Transcript Endocrinology

Paediatric Endocrine Review
Questions
Abdulmoein Eid Al-Agha, MBBS, DCH, CABP,
FRCPCH
Professor of Pediatric Endocrinology,
King Abdulaziz University Hospital
Pediatric Department
A 2-year-old boy was referred for further
assessment of his increasingly bow legs.
His mother was known to have rickets. Xrays show bowing of the tibial shafts. The
following blood measurements were
obtained:
calcium 2.37mmol/L,
phosphate 0.13mmol/L , alkaline
phosphatase 805IU/L, PTH 1.3pmol/L.
Which one of the following statements is
true?
A. This boy has 25% chance of inheriting
rickets from his mother
B. With this inherited form, he would be
expected to be less severely affected than
his mother
C. A simultaneous blood and urine sample
should be obtained for the measurement
of phosphate and creatinine so that the
renal threshold phosphate concentration
can be calculated
D. 1,25 dihydroxy vitamin D3 is usually
normal or high
Hypophosphatemic rickets
An otherwise healthy 6-week infant presents with a
generalized seizure. She is exclusively breast fed. The
child is somewhat sleepy with normal examinations.
Lab data:
Glucose
4.1 mmol/l
Sodium
141 mEq/L
Calcium
1.5 mmol/l
Phosphorus
2.1 mmol/l
Magnesium
0.8 mmol/l
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
What is an important diagnostic consideration
(i.e. what else is the child at risk for)
Causes ??
Permanent hypoparathyroidism
– DiGeorge syndrome (hypoparathyroidism,
absence of thymus gland with T-cell
abnormalities, and cardiac anomalies) is
associated with abnormal development of the
third and fourth pharyngeal pouches from
which the parathyroids derive embryologically
and represents an example of a defect in
parathyroid gland development.
– DiGeorge syndrome and velocardiofacial
syndrome are variants of the chromosome
arm 22q11 microdeletion syndrome.
X-linked recessive hypoparathyroidism
has been associated with parathyroid
agenesis and has been mapped to
chromosome arm Xq26-q27, the location
of a putative developmental gene.
Familial cases of hypoparathyroidism due
to mutations of the PTH gene located on
chromosome arm 11p15 have been
identified. These mutations have been
both dominantly and recessively inherited.
The hypoparathyroidism, deafness, and
renal dysplasia (HDR) syndrome is
associated with partial monosomy of
chromosome arm 10p
Mitochondrial cytopathies, such as
Kearns-Sayre syndrome (external
ophthalmoplegia, ataxia, sensorineural
deafness, heart block, and elevated
cerebral spinal fluid protein), are
associated with hypoparathyroidism.
• Autosomal dominant and sporadic gain-of-
function mutations of the Calcium sensing
receptor, a G-protein coupled receptor,
cause hypocalcemic hypercalciuria by
lowering the serum calcium concentration
that is required for PTH secretion and urinary
calcium reabsorption
• These individuals must be differentiated from
individuals with true hypoparathyroidism
because treatment with active vitamin D
(calcitriol) can cause nephrocalcinosis and
renal insufficiency by exacerbating the
already high urinary calcium excretion
• Sanjad Sakati syndrome (SSS) is an autosomal
recessive disorder found exclusively in people of
Arabian origin.
• It was first reported from the Kingdom of Saudi
Arabia in 1988 as a newly described syndrome
mainly from the Middle East and the Arabian Gulf
countries.
• Children affected with this condition are born
small for gestational age and present with
hypocalcemic tetany or seizures due to
hypoparathyroidism at an early stage in their lives.
• They have typical physical features, namely; long
narrow face, deep set small eyes, beaked nose,
large floppy ears, micrognathia, severe failure to
grow both intrauterine and extra uterine and mild
to moderate mental retardation.
A newborn screening tests showed the following:
TSH
fT4
27 IU/ml
18 nmol/l
This baby:
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 thyroxin replacement immediately
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 has an abnormal newborn
thyroid screen at 3 days which revealed a low T4 and
normal TSH.
Repeat venipuncture showed:
fT4
10 pmol/l
(12-22)
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
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


16 year 7 month, male
Growth failure x 3 1/2 years
Labs:
TSH:
fT4:
1008 µIU/ ml
<4 pmol/l
(0.3-5.0)
(12-22)
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)
Start of thyroxine
Which one of the following statement is true
regarding Graves’ ophthalmopathy?
A. Graves’ disease is the least common cause
of hyperthyroidism in childhood
B. It results from antibodies that block the
thyroid-stimulating hormone (TSH) receptor.
C. Exophthalmos occurs in only one third of
children.
D. Ophthalmopathy is more severe in children
and teens with Graves’ disease than it is in
adults
Proptosis
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
Childhood thyroid eye disease
Proptosis in childhood thyroid eye disease is
usually associated with a hyperthyroid state
The proptosis can be dramatic, but corneal
exposure and restrictive myopathy occur in only
some patients
Neuroimaging shows enlarged extraocular muscles
Most children with this complication can be treated
conservatively with topical lubrication, but orbital
fat decompression may be considered in patients
with more advanced conditions
A 12-yr female has diffuse enlargement of the
thyroid. Thyroid function tests suggesting
hyperthyroidism Her disorder is most likely
associated with which of the following
pathological processes
a)
b)
c)
d)
e)
Infectious
Inflammatory
Autoimmune
Toxic (drug)
Neoplastic
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
Three years old boy presented with
goiter, short stature, deafness and
symptoms suggestive of mild
hypothyroidism. On examination, was
having normal mentality, diffuse goiter,
deaf and mute with normal CNS
examination apart from sluggish
reflexes. His bone age was retarded and
has raised level of circulating TSH, fT4
and fT3.
Among which of the following is most
likely diagnosis?
A. Generalized resistance to thyroid
hormone (GRTH)
B. Pituitary resistance to thyroid hormone
(PRTH)
C. Pendred's syndrome
D. TSH secreting Adenoma
Answer:
Generalized resistance to thyroid
hormone
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Resistance to thyroid hormone (RTH)
• Is usually dominantly inherited
• Is characterized by elevated fT3 &fT4 and
failure to suppress TSH secretion
• variable refractoriness to hormone action in
peripheral tissues
• Two major forms:
– asymptomatic individuals with generalized
resistance (GRTH)
– patients with thyrotoxicosis features, suggesting
predominant pituitary resistance (PRTH)
• Recognized features of RTH include failure
to thrive, growth retardation and ADHD in
childhood, and goitre and thyrotoxic cardiac
symptoms in adults
• The most common cause of the syndrome
are mutations of the β (beta) form (THRB
gene) of the thyroid hormone receptor, of
which over 100 different mutations have
been documented
• Thyroid hormone resistance syndrome is
rare, incidence is variously quoted as 1 in
50,000 or 1 in 40,000 live births
Resistance to thyroid hormone
(RTH)
The characteristic blood test results for
this disorder can also be found in other
disorders (for example TSH-oma (pituitary
adenoma), or other pituitary disorders).
The diagnosis may involve identifying a
mutation of the thyroid receptor, which is
present in approximately 85% of cases
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
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
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?
15 year female presents with primary amenorrhea
Breast development began at 10 years
Examination
Height: 155Weight 45kg, Tanner 5 breast development
Scant pubic hair
Which of the following clinical features is the most likely to
give you the correct diagnosis
a) Blood pressure in all 4 extremities
b) Careful fundoscopic examination
c) Rectal examination
d) Measurement of blood pressure with postural change
e) Cubitus valgus and shield shaped chest
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
Complete androgen insensitivity
XY Genotype
Testosterone
Estradiol
Androgen
Receptor
Estrogen
Receptor
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)
• A -5-year-old girl presents with breast
enlargement and slight vaginal discharge,
together with moodiness and body odor.
There is no relevant past history and she is
well with no headaches, visual disturbance
or polydipsia. Mother and two elder sisters
had early menarche at 10–11 years. On
examination, her height is on the 90th
centile and mid-parental height 50th
centile. Examination shows Tanner stage
B3, P2, A1. What is the most important
diagnostic tool for this girl?
A. Observation of further progression of
pubertal signs
B. Confirm advancing bone age
C. MRI pituitary to look for any CNS tumors
D. Basal &LHRH stimulation test if needed
Investigations done for this case
Pelvic ultrasound shows enlarged uterus
with 4-mm endometrial echo, uterine
length 5cm.
Ovaries are 3.5mL in volume with five or
six 6-mm follicles in each
GnRH test shows basal/stimulated values
of 2.6/20 units/L for LH, and 3.2/15 units/L
for FSH
• This girl has true precocious puberty
• Onset of pubertal development before the
age of 8 years in a girl with a pubertal
LHRH test
• Idiopathic CPP is the likeliest cause but it
is now regarded as good practice to carry
out pituitary imaging with MRI in girls as
well as boys with CPP
• Given the age of the girl, the intensity of
pubertal tempo and the behavior
disturbances, suppressive therapy with an
LHRH
• Central precocious puberty (CPP) can be
considered as GnRH‐driven precocious
puberty; the physiology is the same as
puberty occurring at the usual age except for
age of onset.
• Peripheral precocious puberty (PPP) is
GnRH‐independent and thus includes all
pubertal development that is the result of
hormonal stimulation other than hypothalamic
GnRH pulsatile release stimulating pituitary
gonadotropin pulsatile secretion
Etiology of central precocious puberty
Gonadotropin‐releasing hormone (GnRH)–driven CPP
can be categorized as idiopathic when there is no
demonstrable abnormality and as central nervous
system (CNS)–related when an abnormality could be
documented on history, physical examination, or
otherwise.
Any insult that could affect influences on the
hypothalamus may be implicated.
Hypothalamic hamartomas are congenital and generally
present with precocious puberty at a young age
Optic glioma, occurring as an isolated finding or
associated with neurofibromatosis, is a frequent cause of
CNS‐related CPP
Causes of peripheral precocious
puberty (PPP) in females
Exogenous hormone administration, some
instances of primary hypothyroidism in which
the excessive thyroid‐stimulating hormone
(TSH) stimulates the follicle‐stimulating
hormone (FSH) receptor, oestrogen‐secreting
ovarian or (very rarely) adrenal tumours,
oestrogen‐secreting ovarian cysts (which also
may occur in central precocious puberty), and
in instances of activation mutations such as
the McCune‐Albright syndrome
Premature thelarche
Breast development in a 2‐year‐old girl not associated
with pubertal hormone levels with growth acceleration
and significant skeletal age advance.
Thelarche occurring prematurely is not associated with
pubertal physical or hormonal changes.
It most frequently presents during infancy or after age
6, before or after full hypothalamic‐pituitary‐ovarian
axis childhood quiescence (ages 3 through 5)
It may be associated with functional follicular cysts that
spontaneously regress and perhaps with especially
responsive breast tissue
Two- year old girl, brought by her
mother because of bilateral breast
enlargement and spotty vaginal
discharges. On examination (see
photo). Which is the most
important confirmatory
investigation you will order?
A. Basal LH/FSH and estrogen
B. HCG
C. Thyroid function test
D. GnRH stimulation test
• McCune-Albright syndrome (MAS) consists of at least
2 of the following 3 features:
– polyostotic fibrous dysplasia (PFD),
– café-au-lait skin pigmentation,
– autonomous endocrine hyperfunction (e.g., gonadotropinindependentprecocious puberty).
– Other endocrine syndromes may be present, including
hyperthyroidism, acromegaly, and Cushing syndrome
– Within the syndrome there are bone fractures and deformity
of the legs, arms and skull, different pigment patches on the
skin, and early puberty with increased rate of growth.
• Genetically, mutation of the gene GNAS1, on the
long (q) arm of chromosome 20 at position 13.3,
which is involved in G-protein signaling
•
Which one of the following is not a
cause of Hirsutism in females?
A. Congenital adrenal hyperplasia
B. Cushing’s syndrome
C. Androgen-producing ovarian
tumor
D. Androgen insensitivity syndrome
Hirsutism vs virilization
• Virilization includes clitoromegaly, male‐pattern
•
•
•
•
baldness, deepening of the voice, and increased
muscle mass in addition to the clinical features of
Hirsutism and chronic anovulation
The magnitude or amount of excessive hair growth can
be approximated by the Ferriman‐Gallwey score
With this method, the amount of hair growth in nine
androgen‐dependent areas is compared to a standard
chart (grades 1 to 4) from which a score is derived.
Grade 1 indicates minimal terminal hair growth and
grade 4 indicates dense terminal hair growth.
Scores greater than 8 are considered to indicate
hirsutism
Hypertrichosis / Hirsutism
Generalized hypertrichosis is a common adverse side effect of
several medications.
Starvation, whether due to malnutrition or anorexia nervosa, and
hypothyroidism can cause acquired Hypertrichosis.
Several genetic disorders can be associated with excessive
generalized hair growth.
Leprechaunism is characterized by Hypertrichosis and insulin
resistance due to mutations in the insulin receptor gene
Hirsutism is defined as excessive growth of coarse terminal hairs in
androgen‐dependent areas such as the face, upper chest, abdomen,
and back
Hypertrichosis is excessive hair growth in both androgen‐dependent
and androgen‐independent regions. For example, hair growth over
the whole body including arms and legs would be considered
Hypertrichosis because androgen‐independent regions are involved.
Ferriman‐Gallwey score
A 12-year-old girl was referred with growth
failure and delayed puberty. On
examination her height was below the
0.4th centile and her weight was on the
25th centile. Her height velocity was 1.8
cm/year. What is the most important initial
diagnostic approach?
A. Celiac antibody screening
B. Bone age
C. Chromosomal analysis
D. Thyroid function test
Turner syndrome
•
•
•
•
•
•
•
This syndrome of short stature, primary amenorrhea (ovarian
dysgenesis), webbed neck, lymphedema, and Cubitus valgus
incidence among live born female infants of one in 5000
More than half have a 45, X karyotype without evidence of
mosaicism.
The remainder show mosaicism and/or more complex
rearrangements involving the X chromosome.
Between 20% and 40% of girls with Turner syndrome have
significant heart defects, most commonly coarctation of the
aorta (70%), often bicommissural aortic valve, and aortic
stenosis—lesions generally not common in girls.
In fact, girls with Turner syndrome are prone to a spectrum
of left‐sided lesions ranging in severity from asymptomatic
bicommissural aortic valve to hypoplastic left heart syndrome
They are also at risk for aortic dilatation, dissection, and
rupture
Short stature
Categorization of children with short stature.
Short stature is commonly defined as height below
the third percentile.
It is estimated that 10% to 15% of children whose
height is below the third percentile have a
pathologic growth disorder.
The possibility of a growth disorder should be
considered in children whose linear growth is
below the third percentile, whose growth crosses
two major percentile lines in a downward fashion,
or who are unusually small for their family.
The key to the evaluation of short stature is a careful
history and determination of the growth parameters.
Children with a height within two standard deviations of
the mean for age and a normal height velocity are
unlikely to have a pathologic cause of their short stature
In the history, particular attention should be directed to
the birth history, the past growth pattern, parental
heights, and developmental milestones as well as to
nutrition and evidence of systemic disease.
On physical examination, particular attention should be
paid to anomalies suggestive of chromosomal disease,
as well as to arm span.
Preliminary investigations can include a free thyroxine
(T4) and thyroid-stimulating hormone (TSH), blood urea
nitrogen (BUN) or creatinine, erythrocyte sedimentation
rate (ESR), complete blood count (CBC), and an
assessment of skeletal maturation (bone age).
karyotype should be obtained in females and in those
males with significant physical anomalies
Three years old boy presented with
goiter, short stature, deafness and
symptoms suggestive of mild
hypothyroidism. On examination, was
having normal mentality, diffuse goiter,
deaf and mute with normal CNS
examination apart from sluggish reflexes.
His bone age was retarded and has
raised level of circulating TSH, fT4 and
fT3.
Among which of the following is most
likely diagnosis?
A. Generalized resistance to thyroid
hormone (GRTH)
B. Pituitary resistance to thyroid hormone
(PRTH)
C. Pendred's syndrome
D. TSH secreting Adenoma
Answer:
Generalized resistance to thyroid
hormone
4/5/2017
80
Resistance to thyroid hormone (RTH)
• Is usually dominantly inherited
• Is characterized by elevated fT3 &fT4 and
failure to suppress TSH secretion
• variable refractoriness to hormone action in
peripheral tissues
• Two major forms:
– asymptomatic individuals with generalized
resistance (GRTH)
– patients with thyrotoxicosis features, suggesting
predominant pituitary resistance (PRTH)
• Recognized features of RTH include failure
to thrive, growth retardation and ADHD in
childhood, and goitre and thyrotoxic cardiac
symptoms in adults
• The most common cause of the syndrome
are mutations of the β (beta) form (THRB
gene) of the thyroid hormone receptor, of
which over 100 different mutations have
been documented
• Thyroid hormone resistance syndrome is
rare, incidence is variously quoted as 1 in
50,000 or 1 in 40,000 live births
Resistance to thyroid hormone
(RTH)
The characteristic blood test results for
this disorder can also be found in other
disorders (for example TSH-oma (pituitary
adenoma), or other pituitary disorders).
The diagnosis may involve identifying a
mutation of the thyroid receptor, which is
present in approximately 85% of cases
5 year old girl with pubic hair and rapid growth.
She has no breast development
Possible sources of androgens:
1.Liver
2.Adrenal
3.Ovary
4.Pituitary
5.Pineal
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
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:
 Café au lait macules
 Gonadotropin independent
precocious puberty
 Polyostotic fibrous dysplasia
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
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
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
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’s 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)
b)
c)
d)
e)
Cushing syndrome
Polycystic ovarian syndrome
Virilizing adrenal tumor
Non-classical CAH
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
A 13-year-old girl presented at clinic
having been diagnosed as having
hypothyroidism by her family doctor who
had confirmed the diagnosis with thyroid
function tests. She also had a 2-year
history of a limp in her left leg. On
examination she was short and obese with
a goiter and other signs of hypothyroidism.
She had limitation of movement of her left
hip and a limp. What is the most likely
diagnosis?
A. Slipped capital femoral epiphysis (SCFE)
B. Chronic osteomyelitis
C. Vitamin D deficiency
D. Monoarticular rheumatoid arthritis
Slipped capital femoral epiphysis
(SCFE)
• Slipped femoral epiphysis and Hashimoto’s
•
•
•
•
•
•
disease
Anterioposterior and ‘frog-leg’ view X-rays (an A–
P) is recommended for diagnosis
X-ray alone may not demonstrate the slipped
epiphysis) and thyroid autoantibodies.
Orthopedic surgeon and urgent surgery are
necessary.
An acute on chronic slippage of the epiphysis may
cause a vascular necrosis of the femoral head.
Prophylactic pinning of the other femoral head is
advocated by some surgeons.
Thyroxin treatment should also be started.
SCFE
• Both boys and girls get SCFE
• They are almost always approaching their teenage
years or just into them (adolescents) when the
problem occurs.
• Several other factors can contribute to a child's
chances of having the problem:
– Overweight children
– Children with a family history of SCFE
– Children who have diseases of the endocrine system,
which produces hormones. Diabetes and Cushing
syndrome are examples of endocrine system
diseases.
– Children with kidney failure, thyroid problems or
growth hormone abnormalities
Eleven year old young boy who
had presented to the clinic
because of short stature. Height
was much below 3rd. percentile
and weight was on 75th.
percentile. Which is the following
is important in your initial
evaluation?
A. Measure parents height and
calculate mid-parental height
B. Assure him that his short stature is
not pathological
C. Admit immediately to do growth
hormone stimulation test
D. Start short trial of growth hormone
and see the response
Answer:
Measure parent's height and calculate
mid-parental height (an important initial
evaluation measure in child with short
stature)
A.
B.
C.
D.
20 days old, baby boy was seen in a
pediatric clinic for hypoglycemia . He had
dysmorphic features, cleft lip and palate
with a small mid-face. Both testes were
palpable, but the penis was rather small.
length was below the 3rd centile, weight on
the 10th centile. What is your next best
approach in order to reach diagnosis?
Look for other dysmorphic features
Admit and do critical sample during his
hypoglycemia attack
Do GH stimulation test
Do MRI brain
Holoprosencephaly
•
•
•
An infant with this malformation.
Up to one third of patients may have normal facial appearance.
Mutations in the human sonic hedgehog (SHH) gene cause
holoprosencephaly.
• About one third of cases have various chromosomal
abnormalities, such as trisomy 13 or 18, or deletion (7q), (13q),
or (18q).
• Some degree of holoprosencephaly is present in about 70% of
trisomy 13 patients and 30% of those with 7q32-ter deletions.
• Holoprosencephaly has been seen in infants of diabetic mothers
and also with a number of associations and genetic syndromes,
including the autosomal recessive pseudotrisomy 13, MeckelGruber syndrome, and Smith-Lemli-Opitz syndrome
GH deficiency
• Growth hormone (GH) deficiency occurs in
•
•
•
•
approximately 1 per 10,000 children
The severely GH‐deficient child may present with
hypoglycaemia in the newborn period, usually
indicating concomitant glucocorticoid deficiency and
panhypopituitarism.
After the first 6 months of life, linear growth rate slows
in the GH‐deficient child, resulting in downward
crossing of percentiles and subsequent growth
retardation.
The classically GH‐deficient child has a chubby
appearance with increased peritruncal fat and
decreased muscle mass.
Skeletal age is delayed, as is pubertal development in
the older child.
Diagnosis of GH deficiency
A poor response to provocative tests of GH secretion
(ie, demonstrating a peak serum GH level of <10 ng/mL in a
polyclonal assay to two of the following stimuli: L‐dopa,
clonidine, insulin‐induced hypoglycemia, arginine, glucagon)
remains the gold standard for diagnosis of GH deficiency,
despite the acknowledged lack of sensitivity and specificity of
these studies.
Useful screening blood studies for GH deficiency in the
well‐nourished child who is otherwise healthy include
measurement of serum insulin‐like growth factor‐1 (IGF‐1) and
IGF binding protein‐3 (IGFBP‐3), the levels of which usually are
low in GH deficiency.
GH‐resistant patients have low IGF‐1 and IGFBP‐3
concentrations, but elevated GH levels.
Circulating concentrations of GH‐binding protein, the product of
proteolytic cleavage of the extracellular component of the GH
receptor, may be low in some forms of GH resistance.
Which one of the following is an absolute
contraindication for growth hormone
replacement therapy in children?
A. Active malignancy
B. Proliferative retinopathy in a child with
diabetes and growth hormone deficiency
C. Scoliosis
D. Within six months of post surgical removal
of pituitary tumor
Answer: Active malignancy
Contraindications of GH therapy
• GH should not be used for pediatric treatment
if patient's growth plates (epiphyses) are
closed
• Active proliferative or severe non-proliferative
diabetic retinopathy.
• GH should not be used in patients with any
evidence of any tumor
• GH should not be used in patients preexisting or active malignancy
Contraindications of GH therapy
• GH should not be used in patients with
complication due to open heart or abdominal
surgery and with acute respiratory failure
• GH is contraindicated in severely obese
patients or with respiratory impairments
• GH is contraindicated in patients with PraderWilli syndrome who are severely obese or
have severe respiratory impairment
• GH is not indicated for children with growth
failure due to genetic Prader-Willi syndrome
Which one of the following is not proven
adverse effect of growth hormone
replacement?
A. Carpal tunnel syndrome
B. Arthralgia and myalgia
C. Benign intracranial hypertension
D. Increase incidence and recurrences of
brain tumor
Answer:
Increase incidence and recurrences of brain
tumor is never documented and is not
proven adverse effect of growth hormone
therapy
GH side effects
•
•
•
•
•
•
•
•
•
Allergic reaction
Ongoing injection site discomfort
Pain in wrist (carpal tunnel)
Curvature of the spine (scoliosis)
Joint pain
Puffy hands and/or feet (caused by fluid retention)
Changes in vision, a bad headache, or nausea
Hip or knee pain
Limping
A.
B.
C.
D.
Six-year-old girl was referred with growth
failure, poor appetite, recurrent abdominal
pain, ‘thick custard’ stools and vomiting.
What is the most diagnostic tool?
Bone age
Anti-tissue transglutaminase antibody
Jejunal biopsy
Serum iron and ferritin
Jejunal biopsy which will show villous
atrophy and lymphocytic infiltrate in the
lamina propria with hyperplastic crypts.
This confirmed a diagnosis of celiac
disease
Child with celiac disease
Note the protuberant abdomen and the
marked muscle wasting and evidence of
malnutrition
Children with celiac disease may exhibit no
unusual findings on physical examination
and rarely are as severely affected as this
girl.
Usually, they responded very well to a
strict gluten‐free diet that she must follow
for the rest of her life
• A 9-year-old girl was referred because of
tall stature. She has on & off headache.
On examination there were no dysmorphic
features. Her height was just above the
99th centile and her parents’ heights were
on the 50th and 75th centile. Pubertal
development was: breast, stage 2; pubic
hair, stage 3; and no menarche. Bone age
was 12.4 years and final height prediction
was 188 cm. Which one of the following
statement is most appropriate?
A. Most likely familial and need to observe
growth velocity
B. Need to do basal and stimulated GH test
C. Need to do IGF -1
D. Need to do an oral glucose tolerance test
for GH suppression
Tall stature
Children and adolescents with a height in excess of two
standard deviations above the mean height for age are
considered tall.
Obesity can also lead to tall stature in childhood.
However, in such children, puberty usually occurs early,
with a resulting normal final adult height.
Other causes of tall stature can include excessive
secretion of growth hormone or sex hormones
In the presence of excessive sex hormones, there will
be early growth acceleration, initially leading to tall
stature, subsequently, there will usually be early
epiphyseal closure, resulting in short stature after
puberty.
An extra X or Y chromosome can also be associated with excessive
linear growth, as can a spectrum of dysmorphic disorders, such as
homocystinuria, Marfan syndrome, Weaver syndrome, which is
accompanied by macrocephaly, large ears, and micrognathia, and Soto’s
syndrome, also known as cerebral gigantism.
Assessment of tall stature should begin with an evaluation of the height
velocity and determination of bone age.
An increased height velocity and advanced bone age suggest excessive
production of sex hormones, growth hormone, or, occasionally, thyroid
hormone.
Familial tall stature is a normal variant and is associated with normal
height velocity and tall parents
Long extremities are associated with homocystinuria, Marfan’s
syndrome, and Y chromosome disorders, whereas normal extremities
are found in estrogen insensitivity and the other syndromes associated
with tall stature.
More girls than boys seek medical attention for tallness because of the
perceived negative social consequences of the condition.
In the rare instances in which treatment is indicated, relatively high doses
of sex steroids are introduced early to advance osseous maturation.
Six month old male infant presented with
failure to thrive, constipation. His mother
was complaining of too many diaper
change and urine was leaking out of
diapers most of the time. On examination
he was having moderate to severe
dehydration. His initial sodium was high
175 mmol/l., very low urine osmolality.
Which one of the following is least
common cause in the differential
diagnosis of this infant?
a) Langerhans cell histiocytosis
b) X-linked recessive form of
nephrogenic diabetes insipidus
c) DIDMOAD syndrome
d) Psychological polydipsia
Answer:
Because the age of this infant of six
months, the least common cause will be in
this scenario is Psychological polydipsia
Central DI
The three most common causes of cranial
diabetes insipidus are:
– brain tumor that damages the hypothalamus
or pituitary gland, which accounts for 25% of
cases
– severe head injury that damages the
hypothalamus or pituitary gland, which
accounts for 16% of cases
– complications that occur during brain surgery,
which account for 20% of cases
Central DI
• Less common causes of cranial diabetic
insipidus include:
– cancers that spread from another part of the
body, such as the lungs or the bone marrow, to
the brain
– Wolfram syndrome, a rare genetic disorder that
also causes sight and vision loss
– brain damage caused by a sudden loss of
oxygen, which can occur during a stroke or
drowning
– infections, such as meningitis and encephalitis,
that can damage the brain
Which one of the following is first
line treatment of acute
hypercalcemia?
A. Calcitonin
B. Diuretics
C. Intravenous hydration
D. Bisphosphonate therapy
Answer: C
• Which one of the following is commonest
cause of 46 XX DSD?
A. Partial AIS
B. CAH (21- OH deficiency)
C. Virilizing ovarian or adrenal tumors
D. Placental Aromatase enzyme deficiency
Answer
CAH (21- OH deficiency) is the major
cause in 46 XX DSD not in 46 XY DSD.
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151
• Which one of the following is commonest
cause of 46 XY DSD?
A. Testicular Aplasia / Hypoplasia
B. Partial AIS
C. Testosterone biosynthesis defects
D. 5  - Reductase deficiency
Answer:
PAIS
• The following is true regarding primary adrenal
failure?
A. Is least commonly due to autoimmune
damage to the adrenal gland
B. Hemorrhage into adrenal gland due to
meningococcal infection (WaterhouseFrederickson syndrome is common cause
C. The long and short synacthen tests are useful
diagnostic tools in primary adrenal failure
D. Management is usually by lifelong
hydrocortisone administered orally at night.
Answer C
• Management is usually by lifelong
hydrocortisone administered orally at night
which is not true statement,
hydrocortisone usually given 2-3 times
daily, morning dose is usually higher than
other doses except in CAH where we need
to suppress early morning androgens, so
night dose will be higher one.
GOOD LUCK