Endocrine System
PART II
DISORDERS OF THE GONADS
NOONAN SYNDROME
• SHORT STATURE, webbing of the neck, pectus
carinatum/excavatum, cubitus valgus, R sided
congenital HD, characteristic facies.
• Hypertelorism, epicanthus, downward slanted
palpebral fissures, ptosis, micrognathia, ear
abnormalities
• Mean IQ 86 (53-127)
• Verbal IQ> performance IQ
NOONAN SYNDROME
• PULMONARY VALVULAR STENOSIS, HYPERTROPHIC
CM, ASD
• Hepatosplenomegaly, low clotting factors XI XII, ALL,
CML
• CRYPTORHIDISM, SMALL TESTES, hypogonadal or
normal
• Delayed puberty (2yrs), ADULT HEIGHT 2nd DECADE,
usually reaches the lowest limit of the normal
population
• PRENATAL DX: Normal karyotype, edema, hydrops and
short femur length
• TREATMENT: HUMAN GH
KLINEFELTER SYNDROME
• 1/500 MALES: 47,XXY
• ALL BOYS WITH MR and in children with
PSYCHOSOCIAL, LEARNING, or SCHOOL ADJUSTMENT
problems
• Tall, slim, underweight, long legs, body habitus can
vary markedly
• Testes tend to be small for age, phallus tends to be
smaller than average, cryptorchidism or hypospadias
may occur in a few patients; SPERMATOGENIC ARREST
and SERTOLI CELL PREDOMINANCE
• GYNECOMASTIA (80%)
• Height tends to be increased
12-yr-old boy with 48,XXXY/49,XXXXY
mosaicism who has prognathism,
epicanthal folds, scoliosis, small
testes, severe mental retardation,
clinodactyly, and radioulnar
synostoses
KLINEFELTER SYNDROME
• Increased incidence of pulmonary disease,
varicose veins, cancer of the breast
• Male breast cancer (7.5%), Mediastinal GCT,
Leukemia, Lymphoma. Higher cancer risk (RR
2.7): 15-30y age group
KLINEFELTER SYNDROME
• Replacement therapy
– Long-acting TESTOSTERONE preparation
– 11-12 yrs of age
– ENANTHATE ESTER 25-50mg IM q3-4w,
50mg increments q6-9mo until a maintenance
dose for adults achieved (200-250mg q3-4w)
– TESTOSTERONE PATCHES/GEL
• Rapid increase in prostate volume and PSA
levels
HYPOGONADOTROPIC HYPOGONADISM in the MALE
(SECONDARY HYPOGONADISM)
• Deficiency of LH or FSH, or both
• Primary defect: anterior pituitary/ hypothalamus – deficiency of
GnRH
• N testes, prepubertal
• KALLMAN SYNDROME - +anosmia/hyposmia
– Xlinked mutation KAL gene – failure of the olfactory axons and GnRHexpressing neurons to migrate from their common origin in the
olfactory placode to the brain
• TESTOSTERONE ENANTHATE 100mg IM qMo for 4-6mo  increase
in signs of secondary sexual characteristics, increase in growth
velocity
• hCG 500-1000IU, SC or IM, 3x/wk  growth of testes and
spermatogenesis
• human menopausal gonadotrophin 37.5-150 IU, 3x/wk, may require
2yrs of tx
PSEUDOPRECOCITY resulting from
Tumors of the testes
• Leydig Cell Tumors – REINKE CRYSTALLOIDS
• Adrenal Rest Tumors
– bilateral
• FRAGILE X SYNDROME
– B Testicular enlargement MACROORCHIDISM, 4050mL
GYNECOMASTIA
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TRUE vs PSEUDOGYNECOMASTIA (adipose)
ESTROGEN-ANDROGEN IMBALANCE
Aromatase
Treatment: Reassurance
– Medical: Anastrozole (Ar In) 1mg = placebo
– Surgical: Removal ENDOSCOPICALLY ASSISTED
TRANSAXILLARY REMOVAL
HYPOFUNCTION OF THE OVARIES
TURNER SYNDROME
• Sexual infantilism, webbed neck, cubitus valgus
• Complete or partial absence of second X chr
• BIRTH: edema of dorsum of hands & feet, loose
skin folds at the nape. LOW BW and DECREASED
LENGTH
• CHILDHOOD: webbing of the neck, low posterior
hairline, small mandible, prominent ears,
epicanthal folds, high arched palate, broad chest,
cubitus valgus, hyperconvex fingernails
• SHORT STATURE (US MAH: 143-144cm), MPH
Turner syndrome in a 15-yr-old girl
exhibiting failure of sexual
maturation, short stature, cubitus
valgus, and a goiter. There is no
webbing of the neck. Karyotyping
revealed 45,X/46,XX chromosome
complement
TURNER SYNDROME
• Isolated nonstenotic bicuspid aortic valves,
aortic coarctation, AS, MVP
• Pelvic kidney, horseshoe kidney, double collecting
system, complete absence of 1kidney, UPJ
obstruction
• Autoimmune thyroid disease
• IBD: Chron disease and UC
• Sternal malformations
• Recurrent Bilateral OM, SNH defects
TURNER SYNDROME
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Chromosomal Analysis
Ultrasonography
Plasma Gn: FSH
Thyroid antiPO Ab, T4, TSH
Treatment: RECOMBINANT hGH
– Replacement E2 Therapy
• Conjugated estrogen 0.3-0.625mg
• Micronized E2 0.5mg daily x3-6mo
CONGENITAL ADRENAL HYPERPLASIA
• Ambiguous genitalia
• 21-OH deficiency
Cholesterol
P450scc
3(B)HSD
Pregnelonone
P450c17
3(B)HSD
170H
Pregnenolone
P450c21
Progesterone
DOC
P450c11
Corticosterone
P450c11
180H
Aldosterone
Corticosterone
P450c17
P450c21
170H
Progesterone
3(B)HSD
DHEA
P450c11
Androstenedione
17(B)HSD
11 Deoxycortisol
Testosterone
P450c11
P450aro
Cortisol
Estradiol
CONGENITAL ADRENAL HYPERPLASIA
• SALT WASTING
• Progressive weight loss, anorexia, vomiting,
dehydration, weakness, hypOtension,
hypOglycemia, hypOnatremia, hypErkalemia
• 2 Wks of age
• GLUCOCORTICOID 15-20mg/m²/24
• FLUDROCORTISONE 0.1-0.3mg/day
WAGR
WILMS TUMOR, ANIRIDIA,
GENITOURINARY MALFORMATIONS, RETARDATION
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Deletion c11p13 (aniridia gene PAX6, WT1)
46,XY males have genital abnormalities
Cryptorchidism
Virilization
ANDROGEN INSENSITIVITY
SYNDROMES
• 46,XY
• Phenotypic females (COMPLETE AIS) to males with
various ambiguous genitals and undervirilization
(PARTIAL)
• Complete: female at birth, F external genitals, blind
vaginal pouch, absent uterus, FT remnants,
intraabdominal testes.
– Puberty: N breast development, female habitus,
menstruation does not occur, absent sexual hair
– Adult height same with N males
– N testosterone and DHT levels
– Testicular removal (seminoma); ESTROGEN
DIABETES MELLITUS
Type 1 DM
• IDDM, juvenile diabetes
• Low/ absent levels of endogenously produced
insulin and dependence on exogenous insulin to
prevent DKA
• 4 stages:
1. Preclinical β-cell autoimmunity with progressive
defect of insulin secretion
2. Onset of clinical diabetes
3. Transient remission “honeymoon period”
4. Established diabetes associated with acute and
chronic complications and decreased life expectancy
Type 1 DM
• Onset: 7-15 y/o
• Autoimmune destruction
T2 DM
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Usually obese but are not insulin dependent
NIDDM, adult-onset DM, MODY
More insidious
Excessive weight gain, fatigue
ACANTHOSIS NIGRICANS
T2 DM CRITERIA
•
OVERWEIGHT (BMI>85th % A,S; WFH>85th %; Wt>120% of ideal for ht)
PLUS:
Any 2 of the ff:
• FH T2DM in 1st or 2nd degree relative
• Race/Ethnicity
• Signs of Insulin Resistance or conditions associated with insulin resistance (AN,
hypertension, dyslipidemia, PCOS)
• Age of initiation: age 10yrs or at onset of puberty if puberty occurs at a younger
age
• Frequency: every 2 yrs
• Test: FPG preferred
Diagnosis
• “inappropriate polyuria in any child with dehydration,
poor weight gain, or the flu”
• RBS>200mg/dL (11.1
Treatment
Insulin therapy
prepubertal 0.7 U/Kg/d
midpuberty 1.0 U/Kg/d
end
1.2 U/Kg/d
Nutritional Education
Improved Exercise Level
Long Term Complications
1. Microvascular
– Retinopathy
– Nephropathy
2. Macrovascular
– CAD
– CVD
– PVD
3. Neuropathies
– Peripheral
– Autonomic
TRANSIENT DM of the
NEWBORN
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1st week of life
SGA
Hyperglycemia, pronounced glycosuria
Severe dehydration, metabolic acidosis but
with only minimal or no ketonemia/ketonuria
• 1-2U/Kg/24h intermediate actingINSULIN
insulin
DEFECTS OF CARBOHYDRATE
METABOLISM
Glycogen Storage Disease type I
(GLUCOSE-6-PHOSPHATASE/ TRANSLOCASE/ VON GIERKE DISEASE)
• Neonatal period: Hypoglycemia and lactic acidosis
• 3-4mo: hepatomegaly, hypoglycemic seizures
• Doll like faces with fat cheeks, relatively thin
extremities, short stature, protruberant abdomen,
enlarged kidneys
• Hypoglycemia, Lactic Acidosis, Hyperuricemia,
Hyperlipidemia
• NORMAL transaminases
• Tx: NGT infusion of glucose/ oral uncooked cornstarch
Glycogen Storage Disease type III
(DEBRANCHER DEFICIENCY)
• Deficiency of glycogen debranching enzyme
activity
• Hepatomegaly, hypoglycemia, short stature,
variable skeletal myopathy, variable CM
• BOTH LIVER AND MUSCLE INVOLVEMENT (IIIa)
• LIVER (IIIb)
• ELEVATION OF LIVER TRANSAMINASES
• HEPATOCELLULAR CARCINOMA
• Tx: Frequent meals with high in CHO, high CHON
diet
GSDIIIb
Growth and development in a patient
with type IIIb glycogen storage
disease.
The patient has debrancher deficiency
in liver but normal activity in muscle.
As a child, he had hepatomegaly,
hypoglycemia, and growth retardation.
After puberty, he no longer had
hepatomegaly or hypoglycemia, and
his final adult height is normal.
He had no muscle weakness or
atrophy; this is in contrast to type IIIa
patients, in whom a progressive
myopathy is seen in adulthood.
Glycogen Storage Disease type IV
(Branching Enzyme Deficiency/ Amylopectinosis/ Andersen Disease)
• Accumulation of an abnormal glycogen with poor
solubility
• Fewer branch points
• Progressive cirrhosis of the liver
• 1st 18 mo: hepatosplenomegaly, FTT
• Cirrhosis progresses to portal HPN, ascites,
esophageal varices, liver failure
• Death by 5 y/o
• NO SPECIFIC TX, poor prognosis
Glycogen Storage Disease type II
(LYSOSOMAL ACID a1-4-GLUCOSIDASE DEFICIENCY/ POMPE DISEASE)
• Lysosomal glycogen accumulation in multiple tissues,
cardiac, skeleletal, SMOOTH MUSCLE CELLS
• Myopathy, “floppy infant appearance”, feeding
difficulties, macroglossia, hepatomegaly, hypertrophic
CM
• Slowly progressive proximal muscle weakness with
truncal involvement
• LE> UE
• Lab: elevated CK, AST, LDH; muscle def a-glucosidase
• Tx: Supportive/ Palliative
GALACTOSEMIA
(Galactose-1-Phosphate Uridyl Transferase Deficiency)
• 2nd half of the 1st week of life
• Accumulation of galactose-1-phosphate 
kidney/liver/brain injury
• Jaundice, hepatomegaly, vomiting, hypoglycemia,
convulsions, lethargy, irritability, feeding
difficulties, FTT, aminoaciduria, nuclear cataracts,
vitreous hge, hepatic failure, liver cirrhosis,
ascites, splenomegaly, mental retardation.
• Dx: Reducing substance in urine
• Tx: Elimination of galactose from the diet
MUCOPOLYSACCHARIDOSIS I
HURLER DISEASE
• 6 to 24 months old
• Hepatosplenomegaly, coarse facial features,
corneal clouding, large tongue, prominent
forehead, joint stiffness, short stature and
skeletal dysplasia, developmental delay
MUCOPOLYSACCHARIDOSIS II
HUNTER DISEASE
• Almost exclusively in MALES
• Same with Hurler EXCEPT for LACK OF
CORNEAL CLOUDING and somewhat SLOWER
progression of somatic and CNS deterioration
MUCOPOLYSACCHARIDOSIS
• Treatment
– BM transplantation
– CORD BLOOD transplantation
– Enzyme replacement
Thank You