Reviewed by Daniel Mercer on 18th October 2019
Where is TSH produced in the body?
Anterior pituitary gland (APG), specifically the thyrotropic cells. The APG is also known as the adenohypophysis.
If the child had primary hypothyroidism, how would their TSH and T4 levels differ from normal?
High TSH and low T4
‘Primary hypothyroidism’ means that there is a problem with the thyroid itself, and it’s not producing enough thyroid hormone (hence ‘hypo-‘). As T4 is low, there is less negative feedback to the anterior piruitary gland so it continues pumping out TSH (thyroid stimulating hormone).
Describe and explain three other physiological reasons a patient may appear to have an underactive thyroid
Dietary deficiency in iodine/iodide
Genetic disorder inhibiting uptake of iodine from the GI tract
Genetic disorder involving iodine transport in the thyroid e.g. Na/I cotransporter or pendrin
Problems with thyroglobulin synthesis
Problems with thyroid peroxidase
Genetic disorder involving problems with TSH receptor
Autoimmune response e.g. Hashimoto’s disease which targets the thyroid gland for destruction
Deficiency in thyroxin binding globulin (that’s the next question – hope you didn’t cheat!)
A lack of iodine in the diet/body would mean that the body can’t produce enough thyroid hormones so there would be less T4 in the blood and consequently more TSH (due to the lack of negative feedback).
Equally, other deficits that prevent the production of thyroid hormones would also have the same effect.
If you said tyrosine deficiency: good effort, but it’s probably a stretch. Tyrosine is a non-essential amino acid, meaning it can be synthesised by the body; however, if there was a significant lack of protein in the diet (e.g. Kwashiokor syndrome), that could account for reduced T4 production (see https://www.ncbi.nlm.nih.gov/pubmed/6406110) – but in that case an underactive thyroid is the least of your problems!
The six-year old is referred to a paediatric endocrinologist. After more tests, the endocrinologist discovers the child has a rare genetic disorder and cannot make thyroxin binding globulin (TBG).
What is the role of TBG?
Binds T4 (thyroxine) to allow it to be transported in the blood.
How could deficiency in TBG cause signs and symptoms similar to hypothyroidism?
The lack of TBG means the blood has less carrying capacity for T4 and therefore there is more T4 free in the blood. As there is more free T4 it can more-readily bind to receptors in the hypothalamus and anterior pituitary gland to downregulate TSH release/T3 and T4 production. Therefore, there is less T3 and T4 available to stimulate metabolic activity.
Symptoms of hypothyroidism include constipation, lower body temperature, depression and weight gain although, in growing children, it can also cause stunted-growth/short stature. Interestingly, girls with TBG deficiency often present with signs of Turner syndrome (a genetic condition where females only have a single X chromosome) including a webbed neck.