Transcript Endocrinology

Pediatric Board Review
Endocrinology
Graeme Frank, MD
Calcium
An otherwise healthy 6-week infant presents with a
generalized seizure. She is exclusively breast fed. The
child is somewhat sleepy with a non focal examination.
Lab data:
Glucose
88 mg/dL
Sodium
141 mEq/L
Calcium
5.1 mg/dL
Phosphorus
9.1 mg/dL
Magnesium
2.1 mg/dL
The most likely diagnosis is:
a) Pseudohypoparathyroidism
b) Hypoparathyroidism
c) Vitamin D deficiency
d) Albright’s hereditary osteodystrophy
Actions of PTH
Ca
1.
2.
3.
25 OH Vit D
1 hydroxylase
1,25 (OH)2 Vit D
Gut
NET EFFECT
PO4
An otherwise healthy 6-week infant presents with a
generalized seizure. She is exclusively breast fed. The
child is somewhat sleepy with a non focal examination.
Lab data:
Glucose
88 mg/dL
Sodium
141 mEq/L
Calcium
5.1 mg/dL
Phosphorus
9.1 mg/dL
Magnesium
2.1 mg/dL
The most likely diagnosis is:
a) Pseudohypoparathyroidism
b) Hypoparathyroidism
c) Vitamin D deficiency
d) Albright’s hereditary osteodystrophy
An otherwise healthy 6-week infant presents with a
generalized seizure. She is exclusively breast fed. The
child is somewhat sleepy with a non focal
examination.
Lab data:
Glucose
88 mg/dL
Sodium
141 mEq/L
Calcium
5.1 mg/dL
Phosphorus
9.1 mg/dL
Magnesium
2.1 mg/dL
What is an important diagnostic consideration
(i.e. what else is the child at risk for)
DiGeorge syndrome – thymic aplasia, congenital heart
disease, immune deficiency
Biochemical changes in rickets
Ca
Stage 1
Stage 2
PO4
N
N
Bone
Urine
Minimal
changes
Rickets
Aminoaciduria
Phosphaturia
Initial
Ca:
PO4:
Alk Phos:
9.7
3.1
2514
2 ½ weeks
9.8
3.5
2185
4 months
10.5
6.5
518
Which is consistent with
vitamin D deficiency rickets?
CALCIUM
PHOS
ALK PHOS
A. Normal
Normal
Low
B. Low
Low
Low
C. Low
Increased
Increased
D. Low
Normal
Normal
E. Normal
Low
Increased
Choose correct answer
A. Vitamin D deficiency rickets
B. Renal osteodystrophy (renal rickets)
C. Both
D. Neither
1. Increased phosphate level
B
2. Increased PTH level
C
3. Increased creatinine level
B
THYROID
A 15 day infant has an abnormal newborn thyroid
screen result:
The baby was born on 5/27/07. His newborn screening
tests, performed on 5/29/07 revealed:
TSH
T4
37 IU/ml
10.1 g/dl
Normal range
< 20
9-19
This child:
a) Has congenital hypothyroidism and should be referred
to a congenital hypothyroidism treatment center
b) Will likely develop mental retardation if untreated
c) Likely does not have any thyroid abnormality
d) Has an altered hypothalamic set-point for T4
e) Should be started on thyroxine replacement
immediately
You are contacted by your state Neonatal Thyroid
Screening Program. Baby X was born on 1/4/01.
His newborn screening tests, performed on 1/6/01
revealed:
Initial filter paper
TSH
T4
Normal range
>200 IU/ml
< 20
2.1 g/dl
9-19
Venipuncture: (1/25/01)
TSH 488 IU/ml
T4
1.2 g/dl
Normal range
(0.3-5.5)
(4.5-12.5)
Congenital hypothyroidism
 Thyroid dysgenesis/agenesis
 Prevalence 1 in 4,000 [Whites 1 in 2,000; Blacks
1 in 32,000]
 2:1 female to male ratio
 Clinical features include:
hypotonia, enlarged posterior fontanelle,
umbilical hernia, indirect hyperbilirubinemia
 Laboratory findings: Very high TSH and low T4
 Therapy: Thyroxine – keep TSH in normal range
6 month female with
congenital hypothyroidism
..following 4 months
therapy
A baby who was born with gastroschisis has an
abnormal newborn thyroid screen at 3 days which
revealed a low T4 and normal TSH.
Repeat venipuncture showed:
T4
2.1 μg/dL
(4.5-12.5)
TSH
2.3 μIU/mL (0.3-5.0)
a)
b)
c)
d)
e)
The most likely diagnosis is:
Hypothyroidism due to dysgenesis of the thyroid gland
Central hypothyroidism
TBG deficiency
Hypothyroidism from excess iodine exposure
Normal thyroid function (as the TSH is normal)
Central hypothyroidism - rare
vs.
TBG deficiency
1:2800
Thyroxine (T4)
 Major product secreted by the thyroid
 Circulates bound to thyroid binding proteins
- thyroid binding globulin (TBG)
 Only a tiny fraction (< 0.1%) is free and diffuses
into tissues
 When we measure T4, we measure the T4 that is
bound to protein
 The level of T4 is therefore largely dependent on
the amount of TBG
 Changes in T4 may reflect TBG variation rather
than underlying pathology
Central
hypothyroidism
TBG
deficiency
Free T4
Low
Normal
TBG level
Normal
Low
T3RU
Low
High
17 year old female who complains of easy fatigability.
Her mother developed Graves’ disease at the same
age.
Thyroid function:
TSH: 3.7 IU/ml
T4:
13.4 g/dl
Normal range
0.3-5.5
4.5-12
17 year old female who complains of easy fatigability.
Her mother developed Graves’ disease at the same
age.
Thyroid function:
TSH: 3.7 IU/ml
T4:
13.4 g/dl
Normal range
0.3-5.5
4.5-12
Which of the following medication could explain the thyroid
function abnormality
a)
b)
c)
d)
e)
INH
Ortho Tri-Cylen
Retinoid acid
Ciprofloxacin
Doxycycline
Conditions that cause alterations in TBG
Increased TBG
Infancy
Estrogen
- OC Pill
- pregnancy
Familial excess
Hepatitis
Tamoxifen treatment
Decreased TBG
Familial deficiency
Androgenic steroid treatment
Glucocorticoids (large dose)
Nephrotic syndrome
Acromegaly
A 12-yr female has diffuse enlargement of the
thyroid. She is asymptomatic. Her disorder is
most likely associated with which of the following
pathological processes
a)
b)
c)
d)
e)
Infectious
Inflammatory
Autoimmune
Toxic (drug)
Neoplastic
Normal thyroid
Hashimoto thyroiditis
DC


16 year 7 month
Growth failure x 1 1/2 years
Labs:
TSH:
T4:
1008 µIU/ ml
<1.0 µg/dl
(0.3-5.0)
(4-12)
Antithyro Ab.
A-perox Ab.
232 U/ml
592 IU/ml
(0-1)
(<0.3)
Prolactin:
29
ng/ml
Cholesterol:
406 mg/dl
(2-18)
(100-170)
DC
Start of thyroxine
Hashimoto thyroiditis
Background:
Autoimmune destruction of the thyroid
Family history in 30-40%
Lymphocytic infiltration
Clinical:
Growth failure, constipation, goiter, dry skin, weight
gain, slow recoil of DTR
Laboratory:
High TSH
Anti-thyroglobulin and anti-peroxidase antibodies
Therapy:
Thyroxine
15 year old female with a history of easy fatigability.
Found to have an elevated pulse rate at recent MD visit
Thyroid function:
TSH < 0.1 IU/ml
T4
14.8 g/dl
T3
580 ng/dl
Normal range
0.3-5.5
4.5-12
90-190
Eye changes
Restlessness,
poor attention span
Goiter
Tachycardia, wide pulse
pressure
Increased GFR
- polyuria
Menstrual
abnormalities
Myopathy
Diarrhea
Therapy for Graves disease:
Antithyroid medication (Methimazole or Propylthiouracil [PTU])
Pros : 25% remission rate every 2 years
Cons: Drug induced side effects
- skin rashes, agranulocytosis, lupus-like reaction
Radioactive iodine (131I)
Pros : Easy. Essentially free of side effects
Cons: Long term hypothyroidism
Surgery
 Blockers if markedly hyperthyroid
Sexual differentiation
Ambiguous genitalia is found in a newborn.
The baby is noted to be hyperpigmented.
Ultrasound demonstrates the presence of a
uterus. The most useful test to aid in the
diagnosis of this medical condition is:
a)
b)
c)
d)
e)
Testosterone
17-hydroxyprogesterone
Serum sodium and potassium
DHEAS
DHEAS/androstenedione ratio
Cholesterol
Desmolase
Pregnenolone
17-OH
3--HSD
Progesterone
17 (OH) pregnenolone
3--HSD
17-OH
21-OH
DOCA
11-OH
Corticosterone
ALDOSTERONE
17 (OH) progesterone
DHEA
3--HSD
Androstenedione
21-OH
Compound S
11-OH
CORTISOL
TESTOSTERONE
If she has salt wasting congenital adrenal
hyperplasia, which abnormalities are likely to
develop. True or False for each
a)
b)
c)
d)
e)
Increased serum potassium
Decreased serum sodium
Decreased bicarbonate
Decreased plasma cortisol
Increased plasma renin activity
T
T
T
T
T
A 1-year male infant has non palpable testes.
Of the following, the most appropriate next step
would be
a)
b)
c)
d)
Schedule a re-examination in 18 months
Refer the patient for an exploratory laparotomy
Begin therapy with LHRH
Measure the plasma testosterone after
stimulation with HCG
e) Begin therapy with testosterone enanthate, 50
mg IM monthly for 3 months.
History
9 day old male infant
1 day history of decrease feeding, vomiting and lethargy.
Examination
Ill appearing infant with poor respiratory effort
Vital signs: T 99 F HR 100/min BP 61/40 RR 24/min
Resp:
Subcostal retractions but clear to auscultation
Cardiac:
Regular rate and rhythm. Normal S1 and S2
Abdomen: Soft, non distended. Non tender. No HSM
Neuro:
Lethargic. No focal deficit
Genitalia:
Normal male. Bilateral descended testes
Laboratory data:
WBC 16.7
Hb
16.4
Hct
49
Plt
537 K
CSF:
Chemistry: Protein 74
Microscopy: WBC 6
Na
K
Cl
CO2
Glucose
BUN/Creat
Glucose
RBC
82
100
121
9.3
83
6.7
163
33/0.2
Emergency therapy
Fluid resuscitation:
20 ml/kg Normal saline
Glucocorticoid
2 mg/kg Solucortef IV
Monitor EKG
Modes of presentation
Classical
Simple virilizing
Virilizing with salt loss
“Non classical” / Late onset
Therapy and evaluation of therapy
Glucocorticoid (Hydrocortisone)
Monitor growth, 17-OHP, urinary pregnanetriol
Fluorocortisol (Florinef 0.1 – 0.45 mg/day)
Blood pressure, plasma renin activity (PRA)
Supplemental salt
Until introduction of infant food
History
15 year female presents with primary amenorrhea
Breast development began at 10 years
Examination
Height: 5 ft 7 in Weight 130 lb
Tanner 5 breast development
Scant pubic hair
What is your diagnosis?
Complete androgen insensitivity
XY Genotype
Testosterone
Estradiol
Androgen
Receptor
Estrogen
Receptor
History
15 year female presents with primary amenorrhea
Breast development began at 10 years
Examination
Height: 5 ft 7 in Weight 130 lb
Tanner 5 breast development
Scant pubic hair
a)
b)
c)
d)
e)
Which of the following clinical features is the most likely
to give you the correct diagnosis
Blood pressure in all 4 extremities
Careful fundoscopic examination
Rectal examination
Measurement of blood pressure with postural change
Cubitus valgus and shield shaped chest
Early Puberty
The earliest sign of puberty in a male is:
a)
b)
c)
d)
e)
Enlargement of the penis
Enlargement of the testes
Growth acceleration
Pubic hair growth
Axillary hair growth
2 year old girl with breast development
– No growth acceleration
– No bone age advancement
– No detectable estradiol, LH or FSH
The most likely diagnosis is:
a) Ingestion of her mother’s OCPs
b) Precocious puberty
c) Premature adrenarche
d) Premature thelarche
e) McCune Albright Syndrome
Benign Premature Thelarche
Isolated breast development
– 80% before age 2
– Rarely after age 4
Not associated with other signs of puberty
(growth acceleration, advancement of bone age)
Children go on to normal timing of puberty and
normal fertility
Benign process
Routine follow-up
5 year female with 6 months of pubic hair growth.
Very fine axillary hair as well as adult odor to sweat.
No breast development
No exposure to
androgens
Growth chart:
Normal growth without
growth acceleration
Most likely diagnosis:
1. Precocious puberty
2. Benign premature adrenarche
3. Non-classical congenital adrenal hyperplasia
4. Adrenal tumor
5. Pinealoma
Benign Premature Adrenarche
Production of adrenal androgens before true
pubertal development begins
Presents as isolated pubic hair in mid childhood
– No growth acceleration
– No testicular enlargement in boys
If normal growth rate, routine follow-up
If accelerated growth and/or bone age
advancement, screen for
– CAH
– Virilizing tumor (adrenal/gonadal)
Choose correct answer
A. Premature theralche
B. Premature adrenarche
C. Both
D. Neither
1. Growth acceleration
D
2. Normal adolescent sexual development
C
3. Onset of gonadal function usually in 2-3 years
B
You suspect a 16 year female has Turner
syndrome. The most definitive diagnostic test is
a)
b)
c)
d)
e)
Buccal smear
Chromosome analysis
Measuring her FSH and LH
Determining her bone age
Determining her testosterone level
5 year old girl with pubic hair and rapid growth.
She has no breast development
Possible sources of androgens:
1.Liver
F
2.Adrenal
T
3.Ovary
T
4.Pituitary
F
5.Pineal
F
5 year old girl with pubic hair and rapid growth.
She has no breast development
Which of the following should be considered
Answer T or F for each:
a) Central precocious puberty
F
b) Congenital adrenal hyperplasia
T
c) McCune Albright syndrome
F
d) Benign premature adrenarche
F
e) Adrenal tumor
T
When does puberty occur?
Classic teaching
– 8 -13 in girls
(menarche ~ 2 years
after onset of puberty)
– 9 -14 in boys
Case:
Breast development:
Mother had menarche:
6 years
9.5 years
Why
Reactivation of
hypothalamic –
pituitary –gonadal
axis
Gonadatropin dependent
(central) precocious puberty
Clock turns on early
Idiopathic
> 95 % girls
~ 50 % boys
– Hypothalamic hamartoma (Gelastic seizures)
– NF (optic glioma)
– Head trauma
– Neurosurgery
– Anoxic injury
– Hydrocephalus
Treatment
Why
– Psychosocial
– Height
What
– GnRH agonist
Gonadotropin independent
precocious puberty
7 year male presents with 6 month history of pubic
and axillary hair growth as well as adult body odor.
Mother thinks he is growing faster than his peers
No exposure to androgens
PM&SH – nil of note
Mother had menarche at 12 yr
Father had normal timing of his puberty
Medications – none
Height 50th percentile (last height at 25th)
Weight 40th percentile
No café au lait macules
No goiter
Heart and lungs: normal
Abdomen: Firm hepatomegaly with irregular border
Prepubertal
Adrenal source
Asymmetric
Enlarged testicle
Pubertal
Precocious puberty
Height 50th percentile (last height at 25th)
Weight 40th percentile
No café au lait macules
No goiter
Heart and lungs: normal
Abdomen: Firm hepatomegaly with irregular border
Genitalia:
Pubic hair - Tanner 2
Scrotal thinning
Testes 5 ml bilaterally (pubertal >3 ml)
Rest unremarkable
7 year male with signs of puberty
Gonadotropins
LABS:
Testosterone 48 ng/dl (<10)
FSH
<0.1 mIU/mL
LH
<0.1 mIU/mL
TSH
T4
1.0 μIU/mL
8.9 μg/dL
Pubertal
Central precocious
puberty
LH
G
Leydig cell
Precocious puberty in the male
Gonadotropins
Prepubertal
Pubertal
Gonadotropin independent
precocious puberty
HCG
Central precocious
puberty
LH
*
*
G
McCune Albright
Familial male
syndrome
Precocious puberty
(testotoxicosis)
G
Leydig cell
1. Gonadotropin independent PP
2. Polyostotic Fibrous Dysplasia
3. Café au lait macules
Final diagnosis: Gonadotropin independent precocious
puberty secondary to an βHCG secreting hepatoblastoma
5 year old with breast development
and growth acceleration
- Estradiol 62 pg/ml (<10)
- FSH
<0.1 mIU/mL
- LH
<0.1 mIU/mL
Gonadotropin independent
precocious puberty
McCune Albright syndrome:
1. Café au lait macules
2. Gonadotropin independent
precocious puberty
3. Polyostotic fibrous dysplasia
Growth disorders and
delayed puberty
Delayed puberty
Hypogonadism
Hypergonadotropic
Hypogonadism (↑FSH, LH)
Primary gonadal failure
- Chromosomal
- iatrogenic (cancer therapy)
- autoimmune oophoritis
- galactosemia
- test. biosynthetic defect
Hypogonadotropic
Hypogonadism (FSH, LH)
Constitutional
delay
Central
Hypogonadism
- Isolate gonad. def.
- MPHD
- Kallmann (anosmia)
- Functional
A 15 yr boy has short stature and delayed
puberty. He is now in early puberty (Tanner 2).
His parents are of average stature. His height
and weight are just below 3rd percentile.
All of the following are likely except:
a)
b)
c)
d)
A bone age of 12 ½ years
Growth hormone deficiency
Adult height in the normal range
Acceleration of growth and sexual maturation
over the next 2 years.
e) History of normal length and weight at birth
A 15 yr male has delayed puberty. He also has
headaches, diplopia and increased urination.
His height is < 3rd percentille
Which of the following is the most likely
diagnosis?
a)
b)
c)
d)
e)
Diabetes mellitus
Pinealoma
Cerebellar tumor
Craniopharyngioma
Pituitary adenoma
A 14 yr male has tender gynecomastia (3 cm in
diameter bilaterally). He is in early to mid
puberty. In most cases the best management for
this gynecomastia is:
a) Treatment with an anti-estrogen (e.g. Tamoxifen)
b) Treatment with an aromatase inhibitor
c) Treatment with a dopamine agonist
(bromocryptine)
d) Surgery
e) Reassurance
Diabetes
A 12 year female patient presents with a 4 week history
of polyuria, polydipsia, and marked weight loss.
She is noted to have deep, sighing respiration.
Glucose is 498 mg/dL, pH is 7.06. Her electrolytes
show Na 132, K 4.8, Cl 95 CO2 6 BUN 20 Creat 0.9.
The MOST important initial management is:
a) insulin drip 0.1 units/kg/hour
b) ½ Normal Saline with 40 meq K at 2x maintenance
c) Bicarbonate 1 meq/kg slowly over 1 hour
d) 20 ml/kg normal saline bolus IV
An obese 16 year male is found to have glycosuria at
routine urinalysis done as part of regular health care
maintenance. You order a glucose tolerance test.
GTT
Time
Glucose (mg/dL)
-0109
-120188
Which of the following statements are correct?
This patient has:
a)
b)
c)
d)
Type 2 diabetes
Impaired glucose tolerance but normal fasting glucose
Normal glucose tolerance
Both impaired fasting glucose and impaired glucose tolerance
Definition of diabetes
Diabetes
≥ 126
≥ 200
< 126
< 200
Pre-diabetes
≥ 100
≥ 140
< 100
< 140
Normal
Fasting
2 hr post load
An obese 14 year male is found to have glycosuria.
Fasting GTT is ordered and the results are as follows:
Time
Glucose (mg/dL)
-0109
-120188
This patient is at risk for the development of all the
following EXCEPT
a)
b)
c)
d)
e)
Type 2 diabetes
Dyslipidemia
Hypertension
Slipped capital femoral epiphysis
Hashimoto thyroiditis
A 13 year male has new onset type 1 diabetes
mellitus. Therapy for this child may include all
of the following EXCEPT:
a) Glargine (Lantus) and Lipro insulin (Humalog)
b) Detemir (Levemir) and Aspart insulin (Novolog)
c) Metformin
d) Analog insulin administered via an insulin pump
Miscellaneous
Hypoglycemia
Decreased substrate
– Poor intake
– Defective glycogenolysis or gluconeogenesis
Increase utilization
– Sepsis
– Hyperinsulinism
Absent counter regulatory hormones
– GH
– Cortisol
Choose correct answer
A. Hypoglycemia from hyperinsulinemia
B. Hypoglycemia from metabolic fuel depletion
C. Both
D. Neither
1. Usually preceded by ketosis
B
2. Brisk respones to glucagon
A
3. Usually responds to oral glucose
B
Side effects of corticosteroids include all of the
following except
a)
b)
c)
d)
e)
hypertension
hypoglycemia
decrease bone mineralization
myopathy
cataracts
What is the most likely diagnosis in this newborn infant?
1.
2.
3.
4.
5.
Mother has SLE
Anasarca from cardiac failure
Systemic allergic reaction
Congenital nephrotic syndrome
Turner syndrome
5 year old male with short stature
1.
2.
3.
4.
5.
Turner syndrome
VATER syndrome
Albright’s hereditary osteodystrophy
Noonan syndrome
Goldenhar syndrome
A moderately obese adolescent female has
irregular periods, hirsutism and acne
Of the following, which is the most likely
diagnosis?
a) Cushing syndrome
b) Polycystic ovarian syndrome
c) Virilizing adrenal tumor
d) Non-classical CAH
e) Hyperprolactinemia
Choose correct answer
A. Diabetes mellitus
B. Diabetes insipidus
C. Both
D. Neither
2 Na + BUN/2.8 + Gluc/18
1. Osmolality of serum > 300 Osm/L
C
2. Osmolality of urine > 500 mOsm/L
A
3. Hypernatremia
B