P E D I A T R I C S II

TOPIC 10.2 PEDIATRIC ENDOCRINOLOGY

Dr. Kristine Laygo ● April 8, 2022 ● 2nd Semester (Finals)
LEGEND

LEGEND (anorexia, nutrient losses through a form of malabsorption, or

Black:PPT ● Blue:BOOK ● Red: AUDIO (from SIGLAT Trans) hypermetabolism caused by hyperthyroidism or other causes).
● Violet:TAKE-NOTE! o If the mother is malnourished or if the mother is suffering
from anorexia, then expect the child to be also malnourished
TOPIC OUTLINE
 Psychological difficulties also can affect growth, as in
I. ENDOCRINE EVALUATION OF GH SECRETION psychosocial or deprivation dwarfism, in which the child (when
A. GH SECRETION stressed or has a psychological disturbance) develops
B. ABNORMALITIES OF GROWTH functional temporary GH deficiency and poor growth as a
a. Short Stature of Nonedocrine Causes result of psychological abuse
b. Short Stature Caused by GH Deficiency  When placed in a different, healthier psychosocial
II. DISORDERS OF PUBERTY environment, GH physiology normalizes, and growth occurs
A. PHYSIOLOGY  The common condition known as constitutional delay in
B. DELAYED PUBERTY growth or puberty or both is considered a variation of normal
C. SEXUAL PRECOCITY growth, caused by a reduced tempo or cadence, of physiologic
III. THYROID DISEASE development.
A. THYROID PHYSIOLOGY AND DEVELOPMENT  Constitutional delay usually leads to a delay in secondary
B. THYROID DISORDERS sexual development.
C. NODULES OR TUMORS OF THE THYROID  Genetic or familial short stature refers to the stature of a
IV. REFERENCES AND CITATIONS child of short parents, who is expected to reach a lower than
average height and yet normal for these parents.
I. ENDOCRINE EVALUATION OF GH  If the parents were malnourished as children, grew up in a
SECRETION zone of war or suffered famine, the heights of the parents are
less predictive.
A. GH SECRETION
 Genetic Causes:
 Growth hormone is secreted by the pituitary gland under the
1. Prader-Willi syndrome
control of the GRH and Somatotropin release inhibiting factor
o Includes fetal and infantile hypotonia, small hands and
(SRIF) of the hypothalamus feet (acromicria), postnatal acquired obesity with an
 GH secretion is enhanced by: insatiable appetite, developmental delay,
o alpha adrenergic stimulation hypogonadism, almond-shaped eyes and
o hypoglycemia abnormalities of the small nuclear ribonucleic particle
o Starvation (snRNP) portion of the 15th chromosome at 15q11-
o Exercise q13.
o early stages of sleep and stress
 It is inhibited by
o beta adrenergic stimulation
o hyperglycemia
 Concentrations of GH are low throughout the day
 With brief secretory peaks in the middle of the night or early
morning
 Daytime assessment of GH deficiency or sufficiency on the
basis of a single random GH concentration determination is
impossible
B. ABNORMALITIES OF GROWTH
a. Short Stature of Nonendocrine Cause
 First manifestation that will come to mind; child did not grow at
a normal rate or length
 Short stature is defined as subnormal height relative to
other children of the same gender and age, taking family
heights into consideration. Figure 1. Prader-Willi Syndrome
 The CDC growth charts use the 3rd percentile of the growth 2. Laurence-Moon-Bardet-Biedl syndrome
curve as the demarcation of the lower limit. o characterized by retinitis pigmentosa, hypogonadism,
 Growth failure denotes a slow growth rate regardless of and developmental delay with an autosomal dominant
stature. inheritance pattern.
 Ultimately, a slow growth rate leads to short stature, but a o Laurence-Moon syndrome is associated with spastic
disease process is detected sooner if the decreased growth paraplegia;
rate is noted before the stature becomes short. o Bardet-Biedl syndrome is associated with obesity and
 Nutrition is the most important factor affecting growth on a polydactyly.
worldwide basis 3. Pseudohypoparathyroidism
 There is a short stature of non-endocrine process and nutrition o Leads to short stature and developmental delay with
is one factor, so don’t label a child who has short stature of short fourth and fifth digits (Albright hereditary
having endocrine problems immediately. osteodystrophy phenotype), resistance to parathyroid
 Failure to thrive may develop in the infant as a result of hormone and resultant hypocalcemia and elevated levels
maternal deprivation (nutritional deficiency or aberrant of serum phosphorus.
psychosocial interaction) or as a result of organic illness

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Pediatric Endocrinology
4. Turner Syndrome
o Characterized by karyotype of 45XO or by a mosaic
karyotype and clinically presents with short stature,
shield chest, wide-spaced nipples, wide-carrying
angle of the upper extremities, high-arched palate,
gonadal failure, kidney dysplasias with normal
function and aortic arch abnormalities.
o Affected girls are often susceptible to autoimmune
disorders

Figure 3. Classic congenital or Idiopathic GH deficiency

o The patient has normal intellectual growth and age-
appropriate speech unless
 Severe hypoglycemia occurs
Figure 2. Turner Syndrome
 Dysraphism (midline defects) of the head includes a
b. Short Stature Caused by GH Deficiency CNS defect that affects mentation
1. Classic congenital or Idiopathic GH deficiency o Male neonates with isolated GH deficiency with or
 Unspecified, etiology is unknown without gonadotropin deficiency may have a
 Most common cause of both congenital and acquired microphallus (a stretched penile length of <2cm [normal
growth hormone deficiency is 3 to 5 cm]) and fasting hypoglycemia.
 Refers to a very reduced to absent secretion of GH 2. GH resistance or GH Insensitivity
 Numerous short children may have intermediate forms of  Caused by abnormal number or function of GH
decrease GH secretion receptors or by a post-receptor defect
a. Idiopathic GH deficiency, of unidentified specific  Laron syndrome: Autosomal recessive involving
etiology, is the most common cause of both congenital mutations of the GH receptor
and acquired GH deficiency. o Have a prominent forehead, hypoplastic nasal
b. Less often, GH deficiency is caused by anatomic bridge, delayed dentition, sparse hair, blue sclerae,
defects of the pituitary gland, such as pituitary aplasia delayed bone maturation and osteoporosis,
or other midline defects, with variable degrees of progressive adiposity, hypercholesterolemia and low
deficiency of other pituitary functions blood glucose
c. Classic GH deficiency refers to very reduced to o Have elevated serum GH concentrations, although
absent secretion of GH serum IGF-1 and IGF-BP3 concentrations are low.
d. Numerous short children may have intermediate forms 3. Acquired GH Deficiency
of decreased GH secretion. Acquired GH deficiency  Causes late-onset growth failure
causing late-onset growth failure suggests the  May be caused by a tumor of the hypothalamus or
possibility of a tumor of the hypothalamus or pituitary pituitary causing compression of the area
causing compression of the area 4. Acquired GH resistance
 Clinical Manifestations:  Malnutrition, medications (corticosteroids) or severe
o Infants with congenital GH deficiency achieve a normal liver disease may also cause this disorder
or near-normal birth length and weight at term (so  Serum GH is elevated and IGF-1 is decreased
normal at delivery), but the growth rate slows after  So the GH is actually elevated but there is short stature
birth, most noticeably after age 2 to 3 years. because the body is resistant to the hormone
o These children become progressively shorter for age  Diagnosis
and tend to have an elevated weight-to-height ratio, o If family or other medical history does not provide a
appearing chubby and short. likely diagnosis, screening tests should include a
o A patient with classic GH deficiency has the metabolic panel to evaluate kidney and liver function,
appearance of a cherub (a chubby, immature a complete blood count to rule out anemia, a celiac
appearance), with a high-pitched voice resulting from panel to rule out celiac disease and carotene and
an immature larynx. folate levels to reflect nutrition and rule out
malabsorption.
o Urinalysis aids in the evaluation of renal function.
o Urinary pH and serum bicarbonate can assess for
renal tubular acidosis.
o In a girl without another explanation for short stature,
a karyotype may rule out Turner syndrome.

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Pediatric Endocrinology
o A bone age will establish skeletal maturation.  A family history of delayed puberty in a parent or sibling is
o If chronic disease or familial short stature are ruled reassuring.
out and routine laboratory testing is normal, two GH  Spontaneous puberty usually begins in these patients by the
stimulatory tests are commonly performed. time the bone age reaches 12 years in boys and 11 years in
o GH testing should be offered to a patient who is short girl
(<5th percentile and usually >3.5 SDs below the  Other causes of delayed puberty must be eliminated before a
mean), growing poorly (<5th percentile growth rate diagnosis of constitutional delay in puberty is made.
for age), or whose height projection, based on bone  Observation and reassurance are appropriate.
age, is considerably below the target height when  In some cases, boys may be treated with low-dose
corrected for family height testosterone for a few months if the bone age is at least 11 to
o Classic GH-deficient patients do not show an 12 years.
increase in serum GH levels after stimulation.  Treatment is not required for longer than 4 to 8 months
o Some patients release GH in response to because endogenous hormone production usually ensues.
secretagogue testing but cannot release GH  Boys who do not initiate endogenous hormone production
spontaneously during the day or night. should be evaluated for other causes of hypogonadism.
 Treatment
 Estrogen treatment has been used in girls with constitutional
o GH deficiency is treated with biosynthetic
delay. Young women with delayed puberty may need to be
recombinant DNA-derived GH.
evaluated for primary amenorrhea
o Dosage is titrated to the growth rate.
o Treatment with GH carries the risk of an increased b. Hypogonadothrophic Hypogonadism
incidence of slipped capital femoral epiphysis,  As a cause of delayed or absent puberty, may be difficult to
especially in rapidly growing adolescents, and of distinguish from constitutional delay.
pseudotumor cerebri.  Patients with hypogonadotrophic hypogonadism have normal
proportions and growth.
II. DISORDERS OF PUBERTY  When these patients reach adulthood, eunuchoid proportions
A. PHYSIOLOGY may ensue because their long bones grow for longer than
normal, producing an upper-to-lower ratio below the lower
 The onset of puberty is marked by pubarche and gonadarche
limit of normal of 0.9 and an arm span greater than their
 PUBARCHE - results from adrenal maturation or
height.
adrenarche and is marked with appearance of pubic hair;
 If a patient has concurrent GH deficiency, stature is
other features include oiliness of hair and skin, acne, axillary
exceptionally short, and the condition may have been
hair, and body odor.
diagnosed in infancy with a microphallus.
 GONADARCHE - characterized by increasing secretion of
gonadal sex steroids as a result of the maturation of the c. Isolated Gonadotropin Deficiency
hypothalamic-pituitary-gonadal axis.  Disorders that can cause hypogonadism include congenital
 Hypothalamic gonadotropin-releasing hormone (GnRH), hypopituitarism, such as midline defects, tumors, infiltrative
produced by cells in the arcuate nucleus, is secreted from the disease (hemochromatosis) and many syndromes including:
median eminence of the hypothalamus into the pituitary o Laurence-Moon-Bardet-Biedl syndrome
portal system to cause the production and release of o Prader-Willi syndrome
luteinizing hormone (LH) and follicle-stimulating hormone o Kallmann syndrome
(FSH) into the circulation.  If there is an inability to release gonadotrophins but no
 The hypothalamic-pituitary-gonadal axis is active in the fetus other pituitary abnormality, the patient has isolated
and newborn but is suppressed in the childhood years until gonadotrophin deficiency (almost universally a result of absent
activity increases again at the onset of puberty. GnRH).
 In females, FSH stimulates the ovarian production of estrogen  Patients grow normally until the time of the pubertal growth
and later in puberty, causes the formation and support of spurt, when they fail to experience the accelerated growth
corpus luteum. characteristic of the normal growth spurt.
 In males LH stimulates the production of testosterone from d. Abnormalities of the CNS
the Leydig cells, later in puberty, FSH stimulates the  Abnormalities of the CNS can also cause hypogonadotropic
development and support of the seminiferous tubules. hypogonadism which includes the ff: CNS tumors and other
 The gonads also produce the protein inhibin. tumors that may affect pubertal development including
 Both sex steroids and inhibin suppress the secretion of astrocytomas and gliomas
gonadotropins.  CNS tumors including pituitary adenoma, glioma,
 The normal developmental sequence in girls is thelarche (due prolactinoma or craniopharyngoma are important causes of
to gonadarche)  followed closely by pubarche (due to gonadotrophin deficiency.
adrenarche)  menarche (2 to 3 years later).  Other tumors that may affect pubertal development include
(Mnemonics: TgPaM) astrocytomas and gliomas
 In boys, the first normal event is scrotal thinning  the  Idiopathic hypopituitarism is the congenital absence of
enlargement of testes and by the appearance of pubic hair. various combinations of pituitary hormones.
Most of the enlargement of testes during puberty is the result  Congenital hypopituitarism may manifest in a male with GH
of seminiferous tubule maturation. deficiency and associated gonadotrophin deficiency with a
 Puberty is delayed when there is no sign of pubertal microphallus or with hypoglycemia with seizures, especially if
development by age 13 years in girls and 14 years in boys adrenocorticotropic hormone and GH deficiency occurs as
well.
B. DELAYED PUBERTY e. Syndromes of Hypogonadotropic Hypogonadism
a. Constitutional Delay in Growth and Adolescence  Decreased gonadotropin function occurs when voluntary
 Patients with constitutional delay have delayed onset of dieting, malnutrition, or chronic disease results in weight low to
pubertal development and significant bone age delay (2 SD less than 80% of ideal weight.
below the mean)  ANOREXIA NERVOSA: characterized by striking weight loss
and psychiatric disorders.

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Pediatric Endocrinology
 Primary or secondary amenorrhea frequently is found in the patient has a hypogonadotrophic or
affected girls and pubertal development is absent or minimal, hypergonadotrophic hypogonadism.
depending on the level of weight loss and the age of onset.  Based on gonadotropin measurements only, the differentiation
 Regaining weight to the ideal level may not immediately between constitutional delay in growth and hypogonadotrophic
reverse the condition. hypogonadism is difficult; the gonadotrophin levels are low in
 Increased physical activity, even without weight loss, can both conditions.
lead to decreased menstrual frequency and gonadotrophin  Sometimes observation for months or years is necessary
deficiency in athletic amenorrhea; when physical activity is before the diagnosis is confirmed.
interrupted, menstrual function may return.  Ultrasound of the pelvic structures in females would be
 Chronic or systemic illness (eg cystic fibrosis, DM, helpful in the workup of delayed puberty.
inflammatory bowel disease or hematologic diseases) can lead TREATMENT
to pubertal delay or to amenorrhea from hypothalamic  If a permanent condition is apparent, replacement with sex
dysfunction. steroids is indicated.
 Hypothyroidism inhibits the onset of puberty and delays  Females are given transdermal estradiol, low dose ethinyl
menstrual periods. estradiol (5 to 10 μg) or conjugated estrogens (starting at 0.3
 Conversely, severe primary hypothyroidism may lead to mg daily, increasing to 0.625 mg or 0.9 mg by 6 to 12 months
precocious puberty later) in low daily doses until breakthrough bleeding occurs, at
f. Hypergonadotrophic Hypogonadism which time cycling is started with a dose for 25 days
 Characterized by elevated gonadotrophins and low sex  On days 20 to 25 after bleeding, a progestational agent, such
steroid levels resulting from primary gonadal failure. as medroxyprogesterone acetate (5 mg), is added to mimic the
 This permanent condition is almost always diagnosed normal increases in gonadal hormones and to induce a normal
following the lack of entry into gonadarche and is not menstrual period.
suspected throughout childhood.  In males, testosterone enanthate or cypionate (50 to 100 mg
 Gonadotropins do not increase to greater than normal until monthly with a progressive increase to 100 to 200 mg) is given
shortly before or around the normal time of puberty intramuscularly once every 4 weeks. Oral agents are not used
 Ovarian failure is diagnosed by elevated gonadotropins. for fear of hepatotoxicity.
TURNER SYNDROME  All patients with any form of delayed puberty are at risk for
 Syndrome of gonadal dysgenesis is a common cause of decreased bone density; adequate calcium intake is essential.
ovarian failure and short stature.  Subjects with hypergonadotrophic hypogonadism have a
 The karyotype is basically 45 XO, but other abnormalities of X primary gonadal problem and are unlikely to achieve
chromosome or mosaicism are possible. spontaneous fertility.
 Features of a girl with Turner syndrome need not be evident
on physical examination or by history.
C. SEXUAL PRECOCITY
 The diagnosis must be considered in any girl who is short
 SEXUAL PRECOCITY (precocious puberty): Classically
without a contributory history. defined as secondary sexual development occurring
 Patients with other types of gonadal dysgenesis and
before the age of 9 years in boys or 8 years in girls.
galactosemia as well as patients treated undergoing a. Classification
radiation therapy or chemotherapy for malignancy may  CENTRAL PRECOCIOUS PUBERTY: resulting in
develop ovarian failure. gonadarche, emanates from premature activation of the
KLINEFELTER SYNDROME hypothalamicpituitary- gonadal axis (GnRH-dependent)
 Seminiferous tubular dysgenesis  PERIPHERAL PRECOCIOUS PUBERTY: gonadarche or
 The most common type of testicular failure adrenarche does not involve the hypothalamic-pituitarygonadal
 The karyotype is 47, XXY but variants with more X axis (GnRH-independent)
chromosomes are possible. b. GnRH Dependent Precocious Puberty (Central
 Testosterone levels may be close to normal, at least until Precocious Puberty)
mid-puberty, because Leydig cell function may be spared  In central precocious puberty, every endocrine and physical
 Seminiferous tubular function characteristically is lost causing aspect of pubertal development is normal but too early
infertility  This includes tall stature, advanced bone age consistent with
 Commonly LH levels may be normal to elevated, whereas somatic age, increased sex steroid and pulsatile gonadotropin
FSH levels are usually more unequivocally elevated. secretion and increased response of LH to GnRH.
 Age of onset of puberty is usually normal but secondary sexual  Clinical course may wax and wane
changes may not progress because of inadequate Leydig cell
 Benign precocious puberty is the presumptive diagnosis in
function individuals who begin puberty early on a constitutional or
g. Primary Amenorrhea familial basis.
 Anatomic obstruction by imperforate hymen or vaginal septum  If no cause can be determined, the diagnosis is idiopathic
also presents with normal secondary sexual development precocious puberty which occurs more often in girls than in
without menstruation. boys.
 The complete syndrome of androgen insensitivity includes  Obese girls have earlier adrenarche and sometimes menarche
normal feminization, absence of pubic or axillary hair and as well.
primary amenorrhea.  Compared with girls, boys with precocious puberty have a
 In this syndrome, all mullerian structures, including ovaries, higher incidence of CNS disorders, such as tumors and
uterus, fallopian tubes and upper third of the vagina are hamartomas, precipitating the precocious puberty. Male
lacking; the karyotype is 46 XY and subjects have patients with precocious puberty are more aggressive in the
intraabdominal testes. workup.
EVALUATION  Almost any condition that affects the CNS, including
 When no secondary sexual development is present after the hydrocephalus, meningitis, encephalitis, suprasellar cysts,
upper age limits of normal pubertal development; serum head trauma, epilepsy, mental retardation, and irradiation can
gonadotropin levels should be obtained to determine whether precipitate central precocious puberty.

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Pediatric Endocrinology
 Hamartomas: not true neoplasms, nonmalignant tumor of the o If there is a probable CNS anomaly or tumor (CNS, hepatic,
tuber cinereum, the mass of GnRH neurons secrete GnRH adrenal, ovarian, or testicular), MRI is indicated.
and cause precocious puberty. May require neurosurgical TREATMENT
attention.  Long-acting, superactive analogs of GnRH (leuprolide
 Other masses that cause precocious puberty are not benign. depot, histrelin depot) are the treatment of choice for central
 Germinomas: noncalcifying hypothalamic or pineal tumors precocious puberty.
that frequently produce HCG  They suppress gonadotropin secretion by downregulating
 Optic or hypothalamic gliomas (with or without GnRH receptors in the pituitary gonadotropes causing gonadal
neurofibromatosis), astrocytomas, and ependymomas: May secretion to revert to the prepubertal state.
cause precocious puberty by disrupting the negative restraint  Boys with GnRH independent precocious puberty will require
of the areas of the CNS that normally inhibit pubertal treatment with an inhibitor of testosterone synthesis (e.g.,
development throughout childhood. These tumors require ketoconazole), an antiandrogen (e.g., spironolactone) or an
radiotherapy, which contributes to hypopituitarism. aromatase inhibitor (e.g., testolactone or letrozole).
c. GnRH Independent Precocious Puberty  Patients with precocious puberty from a hormone-secreting
tumor require surgical removal.
 The most common cause of GnRH-independent precocious
 The precocious puberty of McCune Albright syndrome is
puberty is: McCUNE-ALBRIGHT SYNDROME:
o More frequent in girls than in boys GnRH independent and unresponsive to GnRH analog.
o Includes precocious gonadarche, a bone disorder with Treatment is provided with testolactone and antiandrogens or
antiestrogens such as tamoxifen.
polyostotic fibrous dysplasia and hyperpigmented cutaneous
 RECAP:
macules (café au lait spots)
o For sexual disorders, you have now your gonadotropins, so
you have to determine whether the patient has pubertal
delay or sexual precocity
o Maaga ba yung sexual development or is it late? o If it is
late, then you determine if it’s constitutional delay or
hypogonadotropic or hypergonadotropic hypogonadism o
For early pubertal development, determine if it is central
precocious puberty or peripheral
III. THYROID DISEASE
A. THYROID PHYSIOLOGY AND DEVELOPMENT
 Thyrotropin releasing hormone (TRH) synthesized in the
hypothalamus stimulates the release of pituitary thyroid
stimulating hormone (TSH).
 TSH stimulates the synthesis and release of thyroid hormones
by the thyroid gland.
 The thyroid gland concentrates iodine and binds it to
Figure 4. McCune-Albright Syndrome tyrosine molecules to produce either monoiodotyrosine or
 ADRENAL CARCINOMAS: Usually secrete adrenal diiodotyrosine.
androgens such as DHEA  With subsequent coupling of two tyrosines, T3 or T4 is
 ADRENAL ADENOMAS: May virilize a child as a result of the produced
production of androgen or may feminize a child as a result of  T3: the major fraction circulating, approx. 2/3 is derived from
the production of estrogen. the peripheral deiodination of T4 to T3 but some is produced
 Familial GnRH-independent sexual precocity with by the thyroid gland itself.
premature Leydig cell maturation: boys may have this  T4 and T3 are noncovalently bound to a specific serum carrier
precocious gonadarche on the basis of a rare entity; produces protein, thyroxine binding globulin, and to a lesser extent,
constitutive activation of the LH receptor that leads to albumin.
continuous production and secretion of testosterone without  Only small fractions (<0.02%) of T4 and T3 are not bound.
requiring LH or hCG.  Free T4 and free T3 are biologically active.
 hCG SECRETING TUMORS: stimulate LH receptors and  Free T3 exerts metabolic effects and negative feedback on
increase testosterone secretion. May be found in various TSH release.
places, including the pineal gland (dysgerminomas) or the liver  It is important to refer to age-adjusted normative data to
(hepatoblastoma). interpret thyroid function tests properly.
 OVARIAN CYSTS: May occur once or may be recurrent. High  Free T4 is the test of choice because it eliminates the effects
serum estrogen values may mimic ovarian tumors. of variation in protein binding, which can be substantial.
 CONGENITAL ADRENAL HYPERPLASIA: A cause of
 Thyroid scans with 99m-pertechnetate or 123-I-iodine are
virilization in girls
occasionally indicated in the evaluation of pediatric thyroid
EVALUATION OF SEXUAL PRECOCITY disease. They can be useful in identifying thyroid agenesis or
 The first step in evaluating sexual precocity is to determine ectopic thyroid tissue
which characteristics of normal puberty are apparent
B. THYROID DISORDERS
 Evaluate whether estrogen effects, androgen effects or both
are present. a. Hypothyroidism
 Laboratory evaluation:  Diagnosed by a decreased serum free T4 and may be the
o Determination of sex steroid levels (testosterone, estradiol, result of diseases of the thyroid gland (primary), abnormalities
DHEAS or androstenedione) of the pituitary gland (secondary) or abnormalities of the
o Determination of baseline gonadotropin concentrations hypothalamus (tertiary).
o Thyroid hormone determination also is useful because  May be congenital or acquired and may be associated with a
severe primary hypothyroidism can cause incomplete goiter.
precocious puberty.

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Pediatric Endocrinology
CONGENITAL HYPOTHYROIDISM o Autoimmune polyglandular syndrome type I consists of
 Caused by dysgenesis (agenesis, aplasia, ectopia) or less hypoparathyroidism, Addison disease, mucocutaneous
often, dyshormogenesis. candidiasis and, often, hypothyroidism.
 Thyroid tissue is usually not palpable in these sporadic o Autoimmune polyglandular syndrome type II consists of
nongoitrous conditions. Addison disease, DM1, and frequently autoimmune
 The free T4 concentration is low and the TSH is elevated. hypothyroidism. Trisomy 21 and Turner syndrome are
 Routine neonatal screening programs to measure cord blood predisposed to the development of autoimmune thyroiditis.
or often heel stick is available o Diagnosis can be confirmed by serum antithyroid peroxidase
 An immediate confirmatory serum sample should be obtained and antithyroglobulin antibodies.
from any infant having a positive result on a screening test. o Neither biopsy nor thyroid scan is indicated in Hashimoto
 A low free T4 and high TSH confirm the finding. thyroiditis, although the thyroid scan with reduced uptake
may differentiate hashitoxicosis from Grave’s disease
 When tertiary or secondary hypothyroidism is detected,
o Treatment with thyroid hormone sufficient to normalize TSH
assessment of other pituitary hormones and investigation of
and free T4 is indicated for hypothyroidism in Hashimoto
pituitary-hypothalamic anatomy via MRI are indicated.
thyroiditis.
 Congenital thyroxine-binding globulin deficiency is
associated with low serum total T4 concentration, normal TSH b. Hyperthyroidism
and normal serum free T4. This is a euthyroid condition; does GRAVES DISEASE
not require treatment because it is merely a binding protein  Presents as hyperthyroidism and is about five times more
abnormality. common in girls than in boys with a peak incidence in
 Clinical manifestations of congenital hypothyroidism are adolescence.
subtle but become more evident weeks or months after  Personality changes, mood instability and poor school
birth. performance are common initial problems.
 Newborn screening is crucial to make an early diagnosis and  Tremors, anxiety, inability to concentrate and weight loss may
initiate thyroid replacement therapy by younger than 1 month be insidious and confused with a psychological disorder until
of age. thyroid function tests reveal the elevated serum free T4 level.
 Findings are:  A firm homogenous goiter is usually present.
o Hypothermia, acrocyanosis, respiratory distress, large  Many patients complain of neck fullness.
fontanels, abdominal distension, lethargy, poor feeding,
 Auscultation may reveal a bruit over the gland that needs to
prolonged jaundice, edema, umbilical hernia, mottled skin,
be differentiated from a carotid bruit.
constipation, large tongue, dry skin, and hoarse cry
 Three treatment choices are available: pharmacologic,
 When treatment (with levothyroxine) is initiated within 1 month
radioactive iodine and surgical.
or less after birth, the prognosis for normal intellectual
 Medical therapy to block thyroid hormone synthesis consists of
development is excellent.
methimazole (0.4 to 0.6 mg/kg/day once or twice daily) or
 If therapy is instituted after 6 months, when the signs of severe
propylthiouracil (5 to 7 mg/kg/day divided every 8 hours).
hypothyroidism are present, the likelihood of normal
 Both medications are equally effective, however,
intellectual function is markedly decrease.
propylthiouracil is no longer a first-line therapy secondary to
 Growth improves after thyroid replacement even in the late
concerns of severe liver injury and acute liver failure.
diagnosed cases.
 A beta blocker, such as propranolol or atenolol, is started if
ACQUIRED HYPOTHYROIDISM symptoms are severe to control cardiac manifestations and is
 Clinical manifestations may be subtle. tapered as methimazole takes effect.
 Should be suspected in any child who has a decline in growth  Radioiodine (131I) is slower in exerting therapeutic effects,
velocity, especially if not associated with weight loss. may require repeated dosing, and is likely to cause permanent
 The most common cause of acquired hypothyroidism in older hypothyroidism.
children is lymphocytic autoimmune thyroiditis (Hashimoto  Surgical treatment consists of partial or complete
thyroiditis) thyroidectomy.
 In many areas of the world, iodine deficiency is the etiology of THYROID STORM
endemic goiter (endemic cretinism).
 A rare medical emergency consisting of tachycardia,
 The failure of the thyroid gland may be heralded by an disorientation, elevated blood pressure and hyperthermia.
increase of TSH before T4 level decrease.
 Treatment includes reducing the hyperthermia with a cooling
 Acquired hypothyroidism is not a cause of permanent blanket and administering a beta blocker to control the
developmental delay. tachycardia, hypertension and autonomic hyperfunction
Hashimoto Thyroiditis symptoms.
o Also known as autoimmune or lymphocytic thyroiditis.  Iodine may be given to block thyroid hormone release after an
o A common cause of goiter and acquired thyroid disease antithyroid medication is started.
in older children and adolescents.  Hydrocortisone may be indicated for relative adrenal
o A family history of thyroid disease is present in 25 to 35% of insufficiency and therapy for heart failure includes diuretics
patients. and digoxin
o The etiology is an autoimmune process targeted against the CONGENITAL HYPERTHYROIDISM
thyroid gland with lymphocytic infiltration and lymphoid follicle
 Results from transplacental passage of maternal TSIs
and germinal center formation preceding fibrosis and atrophy.
antibodies and may be masked for several days until the short-
o Clinical manifestations include a firm, nontender euthyroid,
lived effects of transplacental maternal antithyroid medication
hypothyroid or rarely, hyperthyroid (hashitoxicosis)
wear off.
diffuse goiter with a pebble-like surface.
 Clinical hallmarks:
o Onset typically occurs after 6 years of age with a peak
incidence in adolescence with a female preponderance. o Irritability, tachycardia, polycythemia, craniosynostosis, bone
o Associated autoimmune diseases include DM1, adrenal age advancement, poor feeding, failure to thrive
insufficiency and hypoparathyroidism.  This condition may be anticipated if the mother is known to be
thyrotoxic in pregnancy.

6 | 7 Trans No. 10.2 Associate Editors CAMA, BAWAGAN, DEL ROSARIO, CARDENAS | Co-Chief Editor CABALQUINTO
Pediatric Endocrinology
 Treatment for a severely affected neonate includes
methimazole and as needed a beta blocker to help decrease
symptoms.
 Because half-life of the immunoglobulin is several weeks,
spontaneous resolution of neonatal thyrotoxicosis resulting
from transplacental passage of immunoglobulins usually
occurs by 2 to 3 months of age
C. NODULES OR TUMORS OF THE THYROID
 About 2% of children develop solitary thyroid nodules, most of
which are benign.
 Evaluation of a nodule includes thyroid function tests, neck
ultrasound and if needed, fine needle aspiration (FNA).
 Ultrasound guidance may be needed for aspiration of small
nodules or those not palpable.
 Nodules found to be benign on FNA may be monitored
through clinical exam and ultrasound.
 Carcinoma of the thyroid is rare in children.
o Papillary and follicular carcinomas represent 90% of
childhood thyroid cancers.
o A history of therapeutic head or neck irradiation or radiation
exposure from nuclear accidents predisposes a child to
thyroid cancer.
o Carcinoma presents as a firm to hard, painless
nonfunctional solitary nodule and may spread to
adjacent lymph nodes.
o Rapid growth, hoarseness (recurrent laryngeal nerve
involvement) and lung metastasis may be present.
o If the nodule is solid on ultrasound, is cold on radioiodine
scanning and feels hard, the likelihood of carcinoma is high.
o Excisional biopsy usually is performed, but FNA biopsy also
may be diagnostic.
o Treatment includes total thyroidectomy, selective regional
node dissection and radioablation for residual or recurrent
disease.
o The prognosis is usually good if the disease is diagnosed
early.
 Medullary carcinoma of the thyroid may be asymptomatic
except for a mass.
o Diagnosis is based on the presence of elevated calcitonin
levels, either in the basal state or after pentagastrin
stimulation (difficult to obtain) and histologic examination.
o This tumor most often occurs with multiple endocrine
neoplasia 2a or 2b (MEN) possibly in a familial pattern.
o In some families, the presence of mutations of the RET
proto-oncogene is predictive of the development of
medullary carcinoma of the thyroid.
o Genetic screening of other members of the family is
indicated.
o Prophylactic thyroidectomy is indicated for family members
with the same allele.
IV. REFERENCES AND CITATIONS
 Laygo, KA. (2022). Pediatric Endocrinology (Part 2). Powerpoint
Presentation. April 8, 2022. University of Northern Philippines –
College of Medicine (UNP-CMed).
 Palma Sisto, P. A. (2015). Section 23: Endocrinology. In M. K.
Heneghan (Ed.), Nelson Essentials of Pediatrics (7th ed., pp. 583–
601). essay, Saunders.

7 | 7 Trans No. 10.2 Associate Editors CAMA, BAWAGAN, DEL ROSARIO, CARDENAS | Co-Chief Editor CABALQUINTO