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.
Glucose 88; Na 141, Ca 5.1, Phos 9.1, Mag 2.1
The most likely diagnosis is:
1.
2.
3.
4.
Pseudohypoparathyroidism
Hypoparathyroidism
Vitamin D deficiency
Albright’s hereditary
osteodystrophy
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4
Actions of PTH
Ca
1.
2.
3.
25 OH Vit D
1 hydroxylase
1,25 (OH)2 Vit D
Gut
NET EFFECT
PO4
This same 6-week infant with hypoparathyroidism
(Glucose 88; Na 141, Ca 5.1, Phos 9.1, Mag 2.1)
What is an important diagnostic consideration
(i.e. what is the underling disorder causing the
hypoparathyroidism)?
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
Glycosuria
Bicarbonaturia
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
1.
2.
3.
4.
5.
Normal
Low
Low
Low
Normal
Phos
Normal
Low
High
Normal
Low
Alk Phos
Low
Low
High
Normal
High
0%
1
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2
3
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4
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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
Baby A, born on 5/27/10. Newborn screening tests,
performed on 5/29/10 revealed:
Normal range
TSH
37 µIU/ml
< 20
T4
10.1 µg/dl
9-19
Which statement is most accurate:
1.
2.
3.
4.
Baby A has congenital
hypothyroidism warranting urgent
therapy
Baby A will develop mental
retardation if untreated
Baby A likely does not have any
0%
thyroid abnormality
Baby A has an altered hypothalamic1
set-point for T4
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3
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You are contacted by your state Neonatal Thyroid
Screening Program. Baby X was born on 1/4/10.
His newborn screening tests, performed on 1/6/10
revealed:
Initial filter paper
TSH
T4
Normal range
>200 IU/ml
< 20
2.1 g/dl
9-19
Venipuncture: (1/25/10)
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 with gastroschisis has the following TFTs on day 5
of life:
T4
2.1 μg/dL
(4.5-12.5)
TSH
2.3 μIU/mL (0.3-5.0)
The most likely diagnosis is:
1.
2.
3.
4.
5.
Hypothyroidism due to
thyroid dysgenesis
Central hypothyroidism
TBG deficiency
Hypothyroidism from
excess iodine exposure
Normal thyroid function
(as the TSH is normal)
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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
Thyroid function in a 17 year old:
TSH:
3.7
µIU/ml
T4:
13.4 µg/dl
Normal range
0.3-5.5
4.5-12
Which of the following medication could explain the thyroid
function abnormality
1. INH
2. Retinoid acid
3. Ciprofloxacin
4. Ortho Tri-Cylen
5. Doxycycline
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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
1. Infectious
2. Inflammatory
3. Autoimmune
4. Toxic (drug)
5. Neoplastic
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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:
1.
2.
3.
4.
5.
Testosterone
17-hydroxyprogesterone
Serum sodium and
potassium
DHEAS
DHEAS/androstenedione
ratio
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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:
1.
2.
3.
4.
5.
Re-examination in 18
months
Refer the patient for an
exploratory laparotomy
Begin therapy with
LHRH
Measure the plasma
testosterone after
stimulation with HCG
Begin therapy with
testosterone enanthate,
50 mg IM monthly for 3
months.
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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
15 yr female presents with primary amenorrhea.
Breast development began at 10 y
Tanner 5 breasts, scant pubic hair
Which of the following clinical features is the most likely to
give you the correct diagnosis
1.
2.
3.
4.
5.
Blood pressure in all 4
extremities
Careful fundoscopic
examination
Rectal examination
Measurement of blood
pressure with postural
change
Cubitus valgus and
shield shaped chest
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Gonadal Primordia
Female
No SRY
TESTIS
OVARY
No AMH
No testosterone
nor DHT
Mullerian Wolfian duct
regression
ducts
Fallopian tubes
Uterus
Upper vagina
Sertoli
cells
Leydig
cells
Testosterone
No AMH
Mullerian duct
regression
Wolfian ducts
DHT
Normal female
external genitalia
Epidymus
Normal male
Vas deferens
Seminal vesicles ext. genitalia
Gonadal Primordia
Y
Chromosome
No AMH
SRY
TESTIS
Sertoli
cells
No testosterone
nor DHT
AMH
Mullerian Wolfian duct
regression
ducts
Fallopian tubes
Uterus
Upper vagina
Mullerian duct
regression
Normal female
external genitalia
Leydig
cells
Testosterone
Wolfian ducts
DHT
Epidymus
Normal male
Vas deferens
Seminal vesicles ext. genitalia
Gonadal Primordia
Y
Chromosome
No AMH
SRY
TESTIS
Sertoli
cells
No testosterone
nor DHT
AMH
Mullerian Wolfian duct
regression
ducts
Fallopian tubes
Uterus
Upper vagina
Mullerian duct
regression
Normal female
external genitalia
Leydig
cells
Testosterone
Wolfian ducts
DHT
Epidymus
Normal male
Vas deferens
Seminal vesicles ext. genitalia
Early Puberty
The earliest sign of puberty in a male is:
1.
2.
3.
4.
5.
Enlargement of the
penis
Enlargement of the
testes
Growth acceleration
Pubic hair growth
Axillary hair growth
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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:
1.
2.
3.
4.
5.
Ingestion of her
mother’s OCPs
Precocious puberty
Premature
adrenarche
Premature thelarche
McCune Albright
Syndrome
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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 growth spurt
The most likely diagnosis is:
1.
2.
3.
4.
5.
Precocious puberty
Benign premature
adrenarche
Non-classical congenital
adrenal hyperplasia
Adrenal tumor
Pinealoma
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2
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0%
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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 3-4 years
B
You suspect a 16 year female has Turner syndrome. The
most definitive diagnostic test is
1.
2.
3.
4.
5.
Buccal smear
Chromosome
analysis
Measuring her FSH
and LH
Determining her
bone age
Determining her
testosterone level
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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:
1.
2.
3.
4.
5.
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.
History of normal length
and weight at birth
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1
2
5
A 15 yr male has delayed puberty. He also has headaches,
diplopia and increased urination. His height is < 3rd
percentile.
Which of the following is the most likely diagnosis?
1.
2.
3.
4.
5.
Diabetes mellitus
Pinealoma
Cerebellar tumor
Craniopharyngioma
Pituitary adenoma
0%
1
0%
2
0%
0%
3
4
0%
6
5
Countdown
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:
1.
2.
3.
4.
5.
Treatment with an antiestrogen (e.g. Tamoxifen)
Treatment with an
aromatase inhibitor
Treatment with a dopamine
agonist (bromocryptine)
Surgery
Reassurance
0%
1
0%
2
0%
0%
3
4
0%
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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:
1.
2.
3.
4.
insulin drip 0.1 u/kg/hr
½ NS with 40 meq K at 2x
maintenance
Bicarb 1 meq/kg slowly
over 1 hour
20 ml/kg normal saline
bolus IV
0%
0%
0%
0%
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1
2
3
4
GTT in a 16 year obese female:
Time
Glucose (mg/dL)
-0109
-120188
Which of the following statements are correct?
This patient has:
1.
2.
3.
4.
Type 2 diabetes
Impaired glucose
tolerance but normal
fasting glucose
Normal glucose
tolerance
Both impaired fasting
glucose and impaired
glucose tolerance
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1
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2
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3
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Definition of diabetes
Diabetes
≥ 126
≥ 200
< 126
< 200
Pre-diabetes
≥ 100
≥ 140
< 100
< 140
Normal
Fasting
2 hr post load
This obese patient with IFG and IGT is at risk for the
development of all the following EXCEPT
1.
2.
3.
4.
5.
Type 2 diabetes
Dyslipidemia
Hypertension
Slipped capital femoral
epiphysis
Hashimoto thyroiditis
Metabolic syndrome
0%
1
0%
2
0%
0%
3
4
0%
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A 13 year male has new onset type 1 diabetes mellitus.
Therapy for this child may include all of the following
EXCEPT:
1.
Glargine (Lantus) and
Lipro insulin (Humalog)
2.
Detemir (Levemir) and
Aspart insulin (Novolog)
3.
Metformin
4.
Analog insulin
administered via an
insulin pump
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1
0%
2
0%
3
0%
4
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Miscellaneous
Side effects of corticosteroids include all of the following
except
1. hypertension
2. hypoglycemia
3. decrease bone
mineralization
4. myopathy
5. cataracts
0%
1
0%
2
0%
0%
3
4
0%
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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
33%
27%
17%
13%
10%
1
2
3
4
5
5 year old male with short stature
1.
2.
3.
4.
5.
Turner syndrome
VATER syndrome
Albright’s hereditary
osteodystrophy
20%
Noonan syndrome
Goldenhar syndrome
23%
23%
23%
10%
1
2
3
4
5
A moderately obese adolescent female has irregular
periods, hirsutism and acne.
Of the following, which is the most likely diagnosis?
33%
1.
2.
3.
4.
5.
Cushing syndrome
Polycystic ovarian
syndrome
Virilizing adrenal tumor
Non-classical CAH
Hyperprolactinemia
23%
17%
1
2
13%
13%
3
4
5
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
2. Osmolality of urine > 500 mOsm/L
3. Hypernatremia
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