Congen~1

CONGENITAL HYPOTHYROIDISM

General Hospital of Tianjing Medicine University

Introduction

Congenital hypothyroidism results from deficient production of thyroid hormone or a defect of thyroid hormonal receptor activity. The disorder may be manifested from birth. The major clinical characteristics of congenital hypothyroidism are retardation in growth and mental development.

Introduction

Congenital hypothyroidism

sporadic endemic

Etiology

Thyroid dysgenesis

Development defects (thyroid dysgenesis) account for 90% of infants in whom hypothyroidism is detected.

Aplasia In about one third, even sensitive radionuclide scans can find no remnants of thyroid tissue .

Ectopia In the other two thirds of infants, rudiments of thyroid tissue are found in an ectopic location ,such as lingual thyroid .

Defective synthesis of thyroxin

• A variety of defects in the biosynthesis of thyroid hormone (for example, enzyme deficiency) may result in congenital hypothyroidism. A goiter is almost always present in these patients. These defects are transmitted in an autosomal recessive manner.

Thyrotropin deficiency

• multiple hormones deficiency of pituitary or hypothalamus

• Hypothyriodism is one of many symptoms

• There are accompanied by hypoglycemia, and other Clinical manifestations

Thyroid gland or peripheral target organ unresponsiveness (receptor disorder)

thyroid tissue does not response to TSH

peripheral tissue does not respond to T4

and T3

Biosynthesis of thyroid hormones

The major materials

for synthesis of

thyroid hormone

tyrosine

iodine


Trapping of iodide Thyroid follicular cells have an active iodide pump, which can

concentrate iodide against a steep concentration gradient,iodide is transported from the blood into the thyroid.

Iodide oxidized Iodide first be oxidized . This reaction is catalyzed by thyroid

peroxidase.

Tyrosine iodination Iodination of tyrosine forms monoiodotyrosine (MIT)

and diiodotyrosine (DIT) bound in the thyroglobulin.


Iodotyrosine condensation (coupling) 2 DIT →T4, 1 DIT+1 MIT→T3 (coupling enzyme ) T4 or T3 are stored as thyroglobulin in the lumen of the follicle until that time when the hormone is to be secreted into th

e bloodstream (proteolytic enzymes ) and then delivered to the body cells.

thyroxine-binding globulin (TBG) is the most important plasma proteins which transport thyroid hormone

Regulation of thyroid function

The thyroid is regulated by thyroid-stimulating hormone (TSH) which is secreted by the anterior pituitary. TSH synthesis and release are stimulated by TSH –releasing hormone (TRH), which is synthesized in the hypothalamus and secreted into the hypophyseal portal which enters the pituitary. In a state of decreased production of thyroid hormone, TSH and TRH are increased. Exogenous thyroid hormone or increased thyroid hormone synthesis causing elevated blood levels inhibits TSH and TRH production. This is called negative feedback. (see Fig)

Action of thyroid hormones

Growth and development Nervous system

development increase DNA concentration in the nervous

system and the number of neurons . promote maturation of the nervous system .

Metabolism

promotes heat production

increases glucose absorption

Increases blood cholesterol

accelerates both synthesis and

degradation of protein.

Incidence

Europe and American: 1 in 4,000

1 in 5000-7000 in China

Clinical manifestations

• Congenital hypothyroidism is twice as common in girls as in boys.

• The severity of the findings in cases of thyroid deficiency depends on the degree of deficiency of production of thyroid hormone.

• Most infants with congenital hypothyroidism are asymptomatic at birth even if there is complete agenesis of the thyroid gland.

• This situation is attributed to the transplacental passage of moderate amounts of maternal thyroxine, which provides fetal levels that are 25-50% of normal at birth.

• these low serum levels of T4 and concomitantly elevated levels of thyroid-stimulating hormone (TSH) make it possible to screen and detect most hypothyriod neonatales.


Neonatal The signs and symptoms are usually not sufficiently developed in the newborn.

Birth weight and length are normal,but head size may be slightly increased because of myxedema of the brain.

Prolongation of physiologic icterus may be theearliest sign Feeding difficulties , hoarse voice or cry .Skin may be dry, coarse and mottled; hypothermia Decreased stooling or constipation


Umbilical hernia

Characteristics of typical hypothyroidism

Physiological hypofunction.

Hypothermia; bradycardia ;diminished

sweating ;hoarse voice or cry ;poor

appetite

sometimes constipation


Retardation of growth and development


short stature Delays in formation and eruption of teeth may occur

short stature

Delay in central nervous system development


Thyroid hormone deficiency presented from birth leads to marked delay in central nervous system development.

Hypothyroid infants appear lethargic and are late in learning to sit, stand and talk

the mental retardation becomes irreversible if treatment is delayed

Characteristic facies.


The skin may be dry, thick, and scaly

eyes appear far apart; bridge of the nose is depressed palpebral fissures are narrow and eyelids swollen. The mouth is kept open, and the thick and broad tongue protrudes from it

Coarse facial features

Laboratory findings

Early diagnosis is very important

Therefore neonatal screening programs is of first importance.

assay serum T4 and TSH or TSH alone.

serum T4 values are very low and TSH concentrations high in a newborn with primary hypothyroidism.

Filter blood spots

(blood of heel )

Laboratory findings

Serum T3, T4, TSH.

T4 TSH

Skeletal X-ray (bone age). Epiphysis development (bone age) is delayed.

Scanning (radioisotope using 99mTC(technetium, a element)) of the thyroid gland.

determine morphological development and function of thyroid.

radionuclide scans

Normal thyroid

Thyriod under tongue and displasia

Diagnosis

A.Growth Retardation, diminished physical activity, impaired tissue perfusion, constipation, thick tongue, poor muscle tone, hoarseness, anemia; intellectual retardation if the hypothyroid infant is untreated.

B. Delayed dental and skeletal maturation

C. Thyroid functions studies to show low T4; TSH levels elevated

Note: The importance of the newborn screening procedure must be underscored.

Differential diagnosis

• Rickets

• Down `s syndrome

• Pituitary dwarfism (Growth hormone deficiency)

• Congenital giant colon

mental is normal.

Bone age is normal.

Skeletal X –ray

No characteristic facies

Serum levels of T4 and TSH are normal.

Rickets

Down `s syndrome

Chromosome abnormalityMental retardation No myxedema Characteristic facies.

Pituitary dwarfism (Growth hormone deficiency)

Short stature

Bone age is delayed

Intelligence is usually normal

No characteristic facies or physiological hypofunction.

Congenital giant colon

Distention and constipationno other manifestation of congenital hypothyroidism

Treatment

• Principle : 1 Treatment of hypothyroidism requires exogenous thyroid

hormone 2 Treatment of entire life 3 In order to maintain normal physiological functions. Serum T4, TSH and the condition of growth and development should be periodically measured

during treatment. 4 Dosage should be adjusted according to the concentration of serum T4, TSH and the states of growth and development.

Treatment

Dry thyroid

Preparation (drug):

Sodium-L thyroxine

a dried and powdered preparation of porcine or bovine thyroid gland.

Synthetic levothyroxine L-T4

treatment:

• Method of treatment: start dose(L-T4):infant is 8-14 ug/kg; child is 4ug/kg. Every one to two weeks a dosage are added ,until clin

ical symptoms improve , T4 and TSH return to normal ,then a constant dosage are given

• Follow up: One to two weeks are needed initially; every 3 mont

hs after dosage stability; every a half of year follow up after 1-2 years.

Prognosis

Early diagnosis and adequate treatment from the first weeks of life may result in normal linear growth and intelligence.

Delay in diagnosis, inadequate treatment, result in variable degrees of brain damage.

Without treatment, affected infants may become mentally deficient dwarfs.

An infant of 6 mo. A before treatment B four mo after treatment

Key point

1 Main types of Congenital hypothyroidism 2 Etiology :thyroid dysgenesis (aplasia,ectopia );defective synthesis ;thyrotropin deficiency;thyroid gland or peripheral target organ unresponsiveness3 Neonatal earliest sign may be prolongation of physiologic icterus4 Characteristic of typical hypothyroidism(main)5 Early diagnosis is very important and neonatal screening programs is of first im

portance6 Essentials of diagnosis 7 Principle of treatment 8 Definition of congenital hypothyroidism