Biochemistry Thyroid Flashcards
Thyroid Hormone
T3 is 5x more active as T4
T4 secretion
T3 secretion
T3 secretion
<20% secreted from thyroid, majority from peripheral de-iodination of T4.
3 proteins which bind thyroid hormone
Thyroid binding globulin (TBG)
Thyroid binding pre-albumin
Albumin
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)
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
Primary Hypothyroidism: Biochemical Features
Raised TSH
Low Ft4
Ft3 – not helpful
Primary Hypothyroidism:Clinical Features
Lethargy, tiredness Weight gain Cold intolerance Coarsening of hair and skin Slow reflexes, hoarseness Constipation Menstrual abnormalities Bradycardia
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
Compensated Hypothyroidism: Biochemical Features
Raised TSH (4-15 min/L)
Low normal FT4
+ve Anti-thyroid peroxidase antibodies
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.
Patient 3 → T.S.H – 10 Free T4 --- Free T3 --- Clinical information: On Thyroxine Diagnosis
This patient requires increased dose to suppress TSH
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)
Thyroxin Replacement → Inadequate replacement – low dose or poor compliance
T.S.H – 20.0
Free T4 – 5.0
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
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
Thyroxin Replacement →Over replacement
T.S.H <0.02
Free T4 34.0
Free T 3 —
Thyroxin Replacement → Special situations
Patients with thyroid cancer on thyroxine
Some patients may be given T3 (deliberately supress TSH)
Thyroxin Replacement → Using T3 for replacement is difficult because
- More potent
- Increased risk
- T0.5 shorter therefore management and dosing difficult
Patient 4 → T.S.H <0.02 Free T4 50.2 Free T3 22.0 Clinical Information: Weight loss, palpitations
Diagnosis
Thyrotoxicosis
Primary Hyper-thryoidism: Biochemical Features
Undetectable TSH
Raised FT4
Raised Ft3
Primary Hyper-thryoidism: Clinical Features
Weight los Heat intolerance Palpitations Agitation, tremor Muscle Weakness Diarrhoea Thyroid eye disease Menstrual abnormalities
Best discrimination of hyperthyroidism
FT3 then FT4
T3 toxicoisis serum levels
T.S.H <0.02
Free T4 23.0
Free T3 12.0
T3 toxicoisis diagnosis requires
Need FT3 measurement in patients with high normal – slight increased FT4
Not Clear thyrotoxicosis
T.S.H <0.02 (low)
Free T3 23.0 (normal/high)
Free T4 6.8 (normal)
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.
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.
Causes of TSH suppression
• TNF • IL-1 • Low TRH • Somatostatin • Glucocorticoids Dopamine
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.
Etiological classification of Secondary Hypertension
Endocrine hypertension – primary aldosteronism
- Endocrine hypertension
Primary aldosteronism, Phaeochromocytoma, Cushings syndrome, Adrenal
- Renal Hypertension
Renal artery stenosis, renal parenchymal disease
- Drug induced causes
OC, excess liquorice (mineral corticoids acts like aldosterone)
Causes hypertension
- Endocrine hypertension
- Renal Hypertension
- Drug induced causes
- Co-arctation of the aorta
Mineralocorticoid hypertension: Types
- Aldosterone-producing adenoma (APA) – 2/3 cases
- Bilateral idiopathic hyperplasia (IHA) – majority remainder (overproduction form both adrenals)
- Primary (unilateral) adrenal hyperplasia
- Aldosterone-producing adrenocortical carcinoma
- Familial hyperaldosteronism
Mineralocorticoid hypertension: Familial hyperaldosteronism
- Glucocorticoid-remediable aldosteronism (FH type 1)
7. Familial APA or IHA (FH type II)
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
Mineralocorticoid hypertension: How should they be screened?
Plasma renin activity Plasma aldosterone concentration • Morning blood sample in ambulant patient • Correct hypokaaemia (?) • Discontinue anti-hypertensives (?)
Saline infusion test
Aldosterone secretion is not suppressed in response to an excessive salt and water load.
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.
Interpretation both test:
Serum aldosterone >140 pmol/L at the end of the study confirms a diagnosis of Primary hyperaldosteronsim.
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.
Calcium channel blockers
Decrease aldosterone, may increase PRA
Discontinue for 1 weeks
Diuretics and vasodilators
Increase PRA and therefore aldosterone
Beta Blockers
Decrease PRA and aldosterone
ACE inhibitors
Prevent angiotensin II production, decrease aldosterone and increase PRA
Discontinue for 2 weeks
Spironolacetone (aldosterone antagonist)
Variable effect depending on duration of treatment
Discontinue for 6 weeks
Phaeochromocytomas: Incidence and important
Rare tumour (<1% hypertnsives) Potential to be lethal and for cure if diagnosed
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)
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.
Phaeochromocytomas: Diagnostic problems
Poorly controlled BP may increase catecholamines by 50-100% (95% reference range therefore innapropriate)
Phaeochromocytomas: Many medical disorders may increase catecholamine’s
Surgery Myocardial infarction Diabetic ketoacidosis Obstructive sleep apnoea Stroke Severe heart failure
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
Phaeochromocytomas: Testing for Phaechromocytoma
- Urine (see slides 106)
* Follow-up of initial positive urine test
