Endocrine Biomed Capstone

What causes hyperthyroidism

overstimulation of thyroid producing excess thyroid hormones. graves disease, multi-nodular goitre, pituitary tumour, increased T3

more common than hypothyroidism

What causes hypothyroidism

chronically low plasma TH levels mostly due to primary loss of thyroid gland func

Two types of hypothyroidism

Primary (thyroid gland problem) = low T3 + T4, HIGH TSH (caused by iodine deficiency, hashimotos disease)

• deficiency in thyroid gland, doesn’t recognise TSH

Secondary (anterior pituitary problem) = low T3, T4, TSH

TSH and impact on thyroid function

TSH inversely related to thyroid gland activity

If primary hypothyroidism -> Increase TSH -> Decrease T3 + T4

If hyperthyroidism -> Decrease TSH -> Increase T3 + T4

TSH impact on follicles

Increase T3 + T4 -> Decrease TRH + TSH -> follicles shut down

Decrease T3 + T4 -> TSH secretion -> follicles activated

Cushings syndrome pathology

caused by high blood cortisol, adrenal hyperplasia due to excess ACTH stimulation from anterior pituitary due to pituitary neoplasms

Cushings syndrome symptoms

Increased fat + redistribution to central areas, increased protein breakdown + gluconeogenesis, muscle wasting, hyperglycemia

Addisons vs Cushings disease

Addisons = adrenal HYPOfunction

- low cortisol, hypoglycaemia, weight loss

Cushings = adrenal HYPERfunction

- high cortisol, hyperglycaemia, weight gain

Iodine degrades TG into T3 + T4

1. TSH binds to receptor -> TG synthesised in apical membrane + secreted into colloid

2. TG is iodinised and translocates back into apical membrane

3. Endocytosis + degradation of TG into T3 + T4 occurs

4. T3 + T4 released to peripheral tissues

How does iodine deficiency cause a goiter

Without iodine degrading TG into T3 + T4, TSH overstimulation occurs to compensate for decrease in circulating T3 + T4. Causes thyroid to enlarge = goiter

Regions of the adrenal gland

Outer cortex = produces steroid hormones (glucocorticoids, mineralocorticoids, gonadocorticoids)

Inner Medulla = produces catecholamines (adrenaline, noradrenaline, dopamine)

Conn's disease

primary hyperaldosteronism. affects aldosterone producing adrenal adenoma of zona glomerulosa. pathology = increased blood pressure, decreased potassium, decreased H+ (alkalosis)

Hypersecretion of growth hormone can lead to 2 disorders based on timing of hypersecretion :

If hypersecretion occurs during childhood = gigantism

If hypersecretion occurs during adulthood = acromegaly (thickening of features)

Suspect thyroid disorder

Clinical Features Hypothyroidism (low concentraiton)

enlarged thyroid (Goiter)

cold intolerance

weight gain

Clinical Features Hyperthyroidism (higher concentration)

enlarged thyroid (goiter)

heat intolerance

weight loss

Hashimoto’s Disease

autoimmune body attacks thyroid

• inflamed thyroid, thyroid autoimmune disease (Cell and Ab mediated), detect anti-thyroid peroxidase

treatment = thyroid hormone replacement therapy

most common hypothyroidism in USA

Graves Disease

autoimmune disease (more prevalent in females)

Abs stimulate TSK (or thyrotrophin) receptor

increase T3 and T4 feedback onto hypothalamus / pituitary and supress TSH —> antibodies biding to TSH receptors because increase T3 and T4 message to hypothalamus to stop producing TSH

thyroid gland atrophies due to constant stimulation

Clinical signs Graves Disease

exophthalmos (bulging eyes)

goitre —> irregular growth of thyroid gland (TSH overstimulation of thyroid due to increased circulating T3 and T4

Iron deficiency and thyroid hormone *** IMPROTANT SHORT RESPONSE Q****

Thyroglobulin (TG) is precursor of T3 and T4

TSH binds to receptor leading to TG production

Iodine translocated to basolateral membrane to iodises TG which promotes endocytosis then degradation into T3 T4

process

TSH leaves blood vessels and binds to TSHR in basolateral membrane —> protein synthesis —> TG —> secretion across the apical membrane —> iodination —> internalised via endocytosis (splits into T3 and T4) —> Iodotyrosines —> DEHAL 1 —> in endosome fuse with lysosome

Normal, hyer, hypo primary and seocndary TSH & T4

Normal - TSH = Normal, T4 = Normal

Hyperthyroidism - TSH = Low, T4 = High

Hypothyroidism Primary - TSH = High, T4 = low

Hypothyroidism Secondary - TSH = Low, T4 = low

Pituitary Disorders - hypersecretion and hyposecretion of GH

hypersecretion

• during childhood = gigantism

• during adult hood = acromegaly (thickening of features)

hyposecretion

• pituitary dwarfism (lower somatic growth)

Acromegaly

hypersecretion of somatotropin during childhood

over production of growth hormone throughout development

excessive amount of growth hormone in adulthood

causes = thickening of bones in hands, feet, cheeks, jaws (happens in adults)

Adrenal Cortex

adrenal corticosteroid hormones

• glucocorticoids (cortisol, corticosterone)

• mineralocorticoids (aldosterone) (regulates renal function)

• gonadocorticoids

Adrenal Medulla

Catecholamine

• adrenaline (epinephrine)

• noradrenaline (norepinephrine)

• dopamine

Adrenal cortex compoenents

Zona glomerulosa = mineralocorticoids

zona fasciculata = glucocorticoids

zona recticulans = gonadocorticoids

Adrenal Hormones - NEED TO KNOW

Addisons Disease

Adrenal Cortex Hyposecretion

• low cortisol

• hypoglycemia

• frail and weak (low weight)

• hyperkalaemia and ST elevation

• hyponatraemia and salt craving

Cushings Disease

Adrenal Cortex hypersecretion

• excess cortisol

• hyperglycemia

• hyperatreamia

• hypokalaemia

• truncal obesity