Broadly discuss clinical manifestations of hyperthyroidism
Runs spectrym form subclinical hyperthyroidism to thyrotoxicosis. Thyrotoxicosis is a hypermetabolic condition that results form eleaveted levels of thyroid hormones t4 and t3
Discuss broad fucntion of the thyroid hormone
Influences metabolism of cells by increasing their basal metabolic rate.
It has a role in protein synthesis and fucntions together with other hormones necessary for normal growth and developmet
increases the expression and sensitivity of B adrenergic receptors dramatically increasing response to endogenous catehcolamines
Discuss aetiology of hyperthryoidism - overproduction
Toxic multinodular goiter
Overproduction
#Graves disease
-most common form of hyperthyroidism
-autoantibodies bind to the TSH receptor and stimulate thyroid hormone production and release
-Strong genetic relationship with frequent occurence in the setting of toher autimmune disorders and positive family hitory
- TMG is the second leading cause of hyperthyroidism
- It is characterized by multiple autonomously funcitoning nodules usually in women older than 50 years of age
- hyperthyroidism with TMG is much midler than Graves
# Toxic adenoma -Is a single hyperfunctioning nodule within the thyroid - it typically affects the same population as TGM
Discuss Aetiology of hyperthyroidism - injury to the gland
Thyroiditis
- any inflammatory process taht results in thyroid gland inflammation can lead to thyroiditis
- Inciting process may be autoimmune, drug induced, infectious or traumatic
- Inflamation leads to follicular cell breakdown with reusltant release of preformed thyroid hromone.
- Commenest cause is hashimotos - most present with painless goiter and hypothyrodism but some have transiet hyperthroidism
- 5-10% of womenw ill develop postpartum thyroiditis
- THe diagnostic triad consists of the lack of previous history of thyroid disease and abnormal TSH concentration during the first postpartum year and the absence of TSH receptor antibodies or a toxic nodule.
- Triphasic coure
1) thyrotoxicosise 2-6 months postpartum
2) hypothyroid state lasting 2-3 months
3) finally euthyroid state by the end of the first postpartum year.
- Caused by a viral infection of the thyroid
- viral prodrom followed by anteiror neck pain
- neck pain radiates to the jaw ears or occiptal area.
- exquisitely tender thyroid and pain occurs on head movement or swalloing.
- rare potentially life threatening infection of the thyroid
- present with fever and anterior neck pain, swelling, induration, erythema dysphonia and dysphagia.
- Infectious causes are overwhelmingly bacterial and very rarely parasitic, mycobacterial or fungal.
- most have pre-exisiting thyroid disease and are immunocompromised
-Amiodarone contans are a high amount of iodine
5-20% of patient on amiodarone develop thyrotoxicis
factitious thyroiditis
Discuss symptoms of hyperthyroidism
Consitutional
- weight loss despite hyperphagia
- fatigue
- generalized weakness
Hypermetabolic
- Heat intolerance
- excessive percperation
Cardioresp
- Palpitation
- Dyspnoea/dyspnoea on exertion
- Chest pains
- poor exercise tolerance
GIT
- nausea and vomiting
- diarrheoa
- dysphagia
Neuropsych
- ANxiety
- restlesness, hyperkinesis
- emotional lability
- confusion
- insomnia
- poor attention
Neuromuscualr
- myopathy
- myalgias
- tremor
- proximal muscle weakness
Opthal
- tearing
- irritation
- wind sensativity
- diplopia
- foriegn body sensation
Thyroid gland
- neck fullness
- dysphagia
- dysphonia
Repro
- oligomenorrhea
- amenorrhea
- decreased libido
- gynaecoastia
- infertility
Discuss physical finding
Classical pretibial myxoedema in which mucopolysaccharide infiltration of the dermis yeilds marked thickening of the pretibial skin - almost alway associated with GraveOpthalmopathy
Vitals:
- Tachy with widened pulse pressure
- Bounding puses
- Fever
CVS
- Hyperdynamic precordium
- systolicflow murmur
- prominent heart sounds
- systolic rub
- AF
- Hyperdynamic heart faiure
Opthal
- Widened palpebral fissures
- lid lag
- globe lage
- conjunctival injection
- periorbital oedema
- proptosis
- limitation of superior gaze
Neuro
- fine tremor
- hyperreflexia
- proximal muscle weakness
Psych
- fidgety
- emotionally labile
- poor cpncentration
Derm
- Warm, moist smooth skin
- fine britlle hiar alopecia
- hyperpigmented pretibial plques
Neck
- diffuse symmetric thyroid enlargement
- can have pembertons sign if significnt retrosternal goitre
Discuss thyroid storm
Rare life threatening form of severe thyrotoxicosis
Although it can occur as the result of unrecognized or undertreated thyrotoxicosis more often is an acute reaction to thyroid or non thyroid surgery, trauma, infection, iodine load (contrast or amiodarone) or parturition
Other precipitants include
- ACute MI
- PE
- Hyperemesis gravitum
- toxemia of pregnacny
- DKA
Untreated mortaility reaching almost 100% - prompt recognition and therapy lowers this to 10-30%
Typical clinicall features are signifiacnt fever 40-41 degree, extreme tachycardia and altered Mental state.
These finding coupled with signs of hyperthyroidism should raise concern for storm
Cardiovasculur collapse can reuslt in CCF hypotension and arryhtmia
Discuss the Burch & Wartofsky diagnostic criteria for thyroid storm
Score of 45 likley in storm- 25 to 45 predicts impending storm, below 25 is unlikley
Temperature 37.2 -0 -37.2-37.7 +5 37.8-38.2 +10 38.3-38.8 +15 38.9-39.2 +20 39.3-39.9 +25 >40 +30
CNS/mental state
- Normal 0
- agitation +10
- extreme lethargy +20
- seizure +30
Tachycarida 90-109 +5 110-120 +10 120-129 +15 130-139 +20 >140 +25
CCF absent 0 Mild (oedema) +5 Moderate (rales) +10 Puolmonary oedema +15
GIT
Absent 0
Nasuea and vomting or diarrhoea/abdo oain +10
unexplained jaundice +20
AF +10
Precipitating event
no0
ýes +10
Discuss DDX of hyperthyroidism
- Hyperadrenergic states
- sympathomimetic OD
- Anticholinergic crisis
- withdrawals from EOTH or sedative hypnotic
- Heat Stroke
- NMS
- Serotonin syndrome
- Bacterial mengitis and sepsis
DIscuss supprotive and symptomatic treatment of hyperthyroidism
Supprotive therapy for thyroid storm patients include management of hyperthermia with active cooling and paracetamol
- Aspirin should be avoided as it impairs the protein binding of t3 and t4
- Agitation is controlled with benzo
- Fluid resus is needed to compensate for insensible and GIT losses
- Electrolyte treatment as needed per labs
Symptomatic treatment
- consist primarily of beta blocakde to diminish the adrenergic response
- Propanolol has been the blocker of choice as it has the added benefit of blocking converison of t4-t3 - is non selevtive and improves tremor, weakness, hyperpyrexia restlessness irritability and emotional lability, dose of 60-80mg po every 4 hours - onset after about 1 bhour
- FOr rapid effect bolus 0.5-1mg via slow IV push
- Short acting agent such as esmolol may be used when concerns about B blockade exist. loading dose of 250 to 500 mic than 50-100mic/kg/min
DIscuss thyroid direceted therapy in thyroid storm
Three goals reduce thyroid hormone production, prevent thyroid hormone release and block conversion of t4-t3
Reduce thyroid hormone production
- thionamides inhibit oxidation and organic binding of iodine to thyroglobulin- thereby blocking the sy thesis of thyroid hormone
- Propylthiouracil (PTU) has the added benifit of impairing conversion of T4-t3
- Initial loading dose of TU is 500-1000mg orally followed by 250mg Q4hourly
- Methimazole has a longer duration of action
- Methimazole dose is 80-120mg divided every 4-6 hours
- Side effects of thionamides range from miold to life threatening. - mild reaction include urticaria or macular rash, arthralgia and GI upset
- life threatening side effects include agranulocytosis and can occur with either drug - assocaited with ongoing therapy usually occurs wihtin the first 90 days
- PTU induced hepatotoxicity has earned the drug a black box warning
Inhibiting thyroid hormone release
- Inorganic iodine blocks the release of stored thyroid hormone release.
- As an iodine load can increase the synthesis of thyroid hormone these agents should not be administered until after thionamide therapy
- Lithium can be considered as an alternative for iodine allergic patients
- Lugol’s solution
Inhibition of Conversion of t4-t3
- Corticosteoids are capable of inhibitng the peripheral conversion of T4 TO T3 and blocking the relase of horone form the thyroid gland. WHen steroids are used in conjunction with PTU and iodine the concentration of T3 can return to normla in 48 horusl.
- also treated adrenal insuffiecny that can be seen in thyroid storm due ot increased clearance of cortisol in these critically ill patients
- Hydrocort dose is 300mg IV than 100mg TID for several days
Discuss miscellaneous therapies for hyperthyroidism
Cholestyramine an anion exchange resin interrupts the enterohepatic recirculation of thyroid hormone by binding it in the bowel lumen
Results in more rapid decline comapred to thionamides alone it require weeks of therapy and as asuch is reserverd for OPD treatemnt
1-4G BD
Plasmapheresis and dialysis have been used in thyroid storm as an attempt to remove cirucalting hormone
Briefly discuss pathophys of hypothyroidism
Intrinsic gland failure accounts for up to 99% of all cases of hypothyroism. Factors that may result in priamary hypothyroidism include
1) autoimmune
2) infiltrative disorders
3) congenital thyroid dysufnction
4) pregnancy
5) radiotherapy
6) medications
7) infection
8) surgery
9) inadeqaute dietary iodine intake
10) thyroid medication noncompliance
Central causes are rare and result from hypothalamic dysfunction in the secretion of TRH or pituitary dyfunction in secretion of TSH. Other causes include Sheehan’s syndrome or postpartum pituitary haemorrahge.
List features of hypothyroidism
Typically develop insidiously and include in general
- fatigue
- weakness
- constipation
- heavy mensturation
- weight gain
- cold intolerance
- htn
- bradycardai.
The thyoid has a fundamental role in maintaining cardiovascular homeostasis in physiological and pathalogical states. It influence contractility heart rate diastolic function and SVR.
Accelerated atherosclerosis is also seen
Pregnancy
- TSH is vital to the growing foetus
Describe myxoedema coma
Severe hypothyroidism leading to decreased mental status, hypothermia and other symptoms related to slowing of function in multiple organs.
Discuss clinical features of myxoedema coma
Hallmark finding are
1) decreased mental state
- Despite the name patients frequently do not present in coma but do manifest less degrees of ALOC
- Can present with prominent psychotic features so called myxoedema madness
- seizure may occur sometimes due to cocurrent hyponatraemia
2) Hyponatraemia
- present in half of patients and can be severe enough to contribute to mental state
3) hypothermia
- Present in most patients
4) hypoventilation
- Hypoventilation with respiratoyr acidosis results primarily from the central depression of ventilatory drive with decreased responsiveness to hypoxia and hypercapnia
5) hypoglycaemia
- Can be due to hypothyroidism alone but more comonly with concurrent autoimmune disease
6) CVS abnormalities
- may have diastolic htn even though CO is reduce and a narrowed pulse pressure.
- May have bradycardia with decreased contractility and low output
- somtimes hypotension
List aggravating factors for Myxoedema coma
Neuro
-CVA
Infection
CVS
- MI
- CCF
Trauma or burns
Metabolic
- hyponatreamia
- hypoglycaemia
- hypercalcaemia
- DKA
Drug affect
-altered sensorium (sedative hypontics, narcotis, neuroleptics)
-Decreased t4-t3 release (amiodarone, lithium, iodides)
-enhanced eliiantion of t4-3 (phenytoin, rifampin)
-
Discuss management of hypothyroidism and myxoedema coma
Hypothyroidism - levothyroxine
Coma:
1) Thyroid hormone replacement
- 200-400 mic IV with the lower dose being used for smaller older patients or those with history of coronary artery dsiease or arrhythmia .
- controversy about co-administration of t3
2) Steroids
- Until possibility of co-existing adrenal insuffiency has been excluded stress dose steroids should be given
- 100mg of hydrocort Q8hourly
3) Fluids + pressors
- caution with unmaksing CHF
4) supprotive
- rewarming
- management of hyponatraemia if present
5) treatment of triggering underlying event
List causes of primary adrenal insufficiency
Primary CHRONIC 1) Autoimmune (addisons) 2) metastatic cancer 3) Infilatraive -sarcoid, haemochromatosis, amyloid 4) Congenital 5) bilateral adenalectomy 6) drug toxicity (ketoconazole, rifampicin)
ACUTE
1) adrenal haemorrahge
- meingococcemia and other sepsis
- anticoagulation
- anticardiolipin antibody
- trauma
List causes of secondary adrenal insufficiency
CHRONIC
1) pituitary tumor
2) pituiatry surgery or irradiation
3) Chronci steroid use
4) Infiltrative
5) TBI
6) post partum sheehan’s
7) empty sella syndrome
ACUTE
1) pituiary apoplexy (haemorrahge into pituiraty tumour)
2) postpartum pit necrosis
3) Traumatic brain injury
4) Relative
- sepsis
- hepatic failure
- severe acute pancreatitis
- trauam
Discuss ix of adrenal insuffiency
Free cortisol level
- measured within one hour of waking
- <150 nmol/L strongly suggest adrenal insufficiency
- > 500 nmolL excludes the diagnosis
- 200-500nmol/L requires an ACTH stimulation test
ACTH (Synacthen) stimulation test
- Synacthen givin IM 250mic in 1 ml
- Cortisol level is take at 30-60 minutes post
- baseline or post synacthen cortisol of >550 indicates a normal adrenal response
Classic lab finding are
- hyponatraemia
- hyperkalaemia
- acidosis NAGMA
- Hypoglycema
Discuss treatment of adrenal insuffiency
Steroid replacement
- 100mg hydrocort q8 hourly
- 10 mg dex as a stat followed by 4mg q8hrly - preferred as does not interfere with cortisol assay.
Fluid replacement
- 20-40ml/kg
- pressor
BSL control
-hypoglycaemia can be present due to loss of counter-regulatory hormones
