Week 5: Endocrine (2) Flashcards
thyroid hormone investigation
- HISTORY
- Blood test e.g. TSH, TRH, T4
- distinguish between hypo and hyper thyroidism
- Thyroid ultrasound
- Best way – structural isotope
- Radioisotope scan
- Give technetium- 99m via IV- a good uptake of iodine
Effect of T4 (thyroxin)
- Controls your metabolism e.g. heart rate , body temp and the rate at which intestine digest food
Diagnosis of thyroid disorder
- History
- symptoms and signs
- family history etc
- Blood test e.g. TSH, TRH, T4
- Imaging
-
Thyroid ultrasound- most useful at distinguishing bw cystic (fluid filled) and solid nodules.
- Can guide biopsy of a thyroid lesion.
-
Radioisotope scan
- Give technetium- 99m via IV- a good uptake of iodine
- hyperthyroidsims and thyorid cancer
- gamma camera used to detect gamma rays emitted from radioactive iodine
-
Thyroid ultrasound- most useful at distinguishing bw cystic (fluid filled) and solid nodules.
thryoid radioisotope scan findings
- Diffuse high uptake is found in Grave’s Disease
- Focal high uptake is found in toxic multinodular goitre and adenomas
- “Cold” areas (i.e. abnormally low uptake) can indicate thyroid cancer
thyroid feedback system
- The hypothalamus secretes thyroid releasing hormone
- TRH stimulates the anterior pituitary to secrete thyroid stimulating hormone
- TSH stimulates the thyroid to secrete T4
primary hypothryodisms
(underactive thyroid- usually autoimmune origin)
- T4 low (2.4 pmol/L (8-25)
- TSH high (150 miU/L (1-4.5)
primary hypothryodisms
(underactive thyroid- usually autoimmune origin)
- T4 low (2.4 pmol/L (8-25)
- TSH high (150 miU/L (1-4.5)
primary hypothryodisms
(underactive thyroid- usually autoimmune origin)
- T4 low (2.4 pmol/L (8-25)
- TSH high (150 miU/L (1-4.5)
primary hypothryodisms
(underactive thyroid- usually autoimmune origin)
- T4 low (2.4 pmol/L (8-25)
- TSH high (150 miU/L (1-4.5)
secondary hypothyroidism
- Due to TSH deficiency and usually due to pituitary disease
- Low T3 levels and non-elevated TSH
primary hyperthyroidism
- T4 high (86 pmol/L (8-25)
- TSH low (<0.05miU/L (1-4.5)
hypothyroidism presentation
Symptoms
- Tiredness
- Weight gain
- Cold intolerance
- Change in appearance
- Depression
- Psychosis
- Joint/ muscle ache
- Dry hair/ skin
- Constipation
- Puffy eyes
Signs
- Peri-orbital oedema- swelling of the eyes
- Loss of lateral eyebrows
- Dry, thin hair
- Bradycardia
- Slow-relaxing reflexes
- Carpal tunnel syndrome
- Cold peripheries
causes of myxoedema (old fashioned descriptive word for hypothyroidism meaning swelling of eye and thickening of the skin
- Autoimmune atrophic
- Hashimotos’ thyroiditis
- Post-partum thyroiditis
- Dyshormonogenesis (babies born with under active thyroid)
- Medication
- Iodine deficiency
children who have hypothyroidism have
reduced I- cretinism
Special situations in hypothyroidism
Myxoedema coma
borderline or subclinical hypothyroidism
Myxoedema coma
Severe hypothyroidism usually in the elderly.
- Hypothermia and fluid overload in heart
- 50% mortality
Borderline or sub-clinical hypothyroidism
- Low/normal T4 and high TSH
- More common than severe hypothyroidism
- Can be monitored until symptoms warrant treatment
Treatment of hypothyroidism
Thyroxine
replacement therapy
- Levothyroxine (T4) for life
- Starting dose depends on severity
- 100ug for young and fit person
- More caution in elderly and heart disease
Aims
- Resolution of symptoms
- Normalisation of blood tests (6-8 weeks)
- High TSH suggests under replacement
- Low TSH suggests over replacement
presentation of hyperthyroidism
Symptoms
- Weight loss
- Irritability
- Restlessness
- Insomnia
- Malaise
- Itching
- Sweating
- Palpitation
- Tremor
- Muscle ache
- Diarrhoea
Signs
- Tremor
- Hyperkinesis
- Tachycardia
- Atrial fibrillation (irreg irreg)
- Warm peripheries
- Hypertension
- Proximal myopathy
- Lid lag
lid lag and hyperthyroidism
causes of hyperthyroidism
Causes
- Graves disease
- Nodular thyroid disease
- Thyroiditis
graves disease
- Most common cause of hyperthyroidism
- Autoimmune mediated stimulation of TSH receptor on thyroid gland stimulates thyroid hormone synthesis
Effects
- Graves ophthalmopathy
- Pretibial myxoedema (Graves dermopathy)
- Thyroid acropathy
thyroiditis
- Inflammation of thyroid
- Release of thyroxine into circulation
- Viral infection- de quervains thyroiditis
- After birth- post partum
- Medication- amiodarone
nodular hyperthryodiisms
- Single toxic nodule
- Toxic multi-nodular goitre
treatment of hyperthyroidism
Medication
- Carbimazole
- Beware of agranulocytosis (reduces neutrophils)
- Beta blocker for symptom control
Surgery
- If side effects on medication or patient preference
- Good cosmetic results
- Small risk of laryngeal nerves palsy’s and hypocalcaemia
Radioactive iodine
- Good definitive non-surgical option
- Contra-indicated in pregnancy
- Radiation restriction guidance after treatment
special situations in hyperthyroidism
thyroid crisis
hyperthyroidism and pregnancy
Thyroid crisis or thyroid storm
- Rare condition with 10% mortality
- Hyperpyrexia
- Tachycardia
- Cardiac failure
- Liver dysfunction
- Urgent treatment
Hyperthyroidism and pregnancy
- In graves disease antibodies can cross placenta
- Baby can be born with hyperthyroidism
- Requires close monitoring in pregnancy
Types of goitre
Diffuse goitre
- Simple goitre
- Auto-immune
- Thyroiditis
Nodular goitre
- Multinodular goitre
- solitary nodule (red flag )
Fibrotic goitre
- Riedel’s thyroiditis – rare
Iodine deficiency
- Common worldwide
- Rare in UK
red flag symptoms of thyroid cancer : history
- Very young or old patient
- Rapid enlargement of lump in neck
- Hoarse voice and dysphagia
- Family history of thyroid cancer
red flag symptoms of thyroid cancer: examination
- Hard irregular thyroid mass
- Fixed to surrounding structures
- Cervical lymph nodes
Investigation of suspected thyroid cancer
- Thyroid ultra-sound
- Fine need aspiration
- CT scan thorax and mediastinum
if cytology suggest thyroid cancer
surgical removale
MUST BE DONE BY EXPERT TO PREVENT DAMAGE TO THE PARATHYROID GLANDS AND NOT DAMAGE TO THE RECURRENT LARYNGEAL NERVE -→ PALSY
Anatomy of the adrenal gland
- Pyramidal shape
- Sits on top of the kidney
- made up of cortex and medulla
SALT SUGAR SEX (DEEPER YOU GET THE SWEETER)
layers of the cortex
GFR
zona glomerulosa
zona fasiculata
zona reticularis
Zona glomerulosa- aldosterone
- Salt and water
- Mineralocorticoids e.g. aldosterone
- Regulated by RAAS
- RAAS: In response to low circulating blood volume, hyponatraemia or hyperkalaemia, renin is activated to catalyse the conversion of angiotensinogen to angiotensin I, which is converted by angiotensin-converting enzyme (ACE) to angiotensin II. Angiotensin II stimulates aldosterone release upon binding to the angiotensin receptor. Aldosterone acts mainly at the renal distal convoluted tubule on its receptor to cause sodium retention and potassium loss.
Zona fasciculata- cortisol
- Sugar
- Glucocorticoids- cortisol
- Cortisol synthesis is regulated by ACTH
- Cortisol exerts a negative feedback on the hypothalamus top reduce CRH (and vasopressin) and on the anterior pituitary to reduce ACTH
- Cortisol is highest at 0800 and lowest midnight
- Investigation- cortisol immunoassays measure total (bound and free) cortisol, hence conditions which stimulate CBG (capillary blood glucose) e,g. oestrogen therapy, may increase measure cortisol levels without affecting biologically active free levels
zona reticularis -testosterone
- Sex
- Androgens- Testosterone
- Controlled by ACTH
- More important role in women (in both sexes pre-pubertally), as adult men rely mainly on testicular production of androgens
- DHEA and DHEA-S and androstenedione are converted to more potent testosterone and dihydrotestosterone in peripheral tissue
- Androgens exert their effect on: sebaceous glands, hair follicles, the prostate gland and external genitalia
adrenal medulla disease presentation
Presentation of adrenal medulla disease (noradrenaline/ adrenaline)
- Excessive catecholamine secretion
- Acute episodes
- Sweating
- Palpitations
- High or low BP
- Collapse
- SUDDEN DEATH
Biochemical assessment of adrenal medulla
-
24 hour urine catecholamines
- adrenaline (short half life)
- noradrenaline (short half lif)
- dopamine etc
Measuring 24 hour urine catecholamines gives an idea of how much adrenaline is being secreted by the tumour over the 24 hour period.
or
-
Plasma free metanephrines
- metanephrines are breakdown products of catecholamine- longer half life- therefore more reliable diagnostic tool
- Avoid certain foods: coffee, coke, bananas, chocolate, vanilla
Adrenal hormone deficiency’s presentation
-
Cortisol (lack of glucocorticoid) deficiency (addisons disease) - weakness, tiredness, weight loss, hypoglycaemia
- Cortisol does the opposite to insulin
- Mineralocorticoid (aldosterone) deficiency– dizziness, hypotension, low Na, high K
-
Androgen deficiency– e.g. Addisons
-
In women- low libido and loss of body hair in women
- Testosterone only produced in adrenal gland in women
- In men- no symptoms because produced in testicals
-
In women- low libido and loss of body hair in women
Adrenal hormone excess presentation
-
Cortisol excess- weight gain and cushingoid features (cushing’s syndrome)
- Diabetes
- Bone weakness
- Mineralocorticoid excess (aldosterone)- high BP and low K
- Androgen excess – increased male characteristics in women
ACTH excess from pit
- Skin pigmentation due to melanocyte stimulation
- Pigmentation seen in Addisons and ACTH- driven cushings
Diagnosis of suspected adrenocortical disease
- Measurement of cortisol and ACTH
- Measurement of 24hr urinary excretion of cortisol and its breakdown products
- Dynamic function tests
- Dexamethasone suppression test
- Suppression of plasma cortisol by >50% is characteristic of Cushing’s disease, but suppression doesn’t normally occur in adrenal tumour or ectopic ACTH production
- ACTH stimulation test
- Admission of Synacthen would normally increase plasma cortisol, and a normal response to this usually excludes Addison’s disease
- Dexamethasone suppression test
- CT
- MRI
- Functional imaging: MIBG scan
- PET scan
Hyperaldosteronisms
A condition in which there is excessive production of aldosterone.
Primary hyperaldosteronism
excess aldosterone production due to a defect in the adrenal cortex. Commonest form of endocrine hypertension.
- Bilateral idiopathic adrenal hyperplasia
- Or Aldosterone-secreting adenoma (Conns syndrome)
primary hyperaldosteronism diagnosis
- Hypertension and hypokalaemia
- Elevated aldosterone independent of RAAS (suppressed renin)
- Scan- shows adrenal adenoma or bilateral hyperplasia
secondary hyperaldosteronism
excess aldosterone production due to overactivity of the RAAS
- Renin- producing tumour or renal artery stenosis
signs and symptoms fo hyperaldosteronism
- High blood pressure
- Left ventricular hypertrophy
- Stroke
- Hypernatremia
- Hypokalaemia
treatment of hyperaldosteronism
- Dependent on cause
- Surgical treatment for aldosterone-secreting adenomas or
- Spironolactone (a mineralocorticoid receptor agonists) can be used for other causes
cushings syndrome
A syndrome caused by excessive exposure to cortisol
→ different to disease
causes of cushings syndrome can be
exogenous
endogenous
ecogenous causes of cushings syndrome
main cause is being prescribed glucocorticoids e.g. being prescribed dexamethasone
endogenous causes of cushings syndrome
- Cushing’s disease: benign pituitary adenoma that secretes ACTH
- Adrenal cushing’s: Adrenal tumour secreting glucocorticoids
- Non- pituitary-adrenal tumours producing ACTH and/ or CRH (e.g. small cell lung cancer- very rare)
cushings syndrome presentation
- Moon shaped face
- Buffalo hump
- Abdominal obesity
- Striae
- Acute weight gain
- Hyperglycaemia – increased gluconeogenesis
- Hypertension- mineralocorticoid effects of excess cortisol
steroid drug and cushings
(e.g. prednisolone and dexamethasone) are the same as the effects of higher levels of cortisol.
→ steroid dosage should always be decreased gradually and never stopped suddenly
adrenal cushings syndrome
adrenal tumour
- ACTH is suppressed- ACTH independent
- Unlike pituitary and ectopic ACTH
-
Symptoms
- Androgenic symptoms may be present
- Hirsutism
- Acne
- Greasy skin
- Virilising features in large tumours
- Androgenic alopecia
- Deep voice
- Clitoromegaly
- Androgenic symptoms may be present
-
Treatment
- Adrenalectomy- laparoscopic
- Large tumours need open surgery
-
Symptoms
androgens
Androgens are partially regulated by ACTH and CRH.
- Promote axillary and pubic hair growth in both males and females
androgens in males
- In prepubescent males dehydroepiandrosterone (DHEA) released from the adrenal glands is converted to testosterone in the testes.
- After puberty this production is insignificant as the testes themselves release testosterone
androgens in females
- Adrenal androgens promote libido and are converted to oestrogen in tissues
- After menopause this is the only source of oestrogen in the body
genital ambiguity in female infants
a rare condition in which an infant’s external genitals don’t appear to be clearly either male or female.
- Genetic defect- deficiency of the 21-hydroxylase enzyme
- Results in decreased glucocorticoid and mineralocorticoid production
- Precursor of these hormones- 17a-hydroxypregnenolone is therefore diverted to more androgen synthesis (e.g. testosterone)-→ excessive testosterone
- Can also cause salt wasting crises- high rate of sodium lost
addisons disease
‘Primary adrenal insufficiency”
Hypocortisolism
causes of addisons disease
- Destructive atrophy of the adrenal glands by autoimmune response
- Fungal infections
- Adrenal cancer
- Adrenal haemorrhage
- TB (in old times- good time lol)
presentation of addisons disease
- Postural hypotension
- Lethargy
- Weight loss
- Anorexia
- Increased skin pigmentation hypoglycaemia
addisons disease and increased skin pigmentation
- Decrease in cortisol
- Reduced negative feedback on the anterior pituitary
- More POMC produced to synthesis ACTH
- POMC also produces alpha-MSH
- Increase in MSH= increase in melanin synthesis- hyperpigmentation
- ACTH can also activate melanocortin receptors on melanocytes- hyperpigmentation
maintence treatment of addisons
- Lifelong replacement
- Glucocorticoid: hydrocortisone, prednisolone
- Mineralocorticoid: fludrocortisone
- Education
- Double dose of glucocorticoid at time of illness
- Emergency HC injection if vomiting
- Steroid card and bracelet
Addisonian crisis
Life threatening emergency due to adrenal insufficiency
causes of addisonian crisis
- Abrupt steroid drug withdrawal
- Severe stress
- Salt depravation
- Infection
- Trauma
- Cold exposure
- Over exertion
presentation of addisonian crisis
Signs and symptoms
- Collapse
- Nausea
- Vomiting
- Pyrexia
- Hypotension
- Vascular collapse
treatment of addisonian crisis
fluid replacement and cortisol
Congenital adrenal hyperplasia (CAH)
Congenital adrenal hyperplasia (CAH) is a group of rare inherited autosomal recessive disorders characterized by a deficiency of one of the enzymes needed to make specific hormones.
- CAH effects the adrenal glands located at the top of each kidney.
- Normally, the adrenal glands are responsible for producing three different hormones:
- corticosteroids, which gauge the body’s response to illness or injury;
- mineralocorticoids, which regulate salt and water levels; and
- androgens, which are male sex hormones.
- An enzyme deficiency will make the body unable to produce one or more of these hormones, which in turn will result in the overproduction of another type of hormone precursor in order to compensate for the loss.
most common cause of congenital adrenal hyperplasia
enzyme 21-hydroxylase
CAH can cause
adrenal crisis and ambigious genitalia
how can CAH cause ambigious genitalia and adrenal crisis
- Block in adrenal cortex pathway
- Presentation depends on enzyme defect
- Lack of enzyme leads to:
- Low cortisol and aldosterone
- High male hormones (androgens)
presentation of CAH
Presentation
- Hypotension
- Hyponatraemia
- Hyperkalaemia
- Hypoglycaemia
- Virilisation – development of male body parts
disorders of the adrenal meduall
Pheochromocytoma and paraganglioma
Pheochromocytoma and paraganglioma presentation
a type of neuroendocrine tumor that grows from cells called chromaffin cells. These cells produce hormones needed for the body and are found in the adrenal glands. The adrenal glands are small organs located in the upper region of the abdomen on top of the kidneys.
- Acute episodes
- Sweating
- Panic attacks
- Palpitations
- High or low BP
- Collapse
Acute crisis
- Hypertensive crisis
- Encephalopathy
- Hyperglycaemia
- Cardiac arrhythmias
- Sudden death
investigations for Pheochromocytoma and paraganglioma
- 24h urine metanephrines
- 2-3 x collections needed
- Plasma metanephrine
- Neuro-endocrine marker: Chromogranin A
Pheochromocytoma and paraganglioma managemetn
- Alpha blockade- phenoxybenzamine
- Always do alpha-block before b-block
- B blockade- bisoprolol
- Surgical excision
- Perioperative management
- Specialist anaesthetic team
- Risk of crisis during operation
- Maximal vasodilation and filling with IV fluids
- Perioperative management
in an acute phaechromocytome crisis why always alpha block. before b-block
Unopposed alpha stimulation can cause hypertensive crisis
