Flashcards in Biochemistry Thyroid Deck (55):
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Thyroid Hormone
T3 is 5x more active as T4
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T4 secretion
T3 secretion
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T3 secretion
<20% secreted from thyroid, majority from peripheral de-iodination of T4.
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3 proteins which bind thyroid hormone
Thyroid binding globulin (TBG)
Thyroid binding pre-albumin
Albumin
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Bound T4 proportions
• 99.98% of T4 is bound (70% TB, 20% TBPA, - 10% Alb
• 99.7% T3 is bound
• Only the free forms (unbound are active)
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Patient 1: serum results
T.S.H 60.0
Free T4 4.4
Free T3 ---
Clinical information: tired, weight gain
Diagnosis
1o hypothyroidism – impaired T4 production and loss of negative feedback
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Primary Hypothyroidism: Biochemical Features
Raised TSH
Low Ft4
Ft3 – not helpful
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Primary Hypothyroidism:Clinical Features
Lethargy, tiredness
Weight gain
Cold intolerance
Coarsening of hair and skin
Slow reflexes, hoarseness
Constipation
Menstrual abnormalities
Bradycardia
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Patient 2 →
T.S.H -10.0 (abnormal)
Free T4 – 13.2 (decreased slightly but not abnormal)
Free T3 ---
Clinical Information
Cold intolerance, constipation
Diagnosis
Compensated Hypothyroidism
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Compensated Hypothyroidism: Biochemical Features
Raised TSH (4-15 min/L)
Low normal FT4
+ve Anti-thyroid peroxidase antibodies
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Compensated Hypothyroidism: Wickham study
Management of this form of hypothyroidism is looking at the annual risk of overt hypothyroidism of TSH >6.0min/L and or TPOAb positive – thyroxine guidelines → TSH +10 even if T4 is low/normal.
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Patient 3 →
T.S.H – 10
Free T4 ---
Free T3 ---
Clinical information: On Thyroxine
Diagnosis
This patient requires increased dose to suppress TSH
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Thyroxin Replacement → Aiming for levels of T.S.H and FT4 of
Ideal – adequate replacement
T.S.H – 2.0 (0.3-4.0)
Free T4 of 16.8 (10.0-24.0)
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Thyroxin Replacement → Inadequate replacement – low dose or poor compliance
T.S.H – 20.0
Free T4 – 5.0
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Thyroxin Replacement → Irregular compliance or recent change in dose (need to be on stable dose for 6 weeks)
T.S.H 12.0
Free T4 16.8
→ Under replaced but normal = adequate therefore need to take results after 6 weeks
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Thyroxin Replacement → Adequate/over replacement increased risk AF (not normal to measure FT3)
T.S.H <0.02 (suppressed)
Free T4 – 23.0
Free T3 – 3.0
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Thyroxin Replacement →Over replacement
T.S.H <0.02
Free T4 34.0
Free T 3 ---
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Thyroxin Replacement → Special situations
Patients with thyroid cancer on thyroxine
Some patients may be given T3 (deliberately supress TSH)
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Thyroxin Replacement → Using T3 for replacement is difficult because
• More potent
• Increased risk
• T0.5 shorter therefore management and dosing difficult
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Patient 4 →
T.S.H <0.02
Free T4 50.2
Free T3 22.0
Clinical Information: Weight loss, palpitations
Diagnosis
Thyrotoxicosis
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Primary Hyper-thryoidism: Biochemical Features
Undetectable TSH
Raised FT4
Raised Ft3
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Primary Hyper-thryoidism: Clinical Features
Weight los
Heat intolerance
Palpitations
Agitation, tremor
Muscle Weakness
Diarrhoea
Thyroid eye disease
Menstrual abnormalities
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Best discrimination of hyperthyroidism
FT3 then FT4
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T3 toxicoisis serum levels
T.S.H <0.02
Free T4 23.0
Free T3 12.0
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T3 toxicoisis diagnosis requires
Need FT3 measurement in patients with high normal – slight increased FT4
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Not Clear thyrotoxicosis
T.S.H <0.02 (low)
Free T3 23.0 (normal/high)
Free T4 6.8 (normal)
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Not Clear thyrotoxicosis management
Recheck in recouple of months to confirm
Remains suppressed (due to risks) then therefore confirm anti-thyroid treatment but evidence not 100% clear.
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Effects of non-thyroidal illness→
• Common in hospitalised patients
• Occurs in a variety of pathological conditions
• Pattern of results
o TSH low (may be increased in recovery phase)
o FT4/FT3 low or normal – metabolic response to illness
o Increased reverse T3 – metabolically inactive
→ Basal metabolism slowed down to protect body from illness.
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Causes of TSH suppression
• TNF
• IL-1
• Low TRH
• Somatostatin
• Glucocorticoids
Dopamine
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Amiodarone
→ hypo and hyperthyroidism (contains lots of iodine → long half-life (weeks) therefore can stop and wait to identify if its drug induced or has hypo/hyper primary.
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Etiological classification of Secondary Hypertension
Endocrine hypertension – primary aldosteronism
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1. Endocrine hypertension
Primary aldosteronism, Phaeochromocytoma, Cushings syndrome, Adrenal
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2. Renal Hypertension
Renal artery stenosis, renal parenchymal disease
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3. Drug induced causes
OC, excess liquorice (mineral corticoids acts like aldosterone)
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Causes hypertension
1. Endocrine hypertension
2. Renal Hypertension
3. Drug induced causes
4. Co-arctation of the aorta
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Mineralocorticoid hypertension: Types
1. Aldosterone-producing adenoma (APA) – 2/3 cases
2. Bilateral idiopathic hyperplasia (IHA) – majority remainder (overproduction form both adrenals)
3. Primary (unilateral) adrenal hyperplasia
4. Aldosterone-producing adrenocortical carcinoma
5. Familial hyperaldosteronism
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Mineralocorticoid hypertension: Familial hyperaldosteronism
6. Glucocorticoid-remediable aldosteronism (FH type 1)
7. Familial APA or IHA (FH type II)
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Mineralocorticoid hypertension:Who should be screened
Hypertension with hypokalaemia (Conn’s as increased Na+ = Reduced K+)
Particularly if sodium is high
60-70% of patients are normokalaemia
Resistant hypertension
Adrenal incidentalomma and hypertension
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Mineralocorticoid hypertension: How should they be screened?
Plasma renin activity
Plasma aldosterone concentration
• Morning blood sample in ambulant patient
• Correct hypokaaemia (?)
• Discontinue anti-hypertensives (?)
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Saline infusion test
Aldosterone secretion is not suppressed in response to an excessive salt and water load.
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Fludrocortisone suppression
Further sodium loading with a sodium retaining steroid will have no effect on plasma aldosterone because patients are in a salt retaining state.
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Interpretation both test:
Serum aldosterone >140 pmol/L at the end of the study confirms a diagnosis of Primary hyperaldosteronsim.
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Localisation of tumour
Selective venous catheterisation – 2 adrenals and look for v. difficult
Ct or MRI (nodules >7 mm, incidentalomas) = detection limit or not aldosterone producing.
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Calcium channel blockers
Decrease aldosterone, may increase PRA
Discontinue for 1 weeks
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Diuretics and vasodilators
Increase PRA and therefore aldosterone
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Beta Blockers
Decrease PRA and aldosterone
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ACE inhibitors
Prevent angiotensin II production, decrease aldosterone and increase PRA
Discontinue for 2 weeks
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Spironolacetone (aldosterone antagonist)
Variable effect depending on duration of treatment
Discontinue for 6 weeks
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Phaeochromocytomas: Incidence and important
Rare tumour (<1% hypertnsives)
Potential to be lethal and for cure if diagnosed
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Phaeochromocytomas: Pathology (rule of 10’s)
• Arises in chromaffin tissue of the sympathetic nervous sytem
• Majority arise from the adrenal medulla, others from paraganglia at other sites (10%)
• Most are benign (10% malignant)
• Most are sporadic
• Some familial (10%) – MEN type II and Von Hippel landau syndrome)
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Phaeochromocytomas:Who should be tested
Hypertension (resistant, malignant, intra-operative, pregnancy)
• Paroxysmal (45%)
• Persistent (50%)
Headache
Diaphoresis or sweating, flushing attacks
Palpitations
Anxiety, feelings or impending doom
Pallor
Tremor
→ May associated with symptomatic episodes of an hour or less on a daily basis to once every few months.
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Phaeochromocytomas: Diagnostic problems
Poorly controlled BP may increase catecholamines by 50-100% (95% reference range therefore innapropriate)
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Phaeochromocytomas: Many medical disorders may increase catecholamine’s
Surgery
Myocardial infarction
Diabetic ketoacidosis
Obstructive sleep apnoea
Stroke
Severe heart failure
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Phaeochromocytomas: 24-hour urine catecholamine or metabolites
• Integral of overall production
• Relatively high concentration
• Relatively high stability (but needs 6M HCI)
• One collection usually sufficient
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