Endocrinology: Thyroid gland anatomy and physiology

location

anterior region of the neck, wraps around the trachea from vertebrae C5 - T1

two lobes connected by isthmus

thyroid gland blood supply

superior thyroid artery and inferior thyroid artery

related structure to thyroid gland

parathyroid glands

thyroid gland hormones

thyroid hormone: production and release stimulated by TSH (from the anterior pituitary which in turn is stimulated by TRH from the hypothalamus)

calcitonin: secreted by C cells in response to high blood calcium

calcitonin

secreted by thyroid gland in response to high blood calcium levels

inhibits osteoclast activity (cells that break down bone) and stimulates osteoblasts, reduces calcium release from bone, inhibits parathyroid hormone and vitamin D, inhibits calcium reabsorption by the kidneys and intestine, promotes calcium deposition into bones

regulation of thyroid hormones (HPT axis)

hypothalamus releases TRH which stimulates pituitary gland to release TSH which acts on the thyroid gland to release T3 and T4, which inhibit hypothalamus and pituitary

thyroid follicles

thyroid gland is made up of a large number of thyroid follicles, single layer of follicular cells surrounds a pool of colloid which contains stored thyroglobulin bound to thyroid hormones, mainly T4

thyroid hormone production

1. initiated by stimulation by TSH: pituitary TSH binds to receptors on follicular cells to start synthesis

2. follicular cells capture iodine from the blood and transport it into the lumen/colloid

3. thyroid peroxidase (TPO) converts iodide (I^-) to iodine (I₂)

4. iodine binds thyroglobulin and eventually T3 and T4 molecules are formed through the formation of intermediate molecules and under the influence of TPO

5. T3 and T4 remain attached to thyroglobulin within the colloid

6. when needed, follicular cells endocytose thyroglobulin from the colloid into the follicular cell

7. T3 and T4 are lipophilic and travel bound to proteins, TBG, TTR, Albumin. only the free hormones are biologically active

conversion of T4 to T3

T4 (thyroxine) is mostly inactive and works like a storage form of the hormone, most secreted hormone is T4

T4 needs to be converted into T3 (triiodothyronine) which is the active form

deiodinases convert T4 to T3 mainly in the kidneys, liver and peripheral tissues

breakdown of thyroid hormones

the liver modifies thyroid hormones and sends them to the bile which is eventually removed through the intestines

the kidneys filter out some of the free thyroid hormones which are excreted in urine

main role of thyroid hormones

increase BMR and enhance energy use

thyroid hormones on cardiovascular system

increase HR and CO

thyroid hormones on bone

increase of bone turnover and reabsorption

thyroid hormones on the respiratory system

maintains normal hypoxic and hypercapnic drive in respiratory center

thyroid hormone on gastrointestinal system

increases gut motility

thyroid hormone on blood

facilitates oxygen release to tissues

thyroid hormone on neuromuscular function

increases speed of muscle contraction or relaxation and muscle protein turnover

thyroid hormone on carbohydrate metabolism

increases hepatic gluconeogenesis/glycolysis and intestinal glucose absorption

thyroid hormone on lipid metabolism

increases lipolysis and cholesterol synthesis and degradation

thyroid hormone on symphatetic nervous system

increases catecholamine sensitivity and beta adrenergic receptor numbers in the heart, skeletal and adipose tissue, and lymphocytes, decreases cardiac alpha adrenergic receptors

thyroid function tests

TSH, free T3 and T4 levels

interpreting thyroid function tests

always interpret in context, levels affected by severe illness, pregnancy, oral contraceptives and certain drugs can interfere with protein binding or influence T4 to T3 conversion and therefore make interpretation difficult or less reliable

hypothyroidism

underactivity of thyroid is usually primary (caused by disease of the thyroid), but may be secondary (hypothalamic-pituitary disease)

major cause of hypothyroidism

1. iodine deficiency

2. in regions with iodine sufficiency autoimmune and iatrogenic causes are most frequent

   1. congenital (screened for in newborns)

adult symptoms of hypothyroidism

exhaustion, depressiveness, sensitivity to the cold, reduced sweating, low pulse rate, weight gain, constipation, memory disorders, slowed speech, brittle hair, skin swelling on the face, dull expression, scaly yellowish skin, enlarged thyroid gland

myxedema

thickened, nonpitting edematous changes to the soft tissues, deposition of myopolysaccharides in the dermis leading to swelling of the affected area

precise mechanisms unknown, studies suggest that elevated TSH leads to stimulation of fibroblasts

myxedema coma

acute hypothyroidism resulting in hypotension, hypoglycaemia, hypothermia and loss of consciousness, life-threatening complication more frequently occurring in undiagnosed or untreated elderly patients

iodine deficiency

iodine intake is insufficient for thyroid hormone synthesis so thyroid cannot make T3/T4, pituitary increases TSH production leading to thyroid hypertrophy and thus goitre

causes hypothyroid symptoms, infertility, growth delay and cognitive impairment in children due to severe brain damage in fetus (cretinism); in areas with dietary iodine deficiency known as endemic goitre

prevented by salt iodization programs

goitre

enlargement of the thyroid gland

type can sometimes be distinguished by physical exam, but use ultrasound and CT to see the structure (gold standard)

Pemberton’s sign

physical test used to assess whether an enlarged thyroid gland (goitre) is pressing on blood vessels or the windpipe in the neck, helps detect obstruction or compression especially in one that extends behind the sternum

positive: facial flushing, bulging veins in neck, shortness of breath and dizziness

suggests extension of the goitre

Hashimoto’s thyroiditis

more frequent in middle aged women

autoimmune destruction of thyroid tissue

anti TPO antibodies, anti-thyroglobulin antibodies can be measured

infiltration of the gland causing goitre, eventually develops into atrophy and fibrosis

symptoms develop gradually (fatigue, weight gain, hair loss, constipation)

thyroid hormone replacement therapy

postpartum thyroiditis

lymphocytic thyroiditis due to modifications of the immune system during pregnancy, often self-limiting (temporary and naturally resolving), may be misdiagnosed for postnatal depression