannitol at bedside for the 1st 36 hours
COMPLICATIONS

HYPOGLYCEMIA

Increased sensitivity to exogenous insulin and
insufficient serum glucose to metabolize

Rx: 5-10% dextrose to IVF when CBS = <250 mg.dl

PERSISTENT ACIDOSIS

Persistence of HCO3 value of <10 mmol/L after
8-10 hours of treatment

Usual cause: Inadequate insulin effect

HYPOKALEMIA

As result of K reentering the cells → fall in the
extracellular K

Arrythmia can also happen in this

Rx: Incorporate KPO4/K acetate 20-60 meq/L to
IVF especially if initial serum K is <3mmol/L

MUCOR INFECTION

Rare

Frequently fatal

CEREBRAL EDEMA

Most serious and frequent complication (0.7-1%)

Occurs about 6-12 hours after initiation of
therapy, rarely after 22 hours

Causes: multifactorial

Too rapid infusion of fluids and
electrolytes

Over
and
overly
aggressive
correction
of
acidosis
or
hyperglycemia

Manifestation: Persistent headache, evidence
of increasing ICP, altered mental status

Treatment:

Fluid restriction (2/3 maintenance)

Intubate
and
hyperventilation
(PaCO2 of 25-30)

Mannitol infusion (1-2 g/kg) over 2030 mins

Elevate head of the bed to 30
degrees

Head CT scan (initially normal)

Dexamethasone no proven role
Time of Activity of Human Insulins

Humalog - rapid acting; 5-10 mins after SQ injection; peak
effect: 2 hours: duration 4 hours

Regular insulin - 30-60 minsafter SQ injection; peak effect: 24 hours; gone in 6-8 hours
12
PEDIATRICS 2021
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
TRANS-OUT TO WARD

In our patient, the total insulin dose: 15-30 units

AM - 20 units (2/3):

5 u of Humulin R

15 u of Humulin N

PM - 10 units (1/3):

5 u of Humulin R

5 u of Humulin N
SURVIVAL SKILLS

The new rules of life

Daily glucose monitoring

Continuous glucose monitor

Measures every 5 minutes for 72 hours

Helpful in detecting asymptomatic
nocturnal hypoglycemia

Expensive

Use of glucometer

FBS of 80 - 140mg/dl

Glycosylated hemoglobin

Reflects the average blood glucose
concentration of the preceding 2-3
months (6-8.5%)

Use of logbook to log in the daily CBS result

Daily insulin injection

Tough reality

Patient or parent is now responsible
for giving the proper amount of
insulin

Avoid hypoglycemia (limitation)

Diet modification

Sick-day rules

NEVER OMIT INSULIN
OUTPATIENT FOLLOW-UP

Follow-up at the clinic every 3 months

HbA1C every 3 months

Yearly laboratories:

Urine microalbumin

Thyroid functions

Lipid panel

Ophthalmologic exam

Pitfalls:

Depression and anxiety

20-26% of adolescents

Nonadherence

Eating disorders

1-6.9% of female patients

Fear of self

Injecting and self-testing
PREVENTION

Good physician-patient relationship

Noncompliance (insulin omission)

Inappropriate intervention

Sick day rules need to be understood and
followed

Comprehensive diabetes health care and education for
newly diagnosed and diagnosed patients since 50% of
DKA admissions are known persons with diabetes

Genetic and immunologic screening of high-risk children
Congenital Adrenal Hyperplasia (CAH)









You have to know this pathway to understand the
pathophysiology
21-hydroxylase - most common enzyme deficiency in CAH;
(90%)
11B-hydroxylase - 2nd most common
17-a hydroxylase - 3rd most common
Non-classical CAH - late onset; no problem at birth;
hyperandrogenism after birth, no salt wasting
Classical CAH - problem at birth;

Types:

Salt wasting (aldosterone is low; Na-K
hyponatremia and hyperkalemia)

Simple virilizing
Adrenal is situated on top of kidney
Cortisol hypothalamo-pituitary area regulated
ACTH - stimulus to adrenal gland to secrete cortisol
13
PEDIATRICS 2021



Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
There will be a shift into the androgen production
(testosterone) → formation of increased testosterone
Term baby, F, 2 days old, 17-hydroxyprogesterone elevated
(>14 nmol per L), big girl with normal female external
genitalia

FALSE POSITIVE RESULT (this could be due to
stress, prematurity)

Ambiguity should have been seen
Term baby, M, 2 days old, 17-hydroxyprogesterone
elevated (>14 nmol per L), CAH (+) in newborn, normal
male external genitalia

THIS BABY HAS SUSPECTED CAH
NORMAL SEXUAL DIFFERENTIATION
This happens during the 1st trimester of life
FOR MALES:






Primodial gonads (has not differentiated yet), with the
presence of SRY gene , will form into the testis
2 components of testis:

Seminiferous tubules - produce the AMH

Interstitial cell of Leydig
If there is disintegration of the Mullerian duct, there is no
formation of the uterus and fallopian tube
Testosterone will be converted to dihydrotestosterone by 5alpha-reductase enzyme to form the external features of
male external genitalia
Increased male hormones in utero → formation of external
genitalia
At 6 weeks gestation, males and females are the same (no
definite sex organs)

Labia majora form into the scrotum

Labia minora form into the ventral surface of the
phallus

Clitoris enlarge into penis

Genital tubercule form into glans penis



Weight: 2150 g (<10th); head circumference 29.5 cm
(<10th); length 47 cm (>10th); SGA
Routine newborn care done
Dark-skinned
Physical Examination

Genitalia: hyperpigmented; 2 cm; penis-like structure;
scrotum-like labia majora; (+) vaginal opening; (+) urethral
meatus; no gonads palpated (this finding is very important
because if gonads are palpated, you cannot say that this
is a case of CAH due to 21-hydroxylase deficiency)
Note:

A genotypically male (destined to be male) with CAH due
21-hydroxylase deficiency → 17-hydroxyprogesterone
increases → increase androstenedione and testosterone in
the 1st trimester → external male genitalia formation

Labia majora form into the scrotum

Labia minora form into the ventral surface of the
phallus

Clitoris enlarge into penis

Genital tubercule form into glans penis

A genotypically male (destined to be male) with CAH due
21-hydroxylase deficiency will not have an ambiguous
genitalia, instead he will have a dark-skin, which makes
diagnosis very difficult.
CLINICAL AND LABORATORY FEATURES OF VARIOUS DISORDERS
OF ADRENAL STEROIDOGENESIS
FOR FEMALES:



For fetuses destined to be females
Formation of ovary at 10 weeks gestation
Ovaries contain granulosa and theca cells; granulosa cells
stimulated by FSH form estrogen
CAH CASE
History Of Present Illness

Hospital delivery via normal spontaneous delivery (NSD), full
term AS 9,10
14
PEDIATRICS 2021
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
Note:

Non-classical CAH/ late onset - no manifestations at birth


COMPARISON OF CLASSICAL AND
HYDROXYLASE DEFICIENCY
Feature
CLASSICAL
Disease frequency
1: 14,000
Prenatal virilization
Postnatal virilization
Salt wasting
17-hydroxyprogesterone
levels
after
adrenocorticotropic
hormone challenge
Genotype of CYP21
Common mutation:
Simple virilizing
Salt-wasting
NON-CLASSICAL
Females
Males and females
60-75% cases
Extreme elevation
(>20,000 mg/dl)
Severe
allele/
severe
allele
occasionally
severe/ mild
I172N
Intron 2,A →G
21-
NONCLASSICAL
1:100
all
Caucasians
1:27 Ashkenazi
Jews
No
Variable
No
Moderate
elevation
(2000-15,000
mg/dl)
Mild allele/mild
allele
mild
allele/ severe
allele
V281L
P30L
P4538
Deletion
Lg Conversion
Intron 2,A →G
Exon 3, -8 bp
Codons 234-238
Q318→
Stop
codon
R356W
For a normal term infant the 17-HP level should not be
more than 40 nmol/L
For a premature infant the 17-HP level should not be more
than 50 nmol/L
MEAN VALUES OF 17-HP BY BIRTH WEIGHT

The lower the birthweight, the
hydroxyprogesterone level in nmol/L
higher
is
the
17-
ALGORITHM DEPICTING EVALUATION OF INFANTS WITH POSITIVE
NEWBORN SCREEN
CLINICAL SPECTRUM OF 21-HYDROXYLASE DEFICIENCY
PERCENTILE VALUES OF 17-HP BY GESTATIONAL AGE



The more premature the infant, the higher is the 17hydroxyprogesterone level in nmol/L

When mother is pregnant and with a CAH child,
dexamethasone is given since chromosomal testing
cannot be done
With chorionic villus sampling (9 - 11 weeks AOG):

If
genotypically
female
continue
dexamethasone

If genotypically male - stop dexamethasone
Amniocentesis is done during 15- 18 weeks AOG:

If
genotypically
female
continue
dexamethasone until term to avoid ambiguous
genitalia
15
PEDIATRICS 2021

Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
If genotypically male - stop dexamethasone
FLOWCHART FOR PRENATAL DECISIONS OF 21-HYDROXYLASE
DEFICIENCY
PRENATAL TREATMENT WITH DEXAMETHASONE

Prevent or reduce virilization in 75% of cases

No
fetal
congenital
malformation
related
to
dexamethasone has been found

Long term follow up of CAH affected or unaffected
children shows to be developing normally
GLUCOCORTICOID DOSE EQUIVALENCIES



In CAH due to 21-hydroxylase deficiency, 2 hormones are
affected, cortisol and aldosterone (salt-wasting form)
When giving hydrocortisone, the physiological dose is 1015mg/m2/day

Calculated surface area (m2) x 10-15 mg =
dosage for the whole day

Since this is short-acting, you divide the dosage
by 3 or 4
Prednisone is intermediate acting

Potency is 4-5x that of hydrocortisone
THYROID DISORDERS IN INFANCY

Hypothyroidism

Acquired

Autoimmune dysfunction causing the
thyroid gland to enlarge causing
goiter

Monitor thyroid levels

Congenital

Detected by newborn screening test

They do not present with goiter

Most
common
cause:
Thyroid
dysgenesis

Patients
with
true
congenital
hypothyroidism requires to be treated
for his or her whole life

Hyperthyroidism

Acquired hyperthyroidism

Graves’ disease

Exophthalmos; voracious
appetite (huge appetite);
slight increase in BP; may
not gain weight; wide
pulse pressure; warm to
touch; sweating

TSH suppressed

Congenital hyperthyroidism

Rare

May
have
thyroid-stimulating
immunoglobulin transferred from the
mother’s circulation to the baby

If the baby’s heart rate is very high,
consider giving methimazole

3 modes of approach:

Give
medications
(methimazole,
thiamazole)

Surgical

Radioactive iodine (depend on age;
patient should not be pregnant for 6
months)

After undergoing thyroidectomy or radioactive
iodine procedures, monitor the patient because
there is a possibility that the patient will go into
hypothyroidism and may need levothyroxine for
life

Neoplasm

Solitary neoplasm: red flag for malignancy need thyroid ultrasound → do FNAB → surgery
GUIDELINES FOR MANAGING THE PERIOPERATIVE CAH PATIENT



In state of stress or surgery, physiological doses is not
applicable
If patient is with fever, physiological dose is increased to 3fold depending on how many times per day
If stress or illness is gone, the patient may return to his or her
physiological dose
16
PEDIATRICS 2021
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
Puberty


Refers to the bodily changes of sexual maturation by which
a child’s body becomes an adult body capable of
reproduction
A process of physical changes rather than psychosocial
and cultural aspects of adolescent development
AGE OF PUBERTY IN GIRLS

The mean age of Tanner stage
development:
Tanner stage
2
mean age
White girls
10.4 years
Black girls
9.5 years
Mexican-American
9.8 years
girls

2
and
5
breast
Tanner
stage
mean age
15.2 years
13.5 years
14.7 years
5
BREAST DEVELOPMENT
TANNER
DESCRIPTION
STAGE
1
Prepubertal
2
A firm, lump under the center of the areola(e) of
one or both breasts
3
The swelling has begun on both sides softened, and
can be felt extending beyond the edges of the
areolae
4
The breasts are approaching mature size and
shape, with areolae and papillae forming a
secondary mound
5
The mound disappears into the contour of the
mature breast
Range of beginning of thelarche: 8-13 years old
TERMINOLOGY

Gonadarche

Refers to an increase in the activity of the
hypothalamic-pituitary ovarian (HPO) axis
during puberty

Thelarche

Refers to the onset of breast development

Menarche

First menstrual period

Adrenarche (Pubarche)

Refers to the onset of sexual hair growth

Primarily by the adrenal androgen
PUBIC HAIR IN GIRLS
TANNER
STAGE
1
Prepubertal
2
Pubic hairs are usually visible first along the labia
3
Hairs are too numerous to count and appear on the
mons as well
4
The hairs densely fill the “pubic triangle”
5
Hairs distributed as an inverse triangle; spread of
hairs to medial surface of the thighs
Two types of hair:

Vellus hair - not testosterone mediated; short, fine hair,
almost invisible hair

Terminal hair - due to testosterone effect; course and curly;
true pubic hair



Note:

The 1st gonadotropin developed or secreted is FSH

FSH stimulate -- Estradiol affects breast enlargement

FSH stimulate the seminiferous tubules (80%) - testicular
enlargement

LH - leydig cells to produce testosterone - enlarge the follic
size
Girls
PHYSICAL CHANGES OF PUBERTY IN GIRLS

Breast development

Pubic hair

Height growth

Vagina, uterus, ovaries

Menstruation and fertility

Pelvis shape, fat distribution, and body composition

Body odor, skin changes, and acne
Female: estrogen ; small amount of testosterone
Too much testosterone can lead to hirsutism, increased
acne, baldness, irregular menstruation, and fertility
problems
Male: testosterone ; small amount of estrogen
HEIGHT GROWTH IN GIRLS

Tanner stage 2-3

The estrogen-induced pubertal growth spurt in girls begins
at the same time the earliest breast changes begin

The rate of growth reaches a peak velocity midway
between thelarche and menarche

In the 2 years following menarche, most girls grow about 5
cm before growth ceases at maximal adult height
Note:

GnRH analog - used to delay puberty
VAGINA, UTERUS, OVARIES

The mucosal surface of the vagina becomes thicker and a
duller pink in color

Whitish secretions (physiologic leukorrhea)

The uterus and ovaries increases in size
Prepubertal and Pubertal
17
PEDIATRICS 2021
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
MENSTRUATION AND FERTILITY

The onset of menarche is usually about 2 years after
thelarche

Menses are not always regular and monthly in the 1st 2
years after menarche

Ovulation is necessary for fertility, and may or may not
accompany the earliest menses
PELVIC SHAPE, FAT DISTRIBUTION, AND BODY COMPOSITION

In response to rising levels of estrogen, the lower half of the
pelvis widens

Fat tissue increases to a greater percentage of the body
composition than in males

The fat goes to the breasts, hips, thighs, and buttocks
BODY ODOR, SKIN CHANGES, AND ACNE

Raising levels of androgens can change the fatty acid
composition of perspiration

Androgens also increase secretion of sebum from the skin.
This change increases the susceptibility to acne

Pubic hair in the inguinal area + penile enlargement +
testicular volume: 20cc = peak of growth spurt
MALE MUSCULATURE AND BODY SHAPE

Adult men have heavier bones and nearly twice as much
skeletal muscle

This is due to the androgen and testosterone

The muscle develops mainly during the later stages of
puberty, and muscle growth can continue even after a
male is biologically adult
BODY ODOR, SKIN CHANGES, ACNE

Rising levels of androgens can change the fatty acid
composition of perspiration, resulting in a more “adult”
body odor

Another androgen effect is increase secretions of sebum
from the skin and resultant variable amounts of acne
Note:

If there is too much acne, think of hyperandrogenism
especially in females
Boys
TESTICULAR SIZE, FUNCTION, AND FERTILITY

Testicular enlargement is the 1st physical manifestation of
puberty in males

The testes have 2 primary functions:

To produce hormones (testosterone)

To produce sperm
GENITALIA IN BOYS

Rising levels of testosterone promote growth of the penis
and scrotum

Average adult penis size 10-16 cm in length

Erections and orgasm become much more common
during puberty, accompanied by a markedly increased
libido

Ejaculation becomes possible early in puberty

Emission of seminal fluids may occur spontaneously during
sleep (Wet dream)

Stage 3 or more: penile enlargement and scrotal
enlargement is present
PUBIC HAIR IN BOYS
TANNER
Description
STAGE
1
Prepubertal
2
The 1st few pubic hairs are usually first visible at te
dorsal base of the penis
3
The hairs are too numerous to count at the mons
4
The pubic hair densely fill the “pubic triangle”
5
Spread of pubic hair to the thighs and upward
towards the umbilicus
Note:

If you observe spread of pubic hair to the thighs and
upward towards the umbilicus in females, think of
hyperandrogenism (characterized by high levels of
androgens in girls)
BODY AND FACIAL HAIR IN BOYS

Other areas of skin which respond to androgens develop
heavier hair in roughly the following sequence:

Axillary hair

Perianal hair

Upper lip hair

Preauricular hair

Periareolar hair

The rest of the beard area
Note:

For boys, the growth acceleration go slowly and last longer

Growth begins to accelerate a year after the signs of
testicular enlargement

Tanner stage 3 - start of peak height velocity of boys

Tanner stage 4 - peak growth spurt in boys
Note:

If a girl had her menarche at 10, you would assume that
she started puberty at 8

Remember, this:
��� �� �������� − � = ��� �� ����� �� �������
Kisspeptin


KISSPEPTIN

Initiate the puberty by resetting the gonadostat

Critical switch for puberty

Allan E. Herbison et al, Centre for
Neuroendocrinology
and
Department of Physiology, University
of Otago, Dunedin, New Zealand

The 4th Biennial Scientific Meeting
Asia Pacific Paediatric Endocrine
Society 2006
GPR54 (19p13.3)

Key regulator in the control of puberty

Expressed: hypothalamus, pituitary

Loss of function mutation of GPR54 results in
hypogonadotropic hypogonadism

Regulates GnRH release at hypothalamus
 Pituitary response to GnRH
18
PEDIATRICS 2021





Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
A hormone has a specific receptor site and they will form a
specific complex.
Then, this complex will stimulate the inactive adenylate
cyclase forming cAMP
This cAMP will serve as a 2nd messenger and go inside the
nucleus to initiate the transcription-translation process
forming a biological effect
The receptor sites of peptides or polypeptide hormones are
in the cell membrane
The receptor sites of thyroid or steroid hormones are
intracellularly located

This means that formation of complexes takes
longer compared to cell membrane receptor
sites
ABNORMALITIES OF PUBERTY

Timing of puberty: Wide variation

Girls: 8 - 13 years old

Boys: 9 - 14 years old
Note:

In severe primary hypothyroidism, the thyroid hormone
levels are very low and it will send a passive feedback to
the hypothalamo-pituitary area so it will increase the TRH.
This increase in TRH will stimulate the anterior pituitary to
secrete increased levels of TSH. TSH is composed of alpha
and beta glycoprotein. Its alpha subunit of glycoprotein
share with the LH and FSH, which gives the possibility of a
child going into precocious puberty

Leydig cell tumor will mimic puberty

Ectopic HCG secreting tumor: HCG will act like LH
hormones, which will stimulate the testes to produce
testosterone. As testosterone increases, the phallic size
increases.

GnRH stimulates the anterior pituitary to produce
gonadotropin causing increase FSH and LH release.
CENTRAL/GnRH DEPENDENT
PERIPHERAL/ GnRH INDEPENDENT
STEROID BIOSYNTHETIC PATHWAY IN THE ADRENAL CORTEX
CLASSIFICATION OF PRECOCIOUS PUBERTY
CENTRAL PRECOCIOUS
PERIPHERAL PRECOCIOUS PUBERTY
PUBERTY
GnRH dependent
GnRH independent

More common in girls 
The puberty did not occur

Idiopathic in origin in
because of stimulation of
90% of cases
hypothalamus to produce

Less common in boys
GnRH

Pathology may exist
in 50% of boys
1.
CNS
tumors 1.
Adrenal
(hypothalamic
a)
CAH:
21/
11hamartoma; Glioma
hydroxylase deficiency
[neurofibromatosis])
(males)
2.
Head trauma
b)
Tumor
3.
Infections:
2.
Gonadal (ovary/ testes)
meningitis/
i.
McCune Albright
encephalitis
Syndrome
4.
Hydrocephalus
ii.
Testoxicosis
5.
Severe
primary
(familial
malehypothyroidism
limited precocious
6.
Idiopathic
puberty)
iii.
Tumor - Leydig cell
tumor
iv.
Ectopic
HCG
secreting tumor
3.
Exposure to sex steroids
MCCUNE ALBRIGHT SYNDROME (MAS)

More frequent in females than males

Activating mutation of the GNAS1 gene encoding the
alpha subunit of Gsα

Autonomous hormone production that involves the gonads,
adrenal cortex, thyroid, pituitary gland, and parathyroid
glands

Breast maturation and vaginal bleeding - enlarged ovaries
that secrete estrogen

Features:

Fibrous dysplasia of bone

Peripheral precocious puberty

Cafe au lait spots - irregular borders
Note:

Get the history (e.g. history of exogenous steroids, mother’s
menarche, history of early or precocious puberty in the
family) and physical exam (e.g. height, weight, skin
pigmentations, bone deformities, Tanner staging, testicular
volume)

For girls:

assess for signs of estrogen excess (FSH LH
estradiol);

pelvic imaging to check if the uterus is enlarged;

bone age to determine if it is advanced or not
compared to chronological age;

MRI of the brain - focus on the hypothalamopituitary area, especially for idiopathic causes

For boys:

bone age
19
PEDIATRICS 2021
Source: John S Uy, MD ppt; internet; Nelson’s 21st ed
FSH LH testosterone;
17-hydroxyprogesterone level to make sure you
are not dealing with late onset CAH;

HCG level to check for HCG producing tumors

MRI of the brain - focus on the hypothalamopituitary area

Prevalence of intracraniopathology is
close to 50% in boys
GnRH analog is the current treatment for central
precocious puberty

Too much GnRH analog → downregulation or
hiding of receptor sites → no formation of
complexes → no 2nd messenger formation → no
initiation of transcription-translation process to
form a biologic response

It
causes
pituitary
desensitization
with
compression of gonadotropin secretion
Testolactone is the treatment for peripheral precocious
puberty

A non-selective, irreversible, steroidal aromatase
inhibitor
Sometimes, tamoxifen is given.





20