Thyroid Notes

http://www.youtube.com/watch?v=krXoyP5j5lk - St. George’s thyroid exam

Thyroid

HypothalamusTRH (thyrotrophin releasing hormone)Anterior pituitaryTSH (thyroid stimulating hormone)ThyroidT4T3 in peripheries

http://www.youtube.com/watch?v=krXoyP5j5lk

http://upload.wikimedia.org/wikipedia/commons/8/82/Thyroid_hormone_synthesis.png


Primary disease= in the thyroid itselfSecondary=in pituiaty (very rare)

Tests Free T4 and t3 (sometimes in hyperthyroidism), more useful than total

levels as this is affected by protein carrier levels (which is affected by drugs, pregnancy, hepatitis, nephrotic syndrome..etc)

TSH Thyroid autoantibodies – antithyroid peroxidase and antithyroglobulin

antibodies. Maybe increased in autoimmune disease (Hashimotos or Graves)

TSH receptor antibodies (Graves) US – determines cystic (usually benign) from solid nodules Isotope scan – can detect ectopic thyroid tissue or carcinoma. Hot

(increased uptake), cold and neutral nodules – hot and neutral nodules are usually not malignant.

TSH, T4 HypothyroidismTSH, normal T4 Treated/subclinical hypothyroidismTSH, T4 TSH tumour or hormone resistanceTSH, T4 HyperthyroidismTSH, normal T4 Subclinical hyperthyroidismTSH, T4 Sick euthyroidism

Sick euthyroidism = deranged TFTs in illness (usually everything becomes low)

Goitre Can be associated with hypothyroidism or hyperthyroidism. Most causes

can lead to a goitre Most common cause worldwide is iodine deficiency Can be caused by a diffuse enlargement (iodine) or due to nodular

enlargement (neoplasm) Nodules can be inactive or active (aka toxic)

Hyperthyroidism Thyrotoxicosis often used synonymously Causes

o Autoimmune = Graves diseaseo Infective = De Quervain’s thyroiditis

A self limiting, acute, severe post viral hyperthyroidism (coxsackie, adenovirus or URTI). Leads to a characteristically painful goitre

o Neoplastic = toxic adenomao Iatrogenic = drugs such as amiodarone or lithium. Also from over

treating hypothyroidism Symptoms

o Increased metabolismweight loss and increased appetiteo Heat intoleranceo Sweating



o Diarrhoeao Tremoro Irritability/restlessnesso Psychosiso Itcho Oligomenorrhoea

Signso Increased pulse rateo atrial fibrillationo palmar erythemao hair thinningo lid retractiono goiter, nodules or bruiteso Graves

eye signs – exophthalmos (abnormal connective tissue deposition in the orbit and extraocular muscles due to fibrosis following lymphocyte infiltration), ophthalmoplegia (paralysis of muscles by similar mechanism), lid retraction and lid lag. Eyelid retraction is the most common sign of ophthalmopathy. Von Graefe's sign (lid lag sign) is the immobility or lagging of the upper eyelid on downward rotation of the eye . Abnormal wideness of the eye due to retraction of both lids is called Dalrymple’s sign and is noticed due to large area of whiteness above and below the iris (particularly above). In moderate active disease, the signs and symptoms are persistent and increasing and include myopathy. The inflammation and edema of the extraocular muscles lead to gaze abnormalities. The inferior rectus muscle is the most commonly affected muscle and patient may experience vertical diplopia on upgaze and limitation of elevation of the eyes due to fibrosis of the muscle. Protosis is a description of bulging eyes

Pretibial myxoedema - It usually presents itself as a waxy, discolored induration of the skin—classically described as having a so-called peau d'orange (orange peel) appearance

thyroid acropatchy - painful clubbing of fingers or toes and periosteal limb bone reaction

Treatmentso Medical

beta blockers for symptoms either titrate with carbimazole or block with carbimazole and replace with thyroxine SE of carbimazole is agranulocytosis (can septic

neutropaenia, watch out for illness) Propylthiouracil is another alternative Antithyroid medicines inhibit thyroid peroxidase Radioiodine can be used to ablate the thyroid but almost

invariably leads to hypothyroidism. Can thyroid storm


http://en.wikipedia.org/wiki/Skin




http://en.wikipedia.org/wiki/Fibrosis

http://en.wikipedia.org/wiki/Fibrosis

http://en.wikipedia.org/wiki/Diplopia

http://en.wikipedia.org/wiki/Diplopia

http://en.wikipedia.org/wiki/Inferior_rectus_muscle



http://en.wikipedia.org/wiki/Edema

http://en.wikipedia.org/wiki/Edema

http://en.wikipedia.org/wiki/Myopathy

http://en.wikipedia.org/wiki/Human_eye

http://en.wikipedia.org/wiki/Eyelid

http://en.wikipedia.org/wiki/Eyelid


2 major contraindications to radioiodine are pregnancy and lactation

o Surgery Subtotal thyroidectomy

Thyroid storm - also referred to as thyrotoxic crisis, is an acute, life-threatening, hypermetabolic state induced by excessive release of thyroid hormones (THs) in individuals with thyrotoxicosis. Thyroid storm may be the initial presentation of thyrotoxicosis in undiagnosed children, particularly in neonates. The clinical presentation includes fever, tachycardia, hypertension, and neurological and GI abnormalities. Hypertension may be followed by congestive heart failure that is associated with hypotension and shock. Because thyroid storm is almost invariably fatal if left untreated, rapid diagnosis and aggressive treatment are critical.

Graves diseaseo Autoimmune – antibodies stimulating TSH receptorso 60% have eye signso strong genetic component – many genes involved (incl. HLA-DR3)o TSH antibodies not routinely testedo Other antibodies against thyroid peroxidase and thyroglobulin in

75% of patients which can be measured using agglutination/ELISA/immunofluorescence

Hypothyroidism Causes

o Autoimmune Hashimoto’s thyroiditis – goiter. Destruction of thyroid

tissue, mechanism not understood. May start as hyperthyroidism. HLA DR4 and 3. Acute phase may be hyperthyroidism.

Primary myxedema – no goiter, atrophy. Blocking of TSH receptor with autoantibodies (same as Grave’s but opposite effect). HLA DR4

o Environmental/dietary – iodine deficiency. In countries without iodinised salt

o Iatrogenic – thyroidectomy or drugs (amiodorone, lithium)o Congenital cretinism. Now screened for using the Guthrie heel

prick test 5 days postnatally. Symptoms

o Tirednesso Lethargyo Depressiono Cold intoleranceo Weight gaino Constipationo Menorrhagiao Hoarse voiceo Dementia

Signso Bradycardia



o Dry skin and hairo Ataxiao Slow reflexeso Peripheral neuropathy

Treatmento Replace what is missing – give levothyroxine

Thyroid function screeningo Those with other autoimmune conditions – vitiligo, Addison’s or

type 1 (or gestational) diabeteso Those on amiodorone or lithium (6 monthly)o Hyperlipidaemiao Atrial fibrillationo Certain genetic conditions that have a strong association eg

Turner’s and Down’s syndrome

Reference ranges:

Calcium 2.1-2.6 mmol/l

Phosphate 0.8-1.4 mmol/l

CRP < 10 mg/l

Thyroid stimulating hormone (TSH) 0.5-5.5 mu/l

Free thyroxine (T4) 9-22 pmol/l

Total thyroxine (T4) 70-140 nmol/l

Amylase 70-300 u/l

Uric acid 0.18-0.48 mmol/l

SBAs

1. A 23-year-old woman presents with sweating and tremor. Her thyroid function tests are as follows:

TSH <0.05 mU/l

Free T4

25 pmol/l

What is the most common cause of this presentation?



A.

Hashimoto's thyroiditis

B.

Graves' disease

C.

Toxic nodular goitre

D.

De Quervain's thyroiditis

E.

Toxic adenoma

2. A 33-year-old female is referred by her GP with thyrotoxicosis. Following a discussion of management options she elects to have radioiodine therapy. Which one of the following is the most likely adverse effect?

A.

Hypothyroidism

B.

Thyroid malignancy

C.

Agranulocytosis

D.

Oesophagitis

E.

Precipitation of thyroid eye disease

3. A 36-year-old woman presents with feeling tired and cold all the time. On examination a firm, non-tender goitre is noted. Blood tests reveal the following:

TSH 34.2 mU/l

Free T4

5.4 pmol/l

What is the most likely diagnosis?

A.

Primary atrophic hypothyroidism

B.

Pituitary failure

C.

De Quervain's thyroiditis



D.

Iodine deficiency

E.


4. A 43-year-old woman presents for follow-up in clinic. She was diagnosed with Hashimoto's thyroiditis four months ago and is currently being treated with levothyroxine 75 mcg od. What is the single most important blood test to assess her response to treatment?

A.

ESR

B.

TSH

C.

Free T4

D.

Total T4

E.

Free T3

5. A 40-year-old woman complains of feeling tired all the time and putting on weight. On examination a diffuse, non-tender goitre is noted. Blood tests are ordered:

TSH 15.1 mU/l

Free T4 7.1 pmol/l

ESR 14 mm/hr

Anti-TSH receptor stimulating antibodies Negative

Anti-thyroid peroxidase antibodies Positive

What is the most likely diagnosis?

A.

Pituitary failure

B.

Primary atrophic hypothyroidism

C De Quervain's thyroiditis



.

D.


E.

Grave's disease

6. A 52-year-old woman who was diagnosed as having primary atrophic hypothyroidism 12 months ago is reviewed following recent thyroid function tests (TFTs):

TSH 12.5 mU/l

Free T4

14 pmol/l

She is currently taking 75mcg of levothyroxine once a day. How should these results be interpreted?

A.

Poor compliance with medication

B.

Taking extra thyroxine

C.

Evidence of recent systemic steroid therapy

D.

Keep on same dose

E.

T4 to T3 conversion disorder

Answers

1. Graves' disease is the most common cause of thyrotoxicosis in the UK. All the other conditions can cause thyrotoxicosis but are less common.

Thyrotoxicosis

Graves' disease accounts for around 50-60% of cases of thyrotoxicosis.

Causes• Graves' disease• toxic nodular goitre• subacute (de Quervain's) thyroiditis• post-partum thyroiditis• acute phase of Hashimoto's thyroiditis (later results in hypothyroidism)



• toxic adenoma (Plummer's disease)• amiodarone therapy

Investigation• TSH down, T4 and T3 up• thyroid autoantibodies• other investigations are not routinely done but includes isotope scanning

2. It is well documented that radioiodine therapy can precipitate thyroid eye disease but a majority of patients eventually require thyroxine replacement

Graves' disease: management

Despite many trials there is no clear guidance on the optimal management of Graves' disease. Treatment options include titration of anti-thyroid drugs (ATDs, for example carbimazole), block-and-replace regimes, radioiodine treatment and surgery. Propranolol is often given initially to block adrenergic effects

ATD titration• carbimazole is started at 40mg and reduced gradually to maintain

euthyroidism• typically continued for 12-18 months• patients following an ATD titration regime have been shown to suffer fewer

side-effects than those on a block-and-replace regime

Block-and-replace• carbimazole is started at 40mg• thyroxine is added when the patient is euthyroid• treatment typically lasts for 6-9 months

The major complication of carbimazole therapy is agranulocytosis

Radioiodine treatment• contraindications include pregnancy (should be avoided for 4-6 months

following treatment) and age < 16 years. Thyroid eye disease is a relative contraindication, as it may worsen the condition

• the proportion of patients who become hypothyroid depends on the dose given, but as a rule the majority of patient will require thyroxine supplementation after 5 years

3.

Hashimoto's thyroiditis = hypothyroidism + goitre + anti-TPO

The combination of a goitre with hypothyroidism points to a diagnosis of Hashimoto's. De Quervain's thyroiditis typically causes a painful goitre.




Hashimoto's thyroiditis is an autoimmune disorder of the thyroid gland. It is typically associated with hypothyroidism although there may be a transient thyrotoxicosis in the acute phase. It is 10 times more common in women

Features• features of hypothyroidism• goitre: firm, non-tenderanti-thyroid peroxidase and also anti-Tg antibodies

4. Hypothyroidism: management

Key points• initial starting dose of levothyroxine should be lower in elderly patients and

those with ischaemic heart disease (e.g. 25-50 mcg/day)• following a change in thyroxine dose thyroid function tests should be checked

after 6-8 weeks• the therapeutic goal is 'normalisation' of the thyroid stimulating hormone

(TSH) level. As the majority unaffected people have a TSH value 0.5-2.5 mU/l it is now thought preferable to aim for a TSH in this range

• there is no evidence to support combination therapy with levothyroxine and liothyronine

Side-effects of thyroxine therapy• hyperthyroidism: due to over treatment• reduced bone mineral density• worsening of angina• atrial fibrillation

5. this patient has Hashimoto's thyroiditis, as evidenced by the hypothyroidism, goitre and anti-thyroid peroxidase antibodies. De Quervain's thyroiditis typically causes a painful goitre and a raised ESR. Around 90% of patients with Grave's disease have anti-TSH receptor stimulating antibodies.

6. Thyroid function tests

The interpretation of thyroid function tests is usually straightforward:

TSH Free T4

Thyrotoxicosis (e.g. Graves' disease) Low High In T3 thyrotoxicosis the free T4 will be normal

Primary hypothyroidism (primary atrophic hypothyroidism)

High

Low

Secondary hypothyroidism Low Low Replacement steroid therapy is required prior to thyroxine



Sick euthyroid syndrome* Low**

Low Common in hospital inpatients

Poor compliance with thyroxine High

Normal / high

Steroid therapy Low Normal

*now referred to as non-thyroidal illness

**TSH may be normal in some cases

OSCE 1. Wash hands, introduce, gain permission, expose (down to clavicles),

reposition (sitting). Ask if they have any pain2. General inspection

a. Body habitus – overweight = hypo, under=hyperb. Clothing – appropriate for weather? Over dressed = hypo,

under =hyperc. Hair – greasy=hyper, dry=hypod. Eye brows – lost outer 2/3rds = hypoe. Anxious/restless

3. Inspection of hands (VET SOAP)



V – vitiligo (indicator of autoimmune disease)E – erythema of palmsT – tremor (ask patient to hold hands out and can put a piece of paper

on top to highlight fine tremor)S - sweatingO - onycholysisA – acropatchy – Graves disease specificP – pulse (bradycardia=hypo, tachycardia/AF=hyper)

4. Inspection of necka. Scars, Sinuses, Swellings, Skin changesb. Ask patient to stick tongue out – thyroglossal cysts move upc. Ask patient to swallow water – goitres move up as attached to

pre-tracheal fascia5. Inspection of eyes (Grave’s disease)

a. Look – from above and to sides do the eyes protrude beyond the supraorbital ridge i.e. proptosis/exophthalmos

b. Ask patient to follow an H and ask them to tell you if they see any diplopia to test for Ophthalmoplegia

c. Ask patient to follow finger from top to bottom for lid lag6. Palpate the neck

a. Stand behind and palpate bimanuallyb. Describe size, shape, site, smoothness, symmetry, consistency,

fluctuance, tenderness, tethering. Thyroid specific – diffuse or single. Smooth or multinodular. Could offer to transluminate (cysts).

c. Palpate asking patient to stick tongue out and swallow waterd. Palpate for lymph nodese. Palpate for centrally located trachea

7. Percuss retrosternally for retrosternal goitre8. Auscultate for thyroid bruit while patient holds their breath(very

suggestive of Grave’s)9. Legs

a. Inspect for pretibial myxoedemab. Ask patient to hold arms out like a chicken against resistance

and stand from sitting with their arms crossed– proximal myopathy (hypothyroidism)

c. Test reflexes. Brisk = hyper, slow=hypo10. Thank the patient, offer to help them get dressed11. Wash hands


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