hypothyrodism Flashcards
thyroid development
The thyroid gland develops from the buccopharyngeal cavity between 4 and 10 weeks gestation.
The thyroid arises from the fourth branchial pouches.
Connected to tongue by thyroglossal duct, which normally disappears but may persist as pyramidal lobe of thyroid.
By 10-11 weeks gestation, the fetal thyroid is capable of producing thyroid hormone.
By 18-20 weeks gestation, blood levels of T4 have reached term levels.
Thyroid hormone functions
T3 is the primary mediator of the biologic effects of thyroid hormone and does so by interacting with a specific nuclear receptor. Bone growth (synergism with GH)
CNS maturation
Increase β1 receptors in heart = increase CO, HR, SV, contractility
Increase basal metabolic rate via increase Na+/K+-ATPase activity = increase O2 consumption, RR, body temperature
Increase glycogenolysis, gluconeogenesis, lipolysis.
Etiology of primary hypothyroidism
Primary Hypothyroidism: Defect of fetal thyroid development (dysgenesis). Defect in thyroid hormone synthesis (dyshormonogenesis). Thyrotropin Hormone Unresponsiveness. Defects in Thyroid Hormone Transport. Resistance to Thyroid Hormone. Maternal antibodies: thyrotropin receptor–blocking antibody Iodine deficiency Maternal medications Iodides, amiodarone Propylthiouracil, methimazole Radioiodine
Central (hypopituitary) hypothyroidism causes
Central (hypopituitary) hypothyroidism
Isolated TSH deficiency: mutation in TSH β-subunit gene
Isolated TRH deficiency: mutation in TRH gene
TRH unresponsiveness: mutation in TRH receptor gene
Multiple congenital pituitary hormone deficiencies (e.g., septooptic dysplasia)
PIT-1 mutations
- Deficiency of TSH
- Deficiency of growth hormone
- Deficiency of prolactin
PROP-1 mutations
Deficiency of TSH • Deficiency of growth hormone • Deficiency of prolactin • Deficiency of LH • Deficiency of FSH • ±Deficiency of ACTH
Defect of fetal thyroid development (dysgenesis)
Thyroid dysgenesis means: aplasia, hypoplasia, or an ectopic gland
Is the most common cause of permanent congenital hypothyroidism, accounting for 80-85% of cases.
In approximately 33% of cases of dysgenesis can find no remnants of thyroid tissue (aplasia).
In the other 66% of infants, rudiments of thyroid tissue are found in an ectopic location, anywhere from the base of the tongue (lingual thyroid) to the normal position in the neck (hypoplasia).
Thyroid dysgenesis has a 2 : 1 female : male ratio.
The cause of thyroid dysgenesis is unknown in most cases.
Thyroid dysgenesis occurs sporadically, but familial cases occasionally have been reported.
Defect in thyroid hormone synthesis (dyshormonogenesis)
These defects are transmitted in an autosomal recessive manner.
A goiter is almost always present
Defect of Iodide Transport:
Rare and involves mutations in the sodium–iodide symporter.
Thyroid Peroxidase Defects of Organification and Coupling:
The most common of the thyroxine (T4) synthetic defects.
Defects of Thyroglobulin Synthesis:
Heterogeneous group of disorders characterized by: goiter, elevated serum TSH, low T4 levels, and absent or low levels of thyroglobulin.
Defects in Deiodination:
Monoiodotyrosine and diiodotyrosine released from thyroglobulin are normally deiodinated within the thyroid or in peripheral tissues by a deiodinase.
Patients with deiodinase deficiency experience severe iodine loss from the constant urinary excretion of nondeiodinated tyrosines, leading to hormonal deficiency and goiter.
The deiodination defect may be limited to thyroid tissue only or to peripheral tissue only, or it may be universal.
Thyrotropin Hormone Unresponsiveness:
A mutation in the TSH receptor gene is a relatively uncommon autosomal recessive cause of congenital hypothyroidism.
Infants with a severe defect have elevated TSH levels and will be detected by newborn screening, whereas other patients with a mild defect remain euthyroid without treatment
Clinical Manifestations
Birthweight and length are normal, but head size may be slightly increased
The anterior and posterior fontanels are open widely
Prolongation of physiologic jaundice
Feeding difficulties
somnolence, and choking spells during nursing
Respiratory difficulties
constipation
abdomen is large, and an umbilical hernia
The temperature is subnormal
cold and mottled
Edema of the genitals and extremities
The pulse is slow, and heart murmurs, cardiomegaly, and asymptomatic pericardial effusion are common
Macrocytic anemia
congenital anomalies. Cardiac anomalies are most common
hearing loss
the extremities are short
eyes appear far apart, and the bridge of the broad nose is depressed.
palpebral fissures are narrow and the eyelids are swollen.
The neck is short and thick
hands are broad and the fingers are short
The skin is pale, dry and scaly
Carotenemia
scalp is thickened, and the hair is coarse, brittle, and scanty.
Development and sexual maturation is usually delayed
The muscles are usually hypotonic, but in rare instances generalized muscular pseudohypertrophy occurs (Kocher-Debré-Sémélaigne syndrome).
Retardation of osseous development
Retardation of osseous development
Retardation of osseous development
Can be shown radiographically at birth in approximately 60% of congenitally hypothyroid infants and indicates some deprivation of thyroid hormone during intrauterine life.
The distal femoral and proximal tibial epiphyses, normally present at birth, are often absent.
In undetected and untreated patients, the discrepancy between chronologic age and osseous development increases.
The epiphyses often have multiple foci of ossification deformity (“beaking”) of the 12th thoracic or 1st or 2nd lumbar vertebra is common.
X-rays of the skull show large fontanels and wide sutures; intersutural (wormian) bones are common.
Formation and eruption of teeth can be delayed.
Laboratory Findings
Serum levels of T4 or free T4 are low.
Serum levels of T3 may be normal and are not helpful in the diagnosis.
If the defect is primarily in the thyroid, levels of TSH are elevated, often to >100 mU/L.
Serum levels of thyroglobulin are usually low in infants with thyroid agenesis or defects of thyroglobulin synthesis or secretion, whereas they are elevated with ectopic glands and other inborn errors of T4 synthesis, but there is a wide overlap of ranges.
Scintigraphy can help to pinpoint the underlying cause in infants with congenital hypothyroidism, but treatment should not be unduly delayed for this study.
Ultrasonographic examination of the thyroid is helpful, but studies show it can miss some ectopic glands shown by scintigraphy.
Demonstration of ectopic thyroid tissue is diagnostic of thyroid dysgenesis and establishes the need for lifelong treatment with T4.
Failure to demonstrate any thyroid tissue suggests thyroid aplasia, but this also occurs in neonates with hypothyroidism caused by maternal TRBAb and in infants with the iodide-trapping defect.
A normally situated thyroid gland with a normal or avid uptake of radionuclide indicates a defect in thyroid hormone biosynthesis.
Treatment
Levothyroxine (l-T4) given orally is the treatment of choice.
Newborns with more severe hypothyroidism, as judged by a serum T4 <5 μg/dL and/or imaging studies confirming aplasia, should be started at the higher end of the dosage range.
The daily tablets should be crushed and mixed with a small volume of liquid. l-T4 tablets should not be mixed with soy protein formulas, concentrated iron, or calcium, because these can bind T4 and inhibit its absorption. Although it is recommended to administer l-T4 on an empty stomach and avoid food for 30-60 min.
Levels of serum T4 or free T4 and TSH should be monitored at recommended intervals (every 1-2 mo in the 1st 6 mo of life, and then every 2-4 mo between 6 mo and 3 yr of age).
The goals of treatment are to maintain the serum free T4 or total T4 in the upper half of the reference range for age.
