Pediatric Endocrinology Review

MCQs 2018-2019

Abdulmoein Eid Al-Agha, FRCPCH

Professor of Pediatric Endocrinology,
Website: http://aagha.kau.edu.sa
• A 2-year-old boy was referred for further
assessment of his increasingly bow legs. His
mother was known to have rickets. X-rays
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?
1) This boy has a 25% chance of inheriting
rickets from his mother
2) With this inherited form, he would be
expected to be less severely affected than his
mother
3) 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
4) 1,25 dihydroxy vitamin D3 is usually normal
or high
Hypophosphatemic rickets
• 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?
1) Observation of further progression of
pubertal signs
2) Confirm advancing bone age
3) MRI pituitary to look for any CNS tumors
4) 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?
1) Basal LH/FSH and estrogen
2) HCG
3) Thyroid function test
4) 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 (eg, gonadotropin-
independentprecocious 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 signalling
• A- 15 Year old young lady, who has presented
with exophthalmos and weight loss. Her
laboratory tests confirm Graves disease. Which
most likely cause for exophthalmos in Graves
disease?
a) Fat tissue deposition.
b) Ocular muscle hyperplasia.
c) Inflammatory infiltrate.
d) Globe enlargement.
Answer is C
• In Graves' disease, the main autoantigen is the
thyroid-stimulating hormone (TSH) receptor
(TSHR), which is expressed primarily in the
thyroid but also in adipocytes, fibroblasts, and
a variety of additional sites.
• TSHR antibody and activated T cells also play
an important role in the pathogenesis of
Graves' orbitopathy by activating retroocular
fibroblast and adipocytes TSHR
Disrupted muscle fibers and an area of inflammatory cell accumulation in the
superior rectus muscle of a patient with ophthalmic Graves' disease. The extra ocular
muscles are swollen, and some muscle fibers show loss of striation, fragmentation,
and infiltration with lymphocytes, most of which are T lymphocytes.
 Graves Ophthalmopathy
• A gritty or foreign object sensation in the eyes
• Excessive tearing that is often made worse by
exposure to cold air, wind, or bright lights
• Eye or retroocular discomfort or pain
• Blurring of vision
• Diplopia
• Occasionally loss of vision
• Presentation of thyrotoxicosis varies, as follows :
• Younger patients tend to exhibit symptoms of
sympathetic activation (e.g., anxiety, hyperactivity,
tremor)
• Older patients have more cardiovascular
symptoms (e.g., dyspnea, atrial fibrillation) and
unexplained weight loss
• Patients with Graves disease often have more
marked symptoms than patients with
thyrotoxicosis from other causes
• Ophthalmopathy (e.g., periorbital edema,
diplopia, or proptosis) suggests Graves disease
Therapeutic options for Thyrotoxicosis
 Anti-Thyroid medications
• Used for long-term control of hyperthyroidism in children,
adolescents, and pregnant women
• In adult men and nonpregnant women, used to control
hyperthyroidism before definitive therapy with radioactive
iodine
• Methimazole is more potent and longer-acting than
propylthiouracil
• Propylthiouracil is reserved for use in thyroid storm, first
trimester of pregnancy, and methimazole allergy or intolerance
• Antithyroid drug doses are titrated every 4 weeks until thyroid
functions normalize
• Patients with Graves disease may experience remission after
treatment for 12-18 months, but recurrences are common
within the following year
• Toxic multinodular goiter and toxic adenoma will not go into
remission
 Radioactive iodine treatment
• Preferred therapy for hyperthyroidism
• Administered orally as a single dose in capsule or liquid
form
• Causes fibrosis and destruction of the thyroid over weeks
to many months
• Hypothyroidism is expected
• Pregnancy, breast feeding, and recent lactation are
contraindications
• Radioactive iodine should be avoided in children younger
than 5 years [3]
• Radioactive iodine is usually not given to patients with
severe Ophthalmopathy
 Thyroidectomy
• Is reserved for special circumstances, including the
following:
• Severe hyperthyroidism in children
• Pregnant women who are noncompliant with or intolerant
of antithyroid medication
• Patients with very large goiters or severe Ophthalmopathy
• Patients who refuse radioactive iodine therapy
• Refractory amiodarone-induced hyperthyroidism
• Patients who require normalization of thyroid functions
quickly, such as pregnant women, women who desire
pregnancy in the next 6 months, or patients with unstable
cardiac conditions
• What is the most serious side effect of PTU
anti thyroid?

a) Fever
b) Rash
c) Granulocytopenia
d) Hepatotoxicity
• Thionamide compounds were found in 1943 to
inhibit thyroid hormone synthesis.
• They are actively transported into the thyroid
gland where they inhibit both the
organification of iodine to tyrosine residues in
thyroglobulin and the coupling of
iodotyrosines
• Adverse effects of Thionamide include
common, minor side effects (e.g., rash) and
rare but serious adverse effects, such as
agranulocytosis and hepatotoxicity
• 16 year old boy presented with thyroticosis
has developed bilateral, firm, non- pitting,
asymmetrical plaques . Which of the following
describes skin lesion?

a) Pretibial myxedema.
b) Scleroderma.
c) Eczematous lesions.
d) Dermatomyositis.
Pretibial myxedema (PTM) or, more appropriately, thyroid dermopathy is a term used to describe
localized lesions of the skin resulting from the deposition of hyaluronic acid, usually as a
component of thyroid disease. Thyroid dermopathy occurs rarely. Although PTM is most often
confined to the pretibial area, it may occur anywhere on the skin, especially the ankle, dorsum of
the foot, knees, shoulders, elbows, upper back, pinnae, nose, and neck. It is nearly always
associated with autoimmune thyroid disease
• A 6 year old boy with obesity, mental
retardation and subcapsular cataract. Which
one of the following is expected laboratory
finding?

a) Low calcium, low phosphate

b) High calcium, high phosphate
c) Low calcium, high phosphate
d) Normal calcium, normal phosphate
Answer is C
• The clinical picture is indicating diagnosis of
Albright hereditary osteodystrophy.
• The etiology of hypocalcaemia can be related
to failure of a component of this system, such
as deficiency of or resistance to parathyroid
hormone (PTH) or vitamin D, or a defect of the
calcium-sensing receptor (CaSR).
 Pseudohypoparathyrodism (PHP)
• A heterogeneous group of rare endocrine disorders
characterized by normal renal function and resistance
to the action of parathyroid hormone (PTH),
manifesting with hypocalcaemia, hyperphosphatemia,
and increased serum concentration of PTH.
• There are 5 variants of Pseudohypoparathyrodism:
– PHP type 1a (PHP-1a), PHP type 1b (PHP-1b), PHP type 1c
(PHP-1c), PHP type 2 (PHP-2), &
pseudopseudohypoparathyroidism (PPHP).
– PHP type 1a is the most common subtype and represents
70% of cases.
 Pseudohypoparathyrodism (PHP)
• In 1942, Fuller Albright first introduced the term
Pseudohypoparathyrodism to describe patients who
presented with PTH-resistant hypocalcaemia and
hyperphosphatemia along with an unusual constellation of
developmental and skeletal defects, collectively termed
Albright hereditary osteodystrophy (AHO).
• These features included short stature, rounded face,
shortened fourth metacarpals and other bones of the hands
and feet, obesity, dental hypoplasia, and soft-tissue
calcifications/ossifications. In addition, administration of
PTH failed to produce the expected phosphaturia or to
stimulate renal production of cyclic adenosine
monophosphate (cAMP).
• AHO phenotype is not a feature of PHP-1b or PHP-2.
• A 15 year old girl with obesity, retinitis
pigmentosa and hypogonadism. Which of the
following is most likely diagnosis?

a) Prader –Willi syndrome

b) Laurence- Moon- Beidl syndrome
c) Lowe oculocerebral syndrome
d) Familial cerebellar ataxia
Answer is A
• Genetic syndromes associated with childhood
obesity include the following:
• Prader-Willi syndrome
• Pseudohypoparathyroidism
• Laurence-Moon-Biedl (Bardet-Biedl) syndrome
• Cohen syndrome
• Down syndrome
• Turner syndrome
 Bardet–Biedl syndrome (BBS)
• A rare autosomal recessive syndrome
• Characterized by retinal dystrophy, obesity,
post-axial polydactyly, renal dysfunction,
learning difficulties and hypogonadism.
• The diagnosis is based on clinical findings and
can be confirmed by sequencing of known
disease-causing genes in 80% of patients.
• A 16 year old boy presented with
Gynecomastia. Which of the following
medications could be the cause?

a) Hydralazine.
b) Tamoxifen.
c) Spirinolactone.
d) Danazol.
Answer is C: Spirinolactone
• Gynecomastia is a benign enlargement of the
male breast (usually bilateral but sometimes
unilateral) resulting from a proliferation of the
glandular component of the breast.
• It is defined clinically by the presence of a
rubbery or firm mass extending concentrically
from the nipples.
• Gynecomastia should be differentiated from
pseudogynecomastia (lipomastia), which is
characterized by fat deposition without
glandular proliferation
A thorough history should be obtained that
addresses the following:
• Age of onset and duration of the condition
• Any recent changes in nipple size and any pain
or discharge from the nipples
• History of mumps, testicular trauma, alcohol
use, or drug use
• Family history of Gynecomastia
• History of sexual dysfunction, infertility, or
hypogonadism
Physical examination should include the following:
• Thorough examination of the breasts, with
attention to size and consistency
• Assessment for any nipple discharge or axillary
lymphadenopathy
• Testing to differentiate between true
Gynecomastia and pseudogynecomastia
• Assessment of glandular tissue
• Examination of the testicles, with attention to
size and consistency, as well as nodules or
asymmetry
• Observation of any signs of feminization
• Checking for any stigmata of chronic liver disease,
thyroid disease, or renal disease
Approach Considerations
• Generally, no treatment is required for physiologic
Gynecomastia.
• Pubertal Gynecomastia resolves spontaneously within
several weeks to 3 years in approximately 90% of patients.
• Breasts greater than 4 cm in diameter may not completely
regress.
• If hypogonadism (primary or secondary) is the cause of
Gynecomastia, parenteral or transdermal testosterone
replacement therapy is instituted.
• However, testosterone does have the potential to exacerbate
Gynecomastia through the aromatization of the exogenous
hormone into estradiol.
• idiopathic Gynecomastia or with residual Gynecomastia after
treatment of the primary cause, medical or surgical
treatment may be considered.
Pharmacologic Therapy
• With the administration of clomiphene, an antiestrogen,
approximately 50% of patients achieve partial reduction in
breast size, and approximately 20% of patients note
complete resolution.
– Adverse effects, while rare, include visual problems, rash, and
nausea.
• Tamoxifen, an estrogen antagonist, is effective for recent-
onset and tender Gynecomastia.
• Up to 80% of patients report partial to complete resolution.
Nausea and epigastric discomfort are the main adverse
effects.
• Other drugs used, albeit less frequently, include
danazol. Danazol, a synthetic derivative of testosterone,
inhibits pituitary secretion of LH and follicle-stimulating
hormone (FSH), which decreases estrogen synthesis from
the testicles.
• A 10 day old boy presented with hypertension
and metabolic alkalosis. He was diagnosed as
congenital adrenal hyperplasia. Which of the
following enzyme deficiency could be the
cause?

a) Aldosterone synthase deficiency.

b) 21-beat hydroxylase deficiency
c) 3-beta-hydroxysteroid dehydrogenase deficiency
d) 17-beta hydroxylase deficiency
Answer is 17-beta hydroxylase deficiency
• 17-Hydroxylase (17-OH) deficiency syndrome is a rare
genetic disorder of steroid biosynthesis that causes
decreased production of glucocorticoids and sex steroids,
resulting in sexual infantilism in 46,XX females &
ambiguous genitalia in 46,XY males
• Increased synthesis of mineralocorticoids precursors,
resulting in varying degrees of hypertension and
hypokalaemia
• It is a rare form of congenital adrenal hyperplasia resulting
from loss-of-function mutations involving the CYP17 gene.
• Exogenous glucocorticoid therapy is the treatment of
choice and suppresses adrenocorticotropic hormone
(ACTH) secretion, decreases 11-DOC and corticosterone
levels, and normalizes serum potassium and blood
pressure.
• 12 year old boy presented with proptosis and
tachycardia with fine tremor. He was
confirmed to have Graves disease. Which of
the following is most accurate statement?

a) Radioactive iodine therapy in this case is first line of

management.
b) PTU is more preferable than MTZ.
c) Granulocytopenia is a complication of anti thyroid
medications.
d) Surgery is good option for this child.
• 11 year old boy presented with central
obesity, striae, hypertension and
osteoporosis. What is the most likely
underlying cause?

a) Craniopharyngioma
b) Renal failure
c) Bilateral adrenal hyperplasia
d) Lipoid adrenal hyperplasia
• The symptoms and signs of Cushing's syndrome result
directly from chronic exposure to excess glucocorticoid.
• Establishing the diagnosis is often difficult because few
of the symptoms or signs are pathognomonic of the
syndrome in isolation.
• There is a large spectrum of manifestations from
subclinical to overt syndrome, depending on duration
and intensity of excess steroid production.
• Cushing's disease – Pituitary ACTH-dependent
Cushing's syndrome is five to six times more common
than Cushing's syndrome caused by benign and
malignant adrenal tumors combined
ACTH-independent Cushing syndrome
• Overproduction of glucocorticoid may be due to an
adrenal adenoma, adrenal carcinoma, or macronodular
or micronodular adrenal hyperplasia.
• The zona fasciculate and zona reticularis layers of the
adrenal cortex normally produce glucocorticoid and
androgens.
• Glucocorticoid-secreting tumors are derived from these
cells and, thus, may secrete both glucocorticoid and
androgens.
• In general, excess androgen secretion is suggestive of
an adrenal carcinoma rather than an adrenal adenoma.
• These glucocorticoid-producing tumors do not usually
secrete Aldosterone, which is produced in the zona
glomerulosa layer of the adrenal cortex.
ACTH-independent Cushing syndrome
• The Carney complex is a familial form of micronodular hyperplasia of
the adrenal gland.
– It is an autosomal dominant disorder and ACTH-independent cause of
Cushing syndrome.
– Pigmented skin lesions and mesenchymal and endocrine tumors
characterize this disorder.
• Cushing syndrome may be overt, subclinical, cyclical, or periodic.
• Primary bilateral macronodular adrenal hyperplasia is uncommon
and characterized by multiple nonpigmented nodules that are
greater than 10 mm in diameter and enlarged adrenal glands.
• The exact etiology of this condition is not quite clear, however,
genetic mutations, paracrine ACTH secretion, and aberrant hormone
receptors have been reported to play a role in its pathogenesis.
• McCune-Albright syndrome is a rare cause of precocious puberty.
– It is associated with hyperfunction of the adrenal glands that may lead
to Cushing syndrome.
• Ectopic cortisol secretion from a case of ovarian carcinoma has been
reported as a cause of ACTH independent Cushing syndrome.
• A 15 year old boy who was diagnosed with
Conn’s syndrome. Which of the following
electrolyte disturbances is expected?

a) Low sodium, low potassium

b) Low sodium and high potassium
c) High sodium and low potassium
d) High sodium and normal potassium
High sodium and low potassium
• No suppressible (primary) hypersecretion of
Aldosterone is cause of hypertension.
• The classic presenting signs of primary Aldosteronism
are hypertension and hypokalaemia, but potassium
levels are frequently normal in modern-day series of
primary Aldosteronism.
• The most common subtypes of primary Aldosteronism
are:
– Aldosterone-producing adenomas (APAs)
– Bilateral idiopathic Hyperalsosteronism (IHA; bilateral
adrenal hyperplasia)
– Less common forms include familial Hyperalsosteronism
(FH) types I to IV.
• Hyperalsosteronism is characterized by
excessive secretion of Aldosterone, which
causes increases in sodium reabsorption and
loss of potassium and hydrogen ions.
• It may be either primary (autonomous) or
secondary
• Hyperalsosteronism represents part of a larger
entity of hypermineralocorticoidism that may
be caused by Aldosterone, its
mineralocorticoids precursors, or defects that
modulate Aldosterone effects on its target
tissues
• The principal site of action of Aldosterone is the
distal nephron, though several other sites of
Aldosterone-sensitive sodium regulation are
noted, including the sweat glands and the
gastrointestinal (GI) tract.
• The principal regulators of Aldosterone synthesis
and secretion are the renin-angiotensin system
and the potassium ion concentration.
• Minor regulators include adrenocorticotropic
hormone (ACTH) from the pituitary, atrial
natriuretic peptide from the heart, and local
adrenal secretion of dopamine.
• Which one of the following is not HLA related
disorder?

a) Hashimoto’s thyroiditis.
b) Type 2 diabetes.
c) Addison’s disease.
d) Ankylosing spondylitis.
Answer is B
• The major histocompatibility complex (MHC) is a term
used to describe a group of genes in animals and
humans that encode a variety of cell surface markers,
antigen-presenting molecules, and other proteins
involved in immune function.
• The human leukocyte antigen (HLA) complex is
synonymous with the human MHC.
• The earliest HLA associations with rheumatic diseases,
such as the association of the HLA-B*27 allele at the
HLA-B gene with ankylosing spondylitis (AS) risk and
the association of the HLA-DRB1*04 allele at the HLA-
DRB1 gene with rheumatoid arthritis (RA), were
discovered several decades ago.
• A 10 year old boy with Cushing syndrome
presented acutely in the emergency room
with Addisonian crisis. Which statement is
most accurate?

a) This is impossible, as diagnosis must be

inaccurate.
b) The patient should be reinvestigated again.
c) The patient should be treated as Addisonian
crisis.
d) The patient is likely to have mixed pituitary
tumor causing both diseases.
Answer is C
• The most common cause of Cushing syndrome
in children is prolonged exposure to steroids.
• This often lead to suppression of H-P-A axis, so
patient will not be able to produce cortisol in
stress situations.
• This result in Addisonian crisis if steroid doses
were not increased during stress.
• A 15 year old young man noted to have firm
mass behind the right nipple. The mass is
mobile, non tender. Select the most likely
diagnosis?

a) Lymphoma
b) Intraductal papilloma
c) Gynecomastia
d) Benign cyst
Answer is C
• Pubertal Gynecomastia is common from puberty
till age of 25.
• It resolves spontaneously without any
intervention.
• It is most likely due to aromatization of
testosterone into estrogen.
• Gynecomastia is the benign proliferation of
glandular breast tissue in males. It differs from
proliferation of breast tissue in females in that
there is no terminal alveolar development in
response to progesterone
• Delayed puberty in girls is defined as absence
of secondary sex characteristics after age of?

a) 11- year old.

b) 13- year old.
c) 15- year old.
d) 16 - year old.
• Delayed puberty is defined as the absence of the first signs of
pubertal development beyond the normal range for the population.
• In the United States, this means the absence of breast development
by age 13 years in girls, or absence of testicular enlargement by age
14 years in boys. However, there are clear racial and ethnic
variations in the timing of puberty, such as earlier onset of puberty
in African American girls compared with Caucasian counterparts
• These racial, social, and ethnic differences should be incorporated
into decisions regarding the evaluation and therapy of pubertal
disorders
• The most common cause of delayed puberty is a functional defect in
production of gonadotropin-releasing hormone (GnRH) from the
hypothalamus.
• This may be due to physiologic individual variation, known as
constitutional delay of growth and puberty, or other functional
defects, such as under nutrition or chronic illness
• What is the most common cause of primary
hyperthyroidism in children?

a) Parathyroid carcinoma.
b) Parathyroid adenoma.
c) Parathyroid hyperplasia.
d) As complication of thyroidectomy.
Answer is B
• The diagnosis of hyperparathyroidism is
usually first suspected because of the finding
of an elevated serum calcium concentration
• The diagnosis of primary hyperparathyroidism
(PHPT) is usually made by finding a PTH
concentration that is frankly elevated or
within the normal range but inappropriately
normal given the patient's hypercalcemia
• In approximately 85% of cases, primary
hyperparathyroidism is caused by a single adenoma.
• In 15% of cases, multiple glands are involved (i.e.,
either multiple adenomas or hyperplasia).
• Rarely, primary hyperparathyroidism is caused by
parathyroid carcinoma.
• Familial cases can occur as either part of the multiple
endocrine neoplasia syndromes (MEN 1 or MEN 2a),
hyperparathyroid-jaw tumor (HPT-JT) syndrome, or
familial isolated hyperparathyroidism (FIHPT).
• Familial hypocalciuric hypercalcemia and neonatal
severe hyperparathyroidism also belong to this
category.
• Which of the following medications is used in
treating adolescent female with hirsutism?

a) Thiazide diuretic.
b) Oral contraceptives.
c) Sildenafil.
d) Minoxidil.
Answer is B
• Contraceptives can treat hirsutism in 2/3 of
cases.
• Direct suppression of ovarian steroid
production and increase hepatic binding
globulin production, which binds circulating
androgens which lead to decrease free
androgens.
• Hirsutism is a clinical diagnosis defined by the presence of
excess terminal hair growth (dark, coarse hairs) in
androgen-dependent areas (e.g., upper lip, chin,
midsternum, upper abdomen, back, and buttocks)
• Hair growth can be graded as either normal or excessive
based upon the Ferriman-Gallwey score.
• There are several conditions characterized by generalized
or "excess" hair growth that do not represent hirsutism
and do not require biochemical evaluation with serum
androgens, including hypertrichosis and "unwanted hair"
(any hair growth [usually light, unpigmented facial hair]
• This type of hair is not a sign of androgen excess, and it
does not respond to androgen suppression therapies.
However, there are hair removal techniques that can be
used.
• Systemic therapies directed at hirsutism can be
divided into those that decrease ovarian or
adrenal androgen production and those that
inhibit androgen action in the skin.
• The systemic therapies include glucocorticoids,
oral contraceptives (OCs), Spirinolactone,
flutamide, finasteride, cyproterone acetate, and
insulin sensitizers (metformin and rosiglitazone).
• Laser therapy has been shown not only to reduce
unwanted hair but also to improve depression
and anxiety in women with hirsutism.
• In many patients, hirsutism can be controlled just
with laser, without using any drugs
 Hirsutism versus 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
 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

5/26/2019 79
Among which of the following is most likely
diagnosis?
1) Generalized resistance to thyroid hormone
(GRTH)
2) Pituitary resistance to thyroid hormone
(PRTH)
3) Pendred's syndrome
4) TSH secreting Adenoma

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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)
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• 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

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 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

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• 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?
1) Slipped capital femoral epiphysis (SCFE)
2) Chronic osteomyelitis
3) Vitamin D deficiency
4) 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.
• Orthopaedic surgeon and urgent surgery are
necessary.
• An acute on chronic slippage of the epiphysis may
cause avascular necrosis of the femoral head.
• Prophylactic pinning of the other femoral head is
advocated by some surgeons.
• Thyroxine 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
A 8-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. She has
webbing of the neck. Which one of the
following findings could be found in this child?
a) Constitutional delay of Puberty
b) Hypogonadotrophic hypogonadism
c) Thyrotoxicosis
d) Hypergonadotrophic hypogonadism
Answer is D
 Turner syndrome
• This syndrome of short stature, primary amenorrhea (ovarian
dysgenesis), webbed neck, lymphedema, and cubitus valgus
• incidence among liveborn 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
• 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
 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?
1) Look for other dysmorphic features
2) Admit and do critical sample during his
hypoglycemia attack
3) Do GH stimulation test
4) 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, Meckel-Gruber syndrome, and Smith-Lemli-Opitz
syndrome
 GH def
• Growth hormone (GH) deficiency occurs in approximately 1
per 10,000 children
• The severely GH‐deficient child may present with
hypoglycemia 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 growth hormone (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.
• A 14 year old young lady, presented with
irregular menses and hirsutism. Which of the
following supports the diagnosis of PCOS?

a) Low free testosterone level

b) LH: FSH ratio of 3:1
c) Low DHEAS
d) Low androstendione level
Answer is B
• Polycystic ovary syndrome (PCOS), frequently becomes
manifest during adolescence, and is primarily
characterized by ovulatory dysfunction and
hyperandrogenism.
• The syndrome is heterogeneous clinically and
biochemically.
• The diagnosis of PCOS has lifelong implications with
increased risk for metabolic syndrome, type 2 diabetes
mellitus, and possibly cardiovascular disease and
endometrial carcinoma.
• PCOS should be considered in any adolescent girl
presenting with a chief complaint of hirsutism,
treatment-resistant acne, menstrual irregularity,
acanthosis nigricans, and/or obesity
• Females with (PCOS) have abnormalities in the
metabolism of androgens & estrogen and in the
control of androgen production.
• Polycystic ovaries should have a 12 or more
follicles in at least 1 ovary
• Other causes of menstrual irregularity &
hyperandrogenism, should be excluded, including:
– adrenal or ovarian tumors
– thyroid dysfunction
– congenital adrenal hyperplasia,
– hyperprolactinemia
– Cushing syndrome