HYPOTHYROIDISM/THYROIDIT IS Flashcards
Hypothyroidism is one of the most common endocrine disorders of childhood.
Hypothyroidism may be congenital or can be acquired.
Failure to institute early treatment in congenital cases causes _________ .
Untreated hypothyroidism in older children leads to __________ as well as ____________ and ______________.
mental retardation
growth failure
slowed metabolism and impaired memory
EMBRYOLOGY
The thyroid gland is the first of the body’s endocrine glands to develop.
Develops from
a __________ derived from the primitive ___________[ and
_______________ from the ___________________________.
median anlage; pharyngeal floor
paired lateral anlagen
4th pharyngobronchial pouch
MOLECULAR BASIS
Growth and differentiation of thyroid gland is linked to
2 transcription factors:
_______ and
_______
Paired box family of DNA binding protein, _______
TTF-1
TTF-2
PAX-8
Organogenesis
The developing thyroid is first visible in the floor of the primitive _________ by embryonic day E20-22.
_________ _________ cells form the thyroid anlage, distinguishing themselves from their neighbors in a process defined as _________. A defect in this process should result in _________.
During the second stage of early thyroid morphogenesis the thyroid anlage invades the surrounding mesenchyme, forming a bud which proliferates and migrates from the pharyngeal floor through the anterior midline of the neck.
The thyroid primordium becomes a bilobed structure by day _________ and reaches its final position around day _________. An error during lobulation results in _________, and an impaired descent results in _________
pharynx ; Endodermal epithelium
specification.; thyroid agenesis.
E24-32 ; E48-50.
hemiagenesis ; ectopic thyroid tissue.
Thyroid hormone synthesis.
_________________________ stimulates iodi(ne or de?) transport into the thyroid
gland by the __________________.
_________ , a __________________ is thought to transport iodide into the colloid from the thyrocyte.
Iodide is ________ by hydrogen peroxide, generated by NADPH oxidase system (ThOX)
TSH receptor (TSHR) bound to TSH
Iodide; sodium iodide symporter (NIS)
Pendrin; chloride-iodide transporter
oxidised
Thyroid hormone synthesis (2)
Iodine is Bound to _______ residues in ____________ to form ____________ (iodide organification).
Some of these hormonally inactive iodotyrosine residues [ __________ and ____________ ] couple to form the hormonally active iodothyronines, ______ and _______
tyrosine; thyroglobulin (TG); iodotyrosine
monoiodotyrosine (MIT) and diiodotyrosine DIT
T4 and T3.
___________________ catalyses the oxidation, organification, and coupling reactions.
Thyroid peroxidase (TPO)
Functions of Thyroid Hormones
CNS – Brain __________
Growth and development
__________ hormone metabolism
Increases __________ and __________ production
__________ closure
Brain maturation
Growth hormone ; basal metabolic rate
heat production ; Cerebral fontanelle
Functions of Thyroid hormone
GIT - _____________ activities
Regulates _________ of carbohydrates, proteins and fats
INTEGUMENTARY – ______ maturation SKELETAL – _________ maturation
Hepatic enzymes
metabolism
Skin ; Epiphyseal
Aetiology of CH
Primary
- Thyroid dysgenesis (_____,_______,_______) a) __________
b) __________ and
c) ectopic usually __________ - Synthetic defects
a) genetic defect of thyroid hormone biosynthesis (TPO, NIS, pendrin, TG, oxidase, G protein, diiodinase, other enzymes)
b) thyroid hypoplasia as a result of ________ loss of function mutation (~5%) - __________ ____________ disease and/or treatment
- Maternal use of ___________
TTF-1, TTF-2, PAX-8
agenesis; dysplasia ; sublingual gland
TSHR ; Maternal Autoimmune thyroid
amiodarone
Aetiology of CH (2)
B. Secondary (________) hypothyroidism
C. Tertiary (_____________) hypothyroidism
•___________ to thyroid hormones (peripheral and pituitary receptors)
pituitary
hypothalamic
Resistance
Newborn Screening
Now routine in most developed countries
Treatment initiated within _______ with ______________ and normal mental outcome.
_________________ samples via skin puncture:3 most common methods-
primary _____ screen
primary _____ screen with _________
Primary ______ and ______ screen
45days
Thyroxine replacement
Dried blood spot; TSH
T4; confirmatory TSH
TSH ; T4
Evaluation and Management
High index of suspicion
Maternal history of ___________ disease
Maternal treatment with ________ drugs or _________
Maternal ____________
Exposure of mother and/neonate to ___________ amounts of iodide may cause transient neonatal goitre & hypothyroidism.
autoimmune thyroid
antithyroid; amiodarone
iodine deficiency
supraphysiologic
Congenital Hypothyroidism Score
Score >__= hypothyroidism but requires more evaluation
5
Other Investigations in hypothyroidism
Thyroid imaging- _____ or __________ scan
Serum Thyroglobulin (Tg)- __________ confirms absence of thyroid tissue or Tg synthetic defects.
Neonates with _____ total & free T4 and ________ or ___________ TSH must be evaluated for hypothalamo-pituitary hypothyroidism. (combined or isolated defects).
USS or Technetium
undetectable
low; normal or mildly elevated
Treatment of hypothyroidism
L-T4: —— μg/kg by _____ _______ daily.
_____________ tablets are easily crushed and can be given in a spoon with a small amount of water, formula, or cereal.
Suspensions are not commercially available and are not recommended because maintaining a consistent concentration of levothyroxine in solution is difficult.
10; mouth; once
Levothyroxine
Goal of therapy in hypothyroidism
__________ TSH and maintain T4 and FT4 in ________ half of reference range.
Assess permanence of CH:
Thyroid scan shows ectopic/absent gland - CH is permanent
TSH is <50 mU/L and there is no increase in TSH after newborn period, then _______________________
If TSH increases off therapy, consider _______________
Normalize; upper
tail off therapy at 3 yr of age
permanent CH
Treatment of hypothyroidism
Caution: therapy in cases of combined pituitary hormone deficiency: ___________ is required before L-thyroxine therapy.
Neonates with low cortisol must be treated with ____________ before T4 therapy.
This reduces the risk of ___________ resulting from _________________________________ from thyroid hormone replacement.
Serum cortisol
hydrocortisone
adrenal crisis
increased demands from enhanced metabolism
Monitoring of Therapy
Recheck T4, TSH
2–4 wk after initial treatment is begun Every 1–2 months in the first 6 months Every 3–4 months between 6 months
and 3 yrs of age
Every 6–12 months from 3 yrs of age to
end of growth
___________ monitoring is essential!
Growth
TRANSIENT CONGENITAL HYPOTHYROIDISM
Caused by:
•_________ deficiency
•__________________ (to 3 month of life)
•Foetal or neonatal ___________________
•Maternal __________ therapy
•_________ infants
Iodine
TSHR-blocking antibodies
exposure to high amounts of iodine
amiodarone; premature
ACQUIRED HYPOTHYROIDISM (AH)
Aetiology
Primary hypothyroidism
• _______________________ thyroiditis:
__________ (_________)
__________ (primary _________)
•__________ thyroiditis
Iodine deficiency (endemic goiter)
Chronic lymphocytic
Goitrous ; Hashimoto’s
Atrophic; myxedema
Subacute
ACQUIRED HYPOTHYROIDISM (AH)
Aetiology
Primary hypothyroidism
Drugs or goitrogens
Antithyroid drugs (PTU, MMI, carbimazole) Anticonvulsants
Other (lithium, thionamides, aminosalicylic acid, aminoglutethimide)
Goitrogens (cassava, water pollutants, cabbage, sweet potatoes, cauliflower, broccoli, soybeans)
Iodine deficiency goitre
Okay🌚
Acquired hypothyroidism- Aetiology
Secondary or tertiary hypothyroidism
Hypothalamic or pituitary ________ (especially ______________ )
Treatment of brain and other tumors
_________
__________
tumor
craniopharyngioma
Surgery
Radiation
Acquired hypothyroidism-Clinical Features
Typically ___________ in onset.
•___________
•Local symptoms : ___________, ___________, or of a ___________ sensation in their neck and/or throat.
•________ growth
•___________ maturation
insidious ; Goiter
dysphagia ; hoarseness, ;?pressure
Slow; Delayed osseous
Acquired hypothyroidism-Clinical Features
•Mild weight _______ despite _______eased appetite is characteristic of the child who has a hypothyroid condition.
•Moderate-to-severe _______ in children is not typical for hypothyroidism.
•A decreased _______ is a more constant finding than weight _______.
gain ; decreased
obesity
growth rate ; weight gain.
Acquired hypothyroidism-Clinical Features
Lethargy
_________________ body proportions
___________ hair
_______ dentition
Cool, dry, skin
_______ nails
Delayed relaxation phase of deep tendon reflexes
Decreased energy
________
Sleep disturbance, typically _______________
_______ intolerance
Constipation
Immature upper-to-lower
Dey Coarse
Delayed; Brittle; Puffiness
obstructive sleep apnea
Cold
Acquired hypothyroidism-Clinical Features
Galactorrhea:
develops in primary hypothyroidism secondary to TRH secretion from the hypothalamus.
TRH stimulates the _____________ to release ________ and ————- .
Resolves as prolactin concentrations fall with thyroid replacement.
anterior pituitary
TSH and prolactin
THYROIDITIS
Inflammation of the thyroid gland.
Major classes:
(1) ______________ thyroiditis
(2) ____________ thyroiditis (___________ Syndrome)
(3) _______________ thyroiditis (___________).
(1) Acute suppurative thyroiditis
(2) Subacute thyroiditis (De Quervain Syndrome)
(3) Chronic lymphocytic thyroiditis (Hashimoto’s).
Acute Suppurative Thyroiditis
Is due to _____________ .
(Common or Rare?) in childhood because the thyroid is remarkably ________________.
May be associated with other head and neck infections.
bacterial infection.
rare ; resistant to haematogenously spread infection.
Acute Suppurative Thyroiditis
Most cases involve the _______ lobe of the thyroid and are associated with a developmental abnormality of thyroid __________ and the persistence of a pyriform sinus from the pharynx to the thyroid capsule.
Usual organisms responsible include __________,____________, and ___________. Other aerobic or anaerobic bacteria may also be involved.
left; migration
Staph aureus, Strep hemolyticus, and Pneumococcus
Acute Suppurative Thyroiditis
Present with:
______ onset of pain
_______
_________
Unilateral or bilateral thyroid _________
Local _________
Regional __________
_________ may develop
Signs of hyperthyroidism are rare
Acute Suppurative Thyroiditis
Present with:
Acute onset of pain
Dysphagia
Fever
Unilateral or bilateral thyroid enlargement Local tenderness
Regional lymphadenopathy
Abscess may develop
Signs of hyperthyroidism are rare
Acute Suppurative Thyroiditis
Investigations
_________
TFTs usually _______
Thyroid Scan
Thin needle aspiration and culture may be helpful in antimicrobial selection.
Treatment with antibiotics and antipyretics.
Course usually limited to 2-4weeks.
Leucocytosis; normal
Subacute thyroiditis
Due to viral processes it usually follows a _________ _________.
Viral illnesses like _________ , _________, influenza, infectious mononucleosis, adenoviral or Coxsackie , myocarditis, or the common cold.
Other illnesses or situations associated with subacute thyroiditis include catscratch fever, sarcoidosis, Q fever, malaria.
The disease is more common in individuals with ______________________
prodromal viral illness
Measles, mumps
human leukocyte antigen (HLA)–Bw35.
Subacute Thyroiditis
Neck ____________ and ____________ may occur, and it may be mildly or severely tender.
Occasionally, the initial symptoms are those of ____________.
Fever is usually _________ grade.
Systemic symptoms such as weakness, fatigue, malaise may be present.
tenderness ; swelling
hyperthyroidism.
low
Subacute Thyroiditis
Serum T3 and T4 levels usually __________ .
Thyroidal Radioiodine Uptake is _______ or _______ [thyroidal cell damage].
S & S of hyperthyroidism persist for 1-4weeks
Subsequent period of transient hypothyroidism [as the thyroid gland recovers]
Total course runs 2 to 9 months.
increased.
low or absent
Subacute Thyroiditis
Self-limiting, therefore, the goals of treatment are to ____________ and to control the _______ thyroid function.
Treatment:
Large doses of _________________ agents
In severe cases, ____________ Rx may be helpful.
relieve discomfort
abnormal
anti-inflammatory ; corticosteroid
Subacute thyroiditis
___________ can be used to reduce signs and symptoms of hyperthyroidism.
Low-dose ___________ may be necessary in some patients who develop hypothyroidism.
Most patients recover without a residual defect in thyroid function.
Propranolol
levothyroxine
Chronic Lymphocytic Thyroiditis (CLT, Hashimoto’s)
Is the most common cause of acquired hypothyroidism and goiter in children living in iodine-sufficient areas.
CLT appears to require both _________________ trigger and a ____________ defect in immune surveillance.
HLA-DR3, 4 and 5 have been associated.
an environmental
genetically determined
Chronic Lymphocytic Thyroiditis (CLT)
Family history in 30-40% of patients.
2:1 _____________ preponderance
Typically presents during _____________ ; however, it may present any time in life.
female-to-male
adolescence
Chronic Lymphocytic Thyroiditis
Asymptomatic thyroiditis with or without thyroid function abnormalities may be discovered upon routine screening of children at high risk:
_________,
Kline-Felter’s
_________ syndrome
Other autoimmune endocrine disorders (eg, Type 1 diabetes, Addison disease, Vitiligo).
Down syndrome; Turner
Chronic Lymphocytic Thyroiditis (CLT)
Observed in the following 3 patterns:
(1) Goiter that is usually _________ and ____________ . The thyroid gland is frequently ______ times its normal size and may be larger.
Although it may not be enlarged symmetrically.
The gland may initially be ______ but then takes on a ______ feeling with _________ consistency and a seedlike surface secondary to hyperplasia of the normal lobular architecture.
diffuse and non-tender
2-3
soft; firm; rubbery
Chronic Lymphocytic Thyroiditis
Observed in the following 3 patterns:
(2) approximately 5-10% of children with CLT initially present with symptoms of ____________: poor attention span, hyperactivity, restlessness, heat intolerance, weight loss, and tremors or loose stools.
This _____-lived _________ phase may be secondary to autonomous release of stored T4 and T3 (with progressive inflammatory lymphocytic infiltration of the thyroid)
or secondary to an initial predominance of TSH-receptor stimulating immunoglobulins (termed “ ___________”).
hyperthyroidism; short
thyrotoxic; Hashitoxicosis
Hashitoxicosis-2/2
This clinical picture may suggest a diagnosis of ______________ .
Graves disease
The thyrotoxic phase of CLT can be differentiated from Graves disease in that, in CLT
it is ___________,
is not associated with __________,
and is usually associated with a decreased and nonuniform uptake of radioactive iodine.
This “Hashitoxicosis” phase is usually followed by the more characteristic ___________ phase.
transient; exophthalmos
hypothyroid
Chronic Lymphocytic Thyroiditis
Observed in the following 3 patterns:
(3) Symptoms of hypothyroidism:
In children, this frequently includes _____ growth or _______ stature.
Adolescent girls may have primary or secondary _________.
Boys may have _______ _______.
Because the disease develops slowly, the patient or parent may not notice other signs of hypothyroidism, including constipation, lethargy, and cold intolerance.
Child with diabetes may have _____easing insulin requirement
poor; short
amenorrhea ; Delayed puberty
Decreasing
Chronic Lymphocytic Thyroiditis
Initially, an enlarged, lumpy, bumpy, and (tender or nontender?) thyroid is often present.
The gland may not be enlarged, particularly in children who have _______________.
The histologic appearance of CLT includes lymphocytic infiltration, formation of lymphoid follicles, and follicular cell hyperplasia.
nontender
profound hypothyroidism
Acquired Hypothyroidism- Follow up
_________ is the optimal parameter to guide dosing of thyroid hormone replacement,
except in patients with secondary or tertiary hypothyroidism where measuring _________ is a more reliable indicator.
In the rare syndromes of thyroid hormone resistance, serum TSH levels are __________ in the presence of _____________ serum total T4 concentration.
Serum TSH
serum free T4
elevated
Children with AH who receive adequate treatment at least ______ before the onset of puberty typically achieve a final adult height consistent with their genetic potential.
Over-treating with thyroid hormone does not ______________________ and may compromise ____________ by advancing skeletal maturation.
5 years
enhance catch-up growth
final adult height
