ENDOCRINE SYSTEM

Dr Grandelee Daquioag-Taquiqui
 DISORDERS OF THE
HYPOTHALAMUS AND
PITUITARY GLAND
 HORMONES OF THE
HYPOTHALAMUS AND
PITUITARY
 Pituitary gland- major regulator of an
elaborate hormonal system
 -receives signals from the hypothalamus and

responds by sending pituitary hormones to

target glands
 Target glands produce hormones that provide

negative feedback at the level of the

hypothalamus and pituitary
ANATOMY
 Pituitary gland – located at the base of the
skull in a saddle-shaped cavity of the
sphenoid bone called sella turcica
 Dura- dense layer of connective tissue, forms

the roof of the sella

 Pituitary stalk-connects the pituitary gland to

the hypothalamus
 Anterior lobe-constitutes approx 80%
EMBRYOLOGY
 Anterior pituitary gland – originates from the
Rathke pouch as an invagination of the oral
ectoderm
 6 wks of gestation, connection between

rathke pouch and oropharynx is completely

obliterated
 Pouch establishes a direct connection with

downward extension of hypothalamus

VASCULAR SUPPLY
 Arterial blood supply of pituitary gland –
originates from the internal carotid via
inferior, middle and superior hypophyseal
arteries
 Forms a unique portal circulation connecting

the hypothalamus and pituitary

ANTERIOR PITUITARY CELL TYPES
 GROWTH HORMONES
 Human GH- synthesized, stored and secreted

by somatotropes in the pituitary

 GH is secreted in a pulsatile fashion under

the regulation of hypothalamic hormones

 Somatostatin inhibits GH release
 Growth hormone-releasing hormone-

stimulates GH release
 Ghrelin- stimulates GH release
 Physiologic factors that stimulates release of
GH
 Sleep
 Exercise
 Physical stress
 Trauma
 Acute illness
 Puberty
 Fasting
 hypoglycemia
 Physiologic factors that inhibit release of GH
 Hyperglycemia
 Hypothyroidism
 glucocorticoids
 PROLACTIN
 PRL- peptide made in pituitary lactotropes
 Consistently secreted unless actively

inhibited by dopamine
 Primary physiologic role is initiation and

maintenance of lactation
 THYROID STIMULATING HORMONE
 Stored in secretory granules and released into

circulation primarily in response to TRH.

 TSH- stimulates release of thyroxine(T4) and

triiodothyronine (T3) from the thyroid gland

 Deficiency of TSH-inactivity and atrophy of

thyroid
 Excess TSH- results in hypertrophy and

hyperplasia
 ADRENOCORTICOTROPIC HORMONE
 Secretion of ACTH is regulated by

corticotropin-releasing hormone (CRH)

 Secreted in a diurnal pattern
 Acts on adrenal cortex to stimulate cortisol

synthesis and secretion

 Principal pigmentary hormone in humans
 LUTEINIZING HORMONE AND FOLLICLE
STIMULATING HORMONE
 Gonadotropic hormones include 2

glycoproteins-LH and FSH

 secretion of LH is inhibited by androgens

and estrogens
 Secretion of FSH is suppressed by gonadal

production of inhibin
POSTERIOR PITUITARY CELL TYPES
 ANTIDIURETIC HORMONE
 ADH- regulates water conservation at the

level of the kidney by increasing permeability

of renal collecting duct to water
 Stimuli for release:
 Increased plasma osmolality
 Decreased blood volume
 OXYTOCIN
 Oxytocin stimulates uterine contractions at

the time of labor and delivery in response to

distention of reproductive tract
 -stimulates smooth muscle contraction in the

breast during suckling resulting in milk

letdown
 Play a significant role in appetite regulation

and obesity by inducing anorexia.

HYPOPITUITARISM
 HYPOPITUITARISM- denotes underproduction
of growth hormone (GH) alone or in
combination with deficiencies of other
pituitary hormones
MULTIPLE PITUITARY HORMONE
DEFICIENCY
 PROP1
 POU1F1
 HESX1
 LHX3 and LHX4
GROWTH HORMONE INSENSITIVITY
 CONGENITAL HYPOPITUITARISM
 Child with hypopituitarism-usually normal

size and weight at birth

 Present with neonatal emergencies such as:
 Apnea
 Cyanosis
 Severe hypoglycemia w/ or w/out seizures
 Prolonged jaundice
 Micropenis in boys
 ACQUIRED HYPOPITUITARISM
 Child is normal initially and manifestations

similar to those seen in idiopathic pituitary

growth failure gradually appear and progress
 Atrophy results in weight loss, asthenia,

sensitivity to cold, mental torpor and absence

of sweating.
 Growth slows dramatically
 LABORATORY FINDINGS
 GH deficiency-suspected in children w/

severe postnatal growth failure

 Criteria for growth failure include height

below 1st percentile for age and sex or height

>SD below sex adjusted mid parent height
 Definitive diagnosis requires demonstration

of absent or low levels of GH

 RADIOLOGIC FINDINGS
 CT is appropriate for recognizing suprasellar

calcification associated w/
craniopharyngiomas and bony changes
accompanying histiocytosis
 MRI- provides much more detailed view of

hypothalamic and pituitary anatomy

 TREATMENT
 Recombinant hGH has been available by

prescription since 1982.

 Indications for GH treatment:
 GH deficiency Prader-Willi syndrome
 Turner syndrome SHOX gene abnormality
 Chronic renal failure Noonan syndrome
 Idiopathic short stature
 SGA short stature
DIABETES INSIPIDUS
 DIABETES INSIPIDUS (DI)- manifest clinically
with polyuria and polydipsia and can result
from either vasopressin deficiency( central DI)
or vasopressin insensitivity at the level of
kidney (nephrogenic DI)
 CENTRAL DIABETES INSIPIDUS
 Can result from multiple etiologies

including :genetic mutations in vasopressin

gene, trauma
 Congenital malformations
 Neoplasms
 Autoimmune
 Infectious diseases
 Increased metabolism of vasopressin
 NEPHROGENIC DIABETES INSIPIDUS
 Nephrogenic ( vasopressin insensitive ) DI can

result from genetic or acquired causes

 Congenital X-linked NDI results from

inactivating mutations of vasopressin V2

receptor
 Acquired NDI can result from hypercalcemia

or hypokalemia
 TREATMENT FOR CENTRAL DI
 Fluid therapy
 Vasopressin analogs- DDAVP
 Aqueous vasopressin- Pitressin
TREATMENT OF NDI
 Treatment focuses on eliminating underlying

disorder such as offending drugs,

hypercalcemia , hypokalemia or ureteral
obstruction
 Thiazide diuretics are intended to decrease

overall urine output.

 HYPERPITUITARISM, TALL
STATURE, AND OVERGROWTH
SYNDROMES
HYPERPITUITARISM
 Primary hypersecretion of pituitary hormones
rarely occurs in pediatric population
 Primary hypersecretion of pituitary hormones

by adenoma is uncommon in childhood

 Most commonly diagnosed adenoma during

childhood is prolactinoma, corticotropinoma

and somatotropinoma
TALL STATURE
 Overgrowth in the fetus and neonate
 Maternal diabetes is the most common cause of
infants large for gestational age

 Overgrowth in childhood or adolescence

 Normal variant ,constitutional tall stature
 Exogenous obesity
 Klinefelter syndrome
 XYY sundrome
 Marfan syndrome
 homocystinuria
 SOTOS SYNDROME (CEREBRAL GIGANTISM)
 Children with cerebral gigantism are above

the 90th percentile for both length and weight

at birth
 Syndrome is characterized by a large

dolichocephalic head, prominent forehead

and jaw, hypertelorism, antimongoloid slant
of palpebral fissures, high arched palate,
large hands and feet
Treatment of normal variant tall stature
Reaasurance of family and patient
Sex steroids –designed to accelerate puberty
and to promote epiphyseal fusion
 EXCESS GROWTH HORMONE SECRETION AND
PITUITARY GIGANTISM
 In persons w/ open epiphyses, overproduction of
GH results in gigantism
 Closed epiphyses- results in acromegaly
 The cardinal clinical feature – longitudinal
growth acceleration
 Coarse facial features
 Enlarging hands and feet
 Acromegalic features- enlargement of the distal
parts of the body
 TREATMENT
The goals of therapy are to remove or shrink
the pituitary mass, restore GH and secretory
patterns to normal, to restore IGF-1 levels to
normal
Pituitary adenomas-transphenoidal surgery
Somatostatin analogs- highly effective in
treatment of patients w/ GH excess
DISORDERS OF PUBERTAL
DEVELOPMENT
CENTRAL PRECOCIOUS PUBERTY
 central precocious puberty is defined by the
onset of breast development before the age
of 8 yr in girls and by the onset of testicular
development before the age of 9 yr in boys
 Early activation of hypothalamic-pituitary –

gonadal axis
 CLINICAL MANIFESTATIONS
 In affected girls and boys, height, weight and

osseous maturation are advanced

 Increased rate of bone maturation results in

early closure of epiphyses

LABORATORY FINDINGS
Measurement of LH in serial blood samples
IV administration of GnRH agonist –particularly
for boys
Pelvic UTZ- in girls reveal progressive
enlargement of ovaries
 TREATMENT
 Long- acting formulations of GnRH agonists
 1. Leuprolide acetate IM every 4 wks
 2. longer acting preparations of depot

leuprolide every 90 days

 3. histrelin SC-lasting 12 mo
PRECOCIOUS PUBERTY RESULTING
FROM ORGANIC BRAIN LESIONS
 ETIOLOGY
 Hypothalamic hamartomas-most common

brain lesion causing precocious puberty

 CLINICAL MANIFESTATIONS
 Remain static in size, producing no size other

than precocious puberty

 TREATMENT
 Therapy w/ GnRH agonist is effective in brain

lesions causing central precocious puberty

PRECOCIOUS PUBERTY FOLLOWING
IRRADIATION OF THE BRAIN
 Radiation therapy generally for leukemia and
intracranial tumors- increases the risk of
precocious puberty
 TREATMENT
 GnRH analogs are effective in arresting

pubertal progression in this patient

population
McCune Albright Syndrome
 Associated with patchy cutaneous pigmentation
and fibrous dysplasia of the skeletal system
 A classical cause of peripheral precocious
puberty
 It can induce pituitary, thyroid and adrenal
aberrations.
 Extragonadal manifestations: hyperthyroidism
 Cushing syndrome
 Increased GH secretion
DISORDERS OF THE
THYROID GLAND
HYPOTHYROIDISM
 Hypothyroidism- results from deficient
production of thyroid hormone either from
defect in the gland itself or a result of
reduced thyroid- stimulating hormone
stimulation.
CONGENITAL HYPOTHYROIDISM
 Most cases of congenital hypothyroidism are
not hereditary and result from thyroid
dysgenesis
 Prevalence is 1 in 2000.
 PRIMARY HYPOTHYROIDISM
 Thyroid dysgenesis –some form (aplasia,

hypoplasia, ectopic thyroid gland) –is the

most common cause of permanent congenital
hypothyroidism
 80-85% of cases
 Cause of thyroid dysgenesis is unknown in

most cases
 Occurs sporadically
 DEFECTIVE SYNTHESIS OF THYROXINE
 DEFECT OF IODIDE TRANSPORT
 THYROID PEROXIDASE DEFECTS OF

ORGANIFICATION AND COUPLING

 DEFECTS OF THYROGLOBULIN SYNTHESIS
 DEFECTS IN DEIODINATION
 THYROTROPIN HORMONE UNRESPONSIVENESS
 DEFECTS IN THYROID HORMONE TRANSPORT
 THYROTROPIN RECEPTOR BLOCKING

ANTIBODY
CENTRAL (HYPOPITUITARY)
HYPOTHYROIDISM
 THYROTROPIN AND THYROTROPIN-
RELEASING HORMONE DEFICIENCY
 More often in these conditions, the deficiency

of TSH is secondary to a deficiency of TRH

 TSH-deficient hypothyroidism- found in 1 in

30,000-50,000 infants
 CLINICAL MANIFESTATIONS
 Most infants with congenital hypothyroidism

are asymptomatic at birth

 Approximately 10% of infants w/ CH have

associated congenital anomalies

 Cardiac anomalies are most common
 May have associated hearing loss
 If CH goes undetected and untreated- by 3-

6 mos , clinical picture is fully developed

 The child’s growth will be stunted,
extremities are short
 Anterior fontanel is large and posterior

fontanel may remain open

 Eyes appear far apart
 Bridge of broad nose is depressed
 Palpebral fissures are narrow
 Eyelids are swollen
 Mouth kept open, thick, broad tongue

protrudes
 Dentition will be delayed
 Neck is short and thick
 Hands are broad, fingers are broad
 Skin is dry and scaly
 Development –usually delayed
 Late in learning to sit and stand
 Voice is hoarse and do not learn to talk
 Sexual maturation –delayed or none
 LABORATORY FINDINGS
 Identified by newborn screening
 T4 or freeT4 are low,
 Serm levels of T3 – normal
 TSH- elevated > 100 mU/L
 UTZ of thyroid is helpful
TREATMENT
Levothyroxine- given orally is the treatment of
choice
THYROIDITIS
 CHRONIC LYMPHOCYTIC THYROIDITIS
 (HASHIMOTO THYROIDITIS)
 Most common cause of thyroid disease in

children and adolescents

 Most common cause of acquired

hypothyroidism
 ETIOLOGY
 Autoimmune disease results from inheritance

of susceptible genes involved in

immunoregulation and environmental
triggers.
 CLINICAL MANIFESTATIONS
 Goiter and growth retardatio-most common

manifestation
 Goiter can appear insidously
 In most patients, thyroid is diffusely

enlarged, firm and nontender


 LABORATORY FINDINGS
 Thyroid function tests (free T4, TSH) are often

normal
 Positive anti- Tg Abs
 Positive serum TPO-Abs
GOITER
 A goiter or thyromegaly is an enlargement of
the thyroid gland.
 Persons with enlarged thyroids can have

normal function of the gland(euthyroidism),

thyroid deficiency or overproduction of the
hormones
 goiter most often results from increased

pituitary secretion of TSH in response to

decreased circulating levels of thyroid
hormones
CONGENITAL GOITER
-usually sporadic and can result from a fetal
thyroxine (T4) synthetic defect or from
administration of antithyroid drugs
Administration of thyroid hormone to affected
infants may be indicated to treat clinical
hypothyroidism
 ENDEMIC GOITER AND CRETINISM
 ETIOLOGY
 Association between dietary deficiency of

iodine and prevalence of goiter is well

established
Moderate deficiency of iodine can be overcome
by increased efficiency in the synthesis of
thyroid hormone
 CLINICAL MANIFESTATION
 Iodine deficient goiters are more common in

girls than boys

 Endemic cretinism is the most serious

consequence of iodine deficiency

 TREATMENT
 Administration of single IM injection of

iodinated poppy seed oil to women prevents

iodine deficiency during future pregnancies
for 5 yrs
HYPERTHYROIDISM
 Hyperthyroidism- results from excessive
secretion of thyroid hormones during
childhood with few exceptions
 GRAVES disease- an autoimmune disorder,

production of thyroid-stimulating
immunoglobulin that binds to and activates
the G- protein-coupled thyroid stimulating
hormone TSH receptor results in diffuse toxic
goiter.
GRAVES DISEASE
 EPIDEMIOLOGY
 Occurs in approx 0.02% of children
 Peak incidence is 11-15 yr old
 Most children have positive family history of

autoimmune thyroid disease

 ETIOLOGY
 Enlargement of thymus, splenomegaly,

lymphadenopathy, infiltration of thyroid

gland and retroorbital tissues with
lymphocytes and plasma cells, and peripheral
lymphocytosis are well established findings in
Graves disease.
 CLINICAL MANIFESTATIONS
 Approx 5% of all patients with

hyperthyroidism are younger that 15 yr of

age, peak incidence occur during adolescence
 Clinical course is highly variable but usually

not so fulminant as in many adults

 Symptoms develop gradually
 Usual interval bet onset and diagnosis is 6-

12 mos.
 Earliest signs in children- emotional
disturbances accompanied by motor
hyperactivity
 Irritable and excitable, emotional lability
 Short attention span and poor sleep
 Tremor of fingers
 Voracious appetite, loss or no increase in wt
 Acceleration in growth velocity
 Size of thyroid is variable
 Diffuse goiter, soft w/ a smooth surface
 Exopthalmos is noticeable in most patients
 Tachycardia , palpitations, dyspnea, and

cardiac enlargement
 Systolic blood pressure , pulse pressures are

increased
thyroid crisis or thyroid storm- form of
hyperthyroidism manifested by severe
biochemical derangement, acute onset,
hyperthermia, tachycardia, heart failure and
restlessness
Rapid progression to delirium, come and death
 LABORATORY FINDINGS
 Levels of TSH are suppressed to below the

lower range of normal

 Serum levels of T4, T3, free T3 and free T4

are typically elevated

 Antithyroid antibodies, including thyroid

peroxidase antibodies are often present

 Newly diagnosed graves disease have

measurable TRSab.
TREATMENT
Medical therapy using antithyroid drugs
Radioiodine is gaining acceptance as initial
treatment in children older than 10 yr of age
2 antithyroid drugs used are: propylthiouracil
and methimazole
B adrenergic blocking agent such as propanolol
or atenolol is useful supplement in mngt of
severely toxic patients
 Radioiodine is an effective therapy for Graves
disease in children
 In severe thyrotoxicosis- euthyroidism

should be restored prior to radioablation in

order to deplete the gland of preformed
hormone and reduce the risk thyrotoxic flare
from radiation thyroiditis.
 Thyroidectomy- done only after the patient

has been brought to euthyroid state

 CONGENITAL HYPERTHYROIDISM
 Neonatal Graves disease is caused by

transplacental passage of TRSAb

 Clinical onset ,severity and course may be

modified by presence of thyrotropin –

receptor blocking antibody and transplacental
transfer of antithyroid drugs taken by the
mother
 CLINICAL MANIFESTATION
 Many of the infants are premature and appear

to have intrauterine growth restriction

 Most have goiters
 Extremely restless, irritable, and hyperactive
 Microcephaly and ventricular enlargement

may be present
 Eyes opened wide and appear exopthalmic
 Extreme tachycardia and tachypnea, temp

elevated
 Serum levels of T4 or free T4 and T3 are
markedly elevated
 TSH is suppressed.
 Advanced bone age, frontal bossing with

triangular facies and cranial synostosisare

common
 TREAMENT
 Oral administration of propanolol (1-2

mg/kg/24) and methimazole (0.25-1

mg/kg/24)
 Saturated solution of potassium iodide (1

drop per day ) may be added

 Most cases remit by 3-4 mo of age
CARCINOMA OF THE THYROID
 EPIDEMIOLOGY
 Carcinoma of the thyroid is rare in childhood
 Annual incidence in children younger than 15

yr is 2 in 100,000.
 PATHOGENESIS
 Papillary carcinoma (88%) –most common

subtype
 CLINICAL MANIFESTATIONS
 Incidence peaks in adolescence
 Girls are more commonly affected than boys
 Painless nodule in the neck-usual presentation
 Rapid growth
 Large nodule size, firmness , fixation to
adjacent tissues,
 Hoarseness
 Dysphagia
 Neck lymphadenopathy
 DIAGNOSIS
 Nuclear abnormalities that are well identified

by cytology and fine-needle aspiration- gold

standard in the evaluation of adults w/
nodules
 Operative pathology –required to confirm the

diagnosis , stage the extent of disease

 TREATMENT
 Primary therapy is surgical resection.
 Suspicious lymph nodes may be biopsied

preoperatively
 Thyroidectomy is usually followed by

adjunctive therapy w/ both TSH suppression

 Itherapy- to ablate normal thyroid remnant /

treat residual thyroid cancer

SOLITARY THYROID NODULE
 Frequency of thyroid nodules increases w/
age
 Recent studies of children report lower cancer

prevalence (20-26%)
 Benign disorders that can occur as a solitary

thyroid mass include benign adenomatous or

colloid nodules.
 Diagnosis- thru ultrasound
 Biopsy by UTZ-guided FNA
MEDULLARY THYROID CARCINOMA
Medullary thyroid carcinoma (MTC)- arises
from parafollicular cells
 Accounts for 2% of thyroid malignacies
 Palpable thyroid nodule- most common

presentation of sporadic MTC

 Can often be made through routine FNA

cytology
 Total thyroidectomy –indicated for all

children shown by genetic studies to carry

high-risk RET mutations
 DISORDERS OF THE
PARATHYROID GLAND
HYPOPARATHYROIDISM
 ETIOLOGY
 1. APLASIA OR HYPOPLASIA
 2.X-LINKED RECESSIVE

HYPOPARATHYROIDISM
 3. AUTOSOMAL RECESSIVE

HYPOPARATHYROIDISM W/ DYSMORPHIC
FEATURES
 4.HYPOPARATHYROIDISM, SENSORINEURAL

DEAFNESS, AND RENAL ANOMALY SYNDROME

 5. SUPPRESSION OF NEONATAL PARATHYROID
HORMONE SECRETION BECAUSE OF
MATERNAL HYPERPARATHYROIDISM
 6. AUTOSOMAL DOMINANT

HYPOPARATHYROIDISM
 7. HYPOPARATHYROIDISM ASSO W/

MITOCHONDRIAL DISORDERS
 8. SURGICAL HYPOPARATHYROIDISM
 9.AUTOIMMUNE HYPOPARATHYROIDISM
 10.IDIOPATHIC HYPOPARATHYROIDISM
 CLINICAL MANIFESTATIONS
 Muscular pain and cramps are early

manifestations- progress to numbness,

stiffness, tingling of hands and feet
 Positive Chvostek or Trosseau sign, or

laryngeal and carpopedal spasms

 Convulsions w/ or w/out loss of

consciousness
 LABORATORY FINDINGS
 Serum calcium level is low (5-7 mg/dL)
 Phosphorus level is elevated (7-12 mg/dL)
 Levels of PTH are low
 Radiographs of bones occasionally reveal

increased density limited to the metaphyses

 CT scans of skull can reveal calcifications in

basal ganglia
 TREATMENT
 Emergency treatment of neonatal tetany

consists of intravenous injections of 5-10 ml

or 1-3 mg/kg of a 10% solution of calcium
gluconate at rate of 0.5-1.0 mL/min
 Calcitriol should be given
 Adequate intake of calcium
HYPERPARATHYROIDISM
 ETIOLOGY
 Neonatal severe hyperparathyroidism –rare

disorder
 MEN type 1
 Hyperparathyroidism-jaw tumor syndrome
 MEN type 11
 Transient neonatal hyperparathyroidism
 CLINICAL MANIFESTATIONS
 Manifestations of hypercalcemia include:
 Muscle weakness, fatigue, headache
 Anorexia, abdominal pain, nausea, vomiting
 Constipation, polydipsia, polyuria, weight

loss, fever
 LABORATORY FINDINGS
 serum calcium level-elevated >12 mg/dL
 Serum phosphorus level is reduced
 Serum levels of PTH are elevated
 Calcitonin levels are normal
 Resorption of periosteal bone- characteristic

radiologic finding
TREATMENT
Surgical exploration- indicated in all instances
Most neonates w/ severe hypercalcemia require
total parathyroidectomy
Intravenous administration of calcium
gluconate may be required post op
DISORDERS OF THE ADRENAL
GLAND AND RELATED
DISORDERS
CONGENITAL ADRENAL HYPERPLASIA
 CONGENITAL ADRENAL HYPERPLASIA (CAH)-
 Is a family of autosomal recessive disorders

of cortisol biosynthesis
 Cortisol deficiency increases secretion of

corticotropin (ACTH) which in turn leads to

adrenocortical hyperplasia and
overproduction of metabolites
 CONGENITAL ADRENAL HYPERPLASIA CAUSED
BY 21 –HYDROXYLASE DEFICIENCY
 ETIOLOGY
 More than 90% of cases of CAH are caused by

21 hydroxylase deficiency
 P450 enzyme hydroxylates progesterone and

17-hydroxyprogesterone to yield 11-

deoxycorticosterone and 11- deoxycortisol
 Required in synthesis of aldosterone and

cortisol
 EPIDEMIOLOGY
 Classic 21-hydroxylase deficiency occurs in

approximately 1 in 15,000-20,000 livebirths

 70% have salt losing forms
 30% have simple virilizing form
 P ATHOGENESIS AND CLINICAL
MANIFESTATIONS
 ALDOSTERONE AND CORTISOL DEFICIENCY
 Both hormones require 21-hydroxylation for

their synthesis, both are deficient in most

severe salt wasting form of the disease
 Signs and symptoms include:
 Progressive weight loss, anorexia, vomiting,

dehydration, weakness, hypotension,

hypoglycemia, hyponatremia, hyperkalemia
 First develop at 10-14 days of age
 Without treatment, shock, cardiac arrythmias

and death may occur w/in days or weeks

 PRENATAL ANDROGEN EXCESS
 Most impt problem caused by accumulation

of steroid precursor-high levels of

androstenedione converted outside the
adrenal gland to testosterone
 Affected females have masculinized external

genitalia
 Prenatal exposure of the brain to high levels

of androgens may influence sexually

dimorphic behaviors in affected females
 There is an increased frequency of
homosexuality in affected females
 Male infants appear normal at birth
 Diagnosis may not be made in boys until

signs of adrenal insufficiency develop.

 LABORATORY FINDINGS
 Please refer to Nelsons 20th ed table 576-1.
 PRENATAL DIAGNOSIS
 Diagnosis of 21-hydroxylase is possible late

in the 1st trimester by analysis of DNA

obtained by chorionic villus sampling
 During 2nd trimester by amniocentesis
 NEWBORN SCREENING
 All states in the US, and many other countries

have instituted newborn screening programs

 17 hydroxyprogesterone levels in dried blood

is analyzed
 Potentially affected infants are typically

quickly recalled for additional testing at

approx 2 wk of age
 Infants w/ salt wasting disease have

abnormal electrolytes by this age

 TREATMENT
 GLUCOCORTICOID REPLACEMENT
 Cortisol deficiency is treated with

glucocorticoids
 Treament suppresses excessive production of

androgens, minimizes excessive growth and

skeletal maturation and virilization
 Hydrocortisone at 15-20 mg/BSA daily

administered orally in 3 divided doses

 MINERALOCORTICOID REPLACEMENT
 Patients w/ salt wasting disease require

mineralocorticoid replacement w/
fludrocortisone
 1st few mos of life- 0.1-0.3 mg daily in 2

divided dose
 Infants and children-0.05-0.1 mg daily
 SURGICAL MANAGEMENT OF AMBIGUOUS
GENITALIA
 Significantly virilized females usually

undergo surgery bet 2-6 mo of age

 PRENATAL TREATMENT
 Prenatal diagnosis-facilitate appropriate

prenatal treatment of affected females

 Dexamethasone- given at 20 ug/kg

prepregnancy maternal weight

 This suppresses secretion of steroids by the

fetal adrenal
CUSHING SYNDROME
 Is the result of abnormally high blood levels
of cortisol or other glucocorticoids
 Can be iatrogenic or result of endogenous

cortisol secretion
 ETIOLOGY
 The most common cause of Cushing

syndrome is prolonged exogenous

administration of glucocorticoid hormones
 Endogenous Cushing syndrome –most often

caused by functioning adrenocortical tumor

 CLINICAL MANIFESTATIONS
 The face is rounded , prominent cheeks and
flushed appearance ( moon facie)
 Generalized obesity is common in younger
children
 Growth is impaired w/ length falling below 3 rd
percentile
 Increased susceptibilty to infection may lead to
sepsis
 In older children- short stature is a common
presenting feature
 LABORATORY FINDINGS
 Cortisol levels in blood are normally highest

at 8 am and decrease to less than 50% by

midnight
 Midnight cortisol levels >4.4 ug/dL strongly

suggest diagnosis
 TREATMENT
 Transphenoidal pituitary microsurgery is tge

treatment of choice in pituitary Cushing

disease in children
 Management of patients undergoing

adrenalectomy requires adequate preop and

postop replacement therapy w/ a
corticosteroid
DISORDERS OF THE
GONADS
HYPERGONADOTROPIC HYPOGONADISM
IN THE MALE ( PRIMARY HYPOGONADISM
 ETIOLOGY
 1. Congenital anorchia or testicular

regression syndrome
 2. chemotherapy and radiation induced

hypogonadism
 3. Sertoli Cell-only syndrome
 4. testicular dysgenesis syndrome
 CLINICAL MANIFESTATIONS
 Suspected at birth if the testes and penis are

abnormally small
 Condition noticed at puberty when secondary

sex characteristics fail to develop

 Facial, pubic and axillary hair is scant or

absent
 Penis and scrotum remain infantile
 Proportions of the body are described as

eunuchoid
DIAGNOSIS
 serum FSH and LH are elevated to greater

than age- speciifc normal values in infancy

 NOONAN SYNDROME
 ETIOLOGY
 Noonan occurs in 1 in 1,000-2500 live births
 20% 0f cases are familial
 Males and females are equally affected
 CLINICAL MANIFESTATIONS
 The most common abnormalities are short

stature, webbing of the neck, pectus

carinatum or pectus excavatum, cubitus
valgus, right sided congenital heart disease
and characteristic facie
 Hypertelorism, epicanthus, ptosis,

micrognathia, downward slanting palpebral

fissures
 TREATMENT
 Human growth hormone results in

improvement in growth velocity in many

Noonan syndrome patients, comparable to
that seen in patients w/ Turner syndrome.
 KLINEFELTER SYNDROME
 ETIOLOGY
 most common sex chromosomal aneuploidy

in males
 80% of them have 47 XXY chromosome

complement
 CLINICAL MANIFESTATIONS
 Patients tend to be tall, slim ,tendency to

have long legs

 Testes tend to be small for age
 Pubertal development may be delayed
 Approx 80% of adults have gynecomastia
 Azoospermia and infertility are usual
 LABORATORY FINDINGS
 Most males with Klinefelter syndrome go

through life undiagnosed

 Chromosome s should be examined in all

patients suspected of having Klinefelter

syndrome
 MANAGEMENT
 Boys known to have Klinefelter syndrome

should be monitored closely for speech,

learning and behavioral problems
 Testosterone, LH, FSH levels should be

checked at 11-12 yr of age

HYPOFUNCTION OF THE OVARIES
 HYPERGONADOTROPIC HYPOGONADISM IN
FEMALE ( PRIMARY HYPOGONADISM)
 TURNER SYNDROME
 Consist of sexual infantism , webbed neck

and cubitus valgus in adult females

 PATHOGENESIS
 Half the patients with Turner syndrome have

a 45X chromosomal complement

 Occurs in approx 1 in 1,500-2,500 liveborn

females
 CLINICAL MANIFESTATIONS
 Recognizable at birth because of a

characteristic edema of the dorsa of the

hands and feet , loose skinfolds at the nape
of the neck
 Short stature-cardinal finding invirtually all

girls w/ turner syndrome

 Cardiac defects are common
 TREATMENT
 Treatment with recombinat human growth

hormone increases height velocity

 Oxandrolone has been used to treat short

stature asso w/ Turner syndrome

 Replacement therapy with estrogens is

indicated
DIABETES MELLITUS
TYPE 1 DIABETES MELLITUS
 ETIOLOGY
 Accounts for approximately 10% of all cases

of diabetes, affecting up to 3 million people

in the US.
 GENETICS
 There is clear familial clustering of T1DM,

with prevalence in siblings approaching 6%

 PATHOGENESIS AND NATURAL HISTORY OF
T1DM
 Genetically susceptible host develops

autoimmunity against host’s own B cells

 What triggers this autoimmune response

remains unclear
 The natural history of T1 DM involves some
or all of the ff stages:
 1. initiation of autoimmunity
 2.preclinical autoimmunity w/ progressive

loss of B cell function

 3. onset of clinical disease
 4. Transient remission
 5. Established disease
 6. development of complications
CLINICAL MANIFESTATIONS
In Diabetes, decreasing B cell mass with
worsening insulinopenia, progressive
hyperglycemia, and eventual ketoacidosis
Postprandial hyperglycemia
Polyuria
Glycosuria –trigerring compensatory
hyperphagia
Extremely low insulin levels-ketoacids
accumulate
 DIAGNOSIS
 Nonfasting blood glucose greater than 200

mg/dL w/ typical symptoms is diagnostic

with or without ketonuria
 TREATMENT
 Insulin therapy
 Optimal insulin dose can only be determined

emperically
 Insulin pump therapy
 Continuous subcutaneous insulin infusion vis

battery powered pumps

 Continuous glucose monitoring systems
 Basic and advanced diabetes education
 PLEASE READ :
 DIABETIC KETOACIDOSIS TREATMENT

PROTOCOL
 TABLE 589-6
TYPE 2 DIABETES MELLITUS
 Formerly known as non-insulin dependent -
diabetes or adult onset diabetes
 NATURAL HISTORY
 T2DM –considered a polygenic disease

aggravated by environmental factors, such as

low physical activity and excessive caloric
intake
 Most patients are obese
 EPIDEMIOLOGY
 Prevalence of T2DM in 12-19 yr old in US is

1.46 in 1000
 The epidemic of T2DM in children and

adolescents parallels the emergence of the

obesity epidemic
 GENETICS
 T2DM has a strong genetic component
 Low birthweight and intrauterine growth

restriction are associated with increased risk

of T2DM
 Environmental and lifestyle related risk

factors
 Obesity – most important lifestyle factor
 Maternal smoking also increases risk of

diabetes and obesity in the offspring

 CLINICAL FEATURES
Patients are obese and present w/ mild
symptoms of polyuria and polydipsia
Frequently reveals the presence of acanthosis
nigricans- most commonly on the neck
Laboratory testing – elevated HbAic levels
Elevated triglycerides, LDL cholesterol levels
 PLEASE READ:
 TESTING FOR TYPE 2 DIABETES IN CHILDREN
 TABLE 589-13
 TREATMENT
 Type 2 diabetes is a progressive syndrome

that gradually leads to complete insulin

deficiency during the patients life
 No particular dietary or exercise regimen that

has been conclusively shown to superior

 Most centers recommend a low calorie, low

fat diet and 30-60 min of physical activity at

least 5 times/wk
 It is recommended that oral hypoglycemic
agents be introduced at the time of diagnosis
 The most commonly used and only FDA

approved oral agent for the treatment of

T2DM in children and adolescents is
metformin
 COMPLICATIONS
 SEARCH STUDY of diabetes in youth-92% of

patients had 2 or more elements of the

metabolic syndrome ( hypertension,
hypertriglyceridemia, decreased high density
lipoprotein, increased waist circumference)
 PREVENTION
 LIFESTYLE INTERVENTION- reduced the

diabetes incidence by 58%

 Metformin reduced the incidence by 31%
 Screening is indicated for at risk patients
 GOOD DAY!

 THANKYOU FOR YOUR KIND

ATTENTION!