Endocrine Flashcards
What nerves are at risk during thyroidectomy and how do you avoid injuring them? what would be the consequence of injury to them?
This nerve branches off the vagus nerve and passes lateral to the thyroid gland. It is most commonly injured during superior pole mobilisation and to minimise risk - ligate the superior thyroid vessels close to the gland
This branches and the external branch supplies cricothyroid muscle and damage therefore leads to voice fatigue and altered projection. The internal branch provides sensation for the pharynx and epiglottis above the vocal cords and therefore damage leads to poor cough/aspiration risk
These nerves branch off the vagus nerve. They take different paths on left and right. (Left loops under the aortic arch and right loops under the right subclavian artery) to then pass superiorly in the tracheooesophageal groove and posterior to the thyroid gland. This is when they are at risk during posterior mobilisation of the thyroid gland.
They supply all the intrinsic muscles of the larynx (except criothyroid) and the vocal cords. Therefore damage to these nerves results in the cord being fixed in adduction position which if unilateral damage results in hoarse voice and bilateral damage results in obstruction.
These nerves are at even higher irks of injury when the nerves are non-recurrent. This is more common on the right this can occur on the right in an abberant right subclavian (arteria lusoria) or on the left if there is a right sided aortic arch.
Describe the embryology of the thyroid.
The thyroid arises from the endoderm from foramen cecum and descends into the neck.
The C cells arise from the neural crest of the 4th pharyngeal pouch.
The pyramidal lobe is the remnant of the thyroglossal duct.
Describe the suspensory ligaments of the thyroid.
Anterior suspensory ligament suspends the thyroid from the cricoid & thyroid cartilidges. It contians Delphians nodes.
Posterior suspensory ligament suspends the thyroid from the trachea and is close to recurrent laryngeal nerves.
Describe the vascular supply of the thyroid.
- Superior thyroid artery from external carotid. Adjacent to superior laryngeal nerve
- Inferior thyroid artery from thyrocervical trunk off the subclavian artery. Adjacent to the recurrent laryngeal nerve. Usually anterior to the RLN on the right and posterior to it on the left. THis artery also supplies both superior and inferior parathyroids.
- Thyroidea ima artery from the innominate artery (most common) or aorta or carotids. supplies the isthmus in 3-5% of the population.
Venous drainage is via the superior and middle thyroid veins into the internal jugular and via the inferior thyroid vein into the innominate vein.
What cells produce hormones in the thyroid?
Thyroid follicles (spherical groupings of thyrocytes/follicular cells) produce T3/4 and surround a thyroglobulin core.
The parafollicular C cells (scattered in spaces between follicles) produce calcitonin.
What is the process of T3/T4 production in the thyroid?
What are the functions of T3/4 and calcitonin?
T3
- more active than T4
- 87% produced in periphery by deiodinase converting T4 to T3
- increases HR & CO
- increases RR
- increases basal metabolic rate
- potentiates catecholamine effects
T4
- 15x more prevalent than T3
- less active but similar effects at T3
Calcitonin
- decreases calcium and phosphate
- decreases bone osteoclast calcium secretion
- decreases renal reabsorption of calcium
- decreases renal reabsorption of phosphate
- can cause diarrhoea with oversecretion.
*Calci-tone-in: Tones Down Calcium
What would you expect to see on blood tests for
- primary hypothyroidism
- subclinical hypothyrodism
- secondary hypothyroidism
- primary hyperthyroidism
Primary hypothyroidism:
- decreased T4, increased TSH
- Less T4 and T3 are produced due to the thyroid’s reduced capacity to produce hormone or respond to TSH.
- As a result, there is reduced negative feedback on the pituitary and hypothalamus.
- The reduction in negative feedback results in increased production of TRH (which we don’t typically measure) and TSH.
- The end result is low T4 and T3 and a raised TSH.
A normal T4 in the context of a raised TSH may suggest subclinical hypothyroidism (most commonly caused by underlying autoimmune disease).
Pathology which affects the pituitary and hypothalamic glands can result in decreased production of TRH and TSH, causing secondary hypothyroidism.
Secondary hypothyroidism is a rare cause of hypothyroidism, accounting for 1% of all cases.
- Decreased production or secretion of TRH and TSH results in decreased stimulation of the thyroid gland.
- The thyroid gland, therefore, produces less T3 and T4.
- The low T3 and T4 would normally stimulate the pituitary and hypothalamic glands to increase TRH and TSH production, however, they are unable to increase production.
- The end result is low T4 and T3 and a normal/low TSH.
Is excessive T3/T4 production as a result of thyroid gland pathology.
- The thyroid produces excessive amounts of T4 and T3.
- The excessive T4 and T3 cause negative feedback on the pituitary and hypothalamus, resulting in decreased production of TRH and TSH.
- The end result is a raised T3 and T4 and a low TSH.
involves stimulation of the thyroid gland by excessive thyroid-stimulating hormone (TSH).
- TSH production is increased by either the pituitary/hypothalamus or another source (known as ectopic production).
- The excess TSH causes overstimulation of the thyroid gland, resulting in high levels of T3 and T4 production.
- Normally a raised T3 and T4 level would cause negative feedback, decreasing TSH production, however, in this instance, the TSH production is not responsive to any negative feedback, resulting in continued excess production.
What are the clinical features of hypothyroidism?
BRADYCARDIC
Bradycardia
Reflexes slowed
Alopecia
Dry skin
Yawning - fatigue/lethargy
Cold intolerance
Anaemia
Raised weight
Depression
Impaired memory
Constipation
What is thyroiditis?
Inflammation of the thyroid gland. It may initially present as hyperthyroid/thyrotoxicosis but ultimately leads to hypothyroidism.
What are some causes of Hypothyroidism?
Painless thyroiditis:
Can be divided into primary (99%) and secondary (1%). Within primary can divide into thyroiditis that cause painless and painful hypothyroidism and then non-thyroiditis causes. Within secondary can divide into pituitary or hypothalamic causes.
Primary = low T3/T4 production due to inability to respond to TSH stimulation.
- Hashimotos
- Postpartum
- Riedels (fibrous)
- Drug-induced
- De Quervains
- Acute supparative
- Trauma induced
- Radioiodine induced
- Thyroidectomy (hemi or tot)
- Euthyroid sick syndrome
- cervical radiation therapy
- iodine deficiency
- decreased TSH by pituitary
Secondary = low TRH or TSH resulting in low stimulation of the thyroid gland therefore low T3/T4.
- adenoma (most common)
- radiation or surgery that damages pituitary tissue
- hypothalamic or suprasellar tumour
- radiation or surgery that damages hypothalamus tissue
What is Hashimoto’s thyroiditis?
- autoimmune inflammation of the thyroid
- most common cause of hypothyroidism
- autoantibodies include anti-thyroglobulin (anti-Tg), anti-thyroperoxidase (anti-TPO) and anti-microsomal.
- associated with increased iodine intake
- most common in woemn 7:1 aged 30-50
- most assymptomatic and painless.
- increased risk for thyroid lymphoma
- on USS looks heterogenous and diffusely enlarged
- on FNA will show lymphocytic infiltrates with germinal centres, Hurthle cells, fibrosis and small follicles with decreased colloid.
Treat with synthetic thyroxine with goal TSH normal level and to relieve symptoms.
Surgical if symptoms of mass effect, concern for malignancy or cosmesis.
What is post-partum thyroiditis?
- Variant of Hashimotos thyroiditis with autoimmune antibody mediated destruction of the thyroid within 1 year post partum.
- usually self resolving with 6-12 months
- recurrence is common
- may develop permanent hypothyroidism over next 3-12 years.
- on FNA would show lymphocytic infiltrates WITHOUT germinal centres, Hurthle cells or fibrosis.
What is Riedel’s (fibrous) thyroiditis?
- invasive fibrotic replacement of thyroid +/- perithyroid tissue including parathyroids.
- Fibrosis may also involve other extra-thyroidal sites (Retroperitoneum, Mediastinum, Lungs & Parotid Glands
- thyroid gland is typically non tender and stone hard.
- on USS appears hypoechoic, reduced vascularity, difficult demarcation of thyroid from surrounding tissue.
- on biopsy extensive fibrosis and paucity of follicular epithelium.
- Treat with steroids.
- If airway obstruction perform isthmusectomy only (resection of the other lobes high risk for damage to surrounding structures due to loss of normal tissue planes)
What drugs are most commonly implicated in drug-induced thyroditis?
- Amiodarone
- Tyrosine kinase inhibitors e.g. imatinib
- Interferon alpha
- Interleukin 2
- Lithium
What organisms are most commonly implicated in acute supparative thyroiditis and how is it treated?
Staph aureus or strep
most arise from haematogenous spread in immunocompromised patients
treat with abx and perc drainage, may need surgical drainage if abscess.
What are the clinical features of hyperthyroidism?
Remember SWEATING
Sweating
Weight loss (despite increased appetite)
Emotional lability (anxiety and irritability)
Arrhythmia, palpitations and hypertension
Tremor & tachycardia
Intolerance of heat
Nervousness (hyperactivity, restlessness) & Nausea and vomiting
Graves specific = exopthalmos, pretibial myxoedema
What is meant by a thyroid storm?
Thyrotoxic crisis whereby a sudden release of large amounts of thyroid hormone can lead to life threatening sequelae of high output cardiac failure.
Occurs independent of TSH and can be caused by cessation of thioamide medication, due to trauma, severe illness or during thyroid manipulation intraoperatively.
Often have previously undiagnosed Graves disease.
Can be exacerbated by aspirin (decreases protein binding to T3/T4).
What is Amiodarone Induced Thyrotoxicosis?
Amiodarone-Induced Thyrotoxicosis (AIT)
- Can potentially cause both Hypothyroidism & Hyperthyroidism (From High Iodine Content).
- Highly Lipophilic with 100 day half-life therefore can cause toxicity well after drg discontinuation and no immediate benefit to drug discontinuation.
- Type I: Iodine-Induced Increase in Thyroid Hormone Synthesis
More Common in Preexisting Thyroid Disease
US Shows Increased Vascularity
(treat with radioactive iodine or thioamides)
- Type II: Direct Toxicity Causes Destructive Thyroiditis
More Common in Those Without Preexisting Thyroid Disease
US Shows Absent Vascularity
(treat with steroids)
What is Plummer’s disease?
Hyperthyroidism due to Toxic multinodular goitre
What is Jod-Basedow Phenomenon?
Hyperthyroidism as a result of excess iodine given to someone who is iodine deficient.
What are secondary causes of hyperthyroidism?
- TSH secreting tumour
- hcG secreting tumours
- thyroid hormone resistance (resistant to the negative feedback loop)
What would your work up pathway be for someone with Hyperthyroidism?
History and examination:
- key hx points - family hx, radiation hx. surgical hx
- key examination - goitre, lid lag, exopthalmus viewed from side, pretibial myxoedema
Investigations:
Laboratory
- TSH (expect low in primary hyperthyroidism or high in secondary hyperthyroidism), T4 (high)
- thyroid receptor antibodies
Scans
- USS to assess for nodule or MNG or graves
- radioactive iodine scan
> high diffuse uptake = graves
> high assymmetric uptake = Toxic MNG
> high uptake in single hot nodule = solitary toxic nodule
> minimal/no uptake = thyroiditis, iodine induced or excess exogenous hormone administration.
NB: suspicious or non-functioning nodules require FNA
What is the pathophysiology of Graves disease?
- autoimmune induced production of thyroid hormone
- anti-TSH receptor IgG antibody (thyroid stimulating immunoglobulins TSIs) bind to the receptor causing its activation leading to production of T3/T4 despite negative feedback loop on TSH production.
- causes diffuse symmetrical enlargement.
How is Graves disease treated?
Immediate treatment for symptomatic thyrotoxicosis = beta blockers
First line treatment = thioamides e.g. carbimazole.
Usually 12-18months treatment and if this fails then RAI or thyroidectomy.
What are indications for near or total thyroidectomy in Graves?
- suspicious nodule
- refractory to thioamide or radioactive iodine treatment
- contraindication to thioamide or radioactive iodine treatment e.g. desire to become pregnant in <6months
- non compliant with medication
- compressive goitre
- operating in area for other reasons e.g. parathyroidectomy
- moderate to severe orbitopathy
What is the first line treatment for solitary toxic nodules or toxic multinodular goitre?
Surgery or RAI.
Medications reserved for pregnancy as bridge to surgery post partum.
What medications are used to treat thyrotoxicosis and hyperthyroidism and what are their side effects/contraindications?
Thioamides
- treat hyperthyroidism
- inhibit TPO
- carbimazole converts to methimazole and is generally first line however is teratogenic causing cretinism in infant.
- propylthiouracil (PTU) is a thioamide that can be used in pregnancy but has potential hepatotoxicity.
- both drugs have potential to cause agranulocytosis
- NB exopthalmos is resistant to thioamides.
Beta blockers
- reduce sympathetic hyperactivity
- decrease peripheral conversion fo T4 to T3.
- used for immediate control of thyrotoxicosis.
What is Radioactive Iodine? How does it work?
How is it used?
When is it contraindicated?
Sodium Iodide 131
The RAI is taken into thyroid hormone causing ionising destruction of thyroid follicular cells.
It is used as a treatment of hyperthyroidism. Often pretreatment with thioamides and beta blockers is used to reduce chance of transient hyperthyroid exacerbation upon starting the RAI. Usually stop thioamides and beta blocker 2-3 days before commencing RAI and don’t resume them until 2-3 days after cessation of RAI.
Its side effects are transient hyperthyroidism exacerbation, sialolithiasis and neck pain.
It is contraindicated in:
- pregnancy & lactation
- thyroid malignancy
- children <5 yo
- mod-sever orbitopathy (may worsen)
What is the role for preoperative medication in Graves disease prior to thyroidectomy?
- Making a patient Euthyroid preoperatively reduces risk of thyroid storm
- Done by using thioamides and beta blockers and potassium iodide 7-14 days preoperatively
- Lugols solution utilises Wolff-Chaikoff effect of saturating thyroid with high dose iodine leading to inhibition of TSH.
Spot diagnosis.
What is this?
How does it occur?
Who does it affect?
How does it present?
Lingual thyroid
i.e. ectopic thyroid tissue at base of tongue due to embryological maldescent. (Thyroid ususally originates in embryo from the endoderm from foramen cecum and descends into the neck).
Affects women > men 4-7:1
They present
- Most commonly diagnosed with periods of rising TSH causing hypertrophy e.g. during puberty, pregnancy or menopause.
- 70% are hypothyroid and 70% do not have any other functional thyroid tissue
- most are assymptomatic
- can cause bleeding
- dysphonia
- dysphagia
- upper airway obstruction
What is Pembertons sign?
It is facial flushing or cyanosis as well as respiratory distress after one minute of arms raised and indicates thoracic outlet venous obstruction in patients with goitre.
What are the indications for surgery for goitre?
- Large > 4 cm
- Dysphagia
- Airway Compromise
- Local Discomfort
- Substernal Location (Risk of Hidden Malignancy & Further Extension Can Require More Extensive Surgery in the Future)
Approach:
- Unilateral Enlargement = Lobectomy
- Bilateral Enlargement = Total/Near-Total Thyroidectomy
- Substernal Goiters Can Mostly Be Removed Through a Cervical Incision & Rarely Require Sternotomy
What is difference between total and near-total thyroidectomy?
Total thyroidectomy is an operation that involves the surgical removal of the whole thyroid gland. Near‐total thyroidectomy is an operation that involves the surgical removal of both thyroid lobes except for a small amount of thyroid tissue (on one or both sides less than 1.0 mL).
How long does it take for transplanted parathyroid tissue to become functional?
The autotransplanted parathyroid gland takes about 4 to 6 weeks to start working again and during this time patients will need to take calcium supplements and calcitriol (vitamin D).
What percentage of population is thought to have thyroid nodule(s) and what percentage are malignant?
37-57% population have nodule(s).
90% are benign with extremes of age more likely to be malignant (50% benign in kids).
What are risk factors for a thyroid nodule to be malignant?
- male sex
- kids or elderly
- radiation to head or neck (most likely papillary)
- solitary nodule (vs multinodular)
- large >2cm
- concerning features on USS
- cold nodule (i.e. non-functioning, either euthyroid or if hyperthyroid have had scintigraphy and not hot).
What are concerning features on USS for thyroid nodules?
- taller than wide
- microcalcifications
- hypoechoic
- heterogenous
- hypervascular
- solid
- large
- lobulated/irregular margins
What is the TIRADS score?
A system to standardise USS reporting of thyroid nodules and guide management and risk estimation.
Points are given for composition, echogenicity, shape, margin and echogenic foci.
Highest points are given for a solid, hypoechoic, large taller than wide, irregular or lobulated margin nodule with punctate echogenic foci.
TIRADS 1 = normal
TIRADS 2 = benign nodules TIRADS 3 = probably benign TIRADS 4 = suspicious of malignancy,
TIRADS 5 = highly suggestive of malignancy
What would you recommend for a TR3 nodule?
FNA if >2.5cm, follow if >1.5cm for 1, 3 and 5 years.
What would you recommend for a TR4 nodule?
FNA if >1.5cm, follow if >1cm for 1,2,3 and 5 years
What would you recommend for a TR5 nodule?
FNA if >1cm, follow if >0.5cm annually for 5 years.
If there are multiple nodules reported which ones are FNA’d/followed?
If there are multiple nodules receiving TR3-5, the two with the highest ACR TI-RADS scores should be sampled (rather than the two largest), with largest size being used a tie-breaker if there are multiple nodules of the same classification.
What are these cells indicative of and what other features would be typical of this lesion?
These are Orphan Annie Eyes in other words large washed out nuclei (nuclear clearing and powdery chromatin and nuclear grooves)
They are seen in papillary thyroid cancer.
Would also commonly see Psammoma bodies (calcium clumps).
“Little Orphan Annie Wants a Momma & a Pappa”
Orphan Annie – Orphan Annie Nuclei
“s a Momma” – Psammoma Bodies
Pappa – Papillary Thyroid Carcinoma
The second image is the same specimen stained for calcitonin. What cancer is it?
Medullary Thyroid Cancer
This is a neuroendocrine tumour of the parafollicular C cells of the thyroid that produce calcitonin.
How are papillary and follicular (i.e. differentiated) thyroid cancers staged?
TNM staging but age is the most predictive prognostic indicator so staging is different for <55yo and >55yo.
How are anaplastic thyroid cancers staged?
TNM staging but ALL are considered stage 4 due to the aggressive nature of this cancer.
How is medullary thyroid cancer staged?
TNM staging.
What is the typical place to find parathyroids?
Superior = posterolateral to recurrent laryngeal nerve, superior to the inferior thyroid artery.
Inferior = anteromedial to the recurrent laryngeal nerve, inferior to the inferior thyroid artery.
Where are the most common parathyroid ectopic sites?
Superior = retrooesophageal or paraoesophageal
(80% of superior PTs will appear in same place as their contralateral counterpart)
Inferior = tail of thymus.
Much more variable (as further to travel embryologically)
How does Cholecalciferol increase phosphate and calcium?
Converts to active form Calcitriol which in turn
Increases calcium and phosphate absorption from GI tract
Increases renal reabsorption of Calcium
Stimulates osteoblasts to release RANKL which stimulated osteoclasts to secrete calcium from bones.
What do each of these patients have?
A - primary hyperparathyroidism
(increased PTH, increases serum Ca, doesn’t effect urinary Ca and doesn’t effect vit D)
B - vit D deficiency has lead to PTH increasing to compensate to try maintain normal calcium levels.
C - Familial Hypercalcaemia Hypocalciuria is an inactivating mutation in calcium sensing receptor in parathyroid hormone so the parathyroid produces more PTH as ‘thinks’ low Ca even when there isn’t. So leads to hypercalcaemia but also hypocalciuria.
Label this photograph
What post operative labs do you order for post parathyroidectomy? What do you do with the results?
Calcium and PTH day 1 post op.
Also serum calcium at 3-4 months
Serum calcium at 6 months
