cognitive function changes in congenital hypothyroidism eliminated through neonatal screening doina...
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COGNITIVE FUNCTION CHANGES IN COGNITIVE FUNCTION CHANGES IN CONGENITAL HYPOTHYROIDISM CONGENITAL HYPOTHYROIDISM
ELIMINATED THROUGH NEONATAL ELIMINATED THROUGH NEONATAL SCREENINGSCREENING
DOINA TEODORESCU , MD, Ph.D.Assistant Professor
Arad, Romania,,Vasile Goldis,, Western University of Arad
Szeged, 13 december, 2011
MOTTO:MOTTO:
• Every child has the right to an adequate iodine intake for a normal development.
• A particular importance in this context is the right of the unborn child.
• Each mother has the right to an adequate intake of iodine, which would ensure normal mental development of the unborn child.
Declaration on the Child’s Rights, New York, UN, 1989
Historic:Historic:In South America were
discovered sculptures dating from 400 BC representing dwarfs with goiter.
The clinical course of the intellect
in the primary hypothyroidism was described in 1888 by the Clinical Society of London.
The cerebral and socio-economic impact of CH The cerebral and socio-economic impact of CH is enormous.is enormous.
Evolution with thyroid dwarfism, oligophrenia III-rd degree
C.B., an old patient with permanent sporadic CH tardily diagnosed
Untreated patient with irreversible changes in CNS development. Similar clinical aspect to myxedemic cretinism.
Cognitive functionsCognitive functionsThey are defined as the most highly specialized brain functions with cognitive brain substrate
Areas of the brain affected by the HT Areas of the brain affected by the HT concentrations (1)concentrations (1)
Broca's area, "the headquarters of articulate language" of the dominant hemisphere of each individual.
Wernicke-area – short-term memory, understanding written or spoken language
Auditory cortex – role in recognizing and receiving sound waves
(2)(2)
Corpus callosum – connects the hemispheres
Frontal lobe – role in cognition, memory, concentration, attention, thought processes and inhibition, language
Parietal lobe – processing sensory information, recognition of the body scheme, space orientation
(3)(3)
Occipital lobe - primary area of visual perception and association.
Temporal lobe - the receptive area for hearing, associative area with a role in understanding spoken language and evoked memory.
(4)(4)
hippocampus - role in learning and spatial memory
hypothalamus - central relay in the collection and integration of signals from different brain sources with a role in hormonal integration.
The role of HT in brain The role of HT in brain neurogenesisneurogenesisTemporary coordinates brain
development eventsRegulates gene expression by
inducing transcription of specific mRNA through action on its nuclear receptors
Initiation and regulation of protein synthesis
Adjusting the biochemical maturation of the HT brain acts via growth factors (NGF, EGF, IGF1) and through coactivators (SRC1, TIF 2/GRIP 1) and RT corepresors (N-Cor, SMRT).
Chronology of brain neurogenesis and the Chronology of brain neurogenesis and the role of HTrole of HT
Ontogenia of thyroid function and regulation during fetal and early postnatal life in relation to brain growth speed
Delange si Fischer, 2001
Chronology of major CNS impairment in Chronology of major CNS impairment in congenital myxedem vs. endemic congenital myxedem vs. endemic cretinism cretinism
Schematic representation of the chronology of major development events in human brain overlapping changes in fetal availability and sources of T4. The table refers to the initial period of CNS development which is not known whether or not is HT dependent - after Dr. RG Long - 1997
The neuropathological basis of the clinical The neuropathological basis of the clinical changes of HC changes of HC
Bad development of neocortex > mental retardation
Defects of cerebellar maturation > cerebellar ataxia
Abnormalities in the development of pyramidal cells → GM crisis
Bad-development of auditory and visual cortex → deafness, decrease in visual processing and spatial orientation
Physiopathology of cognitive and Physiopathology of cognitive and behavioral functions in hypothyroidismbehavioral functions in hypothyroidism
Hypometabolic status with cognitive functions decline
Mitochondrial alteration with protein release and apoptosis during brain development
Reduced cerebral blood flow and O2 and glucose consumption
Raised cerebro-vascular resistance
Brain electrophysiology in CHBrain electrophysiology in CH
EEG - low voltage, predominance of theta and delta waves. Sleep stages 3 and 4 can be reduced.
The study of visual evoked potentials - short-term decrease of recognition of visual stimuli and spatial memory.
Brain imaging in CHBrain imaging in CH
Spectroscopic magnetic resonance spectroscopic: phosphate metabolism in the frontal lobe increases after treatment with T4
SPECT / SCAN: cerebral hypoperfusion and low metabolic activity
PET shows the relationship between thyroid status, cerebral blood flow and cerebral glucose metabolism
Etiology of congenital Etiology of congenital hypothyroidismhypothyroidism
Permanent HC Primary
Thyroid disgenesis
thyroid agenesis
thyroid ectopy
thyroid hypoplasia
Dishormono-genesis
Iatrogenic (radioiodine maternal therapy)
Secondary and tertiary (hypotalamo-pituitary)
Peripheral resistance to thyroid hormones
Transient HC
Iodine deficitIodine excessMaternal treatment with anti-thyroid drugsBlocked maternal antibodies of TSH receptorIdiopathicTrisomy 21
Psychomotor development in CHPsychomotor development in CH
Over 90% newborns with CH have a cvasinormal psychomotor and somatic development if treatment is initiated soon after birth.
Untreated, CH leads to severe brain damage similar to that of endemic myxedemic cretinism.
Comparative study of endemic cretinism Comparative study of endemic cretinism cognitive changes and congenital cognitive changes and congenital hypothyroidismhypothyroidism
Brain damage from EC due to iodine deficiency which occurs in the first trimester of pregnancy through maternal and subsequently fetal hypothyroxinemia is irreversible.
The main difference between the EC and CH is related to thyroid status of the mother which is normal in most cases of CH.
Transient congenital Transient congenital hypothyroidismhypothyroidism
Hypothyroidism detected through neonatal screening which subsequently disappeares spontaneously and completely
Minimum criteria for diagnosis is the initial screening TSH concentration> 40 mU/l with subsequent return to normal
Iodine deficiency, prematurity, male gender, low birth weight, TSH <100 are suggestive factors of TCH
Congenital hypothyroidism Congenital hypothyroidism screeningscreeningCH screening revolutionized the
prognosis of children with CH through early diagnosis and treatment of the disease
TSH screening does not identify newborns with secondary hypothyroidism (1 / 50 000), those with a delayed increase in TSH concentration (10% of NN with hypothyroidism), those with TBG deficiency
ConclusionsConclusionsThe degree of hypothyroidism in utero, the
etiology and severity of CH, the age at the onset of therapy, T4 levels at diagnosis are the major factors influencing the intellectual development of CH
Children with HC monthly lose 3-5 points from the IQ score if diagnosis and treatment with T4 is inadequate
HC screening demonstrates the importance of communication between the geneticist, pediatrician, endocrinologist, family doctor and patient’s parents