PEDIATRIC ENDOCRINOLOGY PEDIATRICS II

Wilson Cua, M.D. || 19 May 2022 LT 06 TRANS 04 V.02

I. HYPOTHYROIDISM
NOTES and REMINDERS
1. Contact your section’s TC (see footer) for any trans errata or A. THYROID HORMONE
clarifications ● Thyroid gland
2. The lecturer’s asynchronous videos only serve as a guide for the ○ One of the more important glands of the body, secretes mainly
PPT and highlights of the book. Take note of statements being the thyroid hormone

the exam. These will be marked with . 📌

emphasized and repeated since these will most likely come out in ● Thyroid Hormone

INSERT SPACE FONT SIZE

OUTLINE
💬
○ A single hormone with multiple effects on metabolism; governs
metabolic rate
○ Influences growth and development both mentally and physically
I. Hypothyroidism 1 ○ Increases oxygen consumption, stimulate protein synthesis,
A. Thyroid Hormone 1 influence growth and differentiation, and affect carbohydrate,
B. Hypothyroidism 2 lipid, and vitamin metabolism
C. Congenital Hypothyroidism 2 B. HYPOTHYROIDISM
II. Diabetes 3
A. Incidence 3 ● Most commonly caused by thyroid dysgenesis (85%)
B. Insulin 3 ○ Thyroid dysgenesis:
C. Hormonal Control Of Glucose 3 ■ ⅓ with aplasia
D. Type 1 DM 4 ■ ⅔ with ectopic thyroid tissue (lingual) or hypoplastic
E. Type 2 DM
F. Microvascular Complications Of DM
4
4 down to the back of the sternum
● Other causes:
💬
● Usually located in the midline from the base of the tongue

G. Diagnosis Of DM 4
H. Treatment Of Diabetes 4 ○ Inborn error of thyroxine synthesis and maternal transfer of
I. Diabetic Ketoacidosis 5 TRBAb (thyrotropin-receptor blocking antibody)
J. Nonketotic Hyperosmolar Coma 5 ○ Defective thyroxine synthesis
K. Treatment Of DM 6 ○ Defective iodide transport
L. Prognosis 6 ○ Thyroxine peroxidase defects of organification and coupling
III. Short Stature 7 ○ Defective thyroglobulin synthesis
A. Proportionate Short Stature 7 ○ Defective deiodination
B. Disproportionate Short Stature 7 ○ Defective thyroid hormone transport
IV. Ambiguous Genitalia 7 ○ Thyrotropin receptor-blocking antibody (seen in maternal
A. Normal Sexual Differentiation
B. Female Pseudo-Hermaphroditism
7
8 disease) 📌
autoimmune thyroid disease like Hashimoto’s or Grave’s

■ Babies born to mothers with existing or unknown autoimmune

C. Male Pseudo-Hermaphroditism 8
V. Pituitary Gland
A. Anterior Pituitary Gland
8
8
○
💬
thyroiditis; mothers secrete inhibitory or stimulatory antibodies

Radioiodine administration (pregnant or lactating mothers)

B. Posterior Pituitary Gland 8
C. Disorders Of The Anterior Pituitary Gland 8 ○ Thyrotropin deficiency
D. Disorders Of The Posterior Pituitary Gland 8 ○ Thyrotropin hormone unresponsiveness
VI. Diabetes Insipidus (DI) 9 ○ Thyrotropin-releasing hormone receptor antibody
A. Physiology Of Water Balance 9
B. Approach To Patient With Polyuria, Polydipsia, And
Hypernatremia 9
C. Causes Of Hypernatremia 9
D. Treatment 9
VII. SIADH 10
A. Treatment 10
VIII. Precocious Puberty 10
A. Central Precocious Puberty (CPP) 10
B. Peripheral Precocious Puberty 11
Review Questions 12
References 14

OBJECTIVES
No objectives were provided by the lecturer.
SUMMARY OF TERMINOLOGIES

Concept/Terminology Definition
CAH Congenital Adrenal Hyperplasia
DKA Diabetic Ketoacidosis
DI Diabetes Insipidus
DM Diabetes Mellitus Figure 1. The hypothalamic-pituitary-thyroid axis and known genetic defects
associated with congenital hypothyroidism. Hypothalamus secretes the TRH and
SIADH Syndrome of Inappropriate Antidiuretic the pituitary secretes the TSH. TSH will then stimulate the thyroid gland to
Hormone

PED2 6.04 TG Irigayen, Jacinto, Javier, Ip CORE Abrilla, Gomez, Salazar Page 1 of 21
 need to memorize. 💬
secrete T3 and T4: Note from Doc: Just familiarize yourself with this slide. No and no head control. In picture A, notice the puffy face, dull expression, and
hirsute forehead. Tests revealed a negligible uptake of radioiodine. Osseous
development was that of a newborn. Picture B is four months after treatment,
C. CONGENITAL HYPOTHYROIDISM note the decreased puffiness of the face, decreased hirsutism of the forehead,
and the alert appearance.
Note: During the synch session, Doc said that this section is very important; he
will be getting at least one question from this slide. LAB FINDINGS
● Asymptomatic at birth; transplacental transfer of maternal T4 (33%) 📌
📌
● Low serum level of T4 or free T4
● Diagnosed during newborn screening: Increased TSH and low T4 ● Elevated serum TSH
○ TSH at birth is the screening tool
● Normal serum T3 and is not helpful
○ Infants with Trisomy 21 have a higher incidence of congenital
● Bone aging
hypothyroidism and should be screened in the newborn period
○ Absence of distal femoral epiphysis in newborns
○ It is important to wait for 24 hours before doing the newborn
● X-rays of the skull
adjust to the external environment
during synch)
📌
screening because it is the time needed to allow the infant to
(Note: Emphasized by Doc ○ Show large fontanelles and wide sutures with wormian bones
(intersutural bones)
● Scintigraphy
1:4000-1:5000 💬
● Incidence worldwide: 1:4000. In the Philippines, it is between

○ Girls:Boys ratio of 2:1

○ Normally situated thyroid gland with a normal or avid uptake of
radionuclide indicates a defect in thyroid hormone biosynthesis
○ Can locate the thyroid gland, whether aplastic or in an external
● Most commonly caused by some form of thyroid dysgenesis, of
location
which ectopic thyroid is most frequent
○ Demonstrable by thyroid scan or ultrasound: mass at the back of
● Ultrasound of the thyroid gland
the tongue or middle part of the neck at the hyoid level ● EKG
○ Show low-voltage P and T waves with diminished amplitude of
💬
○ Always request for a thyroid scan if ectopic thyroid is suspected
QRS complexes and suggest poor LV function and pericardial
effusion
MANIFESTATIONS OF CONGENITAL HYPOTHYROIDISM
● Normal appearance at birth
○ Birth weight and birth length are normal
○ Due to the transplacental transmission of maternal thyroid
hormone, which is sufficient enough for the physiologic and

📌
developmental requirement of the fetus.
● Prolonged jaundice is the earliest sign
○ Due to delayed maturation of glucuronide conjugation
● Poor temperature control
● Delayed stooling
● Feeding difficulties, somnolence, lack of interest, choking spells
during nursing
● Large tongue - comes in later
● Constipation
● Umbilical hernia at birth, and large abdomen
● Poor muscle tone
● Sluggish
● Cold, mottled skin
Figure 3. Wormian bones seen on skull x-ray. White arrows depict wormian
DIAGNOSIS bones. Skull x-ray is not routinely performed because of exposing the thyroid
gland to more radiation. It may be used if the thyroid panel test is not available in
● Must be diagnosed early in life before manifestations are evident the area.

mental retardation will occur 📌

○ By the latest 2 months (golden period), otherwise physical and

○ At 3-6 months of age, the clinical features are evident and

permanent
■ Myxedema and cretinism
● EKG

Figure 4. Absent distal femoral epiphysis in a 3-month old infant with

congenital hypothyroidism. The location where the patella is supposed to be is

💬
the secondary ossification center. Thus, the lack of calcification in this area as
seen on x-ray is a presumptive diagnosis of congenital hypothyroidism

Figure 2. Congenital hypothyroidism in an infant 5 months of age. The infant ate TREATMENT OF HYPOTHYROIDISM
poorly in the neonatal period and was constipated. She had persistent nasal
discharge and a large tongue: she was very lethargic and had no social smile
● Treatment of choice: Levothyroxine 📌
PED 6.04 Pediatric Endocrinology Page 2 of 21

○ Lifelong in most cases ● ⅔ are Type 1 Diabetes Mellitus
○ Newborn’s dose is 10-15 µg/kg, higher in severe cases
■ Comes in tablet form which needs to be pulverized then
mixed with water, given preferably before the first milk of the
day
○ Total dose of 37.5-50.0 µg/kg/day for most term infants
○ Should not be mixed with soy protein or iron tablets that will bind
T4 and inhibit absorption
○ Maintenance dose: 4 µg/kg/day in children, 2 µg/kg/day in adults
📌
○ Peaks at two age groups
■ At 5 to 7 years old - commonly due to infections
■ At puberty - due to sex hormones
○ Variations in incidence of T1DM are extreme with the lowest in
0.1/100,000 in China, India and Venezuela; 20/100,000 in
Sweden, Norway, Portugal, Great Britain, Canada and New
Zealand
○ Highest incidence is found in Finland with 50/100,000

thing in the morning on an empty stomach.” 💬

○ “Usually, I recommend that the patient take the medication first
B. INSULIN
● Insulin has a critical role in the storage and retrieval of cellular
OVERTREATMENT/OVERDOSAGE fuel
● Craniosynostosis and temperament effects ● In normal metabolism, there are regular swings in insulin secretion
● Pseudotumor cerebri within the first 4 months of treatment between postprandial, high-insulin anabolic state and the fasted,
low-insulin catabolic state that affect liver, muscle and adipose
PROGNOSIS tissue

💬
● Untreated newborns become severely mentally retarded and
growth stunted (also known as cretins ); diagnosis should be
C. HORMONAL CONTROL OF GLUCOSE

📌
● Insulin (anabolic) - released after meals (Note: Effects of insulin
made within 2 months and treatment started as early as diagnosis is
were emphasized by Doc during the synch session)
made
○ Decreases blood glucose (GLUT4 transporter)
● Treatment if started within a few weeks of life provides an excellent ○ Increases glycogen synthesis
prognosis ○ Decreases gluconeogenesis
○ Lipoprotein lipase (lipogenesis)
○ Stimulates protein synthesis
● Glucagon (catabolic) - released in between meals
○ Increases blood glucose
○ Increases glycogen breakdown in liver and muscle
○ Increases gluconeogenesis in liver
○ Activates hormone-sensitive lipase (lipolysis))
○ Mobilizes triglyceride stores (metabolic acidosis
Table 1. Effects of insulin and glucagon compared based on several
parameters
PROCESS INSULIN GLUCAGON
Pathway Anabolic Catabolic
Time of release After meals Before meals
Blood glucose ↓ ↑

Gluconeogenesis ↓ ↑
Figure 5. 14-year-old untreated congenital hypothyroid. The standing 7-year-old

earlier time 💬
girl is normal (used to have congenital hypothyroidism but was treated at an
).
D. TYPE 1 DM
● Insulin-dependent diabetes mellitus or IDDM 📌
CONCEPT CHECKPOINT ● Previously known as juvenile-onset diabetes
1. T/F. Overtreatment of hypothyroidism with Levothyroxine may ● Beta cell destruction leading to absolute insulin deficiency
manifest as craniosynostosis and temperament effects. ○ Immune-related
2. Manifestations of congenital hypothyroidism include all of the ■ Usually a result of an autoimmune disorder affecting the
following, except: pancreas with subsequent destruction of beta cell
a. Prolonged jaundice ○ Idiopathic; multifactorial (genetic and environmental)
b. Delayed stooling ○ Often associated with ketoacidosis
c. Poor temperature control ● Present with polydipsia, polyuria and polyphagia

📌
d. Altered mental status ○ NOTE: Doc told us to remember that the 3Ps are present in both
T1DM and T2DM

💬
ANSWERS:
● 80 to 90% destruction of islet beta cells for clinical T1DM to appear,
1. T. Overtreatment of hypothyroidism may lead to craniosynostosis and

📌
temperament effects seen as ever-increasing blood glucose levels
2. D. Altered mental status is not a manifestation of congenital hypothyroidism. ● Patients are most often lean or thin, with a history of weight loss
All the others are.
● Has a genetic link, but not clearly Mendelian
○ Genetic susceptibility to Type 1 DM
II. DIABETES
■ General population: 0.3%
● A chronic disease characterized by high blood glucose levels ■ Relatives: 2-50%
caused by defects in insulin secretion, insulin action, or both ■ Twins
● Diagnosis via oral glucose tolerance test ● Monozygotic:30%-50%

synch) 📌
○ Fasting: > 126 mg/dL (Note: Emphasized by Doc during

○ Non-fasting: > 200 mg/dL

● Dizygotic: 6%-10%
■ Siblings 5%
■ Offspring
A. INCIDENCE ● Of affected father 7%
● Of affected mother: 2%
● Prevalence in the USA: 1.7-2.5 cases per 1000 ■ Parents: 3%
● Incidence of 15-17/100,000 per year

PED 6.04 Pediatric Endocrinology Page 3 of 21

 ● Hypoinsulinemia: eventually, the pancreas may cease to produce
insulin
○ 40% end up on insulin therapy

Figure 6. Model of pathogenesis and natural history of T1DM. There is an

improved understanding of the significant roles of genetics, immunology, and
environmental factors in the natural history of T1DM. FPIR - First phase
insulin response; GAD - Glutamic acid decarboxylase autoantibodies; IAA-
Insulin autoantibodies; ICA- Islet cell autoantibodies; ICA 512 - autoantibodies
against the islet tyrosine phosphatase; IVGTT - Intravenous glucose tolerance

💬
test Synch: Overt diabetes usually appears at the later part of the evolution of
diabetes. Just familiarize yourself with this picture.
ONSET - CLINICAL PRESENTATION OF T1DM
Figure 7. The pathogenesis of vascular disease in patients with insulin
● “Classic New-Onset” resistance. NOS- nitric oxide synthase; PARP- poly(ADP ribose) polymerase;
● “Silent Diabetes” SNS- sympathetic nervous system. Doc said to just familiarize ourselves with
this.
● “Diabetic Ketoacidosis
CLASSIC ONSET OF T1DM
● Polydipsia, polyphagia, polyuria, lethargy and weight loss due

📌
to prolonged hyperglycemia
● RBS of over 180 mg/dL exceeds the renal threshold resulting in
glucosuria, osmotic diuresis, dehydration and thirst. (Note:
Emphasized by Doc during synch)
● Have enough preserved beta cell function to avoid metabolic
decompensation and DKA

ketoacidosis 💬
○ Destruction of more than 80% of beta cells will result in

● However over time, weight loss occurs due to prolonged poor

glucose uptake, amino acid conversion by gluconeogenesis and fat
breakdown to fatty acids for ketogenesis
E. TYPE 2 DM
● May range from predominantly insulin resistance to a
predominantly secretory defect with insulin resistance
○ Note from Doc during synch: Initially, all regular type 2 DM starts
off as insulin resistance. But as time goes by, the ability of the
pancreas itself to secrete ever-increasing amount of insulin will
Figure 8. The pathogenesis of glucose intolerance in obese subjects. FFA -
free fatty acids; TG - triglycerides, VLDL - very low density lipoproteins; glu-
glucose; IFG - impaired fasting glucose; IGT - impaired glucose tolerance. Doc
said to just familiarize ourselves with this.
F. DIAGNOSIS OF DM 📌
● Fasting blood sugar: >126 mg/dL

start. 💬
disappear. Once it disappears, this is when insulin deficiency will ○ Serves as enough basis for diagnosis of DM
● Oral glucose tolerance test or random blood sugar: >200 mg/dL

📌
● Previously known as adult-onset diabetes ○ Presumptive diagnosis of DM
● Non-insulin dependent diabetes mellitus G. MICROVASCULAR COMPLICATIONS OF DM
○ 90% of all cases
● Coronary heart disease
■ NOTE: In the 2021 exam, it was noted that the most common
type of DM in the pediatric age group is T1DM
○ Very strong genetic component
📌 ●
●
Peripheral vascular disease
Cerebrovascular disease

📌
○ Obesity is a marker of insulin resistance, 80% of T2DM pediatric ● Hypertension
cases are obese ● Dyslipidemia
■ Recent significant increase of the incidence rate of T2DM,
H. DIABETIC KETOACIDOSIS
attributed to the increased incidence of obesity

📌
○ Begins gradually so may go undiagnosed for years ● Only seen in T1DM
○ Begins with insulin resistance ● Most feared complication
● Also presents with polydipsia, polyphagia and polyuria (3Ps) ○ Elevated blood glucose
● Hyperglycemic hyperosmolar syndrome ○ (+) Ketones in the urine or blood
○ Presents similarly with DKA ○ (+) Metabolic acidosis on ABG
○ Treatment is the same with DKA ● Occurs in 20 to 40% of children with new-onset diabetes and in
non-compliant patients
CAUSES OF T2DM
● An average healthy 10 year old child consumes about 50% of 2,000
● Hyperinsulinemia: initially caused by a defect in the mechanism of calories as carbohydrate; as that child becomes diabetic, daily water
GLUT4 transporter (sensitivity of cells to insulin) losses may be 5L and 250g of glucose or 50% of average daily

💬
○ GLUT4 transporter: receptor that transports glucose into the cell caloric intake
● Despite compensatory hyperphagia, because unused calories are

💬
○ Defect in GLUT4 usually presents as insulin resistance wherein lost in the urine
no amount of insulin can help glucose get into the cell ● DKA occurs when extremely low insulin levels are reached

PED 6.04 Pediatric Endocrinology Page 4 of 21

● When blood sugar goes above 180 mg/dL or 10 mmol/L , the📌 ● Later persistent diuresis enuresis (due to loss of unused calories in
renal threshold is exceeded leading to glycosuria the urine)
● Osmotic diuresis leads to loss of further fluids, glucose, and ● Polyphagia and weight loss (due to loss of unused calories in the
electrolytes, causing dehydration and a stress response; increased urine)
secretion of epinephrine, cortisol, growth hormone, and glucagon ● Keto acidosis: nausea, vomiting, abdominal discomfort, dehydration;
● Increased lipolysis and impaired lipid synthesis rapid, heavy breathing (Kussmaul’s)
○ Increased plasma concentrations of total lipids, cholesterol, ● Diminished neurocognitive function, later coma
triglycerides and free fatty acids
TREATMENT
cause of ketoacidosis 💬
○ Increased lipolysis will generate ton load of ketones → main
● Hydration

fuel (basis of the ketogenic diet 💬

● In the absence of glucose in the cell, fatty acids become the primary
). However, due to
overcompensation of free fatty acid production, there will be
● Insulin replacement (low insulin → low blood glucose level)
J. NONKETOTIC HYPEROSMOLAR COMA
excessive keto acids
○ Metabolic acidosis (diabetic ketoacidosis or DKA)
●
●
●
Seen in T2DM 💬
Also known as hyperglycemic hyperosmolar syndrome

Severe hyperglycemia with a blood glucose level of > 800 mg/dL

○ Compensatory hyperventilation (Kussmaul’s respiration) with
fruity odor (acetone) ● Clinical manifestations
PATHOGENESIS ○ Absent or slight ketosis
○ Nonketotic acidosis
Note: The following section is included in the PPT but was not discussed. ○ Severe dehydration

💬
● Excessive glucose production coupled with reduced glucose ○ Depressed sensorium or frank coma
utilization raises serum glucose. This produces an osmotic diuresis, ○ Neurologic signs (may be misleading ):
with loss of fluids and electrolytes, dehydration and activation of the ■ Seizures, hyperthermia, hemiparesis and positive Babinski
renin-angiotensin-aldosterone axis with accelerated potassium loss. sign
If glucose elevation and dehydration are severe and persists for ● Treatment
several hours, cerebral edema may occur ○ Rapid volume repletion and very slow correction of hyperosmolar
● Increased catabolic processes result in cellular losses of sodium, state (same as in DKA)
potassium, and phosphate
K. TREATMENT OF DM
● Increased release of free fatty acids from peripheral fat stores
supplies substrates for hepatic keto acid production. When keto GOALS OF TREATMENT
acids accumulate, buffer systems are depleted and metabolic
acidosis ensues.
● Maintain blood glucose within normal levels

CLINICAL MANIFESTATIONS
●
●
●
Avoid hypoglycemia
Avoid DKA (for T1DM 💬 )
Avoid hyperosmolar hyperglycemic coma in T2DM 💬
Note: The following section is included in the PPT but was not discussed.
● Abdominal discomfort, nausea, vomiting, weakness, dehydration ● Keep lipid levels within normal levels
○ Later progressing to Kussmaul’s breathing (deep, heavy, rapid), ● Prevent or delay complications
fruity breath odor (acetone), diminished neurocognitive function, ● Prolong life and quality of life
and possible coma
● Large amount of ketonuria, an increased anion gap, a decreased GENERAL MANAGEMENT
ion gap, a decreased serum bicarbonate (or total CO2), and pH, and ● Insulin
an elevated effective serum osmolality, indicating hypertonic ● Nutritional management
dehydration ○ Total caloric intake based on age, level of activity, and
developmental stage
○ Cultural differences in diet should be taken into consideration
○ Caloric mix: 55% carbohydrate (70% of which should be complex
carbohydrates), 30% fat and 15% protein
● Physical activity should never be discouraged
● Monitoring
○ Self-monitoring of blood glucose and serum HbA1c

the lifespan of RBCs 💬

■ HbA1c is done every 3 months because it is dependent on

○ Anticipatory guidance and monitoring for long-term complications

in adolescence and adulthood such as retinopathy, nephropathy,
neuropathy (See Table 4)
● Future treatment (not yet available)
○ For the promotion of beta cell proliferation and neogenesis
■ Islet cell transplantation
■ Stem cell therapy
■ Gene therapy
■ Drug therapy
T1DM TREATMENT
● Blood glucose monitoring
Figure 9. Pathogenesis of DKA. This figure outlines the pathophysiology of
insulin deficiency leading to hyperglycemia, hyperketonemia, dehydration and
● Glycosylated hemoglobin
● Primary mode of treatment: insulin regimen 💬
CLINICAL MANIFESTATIONS
acidosis.
day 💬
○ Dependent on metabolic status of patient, usually done twice a

T2DM TREATMENT
💬
● Initially intermittent polyuria and nocturia
● Initial treatment: lifestyle changes
PED 6.04 Pediatric Endocrinology Page 5 of 21
● Oral hypoglycemic agents (primary mode of treatment until such Table 4. Screening guidelines for long-term complications

💬
time that the pancreas and beta cells can no longer sustain the When to Frequency Preferred Other Potential
commence method of screening intervention

○ Start with Metformin 💬

needs of the body; that is when we add insulin to the regimen

○ Insulin secretagogues: sulfonylureas

)
Retinopathy
screening
After 5 years 1-2 yearly
screening
Fundal
methods
Fluorescein Improved
duration in photography angiography glycemic
○ Insulin sensitizers: thiazolidinediones (Avandia) prepubertal Mydriatic control, laser
○ Glucose inhibitors: biguanides (Glucophage) children, after ophthalmosc therapy
2 years in opy
● Insulin pubertal
● Combined therapies children
○ Combination of OHA’s Nephropathy After 5 years Annually Overnight 24-h Improved
○ OHA and insulin
💬
duration in timed urine excretion of glycemic
prepubertal excretion of albumin, control, blood
● Insulin injection is not needed at the onset
children, after albumin urinary pressure
DIET 2 years in albumin/creat control, ACE
pubertal inine ratio inhibitors
children
● Weight loss
● Hypocaloric diet Neuropathy Unclear Unclear Physical Nerve Improved
examination conduction, glycemic
● The exchange diet thermal and control
● Carbohydrate counting vibration
● Glycemic index and load threshold,
pupillometry,
cardiovascula
r reflexes

Macrovascula After age 2 Every 5 years Lipids Blood Statins for

r disease pressure hyperlipidemi
a, blood
pressure
control

Thyroid At diagnosis Every 2-3 TSH Thyroid Thyroxine

disease years peroxidase
antibody

Celiac Tissue Antigliadin Gluten-free

disease transglutamin antibodies diet
ase,
endomysial
antibody

NOTE: The original image from the PPT can be found in the appendix.
L. PROGNOSIS

poorly controlled 💬
● Average lifespan of a diabetic is 10 years less than non-diabetic if

● Puberty may be delayed and final height may be less than genetic
potential though still within normal range

CONCEPT CHECKPOINT
3. T/F. A random blood glucose result of 210 mg/dL is considered
Figure 10. The effects of low and elevated blood glucose levels to be sufficient basis for diagnosing DM.
4. Diabetic ketoacidosis has the following parameters except:
Table 2. Blood glucose values at different times of the day
a. Metabolic acidosis
TIME OF DAY NORMAL TARGET ACTION b. Elevated blood glucose
GOAL SUGGESTED c. Hyperlipidemia
Fasting or preprandial <110 80-120, <100 <80 or >140 d. Ketones in urine or blood
(mg/dL) 5. What is the most common DM type in the pediatric age group?
a. Type 2 DM
After meals (mg/dL) <140 b. Type 1 DM
Bedtime (mg/dL) <120 100-140 <100 or >160
ANSWERS:
Hemoglobin A1C <6% <7%, <6.5% >8% 3. F. RBS of > 210 mg/dL is only presumptive of DM. FBS results of > 126 mg/dL is
considered as enough basis for diagnosing DM.

diagnosis of diabetes 💬
Note: Anything that exceeds the normal values is already a presumptive 4. C. Hyperlipidemia. DKA lab parameters include elevated blood glucose, ketones in urine
or blood and metabolic acidosis.
5. B. T1DM is the most common DM in the pediatric age group.
Table 3. Target pre-meal and 30-day average blood glucose ranges and the
corresponding hemoglobin A 1c for each age group
III. SHORT STATURE
Age group (Yr) Target 30-day Target HBA1c
pre-meal BG average BG ● Subnormal height relative to other children of the same gender and
range range age, taking family height into consideration
(mg/dL) ● Criteria: height below 1st percentile for age and sex or height
<5 100-200 180-250 7.5-9.0 >2SD below sex-adjusted mid-parent height [Nelson, 21st ed]
● Normal variants:
5-11 80-150 150-200 6.5-8.0 ○ Constitutional delay of growth and adolescence
12-15 80-130 120-180 6.0-7.5 ○ Familial or genetic short stature
A. PATHOLOGIC CAUSES OF PROPORTIONATE SHORT STATURE
16-18 70-120 100-150 5.5-7.0
NOTE: In our laboratory, the nondiabetic reference range for HbA1c is 4.5 to 5.7% INCREASED WEIGHT:HEIGHT RATIO
(95% confidence interval)
● Due to the following endocrinopathies:
PED 6.04 Pediatric Endocrinology Page 6 of 21
 ○ GH deficiency
○ GH insensitivity
○ Hypothyroidism
○ Glucocorticoid excess
DECREASED or NORMAL WEIGHT: HEIGHT RATIO
● Inadequate calories
○ Starvation, anorexia nervosa, poorly controlled diabetes mellitus
○ GI pathologies: malabsorption, inflammatory bowel syndrome,
celiac disease
● Renal disease
○ Renal tubular acidosis, renal failure, nephrogenic diabetes
insipidus
● Chronic disease
○ Cardia, renal, pulmonary, liver, chronic infections, AIDS

💬
○ Any chronic disease → slowing down of growth process →
proportionately short person
B. PATHOLOGIC CAUSES OF DISPROPORTIONATE SHORT STATURE
● Skeletal dysplasia
○ Achondroplasia
○ Hypochondroplasia Figure 11b. Schematic demonstration of height and weight growth curves in
● Metabolic bone disease various conditions associated with short stature.
○ Rickets ● Predicted adult height based on parents’ heights [2021]
● Spinal Disorders ○ Boys = (Father’s hgt + Mother’s hgt + 13 cm [or 5 in]) / 2
○ Irradiation ○ Girls = (Father’s hgt + Mother’s hgt - 13 cm [or 5 in]) / 2
○ Congenital hemivertebrae
○ Spondylodysplasias CONCEPT CHECKPOINT
● Hypogonadism (after puberty)
○ Usually associated with Turner syndrome 💬 6. What chromosomal abnormality
hypogonadism (after puberty)?
is associated with

📌
● Associated with dysmorphic features: 7. Which is a cause of disproportionate short stature?
○ Chromosomal abnormalities: Trisomy 21, Turner syndrome a. Starvation
○ Specific Syndromes: b. Hypogonadism
■ Fetal alcohol syndrome, Russell-Silver syndrome, Prader Willi c. GH deficiency
syndrome, Noonan, Seckel, De Lange, Primordial dwarfism d. Glucocorticoid excess

ANSWERS:
6. Turner syndrome
7. B. Disproportionate short stature is caused by skeletal dysplasia, metabolic bone
disease, spinal disorders, hypogonadism and chromosomal abnormalities.

IV. AMBIGUOUS GENITALIA

● Diagnostic dilemma for the pediatrician (especially for the female
baby wherein the external cannot be totally identified); emotional
crisis for the family
○ Considered an emergency 💬
○ Do not label sex of baby until determined genetically 💬
■ When you describe the external genitalia, do not use terms
that are gender specific like penis/clitoris. Always use
descriptions like “phallic structure”
○ Evaluation and diagnosis must proceed rapidly in order to
establish the true sex of the baby early on
○ Involves pediatric endocrinology, geneticists, psychiatry and
surgery
○ If you can’t determine genitalia visually, don’t label as boy/girl,
request for karyotype or chromosomal analysis and write “baby
X” because it would be hard to change information in the census
registry [2022]
Table 5. Proposed revised nomenclature
Previous Proposed
Intersex Disorders of sex development (DFD)
Male pseudohermaphrodite, 46, XY DSD
undervirilization of an XY male
Figure 11a. Hypothalamic - Pituitary - Organ Axis.
Regulation of GH secretion and the role of GH, IGF-1 and IGFBP-3 in growth.
Female pseudohermaphrodite, 46, XX DSD
GH secretion is under the control of the neurotransmitters GH-releasing hormone over-virilization of an XX female,
(GHRH) and somatotropin release inhibiting hormone (SRIF), and negative and masculinization of an XX
feedback by GH and IGF-1 occurs at both pituitary and hypothalamic levels. GH female
stimulates both IGF-1 and IGFBP-3 production by the liver, which allows distant True hermaphrodite Ovotesticular DSD
endocrine action of IGF-1. GH also acts directly on the growth plate and
stimulates local IGF-1 production. XX male or XX sex reversal 46, XX testicular DSD
XY sex reversal 46, XY complete gonadal dysgenesis

PED 6.04 Pediatric Endocrinology Page 7 of 21

● Due to under-masculinization of genetic males or virilization of
genetic females
○ Primordial tissues:
■ Wolffian ducts - male
■ Mullerian ducts - female
○ Male pseudohermaphroditism → due to undervirilization of
genitalia
○ Female pseudohermaphroditism → due to virilization of genitalia

📌
● The vast majority of infants with ambiguous genitalia will be
chromosomal females with 21-hydroxylase deficiency
(emphasized by Doc MGA 10X KAYA PLEASE MEMORIZE )
○ 21-hydroxylase deficiency in females
○ 5 alpha-reductase deficiency in males
● Presence of palpable gonads → indicates that the neonate is a
chromosomal male
○ Palpation + confirmation via ultrasound
● Scrotum is formed by the fusion of the labioscrotal folds only during
the first trimester
Figure 12a. Differentiation of internal genitalias. Differentiation of internal organs.
MALES
The Wolffian duct gives rise to the male reproductive system; the Mullerian duct
1. Testicular synthetic defects in male sex hormone (androgen) gives rise to the female reproductive system. [2021] Was just flashed, not discussed
biosynthesis
2. Resistance to those hormones in the target tissue (male
pseudohermaphroditism)
FEMALES
1. Congenital adrenal hyperplasia (CAH), 21-hydroxylase

androgens (female pseudohermaphroditism)

○ Included in newborn screening
📌
deficiency – an adrenal enzyme defect that leads to excess

diagnosis 📌
■ Detect 17-hydroxyprogesterone to screen and confirm the

○ DHEA (dehydroepiandrosterone) will influence the external

development of genitalia more towards the male [2022]
○ Note: The degree of virilization does not correlate well to the
degree of enzyme deficiency, more on DHEA influence
2. Incomplete gonadal dysgenesis – a condition that involves
partial testis determination in the presence of a Y chromosome
A. NORMAL SEXUAL DIFFERENTIATION
● The innate tendency is for the bipotential fetus to develop into a
female
● For the fetus to develop into a male, the following are required: Figure 12b. Differentiation of genitalia proceeding from a common embryonic
1. Testes: determining factor (sex determining region of the Y anlage (foundation of a subsequent development). Testosterone acts at 9-13
chromosome or SRY) and downstream genes weeks (8 wk) of gestation to virilize the bipotential anlage. In the absence of
2. Testicular production of both anti-mullerian hormone testosterone action, the female phenotype develops. [2021] Was just flashed, not
(AMH), also called mullerian-inhibiting substance (MIS) and discussed
testosterone B. FEMALE PSEUDOHERMAPHRODITISM
○ Will suppress further development of mullerian ducts
● Due to virilization of the genitalia
3.
and testosterone
Normal gonadotropin production by hypothalamic-pituitary
axis (during 2nd and 3rd trimester)
CONGENITAL ANDRENAL HYPERPLASIA 📌 [2022[

4. Conversion of testosterone to dihydrotestosterone (DHT) by

● Most common cause of ambiguous genitalia & of 46XX disorders of
5 alpha-reductase sexual development [Nelson 21ed, p.3012]

📌
● Caused by enzyme deficiencies involved in steroid production

5.
📌
○ DHT: influences the external genitalia to develop into
male genitalia; Elevated in CAH (females)
Organ response to androgen
● 21-hydroxylase deficiency
○ Most common enzyme deficiency in CAH
○ No steroids produced → pituitary secretes ACTH to keep
stimulating adrenals to produce steroids → hypertrophy and
excess in androgen production
○ All steroids are blocked off at 21-hydroxylase level →
accumulation of 17-OH progesterone → metabolism shifted
towards production of DHEA (precursor of testosterone, most
potent influencer of external genitalia) → androgenic effect on
female baby
○ ↑ DHEA = ↑ virilization 📌
● Congenital Virilizing Salt-wasting Hyperplasia
○ Classical type of 21-hydroxylase deficient CAH
○ Raw material normally used to produce aldosterone is channeled
to androgen production

PED 6.04 Pediatric Endocrinology Page 8 of 21

 ○ No 21-OH → no aldosterone → no salt & water retention → loss B. MALE PSEUDOHERMAPHRODITISM
of sodium in urine = salt wasting
● Dysmorphic syndrome
○ Limited salt-retaining capabilities and salt-wasting tendency, may
● Defects in testosterone biosynthesis
lead to death due to hyponatremic dehydration (EMERGENCY)
○ Cholesterol desmolase deficiency (20,22-desmolase)
○ ADRENAL
hypoglycemia 📌
CRISIS: Hyponatremia, hyperkalemia,

■ Since cortisol is a glucocorticoid, “gluco-“ it influences glucose

○
○
17 alpha-hydroxylase deficiency
3 beta-hydroxysteroid dehydrogenase deficiency
○ 17,20 lyase (desmolase) deficiency
metabolism
○ 17 beta hydroxysteroid oxidoreductase (ketoreductase)
surfaces, labioscrotal fold, lips 📌
■ Most of the time also have hyperpigmentation in flexor

● Hyperpigmentation of external genitalia in MALE baby may

deficiency
○ Leydig cell hypoplasia or hCG resistance
be the only indicator of CAH, because a male baby will
● Defects in androgen target tissues
never* have ambiguous genitalia since the hormone ○ 5 alpha-reductase deficiency
affected is testosterone
● Note: Doc might have meant male babies with CAH will males 📌
■ Most common cause of pseudohermaphroditism in

○ Androgen insensitivity (testicular feminization)

not have ambiguous genitalia like in females but may have
underdeveloped male external genitalia (e.g. small penis ○ Incomplete resistance
with hypospadias, chordee, and cryptorchidism) ● Persistent mullerian duct syndrome
● Non-classical type of 21-hydroxylase deficient CAH ● Gonadal dysgenesis
○ Milder signs of androgen excess ● Vanishing testes
○ Presents later in life ● Rare and due to the undervirilization of genitalia
● 11-alpha-hydroxylase deficiency
● 3 beta hydroxysteroid dehydrogenase deficiency

Figure 13a. Partial androgen insensitivity (genetic males).

(L) Bifid labioscrotal folds with descended testis. (R) Full photo of an
Figure 12c. Congenital virilizing hyperplasia undervirilized male.
MATERNAL ANDROGENS [2021[

Note: This section was not further elaborated. The following information are from
2021.
● Endogenous: Maternal virilizing/androgen-producing tumors (rare)
● Benign
○ Adrenal adenoma
○ Ovarian tumors, particularly androblastomas & luteomas
● Malignant
○ Metastatic carcinomas (Krukenberg tumors)
○ Sex-cord stromal tumors—granulosa cell and Sertoli-Leydig
tumors
○ Adrenal cortical carcinoma
● Manifestations
○ Maternal
■ Enlargement of her clitoris
■ Acne
■ Deepening voice
■ Decreased lactation
■ Hirsutism
■ Elevated androgens
○ Infant
■ Enlargement of clitoris (varying degrees)
■ Labial fusion
○ Mothers of children w/ unexplained 46,XX DSDs should:
■ Undergo PE
■ Have measurements of plasma testosterone,
dehydroepiandrosterone (DHEA) sulfate, & androstenedione Figure 13b. Algorithm for evaluating infants with ambiguous genitalia
○ Exogenous (Synthetic androgens): Exposure to androgenic
drugs during pregnancy CONCEPT CHECKPOINT
■ Danazol, Progestins (medroxyprogesterone acetate), 8. What is the most common cause of CAH in females?
potassium-sparing diuretics a. 5 alpha-reductase deficiency
■ Greatest number of cases from use of certain progestational b. 11-alpha-hydroxylase deficiency
compounds/progestins for treatment of threatened abortion c. 21-hydroxylase deficiency
● Largely replaced now

PED 6.04 Pediatric Endocrinology Page 9 of 21

 ANSWERS:
the development of DI 📌
■ Craniopharyngioma: most common tumor associated with

○ Others: Intracranial infections, post-radiation, post-craniotomy for

8. C. Most common cause of CAH in females is 21-hydroxylase deficiency.

V. PITUITARY GLAND pituitary and hypothalamic area 💬

other intracranial tumors, trauma, radiotherapy that involves

📌
● Clinical manifestations:
OVERVIEW
○ Manifests as increased loss of free water
● Sometimes called the hypophysis ■ Increased frequency and volume of diluted urine
● Divided into the anterior (adenohypophysis) and posterior lobes
(neurohypophysis)
■ Polyuria and polydipsia
■ High serum osmolality and low urine osmolality
● Hypernatremia
📌
○ Master gland” due to its central role in the hormonal system and
its ability to interpret and respond to a variety of signals [2022] ■ Patients pass out voluminous colorless urine with very low
○ Pituitary gland receives signals from the hypothalamus and
responds by sending pituitary hormones to target glands [2022] access to water 💬
specific gravity to the point that they get dehydrated without

○ Most of those initially diagnosed with idiopathic DI will

○ Several hormones are either secreted or stored [2022]
● Located at the base of the skull in in the sella turcica
● Types of deficiency pituitary gland 💬
subsequently be diagnosed to have a microadenoma in the

💬
○ If there is a deficiency from the endocrine organs, it is called a ■ Serial or annual CT scan to monitor the possible of an
primary deficiency microadenoma

💬
○ If there is a deficiency of any hormone coming from the pituitary ● Treatment:
gland, it is called a secondary deficiency
○ Example:
○ If the patient can drink on their own and thirst centers are not
affected, allow them to have access to free water
○ Vasopressin replacement therapy
💬
■ Thyroid gland problem = Primary hypothyroidism
■ Deficiency in TSH causes hypothyroidism = Secondary ■ Forms: Oral, infectables, or nasal spray
hypothyroidism SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE
A. ANTERIOR PITUITARY GLAND SECRETION (SIADH)
● Adenohypophysis 📌
📌
● Exact opposite of DI

📌
● Considered as a major organ of the endocrine system ○ Excessive secretion or release of vasopressin
● Secretes the following stimulatory hormones:
○
○
Growth hormone (GH)
Thyroid stimulating hormone (TSH)
serum
● Causes:
💬
○ Forcing the kidney to retain so much free water that it dilutes the

○ Adrenocorticotropic hormone (ACTH) ○ Trauma, infections, radiotherapy, metastasis

○ Prolactin (PRL) ○ May be idiopathic
○ Follicle stimulating hormone (FSH) ● Clinical manifestations:
○ Luteinizing hormone (LH) ○ Present with secretion of concentrated urine of low volume (low
○
💬
These are the only stimulatory hormones secreted by the urine output)

📌
anterior pituitary gland ■ Retention of free water
B. POSTERIOR PITUITARY GLAND ■ Low serum osmolality with high urine osmolality
■ Hyponatremia
● Neurohypophysis
Table 6. Major Differences between DI and SIADH
📌
● Main storage site of hormones secreted by nucleus located in the
hypothalamus DI SIADH
○ Arginine vasopressin Vasopressin secretion ↓ ↑
■ Important in the regulation of serum sodium
■ Regulates the excretion or conservation of free water Free water Loss Retention
■ Affects the kidney Serum osmolality HIGH LOW
■ Deficiency will cause Diabetes Insipidus [2022]
○ Oxytocin Urine osmolality LOW HIGH
○ These are stored, not secreted
Serum sodium HYPERnatremia HYPOnatremia
C. DISORDERS OF THE ANTERIOR PITUITARY GLAND
● May involve one or several hormones CONCEPT CHECKPOINT
● The most common cause of hypopituitarism in the pediatric age 9. The following are stimulatory hormones secreted by the anterior
group is craniopharyngioma or adenoma (prolactinoma) pituitary gland, EXCEPT:
○ Craniopharyngioma develops from the persistent remnant of the a. Growth hormone
original connection between Rathke pouch and oral cavity [2022] b. Oxytocin
● Other causes: c. Adrenocorticotropic hormone
○ Trauma d. Prolactin
○ Infections 10. What is the most common tumor associated with the
○ Metastasis development of diabetes insipidus (DI)?
11.T/F. In DI there is LOW serum osmolality while in SIADH there is
D. DISORDERS OF THE POSTERIOR PITUITARY GLAND HIGH serum osmolality.
● Mainly involves the over- or undersecretion of vasopressin
ANSWERS:
DIABETES INSIPIDUS (DI) 9. B. Oxytocin is stored in the posterior pituitary gland, not secreted by the anterior pituitary

● No vasopressin (under-secretion of vasopressin) 📌 gland

10. Craniopharyngioma

💬📌
11. F. DI has HIGH serum osmolality while SIADH has LOW serum osmolality
● Causes:
○ Idiopathic (majority)
NOTE: DOC GAVE THE FOLLOWING TOPICS AT THE END OF THE PPT AS
○ Tumor ADDITIONAL READINGS. THE NEXT SECTIONS ARE TAKEN FROM NELSON
21st Ed. AND THE 2022 TRANS.

PED 6.04 Pediatric Endocrinology Page 10 of 21

 VI. DIABETES INSIPIDUS (DI) ○ Congenital (X-linked recessive: AVP V2 receptor gene
(Nelson 21st ed, Chapter 574) mutations, autosomal recessive or dominant; aquaporin-2 gene
mutations)
● Manifests clinically with polyuria and polydipsia
○ Drug induced (demeclocycline, lithium, cisplatin, methoxyflurane)
● Can result from either vasopressin deficiency (central DI) or
○ Hypercalcemia, hypokalemia
vasopressin insensitivity (nephrogenic DI) at the level of the
○ Infiltrating lesions
kidney
○ Vascular (sickle cell anemia)
A. PHYSIOLOGY OF WATER BALANCE ○ Mechanical (polycystic kidney disease, bilateral ureteral
● Extracellular fluid tonicity is regulated by water intake and excretion obstruction)
● Extracellular volume is regulated by sodium intake and excretion ○ Solute diuresis (glucose, mannitol, sodium, radiocontrast dyes)
● Volume homeostasis is largely regulated by the D. TREATMENT
renin-angiotensin-aldosterone system, with contributions from both
vasopressin and the natriuretic peptide family ● Central Diabetes Insipidus
● Vasopressin ○ Fluid Therapy
○ Principal regulator of tonicity ■ Neonates and young infants are best treated with this due to
○ Synthesized in the paraventricular and supraoptic nuclei of the their requirement for large volumes
hypothalamus ■ Older children are treated with desmopressin
○ Release is stimulated by increases in plasma tonicity and ● Intranasal preparation (onset: 5-10 mins)
significant decreases in intravascular volume and pressure ○ Administered by rhinal tube or nasal spray
■ During hyperosmolality conditions, it is also released before ● Tablets (onset 15-30 mins)
initiation of thirst which allows retention of ingested water ○ 25-300 ug every 8-12 hours
● Vasopressin release is decreased immediately before ● To prevent water intoxication, patients should have at least
water ingestion to prevent hyponatremia 1 hr of urinary breakthrough between doses each day and
be advised to drink only in response to thirst sensation, if
● Atrial natriuretic peptide
present
○ Stimulates natriuresis
■ Aqueous vasopressin
○ Inhibits sodium resorption
● Administered to Central DI of acute onset following
○ Inhibits vasopressin secretion
neurosurgery
○ Regulates relaxation of arterial smooth muscle
● Nephrogenic Diabetes Insipidus
B. APPROACH TO PATIENT WITH POLYURIA, POLYDIPSIA, AND ○ Eliminating the underlying disorder: drugs, hypercalcemia,
HYPERNATREMIA hypokalemia, or ureteral obstruction
● History taking: quantify child’s fluid intake and output and establish ○ Congenital NDI: difficult to treat
voiding pattern, nocturia, and primary or secondary enuresis ○ Main treatment goals:
● Physical examination: establish patient’s hydration status and ■ Ensure adequate intake of calories for growth
search for any evidence of visual and CNS dysfunction ● Foods with highest ratio of caloric content to osmotic load
● If patient has pathologic polyuria or polydipsia, obtain the following: ■ Avoid severe dehydration
○ Serum and urine for osmolality ○ Pharmacologic approach
■ Likely diabetes insipidus if: ■ Usage of thiazide diuretics to decrease overall urine output
● Serum osmolality = >300 mOsm/kg ● May be combined with indomethacin and amiloride to
● Urine osmolality = <300 mOsm/kg reduce polyuria
■ Unlikely diabetes insipidus if: VII. SIADH
● Serum osmolality = <270 mOsm/kg (Nelson 21st ed, Chapter 575)
● Urine osmolality = >600 mOsm/kg
● Syndrome of Inappropriate Antidiuretic Hormone secretion
■ If serum osmolality if <300 mOsm/kg (but >270 mOsm/kg)
○ Characterized by hyponatremia, inappropriately concentrated
AND pathologic polyuria and polydipsia are present:
urine (>100 mOsm/kg), normal or slightly elevated plasma
■ Water deprivation test is needed to establish diabetes
volume, normal-to-high urine sodium, and low serum uric
insipidus as a diagnosis and to differentiate central from
acid
nephrogenic etiologies
○ Uncommon in children
○ Sodium
○ Most commonly caused by excessive administration of
○ Potassium
vasopressin in treating central diabetes insipidus
○ Blood urea nitrogen
● Also causes 2nd phase of triphasic response seen after
○ Creatinine
hypothalamic-pituitary surgery
○ Glucose
○ Calcium
● Nephrogenic SIADH: gain-of-function mutations in V2 vasopressin
○ Specific gravity receptor gene (AVPR2)
○ Glucose determination A. TREATMENT
C. CAUSES OF HYPERNATREMIA ● Oral fluid restriction
● Central Diabetes Insipidus ○ Best treatment for chronic SIADH
○ Congenital (autosomal dominant, arginine vasopressin [AVP] ○ Oral fluid intake is limited to 1,000 mL/m2/24h in addition to full
neurophysin gene mutations) antidiuresis to avoid hyponatremia
○ Drug or toxin induced (ethanol, diphenylhydantoin, snake ■ Full antidiuresis: urine osmolality of 1,000 mOsm/kg
venom) ○ Not advisable for young children as it might not provide the
○ Neoplastic (craniopharyngioma, lymphoma, leukemia) adequate nutrients needed for growth
○ Infectious (meningitis, tuberculosis) ■ Tolvaptan (not FDA-approved for children): may cause initial
○ Autoimmune hyponatremia correction and allow sufficient fluid intake for
○ Trauma (deceleration injury) normal growth
○ Vascular (cerebral hemorrhage or infarction) VIII. PRECOCIOUS PUBERTY
○ Idiopathic (Nelson 21st ed, Chapter 578)
● Nephrogenic Diabetes Insipidus ● Onset of secondary sexual characteristics:
○ Before 8 years old in females
○ Before 9 years old in males
PED 6.04 Pediatric Endocrinology Page 11 of 21
● Classified depending on the primary source of hormonal production:
○ Central
■ Gonadotropin dependent or true
○ Peripheral
■ Gonadotropin independent or precocious pseudopuberty
● See Appendix for summary of disorders of pubertal development
A. CENTRAL PRECOCIOUS PUBERTY (CPP)
● Always isosexual and stems from hypothalamic-pituitary-gonadal
activation with ensuing sex hormone secretion & progressive sexual
maturation
ETIOLOGY
● Organic brain lesions
○ Hypothalamic hamartomas: most common brain lesion causing
CPP
■ Consists of ectopically located neural tissue, within which glial
cells can produce transforming growth factor-α (TGF-α),
which has the potential to activate the GnRH pulse generator
Figure #. Natural course of precocious puberty with central nervous system
lesion. Photographs at 1.5 (A) and 2.5 (B) yr of age. Accelerated growth,
muscular development, osseous maturation, and testicular development were
consistent with the degree of secondary sexual maturation. In early infancy, the
patient began having frequent spells of rapid, purposeless motion; later in life, he
had episodes of uncontrollable laughing with ocular movements. At 7 yr, he
exhibited emotional lability, aggressive behavior, and destructive tendencies.
Although a hypothalamic hamartoma had been suspected, it was not established
until CT scanning became available when the patient was 23 yr of age.
Epiphyses fused at 9 yr of age; final height was 142 cm (56 in). At 24 yr of age,
he developed an embryonal cell carcinoma of the retroperitoneum.
● Following irradiation of the brain
○ Children treated with cranial radiotherapy at a wide range of
doses have increased risk of developing
gonadotropin-dependent precocious puberty
● Syndrome of precocious puberty and hypothyroidism
○ Up to 50% of children with profound, untreated hypothyroidism of
long duration may paradoxically develop precocious puberty
○ Hashimoto thyroiditis frequently causes such forms of
hypothyroidism
CLINICAL MANIFESTATIONS
● Sexual development begin at any age and follows sequence in
normal puberty
● Height, weight, and height velocity are accelerated
○ This results in early closure of the epiphyses
○ ~30% of females and a larger percentage of males achieved a
height below the 5th percentile as adults without treatment.
● Mental development compatible with chronological age
○ Females: initial cycles are usually anovulatory, but pregnancy
has been reported as early as 5.5 y.o.
○ Males: Spermatogenesis as early as 5-6 y.o.
PED 6.04 Pediatric Endocrinology
Figure #. Natural course of idiopathic central precocious puberty. Patient (A)
at 3 11/12, (B) at 5 8/12, and (C) at 8 1/2 yr of age. Breast development and
vaginal bleeding began at 2 1/2 yr of age. Bone age was 7 1/2 yr at 3 11/12 and
14 yr at 8 yr of age. Intelligence and dental age were normal for chronological
age. Growth was completed at 10 yr; ultimate height was 142 cm (56 in). No
effective therapy was available at the time this patient sought medical attention.
LABORATORY FINDINGS
● Sex hormone concentration are usually appropriate for the
stage of puberty
● Elevated LH, FSH in random blood samples
● Pulsatile LH secretion during sleep
● Pubertal levels of testosterone or estradiol
● GnRH or GnRH agonist leads to pubertal LH response or pubertal
levels of estradiol
iMAGING
● Advanced osseous maturation
● Pelvic Ultrasonography: Females - progressive enlargement of
ovaries, fundus, and whole uterus to pubertal size
● MRI: physiologic enlargement of the pituitary gland
TREATMENT
● GnRH agonist therapy
○ Pituitary gonadotropic cells require pulsatile, rather than
continuous, stimulation of the GnRH to maintain the ongoing
release of gonadotropins
○ MOA: GnRH agonists (after a brief period of stimulation)
desensitize the gonadotropic cells of the pituitary to the
stimulatory effect of endogenous GnRH and effectively halt the
progression of central sexual precocity
○ Long-acting formulations is the choice of treatment for CPP
● Treatment results in:
○ Decrease of the growth rate, generally to age-appropriate
values, and an even greater decrease of the rate of osseous
maturation
○ Decrease in serum sex hormone concentrations to prepubertal
levels (testosterone, <10-20 ng/dL in males; estradiol, <5-10
pg/mL in females)
● Except for a reversible decrease in bone density (of uncertain
clinical significance), no serious adverse effects of GnRH analogs
have been reported in children treated for sexualprecocity
B. PERIPHERAL PRECOCIOUS PUBERTY
● NO ACTIVATION of normal hypothalamic-pituitary-gonadal interplay
● Sex characteristics may be isosexual or heterosexual (contrasexual)
● May also induce maturation of the hypothalamic-pituitary-gonadal
axis and trigger the onset of central puberty
○ This mixed type of precocious puberty occurs commonly when
the bone age reaches the pubertal range (10.5-12.5yr) in
conditions such as:
■ Congenital adrenal hyperplasia
■ McCune-Albright syndrome
■ Familial male-limited precocious puberty
Page 12 of 21
GONADOTROPIN-INDEPENDENT INCOMPLETE (PARTIAL) PRECOCITY / VARIATIONS OF PUBERTY
1. Males: ● Isolated development of the breasts in females and growth of sexual
○ Chorionic gonadotropin-secreting Tumor in males hair in both sexes without other signs of puberty are the 2 most
○ Leydig cell tumor in males common forms of incomplete precocity and not unusual in pediatric
○ Familial, Male-lmited precocious puberty (FMPP), testotoxicosis practice.
○ Virilizing congenital adrenal hyperplasia 1. Premature Thelarche
○ Virilizing adrenal tumor ○ Sporadic, transient condition of isolated breast development that
2. Females: most often appears in the first 2 years of life
○ Granulosa cell tumor ○ Growth and osseous maturation are normal or slightly advanced.
○ Follicular cyst ○ Genitalia show no evidence of estrogenic stimulation
○ Feminizing adrenal tumor ○ Breast development may regress after 2 yr, often persists for 3-5
○ Non-classical congenital adrenal hyperplasia yr, and is rarely progressive
3. In both sexes: 2. Premature Adrenarche (Pubarche)
○ McCune-Albright Syndrome ○ Appearance of sexual hair before the 8 y.o. in females or 9 y.o. in
■ Precocious puberty with polyostotic fibrous dysplasia and males without other evidence of maturation
abnormal pigmentation ■ It is an early maturational event of adrenal androgen
○ Primary Hypothyroidism production
CHORIONIC GONADOTROPIN-SECRETING TUMORS ■ It coincides with precocious maturation of the zona reticularis
○ More frequent in females
● Rare cause of precocious puberty in males ■ Females: Hair appears on the mons and labia majora
○ Males: hCG secretion activates LHCG receptors in the Leydig ■ Males: Perineal and scrotal area; axillary hair generally
cells causing testosterone production and virilization with appears later
minimal testicular enlargement ■ Adult-type axillary odor is common
● DO NOT present with precocious puberty in FEMALES; ovarian ■ Affected children are often slightly advanced in height and
production of estradiol cannot occur in the absence of FSH osseous maturation
stimulation 3. Premature Menarche
○ Hepatic Tumors ○ Rare and is a diagnosis of exclusion
○ Intracranial Tumors ■ If there is only isolated vaginal bleeding in the absence of
○ Other locations: (very rare) other secondary sexual characteristics, rule out the following
■ Mediastinum, gonads, adrenal glands first:
● More common causes
McCUNE-ALBRIGHT SYNDROME
○ Vulvovaginitis
● Overview ○ A foreign body (typically associated with malodorous
○ Syndrome of endocrine dysfunction associated with patchy discharge)
cutaneous pigmentation and fibrous dysplasia of the skeletal ○ Sexual abuse
system ● Uncommon causes
○ Missense mutation in GNAS1 gene which results in the ○ Urethral prolapse
activation of receptors: FSH, LH, ACTH, TSH (FLAT) ○ Sarcoma botryoides
● Clinical Manifestations ○ Most only have 1-3 episodes of bleeding; puberty occurs at the
○ Recurrent ovarian cysts usual time, and menstrual cycles are normal.
○ Bouts of estrogen secretion ○ Plasma levels of gonadotropins are low, but estradiol levels may
○ Vaginal bleeding be occasionally elevated
○ Modest breast development ■ Probably due to episodic ovarian estrogen secretion
○ Onset in females is usually 3-6 y.o. associated with ovarian follicular cysts that can be detected
○ Males are less commonly recognized on ultrasound
● Treatment 4. Delayed or Absent Puberty
○ Aromatase inhibitors (letrozole), long-acting analogs of GnRH, ○ Failure of development of any pubertal feature
antiandrogens (not FDA-approved) ■ Females: 13 y.o.
● Extragonadal Manifestations ■ Males: 14 y.o.
○ Hyperthyroidism: usually clinically mild or subclinical only ○ If child has a strong familial pattern of early puberty: lower cutoff
○ Cushing Syndrome: due to bilateral nodular adrenocortical may be appropriate
hyperplasia
○ Gigantism or acromegaly: due to increased secretion of GH CONCEPT CHECKPOINT
○ Fibrous dysplasia of multiple bones 12.T/F. Onset of secondary sexual characteristics before the age of
9 years in females and 8 years in males.
FAMILIAL MALE GONADOTROPIN-INDEPENDENT PRECOCIOUS 13.This is defined as the failure of development of any pubertal
PUBERTY feature by 13 years old in females and 14 years old in males.
a. Premature Thelarche
● Rare, autosomal dominant form of peripheral precocious puberty
b. Premature Adrenarche
● Transmitted from affected males and unaffected female carriers of
c. Premature Menarche
the gene to their male offspring
d. Delayed or Absent Puberty
● Clinical Manifestations
○ Signs of puberty: appear at 2-3 y.o ANSWERS:
○ Testes only slightly enlarged 12.F. Onset of secondary sexual characteristics before the age of 8 years in females and
○ Hormone level changes: Testosterone levels variably elevated, 9 years in males.
13. D. Delayed or Absent Puberty
baseline LH in pubertal levels
○ Sequence of events: similar to McCune-Albright Syndrome
REVIEW QUESTIONS
(MAS) or with congenital adrenal hyperplasia
● Treatment 2022 REVIEW QUESTIONS | Same lecturer
○ Ketoconazole (inhibits C-17,20-lyase and testosterone 1. The most common enzyme deficiency in adrenal hyperplasia
synthesis), antiandrogens, aromatase inhibitors a. 21 hydroxylase
b. 3 beta hydroxylase
PED 6.04 Pediatric Endocrinology Page 13 of 21
 c. 11 beta hydroxylase Diagnosis of CAH
d. 17 alpha hydroxylase -Screening: Newborn screening (done after 24 hrs of life to allow body to
adapt)
2. The most common type of diabetes mellitus in the pediatric 5 A -Confirmatory: Laboratory test for accumulation of
age group 17-hydroxyprogesterone (17-OHP)
a. Type I -together with the request of 17-OHP, also request for serum electrolytes -
Na, and K, and glucose
b. MODY
c. Type II 6 A Anterior pituitary hormones: GH, TSH, ACTH, PRL, FSH, LH
d. Type III 7 A
Congenital hypothyroidism is diagnosed during newborn screening with
3. The most common intracranial lesion causing acquired TSH at birth as the screening tool.

hypopituitarism is 8 A The others fall under Type II diabetes mellitus

a. Craniopharyngioma Patients with congenital hypothyroidism are asymptomatic at birth (normal
9 A
b. Gliomas looking at birth) due to the transplacental transfer of maternal T4 (33%)
c. Metastasis 10 A
Fludrocortisone is the DOC for severe salt wasters and it also acts as a
d. Ependymomas mineralocorticoid in cases of congenital adrenal hyperplasia (CAH)

4. The most common cause of diabetes insipidus in children Thyroid dysgenesis is the most common cause of congenital
11 A hypothyroidism which may be demonstrated by thyroid scan or through
a. Craniopharyngioma
ultrasound
b. Chromosomal abnormalities
c. Trauma
d. Infections 2021 REVIEW QUESTIONS | Same lecturer
5. The confirmatory test for congenital adrenal hyperplasia 1. Drug of choice for hypothyroidism in the local setting?
a. 17 hydroxy progesterone a. Desiccated thyroid tissue
b. 21 hydroxylase b. T3
c. 17 beta hydroxylase c. T4I
d. 21 hydroxy progesterone d. Iodine
6. Which of the following is not an anterior pituitary hormone 2. Congenital hypothyroidism is detected by the Philippine
a. None newborn screen using?
b. PRL a. T3
c. ACTH b. T4
d. FSH c. TSH
e. GH d. TRH
7. Congenital hypothyroidism is detected by the Philippine 3. In central precocious puberty in boys, which secondary
newborn screening using sexual characteristics is the common initial complaint?
a. TSH a. Increase in muscle mass
b. T4 b. Appearance of hormone sensitive hair
c. TRH c. Increase penile length
d. T3 d. Increasing testicular volume to >4mL
8. Type I diabetes mellitus 4. Which of the following is/are/an anterior pituitary hormone?
a. An autoimmune disease a. FSH
b. Usually present with hyperosmolar hyperglycemia coma b. ACTH
c. Associated with obesity c. GH
d. Is non insulin dependent d. PRL
9. Most infants with Congenital hypothyroidism are normal at e. All of the following choices
birth because of 5. Diabetes insipidus is manifested clinically by:
a. Maternal T4 a. Oliguria + polyuria
b. Elevated TRH b. Polyuria + polydipsia
c. Elevated TSH c. Polyuria + hypodipsia
d. Maternal T3 d. Oliguria + hypodipsia
10.Drug of choice in Salt losing congenital adrenal hyperplasia 6. Guillain-Barre syndrome may follow administration of
a. Fludrocortisone vaccines against?
b. Hydrocortisone a. influenzae
c. Prednisone b. Meningococcemia
d. Dexamethasone c. rabies
11. Congenital hypothyroidism is due to d. Any of the following
a. Thyroid dysgenesis 7. The most common cause of diabetes insipidus in children?
b. Hereditary a. craniopharyngioma
c. Familial b. trauma
d. Intrauterine infections c. infections
d. Chromosomal abnormalities
Answer Key:
8. The most common enzyme deficiency in congenital adrenal
Congenital adrenal hyperplasia is the most common cause of ambiguous
hyperplasia?
genitalia and of 46 XX disorders of sexual development. This is usually
caused by 21-hydroxylase deficiency wherein there are no steroids a. 17-alpha hydroxylase
1 A
produced leading to ACTH secretion of the pituitary to keep stimulating the b. 11-beta hydroxylase
adrenals to produce steroids, which leads to hypertrophy and excess in c. 21 hydroxylase
androgen production.
d. 3-beta hydroxylase
Peak age of Type I Diabetes Mellitus is 5-7 years and at puberty
9. The major hormone that is underproduced alone or with
2 A -at childhood, common due to infections
-at puberty, due to sex hormones other anterior pituitary hormones is?
The most common cause of hypopituitarism in the pediatric age group is
a. Prolactin
craniopharyngioma or adenoma (prolactinoma). Craniopharyngioma b. Growth hormone
3 A
develops from the persistent remnant of the original connection between c. Thyroid stimulating hormone
Rathke pouch and oral cavity.
d. Adrenocorticotropic hormone
Craniopharyngioma is the most common tumor associated with the 10.Type 1 diabetes mellitus is?
4 A
development of diabetes insipidus
a. Usually present with hyperosmolar hyperglycemia coma

PED 6.04 Pediatric Endocrinology Page 14 of 21

 b. Associated with obesity c. Prednisone
c. Non-insulin dependent d. Hydrocortisone
d. Treated with oral hypoglycemic agents 24.Vasopressin is synthesized in the?
11.True about Diabetic ketoacidosis: a. Pineal gland
a. A complication of type 2 DM b. Anterior pituitary
b. Commonly precipitated by stress like an infection c. Posterior pituitary
c. Caused by decreased glycogenesis d. Paraventricular nuclei and supraoptic nuclei
d. Treated with oral hypoglycemic agents 25.The most common type of diabetes mellitus in the pediatric
12.The most common intracranial lesion causing acquired age group is?
hypopituitarism is? a. I
a. Gliomas b. II
b. Ependymomas c. III
c. Metastasis d. MODY
d. Craniopharyngioma
Answer Key: (1) C, (2) C, (3) D, (4) E, (5) B, (6) D, (7) A, (8) C, (9) B, (10) X - None of the
13.Sexual differentiation occurs at this gestational age in choices is correct since all refer to Type 2 DM. Primary mode of treatment for T1DM is insulin.
weeks: (11) B, (12) D, (13) A, (14) B, (15) A, (16) A, (17) B, (18) A, (19) A, (20) B, (21) C, (22) D, (23)
a. 8 A, (24) D, (25) A
b. 10
c. 12 2020 REVIEW QUESTIONS | Same lecturer
d. 30 1. The following are clinical indications for GH replacement,
14.The most common cause of ambiguous genitalia in girls is? EXCEPT:
a. Maternal testosterone exposure a. Constitutional short stature
b. Congenital adrenal hyperplasia b. GH deficiency
c. Virilizing ovarian tumor c. Small for gestational deficiency
d. Drugs d. Turner syndrome
15.Most infants with congenital hypothyroidism are normal at 2. DOC for congenital hypothyroidism
birth because of? a. PTU
a. Maternal T4 b. Propranolol
b. Elevated TRH c. Iodine
c. Maternal T3 d. Levothyroxine
d. Elevated TSH 3. Most common age range for DM type 2?
16.Type II diabetes mellitus is: a. Infancy
a. Associated with obesity b. 5-7 years and at puberty
b. Usually seen in malnourished children c. Adulthood
c. Associated with frequent DKA d. > 60 years
d. Insulin dependent 4. Most useful monitoring in the daily management of DM?
17.The most common cause of acquired hypopituitarism in a. FBS
children is? b. RBS
a. Iodine deficiency c. HbA1C
b. Haashimoto’s thyroiditis d. Urine blood sugar
c. Graves disease 5. Enzyme deficient in congenital adrenal hyperplasia
d. Thyroid tumor a. 11-hydroxylase
18.Congenital hypothyroidism is due to: b. 11-hydroxyprogesterone
a. Thyroid dysgenesis c. 17-hydroxyprogesterone
b. Hereditary d. 21-hydroxylase
c. Intrauterine infections 6. Treatment of DKA
d. Familial a. Insulin
19.Confirmatory test for congenital adrenal hyperplasia b. Hydration
a. 17 hydroxyprogesterone c. Water
b. 17 beta-hydroxylase d. Insulin and hydration
c. 21 hydroxylase 7. Best diagnostic method for the adequacy of glucose
d. 21 hydroxyprogesterone control?
20.Which is NOT a clinical parameter of SIADH? a. FBS
a. High urine output b. RBS
b. Low vasopressin c. HbA1C
c. Low serum sodium d. Urine blood sugar
d. Low urine sodium 8. Endocrine disorder detected in NBS
21.In central precocious puberty in girls, which secondary a. CAH
sexual characteristic is the common initial complaint? b. DM
a. Growth spurt c. GH deficiency
b. Menarche d. Hypoparathyroidism
c. Breast development 9. All the following causes short stature EXCEPT:
d. Pubic hair a. No choices provided
22.Precocious puberty is defined as the onset of secondary 10.Where is GH produced?
sexual characteristics before: a. Anterior pituitary
a. 10 yo in girls, 11 yo in boys b. Posterior pituitary
b. 7 yo in girls, 8 yo in boys c. Adrenal medulla
c. 11 yo in girls, 12 yo in boys d. Liver
d. 8 yo in girls, 9 yo in boys 11.Constitutional short stature is usually secondary to which of
23.Drug of choice in salt losing congenital adrenal hyperplasia the following factors?
a. Fludrocortisone a. Hereditary
b. Dexamethasone b. Environmental

PED 6.04 Pediatric Endocrinology Page 15 of 21

 c. Genetics
12.Important parameters in assessing short stature parameter
except:
a. Bone age
b. Chronologic age
c. Height age
d. Weight

Answer Key:
Normal variant: Constitutional delay and familial short/genetic short
1 A stature;
B, C, and D: pathologic causes
A and B: for hyperthyroidism
2 D C: as supplement for those with goiter
D: for hypothyroidism
3 B 5-7 years and at puberty for T1DM; Usually adult-onset for T2DM
Daily monitoring should be available in and out-patient. Other options done
4 D
in laboratories
5 D 21-hydroxylase deficiency is the most common enzyme deficiency in CAH
6 D
7 C HbA1C measures long term glucose control for ~3 months
Recall
8 A
PH NBS: CAH, PKU, G6PD, MSUD, CH, and GAL
Marfan’s syndrome patients tend to be tall and thin, with long arms, legs,
fingers, and toes and have flexible joints “usually anything with ‘syndrome’
9
are short except for patients with Marfan’s syndrome and homocystinuria
who are tall,”
Recall
10 A Anterior PG: GH, TSH, FSH, LH, and Prolactin, ACTH;
hypothalamus: Oxytocin and ADH
Under normal variant of short stature familial/genetic: due to genetics
11 B
Constitutional: due to lack of nutrition or emotional deprivation
Needed for assessment: growth velocity, midparental height, radiography
12 D
to evaluate bone age, and the chronologic age

REFERENCES
Kliegman, R., St. Geme, J.W. (2020). Nelson Textbook of Pediatrics. (21st ed).
Philadelphia, PA: Elservier.
Cua, W. (2022). Pediatric Endocrinology [lecture powerpoint].
2022 lecture transcriptions
QUICK LINKS

ERRATA SHEET TRANS FEEDBACK FORM

Tinyurl.com/2023Y3ErrataTracker Tinyurl.com/2023Y3TransFeedback

PED 6.04 Pediatric Endocrinology Page 16 of 21

 MUST KNOWS & SUMMARY
DIABETES SHORT STATURE
● A chronic disease characterized by high blood glucose levels ● Overview
caused by defects in insulin secretion, insulin action, or both ○ Subnormal height relative to other children of the same gender
● Diagnosis via oral glucose tolerance test and age, taking family height into consideration
○ Fasting > 126 mg/dL ○ Criteria: height below 1st percentile for age and sex or height
■ Serves as enough basis for diagnosis of DM >2SD below sex-adjusted mid-parent height
○ Non-fasting >200 mg/dL (OGTT or RBS) ○ Normal variants:
■ Presumptive diagnosis of DM ■ Constitutional delay of growth and adolescence
● ⅔ of cases are Type 1 DM with peak ages at 5 to 7 years old and at ■ Familial or genetic short stature
puberty ● Classified as proportionate and disproportionate
● Insulin ○ Causes of proportionate short stature
○ Has a critical role in the storage and retrieval of cellular fuel ■ Increased weight:height ratio: endocrinopathies such as GH
○ Anabolic, released after meals deficiency/insensitivity, hypothyroidism and glucocorticoid
■ Decreased: blood glucose, gluconeogenesis excess
■ Increased: glycogen synthesis, lipogenesis, protein synthesis ■ Decreased or normal weight:height ratio: inadequate calories,
● Glucagon renal diseases, chronic diseases
○ Catabolic, released in between meals ○ Causes of disproportionate short stature
■ Increased: blood glucose, glycogen breakdown, ■ Skeletal dysplasia, metabolic bone disease, spinal disorders,
gluconeogenesis, lipolysis, triglyceride store mobilization hypogonadism and chromosomal abnormalities (associated
● Type 1 DM with dysmorphic features: trisomy 21, turner syndrome)
○ Beta cell destruction → absolute insulin deficiency
○ Insulin-dependent, 80 to 90% are immune-related, idiopathic and AMBIGUOUS GENITALIA
multifactorial; associated with DKA ● Overview
○ Polydipsia, polyphagia, polyuria are found in both T1DM and ○ Due to under masculinization of genetic males of virilization of
T2DM genetic females
○ Lethargy and weight loss symptoms are specific to T1DM ■ Wolffian ducts - male
● Type 2 DM ■ Mullerian ducts - female
○ Insulin resistance → secretory defect with insulin resistance ○ Diagnostic dilemma for the pediatrician (especially for the female
○ Non-insulin dependent DM; most common type in pediatric age baby wherein the external cannot be totally identified); emotional
group crisis for the family
○ Polydipsia, polyphagia and polyuria ■ Male pseudohermaphroditism → due to undervirilization of
○ Associated with hyperglycemic hyperosmolar syndrome genitalia
■ Female pseudohermaphroditism → due to virilization of
● Microvascular complications
genitalia
○ Coronary heart disease, peripheral vascular disease
○ Cerebrovascular disease
■ Presence of palpable gonads → indicates that the neonate
○ Hypertension is a chromosomal male
○ Dyslipidemia ○ Caused by 21-hydroxylase deficienc
○ Congenital adrenal hyperplasia:
● Goals of treatment
■ 21-hydroxylase deficiency in females
○ Maintain blood glucose within normal levels
■ 5 alpha-reductase deficiency in males
○ Avoid hypoglycemia
○ Avoid DKA (for T1DM)
● Normal sexual differentiation
○ Keep lipid levels within normal levels ○ The innate tendency is for the bipotential fetus to develop into a
○ Prevent or delay complications female
○ Prolong life and quality of life ○ To develop into male, the following are required:
■ Testes: determining factor (sex determining region of the Y
● Diabetic ketoacidosis
chromosome or SRY) and downstream genes
○ Only seen in T1DM, most feared complication
■ Testicular production of both anti-mullerian hormone (AMH),
○ Has elevated blood glucose, (+) ketones in urine or blood, (+)
also called mullerian-inhibiting substance (MIS) and
metabolic acidosis
testosterone
○ Occurs when extremely low insulin levels are reached which
■ Normal gonadotropin production by hypothalamic-pituitary
comprises of glycosuria, osmotic diuresis, increased lipolysis and
axis (during 2nd and 3rd trimester)
impaired lipid synthesis and metabolic acidosis
■ Conversion of testosterone to dihydrotestosterone (DHT) by 5
○ Treatment: hydration and insulin replacement
alpha-reductase
● Nonketotic hyperosmolar coma
■ Organ response to androgen
○ Also known as hyperglycemic hyperosmolar syndrome
○ Severe hyperglycemia with a blood glucose level of > 800 mg/dL
PSEUDOHERMAPHRODITISM
with absent or slight ketosis
● Female pseudohermaphroditism
○ Severe dehydration with depressed sensorium or frank coma,
neurologic signs (seizures, hyperthermia, hemiparesis and
○ Due to virilization of the genitalia
positive Babinski) ○ Causes
○ Treatment: rapid volume repletion and very slow correction of ■ Congenital Adrenal Hyperplasia (CAH)
hyperosmolar state ● Most common cause of ambiguous genitalia & of 46XX
● Treatment of DM
○ Insulin ● 21-hydroxylase deficiency (most common) 📌
disorders of sexual dev’t [Nelson 21ed, p.3012]

○ Nutritional management: 55% carbohydrate, 30% fat, 15%

protein [2022[ 📌
○ The more DHEA you have, the more virilized you are

● 11-alpha-hydroxylase deficiency
○ Physical activity should never be discouraged
○ Monitoring of blood glucose and serum HbA1c (every 3 months) ● 3 beta hydroxysteroid dehydrogenase deficiency
● Prognosis ■ Maternal androgens
○ Average lifespan is 10 years less than non-diabetic if poorly ● Male pseudohermaphroditism
controlled ○ Dysmorphic syndrome
PED 6.04 Pediatric Endocrinology Page 17 of 21
 ○ Defects in testosterone biosynthesis PRECOCIOUS PUBERTY
○ Defects in androgen target tissues ● Onset of secondary sexual characteristics:
○ Persistent mullerian duct syndrome ○ Before 8 years old in females
○ Gonadal dysgenesis ○ Before 9 years old in males
○ Vanishing testes ● Central Precocious Puberty (CPP)
○ Gonadotropin-dependent or true precocious puberty
📌 or any
○ Rare and due to the undervirilization of genitalia
○ Most common cause is 5-alpha reductase deficiency ■ Etiology: Organic brain lesions, following brain irradiation,
defect in testosterone biosynthesis uncontrolled hypothyroidism
■ Clinical Manifestations: Sexual development begin at any age
PITUITARY GLAND and follows sequence in normal puberty; Accelerated height,
● Overview weight, height velocity
○ Type of deficiency ■ Laboratory Findings: Sex hormone concentration are usually

primary deficiency 💬
■ If there is a deficiency from the endocrine organs, it is called a appropriate for the stage of puberty
■ Imaging: Advanced osseous maturation
■ If there is a deficiency of any hormone coming from the
pituitary gland, it is called a secondary deficiency
● Anterior Pituitary Gland
💬 ■ Tx: GnRH Agonist Therapy
● Peripheral Precocious Puberty
○ Gonadotropin-independent or pseudoprecocious puberty
○ Adenophysis ■ Gonadotropin-independent conditions:
○ Secretes the following stimulatory hormones: ● In Males: Chorionic gonadotropin-secreting tumor, Leydig
■ Growth hormone (GH) cell tumor, Familial male-limited precocious puberty,
■ Thyroid stimulating hormone (TSH) virilizing congenital adrenal hyperplasia, virilizing adrenal
■ Adrenocorticotropic hormone (ACTH) tumor
■ Prolactin (PRL) ● In Females: Granulosa cell tumor, Follicular cyst,
■ Follicle stimulating hormone (FSH) Feminizing adrenal tumor, Non-classical congenital
■ Luteinizing hormone (LH) adrenal hyperplasia
● Posterior Pituitary Gland ● In both sexes: McCune-Albright Syndrome, Primary
○ Neurophysis Hypothyroidism
○ Main storage site of: ■ Incomplete precocity
■ Arginine vasopressin ● Premature Thelarche
● Deficiency will cause Diabetes Insipidus ● Premature Adrenarche
■ Oxytocin ● Premature Menarche
● Disorders of Anterior Pituitary Gland ● Delayed or Absent Puberty
○ The most common cause of hypopituitarism in the pediatric age
group is craniopharyngioma or adenoma (prolactinoma)
■ Develops from the persistent remnant of the original
connection between Rathke pouch and oral cavity
● Disorders of Posterior Pituitary Gland
○ Diabetes Insipidus (DI)
■ Causes
● No vasopressin (under-secretion of vasopressin)
● Causes: Idiopathic (majority), tumor,
📌
intracranial
infections, post-radiation, post-craniotomy, trauma,
radiotherapy
● Craniopharyngioma - most common tumor associated with
the development of DI
■ Clinical manifestations
● Manifests as increased loss of free water 📌
○ High serum osmolality and low urine osmolality 📌
■ Hypernatremia
○ Microadenoma in the pituitary gland
■ Treatment
● Vasopressin replacement therapy
○ Forms: Oral, infectables, or nasal spray
○ Syndrome of Inappropriate Antidiuretic Hormone Secretion

📌
(SIADH)

📌
■ Exact opposite of DI
■ Excessive secretion or release of vasopressin
■ Causes:
● Trauma, infections, radiotherapy, metastasis
● May be idiopathic
■ Clinical manifestations:
● Present with secretion of concentrated urine of low volume
(low urine output)
○ Retention of free water
○ Low serum osmolality with high urine osmolality
○ Hyponatremia
📌
DI SIADH
Vasopressin ↓ ↑
Free water Loss Retention
Serum osmolality HIGH LOW
Urine osmolality LOW HIGH
Serum sodium HYPERnatremia HYPOnatremia

PED 6.04 Pediatric Endocrinology Page 18 of 21

 CONCEPT CHECKPOINT
HYPOTHYROIDISM
1. Overtreatment of hypothyroidism with Levothyroxine may manifest AMBIGUOUS GENITALIA
as craniosynostosis and temperament effects. 8. What is the most common cause of CAH in females?
○ True. Overtreatment of hypothyroidism may lead to ○ 21-hydroxylase deficiency. Most common cause of CAH in
craniosynostosis and temperament effects females.
2. Manifestations of congenital hypothyroidism include all of the
following, except: PITUITARY GLAND
○ D. Altered mental status is not a manifestation of congenital 9. The following are stimulatory hormones secreted by the anterior
hypothyroidism. All the others are. pituitary gland, EXCEPT:
○ B. Oxytocin is stored in the posterior pituitary gland, not secreted
DIABETES by the anterior pituitary gland
3. T/F. A random blood glucose result of 210 mg/dL is considered to 10. What is the most common tumor associated with the
be sufficient basis for diagnosing DM. development of diabetes insipidus (DI)?
○ False. RBS of > 210 mg/dL is only presumptive of DM. FBS ○ Craniopharyngioma
results of > 126 mg/dL is considered as enough basis for 11. T/F. In DI there is LOW serum osmolality while in SIADH
diagnosing DM there is HIGH serum osmolality.
4. Diabetic ketoacidosis has the following parameters except: ○ F. DI has HIGH serum osmolality while SIADH has LOW serum
○ C. Hyperlipidemia. DKA lab parameters include elevated blood osmolality
glucose, ketones in urine or blood and metabolic acidosis.
5. What is the most common DM type in the pediatric age group? PRECOCIOUS PUBERTY
○ B. T1DM is the most common DM in the pediatric age group. 12. T/F. Onset of secondary sexual characteristics before the
age of 9 years in females and 8 years in males.
SHORT STATURE ○ F. Onset of secondary sexual characteristics before the age of 8
6. What chromosomal abnormality is associated with hypogonadism years in females and 9 years in males.
○ Turner syndrome 13. This is defined as the failure of development of any pubertal
7. Which is a cause of disproportionate short stature? feature by 13 years old in females and 14 years old in males.
○ Hypogonadism. Disproportionate short stature is caused by ○ D. Delayed or Absent Puberty
skeletal dysplasia, metabolic bone disease, spinal disorders,
hypogonadism and chromosomal abnormalities.

APPENDIX

Figure 1. Screening Guidelines for complications of diabetes mellitus in the pediatric age group

PED 6.04 Pediatric Endocrinology Page 19 of 21

 Figure 2. Differential Diagnosis of Sexual Precocity

PED 6.04 Pediatric Endocrinology Page 20 of 21

 Figure 13b. Algorithm for evaluating infants with ambiguous genitalia

PED 6.04 Pediatric Endocrinology Page 21 of 21