99.98% of T4 is bound (70% TB, 20% TBPA, - 10% Alb 99.7% T3 is bound Only the free forms (unbound are active)

Biochemistry Thyroid Flashcards by tish bullman

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

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

1. Endocrine hypertension

Primary aldosteronism, Phaeochromocytoma, Cushings syndrome, Adrenal

2. Renal Hypertension

Renal artery stenosis, renal parenchymal disease

3. Drug induced causes

OC, excess liquorice (mineral corticoids acts like aldosterone)

Causes hypertension

1. Endocrine hypertension 2. Renal Hypertension 3. Drug induced causes 4. Co-arctation of the aorta

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

Mineralocorticoid hypertension: Familial hyperaldosteronism

6. 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