W5 Thyroid disorders and Osteoporosis (MAH) Flashcards
Thyroid Disorders:
Clinical thyroid diseases may be either disorders of? (2)
Symptomatic usually?
What test to determine?
- thyroid function (hyper- or hypo-function)»_space; pharmaceutical management
- thyroid structure (nodules, cancer, or goiter)»_space; managed through MDT collaboration
- Patients present with symptoms or signs that may be vague or undifferentiated
- Blood analysis required
Thyroid gland and hormones:
Where is it located?
What are the functions?
- 2 lobes either side trachea plus isthmus
- Increases the basal metabolic rate
- Control metabolism of carbs, proteins and fats
- Maintenance of water and electrolyte balance
- Regulation of plasma [ca]
- In children, thyroid hormones act synergistically with growth hormone to stimulate bone growth
- The impact of thyroid hormone on CNS is important. During the prenatal period, it is needed for the maturation of the brain
- In adults, it can affect mood. Hyperthyroidism can lead to hyperexcitability and irritability. Hypothyroidism can cause impaired memory, slowed speech, and sleepiness
- Thyroid hormone affects fertility, ovulation, and menstruation
What are the thyroid hormones? (2)
How are they regulated?
Thyroxine or tetraiodothyronine (T4)
Triiodothyronine (T3) - active form
By the hypothalmic-pituitary axis
Hypothalamic-pituitary-thyroid axis:
Which hormones are released and from where? (4)
What feedback mechanism is it regulated by?
- Thyrotropin-releasing hormone (TRH) from the hypothalamus
- Thyroid-stimulating hormone (TSH) from the anterior pituitary gland, and T4 work in synchronous harmony to maintain proper feedback mechanisms and homeostasis.
- Thyroid gland releases T3 and T4
- The HPT axis is regulated via negative feedback, at the level of the hypothalamus and the pituitary.
- Excess concentrations 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 via the HPT axis. This physiological regulation of the HPT axis is lost in thyrotoxicosis.
- Iodine involved e.g. iodine deficient regions = ↑prevalence of goiter
- Target tissue: Heart, Liver, Bone, CNS
Physiology of thyroid hormone production and synthesis
What is the functional unit of the thyroid gland called?
- The functional unit of the thyroid gland is the follicle
- Follicles are composed of a single layer of epithelial cells (thyroid follicular cells) surrounding a central space filled with colloid
- The follicular cells synthesize thyroglobulin, a large tyrosine-rich glycoprotein, and secrete it
- Colloid is essentially a pool of thyroglobulin
- Key thyroid hormones include thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), T4, and T3
- Only 1% of total thyroid hormone is in the unbound or free state and available for metabolic purposes. The rest is bound to globulin, prealbumin, and albumin
- Calcitonin is a peptide produced by the parafollicular cells of the thyroid gland. It reduces resorption of calcium in the bone and lowers the serum calcium
Thyroid hormone synthesis and secretion:
Step 1 Thyroglobulin synthesis
What is produced by Thyrocytes?
Step 2 iodine uptake and hormone synthesis:
Thyrocytes in the thyroid follicles produce a protein called
thyroglobulin (TG).
TG does not contain any iodine, and it is a precursor protein stored in the lumen of follicles. It is produced in the rough endoplasmic reticulum. Golgi apparatus pack it into the vesicles, and then it enters the follicular lumen through exocytosis.
Step 3:
Actions of thyroid hormone?
What are the classes of TRs?
TH is exerted through nuclear TH receptors (TRs), which are ligand-inducible transcription factors (see chemistry lectures)
Two classes of TRs, a and β
α1, α2, α3,
β1, β2, and β3,
3 truncated forms
Rα isoforms - brain, heart, skeletal muscle and adipose tissues
TRβ isoform - liver, heart and pituitary, and mediates the regulation of cholesterol metabolism,
TRβ isoform – regulates –ive feedback regulation of TSH in the pituitary
Actions of Thyroid Hormones
- 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 deiodinases 1 and 2 (D1 and D2)
- Deiodinase 3 (D3) converts T3 to the inactive rT3
- Unliganded TR heterodimerizes with retinoid X receptor (RXR) and binds to a thyroid hormone response elements (TRE) and then to a corepressor; thus, repressing gene expression
- T3 binding to the ligand-binding domain results in movement of the carboxyterminal helix 12, disruption of corepressor binding, and promotion of coactivator binding, which then leads to recruitment of polymerase III and the onset of gene transcription
Thyroid function tests:
What does high levels of TSH mean?
What does low levels of TSH mean?
TSH level high= more TH needed
TSH level low, normal to high T3 and T4, levels= feedback isnt work (hypothyroidism)
- Functional thyroid diseases are extremely common.
- Results often form the entire basis of any diagnosis.
- Even subtle abnormalities in thyroid function are now considered as potential “disease states,” necessitating both accurate biochemical testing and understanding of differing population definitions of “thyroid disease.”
Hypothyroidism symptoms?
- Cold intolerance
- Dec sweating
- Weight gain
- Constipation
- Depression and irritability
- Irregular and heavy periods
- Brittle nails
- Slow HR
- Muscle or joint pain
- Puffy face
- Feeling faint
Hyperthyroidism symptoms?
- Heat intolerance
- Inc sweating
- Weight loss of gain
- Diarrhoea
- Nervousness and anxiety
- Nail thickening and flaking
- Muscles weakness
- Racing heart
- Short and light periods
- Puffy or bulging eyes
(body processes speed up)
Symptoms of hypo and hyperthyroidism? (3)
- Fatigue
- Insomnia
- Hair loss
Thyrotoxicosis (hyperthyroidism):
What is this?
signs and symptoms?
Excess thyroid hormone action on target tissues
Typical features caused by stimulation of metabolism and cateocholamines
e.g. weight loss with increased appetite
S/S:
↑metabolic rate, ↑appetite, Heat intolerance, arrythmias
↑nervousness, hyperkinesis, sweaty, clammy skin
Sympathetic overactivity – tachycardia, sweating and tremor
Extreme: high output heart failure
Upper eyelids retract – wide stare
Treatment depends on the underlying cause
Causes of thyrotoxicosis? (3)
- Graves’ disease
-Organ specific autoimmune disease
-Common in women
-Antibodies to TSH receptor (TRAB)
Remission with antithyroid drugs in 30-40% of cases - Toxic multi-nodular goitre
-No remission with antithyroid drugs - Toxic solitary nodule
-No remission with antithyroid drugs
