Pituitary and Thyroid Glands Flashcards
Where does the pituitary gland lie?
Lies in a packet (sella turcica) of the sphenoid bone at teh base of the brain just below the hypothalamus
How is the pituitary connected to the hypothalamus?
By the infundibulum (pituitary stalk)
What are the different parts to the pituitary?
2 adjacent lobes
- Anterior pituitary (adenohypophysis)
- develops from a dorsal outgrowth from the wall of the embryonic pharynx - Posterior pituitary (neurohypophysis)
- develops from a down growth from the diencephalon
Where does the adenohypophysis develop from?
Dorsal outgrowth from the wall of the embryonic pharynx
Where does the neurohypophysis develop from?
Down growth from the diencephalon
Where do the neurons in the neurohypophysis come from?
Axons of the supraoptic and paraventricular nuclei in the hypothalamic ventricle down the infundibulum into the neurohypophysis
- Neurons do not synapse with others - their terminals end directly on capillaries, releasing hormones into the blood
Are there any neural connections between the hypothalamus and the adenohypophysis?
No important connections
What capillaries combine to form the hypothalamo-hypophyseal portal vessels?
Capillaries from the median eminence
List the hypothalamus-pituitary hormones (adenohypophysis) axises
- GHRH –> GH (somatotrophs -50%) –> multiple
- GnRH –> FSH/LH (gonadotrophs - 10%) –> ovaries/testes
- CRH –> ACTH (corticotrophs - 10-15%) –> adrenal cortex
- TRH –> TSH (thyrotrphs - 5%) –> thyroid
- Dopamine –> Prolactin (-ve; lactotrophes - 20%) –> breasts/uterus
What hormones are produced from the neurohypophysis?
Oxytocin
ADH/vasopressin
What hormone is important in labour and pregnancy and how does it work?
Oxytocin
- Stimulates cervical dilatation and uterine contractions
- Suckling reflex in mammary glands
What hormone causes sexual arousal that’s secreted from the neurohypophysis?
Oxytocin
Define diabetes insipidus
Lack of ADH from neurohypophysis
List common disorders of the anterior pituitary
– Diabetes insipidus (lack of ADH)
– Syndrome of inappropriate anti-diuretic hormone (SIADH)
What is the clinical features of diabetes insipidus?
- Lack of ADH
- No water reabsorption
- Passage of large volumes of DILUTE URINE (>3L/day)
- Polyuria, polydipsia, noctouria
- LOW URINE OSMOLALITY and high plasma osmolality
Describe ADH action
- AVPR2 translocation on basolateral membrane of collecting duct of kidneys (exocytosis)
- Increase aquaporin channels (AQ2) and water reabsorption
What are the causes of diabetes insipidus?
- Cranial cause
- deficiency of ADH (idiopathy/genetic)
- trauma/tumour/infection/inflammation - Nephrogenic cause
- resistance to ADH
- genetic: AVPR2 mutation
- iatrogenic: e.g. lithium drugs
- secondary: metabolic dysfunction or renal disease
How would you test for the cause of diabetes insipidus?
Water Deprivation Test
- Deprive patients of fluid for 8 hours
- Measure plasma and urine osmolality every 2-4hours
- Give synthetic ADH (ddAVP) and re-asses urine osmolality
Results:
Normal Patient
- starting plasma osmolality: normal 300mOsm/L
- 8hour urine osmolality: >600mOsm/L (water retained
- after ddAVP >600mOsm\L
Cranial DI
- starting plasma osmolality: HIGH (low [water])
- 8hour urine osmolality: LOW <300mOsm\L (NO ADH SO NO RETENSION)
- after ddAVP: HIGH >600mOsm/L (Synthetic ADH acts on kidneys to retain water)
Nephrogenic DI
- starting plasma osmolality: HIGH (low [water])
- 8hour urine osmolality: LOW
- after ddAVP: LOW
Tx Diabetes Insipidus
- Cranial cause
- Desmopressin (ADH analogue)
- Orally/nasal
- Spray/injection
* monitor [Na]plasma and osmolality - Nephrogenic cause
- high doses ddAVP
- treat underlying cause (e.g. excise tumour)
Where is the pituitary located relative to the optic chiasm?
Pituitary located inferiorly to optic chiasm
What is the name give to pituitary tumours
Adenoma
What is the potential consequence of a pituitary tumour?
Adenoma can push on the optic chiasm (which lies superior to the pituitary)
Can cause bitemporal hemianopia (loss of peripheral vision)
List the hormones involves in secretory pituitary adenomas
- Prolactinoma - releases excess prolactin
- commonest (30%) - Cushing’s disease - ACTH excess
- 20% - Acromegaly - GH excess
- 15% - TSHomas - TSH excess
- <1% very rare
What condition is caused secretory pituitary adenoma GH secretion?
Acromegaly
What condition is caused secretory pituitary adenoma prolactin secretion?
Prolactinoma
What condition is caused secretory pituitary adenoma TSH secretion?
TSHoma
What condition is caused secretory pituitary adenoma ACTH secretion?
Cushing’s Disease
What are the clinical features and management of prolactinomas?
Clinical features:
- galactorrea: milky nipple discharge
- menstrual disturbance and subfertility in women
- reduced libido and erectile dysfunction in men
Management
- Dopamine agonist (Cabergoline)
- Surgery if large tumour + bitemporal hemianopia
What is Cabergoline? And what is it used to treat?
Dopamine agonist
Used to treat prolactinomas
Increase in dopamine negatively inhibits prolactin secretion from the adenohypophysis
What is acromegaly?
Excessive production of GH (and IGF-1) in adults
What does excessive production of GH cause in children?
Gigantism
What are the clinical features of acromegaly?
• Symptoms
– Sweats, headache, tiredness, increase in ring or
shoe size, joint pains
• Signs – Coarse facial appearance – Enlarged tongue – Enlarged hands and feet – Visual field loss
• Complications
– Hypertension, diabetes or impaired glucose
tolerance, increased risk of bowel cancer, heart
failure
Dx acromegaly
- Glucose tolerance test
- Glucose fails to suppress GH
- May reveal underlying DM or IGT - IGF-1 level
- Produced in the liver in response to GH
- Long half-life; protein-bound - Pituitary MRI
- macroadenoma >1cm
Management of acromegaly
- Surgically
- Trans-sphenoidal or trans-cranial route - Medical
- Before and after surgery
- Somatostatin analogues to inhibit GH secretion - Radiotherapy
- Treat residual tumour
- Risk of hypopituitarism and long-term problems
What can inhibit GH secretion?
Somatostatins
Define hypopituitarism
Failure of adenohypophysis function
What is the name given when hypopituitarism affects ALL hormones?
Panhypopituitarism
What drug would you give first in panhypopituitarism?
Cortisol
What is Sheehan’s syndrome?
Ischaemic necrosis due to blood loss/hypovolaemic shock during or after childbirth
IN MOTHER
What is apoplexy?
Unconsciousness or incapacity resulting from a cerebral haemorrhage or stroke.
Define necrosis
The death of some or all of the cells in an organ or tissue, caused by disease, physical, or chemical injury, or interference with blood supply (ischaemia)
How many layers of cells is the thyroid follicles made up of?
A single layer of cuboidal epithelial cells
And basement membrane
Describe the structure of a thyroid follicle
A single layer of cuboidal epithelial cells
And basement membrane
Surrounding a lumen containing colloid (containing largely thyroglobulin)
What is the epithelial difference in follicular epithelial cells during suppression and stimulation?
- When stimulated = CUBOIDAL; and lumen is depleted of colloid
- When suppressed = SQUAMOUS; and colloid accumulates in lumen
Which is the more important thyroid hormone?
T3
Tri-iodothyronin
How is T4 converted into T3?
T4 converted into T3 by enzymes called 5’deiodinases in target cells
THEY REMOVE 1 IODINE GROUP OFF T4 TO MAKE T3
Where is iodine naturally found?
Sea water
Fruit
Vegetables
What is the required daily amount of iodine?
150-300ug/day
What is the characteristic of iodine deficiency?
Goitre
Describe thyroid hormone biosynthesis
- Iodide actively co-transported with Na+ across basolateral membrane of epithelial cells (iodide trapping) against a chemical gradient. Na+ is pumped back out by Na+/K+-ATPase
- Negatively charge iodide diffuses to the apical membrane and is transported by PENDRIN (integral membrane protein) into colloid
- Iodide is oxidised to iodine in the colloid by THYROID PEROXIDASE
- Iodine is attached to rings of tyrosine in thyroglobulin - by THYROID PEROXIDASE
(thyroglobulin is synthesised by eER in the thyroid follicular cell and exocytosed into the colloid) - Iodine may be added to either of two positions of a given tyrosine within a thyroglobulin
- a tyrosine with 1 iodine attached = mono-iodo-tyrosine (MIT)
- a tyrosine with 2 iodine attached = di-iodo-tyrosine (DIT)
- DIT + DIT = T4
- MIT + DIT = T3
- Once formed, extensions of colloid- facing membranes of follicular epithelial cells engulf portions of the colloid with its iodinated thyroglobulin by endocytosis
- Within the cell, thyroglobulin-MIT/DIT is brought into contact with lysosomes, which proteolyse off thyroglobulin releasing T3/T4 (hydrolysis)
- Free T3/T4 then diffuse out of the follicular epithelial cells (via monocarboxylase transporter - MCT) into the interstitial fluid and then into circulation
What thyroid hormone is released in greater quantity?
T4
Thyroxine
How does thyroid hormone circulate?
- 5% Free
99. 5% bound to thyroid binding protein (transthyretin or albumin)
What type of receptors for thyroid hormones act on?
Nuclear receptors
alpha and beta
What level of action does thyroid hormones work on?
Inducing gene transcription and protein systhesis
How is thyroid hormone regulated?
- Neural inputs from higher cortex
- Hypothalamus secretes TRH to anterior pituitary
- Adenhypophysis secretes TSH to thyroid gland
- Thyroid gland synthesises and releases T3/T4 into the blood
- T3/T4 binds to thyroid binding proteins (transthyretin/albulmin)
- T3/T4 negative control feedback inhibits adenohypophysis (TSH) and hypothalamus (TRH) axis
What is the biochemical findings in primary hypothyroidism?
- Elevated TSH (from anterior pituitary)
- Decreased T4 (dysfunctional thyroid)
What is the biochemical findings in secondary hypothyroidism?
- Decreased TSH
- Decreased T4
What is the biochemical findings in primary hyperthyroidism?
- Decreased TSH
- Elevated T4
Define euthyroid
Euthyroid is the state of having normal thyroid gland function
What is sick euthyroid?
- Euthyroid sick syndrome is low serum levels of thyroid hormones in clinically euthyroid patients with non-thyroidal systemic illness
- Diagnosis is based on excluding hypothyroidism
- Treatment is of the underlying illness; thyroid hormone replacement is not indicated.
What is the aetiology of hyperthyroidism?
- Autoimmune - Most common (Graves’ Disease)
- Toxic adenoma
- Multinodular goitre
- Thyroiditis
- Excess administration of thyroxine
What are the clinical manifestations of hyperthyroidism?
*General increase in metabolism activity
- Weight loss
- Tremer
- Heat intolerance
- Diarrhoea
- Tachycarida and increased cardiac output
- Hypertension
- Palpitations
- Sweating
- Hyperkinetic (too much energy)
What are the specific characteristics to Graves’ Disease
Graves’ disease is an autoimmune (most common) form of hyperthyroidism
- Dysthyroid eye disease (Ophthalmopathy)
- 50% patients
- Periorbital oedema
- Proptosis (bulging of eye)
- Diplopia (double vision) - Dermopathy (skin condition characterised by red swollen skin)
- Pretibial myxoedema
- Thyroid acropachy (digital clubbing, swelling of digits and toes)
Tx Grave’s disease
Graves’ disease is a form of hyperthyroidism
- Thyronamines (e.g. Carbomazole)
- Radio-iodine therapy
- destroys thyroid tissue by b-emission
- may worsen eye disease
- defer conception for at least 4 months
- MAJOR SIDE EFFECT: hypothyroidism - Surgical removal
- Complications: haemorrhage, recurrent laryngeal nerve palsy (voice change), permanent hypocalcaemia, hypothyroidism - iodine drugs
- reduces vascularity
- increases colloid storage
What sex and age group is Graves’ disease most commonly in
Female
20-40
What is Graves’ disease characterised by?
- Hyperthyroidism
- Diffuse goitre
Thyroid gland is diffusely hyperplastic and hperaemic
- bruit on auscultation
Can also present with
- dysthyroid eye disease (omphthalomopathy)
- dermopathy
What are the main causes of hypothyroidism?
- Autoimmune thyroid disease (Hashimotos)
- destruction of the thyroid gland
- anti-thyroperoxidase antibodies) - Thyroiditis
- Thyroidectomy
- Following radio-iodine therapy
- Drug-induced
- e.g.: lithium - Pituitary disease
- secondary hypothyroidism - Severe iodine deficiency
What are the symptoms of hypothyroidism?
*General reduction in metabolic activity
- weight gain
- depression
- lethargy
- constipation
- cold intolerance (in severe cases: hypothermia)
- hoarseness (due to accumulation of mucopolysaccharides)
- menorrhagia (abnormal/heavy bleeding cycle)
- bradycardia
- dry skin
- coarse, thin hair
- anaemia
- slow relaxing reflexes
- may present with goitre
- mental impairment (psychosis)
Tx for hypothyroidism
Levothyroxine
- a manufactured form of the thyroid hormone, thyroxine.
What condition results from anti-thyropereoxidase antibodies?
Hashimoto’s Disease
What condition results from anti-TSH receptor antibody (thyroid stimulating)?
Grave’s disease
What condition results from anti-TSH receptor antibody (thyroid growth)?
Goitre
What condition results from anti-TSH receptor antibody (thyroid receptor blocking)?
Hypothyroidism
Primary myxoedema
What is the name of the condition of hypothyroidism in children? And what does it cause?
Cretinism
Stunned physical and mental growth
What is the name of the condition of hypothyroidism in adults? And what does it cause?
Myxoedema
- Elderly females
- Atrophic thyroid = fibrosis
- Severe hypothyroidism = hypothermia and coma
- Symptoms depend on hormone deficiency
(if due to anti-thyroidperoxidase Ab = Hashimoto’s)
What are they metabolic actions of T3?
- Increases whole-body basal metabolic rate
- Nuclear alpha and beta receptors
- Increases ATP utilisation by increasing Na+/K+-ATPase and increasing mitochondria oxidative metabolism
- Increase lipolysis is also stimulated by cAMP-dependent activation of hormone sensitive lipase
- Increase glycogenolysis and gluconeogenesis (thermogenesis fuel)
How does T3 increase energy production?
- Increases ATP utilisation by increasing Na+/K+-ATPase and increasing mitochondria oxidative metabolism
