Transcript Endocrinology Board Review

ENDOCRINOLOGY BOARD
REVIEW
September 24, 2010
Growth
Growth

After 18mos of age, growth curve should be
followed closely
 Between
4y/o and adolescence, growth below 45cm/yr should be assessed
 Percentiles should not be crossed

Pubertal growth spurt
 early puberty
 Boys  midpuberty
 Girls
Growth Rate per Year
Age
Inches
Centimeters
Birth to 1 year
7 to 10
18 to 25
1 to 2 years
4 to 5
10 to 13
2 to 2.5
5 to 6
Pubertal growth spurt-girls
2.5 to 4.5
6 to 11
Pubertal growth spurt-boys
3 to 5
7 to 13
2 years to puberty
Question 1
Choose the correct statement comparing “familial or
genetically determined short stature” and
“constitutional delay of growth,” in regards to
bone age.
A. Familial = delayed/ constitutional = advanced
B. Familial = equivalent/ constitutional = delayed
C. Familial = delayed/ constitutional = equivalent
D. Both are delayed
Constitutional delay of growth


Variant of normal growth and pubertal
development
Period of decreased linear growth within first 3yrs
of life
 Downward

Linear growth resumes at normal rate
 Along

crossing of percentiles
lower growth percentiles
Family history of “Late Bloomers”
Constitutional Growth Delay:
Note deceleration followed
by normal growth rate
Question 2
The physical findings depicted below corresponds to
which tanner stage?
A. I
B. II
C. III
D. IV
E. V
Tanner Staging

Boys: Staged by genital development and pubic
hair – starts at 9-14
 Testis
volume >= 4mL is pubertal
 Mark

of pubertal onset
Girls: Staged by breast development and pubic
hair – starts at 10 ½
 Stage
II = breast buds
 Mark
 Stage
of pubertal onset
IV = Areola elevated above breast (secondary
mound)
Hypothalamus and Pituitary
Hypothalamus

Neuroectodermal tissue

Inferior third ventricle

Pituitary stalk
Pituitary

Anterior
 Upgrowth
of ectodermal
cells from Rathke’s pouch

Posterior
 Downgrowth
of neural
tissue cells from the
hypothalamus
Question 3
You are evaluating a patient
in clinic and notice the
abnormality pictured.
Which of the following is
most likely to be affected?
A.
B.
C.
D.
Growth hormone levels
Aldosterone levels
Catecholamine levels
Insulin levels
Anterior Pituitary

Growth Hormone
 Secretion
 GH-releasing
factor
 Inhibition
 Somatostatin
 IGF-1,
IGF-BP3
Anterior Pituitary

Growth Hormone
 Deficiency
 Normal
birth weight
 Normal growth pattern x 1 year
 “Kewpie” doll appearance,
“cherubic”
 Short, excess subq fat, retarded
body proportion changes and
high-pitched voices
 Diagnosed with stimulation test
Anterior Pituitary

ACTH
 Secretion
 CRF
from hypothalamus
 Inhibition
 Cortisol
from adrenals
 Prolonged steroid use
Anterior Pituitary

Gonadotropins

Secretion
GnRH
 Hypothalamus sends pulses



Inhibition


Increases during puberty
Inhibin
FSH
Aromatase (androgen to
estrogen)
 Spermatogenesis


LH
Testosterone
 Androstenedione (estradiol)

Anterior Pituitary

TSH
 Secretion
 TRH
 Inhibition
 Thyroid
Hormone
 Actions
 Increases
iodide uptake,
thyroglobulin synthesis
and thyroid hormone
Anterior Pituitary

Prolactin
 Acts
directly on target organ
 Initiation and maintenance of lactation
 Inhibited by dopamine from hypothalamus
 Hyperprolactinemia
 Galactorrhea
 Pituitary
adenomas
 Medication

Neuroleptics, antipsychotics, estrogens and anti-hypertensives
Question 4
You are on call in the PICU and following a very sick
patient admitted with meningococcal meningitis. He
has not had any urine output in the last 8 hours
despite fluid administration. You order a BMP and
his Na is 125. What is the most likely cause of the
hyponatremia in this patient?
A.
B.
C.
D.
Diabetes insipidus
Psychogenic polydipsia
Inappropriate fluid administration
SIADH
Posterior Pituitary


Hormones synthesized in hypothalamus and stored
in posterior pituitary
Vasopressin
 AVP
or ADH
 Released in response to increased osmotic pressure in
the blood
 Water balance
 Increased
reabsorption of water in collecting ducts of
kidneys
 Arteriolar vasoconstriction – HTN
 Increased thirst
Posterior Pituitary

Vasopressin
 Overproduction
 Head
trauma, brain tumors, encephalitis, pneumonia
 SIADH


HA, apathy, nausea, vomiting, impaired consciousness
Decreased plasma osmolarity
 Underproduction
 Central


Diabetes Insipidus (DI)
Pituitary tumors, head trauma, infiltrative diseases, autoimmune
or surgical
Increased plasma osmolarity
Posterior Pituitary

Vasopressin
 Resistant
 Nephrogenic



DI
Tubules in kidney cannot respond
Genetic or acquired (lithium)
Oxytocin
 Released
in response to nerve stimulation
 Contraction of the smooth muscle of the uterus and
myoepithelial cells lining the ducts of mammary glands
Thyroid
Thyroid

Location
 Neck
 Base
of tongue
 Mediastinum

Hormones
 Thyroxine
(T4)
 Tri-iodothyronine (T3)
 Need iodine for synthesis
 Transported by TBG, albumin
and transthyretin
 Free hormone is active
Thyroid

Goiter
 Hyper

or hypo
Nodules
 70-80%
benign or cystic
 1-1.5% of all childhood cancers
 Neck irradiation, family history
of medullary carcinoma, rapid
growth, fixation to adjacent
structures, enlarged lymph nodes
Question 5
A mother brings in her teenage daughter for
hyperactivity and emotional lability. ROS is positive
for diarrhea, weight loss and heat intolerance. On
physical exam you notice tachycardia and a slight
prominence of the eyes. A laboratory evaluation
would most likely reveal:
A. TSH, freeT4, + TSH receptor antibodies
B. TSH, free T4, + antithyroperoxidase antibodies
C. TSH, free T4, + TSH receptor antibodies
D. TSH, free T4, + antithyroperoxidase antibodies
Thyroid

Hyperthyroid
Soft and fleshy gland
 Tachycardia
 Weight loss
 Increased frequency of
bowel movements
 Heat intolerance
 Nervousness
 Widened pulse pressure
 Tremor
 Fatigue

Warm, moist skin
 Fine, friable hair
 Separation of distal
margin of nail bed
 Restlessness
 Inability to sit still
 Emotional lability
 Short attention span
 Excessive sweating

Thyroid

Hyperthyroidism
 Graves
Disease
 Stimulating
antibody to TSH
receptor
 Exopthalmos

Proptosis and lid lag
 Large
gland
 Warm
on palpation
 Bruit
 Labs
 Increased
T3 and T4
 Decreased TSH
Thyroid

Congenital Hypothyroidism
1 in 4000
 Cretinism

Broad nasal bridge
 Coarse facial features
 Mental retardation
 Short stature
 Puffy hands
 Protuberant tongue
 Delayed skeletal maturation

Treatment within 3-4 weeks
 Newborn Screening

Thyroid

Hypothyroid
 Hypothalamic
abnormalities
 Pituitary abnormalities
 Iodine deficiency
 Chronic lymphocytic thyroiditis
 Hashimoto thyroiditis
 Anti-thyroid


antibodies
Thyroglobulin
Thyroperoxidase
 Positive
FH
 Increased TSH, decreased T4
Thyroid

Hypothyroid symptoms
 Firm
or bosselated gland
 Congenital vs Acquired
 Dry skin
 Constipation
 Hair loss
 Fatigue
 Cold intolerance
 Apathy
 Depressed or delayed relaxation
Acquired hypothyroidism: Note the sharp deceleration in growth before the onset of
symptoms. Following initiation of therapy significant catch-up growth is seen.
Calcium and Phos Metabolism
PTH

Bone:
 Increases

Intestine:
 Increased

release of Ca and Phos
re-absorption of Ca and Phos
Kidney:
 Increases
excretion of Phos
 Decreases excretion of Ca
 Stimulates Synthesis of Vit D3
Effects of PTH
Bone
Ca
Phos
Intestine
Kidney
Net Effect
Vitamin D

Bone
 Increases
release of Ca
 Increases release Ph

Intestine
 Increases
absorption of Ca
 Increases absorption of Ph

Kidney
 Improves
reabsorption of Ca
 Increases reabsorption of Ph
Vitamin D
Bone
Ca
Phos
Intestine
Kidney
Net Effect
Calcitonin

Bone
 Inhibits
reabsorption of Ca
 Inhibits reabsorption of Ph

Intestine (no specific effects)

Kidney
 Decreases
reabsorption of Ca
 Decreases reabsorption of Ph
Net Effect of 3 Hormones
Ca
Vit D
PTH
Calcitonin
Phos
Hyperparathyroidism


Results in hypercalcemia
Manifestation of multiple endocrine neoplasia I
(MEN 1)
 Autosomal
dominant
 Islet cell tumors
 Zollinger-Ellison syndrome
 Pituitary tumors
Hypocalcemia
Symptoms:
Paresthesias
Irritability
Muscle Cramps
Tetany
Seizures
Question 6
A two day old infant experiences a prolonged seizure
with respiratory arrest requiring intubation. BMP
reveals hypocalcemia, and CXR demonstrates
absent thymic shadow. Genetic testing is likely to
reveal:
A.
B.
C.
D.
E.
Trisomy 21
Trisomy 18
Deletion of 22q11.2
Deletion of 15q13.3
DF508 Mutation
Hypoparathyroidism


Idiopathic (Autoimmune)
DiGeorge Syndrome
features
Ca
low
 Cardiac defects
P
high
 Immune deficiency
PTH
low
 Thymic aplasia
 Low PTH
 Deletion of 22q11.2
 May present with seizures secondary to hypocalcemia
 Dysmorphic
Pseudohypoparathyroidism

PTH is elevated
 Unresponsiveness

to PTH (Bone/Kidney/Both)
Albright hereditary osteodystrophy
 Suspect
in short child with hypocalcemia
Ca
P
PTH
low
high
high
Albright hereditary osteodystrophy
Vitamin D-Deficient Rickets

Vitamin D deficiency may result from
Inadequate sunlight exposure
 Malabsorption
 Drugs that affect Vit D



Phenytoin, phenobarb
Signs/Symptoms
Poor linear growth
 Delayed walking
 Muscle weakness
 Bone pain
 Hypotonia
 Anorexia

Ca
P
PTH
AlkP
NL/low
low
high
high
Vitamin D-Deficient Rickets
Others

Vitamin D-Resistant Rickets
 Resistance
to Vit D, even when high amounts used
 Findings in first months of life

Pseudovitamin D-Deficiency Rickets
 AKA
1a-hydroxylase deficiency or Vit-D dependent
rickets type I
 Findings
appear in early infancy
 Autosomal recessive
Adrenals
Adrenal Gland

Cortex
 Glucocorticoids
 Mineralocorticoids
 Androgens

Medulla
 Epinephrine
 Norepinephrine
Adrenal Glands

Cushing
 Excessive
glucocorticoids
 Endogenous
or exogenous steroid exposure
 Causes
 Adrenal
tumors
 Pituitary adenomas (Cushing disease)
 Ectopic ACTH production
Adrenal Gland

Features of Cushings
 Rounded
facies
 Plethora
 Central
obesity
 Impaired linear growth
 Fatigue
 Hypertension
 Buffalo hump
 Muscle weakness and muscle wasting
 Skin is thin and easily bruised
 Osteopenia/osteoporosis
Adrenal Gland

Cushings Labs
 Elevated
24-hour
urine free cortisol
excretion
 Elevated salivary
cortisol
 Delineating the cause
 High-
and low-dose
dexamethasone
suppression tests
Adrenal Gland

Addison’s Disease

Insufficiency
Glucocorticoid
 Mineralocorticoid


Causes
Autoimmune destruction
 Tuberculosis
 Autoimmune polyendocrine syndromes
 Adrenoleukodystrophy, Wolman disease, hereditary
unresponsiveness to ACTH, Allgrove syndrome, and congenital
adrenal hypoplasia
 Massive adrenal hemorrhage can occur with meningitis or
traumatic births

Adrenal Gland

Addison’s
 Weight
loss
 Wasting of subcutaneous
tissue
 Hyperpigmentation
 Weak
 Confused
 Decreased circulating
plasma volume
Adrenal Gland

Addison
 Labs
 Hyponatremia
 Hyperkalemia
 Less
pronounced disease in ACTH deficiency
 If untreated
 Weaken
 Vascular
collapse
Question 7
A 3-week-old female infant is brought to the ER for vomiting,
decreased oral intake and lethargy of 3 days’ duration. Because
the infant had not regained her birthweight at the 2-week visit, the
mother was instructed to wake her every 2 hours to breastfeed. On
PE, the infant’s temp is 98.6F, HR 190, BP 60/30. She appears thin
and lethargic and has a poor suck. Her anterior fontanelle and eyes
appear sunken, and her CR is 3 secs. You note an enlarged clitoris
and partial labial fusion. Assessment of serum electrolytes in this
infant is MOST likely to reveal
A.
B.
C.
D.
E.
Hyperchloremia
Hyperglycemia
Hypernatremia
Hypokalemia
Hyponatremia
Adrenal Gland

CAH
Autosomal recessive
 Symptoms reflect specific defect


21-hydroxylase deficiency






Most common
Decreased glucocorticoid
 Hypoglycemia
Decreased mineralocorticoid (severe forms)
 Salt-wasting
 Hyperkalemia/hyponatremia
Elevated 17-hydroxyprogesterone
Excess androgens
 Masculinization
Shock and death if untreated
Adrenal Gland

Other forms of CAH
 Less
severe 21-hydroxylase deficiency
 May
present later
 Premature pubarche, rapid growth, skeletal maturation
 11β-hydroxylase
 17α-hydroxylase
 Delayed puberty
 Undervirilization of
males
Adrenal Gland - Medulla

Pheochromocytoma
Rare
 Catecholamine-secreting tumor



Norepinephrine, Epinephrine, Dopamine (rarely)
Symptoms
HA, diaphoresis, palpitaions, tremor, nausea, weakness, anxiety,
weight loss
 Hypertension (episodic), AMS, arrhythmia


Syndromes


MEN 2A, 2B, NF, VHL
Diagnosis

Plasma metanephrines, 24-hour urine catecholamines and
metanephrine
Sexual Differentiation
Sexual Differentiation

SRY gene
 Short
arm of Y chromosome
 Promotes differentiation of Sertoli cells
 Mutations lead to male to female sex reversal

Ambiguous genitalia
 “the
baby”
 Endocrine, urology, psychologist or social worker
 Palpate for gonads
Sexual Differentiation

Ambiguous Genitalia

CAH



Leydig cell hypoplasia, inborn
errors of testosterone synthesis,
androgen insensitivity



No palpable gonads
17-hydroxyprogesterone
Palpable gonads
LH, FSH, testosterone,
dihydrotestosterone
Complete androgen insensitivity



Externally female
Uterus absent
Labial or inguinal gonads
Sexual Differentiation

Persistent mullerian duct
syndrome
 Persistance
of structures in
normal 46,XY male
 Cryptorchidism or testicular
ectopia
 Defect in anti-mullerian
hormone

Agenesis of the phallus
 Developmental
Question 8
You are examining a 2-week-old male infant for the first
time and note an undescended right testicle. His mother
asks when is the optimal time to correct this problem.
The MOST appropriate time at which to recommend
surgical repair for this infant if spontaneous descent has
not occurred is
A.
B.
C.
D.
E.
4 months
12 months
24 months
36 months
48 months
Cryptorchidism

Migration
 Kidneys
to scrotum
 3% of male infants
 Treatment
 6-12
months
 Orchiopexy
 Increased
risk for
malignancy
 Surgical
intervention does
not alter risk
Precocious Puberty
Precocious Puberty

Girls


Boys


<8
<9
Central

Gonadotropin-dependent

Activation of HPG axis


Hypothalamic hamartomas


FSH, LH
Gelastic seizures
Intracranial neoplasms
Precocious Puberty

Gonadotropinindependent
Increased gonadal steroids
 No HPG axis involvement
 McCune-Albright syndrome

Café-au-lait
 Polyostotic fibrous dysplasia
 Precocious puberty


Gonadal or adrenal
neoplasms


Rare
Familial male-limited
precocious puberty
Question 9
During the hospital discharge examination of a term female
neonate, you palpate a 1-cm mass beneath her right nipple.
There is no erythema at the site and no discharge from
either nipple. The mass is nontender and freely mobile. The
genitalia appear mildly swollen but are otherwise normal.
Of the following, the MOST appropriate treatment is
A.
B.
C.
D.
E.
Excisional biopsy
Fine-needle aspiration of the mass
IM gonadotropin-releasing hormone
Oral cephalexin
Reassurance of the parents
Premature Thelarche

Breast tissue development
Uni or bilateral
 May regress or persist


Diagnosis of exclusion
No other signs of pubertal
development
 Exogenous estrogen




1-2y
Self-limited
Normal in neonates
Premature Pubarche



Pubic hair <8y in girls;
<9.5y boys
Axillary hair, body odor,
acne
Due to
 Premature
adrenal
pubertal maturation
 PCOS
 Late
onset CAH
 Tumor - rare
Delayed Puberty
Delayed Puberty

Constitutional Delay


Normal variant
Central

Kallmann Syndrome


Acquired


Hypothalamic hypogonadism
Trauma, neoplasm, infiltrative disorders, hyperprolactinemia,
chronic illness - anorexia, CF, sickle cell
Gonadal
Turner, Klinefelter
 Trauma, chemotherapy, radiation

Delayed Puberty

Other
 Androgen
insensitivity
 Inguinal
or labial mass
 Primary amenorrhea
 17-hydroxylase
 Cannot
deficiency
produce sex steroids
Turner Syndrome



XO
Short stature
Gonadal failure
 Streak

ovaries
Other
 Cubitus
valgus,
shieldlike chest,
webbed neck
 Cardiac
 Renal

Mosaic
Klinefelter Syndrome

47, XXY

Small, firm testes

Gynecomastia

Neurobehavioral
difficulties
Diabetes
You will get more diabetes than you ever dream
of on Purple team!
Hypoglycemia
Hypoglycemia

Signs and symptoms

ANS, Epinephrine, CNS
glucopenia

Fasting vs. Stress vs. Iatrogenic

Hyperinsulinism



Most common cause in neonates
Mutations of enzymes,
iatrogenic, adenoma
Beckwith-Wiedemann

Macrosomia, macroglossia,
omphalocele, hemihypertrophy
and embryonal tumor
Hypoglycemia

Ketotic hypoglycemia
 Common
cause of childhood hypoglycemia
 18 months to 5 years
 Resolves by 8 to 9 years

Other
 Hypopituitarism,
GSD, disorders of gluconeogenesis
Obesity
Question 10
You care for a 17-year-old boy who is overweight. He has
gained 44 lb (20 kg) in the last year, especially in his
abdominal area. On examination today, his blood pressure
is 158/90 mm Hg using a large, appropriately sized cuff.
His mother has a similar body habitus and is being treated
for type 2 DM. Of the following, the MOST likely
abnormalities to expect in this patient if his presentation
continues into adulthood is
A.
B.
C.
D.
E.
High triglycerides and low HDL
Hypoglycemia from insulin sensitivity
Low concentrations of C-reactive protein in the blood
Low fibrinogen concentration with bleeding diatheses
Low triglycerides and low LDL
Obesity

Look for causes of secondary obesity




Endocrine
Genetic
CNS
Metabolic Syndrome






Obesity
Insulin resistance
Dyslipidemia
HTN
Increased risk of developing Type 2 DM and CV
disease
Look for PCOS

Hyperandrogenism, irregular menses, chronic
anovulation