the thyroid
structure and function
- The thyroid gland is made up of 2 lobes joined by a midline isthmus.
- Firmly bound to the larynx and trachea by the pre-tracheal fascia and hence moves with them during swallowing
- It has a rich blood supply - superior thyroid artery enters the upper pole and is a branch of the external carotid; the inferior thyroid artery enters the middle of the posterior aspect and is a branch of the thyro-cervical trunk of the subclavian artery
- May get central pyramidal lobe as an extension of the isthmus upwards over the thyroid cartliage, which is an embryological remnant of the thyroglossal duct.
- The parathyroid glands are embedded in the posterior surface of the lateral lobes
- Within the gland there are numerous follicles, each made up of an enclosed sphere of highly specialised cells surrounding a core containing a protein rich material - colliod.
- The thyroid follicular cells (columnar epithelium) participate in almost all phases of thyroid hormone synthesis and secretion
- "C" cells are found between the thyroid follicles and they secrete calcitonin
- Calcitonin and PTH, which is secreted by the parathyroid gland, control calcium homeostasis and have significant effects on bone physiology.
- The thyroid produces 2 iodine-containing thyroid hormones: thyroxine (T4) and triiodothyronine (T3)
- These 2 hormones regulate the rate of metabolism.
- T3 and T4 are synthesized from iodine and tyrosine
- T3 is the more potent molecule and T4 is generally converted to T3 by deiodinases.
thyroid hormone sythesis
- Circulating iodine is co-transported with sodium ions across the follicular cell plasma membrane into the lumen of the follicle.
- Iodine cannot diffuse back out as it is too large - this is called iodine trapping.
- Iodine is negatively charged so it diffuses down its electrochemical gradient to the luminal borders of the follicular cells
- The colliod mentioned earlier found in the follicles contains a protein called thyroglobulin, which is sythesised by the follicular cells
- The iodine is oxidised by the colloid to form free radicals which attach to tyrosine found on the thyroglobulin. This is done by thyroid peroxidase. This is also synthesised by the follicular cells
- Thyroid peroxidase is also sythesised by the follicular cells
- When thyroid hormone is required the follicular cells engulf portions of the colloid by endocytosis. The thyroglobulin and its coupled tryosine-iodine (thyroid hormone) is bought back into contact with lysosomes in the cell interior.
- Proteolysis of the thyroglobulin releases T3 and T4 which diffuse into the interstitial fluid and then into the blood.
- An iodinated thryoglobulin store can last several weeks.
actions of thyroid hormones
- Receptors are present in the nuclei of most cells in the body
- In broad terms, thyroid hormone increases metabolic rate and therefore promotes the consumption of calories - has a calorigenic effect
- This leads to increased heat production
- Actions of the sympathetic nervous system are increased but T3 and T4 - called permissive action
- Thyroid hormones are essential for normal growth and development, especially of the NS, during fetal life and childhood
thyroid disorders
HYPERTHYROIDISM
HYPOTHROIDISM
HYPOTHROIDISM
the pituitary gland - anterior and posterior
structure
- The pituitary gland lies in the sella turcica of the sphenoid bone at the base of the brain, just below the hypothalamus
- The pituitary is connected to the hypothalamus by the infundibulum
- The anterior pituitary arises from an invagination of the pharynx called Rathke's pouch
- The posterior pituitary is an extension of the neuronal components of the hypothalamus
- The junction of the hypothalamus and the the infundibulum is called the median eminence. Capillaries recombine here to form the hypothalamo-pituitary portal vesels
- Anterior pituitary has no blood supply - it receives its blood through a portal venous circulation from the hypothalamus
- Posterior pituitary is supplied by the inferior hypophyseal artery
anterior pituitary gland hormones
FSH and LH
target: gonads
function:
Growth hormone
target: liver, many organs and tissues
function:
TSH (thyroid stimulating hormone)
target: thyroid
function:
Prolactin
target: breasts
function: breast development and milk production
ACTH
target: adrenal cortex
function: promote cortisol secretion
target: gonads
function:
- germ cell development - ovum, sperm
- secrete hormones - female estradiol, progesterone; male testosterone
Growth hormone
target: liver, many organs and tissues
function:
- secrete IGF-1
- protein sythesis, carbohydrate and lipid metabolism
TSH (thyroid stimulating hormone)
target: thyroid
function:
- stimualtes follicular cells to secrete thyroxine, triiodothyroxine (T3 and T4)
- in follicular cells: increases protein sythesis, DNA replication, cell division. Therefore if the thyroid is exposed to higher TSH levels it will undergo hypertrophy and lead to goiter
Prolactin
target: breasts
function: breast development and milk production
ACTH
target: adrenal cortex
function: promote cortisol secretion
regulation of anterior pituitary hormones
Regulated by hypophysiotrophic hormones - hypothalamic hormone, secreted by neurones that originate in discrete nuclei of the hypothalamus and end at the median eminence
CRH - Corticotrophin-releasing hormone
TRH - Thyrotropin-releasing hormone
GHRH - Growth hormone-releasing hormone
SS - Somatostatin
GnRH - Gonadotrophin-releasing hormone
DA - Dopamine
DA is a catecholamine, the rest are peptides
CRH - Corticotrophin-releasing hormone
- Stimulates ACTH secretion
TRH - Thyrotropin-releasing hormone
- Stimulates TSH secretion
GHRH - Growth hormone-releasing hormone
- Stimulates GH secretion
SS - Somatostatin
- Inhibits secretion of GH
GnRH - Gonadotrophin-releasing hormone
- Stimulates LH and FSH secretion
DA - Dopamine
- Inhibits secretion of prolactin
DA is a catecholamine, the rest are peptides
posterior pituitary gland hormones
Vasopressin - also known as anti diuretic hormone(ADH) and argonine vasopressin (AVP)
Oxytocin
- controls water secretion into urine
- secreted primarily from supraoptic nuclei of the hypothalamus
- 3 types:
- V1a - acts on vasculature. Makes the smooth muscle contract and causes vascontriction
- V2 - acts on aquaporins in the renal collecting tubule to increase water reabsorption by inserting aquaporin-2 channels in the apical membranes to make it more permeable
- V1b - acts on anterior pituitary to release CRH which increases ACTH levels
- The release is controlled by osmoreceptors in the hypothalamus on a day to day basis
- Baroreceptors in the brainstem and great vessels control it in emergency situations
Oxytocin
- Expression of milk from the glands of the breasts to the nipples - contraction of smooth muscle
- promotes onset of labour - stretch receptors in the cervix send signals to stimulate contraction of uterine smooth muscle
- secreted primarily from the paraventricular nuclei of the hypothalamus
Anterior pituitary tumours
Tumours (adenomas) cause:
Pressure on local structures, e.g. optic nerves
Prolactinoma
Acromegaly
Cushing's syndrome
Treatment:
Pressure on local structures, e.g. optic nerves
- bitemporal heminopia
- hypopituitarism
- prolactinoma
- acromegaly
- cushing's disease
Prolactinoma
- more common in women
- present with galactorrhea/amenorrhoea/infertility
- loss of libido
- visual field defect
- treatment: dopamine agonist e.g. Cabergoline or bromocriptine
Acromegaly
- slow onset
- present with thick skin, big hands, big jaw
- diagnose with GH suppression test (OGTT) and IGF-1
- treatment: transphenoidal surgery is primary treatment; Somatostatin or GH antagonist therapy
Cushing's syndrome
- An adenoma in the pituitary gland produces large amounts of ACTH which causes the adrenal glands to produce high levels of cortisol
- central trunk obesity with limb sparing
- moon face
- diabetes mellitus
- hirsuitism
- high blood pressure
- amenorrhoea/infrequent periods
- loss of libido
- mood swings
- Blood test after taking dexamethasone (suppresses cortisol production). A high cortisol level helps to confirm Cushing's
- Measure ACTH. If it's positive image the pituitary and inferior petrousal sinus sampling. If negative, image the adrenal glands
Treatment:
- Surgery to remove adenoma
- After surgery, hydrocortisone for several months while pituitary gets back to normal
posterior pituitary disorders
Diabetes insipidus - inability to concentrate urine
Diagnosis: measure urine volume - DI is unlikely if urine volume is less than 3L/day
2 types:
Cranial DI
Causes:
Acquired:
Familial: very rare - mutations in the neurophysin of pro-AVP
Management:
Nephrogenic DI
Acquired:
Familial:
Managment:
Syndrome of inappropriate antidiuretic hormone secretion - SIADH
Management:
- polyuria
- polydipsia
- no glycosuria
Diagnosis: measure urine volume - DI is unlikely if urine volume is less than 3L/day
2 types:
- Cranial DI - lack of vasopressin
- Nephrogenic DI - resistance to vasopressin
Cranial DI
Causes:
- Destruction of the hypothalamus
- Interruption of the connection of hypothalamus to the pituitary
Acquired:
- Idiopathic
- Tumours - craniopharyngioma, germinoma, metastases
- Trauma
- Infections - TB
- Vascular - neurosarcoidosis, Langerhan's histocytosis
- Granuloma
Familial: very rare - mutations in the neurophysin of pro-AVP
- Autosomal dominant
- rarely autosomal recessive
Management:
- treat any underlying treatment
- desmopressin
Nephrogenic DI
Acquired:
- Osmotic diuresis (diabetes mellitus)
- Drugs (lithium, demeclocyline, tertracycline)
- Chronic renal failure
- Post-obstructive uropathy
- Metabolic (hypercalcaemia, hypokalaemia)
- Infiltrative (amyloid)
Familial:
- X linked (V2 receptor defect)
- Autosomal recessive (aquaporin 2 defect)
Managment:
- try and avoid precipitating drugs
- congenital DI - very difficult to treat
- free access to water
- high dose desmopressin
- hydrochlorothiazide or indomethacin
Syndrome of inappropriate antidiuretic hormone secretion - SIADH
- common in clinical practice
- too much AVP, when i should not be being secreted
- causes low blood concentraion - low osmolality
- urine is inappropriately concentrated
- plasma sodium is low
Management:
- treat underlying condition
- sometimes demeclocycline
- 'vaptans' - V2 receptor antagonists
Diabetes mellitus
ADRENAL GLANDS
- Located about the kidneys ("suprarenal" glands)
- R gland is pyramidal
- L gland is semi lunar
- Made up cortex and medulla
cortex
Cortex: outer zone
- makes up 80-90% of gland mass
- Mesodermal in origin
- Glomerulosa - produces mineralocorticoids e.g. aldoesterone.
- Fascilulata - Glucoscorticoids e.g. cortisol (cortisol is the most adbundant glucoscorticoid in the body)
- Reticularis - Sex steroids; weak androgens e.g. DHEA. Help maintain secondary sex characteristics
SYNTHESIS of adrenal steriods
- Adrenal steroid hormones are synthesised from cholesterol
- Cholesterol is taken up from plasma via a specific LDL (low density lipoprotein) receptor
- Cholesterol is either used for immediate hormone sythesis or esterified and stored (in cytoplasmic vacuoles)
- Stored cholesterol can be mobilised for increased hormone production when the cell is stimulated
Cortisol synthesis
- several P450 enzymes involved including: side chain cleavage enzyme which is rate limiting; and 17 hydroxylase, 21 hydroxylase, 11 hydroxylase
- Released in response to stress and low serum glucocorticoids
- Acts to increase blood sugar through gluconeogenesis
- Suppresses the immune system - downregulates IL2-R on Helper (CD4+) T-cells
- Aid in fat, protein and carbohydrate metabolism
- Decreases bone formation
Aldosterone synthesis
- requires additional enzyme, aldosterone synthetase - only present in the glomerulosa
regulation of cortisol
Controlled by the hypothalamo-pituitary-adrenal (HPA) axis
CRH
CRH
- produced in the hypothalamus
- released into the median eminence
- carried in the portal vessels to the anterior pituitary gland
- acts on cell surface CRH receptors on corticotroph cells
- stimulates ACTH synthesis and release
- stimulated cortisol secretion
- Release inhibited by high levels of cortisol
addison's disease
Hyposecretion of the adrenal cortices
Cushing's syndrome
Excessive levels of glucocorticoids
Can be caused by:
Can be caused by:
- excessive ACTH production by anterior pituitary gland
- excessive production of adrenal hormones (e.g. because of a tumour) or
- as a result of glucocorticoid therapy for other disorders e.g. rhematoid arthritis, preventing rejection of organ transplant