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34 years of
journey
in
UMMC
Dr Noor Lita Adam
260609
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1975-1980:
6 year old boy was referred for goitre
Clinically euthyroid, no family history of thyroid disorder
Antenatal/developmental – normal
Height: below 10th centile, weight: at 10th centile
Diffuse, soft goitre- 3x2 cm
Ix:
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Protein: 6.6g/100ml
Albumin: 3.8g/100ml
Cholesterol: 17.5 mg/100 ml
PBI: 5.3 g/100 ml
ESR; 8 mm/hr
IMPRESSION: non-toxic goitre
Management:
– L-thyroxine 100 mcg od ? Early Hashimoto’s  goitre regressed
– Trial stopping thyroxine- goitre recurred  thyroxine restarted
– Dose increased to 150 mcg od- ht < 3rd centile, poor school performance
(26th place in class)
• 1980-1990
• Thyroxine continued
• TFT monitoring: T4: 5.4 (5-13 μg/100ml)
T3-uptake: 27.2 (22.1-33.7%)
T-7 (FTI): 1.47 (1.11-4.38)
• Referred to adult 1986, age 17
• Goitre increased in size after stopping thyroxine,
thyroid bruit+, tachycardia, hands tremor
• Thyroid antibodies: microsomal: < 100,
thyroglobulin: 20, TSH: 17.9 uIU/ml (0.41-7.0)
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RAI uptake and Perchlorate discharge test:
2H 131I thyroid uptake: 81%
1/2H 131I thyroid uptake post-perchlorate inj: 38%
1H 131I thyroid uptake post-perchlorate inj: 32%
11/2H 131I thyroid uptake post-perchlorate inj: 28%
2H 131I thyroid uptake post-perchlorate inj: 21%
A drop in excess of 50% of original value indicates
organification defect.
TFT:
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T4: 98
T3-uptake: 34
T7 (FTI): 33
• 1990- till now
• On stable dose of L-thyroxine
• TFT: FT4/TSH- euthyroid, TSH: 0.7-3
iIU/ml
 Congenital primary hypothyrodism
secondary organification defect
Fig. 2-2.: The iodide cycle. Ingested iodide is trapped in the thyroid, oxidized, and
bound to tyrosine to form iodotyrosines in thyroglobulin (TG); coupling of iodotyrosyl
residues forms T4 and T3. Hormone secreted by the gland is transported in serum.
Some T4 is deiodinated to T3. The hormone exerts its metabolic effect on the cell
and is ultimately deiodinated; the iodide is reused or excreted in the kidney. A
second cycle goes on inside the thyroid gland, with deiodination of iodotyrosines
generating iodide, some of which is reused without leaving the thyroid.
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Inborn errors of thyroid hormonogenesis are responsible
for 10-15% of neonatal hypothyroidism.
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A number of different defects have been characterized
and include:
1) decreased thyrotropin (TSH) responsiveness
2) failure to concentrate iodide
3) defective organification of iodide due to an
abnormality in the peroxidase enzyme or in the
H2O2 generating system
4) defective thyroglobulin synthesis or transport
5) abnormal iodotyrosine deiodinase activity.
 The association of an organification defect with sensorineural
deafness is known as Pendred's syndrome.
 Unlike thyroid dysgenesis, a sporadic condition, these inborn errors
of thyroid hormonogenesis tend to have an autosomal recessive
form of inheritance consistent with a single gene mutation. It is not
surprising, therefore, that a molecular basis for many of these
abnormalities has now been identified. These include mutations in
the genes for the TSH receptor, sodium-iodide symporter, thyroid
peroxidase enzyme, and thyroglobulin, respectively; the gene for the
iodotyrosine deiodinase enzyme has not been cloned to date.
 Pendred's syndrome has now been shown to be due to a defect in
the pendrin gene on chromosome 7q22-31, a newly identified porter
of iodide on the apical surface of the thyroid follicular cell with
sequence homology to several sulfate transporters.
 Mutations in THOX2, important in hydrogen peroxide generation,
have been shown recently to cause both transient and permanent
forms of congenital hypothyroidism associated with a defect in
organification.