THYROID DISORDERS

Hypothyroidism

By: Salma Riad, 2019 , Endocrine division

Objectives:

1- Thyroid gland anatomy

2- Thyroid hormone synthesis
3- Thyroid hormone functions
4- Congenital hypothyroidism
5- Acquired hypothyroidism
6- Subclinical hypothyroidism
7- References
Thyroid gland anatomy  Site: Anterior lower neck

Embryological origin: Follicular cells are endodermal

in origin. They develop by the end of the first trimester
and become functional in the second trimester.

Thyroid gland arises from the floor of the primitive

pharynx and descends into the neck. It is connected to
the tongue by thyroglossal duct which normally
disappears leaving foramen cecum.

Abnormalities include: Thyroglossal duct cyst and

ectopic thyroid tissue ( lingual ).
Thyroid hormone
synthesis
Thyroid hormone functions

 Brain maturation ( First 3 years )

 Bone growth ( Synergistic effect with growth hormone )
 Increases heart rate ( B1 receptors )
 Increases basal metabolic rate ( ATPase action )
 Increases blood glucose ( Glycogenolysis and
gluconeogenesis)
 Lipolysis
 Stimulates surfactant synthesis
Congenital hypothyroidism
:Etiology

A) Permanent causes:
1) Primary
- Dysgenesis
- Dyshormonogenesis
- TSH resistance
2) Central due to gene mutations
3) Peripheral due to thyroid hormone resistance
B) Transient causes:

- Maternal TSH blocking antibodies

- Maternal and neonatal iodine deficiency

- Excessive maternal iodine intake ( Wolf

Chaikoff effect )
- Maternal intake of antithyroid medications

- Liver hemangioma ( consumptive

hypothyroidism due to deiodinase effect )
Thyroid dysgenesis

 Agenesis ( most common ) or hypoplasia or ectopic

 Most common cause of congenital hypothyroidism in 85% of the cases
 No palpable thyroid
 Decreased ft4, total t4 , increased TSH , normal TBG
  Familial, autosomal recessive
 More common in twins, females > males
 Could be associated with goiter
 Caused by defect in thyroid hormone synthesis
Dyshormonogenesis ( most commonly affected enzyme is thyroid
peroxidase ) or transplacental passage of
antithyroid drugs
 Pendred syndrome: defect in pendrin
transmembrane protein resulting in hypothyroidism
and deafness
Clinical picture:

 Subtle at birth and becomes more

evident in weeks to months after birth
 Dry skin
 Hoarse cry
 Acrocyanosis
 Umbilical hernia
 Macroglossia
 Hypothermia
 Large fontanel
 Poor feeding
 Constipation
 Prolonged jaundice
:Investigations
Screening program

Heel prick is done for TSH ( most sensitive ) and if more resources are available , free t4 is also
done in the first 48-72 hours.

If the result is positive, immediate confirmation needs to be done.

Heel prick screening test might be falsely negative in premature, low birth weight and sick
babies so second confirmation needs to be done at 10-14 days.

If TSH < 10 mU/L —> transient hypothyroidism

If TSH 10-20 mU/L —> close follow up

If TSH >20 mU/L —> treatment should be started immediately

  Treatment is indicated to be started if TSH > 20 mU/L
 Treatment is started in the first 1-2 weeks and
continued for 3 years ( Period of brain maturation)
 Starting treatment < 1 month of age carries good
prognosis for intellectual development, while starting
treatment > 6 months of age carries poor prognosis
 Dosage: in full term —> 10 -15 mic/kg/day ( 37.5-50
mic/day ), while in older children the dosage is 3-5
Treatment of mic/kg/day.
 L troxin tabs can be crushed and added to formula,
congenital water, breast milk and given 1 hr before feeds ( to
hypothyroidism improve absorption). Soy products, calcium and iron
interfere with L troxin absorption.
 Missed dose can be taken next day.
 Goal : To maintain ft4 in upper half of normal range >
1.5 mU/L and TSH in lower half of normal range < 3
mU/L
 In case of central hypothyroidism, assess adrenal
functions first before giving L troxin. Glucocorticoids
must be given first to prevent adrenal crisis.
 Monitoring and follow up:
- After starting L troxin, follow up TSH and ft4 is done
after 1-2 weeks and repeated every 2 weeks until TSH
normalizes.
- Every 1-3 months till 12 months.
- Every 2-4 months from 12 months to 3 years.
- Every 3-6 months until growth is complete.
 At the end of 3 years, treatment is stopped for 1
month then follow up of thyroid functions done.
 If thyroid function tests normalize —> Transient
hypothyroidism—> follow up is done up to 1 year
every 3 months.
 If thyroid function tests are affected —> Permanent
hypothyroidism—> L troxin is restarted
Acquired hypothyroidism
:Etiology

A) Primary
- Hashimoto thyroidits
- Endemic goiter
- Post ablation ( surgery or irradiation)
- Medications ( Lithium, amiodarone, anticonvulsants )
- Late onset dysgenesis or errors of metabolism
B) Secondary
- Irradiation, craniopharyngioma, head trauma
- Thyroid hormone resistance
  Autoimmune process characterized by
lymphocytic infiltration of the thyroid gland
ending with fibrosis and atrophy.
 Most common cause of hypothyroidism in
older children and adolescents, females
Hashimoto are more affected than males.
 Positive family history in 25-35% of cases.
thyroiditis  Associations: Down syndrome, type 1 DM,
celiac disease, autoimmune polyglandular
syndrome type I and type 2.
 Presents first with thyrotoxicosis
( Hashtoxicosis) then euothyroidism then
hypothyroidism secondary to glandular
fibrosis and atrophy.
:Clinical presentation
Neuromuscular:
• Muscle weakness
• Hypotonia: constipation, potbelly
Ectodermal: • Umbilical hernia
• Poor growth • Myxedema coma: (carbon dioxide narcosis,
• Dull facies: thick lips, large tongue, depressed nasal hypothermia
bridge, periorbital edema • Pseudohypertrophy of muscles
• Dry scaly skin • Myalgia
• Sparse brittle hair • Physical and mental lethargy
• Diminished sweating • Developmental delay
• Carotenemia • Delayed relaxation of reflexes
• vitiligo • Paresthesia (nerve entrapment: carpal tunnel
syndrome)
• Cerebellar ataxia

Metabolic:
• Myxedema
• Serous effusions(pleural, pericardial, ascites) Circulatory:
• Hoarse voice (cry) • Sinus bradycardia/heart block
• Weight gain • Cold extremities
• Menstrual irregularity • Cold intolerance
• Arthralgia • Pallor
• Elevated CK • ECG changes: low voltage QRS complex
• Macrocytosis (anemia)
• Hypercholesterolemia
• Hyperprolactinemia
• Precocious puberty in severe cases
Skeletal:
• Delayed bone age
• Epiphyseal dysgenesis, increased upper to lower
segment ratio
Management:  Diagnosis:
- Antithyroid peroxidase and antithyroglobulin antibodies.
- Radioactive iodine uptake —> decreased intake ( VS Grave’s
disease —> increased intake )
- Urine iodine for iodine deficiency or excess
N.B : If positive antibodies but euthyroid—> follow up thyroid
function tests every 3 months.

 Treatment : L troxin replacement.

  Euthyroid state characterized by Increased TSH and normal
ft4.
 Treatment indications:
1- Subclinical hypothyroidism + goiter
Subclinical hypothyroidism 2- Subclinical hypothyroidism + positive anti thyroid peroxidase
antibody
3- Subclinical hypothyroidism + TSH > 10 mU/L on 2 occasions
separated by 1 month.
 Dosage: 25 mic/ day.
References:

 Nelson essentials
 Pediatrics up to date / hypothyroidism
 First Aid USMLE step 1 / Endocrine chapter
Hyperthyroidism
Congenital hyperthyroidism

By: Asmaa Abdelghany

Definition:

Excess synthesis and

secretion of thyroid
hormones from thyroid
gland.

Vs thyrotoxicosis…
Etiology:
Autoimmune Non-autoimmune
causes: causes:
• Graves disease • TSHR mutation
• Neonatal graves • Hyper functioning thyroid
nodule
• McCune Albright syndrome
• TSH secreting adenoma
• Toxic multinodular goiter
 Graves disease
Incidence:

M/C of hyperthyroidism in children(1:5000).

Peak incidence: 11-15 years

Male : Female 1:5

Seven folds in those carrying HLA-DR3

Associated with other HLA-D3 related disorders as DM type I,

celiac disease.
Wh
y?
Clinical picture:
Interval between onset and diagnosis 6-12 months -gradual development
Takes longer to remit than adult
Thyroid storm:

• >45 highly suggestive of

thyroid storm
• 25-44 impending
thyroid storm
• <25 unlikely
Clinical assessment for patients with graves
ophthalmopathy
Clinical assessment
for patient with
graves
ophthalmopathy
Laboratory findings:
Diagnosis made by prolonged thyrotoxicosis >8wks and diffuse goiter

Radioactive
iodine uptake
test
I 123
Treatment:

Radioactive iodine is not used in age less than 10

years
Anti thyroid drugs:
Methimazole
• Initial dose 0.5-1mg/kg/24hr(max 40mg/day)

• Follow up Thyroid function test after 2weeks

Aim is the least effective dose (TSH higher than normal =over treatment)
Clinical response appears after 3-4 weeks and good control after 3-4months
• Relapses can occur after 1 year of discontinuation therapy
• Radioiodine and surgery are recommended in relapses
B adrenergic blockers:
Inderal
• dose 0.5-1mg/kg/24hr.
• Stop on control of HR.
Treatment of thyroid storm:

Inhibit thyroid
secretion

Sympathetic
blockade

Glucocorticoid

Supportive
therapy
Neonatal hyperthyroidism

Causes

Neonatal TSHR McCune

Graves mutation Albright S
Neonatal Graves:
Is caused by transplacental passage of TRSAbs from
mothers with
• Active Graves disease
• Graves disease in remission
• Prior history of Graves disease
Incidence:
In 2% of infants born to mother with Prior history of Graves
disease

Predisposition :

Transfer of maternal TRSAbs exacerbates infantile onset

autonomous Graves disease

Course:
• Remission in 6-12 weeks (depending on titre and clearance of
TRSAbs)

• Rarely, it can persist for several years.

Clinical picture:
 Premature
 Intrauterine growth restriction
 Goiter +/- tracheal compression
 Staring look
 Retraction of eyelids
 Hyperthermia
 Poor weight gain
 Diarrhea
 Hepatomegaly
 Splenomegaly
 Tachycardia
 Heart failure
Laboratory findings:

 Thrombocytopenia
 Suppressed serum TSH
 Elevated serum level of T3, T4
 TRSAbs markedly elevated at birth
and resolve at age of 3 months-
(more than 3 times the upper limit of
normal)
Treatment :

Initiated with symptoms onset

• Inform of methimazole(0.5-1mg/kg/24hr) + propranolol

• If refractory: lugol solution or k iodide can be added

• Once thyroid hormone started to decrease, ATD are

tapered to keep a state of euthyroidism.

• Block and replace method

Thyroid nodule

By/Ahmed Elaraby
Introduction

Thyroid nodules are solid or fluid-filled lumps that form

within your thyroid, a small gland located at the base of your
neck, just above your breastbone. Most thyroid nodules
aren't serious and don't cause symptoms. Only a small
.percentage of thyroid nodules are cancerous
 Exposure of the thyroid to radiation,
including radiation used to treat other
cancers, increases the risk of developing
thyroid nodules and thyroid cancer.

:Causes Thyroid nodules and cancer can occur as

part of certain genetic conditions. Some of
these conditions may be inherited (familial),
and some can occur just in the child
without being present in the parents. Some
genetic syndromes that increase the risk of
thyroid nodules and cancer .
 PTEN hamartoma tumour syndrome (PHTS) is
a genetic disorder caused by a defect in a
gene called PTEN. It is an umbrella term for
a number of related syndromes, including
Cowden syndrome, PTEN-related Proteus
syndrome, and Proteus-like syndrome.

g e n e t ic Children with PHTS can have a wide range

c o n d it io n of problems, including benign tumor-like
growths (hamartomas), increased cancer
.s risk, and neurodevelopmental disorders.
 Familial adenomatous polyposis (FAP) causes
the growth of numerous polyps (abnormal
growths or tumors) in the gastrointestinal tract.
It also causes an increased risk of other
tumors, including thyroid cancer.

Genetic
Multiple endocrine neoplasia type 2 (MEN2) is
condition a familial condition that causes medullary
thyroid cancer, sometimes in childhood or
even infancy, as well as tumors of the adrenal
glands (pheochromocytomas) and
sometimes the parathyroid glands.
 Familial medullary thyroid carcinoma (FMTC) i s a
fa m ilia l fo r m o f m e d u lla r y t h y r o id c a n c e r t h a t is
Genetic s im ila r t o M E N 2 e x c e p t t h a t it d o e s n o t c a u s e
.a n y o t h e r t y p e s o f t u m o u r s
conditions
Symptoms

a visible lump in the neck.

a sensation of a lump in the

While symptoms may vary
throat when swallowing (or
from child to child, the most
more rarely, difficulty with
common include :
swallowing).

unexplained hoarseness.
 Symptoms

A r a r e t y p e o f t h y r o id n o d u le c a lle d a n a u t o n o m o u s n o d u le (a ls o k n o w n a s
a “t o x ic n o d u le ” o r “h o t n o d u le ”) c a n p r o d u c e t o o m u c h t h y r o id h o r m o n e .
:T h is c a n c a u s e s y m p t o m s lik e

. w e ig h t lo s s -1
.fe e lin g t o o h o t o r s w e a t y -2
.h e a r t p a lp it a t io n s (h e a r t r a c in g , p o u n d in g , o r “s k ip p in g b e a t s ”)-3
. t r e m o r o f t h e h a n d s -4
.fr e q u e n t b o w e l m o v e m e n t s -5
.d iffic u lt y c o n c e n t r a t in g -6
 Blood tests .

Ultrasound is the best imaging technique to visualize a known or suspected

thyroid nodule.

Fine-needle aspiration (sometimes called a biopsy) uses a very thin needle to

take a sample of a thyroid nodule. A pathologist examines the cells in the
sample to determine whether the nodule may be a thyroid cancer.

Diagnosis
Nuclear medicine imaging.

Surgery is sometimes needed to determine whether a thyroid nodule is a

thyroid cancer, if the result of fine-needle aspiration (biopsy) is not definitive.

Genetic testing.
 Observation may be appropriate for thyroid
nodules that do not require biopsy, or for
nodules that are biopsied and found to be
benign. Periodic ultrasounds may be
recommended to monitor these nodules for
changes, and additional biopsies may be
needed in the future if changes are seen.

Tr e a t m e n
t Surgery may be recommended to remove
thyroid nodules that have abnormal biopsy
results that suggest a possible thyroid cancer, or
nodules that cause bothersome symptoms (like
difficulty swallowing).
 Lobectomy i s r e m o v a l o f o n e -h a lf o f t h e
.t h y r o id t h a t c o n t a in s a n o d u le
L o b e c t o m y m a y b e a p p r o p r ia t e t o r e m o v e
n o d u le s t h a t h a v e a lo w r is k o f b e in g c a n c e r ,
Surgical in c lu d in g b e n ig n n o d u le s t h a t a r e r e m o v e d
.ju s t b e c a u s e t h e y c a u s e s y m p t o m s
treatment L o b e c t o m y is a r e la t iv e ly q u ic k a n d s a fe
p r o c e d u r e , a n d m o s t p a t ie n t s d o n o t n e e d t o
.t a k e t h y r o id m e d ic a t io n a ft e r w a r d
 Total thyroidectomy is r e m o v a l o f t h e e n t ir e
.t h y r o id g la n d

Surgical To t a l t h y r o id e c t o m y is u s u a lly a p p r o p r ia t e fo r
.n o d u le s t h a t h a v e a h ig h r is k o f b e in g c a n c e r

treatment L ife lo n g t r e a t m e n t w it h t h y r o id m e d ic a t io n is
.n e e d e d a ft e r t o t a l t h y r o id e c t o m y
T h is p r o c e d u r e is g e n e r a lly s a fe b u t r a r e ly c a n
.h a v e s e r io u s c o m p lic a t io n s
Autonomous nodules a r e u s u a lly b e n ig n . T h e ir
t r e a t m e n t d e p e n d s o n h o w m u c h t h y r o id
h o r m o n e t h e y p r o d u c e , a n d o n w h e t h e r t h is is
.c a u s in g s y m p t o m s o f t h y r o id h o r m o n e e x c e s s
A u t o n o m o u s n o d u le s t h a t a r e s lig h t ly
o v e r a c t iv e a n d c a u s e n o s y m p t o m s c a n o ft e n
.b e o b s e r v e d w it h o u t t r e a t m e n t
N o d u le s t h a t a r e v e r y o v e r a c t iv e o r t h a t c a u s e
s y m p t o m s c a n b e t r e a t e d w it h m e d ic a t io n ,
s u r g e r y , o r (in p a t ie n t s o v e r 18 y e a r s )
r a d io a c t iv e io d in e a b la t io n