Thyroid disorder and osteoporosis

thyroid disorder

Second only to diabetes, thyroid disease are the most common group of endocrine disorders seen in clinical practice

• clinical thyroid disease may be either disorder of 🇦

  • thyroid function

  • thyroid structure

• patient present with symptoms or signs that may be vague or undifferentiated

• blood analysis required

thyroid gland and hormones

• 2 lobes either side trachea plus isthmus

• increase basal metabolic rate

• control metabolism of carbs, protein and fats

• maintenance of water and electrolyte balance

• regulation of plasma

• in children thyroid hormones act synergistically with growth hormone to stimulate bone growth

• the impact of thyroid hormone on CNS is important.

• in adults can affect the mood

• hyperthyroidism can lead to hyperexcitabilty and irritability hypothyroids can cause impaired memory slowed speech and sleepiness

• thyroid hormone affects fertility, ovulation and menstruation

hypothalamic- pituitary thyroid axis

• thyrotropin releasing hormone (TRH) from the hypothalamus

• thyroid stimulating hormone from the anterior pituitary gland and T4 work in synchronous harmony to maintain proper feedback mechanism and homeostasis

• the HPT axis is regulated via negative feedback, at the level of the hypothalamus and the pituitary

• excess concentration of thyroid hormones feedback to both the hypothalamus and the pituitary to cause a reduction in both TRH and TSH production

• this decreases the rate of thyroid hormone production

physiology of thyroid hormone production and synthesis

• the functional unit of the thyroid gland is the follicle

• follicles are composed of the single layer of epithelial cells

• the follicular cells synthesis thyroglobulin a large tyrosine rich glycoproteins and secrete it

• colloid is essentially a pool of thyroglobulin

• key thyroid hormones include thyrotropin releasing hormone and thyroid stimulating hormone

thyroid hormone synthesis and secretion

• thyroglobulin synthesis

• iodine uptake and hormone synthesis

• hormone secretion

thyroglobulin synthesis

thyroxytes in the thyroid follicles produce a protein called thyroglobulin. TG does not contain any iodine and it is a precursor protein stored in the lumen of follicles

it produced in the rough endoplasmic reticulum

glogi apparatus pack it into the vesicles and then it enters the follicular lumen through exocytosis

Iodine uptake and hormone synthesis

• to mantain homeostasis and hormone synthesis, the thyroid absorbed 50-60 ug/day of iodine when supply is sufficient

• iodine is one of the most commne deficiencies and is estimated to affect 35- 40% of the world population

• iodine deficiency is most common cause of gaiter and worldwide is estimated to affect 2.2 billion people, however not all goiters are the result of an iodine deficiency

hormone secretin

• thyrocytes uptake iodinated thyroglobulin via endocytosis

• lysosomes fuse with the endosome containing iodinated thyroglobulin

• proteolytic enzymes in the enodolysomes cloves thyroglobulin into MIT, DIT T3 and T4

• T3 and T4 are released into the menstruated capillaries via MCT8 transporter

• deiodinase enzyme removes iodine molecules from DIT and MIT. Iodine can be salvaged and redistributed to an intracellular iodine pool

T4 is a prohomrone, T3 drives most receptor effects

• transport

• conversion

• nuclear action

transport

• most circulating hormone is protein bound

• only free hormone is available for tissue uptake and feedback

conversion

• deiodinase activate T4 and T3 or inactivate hormone

• illness and medicines can alter conversion

nuclear action

• T3 binds nuclear thyroid hormone receptors and changes gene transcription, metabolism and growth

action of thyroid hormone

• T4 is synthesised more than T3

• highly bound to thyroid binding globin- only free ligand can exert effects

• T4 is converted to T3 in target tissues by deionisnases 1 and 2

• deiodinase 3 converts t3 to the inactive rT3

• unliganded TR heterodimerizes with retinoid X

• receptors and binds to a thyroid hormones response elements and then to a corepressor this repressing gene expression

• T3 binding to the ligand binding domain results in movement of the carboxyterminal helix 12 disruption of corepressor binding and promoting of coactivator binding

thyroid function tests

• functional thyroid diseases are extremely common

• results often form the entire basis of any diagnosis

• even subtle abnormalities in thyroid function are mow considered as potential

hypothyroidism

• pathophysiology

• Insufficient secretion of thyroid hormones \common symptoms: lethargic, weight gain and cold intolerance

• common cause; Autoimmune thyroiditis

• congenital dysfunction

• iodine deficiency

• Tx for thyrotoxicosis

• medicines usch as aminodarone or lithium

thyrotoxicosis hyperthyroidism

• excess thyroid hormone action on target tissue

• typical feature caused by stimulation of metabolism and catecholamines

causes of thyrotoxicosis

graves disease

• organ specific autoimmune disease

• common in women

• antibodies to TSH receptor

toxic multi nodular disease

thyroiditis

thyroid hormone synthesis reveals drug targets

• iodine uptake

• oxidation, organification and coupling

• release and conversion

iodine uptake

• sodium- iodine symporter moves iodine into the follicular cells

oxidation, organification and coupling

thyroid peroxidase forms MIT/ DIT and couples residues on thyroglobulin

release and conversion

T4 predominates: tissue deiodinase generates active t3

thyroid storm

• thyroid suddenly produces and release large amounts of thyroid hormone

• sudden event`; surgery/ infection

• Tx potassium iodine and carbimazole, rehydration B blocker and steroids

• high mortality

link between thyroid disease and osteoporosis

• Thyroid hormones regulates proliferation and differentiated action of multiple cells types in bone including

  • osteoblasts- mineralisation of osteoid

  • Osteoclasts- release Ca2+ and PO4 3-

  • in healthy adults- bone resorption= bone formation

  • TH effects medicated via ligand inducible nuclear receptor/ transcription factors, thyroid hormones receptor

osteoporosis

prolonged untreated hyperthyroidism with other risk factors= bone mineral density scan will help asses your risk of osteoporosis and bone fracture

reducing the risk

• well balanced diet rich in calcium and vitamin D

• limit alcohol intake to within recommended limits

• avoidance of smoking

• regular high impact exercise, such as power walking

• hormone replacement therapy