week 3 Flashcards
define primary and secondary thyroid disease
primary = disease affecting thyroid itself (goitre or non-goitrous)
Secondary - Hypothalamic or pituitary disease (No thyroid gland pathology)
commonest cause of primary thyroid disease?
AI thyroid D most commonly
why are diabetes patients with poor glycemic control more prone to infection?
they are IC - high BG causes WBC to stop working as effectively
what thyroid hormones in inactive and when?
T4, always (free) until converted to T3
what are some thyroid hormones (TH)?
TSH - Thyroid stimulating hormone/thyrotropin.
T4 - thyroxine (80% of TH secreted)
T3 - triiodothyronine (remaining 20%)
how are T3/4 found in the body?
[>99%] bound to plasma proteins (TBG, albumin and pre-albumin)
what is TBG
Thyroxine-binding globulin
what is TSH release by and why?
thyrotroph cells in anterior pituitary in response to thyrotropin releasing hormone (TRH)
what does TSH levels reflect?
Reflects tissue thyroid hormone action
what is the Hypothalamic-pituitary-thyroid (HPT) axis
negative feedback system responsible for the regulation of metabolism..
senses low T3/T4 and releases TRH.
bloods/biochemical PC of primary hypothyroidism
Free T3/4 low
TSH high
bloods/biochemical PC of primary hyperthyroidism
Free T3/4 high
TSH low
bloods/biochemical PC of secondary hyperthyroidism
Free T3/4 high TSH high (or ‘normal’)
bloods/biochemical PC of secondary hypothyroidism
Free T3/4 low TSH low (or ‘normal’)
define hypothyroidism
in insufficient secretion of thyroid hormones from the thyroid gland
define Myxoedema
severe hypothyroidism and is a medical emergency
what is Pretibial myxoedema? why does it occur?
it’s a rare clinical sign of Graves’ disease, an autoimmune thyroid disease which results in hyperthyroidism
what are three risk factors for developing hypothyroidism
white ethnicity
female
area of high iodine intake
causes of primary hypothyroidism
Goitrous:
Chronic thyroiditis, (Hashimoto’s thyroiditis), Iodine deficiency
[Drug-induced (e.g. amiodarone, lithium), Maternally transmitted (e.g. antithyroid drugs), Hereditary biosynthetic defects]
Non-goitrous:
Atrophic thyroiditis
[Post-ablative therapy (e.g. radioiodine, surgery)
Post-radiotherapy (e.g. for lymphoma treatment)
Congenital developmental defect}
Self-limiting
[Following withdrawal of antithyroid drugs
Subacute thyroiditis with transient hypothyroidism
Post-partum thyroiditis]
what are the three commonest causes of primary hypothyroidism?
Chronic thyroiditis (Hashimoto’s thyroiditis)
Iodine deficiency
atrophic thyroiditis
what are the causes of secondary hypothyroidism?
Diseases of the hypothalamus and pituitary gland (multiple!):
[Infiltrative Infectious Malignant Traumatic Congenital Cranial radiotherapy Drug-induced…]
Chronic thyroiditis (Hashimoto’s thyroiditis): how common is it and what is it?
commonest cause of hypothyroidism in the Western world. (F>M, strong FHx)
Autoimmune destruction of thyroid gland and reduced thyroid hormone production
what is Hashimoto’s thyroiditis characterised by?
Antibodies against thyroid peroxidase (TPO)
T-cell infiltrate and inflammation microscopically
clinical features of Hypothyroidism? hair and skin
hair and skin = coarse/sparse hair, dull expressionless face, periorbital puffiness, pale skin cool and doughy to touch, vitiligo, hypercarotenaemia.
clinical features of Hypothyroidism? thermogenesis
intolerant to cold
clinical features of Hypothyroidism? fluid retention
pitting oedema
clinical features of Hypothyroidism? cardiac
Reduced heart rate
Cardiac dilatation
Pericardial effusion
Worsening of heart failure
clinical features of Hypothyroidism? metabolic
hyperlipidaemia.
decreases appetite
weight gain
clinical features of Hypothyroidism? GI
Constipation
(Megacolon and intestinal obstruction)
(Ascites)
clinical features of Hypothyroidism? resp?
Deep hoarse voice
Macroglossia (large tongue)
Obstructive sleep apnoea
clinical features of Hypothyroidism: neuro?
Decreased intellectual and motor activities Depression, psychosis, neuro-psychiatric Muscle stiffness, cramps Peripheral neuropathy Prolongation of the tendon jerks Carpal tunnel syndrome (Cerebellar ataxia, encephalopathy) Decreased visual acuity
clinical features of Hypothyroidism: reproductive?
Menorrhagia
Later oligo- or amenorrhoea
Hyperprolactinaemia - ↑TRH causes ↑ PRL secretion
lab investigations of primary hypothyroidism
↑TSH and ↓fT4/3 – cardinal abnormalities
Other abnormalities: Macrocytosis (↑MCV) ↑Creatine kinase (CK) ↑LDL-cholesterol Hyponatraemia -↓renal tubular water loss Hyperprolactinaemia -↑TRH leads to ↑PRL (often mild)
diagnosis for AI hypothyroidism
anti-TPO antibody (anti-thyroglobulin)
management of hypothyroidism
thyroxine (levothyroxine) gradually until normal metabolic rate restored
check TSH 2 months after any dose change
once stabilised TSH should be checked 12-18 months
Secondary hypothyroidism: TSH unreliable (↓TSH production), Titrate dose of levothyroxine to the fT4 level
why must levothyroxine be given gradually?
Rapid restoration of metabolic rate may precipitate cardiac arrhythmias, also caution in Hx of IHD (lower dose, gradual).
drugs in management of hypothyroidism
levothyroxine mainly.
levothyroxine combination with T3 rarely given (some patients like as onset+ elimination quicker)
[take before breakfast without other medications]
pregnancy and hypothyroidism
inc dose 25%-50% of T4 (as there is inc in TBG)
myxoedema coma
elderly women with long standing but frequently unrecognised or untreated hypothyroidism
Mortality up to 60%
what findings are seen on myxoedema coma?
ECG: bradycardia, low voltage complexes, varying degrees of heart block, T wave inversion, prolongation of the QT interval
Type 2 respiratory failure: hypoxia, hypercarbia, respiratory acidosis
Co-existing adrenal failure is present in 10% of patients
treating myxoedema coma
ABCDE,
Passively rewarm: aim for a slow rise in body temperature
Cardiac monitoring for arrhythmias
Close monitoring of urine output, fluid balance, central venous pressure, blood sugars, oxygenation
Broad spectrum antibiotics
Thyroxine cautiously (hydrocortisone - adrenal failure)
define thyrotoxicosis
the clinical, physiological and biochemical state arising when the tissues are exposed to excess thyroid hormone
define hyperthyroidism
refers specifically to conditions in which overactivity of the thyroid gland leads to thyrotoxicosis
Thyrotoxicosis – symptoms and signs(cardiac)
Palpitation, atrial fibrillation (AF) Cardiac failure (very rare)
Thyrotoxicosis – symptoms and signs (sympathetic)
tremor
sweating
Thyrotoxicosis – symptoms and signs CNS
Anxiety, nervousness, irritability, sleep disturbance
Thyrotoxicosis – symptoms and signs GI
Frequent, loose bowel movements
Thyrotoxicosis – symptoms and signs -vision
Lid retraction (not specific to Graves’) Double vision (diplopia) Proptosis (Graves)
Thyrotoxicosis – symptoms and signs (hair and skin)
Hair change – brittle, thin hair
Rapid fingernail growth
Thyrotoxicosis – symptoms and signs -reproductive
Menstrual cycle changes, including lighter bleeding and less frequent periods
Thyrotoxicosis – symptoms and signs muscles
Muscle weakness, especially in the thighs and upper arms
Thyrotoxicosis – symptoms and signs - metabolism + thermogenesis
weight loss and inc appetite
intolerance to heat
causes of thyrotoxicosis associated with hyperthyroidism
Excessive thyroid stimulation:
Graves’ disease
Hashitoxicosis
Thyrotropinoma (THSoma, very rare)
Thyroid cancer (only very rarely cause thyrotoxicosis)
Choriocarcinoma (trophoblast tumour secreting hCG)
Thyroid nodules with autonomous function:
Toxic solitary nodule
Toxic multinodular goitre
key causes of thyrotoxicosis associated with hyperthyroidism
Graves’ disease
Toxic solitary nodule
Toxic multinodular goitre
key causes of thyrotoxicosis not associated with hyperthyroidism
Subacute (de Quervain’s) thyroiditis
Post-partum thyroiditis
causes of thyrotoxicosis not associated with hyperthyroidism
Thyroid inflammation (thyroiditis):
Subacute (de Quervain’s) thyroiditis
Post-partum thyroiditis
Drug-induced thyroiditis (e.g. amiodarone)
Exogenous thyroid hormones:
Over-treatment with levothyroxine
Thyrotoxicosis factitia
Ectopic thyroid tissue: Metastatic thyroid carcinoma Struma ovarii (teratoma containing thyroid tissue)
Graves’ disease epidemiology
female, 20-50years, genetics susceptible (70%) and FHx in women strong. Smoking important.
Graves’ disease lab findings
↓TSH and ↑fT4/3 – cardinal abnormalities
Other abnormalities: Hypercalcaemia and ↑Alkaline phosphatase Reflective of increased bone turnover Graves’ associated with osteoporosis Leucopenia (↓white cell count) Often mild and related to the disease rather than treatment (ATD-induced agranulocytosis) TSH receptor antibody (TRAb) No need to image thyroid gland if raised titre found
Graves’ disease diagnosis
TSH receptor antibody
anti-TPO of present (70-80% and 40% anti-thyroglobulin)
clinical sign specific to Graves’ disease
pretibial myxoedema
thyroid acropachy
thyroid bruit
graves’ eye-disease
graves’ ophthalmopathy/thyroid eye disease
smoking cessation important
TRAb driven pathophysiology
Most disease is mild but can be severe and sight-threatening (unilateral/bilateral. 20% get and 20% have before graves’ diagnosis)
treatment of graves eye disease
Mild disease treated with topically (e.g. lubricants)
More severe disease: steroids, radiotherapy (poor evidence base), surgery
nodular thyroid disease epidemology
Older patients More insidious onset Thyroid may feel nodular Asymmetrical goitre (smooth in Graves’)
tests for nodular thyroid disease
↑fT4/3, ↓TSH
Antibody negative (TRAb)
Scintigraphy: high uptake
Thyroid US
what is thyroid storm? common signs/sympotms? who is it commonly seen in?
Medical emergency, Severe hyperthyroidism,
Respiratory and cardiac collapse, Hyperthermia, Exaggerated reflexes, May require mechanical ventilation
Typically seen in hyperthyroid patients with an acute infection/illness or recent thyroid surgery
treatment for thyroid storm
Treatment: Lugol’s Iodine, glucocorticoids, PTU, β-blockers, fluids, monitoring
treatment of hyperthyrodism
antithyroid drugs (ATDs), BB, radioiodene, thyroidectomy
name two ATDs and their MOA
carbimazole - 1st line.
PTU/propylthiouracil - 1st line only in 3rd trimester.
MOA: inhibition of TPO thereby blocking thyroid hormone synthesis
difference between carbimazole and PTU?
once vs twice daily dosing. lower rate of side effects with carbimazole. PTU 10x less potent
which ATD carries risk of aplasia in early pregnancy and which drug has risk of liver disease?
PTU - liver
carbimazole - aplasia in pregnacy
side effects of ATDs?
Generally well tolerated drugs
1-5% will develop allergic type reactions – rash, urticaria, arthralgia
Cholestatic jaundice, ↑liver enzymes, fulminant hepatic failure (PTU)
Agranulocytosis (cannot be used again if have - 6 weeks=highest risk. 0.3% people - )
whitest be done when prescribing ATD’s?
tell patient orally and in writing - stop drug and have urgent FBC checked in event of fever, oral ulcer or oropharyngeal infection
(Agranulocytosis)
BB: MOA, BB of choice, side effects in hyperthyrodism
Mechanism: β-adrenoceptor blockade, reduced activity of sympathetic nervous system (Useful for immediate symptomatic relief of thyrotoxic symptoms)
Propranolol is the drug of choice - Additional benefit of inhibition of DIO1
Use with caution in those with asthma as Risk bronchospasm - use CCB
radioiodene when is it used? contraindicated?
1st choice treatment for relapsed Graves’ disease and nodular thyroid disease. Safe, no increased risk of thyroid cancer
Contraindicated in pregnancy; Relatively contraindicated in active thyroid eye disease (can be used with steroid cover); Contact precautions (stay away from children/pregnant)
[High risk of hypothyroidism when used in Graves’ disease]
thyroidectomy when is it used? problems?
Useful when radioiodine is contraindicated,leaves Scar
Surgical/anaesthetic risks:
recurrent laryngeal nerve palsy
Hypothyroidism
Hypoparathyroidism
what is thyroiditis? causes of it?
inflammation of the thyroid
Hashimoto’s De Quervain’s/subacute (viral) Post-partum Drug-induced (amiodarone, lithium) Radiation Acute suppurative thyroiditis (bacterial)
subacute thyroidits course
self-limiting - neck tenderness, fever, or other viral symptoms. (viral trigger)
amiodarone and the thyroid
TFTs anormal in half of patients (inhibition of DIO1- ↑fT4, ↓fT3, normal TSH). hypo in 13% (iodene rich areas) and hyper in 2% (iodine deficient areas)
subclinical thyroid disease is what?
Abnormal TSH with normal thyroid hormone levels.
subclinical hypothyroidism
Risk of progression to overt hypothyroidism
Higher risk if strongly TPO antibody positive
Treatment generally advised if TSH >10
Always treat in pregnancy to maintain normal TSH
Subclinical hyperthyroidism
Risk of progression to overt hyperthyroidism
Often seen in multinodular goitre
Association with osteoporosis and atrial fibrillation
Treatment generally advised if TSH <0.1 (or if co-existing osteoporosis/fracture or AF)
non-thyroidal illness/sick euthyroid syndrome
Commonly encountered in the unwell, hospitalised patient
Refers to the impact of intercurrent illness (e.g. severe infection) on the HPT axis
TSH typically suppressed initially then rises during recovery
Avoid checking TFTs in unwell patients unless clinical suspicion of thyroid disease
68 yr old lady Tiredness Weight gain Slowness Goitre
TSH 42 mU/L
Free T4 4 pmol/L
primary hypothyroidsim
normal ranges of TSH and free t4
TSH 0.4-4.0 mU/L
Free T4 9.8-18.8 pmol/L
68 yr old lady
Family history of thyroid disease
Tiredness
Goitre
TSH 12 mU/L
Free T4 11 pmol/L
TPO Antibodies 200 (elevated)
Subclinical hypothyroidism
52 yr old male Headache Visual field defect Dizziness/weakness Poor libido/loss of erections TSH 0.20 mU/L Free T4 6 pmol/L
Pituitary tumour causing secondary hypothyroidism
32 yr old lady Weight loss and tremor Feels tired Sleep disturbance TSH <0.01 mU/L Free T4 54 pmol/L
Graves’ disease
do additional antibody tests
70 yr old lady Diagnosed with atrial fibrillation No symptoms TSH <0.01 mU/L Free T4 26 pmol/L
Toxic multinodular goitre
32 yr old Sore throat and febrile illness Tired, weight loss, poor sleep GP blood tests: TSH<0.01, T4 36 pmol/L Seen in clinic 6 weeks later TSH 12 mU/L, Free T4 9 pmol/L
Subacute thyroiditis
solitary thyroid lump. how many people have them? how many benign?
5% female population has them, 95% benign
what can cause a benign Solitary Thyroid Nodule
Cyst
Colloid Nodule
Benign Follicular adenoma
Hyperplastic Nodule
what can cause a malignant Solitary Thyroid Nodule
PAPILLARY THYROID CARCINOMA – 80% Follicular Thyroid Carcinoma Medullary Thyroid Carcinoma (Lymphoma) (Poorly Differentiated)
how can you tell if a lump in the neck in a solitary thyroid nodule?
moves on swallowing? (invested in pre-trchela fascia).
pain is an uncommon feature (usually caused by bleed into a cyst causing pain)
Hx, exam, investigation of solitary thyroid nodule
neck irradiation, FHx of thyroid Cancer
LN, hoarseness
TSH, USS-FNA
treatment for malignant solitary thyroid nodule
lobectomy or thyroidectomy (consider radioactive iodine)
Follow up of a Differentiated Thyroid Cancer
TSH lower level of normal (0.4-4 mU/l)
Thyroglobulin – protein precursor of T4/T3; made by thyroid follicular epithelial cell - Use Tg as a tumour cell marker for follow up of patient
Get TSH/Tg measured every 6 months for first 5 years then annually for next 5 years
which thyroid cancer speads by LNs?
papillary (commonest 80%)
what investigation is good at showing is LN involvement?
USS
follicular thyroid carcinoma (how common and prognosis)
10%, diagnosis depends on invasion of the capsule or vascular invasion (minimally to wide invasive) - surgery usually sufficient
how do follicular thyroid carcinomas spread?
Haematogenous spread
treatment of FTC (follicular)
most are minimally invasive and treated with lobectomy - if significant vascular involement then thyroidectomy
thyroid lymphoma clinical picture
long-standing (AI) hypothyroidism, 70-80 female, rapid growth
what is needed to diagnoses thyroid lymphoma
core biopsy
treatment of thyroid lymphoma
steroids if actually unwell, radio/chemotherapy. goodish prognosis
medullary thyroid carcinoma arrises from which cell? why is this important?
rare tumour of the parafollicular cells which secrete CALCITONIN – can be used as a tumour cell marker
how can medullary thyroid carcinoma be diagnosed? what should also be check once diagnosed with MTC?
FNA – presence of amyloid or Calcitonin positive stains
Should always Check 24 hour urinary metanephrines and genetics
what genes can be associated with medullary thyroid cancer?
MEN2a and MEN2b (familial)
[can also be sporadic or non-MEN familial]
MEN2a(b) gene gives increased incidence of what conditions? why is it important to identify MEN2a link?
Medullary TC, Phaeochromocytoma, Hyperparathyroidism
prophylactic thyroidectomy as child possible
what to do if suspect a multi-nodular goitre?
Assess Function
Assess Structure – what is being squashed (symptoms of stridor or choking lying flat)?
TSH
CT scan
in a multi nodular goitre what are the results of the investigations?
TSH – usually normal or slightly suppressed; occasionally needs antithyroid drugs (Radioactive iodine/RAI)
CT scan:
Retrosternal Extension
Tracheal Compression
treatment of multi nodular goitre
Most can leave alone
RAI if significant hyperthyroidism
Surgery if structural problem (or significant retrosternal extension)
who is surgery offered to with retrosternal goitres?
Lifestyle interfering symptoms
Possibility of cancer
Significant tracheal compression (?<7 mm)
Tracheal Flow Loops if other respiratory potential causes of orthopnoea/breathing difficulties
? Audible Stridor
when is a flow volume loop done concerning goitres??
if there is another potential cause for breathlessness.
what does the thyroid gland secrete?
Thyroxine (T4)
Tri-iodothyronine (T3)
Calcitonin
structure of the thyroid gland
bow tie (2 lobes with isthmus)
blood supply to the thyroid gland
highly vascular organ,
sup and inferior thyroid arteries (branch of external carotid +/- thyroidea ima).
Three pairs of veins drain- superior/ middle thyroid vein > internal jugular, inferior thyroid vein> brachiocephalic veins
where is the thyroid located?
5th cervical- 1st thoracic vertebrae/ 2-4th tracheal rings
innervation of the thyroid
autonomic nerve supply (Parasympathetic from vagus nerves, and sympathetic fibers from superior, middle, and inferior ganglia of the sympathetic trunk
what is the posteromedial aspect of the thyroid gland is attached by
berry’s ligament
cells of the thyroid
follicle made up of follicular cells (Colloid is enclosed by follicular cells, colloid is a tyrosine-containing thyroglobulin)
parafolicular C cells (secrete calcitonin)
Release of Thyroid Hormones.
Iodine ions travel from blood supply through follicular cell to colloid thyroglobulin with T3 and T4. pinocytosis then occurs in and binds to lysosomes in follicular cell with causes T3 and T4 to be released and then diffuse into bloodstream
what the the pyramidal lobe of the thyroid
extra lobe
Synthesis and Storage of T3 and T4?
iodine taken up by follicle cells, then done attached to tyrosine residues on thyroglobulin to form MIT and DIT. coupling of MIT-DIT or DIT x2 occurs to form T3/T4 respectively. They are stored in colloid thyroglobulin until required.
what is Inhibited by CARBIMAZOLE & PROPYLTHIOURACIL used to treat hyperthyroidism
iodine attached to tyrosine residues on thyroglobulin to form (MIT) & (DIT)
thyroid hormones. which is secreted more, which is more potent? where does conversion take place?
T4 = 90%, T3 is more potent.
T4 made to T3 in liver and kidney (T3 is major biologically active thyroid hormone)
why do T3 and T4 bind to plasma proteins?
hydrophobic/ lipophillic
which plasma proteins do T3/4 bind to?
thyroxine binding globulin (TBG) ~70%
Transthyretin (TTR) (thyroxine binding prealbumin) ~20%
Albumin (~5%)
[unbound in biologically active form]
what does T3 do once converted from T4?
enters nuclear receptor of target cell → mRNA →proteins → biological resp
effects of thyroid hormones on basal metabolic rate
Thyroid hormones inc basal metabolic rate
Increase number & size of mitochondria
Increase oxygen use and rates of ATP hydrolysis
Increase synthesis of respiratory chain enzymes
effects of thyroid hormones on thermogenesis
inc thermogenesis
effects of thyroid hormones on metabolism
Carbohydrate metabolism:
inc blood glucose – due to stimulation of glycogenolysis and gluconeogenesis.
inc insulin-dependent glucose uptake into cells
Lipid metabolism :
Mobilise fats from adipose tissue
inc fatty acid oxidation in tissues
Protein metabolism
inc protein synthesis
Thyroid Hormone Effects-
Growth and Development
Growth:
Growth hormone releasing hormone (GHRH) production & secretion requires thyroid hormones
Glucocorticoid-induced GHRH release also dependent on thyroid hormones (permissive action)
GH/somatomedins require presence of thyroid hormone for activity (permissive action).
Development of foetal & neonatal brain
Myelinogenesis & axonal growth require thyroid hormones
Normal central nervous system activity:
Hypothyroidism - slow intellectual functions
Hyperthyroidism – nervousness, hyperkinesis & emotional lability
Thyroid Hormones Permissive Sympathomimetic Action
increase responsiveness to adrenaline & sympathetic NS neurotransmitter, noradrenaline, by increasing numbers of receptors
cardiovascular responsiveness also increased due to this effect – increased force and rate of contraction of heart
(BB like propranolol used to treat symptoms)
how are thyroid hormones regulated?
TRH=THYROTROPHIN RELEASING HORMONE
TRH release from hypothalamus stimulates TSH release form anterior pituitary.
inc TSH does what to t3/t4 secretion?
inc TSH = stimulates T3/4 release
t3/4 effect on TRH?
negative feeback (inc T3/4 reduce TRH)
TSH receptor is found where?
thyroid folicular cell
what external factors can regulate thyroid hormones conc?
low temp (inc TRH/TSH), stress(inhibits TRH/TSH), circadian rhythm (low in morning, highest late at night)
what are DeIodinase Enzymes? what do they do?
Subfamily of 3 enzymes (type 1, 2 and 3) important in the activation and deactivation of thyroid hormone (tissue regulation)
add/remove an iodine atom.
3 types of DeIodinase Enzymes another locations?
Type I (D1) is commonly found in the liver and kidney
Type II (D2) is found in the heart and skeletal muscle, CNS, fat, thyroid, and pituitary
Type III (D3) found in fetal tissue and placenta and brain (except pituitary)
what is the main determinant of T3?
D2 (activates T4->T3 in tissues)
what are the four different thyroid hormone recpetors? why is this useful?
Thyroid hormone receptor alpha – TRα1, TRα2
Thyroid hormone receptor beta –TRβ1. TRβ2
(different effect/sensitivity per tissue)
what occurs if person is Resistant to thyroid hormone alpha (RTHα)
delayed bone development
chronic constipation
bradycardia
impaired neurological development
what occurs if person is Resistant to thyroid hormone beta (RTHβ)
impaired HPT axis goitre affected colour vision abnormal cochlea tachycarida impaired neurological development
deficiency of thyroid hormones cause by what? are the conditions goitrous or not?
Primary (gland) failure – may be associated
with enlarged thyroid (goitre)
Secondary to TRH or TSH (no goitre)
Lack of iodine in diet (may be associated with goitre)
what are the symptoms of hypothyroidism?
Reduced BMR Slow pulse rate Fatigue, lethargy, slow response times and mental sluggishness Cold-intolerance Tendency to put on weight easily
what is myxoedema (hypothyroidism in adults) signs
puffy face, hands & feet
what is cretinism (hypothyroidism in kids) signs
dwarfism & limited mental functioning due to deficiency of thyroid hormones present at birth
symptoms of hyperthyroidism
Increased BMR Very fast pulse rate Increased nervousness and excessively emotional. insomnia Sweating & heat intolerance Tendency to lose weight easily
condition commonly causing hyperthyroidism? signs?
Graves’ disease.
Autoimmune disease – Thyroid stimulating immunoglobulin (TSI) acts like TSH but unchecked by T3 & T4.
Exophthalmos
Goitre – enlarged thyroid gland
why does Exophthalmos occur?
bulging eyes due to water retaining carbohydrate build up behind eyes.
whiter the 5 types of thyroid cancer?
papillary, follicular, medullary, anaplastic, other (lymphoma…)
what makes up differentiated thyroid cancer/DTC?
papillary, follicular.
refers to histology, most cancer cells take up Iodine and secrete Thyroglobulin, DTC are TSH driven - good prognosis (95% after 10 years)
what do most DTC present with?
palpable nodule (thyroid or LN)
5% with local/disseminated mets
who does DTC occur in?
white adults with radiation exposure.
papillary thyroid cancer. how common, spread and associations
commonest, LN, spread to lungs, bone, liver, brain; associated with hashimoto’s thyroiditis
follicular thyroid cancer. how common, spread and associations
2nd commonest, haematogenously spread. incidence inc in regions of relative iodine deficiency
investigation of potential DTC
US guided FNA (+excision biopsy of LN).
what do to if suspect DTC and vocal cord palsy?
pre-operative laryngoscopy
[make sure of no recurrent laryngeal nerve injury]
clinical predictors of malignacy in thyroid nodule?
<20 or >50 Nodule increasing in size > 4cm in diameter History of head and neck irradiation Vocal cord palsy
treatment for DTC?
surgery +/- RAI
what are the three types of surgery for DTC and which is preferred?
Thyroid lobectomy with isthmusectomy
Sub-total thyroidectomy
Total thyroidectomy
Sub-total thyroidectomy
why is a Sub-total thyroidectomy operation of choice for DTC?
leave on 5% in situ so chance of recurrence low
leaving decreases chance of complications (vocal cord palsy, parathyroid destruction)
what happens post-op to DTC patients?
risk assessed by AMES(age, mets, extent and size of primary tumour). - basically low and high risk groups made depending on how advanced cancer was before surgery
treatment for low and high risk groups post surgery for DTC?
low -TSH-supression via thyroxine
high- RAI
when whole body iodine scan done? what preparations are necessary?
Usually performed 3-6 months post-op.
use rhTSH is far better as no need to stop T3/T4 - as need high TSH for scan
why is a high TSH needed for a whole body iodine scan?
as sensitivity is determined by ensuring that TSH is elevated
inc TSH helps cancer cells to recognise iodine and uptake it - making results clearer
what is TRA/Thyroid Remnant Ablation?
rhTSH and high dose of RAI given - patient kept in lead room for 2/3 days (inpatient)
side effects of RAI?
few, patients usually well, sore salivary glands/throat possible
how is TRA followed up?
patient maintained on T4 to suppress TSH. this reduced recurrence rates (suppress long-term = extra protection)
thyroglobulin (Tg) can be used as tumour marker, should be undetectable. (very sensitive test)
what is thyroglobulin. why can it be used as a tumour marker? what happens if positive?
a protein produced by thyroid cells and (most) thyroid cancers.
with most of thyroid cells and cancer destroyed in successful treatment, level should be nothing and if increases then shows cancer still there.
if + = do whole body iodine scan
what do to if patient with PMHx of DTC has positive Tg but negative whole body iodine scan? how to treat?
PET scan. positive means cancer has changed an become anaplastic.
use biologics (Sorafenib and Lenvatinib)
recurrence of DTC: when? where? rate?
<2 years after op.
LN>thyroid
30% rate but if it uptakes iodine then is curable (via TRA)
what does TRA increase risk of?
AML (acute myeloid leukaemia). highest at 15 years post-treatment [no other cancer risk or is to fertility/offspring.]
how does cold exposure cause a release of thyroxine?
hypothalamus (TRH), ant pituitary (thyrotropin), thyroid (thyroxine)
(paired) hormones from ant pit?
ATCH - cortisol TSH - thyroxine Lh/FSH - Testosterone/estradiol GH - IGF1 Prolactin
post pituitary hormones?
vasopressin, OXT
what is the difference between micro/macroademona?
≤ 1cm: Microadenoma
> 1cm: Macroadenoma
what are the complications of a non-functioning pit ademona?
Compression on optic chiasma (Bitemporal hemianopia)
Compression on other structures eg cranial nerve 3,4,6
Hypoadrenalism
Hypothyroidism
Hypogonadism
(Diabetes Insipidus)
GH deficiency
what are the benign causes of a raised prolactin?
Physiological - breast feeding - pregnancy - stress - sleep
Drugs - Dopamine antagonists eg metoclopramide - Antipsychotics eg phenothiazines - antidepressants eg TCA, SSRIs - other, estrogens, coccaine
what are the pathological causes of a raised prolactin?
Hypothyroidism
Stalk lesions: iatrogenic, road accident
Prolactinoma
signs and symptoms of raise prolactin in female
EARLY presentation Galactorrhoea 30-80% Menstrual irregularity Ammenorrhoea Infertility
signs and symptoms of raise prolactin in male
LATE Presentation Impotence Visual field abnormal Headache Ant pit malfunction
investigating prolactinoma
prolactin conc, MRI pituitary (tumour, pit stalk, optic chiasma) visual fields (bitemproal hemianopia) pit tests (other Hormones affected?)
treatment of prolacitnoma
Cabergoline (twice oral per week) - dopamine agonists (work very well)
what is acromegaly?
GH excess
acromegaly sings and symptoms
giant, thickened soft tissues - skin, large jaw, sweaty, large hands Hypertension (heart), cardiac failure Headaches (vascular) Snoring/Sleep apnoea Diabetes mellitus Local pituitary effects - visual fields, hypopituitarism Early CV Death Colonic polyps and colon cancer
how is acromegaly diagnosed? other tests that are important to consider?
IGF1
GTT (GH not suppressed)
Visual field
CT or MRI pituitary scan
Pituitary function tests ie the “other hormones
treatment for acromegaly
Pituitary surgery
(+/-External radiotherapy to pituitary fossa)
Retest GTT (if too high need drug therapy)
what drugs can be used in acromegaly?
Dopamine Agonist -Cabergoline
Somatostatin Analogues - octreotide, sandostatin LAR, lanreotide.
GH Antagonist -
Pegvisomant
what is cushion’s syndrome caused by??
excess cortisol
what occurs in cushing’s syndrome due to excess cortisol?
Protein loss Myopathy; wasting Osteoporosis; fractures Thin skin; striae, bruising Altered Carbohydrate/Lipid metabolism; Diabetes mellitus, Obesity Altered psyche; psychosis, depression
what occurs in cushing’s syndrome due to excess mineralocorticoid
hypertension, oedema
what occurs in cushing’s syndrome due to excess androgen
Virilism
Hirsutism
Acne
oligo/amenorrhoea
what does cushion’s cause to be in excess?
cortisol, mineralocorticoid, androgen
what is cushion’s characterise (compared to obesity? )
Thin Skin Proximal myopathy Frontal balding in women Conjunctival oedema (chemosis) Osteoporosis buffalo hump, moon face
what is the diagnostic test for cushing’s?
screening = overnight Dexamethasone suppression test
definitiative = 2day Dexamethasone suppression test
what is the difference between cushings disease and syndrome?
Pituitary (majority) = Cushing’s Disease
ALL others are Cushing’s Syndrome: Adenoma of adrenal (B/M), ectopic (thymus, lung, pancreas), pseudo (steroid meds, alcohol, depression)
DD of cushing’s: blood results pituitary cause (disease)
abn - low dose dexa test
<300 - ACTH
suppress by 50% - high dose exam suppression
DD of cushing’s: blood results ectopic cause
abn - low dose dexa test
>300 - ACTH
nil- high dose exam suppression
DD of cushing’s: blood results adrenal cause
abn - low dose dexa test
<1 - ACTH
nil - high dose exam suppression
treatment of pituitary Cushing’s disease
hypophysectomy +/-radiotherapy (recurrance); bilateral adrenalectomy
treatment of adrenal Cushings syndrome
Adrenalectomy
treatment of ectopic Cushings syndrome
remove source
OR bilateral adrenalectomy
drugs used in the treatment of cushings?
Metyrapone - if other treatments fail - while waiting for radiotherapy to work
- S/E common
Ketoconazole (hepatotoxic)
Pasireotide: (new somatostatin analogue; receptor 2 and 5 blocked)
pan Hypopituitarism causes what?
Anterior Pitutary Growth Hormone; growth failure TSH; hypothyroidism LH/FSH; Hypogonadism ACTH; hypoadrenal Prolactin; none known
Posterior Pituitary
Diabetes Insipidus
causes of Hypopituitarism (many)
Pituitary Tumours Secondary metastatic lesions Local brain tumours Granulomatous diseases (TB, sarcoidosis) Trauma(road accidents, skull fractures) Hypothalamic diseases (Syphilis, meningitis) Iatrogenic; surgery Autoimmune;Sheenan – post pregnancy infarction Infection; meningitis
Symptoms and signs of anterior hypopituitarism
Menstrual irregularities (F) Infertility, impotence Gynaecomastia (M) Abdominal obesity Loss of facial hair (M) Loss of axillary and pubic hair (M&F) Dry skin and hair Hypothyroid faces growth retardation (children)
treatment of pan Hypopituitarism
Thyroxine Hydrocortisone ADH GH Sex Steroids: HRT/Oest/prog pill for female + Testosterone for males
GH in adults
Improves well being and Quality of life Decreases abdominal fat Increases muscle mass, strength, exercise capacity and stamina Improves cardiac function Decreases cholesterol and increases LDL Increases bone density Given by daily SC injection
Testosterone Replacement in hypopituitarism
IM injection every 3-4 weeks (sustanon) Skin gel (testogel, tostran) Prolonged IM injection 10-14 wks (nebido) (Oral tablets (restandol))
risks of testosterone replacement
Prostate Enlargement. Does NOT cause prostate cancer but may make it grow - monitor PR exam and PSA at start
Polycythaemia - monitor FBC
Hepatitis (only for oral tablets) - monitor LFTs
causes of cranial D.insipidus
familail (DIDMOAD = DI, DM, optic atrpohy, deaf)
acquired (idiopathic and trauma (RTA/sugery/skull #))
Rare (tumour, sarcoid, irradtions, meningitis )
how is DI diagnosed?
Water Deprivation test
why do DI occur?
reduced ADH/vasopressin
how is DI treated?
desmopressin (oral, inhale, injection)
