ANATOMY:

Isthmus found at 2nd,3rd and 4th cricoid cartilage.

Connected to trachea by ligament moves on swallowing
ARTERIAL SUPPLY: superior thyroid artery from external carotid art.
Inferior thyroid artery from thyrocervical (branch of subclavian)
VENOUS SUPPLY: superior thyroid vein into IJV
inferior thyroid vein drains into left brachicephalic vein.
NERVE: Superior laryngeal nerve and recurrent laryngeal n. (Parasympathetic)
LYMPHATIC: lateral deep cervical nodes and pre- and paratracheal lymph nodes.

Physiology:

TRH released by (arcuate nucleus and median sulcus) hypothalamus act on anterior
pituitary (activates G protein using PLC,breaks down PIP2 to IP3 and
DAG DAG act on PKC and IP3 increases Ca2+ increase TSH release.
Nb. Anatgonist of TSH release :
1. Somatostatin
2. Dopamine.
3. T3/T4

TSH release by Ant. Pituitary acts on thyroid to increase cAMP which exhibits these effects:
-increase metabolic activity to produce thyroglobulin and generate peroxide (oxidize I- to
I-0 .
- Increase I- uptake and iodination of thyroglobulin(produce MIT)
- Conjugation of iodinated Tg to prodice DIT.
-Endocytosis of DIT and MIT from colloid to follicle.
-protelysis of DIT and MIT to release T3 and T4

T3/T4: -99.5% of T3 is attached to Thyroxin binding globulin (TBG)

-99.98% of T4 attached to TBG
-T3/T4 taken up by carrier mediated transport or diffusion.
- T4 converted by monodeiodinase to T3
- T3 will activate Thyroid hormone Receptor to activate thyroid response
element (DNA) to produce enzymes, proteins and receptors.

Effects of thyroid hormone:

GLUCOSE:

LIPIDS:
PROTEINS:
CNS:

OTHERS:

- Increase GI uptake of glucose

- Increase Glycogenolysis and gluconeogenesis. (LIVER)
- Increase muscle and adipose tissue utilization of glucose.
- Increase lipolysis to prodice FFA.
- Increase oxidation of FFA in tissues.
- Increase protein turnover with overall anabolism.
Important in CNS and PNS dvlpmt. in adults, HYPOthyroidism will cause poor
mental ability and lack of memory and initiative.
in children, HYPOthyroidism will result in neuronal hypoplasia, delayed
myelantion and retardation.
- Increase in specific enzymes, hormonal receptors and membrane receptors.
-Acts as permissive hormone for GH, prolactin, gonadal and adrenal steroids.
-Potentiates effect of catecholamines.

Thyroid Lumps:

Most lumps are benign (95%) :

- Thyroid Adenoma
- Thyroid cysts
- Thyroiditis
- Hyperplastic nodules.

Risk Factors:
- Malignancy increases with age and with previous benign dz.
- Thyroid cancers more common after radiation exposure.

Symtpoms:
- Usually asymptomatic
- Sometimes may cause pain and present with compression of trachea.

-RED FLAG SYMPTOMS:

- Painless mass enlarging over a period of few weeks.
- Child with nodules
- Previous family history of thyroid cancer.
- Unexplained hoarsness or stridor (GOITRE)
- Environmental exposure to radiation.
- Papable cervical lymphadenopathy.
- Persistant/ insidious neck pain for several weeks.

Diferential of enlarged thyroid:

- Cancers: - Thyroid Carcinoma
- Medullary cell carcinoma.
- Thyroid lymphone (non-hodgkins lymphoma)
- Infection: - De Quervains thryroditis : neck pain, fever, and lethargy after URI
or viral illness.
- Acute suppurative thyroiditis: fungal/bacterial infections abscess.
-Immune: -Graves disease
-Hashimotos thyroiditis.
-Goitres: Non-toxic (nonfunctioning) and toxic (functioning) goiters.

Investigations:
- TFTS: most lumps will be euthyroid.
- US: used to detect and characterize most nodules. (shows cystic lesions
2mm wide and solid lesions 3mm wide.
- Fine needle aspiration: usually under US guidance but if palpable can be
done without US
- Translumination: to check for cysts.
- Radionulide imaging: I-123 injected and signal detected
o Normal are warm
o Take up excess amount of iodine: HOT
o Do not take up iodine: COLD
o Nb.cannot distinguish or confirm cancer using I-123
o CT and MRI used to detect local and mediastinal spread to lymph
nodes.

NECK LUMPS AND BUMPS:

Usually benign but could be Malignancy (MC in >40 yrs) vs inflammatory,congenital

and traumatic (MC in younger patients).

If lump ,3 weeks then MC due to self-limiting infection any longer required

referral/

DDx:
Superficial lumps: sebaceous cyst, lipma,abscess, dermoid cyst.

Lymph nodes

Anterior triangle
-If submandibular more likely to be lymph nodes BUT coud be cancer if
older(especially if feels firm and non tender)eg.TB, salivary calculus or tumor
- If doesnt move on swallowing :
1. Carotid aneurysm.
2. carotid body tumour
3. Branchial cyst
4. Cystic hygroma
5 . SCM tumour.
6. Laryngocele.

Posterior triangle:
- Multiple lumps: lymph nodes
1. TB
2. HIV
3. Lymphoma.
4. Metastasis. (could be metastasis from nasopharyngeal carcinoma)
-

Cervical rib
Branchial cyst: It forms when the second branchial cleft fails to disappear
in utero. Discharging sinuses and fistulae may occur. Aspiration may be
pus-like and can be rich in cholesterol crystals. The lump itself is soft and
fluctuant and may transilluminate.
Cystic hygroma : congenital multiloculated lymphatic lesion that can arise
anywhere, but is classically found in the left posterior triangle of the neck.
Due to malformation of lymphatic vessels.
Subclavian artery aneurysm
Pharyngeal pouch.

Investigations:
- Lumps need ENT exam before biopsy.
- FNA, excision biopsy, CXR, US/CT/MRI (US better than CT for malignant
cerv. Lymph nodes)
- Culture samples.

GRAVEs Dz:

AI mediated by B and T lymphocytes. produce IgG directed at TSH receptor

produce effects of TSH (GROWTH of follicles and increase thyroid hormore
production)
Genetic component (CD40, CTLA-4) and HLA-B8
Interaction b/w genetic and environmental factors include:
-Bacteria: Y.enterocolitica, E.coli other gram ves have TSH binding
sites may activate dz.
- Smoking, stress, pollutant, allergens, iodine and selenium intake and
trauma (including surgery)

EPIDEMIOLOGY:
70% of hyperthyroidism. (MC cause)
100-200 per 100000 in uk
women:men 8:1
presents 20-40 yrs.

Differential diagnosis
A long differential list is possible depending on the particular manifestations.

Anxiety
Depression
Hashimoto thyroiditis
Phaeochromocytoma

Pituitary tumours
Papillary carcinoma of thyroid
Drugs (cocaine, amfetamines and other stimulant drugs)
Heart disease
Carcinoma of the colon (causing change in bowel habit)
Other causes of hyperthyroidism (drugs, toxic multinodular goitre, thyroiditis,
iodide)
Amiodarone[5]
Exogenous thyroxine
Toxic thyroid adenoma

INVESTIGATION:
-TFTS:

-FBC:

o TSH assays best way to screen.(suppressed in ppl with thyrotoxiscosis)

o Free T3 and T4 may be increased.
o Thyroid stimulating immunoglobin levels.

o Normocytic normochromic anaemia.

o Low WCC and platelets but get relatve lympho- and monocytosis.
-Biochemistry:
o Reduced cholesterol and TG.
o Reduced free testosterone
o Reduced sex hormone binding protein
o Reduced PTH ?
o Hypocotisolaemia in SEVERE dz.
o HBA1c may be raided indicates worsening diabetic control
o LFTs.
IMAGING:
-

Radioactive iodine useful in differentiating causes of hyperthroiddism.

US and CT.

COMPLICATIONS:
-SE of treatment : mainly agranulocytosis (due to drugs)
- Maternal Graves can lead to neonatal HYPERthyroidism.
- Thyroid cancer
- Heart dz (AF and HF)
- Osteoporosis (which in postmenopausal women will be SEVERE)
- Sarcopenia and myopathy
- Psych cognitive (anxiety and mood)

TESTS (TFTs)

DRUGS AFFECTING THYROID LEVELS

Drugs with a direct effect on thyroid function (mostly suppression) include:

Amiodarone.
Lithium.
Corticosteroids.
Iodinated contrast media and other iodine preparations.
Interferons.
Dopamine, levodopa.

Drugs which may cause analytical interference (increased FT4 by displacement) include:

Heparin.
NSAIDS.
High-dose aspirin (>2 g/day).

Drugs which increase thyroxine replacement requirement (cytochrome P450 inducers):

Phenytoin.
Carbamazepine.
Ritonavir.
Rifampicin.

Intestinal absorbers* include:

Sucralfate, colestyramine and colestipol, antacids containing aluminium.

Ferrous sulfate.
Proton pump inhibitors.

AMIODARONE:
-Has high levels of iodine (one 100 mg tablet contains 250 x the recommended daily intake)
- Has direct toxicity on the thyroid.
It can induce hyperthyroidism (primarily in iodine-deficient areas of the world) or hypothyroidism.
Changes to TFTs in euthyroid patients on amiodarone

Raised FT4 and reverse T3

Initial rise followed by a normalisation of TSH
Lowered FT3
No change in TBG levels

Amiodarone-associated hyperthyroidism is difficult to diagnose and should be based on high FT4 associated with
high or high/normal FT3 and undetectable TSH since, even in euthyroid individuals, amiodarone therapy causes
moderate elevation of FT4 with reduced FT3 because of its effect on the peripheral deiodination of T4 to T3. If this
condition is suspected, refer for specialist assistance, since further investigations may be required and management
is frequently complicated.

HYPERTHYROIDISM

Elderly - commonly have atrial fibrillation and heart failure.

Children - may present with excessive growth or behavioural problems.
if untreated or undiagnosed can lead to thyrotoxic crisis/storm :
-Fever >38.5 , tachycardia, delirium,coma,seizures,vomiting, diarrhea, jaundice
CAUSES:
-

Graves dz

Toxic nodular goiter

Solitary thyroid nodule: palpable toxic adenoma.

De Quervain thyroiditis

Transient HYPERthyroidism after viral infection.

Presents with hyperthyroidism with pyrexia and pain in neck.

Medication.
Follicular carcinoma of thyroid gland: Associated with metastatic dz.
Drugs eg. Amiodarone, lithium, exogenous iodine, dopamine,corticosteroids.
Ovarian teratoma.

HYPOTHYROIDISM
Causes:

- AUTOIMMUNE:
o hashimotos thyroiditis (goiter): painless goiter of variable size with
rubbery consisterncy . Thyroid function could be normal,subclinical
or hypothyroid.
o Atrophic thyroiditis: end-stage of AI thyroiditis hypothyroidism.
- IATROGENIC: radio-iodine, surgery, radiotherapy to neck.

- INFECTION: de Quervains thyroiditis: viral infection nodular thyroid

which is tender (Starts as thyrotoxic as follicles rupture then becomes
hypothyroid)
- Iodine deficiency.
- DRUGS: amiodarone, lithium, antithyroid meds, iodides.
- CONGENITAL: absent gland or altered response to hormones.
- OTHERS: infiltration by amyloidosis, sarcoidosis and haemochramotosis.
- 2ndry: TSH deficiency
o Hypopituitarism: neoplasm, infiltrative, infection and radiotherapy.
o Hypothalamic dz: neoplasms and trauma.
- Transient: withdrawal of meds, postpartum thyroiditis, subacute/chronic
thyroiditis.
Symptoms

Tiredness, lethargy, intolerance to cold.

Dry skin and hair loss.
Slowing of intellectual activity, eg poor memory and difficulty concentrating.
Constipation.
Decreased appetite with weight gain.
Deep hoarse voice.
Menorrhagia and later oligomenorrhoea or amenorrhoea.
Impaired hearing due to fluid in middle ear.
Reduced libido.

Signs

Dry coarse skin, hair loss and cold peripheries.

Puffy face, hands and feet (myxoedema).
Bradycardia.
Delayed tendon reflex relaxation.
Carpal tunnel syndrome.
Serous cavity effusions, eg pericarditis or pleural effusions.

nb. thyroid peroxidase Ab or anti-thyroblogulin Ab are found in 90-95% of AI thyroiditis

Treatment of hypothyroidism:
Give sufficient dose of thyroid (usually LEVOTHYROXINE-T4) to lower TSH to

within normal range(if symtpoms still there after a while then suspect non-thyroid
illness)
Initial dose of levothyroxine= 50-100 micrograms daily, adjusted in steps of 25-50
micrograms every 3-4weeks maintenance dose = 100-200 micrograms daily.
If canrdiac dz, sever hypothyroidism and patients over 50 25 micrograms once
daily, adjusted in steps of 25 micrograms every 4 weeks maintenance= 50-200.

DRUGS USED IN THYROID Dz:

Hyperthroidism:
Toxic nodular goiter (discrete) surgical removal.
Graves dz: reduce T3/T4 w antithyroid therapy or radio-iodine therapy.

Antithyroid therapy (thioureylenes)

-Propylthiouracil and Carbimazole (converted to active metabolite
METHIMAZOLE)
Inhibit peroxidase inhibit iodination of Tg (reduce production if new
DIT and MIT) AND inhibit proteolysis of already formet MIT/DIT.
Propythiouracil also inhibit T4 T3 conversion. propythiouracil faster
than carmbimazole because already formed T3/T4 needs to be used up in
carbimazole.
SE 1. Cross placenta and are excreted in breast milk(Propythiouracil less
because bound to plasma albumin)
2. Skin rashes
3. Agranulocystosis and neutropenia
4. enhanced effects of PTU if giving drugs which compete with
albumin (NSAIDS, sulphonamide Abs, warfarin, oral hypoglycaemic)
Other Treatments
-B-blockers: Propranolol/Atenolol block effects and also can reduce conversion of
T4 to T3
-NA neurone blockers: Guanethidine to help in exophthalmos (relax SM of eyelid
retractor) nb. Severe cases use PREDNISALONE to reduce inflammatory swelling.
-Iiodide (normal 150-300 micrograms/day): but high amount (5-10 mg/day) will
inhibit T3/T4 release (effect is rapid and sustained for only 2 weeks after which the
thyroid will recover BUT thyroid is smaller and firmer use mainly prior to
surgery to reduce bleeding and in treatment of thyroid storm.

-Radioiodine : I-131(normal is I-127) emits B-particles and gamma rays at T1/2 of 8

days.--> used to destroy thyroid partially but overtime will develop
HYPOTHYROIDISM.
SRUGERY
Goitre:
o Euthyroid multinodular goiter do not need intervention BUT do US to
asses size of nodules.
o Large multinodular goiters: use MRI and CT to asses size and compression.
o If TOXIC MN goiter: do biopsy and surgical excision followed by radioiodine.
Surgery is indicated if:
o Compression of surrounding structures (especially trachea)
o Goitre is growing slowly
o Cosmetic reason
o Substernal goiters (hard to biopsy)
Types of surgery:
o Lobectomy: remove nodules of goiters occurring in one lobe.
o Partial lobectomy: remove solitary nodile in one part of thyroid.
o Lobectomy w/isthmectomy: benign Hurthle cell tumours and for
nonaggressive cancer.
o Total thyroidectomy (better than subtotal thyroidectomy) : for tumours
and multinodular goiters and Graves dz.
Complication:
o Serous fluid accumulation resolves spontaneously.
o Bleeding may compress trachea
o Recurrent laryngeal nerve injury (permenant in 1%): supplies all
intrinsic muscle of larynx except cricothyroid. if unilateral=hoarseness
if bilateral then airway obstruction.
o Superior laryngeal nerve: supplies cricothyroid (3.7%) cannot create
high-pitched sound.
o Hypoparathyroidism (1.7% of surgery is permenant, temporary in 8.3%)
o Thyrotoxic storm.
o Hypothyroidism.