Cretinism

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congenital hypothyroidism cretinism

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Cretinism

Cretinism (now more precisely called congenital hypothyroidism in clinical settings) is a severe condition caused by deficiency of thyroid hormone during fetal and early neonatal life, resulting in permanent impairment of physical and mental development if not treated promptly.

Definition

Cretinism is the clinical syndrome that results from a severe deficiency of thyroid hormone in utero or in the neonatal period. It is characterized by:

Growth retardation
Intellectual disability (mental deficiency)
Skeletal abnormalities
Auditory and neurologic disorders

Bone age appears less than chronologic age because epiphyseal development is delayed.

The Developing Human: Clinically Oriented Embryology

Etiology

Sporadic Cretinism

Occurs occasionally in developed countries (less than 1 in 4,000 live births)
Due to congenital metabolic or anatomic disorders of the thyroid gland
At birth the gland is either absent (agenesis) or represented only by cysts - indicating failed development or a destructive lesion
Can also arise from genetic defects in thyroxine synthesis, including mutation of the NIS gene (sodium-iodide symporter), which mediates iodide transport into follicular cells
Adams and Victor's Principles of Neurology, 12th Ed.

Endemic Cretinism

Caused by severe iodine deficiency - the most frequent and most preventable cause worldwide
Estimated incidence of 5-15% in severely affected areas (parts of western China, central Africa, central South America, northern Asia)
Additional factors in some endemic areas: ingestion of cassava, which contains a toxic goitrogen that inhibits thyroid iodine uptake
Concomitant selenium deficiency may worsen neurologic manifestations
Maternal iodine deficiency is key - the fetus depends on maternal thyroid hormone, especially before its own thyroid is functional
Harrison's Principles of Internal Medicine 22E; Adams and Victor's Principles of Neurology

Types of Cretinism

Two distinct clinical forms are recognized in endemic areas (DeLong classification):

1. Neurological (Neurologic) Cretinism

Caused by iodine deficiency during the second and third trimesters of pregnancy, when the cochlea, cerebral cortex neurons, and basal ganglia are forming. At this stage neither mother nor fetus produces adequate thyroxine, causing irreparable damage.

Features:

Deaf-mutism or varying degrees of hearing loss
Dysarthria
Proximal limb and truncal rigid-spastic motor disorder (mainly lower extremities)
Cognitive impairment
In severe cases: strabismus, kyphoscoliosis, underdevelopment of leg muscles, frontal lobe release signs
Bone age, head size, and height are normal
No coarse facial features (distinguishes from myxedematous type)

2. Myxedematous Cretinism (Hypothyroid Cretinism)

Features of frank hypothyroidism:

Short stature, microcephaly
Coarse facial features - pale puffy face, broadened nose, thickened lips, enlarged tongue, thickened eyelids, low forehead
Dry, coarse, scanty hair; dry skin
Delayed psychomotor development
Fat pads above clavicles and in axillae
Protuberant abdomen, often with umbilical hernia
No deafness or spastic rigidity of limbs (distinguishes from neurologic type)
Adams and Victor's Principles of Neurology, 12th Ed.

Spectrum of Iodine Deficiency Disorders (IDD)

Cretinism sits at the severe end of a broader spectrum. In increasing order of severity:

Disorder	Features
Goitre	Grades I-III, multinodular
Hypothyroidism	Variable clinical signs by age and severity
Subnormal intelligence	Variable severity
Delayed motor milestones	-
Hearing/speech defects	Variable
Strabismus, nystagmus	Uni/bilateral
Spasticity, neuromuscular weakness	Diplegia, quadriplegia
Endemic cretinism	Hypothyroid or neurological type
Intrauterine death	Spontaneous abortion, miscarriage

Park's Textbook of Preventive and Social Medicine

Clinical Presentation (Sporadic Type)

Symptoms are not usually recognizable at birth
Diagnosis is often first made between the 6th and 12th month of life
Early clues: severe/prolonged physiologic jaundice (up to 3 months), widened posterior fontanelle, mottled skin
Later: stunted growth, delayed psychomotor development
Placid, good-natured, sleeps excessively
Delayed sitting, standing, and walking
Slow movements; delayed relaxation of tendon reflexes (hallmark)
Low body temperature; cold, cyanotic extremities
Small head, but fontanelles may not close until the 6th-7th year
Delayed ossification

Associated findings may include macroglossia, broadened nose, thickened lips, puffy eyelids, and impaired wound healing.

Adams and Victor's Principles of Neurology; Fitzpatrick's Dermatology

Pathophysiology

The fetal brain is critically dependent on thyroid hormone for neuronal proliferation, migration, myelination, and synaptogenesis. The cochlea and cortical/basal ganglia neuronal populations are especially vulnerable during the latter part of the second trimester. Thyroid hormone deficiency at this window causes irreversible structural damage, which is why neurologic cretinism cannot be fully corrected with postnatal hormone replacement.

Thyroid hormone synthesis itself depends on adequate dietary iodine. When iodine is deficient:

NIS (sodium-iodide symporter) expression is upregulated to try to compensate
But if deficiency is severe, insufficient T4 and T3 are produced
The hypothalamic-pituitary axis responds with elevated TSH, leading to thyroid hyperplasia (goitre)
Harrison's Principles of Internal Medicine 22E

Diagnosis

Neonatal screening (TSH + T4) is the standard in developed countries - enables early diagnosis before symptoms appear
Clinical features as described above if screening is unavailable
Thyroid function tests: elevated TSH, low free T4
Bone X-ray: delayed bone age, epiphyseal dysgenesis
Thyroid ultrasound/scintigraphy to identify gland agenesis or ectopia

Treatment

Levothyroxine (T4) replacement started as early as possible (ideally within the first 2 weeks of life for sporadic cretinism)
Early treatment prevents or minimizes intellectual disability and growth failure
In endemic areas: iodine supplementation of salt, bread, or water is the primary public health intervention
Iodised oil injections for populations without access to iodised salt
Iodine supplementation during pregnancy protects both mother and fetus
Sporadic cretinism is preventable by treatment with thyroid hormone; the intellectual disability of neurologic endemic cretinism, once established, is not fully reversible
Adams and Victor's Principles of Neurology; Harrison's 22E

Key Points Summary

Feature	Neurological Cretinism	Myxedematous Cretinism
Cause	Iodine deficiency (2nd-3rd trimester)	Severe neonatal hypothyroidism
Deafness/deaf-mutism	Yes	No
Spastic rigidity	Yes (lower limbs)	No
Short stature/microcephaly	Normal	Yes
Coarse facies	No	Yes
Goitre	Sometimes	Rarely
Response to T4 therapy	Partial (neurologic damage fixed)	Good (somatic features improve)

The WHO estimates about 2 billion people worldwide are iodine-deficient. Iodine supplementation of salt and food has markedly reduced the prevalence of cretinism, but it remains a common cause of preventable intellectual disability, particularly where societal resistance to food additives or cost barriers exist.

Harrison's Principles of Internal Medicine 22E

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