Endocrine Flashcards

Question 1

Q

Outline your treatment of post-thyroidectomy hypocalcaemia.

Answer

A

Normal levels are 2.2 - 2.6 mmol/L

Check PTH

Decide on amount of Ca and Vit D to give based on Ca and PTH. Don’t need to check a vit D level; helps Ca reabsorption regardless of pre-existing levels.

Also check and replace magnesium as hypomagnesaemia frequently co-exists and potentiates the hypoparathyroidism effect

if only Ca low and pt asymptomatic: give nothing or BD vit D
if Ca low & PTH low & pt asympatomatic: BD vit D and calcium, then try to wean calcium
if Ca & PTH low & pt symptomatic: BD vitD and TDS calcium
- if Ca ≤1.9 then give IV calcium too
if Ca low & PTH unrecordable: BD vitD and TDS/QID Ca
- if Ca low & PTH unrecordable & pt symptomatic - likely needs IV too
- if not responding to oral regimen + IV boluses then may need IV infusion over 1-2days til bone stocks of calcium replenished the wean off IV (with cardiac monitoring)

Vitamin D used is 0.25mcg BD

Oral calcium used is 1g of elemental calcium BD/TDS/QID

IV calcium used is initially 1 ampoule of 10% calcium gluconate in 100mL of normal saline over 10mins

Infusion is 5 ampoules in 500mL over 6-8hours and don’t stop infusion suddenly; taper slowly depending on response and repeat Ca q6-12hrs while on infusion

Discharge on oral calcium with blood tests for Ca and PTH every 3-7 days depending on severity and planned weaning. Aim for Ca ~2.0; if too high into normal range no stimulus for remaining/reimplanted parathyroids to hypertrophy. PTH is a good guide to whether you can continue to wean calcium bc in some people PTs wake up suddenly

Question 2

Q

Outline your management of a patient with thyrotoxicosis who is pregnant.

Answer

A

Confirm diagnosis
- Anti-TSH ABs ?Graves
- TSH, Free T4 and T3 levels
- FNA only if solitary nodule
Optimum medical therapy
- PTU preferred in pregnancy
  - 400mg PO TDS and taper
- Methimazole reserved if PTU fails
- Carbimazole associated with birth defects (imperforate anus)
- Reserve beta-blockers due to IUGR, fetal bradycardia, neonatal hypoglycaemia
  - Propanolol is most studies
- I¹³¹ is contraindicated
  - Note, if I¹³¹ used in the past then mother still has antibodies!
Reserved surgical therapy
- Indicated when
  - Medical therapy fails
  - Intolerable side effects
  - Non-compliant patient
- Aim for total thyroidectomy in 2^nd trimester
Post-partum
- Note future pregancies may be complicated by remaining antiboides
- Grave’s may worsen post partum
Follow up
- Routine TFTs on newborns
- Follow maternal TFTs for one year

Question 3

Q

What is the differential for a rapidly enlarging thyroid mass?

Answer

A

Painless:

Anaplastic thyroid cancer
Thyroid lymphoma
Parapharyngeal sarcoma

Painful:

Bleeding into pre-existing cyst
Riedel’s (fibrotic) thyroiditis
Suppurative thyroiditis

Question 4

Q

What are the radiologically suspicious features of a thyroid nodule on USS?

Answer

A

Irregular margins
Hypoechoic lesion
Loss of a halo
Internal vascularity
Internal calcifications
Increased height:width ratio

All of the above confer high score/risk as per the TIRADS classification (not widely used in USA).

Question 5

Q

What is the role of lymph node dissection in thyroid cancer?

Answer

A

Most surgeons would agree with the 2015 ATA consensus guidelines that CLND is recommended when there are clincally apparent metastases.

The role of prophylactic CLND is controversial. Weak evidence suggests a role for pCLND in PTC, T3/T4 tumours, and where there are positive lateral nodes.

NB: Secondary CLND can be performed in expert hands without added morbidity, and is recommended when proven recurrence in the central compartment is detected; if a CLND was note performed at the index procedure.

The indications for LLND are clear; compartmental LLND is recommended for proven metastatic lateral lymph nodes.

Question 6

Q

What are the indications and principles of Radioactive Iodine in thyroid cancer treatment?

Answer

A

In general can be used for

ablation - to assist follow-up (rarely used in Auckland; strong preference for completion thyroidectomy if RAI indicated rather than ablating but may be exceptions e.g. damaged RLN on other side
- and in pts w low risk DTC, disease surveillance may be accomplished w/o RAI ablation using neck USS & Tg w Tg antibody measurements while on thyroid hormone therapy
adjuvant therapy (intended to improve DFS by theoretically destroying suspected but unproven residual dsiease, espec in pts at risk of disease recurrence
therapy for persistent disease (intended to improve DSS and DFS by treating persistent disease in higher risk patients

Radioactive Iodine Ablation (RIA) is recommended for patients with high risk or some intermediate risk (ATA stratification) patients

Known distant metastases
Gross extrathyroidal extension
Primary tumour >4cm
Regional lymph node metastases
High risk features on histology.

Radioiodine causes cytotoxicity by the emission of short path-length (1 to 2 mm) beta radiation. Iodine uptake is limited by sufficient iodine levels (diet, CT contrast, amiodarone) and so the patient must either be hypothyroid (so TSH increases - w/h thyroxine for 3-4wks prior to RAI therapy) or be given recombinent TSH. RCTs show little difference between the two approaches.

Question 7

Q

Outline the tumourgenesis of thyroid cancer.

Answer

A

RET (Re-arranged during Transfection) proto-oncogene mutation

Characterises MEN IIa and IIb and fMTC

RAS (Rat Sarcoma) oncogene mutations

Seen in 40-50% of PTC, FTC, and ATC

BRAF (B-Rapidly Accelerated Fibrosarcoma) proto-oncogene

Most common genetic alteration in PTC

Question 8

Q

Outline the arguments for and against total thyroidectomy for thyroid cancer.

Answer

A

Firstly, total thyroidectomy is widely recommended for:

Tumours >4cm
Younger than 15, older than 45
Past irradiation
Bilateral nodularity
Known mets
Aggressive variant

For:

Able to use I¹³¹
Able to follow up with Tg
Eliminates contralateral/multifocal cancer
Slight increase in survival and reduced LR

Against:

Increased surgical risk to RLN and parathyroids.
ATA guidelines 2015 recommend lobectomy for tumours <1cm.

Question 9

Q

What are the indications for surgical treatment of thyrotoxicosis?

Answer

A

Manage jointly with endocrinologists; 6Ms

Malignancy
Medical therapy failure
Mechnical compression
Menacing consequences of I¹³¹(pregnancy, eye disease, allergy)
Mediastinal extension
Marred beauty

Question 10

Q

What are the side effects of radioactive iodine therapy?

Answer

A

Short term:
- anorexia, nausea, headache
- transient oligospermia/oligomenorrhoea
- sialadenitis
- neck swelling
- haematological/BM depression
- exacerbation of cardiac arrhythmias espec in older pts
- thyroid storm (rare)
- worsens Graves eye disease in 33%
Long term:
- chronic sialadenitis
- xerostoma
- dental caries
- nasolacrimal duct obstruction
- pneumonitis
- leukaemia
- inc risk secondary malignancies: bone, breast, kidney, salivary glands
men receiving cumulative RAI activities ≥400mCi should be counselled on potential risks of infertility
Pregnancy must be avoided for 6-12 months
Avoid children for ?one week following therapy.
don’t give to breastfeeding women; defer until stopped breastfeeding or pumping for at least 3mo

Question 11

Q

What are the indications for surgical treatment of primary

hyperparathyroidism?

Answer

A

SYMPTOMATIC OR
Age <50
Bone density: T score
Calcium ≥0.25mmol above upper limit normal or CrCl <60
Deposits - ie nephrolithiasis or nephrocalcinosis
Expressed preference by pt
Follow up/surveillance not a good option

Question 12

Q

What are the actions of parathyroid hormone?

Answer

A

PTH is secreted from the chief cells of the parathyroid glands in response to low serum calcium (2.12-2.65)

Increases calcium absorption from gut
Increases calcium reabsorption from DCT
Increases calcium reabsorption from bone
Promotes hydroxylation of 25-OH-Vit to 1,25-OH-Vit D in kidney (which also increases Ca from gut)
Inhibits phosphate reabsorption from PCT
Inhibits HCO^3- resorption from PCT

Question 13

Q

What are the clinical manifestations of hyperparathyroidism?

Answer

A

“Stones, bones, abdominal groans, psychic moans, and fatigue-overtones”

Gastrointestinal:

Nausea, vomiting, pancreatitis, weight loss, consitipation, anorexia

Cardiovascular:

Hypertension, shortened Q-T, wide T-waves, bradycardia, heart block, arrhythmia, valvular calcifications

Renal:

Nephrolithiasis, nephrocalcinosis, polyuria, polydipsia, renal colic, renal failure

Neuropsychiatric:

Anxiety, headaches, tiredness, dementia, paranoia, confusion, depression, fatigue

Skeletal:

Osteopenia, osteoporosis, osteitis fibrosa cystica.

Misc:

Gout, corneal band keratopathy, calciphylaxis.

Question 14

Q

What are the indications for surgical treatment of secondary hyperparathyroidism (even if the calcium is high-normal)?

Who gets a sub-total versus total parathyroidectomy?

Answer

A

Renal osteodystrophy
Calciphylaxis
Pruritis
Impairs vascularity of transplant candidates
Hyperphosphataemia

Patients who are transplant candidates should be considered for sub-total as their native glands should work once transplanted (i.e. secondary stimulus removed).

Question 15

Q

Describe the medical management of secondary hyperparathyroidism.

Answer

A

Restrict phosphate in diet
Phosphate binders
Vitamin-D supplementation
Calcimimetics (bind CSR and reduce PTH driven hypercalcaemia and hyperphosphatemia)
Calcium supplements (losing calcium +++)

Question 16

Q

Describe peri-operative management of a patient undergoing surgery for a phaeochromocytoma.

Answer

A

After diagnosis is established the focus is on pharmacological control of the adverse effects of circulating catecholamines
Phenoxybenzamine, a non-competative, non-selective α-adrenergic receptor antagonist is used
Commenced at 20mg BD and up-titrated until postural hypotension occurs
Usually takes 2-4 weeks
ß-blockers may also be required to counter the tachycardia or arrhythmias but not until α-adrenergic blockade is complete.
Intraoperative careful handling
Post-resection expect increased fluid +/- pressor requirements.

Question 17

Q

Describe the theory and methodology of Dexamethasone suppression tests.

Answer

A

Dexamethasone suppression tests are used to assess the status of the hypothalamic-pituitary-adrenal (HPA) axis and for the differential diagnosis of adrenal hyperfunction.

Low-dose DSTs are used to differentiate patients with Cushing’s syndrome from those that do not have Cushing’s syndrome. If the axis is normal, any supraphysiological dose should suppress ACTH.

High-dose DST are used to distinguish those that have a primary pituitary lesion (Cushing’s disease) from those that have an ectopic source of ACTH. In patients with a pituitary lesion, high supraphysiological doses are still capable of exerting negative feedback on ACTH production from the pituitary.

Question 18

Q

What is Nelson’s syndrome?

Answer

A

A syndrome characterised by a triad of hyperpigmentation, excessive ACTH production, and a corticotroph adenoma.

Seen in patients following bilateral adrenalectomy for Cushing’s disease. Loss of the negative feedback on the pituitary from circulating cortisol results in pituitary adenoma formation.

The incidence is reduced by prior radiotherapy to the pituitary.

Question 19

Q

What is Carcinoid syndrome?

Answer

A

Carcinoid syndrome describes a constellation of symptoms caused by release of vaso-active substances released by neuroendocrine tumours. Secretory diarrhoea is the most common feature of the syndrome, but flushing, bronchospasm, and right-sided valvular disease may occur.

These substances include serotonin, bradykinin, substance-P, prostaglandins, transforming growth factors, platelet-derived growth factors, and occasionally noradrenaline.

Mono-amine oxidase in the liver is usually capable of metabolising these substances, so the presence of carcinoid syndrome implies that there is either metastatic disease to the liver or that the primary is of non-gut origin (ovary, retroperitoneum).

Question 20

Q

What is the distribution of Neuroendocrine Tumours throughout the body?

Answer

A

30% extra-gastrointestinal (lung, thymus, gynae)
25-30% small intestine (cause most carcinoid syn.)
15% rectum
10% colon
5% appendix
5% stomach
<2% duodenum
<1% oesophagus

Question 21

Q

Describe the phenomenon of a “thyroid storm”

Answer

A

Thyroid storm is a rare, life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis.

It is often precipitated by an acute event such as thyroid or nonthyroidal surgery, trauma, infection, an acute iodine load, or parturition.

Cardiovascular symptoms in many patients include tachycardia to rates that can exceed 140 beats/minute and congestive heart failure. Hypotension, cardiac arrhythmia, and death from cardiovascular collapse may occur. Hyperpyrexia, agitation, anxiety, delirium, psychosis, stupor, or coma are also common and are considered by many to be essential to the diagnosis.

Question 22

Q

What is goitre?

What causes goitre?

What are the histopathological features of goitre?

Answer

A

The term goitre refers to abnormal growth of the thyroid gland. Goitres can be diffuse or nodular, depending on the cause, and may be associated with normal, decreased, or increased thyroid hormone production. The clinical manifestations vary with thyroid function and with the size and location of the goitre.
Causes of goitre vary with geography; worldwide the most common cause is Iodine deficiency. In Iodine-replete countries such as New Zealand, the most common causes of goitre are multi nodular goitre, Graves’ disease, and Hashimoto’s disease. Rarer causes include medication induced goitre, tumours, infiltrative diseases, and thyroiditis.
The pathophysiology of goitre in iodine-deficient patients is due to hyperplasia of the gland, due to increased circulating TSH, in order to increase production of thyroid hormone. In the iodine replete patient the pathophysiology is incompletely understood, but probably due to an imbalance of the growth factors acting on the thyroid.
Macroscopically, multi nodular goitre presents as a heterogenous looking gland with nodules of varying size and colour. The capsule is intact and the nodules are typically themselves smooth.
Microscopically, the nodules may contain areas of haemorrhage, calcification, or fibrosis due to the chronicity of the disease.

Question 23

Q

What is Graves’ disease?

Answer

A

Graves’ disease is an autoimmune disease that may consist of hyperthyroidism, goiter, eye disease (orbitopathy), and occasionally a dermopathy referred to as pretibial or localized myxedema. Hyperthyroidism is the most common feature of Graves’ disease, affecting nearly all patients, and is caused by thyroid-stimulating hormone (TSH, thyrotropin)-receptor antibodies (TRAb) that activate the receptor, thereby stimulating thyroid hormone synthesis and secretion as well as thyroid growth (causing a diffuse goiter).

Question 24

Q

Describe the pathophysiology of Graves’ ophthalmopathy

Answer

A

The predominant autoantibody in Graves’ is directed at the TSH receptor, which is also expressed on adipocytes and fibroblasts.
Stimulation of the retro-ocular fibroblasts leads to hyperplasia, inflammation, and production of glycosaminoglycans with subsequent retro-ocular expansion
The accumulation of hydrophilic GAG in turn leads to fluid accumulation, muscle swelling, and an increase in pressure within the orbit. These changes, together with retroocular adipogenesis, displace the eyeball forward, leading to extraocular muscle dysfunction and impaired venous drainage.

Question 25

Q

What are the risk factors for thyroid cancer?

Answer

A

Previous ionising irradiation is the most significant risk factor for papillary thyroid cancer.
Iodine deficiency and endemic goitre are the most significant risk factors for follicular thyroid cancer.
Medullary thyroid cancer is associated closely with the MEN2 syndromes and Familial Medullary Thyroid Cancer as well as sporadic mutations in the RET oncogene.
Anaplastic thyroid cancer arises in well-differentiated thyroid cancer 50% of the time.

Question 26

Q

Classify thyroid cysts.

What cysts warrant surgical removal?

Answer

A

Simple cysts
- Usually benign
- Account for ~1/3^rdof surgically excised nodules.
Mixed solid and fluid cysts
- Up to 10% are malignant
- USS guided FNA for optimal sample

Surgical excision if:

malignant or suspicious cytology
Large >4cm (~20% chance of malignancy)
Rapid refill after aspiration / recurs after x3 aspirations
Heavily blood-stained
History of head and neck irradiation

Question 27

Q

How does the ATA stratify risk in differentiated thyroid cancer?

Why is this useful?

Answer

A

Low risk (~14% recurrence/persistent disease)

Aim for TSH 0.5-2.0mU/L & No RAI

Papillary thyroid ca with all of the following:
- No regional or distant metastases
- Complete macroscopic resection of tumour
- No extrathyroidal invasion of locoregional structures
- No aggressive histology or vascular invasion (eg tall cell, hobnail variant, columnar cell carcinoma)
- No RAI uptake outside of the thyroid bed on first post-treatment RAI scan
- Clinical N0 or ≤5 pathological N1 micromets (<0.2cm in largest dimension)
Intrathyroidal, encapsulated follicular variant of papillary thyroid cancer
Intrathyroidal, well differnetiated follicular thyroid cancer with capsular invasion and no or minimal (<4 foci) vascular invasion
Intrathyroidal papillary microcarcinoma, unifocal or multifocal

Intermediate risk (~45% recurrence/persistent disease)

Aim for TSH 0.1-0.5mU/L + Selective RAI

Microscopic tumour invasion of perithyroidal soft tissue
Cervical node metastases or RAI uptake outside of thyroid bed in neck on first post-treatment scan
Aggressive tumour histology or vascular invasion
Papillary thyroid cancer with vascula rinvasion
Clinical N1 or >5 pathologic N1 with all involved lymmph nodes <3cm in largest dimension
Multifocal papillary microcarcinoma with ETE and BRAF mutated (if known)

High risk (~85% recurrence/persistent disease)

Aim for TSH <0.1mU/L + RAI

Macroscopic tumour invasion into surrounding structures
Incomplete tumour resection
Distant metastases
Thyroglobulinaemia out of proportion to what is seen on post-treatment scan / postop thyroglobulin suggestive of distant mets
Pathologic N1 with any metastatic LN ≥4cm in largest dimension
Follicular thyroid cancer with extensive vascular invasion (>4 foci of vascular invasion)

*from MSKCC series

Question 28

Q

Classify the causes of hypercalcaemia.

Answer

A

Redistributive
- hyperparathyroidism
  - primary
  - tertiary
  - lithium-induced
- malignancy
  - PTH-rP - acts like PTH eg lung, H&N, RCC, leukaemia, lymphoma
  - those that release calcitriol eg Hodgkin’s lymphoma
  - lytic bone mets –> resorption of Ca and PO4 eg MM, breast, RCC, thyroid, lung ca mets
- granulomatous disease
  - eg TB, sarcoid (activate vitD via macrophages in granulomas)
- other endocrine
  - adrenal insufficiency
  - thyrotoxicosis
  - acromegaly
  - phaeochromocytoma
- other bone disease
  - Paget’s, prolonged immobility
Increased intake
- high dose Ca, Vit D, vit A replacement
- pts on PN
- milk alkali syndrome
Decreased output
- drugs; thiazides, lithium
- FHH

Question 29

Q

How is malignancy determined in the context of functioning adrenal tumours?

Answer

A

The Weiss Criteria (3 or more of the following)

Nuclear grade
Mitotic rate
Atypical mitoses
More than 25% clear cells
More than one third diffuse pattern
Venous invasion
Sinusoidal invasion
Capsular invasion

Question 30

Q

What are the causes of bilateral adrenal masses?

Answer

A

Primary adrenal
- Bilateral phaeochromocytomas
- Bilateral cortical adenomas
- CAH
Secondary/ adrenal
- ACTH production
Metastatic
- Breast, lung, GI, melanoma
Infective
- TB, histoplasmosis, cryptococcus
Lymphoma

Question 31

Q

Describe the changes of thyroid physiology during pregnancy

Answer

A

An increase in serum thyroxine-binding globulin driven by increased estrogen.

To maintain adequate free T4/T3 the thyroid gland must produce more total T4/T3. Levels of total thyroid hormone increase by ~50%

Stimulation of the thyrotropin receptor by hCG

hCG and TSH are in the same family of glycoprotein hormones that share an alpha subunit.
hCG producing-tumours, ^e.g. hydatiform mole, can lead to thyrotoxicosis

Question 32

Q

Why are there concerns around the use of contrast CTs in the setting of thyroid cancer?

Answer

A

Iodine-containing contrast agents can interfere with subsequent I¹³¹ radioablative treatment of advanced thyroid cancer.

The washout period is unclear; urinary iodine concentration has been used in some studies to predict clearance though the data is lacking.

Additionally, in some patients iodine contrast agents can precipitate a thyrotoxicosis (see Jod-Basedow effect)

Question 33

Q

What is a sestamibi scan?

What is SPECT?

What is 4D-CT?

Answer

A

Sestamibi is a radiolabelled nucleotide that is taken up by the mitochondria in thyroid and parathyroid tissue.
The radiotracer is retained by the mitochondria-rich oxyphil cells in parathyroid glands longer than in thyroid tissue. Note that chief-cell rich adenomata may not take up as much MIBI.
Planar images are obtained shortly after injection and at 2 hours to identify foci of tracer that approximate the location/side of a parathyroid adenoma.
Sestamibi-single photon emission computed tomography (SPECT or MIBI-SPECT) is a three-dimensional sestamibi scan that provides higher-resolution imaging and improves the performance of sestamibi scanning
SPECT improves the sensitivity for identifying abnormal parathyroid glands to 92 to 98 percent as compared with 71 to 79 percent for planar sestamibi scintigraphy
Four-dimensional computed tomography (4D-CT) scans take advantage of the rapid contrast uptake and washout that is characteristic of parathyroid adenomas for precise anatomic localization
The primary disadvantage of 4D-CT is the radiation exposure, which, compared with sestamibi imaging, results in a >50-fold higher dose of radiation absorbed by the thyroid.

Question 34

Q

What is the Pasieka score?

Answer

A

A 13-item questionnaire developed by Pasieka et al. which may be used to assess the severity of symptoms on a visual analogue from which a parathyroid assessment of symptoms score (PAS) can be calculated.

Includes subjective 0-100 scales for neuropsychaitric symptoms including tiredness, feeling blue, feeling weak, forgetful etc.

Question 35

Q

Describe your approach to management of a thyroid storm.

Answer

A

A multi-pronged approach to management:

Resuscitation and IV fluid
A beta blocker to control the symptoms and signs induced by increased adrenergic stimulation
- decreases HR, SBP, muscle weakness, tremor, degree of irritability/emotional lability
A thionamide to block new hormone synthesis
- includes propylthiouracil (PTU), methimazole, carbimazole
- block synthesis of thyroid hormone & act by inhibiting iodination/organification of tyrosine + coupling of iodotyrosine molecules to form T3 and T4
An iodine solution to block the release of thyroid hormone by altering the organic binding process (Wolff-Chaikoff effect)
Glucocorticoids to reduce T4-to-T3 conversion, promote vasomotor stability, and possibly treat an associated relative adrenal insufficiency
Bile acid sequestrants may also be of benefit in severe cases to decrease enterohepatic recycling of thyroid hormones

Question 36

Q

What specific chemotherapeutic agent is used in Adrenocortical carcinoma?

Answer

A

Originally an insecticide, Mitotane is a lipophilic agent that concentrates in the adrenal cortex and induces necrosis by mitochondrial degeneration.

Used for metastatic disease or recurrence but also improves DFS.

Specific to the adrenals (esp. zona fasciculata and reticularis), also toxic to the contralateral gland and induces adrenal insufficiency.

Question 37

Q

What is the difference between secretion from an adrenal phaeochromocytoma and an extra-adrenal phaeochromocytoma?

Answer

A

Expression of PNMT (phenylethanolamine N methyl-transferase) in extra-adrenal pheochromocytomas (10% of cases) is negligent, which explains the preferential production of norepinephrine by these tumors, compared to both norepinephrine and epinephrine production by adrenal pheochromocytomas.

Both are capable of elaborating Dopamine from Tyrosine by tyrosine hydroxylase, which is present in neurons of the CNS, sympathetic nerves of peripheral nervous system, chromaffin cells of the adrenal medulla and extramedullary paraganglia.

Question 38

Q

ATA risk stratification system to estimate risk of persistent/recurrent disease in differentiated thyroid cancer

Answer

A

The ATA initial risk stratification is used to estimate the risk of persistent/recurrent disease. Designed to stratify pts as having either low (papillary thyroid cancer confined to thyroid), intermediate (regional mets, worrisome histologies, extrathyroidal extension or vascular invasion) or high (gross extrathyroidal extension, distant mets or postop serum Tg suggestive of distant mets) risk of recurrence, primarily based on clinicopathological findings.

The risk of recurrence, however, follows a continuum across the three discrete risk categories.

Additional prognostic variables (eg extent of LN involvement, degree of vascular invasion in FTC) were included in a modified version of the risk stratification system - and included below - though additional variables not been rigorously evaluated

Low risk
- papillary thyroid ca with all of following present:
  - no local or distant mets
  - all macroscopic tumour has been resected
  - no invasion of locoregional tissues
  - tumour does not have aggressive histology (aggressive histologies include tall cell, insular, columnar cell carcinoma, Hurthle cell carcinoma, follicular thyroid cancer, hobnail variant)
  - no vascular invasion
  - no 131I uptake outside thyroid bed on post-treatment scan, if done
  - clinical N0 or ≤5 pathologic N1 micromets (<0.2cm in greatest diameter)
- intrathyroidal, encapsulated follicular variant of PTC
- intrathyroidal, well-differentiated follicular thyroid cancer with capsular invasion and no or minimal (<4 foci) vascular invasion
- intrathyroidal, papillary microcarcinoma, uni or multifocal, including BRAF V600E mutated if known
Intermediate risk - any of following present
- microscopic invasion into perithyroidal soft tissues
- cervical lymph node mets or 131I avid metastatic foci in the neck on the post-treatment scan done after thyroid remnant ablation
- tumour with aggressive histo or vascular invasion
- clinical N1 or >5 pathologic N1 with all involved LNs <4cm in largest dimension
- multifocal papillary thyroid microcarcinoma with extrathyroidal extension and BRAF V600E mutated (if known)
High risk - any of following present:
- macroscopic tumour invasion
- incomplete tumour resection with gross residual disease
- distant mets
- postop serum thyroglobulin suggestive of distant mets
- pathologic N1 with any metastatic LN ≥3cm in largest dimension
- FTC with extensive vascular invasion (>4 foci of vasc invasion)

Question 39

Q

What is the dose of thyroxine to start following a thyroidectomy?

Answer

A

1.6 to 2 mcg/kg per day

Question 40

Q

Surgical management for differentiated thyroid cancer

Answer

A

depends on
- extent of disease (eg primary tumour size and presence of extrathyroidal extension or LN mets)
- pt’s age
- presence of comorbidities
tumour <1cm w/o extrathyroidal extension and no LNs
- thyroid lobectomy preferred unless contralateral thyroid cancer, previous H&N radiotherapy, strong fhx of thyroid ca or imaging abnormalities that will make f/u difficult
tumour 1-4cm w/o extrathyroidal extension and no LNs
- initially can do total or lobectomy
- total would be chosen based on pt preference, decision by tx team that radioiodine therapy may be beneficial either as adjuvant therapy or to facilitate f/u, or factors above
tumour ≥4cm, extrathyroidal extension or mets to LNs or distant sites
- total
multifocal papillary microcarcinoma (<5 foci)
- lobectomy and isthmusectomy ok
multifocal papillary microcarcinoma (>5 foci)
- when multifocal PTC appreciated preop, particularly when large number suspected eg >5, espec if the foci are in the 8-9mm size range, likely total (and same for completion)

Question 41

Q

Risk factors for thyroid nodules

Answer

A

worrying exam findings: vocal cord paralysis, cervical lymphadenopathy, fixation of nodule to surrounding tissue
fhx of thyroid ca/MEN/other familial thyroid ca syndrome (eg PTEN hamartoma tumour syndrome, FAP< Carney complex, Werner syndrome, Gardner syndrome)
risk factors:
- male
  - age <20 or >60
  - rapid growth of nodule
  - hx of radiation in childhood
  - phx of thyroid ca
  - fhx thyroid ca or MEN/other as above
  - FDG avid nodules
  - clinical indicators of potential invasion eg pain or hoarseness

Question 42

Q

Suspicious USS features for thyroid nodule

Answer

A

solid
hypoechoic
taller than wide
lobulated/irregular margins or extra-thyroidal extension
echogenic foci/microcalcification
intranodular vascularity

Question 43

Q

TiRads system and which nodules to FNA

Answer

A

Points for: (CEEMS)

composition
- solid = more points
echogenicity
- hypoechoic = more points
echogenic foci
- none 0pts, macrocalcs 1pt, peripheral (rim calcs) 2pts, punctate echogenic foci 3pts
margin
- smooth/ill-defined ok, lobulated/irregular 2pts, extrathyroidal extension 3pts
shape
- taller than wide = more points

TR1 = benign, no FNA
TR2 = not suspicious, no FNA
TR3 = mildly suspicious, FNA if ≥2.5cm, follow if ≥1.5cm w USS 12-24mo
TR4 = mod suspicious, FNA if ≥1.5cm, follow if ≥1cm w USS 12mo
TR5 = highly suspicious, FNA if ≥1cm, follow if ≥0.5vm w USS 6-12mo

Also FNA any PET-avid thyroid nodule ≥1cm. Avoid FNA in toxic pts due to higher false negs unless clear suspicious features or endocrinologist opinion

Question 44

Q

Causes of increased and decreased radioiodine uptake

Answer

A

increased uptake
- hyperthryoidism - includes Graves toxic nodule, thyroid hormone resistance
- nontoxic goitre = Hashimoto thyroiditis
- decreased renal clearance of iodine (renal insufficiency, severe heart failure)
- iodine deficiency (endemic or sporadic dietary, pregnancy)
- TSH administration
decreased uptake
- hypothyroidism (primary or secondary)
- TSH resistance
- thyroid hormone replacmeent/suppression
- iodine excess (dietary, drugs)

Question 45

Q

Bethesda categories

Answer

A

The Bethesda criteria is a system for reporting thyroid cytopathology. Recognises 6 diagnostic categories & provides an estimation of cancer risk within each category.

Below is estimated/predictive risk of malignancy by Bethesda system, vs actual risk of malignancy in nodules surgically excised in a meta-analysis

I = non-diagnostic/unsatisfactory
- 1-4% vs 20%
II = benign
- 0-3% vs 2.5%
III = atypia of undetermined significance (AUS/FLUS)
- 5-15% vs 14%
IV = follicular neoplasm/suspicious for follicular neoplasm (FN/SF) (also encompasses Hurthle cell neoplasm/suspicious for Hurthle cell neoplasm)
- 15-30% vs 25%
V = suspicious for malignancy (SUSP)
- 60-75% vs 70%
VI = malignant
- 97-99% vs 99%

NB: PTC has discrete cellular cytologic characteristics that make FNA extremely accurate in diagnosing it. FTC dx can’t be made on FNA, though FTCs don’t have same cytologic appearance as benign thyroid tissue & are often categorised as suspicious for follicular neoplasm.

Question 46

Q

What to do with each Bethesda category?

Other reasons to consider surgery for thyroid nodule?

Answer

A

Bethesda I
- repeat FNA with USS guidance
- consider surgery if ≥2 non-diagnostic (risk of ca can’t be considered negligible), espec if high suspicion sonographic pattern, >20% growth in size, clinical risk factors for malignancy
Bethesda II
- no further immediate mx
Bethesda III
- consider second pathologist opinion review
- case by case - repeat FNA vs diagnostic lobectomy vs observation
Bethesda IV
- diagnostic hemithyroidectomy (or consider total if pt preference, significant risk factors for malignancy, sonographically suspicious or >4cm)
Bethesda V
- diagnostic hemi vs total depending on clinical risk factors above, sonographic features, pt preference
Bethesda VI
- total may be recommended, but pt could choose hemi in first instance particularly if small lesion and no adverse features on USS (ie no extrathyroidal extension, no abN LNs)

Other reasons to consider surgery:

pressure symptoms
large (eg >4cm); usu the indication is pressure sypmtoms in this group
- NB up to 34% false negative FNA rate in this group
causing cosmetic deformity
associated with recurrent haemorrhage
thyroid cysts if:
- recurrent (ex 3x reaccumulation after aspiration of symptomatic cyst)
- >3-4cm

Question 47

Q

Epidemiology of papillary, follicular, molecular, anaplastic thyroid ca

Answer

A

papillary = 80% thyroid ca, F>M 3:1, 20-40yrs, LN spread
- PapillarY - paed - occurs in 20s, yellow = LN spread
follicular = 15% thyroid ca, F>M 5:1, 40-50yrs, haematogenous spread
- FolliculaR - forties/fifties, red = blood spread
- Hurthle cell (variant) - mainly in older pts
medullary
- 5% thyroid cas
- M=F
- sporadic 50-70, familial younger eg 20-30
anaplastic
- <1% thyroid ca
- F>>M
- usu >65yrs

Question 48

Q

Aetiology of thyroid ca

Answer

A

papillary
- childhood rad = most important risk factor, commonly causess RET/PTC chromosomal rearrangements and also p53 mutations
  - latency 5-30yrs, risk of malignancy in nodule of someone w hx of rad = 30-40%
- genetic lesions that activate MAPK signalling pathway
  - can be chromosomal rearrangements eg RET & NTRK1 oncogenes
  - or point mutaitons eg BRAF & RAS oncogenes
- familial in 7% - FAP, Werner, Cowden, HNMTC
follicular
- also mutations leading to activation of MAPK but BRAF not implicated in FTC; can have kRAS mutation though
- p53 also occurs in follicular, asosc w more aggressive disease
- low dietary intake of iodine assoc w higher proportion of follicular & anaplastic ca
medullary
- RET proto-oncogene - 50% have identifiable mutation
- 75% sporadic (40-50% of which have acquired RET mutation)
- 25% hereditary - as part of MEN2A or MEN2B or ‘familial MTC (variant of MEN2A)
anaplastic
- may arise from differentiated thyroid ca
- up to 50% have hx of goitire
- low dietary iodine intake assoc
- p53 mutation in 15%

Question 49

Q

What are the clinical features of medullary thyroid cancer and anaplastic thyroid cancer?

Answer

A

medullary may present with
- found on genetic testing or elevated calcitonin +/- CEA
- palpable mass +/- compressive sx +/- systemic sx eg bone pain, flushing, diarrhoea in 10%
anaplastic
- older pt w dysphagia, cervical tenderness & fixed, painful, rapidly enlarging neck mass
- +/- SVC syndrome
- +/- rapidly deteriorate to tracheal obstruction & rapid local invasion of surrounding structures

Question 50

Q

Histo features of papillary thyroid cancer

Answer

A

well-differentiated wtih retained follicular cell differentiation, finger-like (papillary) columnar epithelium projections

unique nuclear features: nuclei have clear/ground-glass appearance, powdery chromatin, overlapping nuclei, irregular nuclear contours w nuclear grooves & pseudoinclusions, fragments of papillae, psamomma bodies (laminated calcifications), orphan Annie eyes (clearing of nuclei in centre)

can make dx on FNA bc features mainly in nuclei

multifocality in up to 80%, 33-50% bilateral disease

lymphatic spread common (up to 90%); distant mets 3-5% at dx (lung & bone)

Question 51

Q

Histo features of follicular thyroid cancer

Answer

A

Wide range of microscopic changes ranging from virtually normal follicular architecture & function to severely altered cellular architecture.

FNA: hypercellular with microfollicular pattern & scant colloid suggests follicular neoplasm (adenoma or carcinoma)

Histo dx depends on demonstration of follicular cells occupying abnormal positions - incl capsular or vasc invasionk; 2 types based on ATA risk categories

low risk = intrathyroidal, well-differentiated FTC with capsular invasion and no or minimal (<4 foci) vascular invasion
high risk = FTC with extensive vascular invasion (>4 foci of vasc invasion)

LN involvement unusual (<10%) though up to 30% for Hurthle cell. Haematogenous spread with mets in 10-15% (lung+bone)

Question 52

Q

Discuss lymph node dissection in papillary thyroid cancer

Answer

A

if known central nodal involvement or pathological nodes found at surgery, do therapeutic central neck dissection
prophylactic central neck dissection controversial, will never be RCT
- consider in higher risk situations eg tumours >4cm, gross extrathyroidal extension & lateral neck nodal disease
- secondary CLND can be done w/o increased risk in expert hands if proven recurrence and CLND not done initially
indications for LLND clear; if known lateral nodal involvement, ipsilateral therapeutic lateral neck dissection; little benefit to prophylactic

Question 53

Q

Discuss surgical management of medullary thyroid cancer

Answer

A

check for phaeo - if found, operate on that first
if preop dx or syndromic predisposition: at least total + prophylactic CLND
if lateral nodes clinically, rad or on biopsy, ipsilateral LLND (some advocate for prophylactic LLND if known level VI disease on that side but not universal)
if distant metastatic disease identified preop: palliative total + CLND to reduce burden of local mass effect, or debulking op if curative resection not possible, leaving functionally important structures eg RLN & PTs
if MTC dx postop in pt who had a hemi, do completion total unless sporadic & unifocal with no C cell hyperplasia, otherwise normal USS of neck, negative surgical magin & normal serum calcitonin all confirmed
autograft any resected/devasc PTs but if RET neg/MEN2B/FMTC - autograft in neck; MEN2A - heterotopic site eg brachioradialis (in case of future PT pathology)
MEN2B RET mutation = prophylactic total within 1st yr of life or at time of dx
other pts w germline RET mutation = prophylactic total before age 5 (depends on particular mutation)
CLND omitted if done before these time cut-offs unless thyroid nodules >5mm, elevated calcitonin or evidence of LN mets

Follow-up:

calcitonin at 3mo - tells you neg for disease or persistent disease
in general, 3monthly til 12mo then annual w clinical exam and biomarkers, +/- USS if clinical or biochemical suspicion
some use stimulated calcitonin instead
no role for TSH suppression or RAI bc not follicular cell origin

Question 54

Q

How is papillary thyroid cancer prognosticated?

Answer

A

TNM staging system - risk based on disease-specific mortality (may not accurately predict risk of recurrence/persistent disease)

ATA risk stratification system - estimates risk of recurrence

MAIS, AMES, AGES - prognosis

NB lymph node mets not shown to be an adverse factor on DFS in some earlier reports butu more recent, large-scale studies suggest increased mortality with regional LN mets

Question 55

Q

AGES/AMES clinical scoring system for prognostic risk classification for pts w differentiated thyroid cancer

Answer

A

Low risk vs high risk

Age:
- <40yrs
- >40yrs
Grade
- well differentiated
- poorly differentiated
Extent
- no local extension, intrathyroidal, no capsular invasion
- capsular invasion, extrathyroidal extension
Size
- <2cm
- >4cm
Sex
- F
- M
Mets
- none
- regional or distant

Question 56

Q

TNM staging for thyroid carcinoma

Answer

A

For papillary, follicular, poorly differentaited and anaplastic thyroid ca

T1 = ≤2cm limited to thyroid
- T1a = <1cm
- T1b = 1-2cm
T2 = >2cm but ≤4cm, limited to thyroid
T3 = >4cm limited to thyroid, or gross extrathyroidal extension invading only strap muscles
- T3a = tumour >4cm limited to thyroid
- T3b = gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid or omohyoid muscles) from a tumour of any size
T4 = includes gross extrathyroidal extension beyond the strap muscles
- T4a = gross extrathyroidal extension invading subcut soft tissues, larynx, trachea, oesohpagus or RLN from a tumour of any size
- T4b = gross extrathyroidal extension invading prevertebral fascia or encasing teh carotid artery or mediastinal vessels from a tumour of any size
N1a = mets to level VI or VII (pretracheal, paratracheal or prelaryngeal/Delphian, or upper mediastinal) lymph nodes; can be unilateral or bilateral disease
N1b = mets to unilateral, bilateral or contralateral lateral neck nodes (levels I, II, III, IV or V) or retropharyngeal lymph nodes
M0 or M1
prognostic stage groups for differentiated thyroid ca include
- <55 yrs vs ≥55yrs
anaplastic is all stage IV (A-C)

Question 57

Q

Discuss the aims of managing differentiated thyroid cancer and the management modalities

Answer

A

Primary treatment = surgical resection
- +/- RAI ablation and TSH suppression
- persistent & recurrent disease also treated with these 3
external-beam radiation & systemic adjuvant chemo = role in a few cases

Aims of initial therapy:

complete resection of primary disease & involved cervical LNs
minimise treatment-related morbidity
accurately stage the disease
facilitate postop RAI therapy if appropriate
- remnant malignant cells or metastatic deposits can only be ablated by RAI if all normal thyroid tissue removed
facilitate long-term surveillance with RAI whole-body scan and serum Tg
- all normal thyroid tissue capable of takin gup iodine & producing Tg needs to be surgically removed & ablated w RAI to enable long-term surveillance by these methods
minimise risk of recurrence or mets

Question 58

Q

Discuss the role of RAI in differentiated thyroid cancer

Answer

A

rationale for RAI:
- ablation of remnant thyroid tissue to facilitate detection of later disease recurrence by imaging & Tg assay
- adjuvant therapy with intention of targeting occult metastatic disease
- primary treatment of known persistent disease
General trend towards being more selective in recommending RAI & towards giving lower doses of RAI
in broad terms, RAI not given for ATA low risk disease, given in select intermediate risk pts and recommended in high risk
to ensure targeted cells have uptake of RAI, need to:
- make cells iodine avid by maintaining low-iodine diet for 1-2wks before RAI administration (can check urine iodine if worried about recent iodinated contrast agent or amiodarone)
- need high TSH to stimulate RAI uptake - may be achieved by withdrawal or thyroid hormone or admin of exogenous recombinant human thyroid-stimulating hormone (if doing withdrawal can use T3 at start so shorter period off thyroid hormone altogether)

Question 59

Q

Discuss adjuvant treatment for differntiated thyroid cancer

Answer

A

postoperative management includes treatment with thyroid suppressive therapy (most patients) and radioiodine (high-risk and selected intermediate risk patients)
post-op mx depends on risk of recurrence/persistent disease which can be broadly assessed using the ATA risk categories
- adjuncts to decision making include a thyroglobulin and thyroglobulin antibody nadir checked 3-4weeks post-op
- post-op diagnostic radioactive iodine whole body scan if presence of residual disease unclear
thyroid hormone suppression - initial TSH aims
- ATA low risk: TSH 0.1-0.5mU/L if detectable Tg levels (w or w/o remnant ablation); TSH 0.5-2.0 if undetectable serum Tg levels or had lobectomy
- ATA intermediate risk: TSH 0.1 to 0.5
- ATA high risk: TSH <0.1
- goals for long-term f/u are based on response to thearpy assessments and comorbid conditions that increse potential risks of prolonged TSH suppression (eg menopause, tachycardia, osteopenia, older age, osteoporosis or AF)
RAI
- low risk - don’t routinely give
- intermediate risk - selected pts incl those w clinically significant LN mets outside of thyroid bed, vascular invasion, more aggressive subtypes eg tall cell, columnar cell, insular or poorly diff histologies
- high risk - give
external beam radiation therapy - may be used after macroscopically complete surgical excision to prevent recurrence, espec for older pts w gross extrathyroid extension at time of surgery or selected younger pts w extensive disease & poor histo features (eg insular or poorly diff histo) whose disease is resected but high likelihood of residual microscopic disease

Question 60

Q

Discuss the follow-up for differentiated thyroid cancer

Answer

A

dynamic risk stratification is key; initial staging systems can be used to guide initial therapeutic & diagnostic f/u strategy decisions but important to recognise that initial risk estimates may need to change as new data are accumulated during f/u
monitoring strategies are based upon the ATA irsk of recurrence and the reassessment of response to therapy at each follow-up visit
response to therapy is assessed primarily with USS and measurements of serum thyroglobulin + anti-TG antibodies
- Tg q3-6mo for first year and USS q6-12mo
- additional imaging (cross-sectional or function imaging) usu reserved for high-risk pts who typically have either a biochemical or structural incomplete response to therapy
- low/int risk pts who demonstrate structural or biochemical incomplete response to therapy during first yr of f/u
- whole-body radioiodine scanning may still have a role in f/u of higher risk pts
check TSH 6wks postop then ongoing

Question 61

Q

What is Trousseau’s sign?

Answer

A

A BP cuff is placed around the arm and inflated to a pressure 20mmHg greater than the SBP and held in place for 3min; in the absence of blood flow, the pt’s hypocalcaemia and subsequent neuromuscula rirritability will induce spasm of the muscles of the hand and forearm. Flexion of wrist and MCPJ, extension of DIP and PIPJs, adduction of fingers.

May be positive before other manifestations of hypocalcaemia such as hyperreflexia and tetany and more sensitive than the Chvostek sign.

Question 62

Q

What is Chvostek’s sign?

Answer

A

A twitch of facial muscles that ocurs when tapping over the facial nerve anterior to the ear as it crosses the zygomatic arch, which represents neuromuscular excitability caused by hypocalcaemia.

Question 63

Q

Management of severe hypercalcaemia

Answer

A

determine underlying cause
stop any contributing medications
first line:
- aggressive IV fluid resus with norma lsaline - 200-500mL/hr initially aiming for U/O >100mL/hr
- once volume replete can add frusemide to further increase calciuresis (by inhibiting Ca resorption in thick asc limb of loop of Henle) - rarely given
- bisphosphonates - zoledronic acid (or palmidronate) - inhibits osteoclast activity, decreases calcium over 24-48hrs
- calcitonin - also inhibits osteoclsts and increases calciuresis, rapid action within 12-24hrs, modest effect, but tachyphylaxis within 48hrs
second line:
- glucocorticoids - augments effect of calcitonin and useful in diseases w vit D excess - inhibits 1alhpa-hydroxylase activity & decreases activation of vit D
- dialysis
- calcimimetics eg Cinacalcet - only available on special authority in NZ

Question 64

Q

What is primary hyperparathyroidism and what are its causes?

Answer

A

Primary hyperparathyroidism = autonomous overproduction of PTH by 1 or more PT glands

4 pathological conditions cause it:

single adenoma (85%)
multiple adenomas (3-5%)
4 gland hyperplasia (5-9%) - more common in elderly & familial
carcinoma <1%

Risk factors: radiation, familial conditions (MEN1, MEN2A, HPT-JT syndrome, familial isolated HPTism), lithium (decreases PT cells sensitivity to calcium & alters set point

Answer 65

A

Tests to establish diagnosis
- Ca, PO4, Cl, PTH, alb, vit D, ALP, Cr, 24hr urine calcium +/- creatinine
  - PO4 low in 50% HPTism; if Ca high & Cr normal, PO4 >1.3 = not primary HPTism
  - Cl:PO4 ratio >33 = indicative of primary HPTism
  - in FHH, 24hr urine Ca <100mg and calcium clearance ratio <0.01
Tests to establish impact of disease
- bloods: renal function
- bone densitometry +/- xrays
- USS of kidneys looking for stones
localising studies if indication to operate
- not strictly required in new dx pts unless considering minimally invasive/targeted op or in recurrent/persistent hyperparathyroidism
- sestamibi scan (ideally with SPEC)
- USS - correlated with sestamibi
- +/- 4D CT if above inconclusive
- +/- venous sampling if complex cases

Answer 66

A

A = age <50

B = bone density: T score

C = calcium ≥0.25mmol above upper limit normal or CrCl <60

D = deposits - ie nephrolithiasis or nephrocalcinosis

E = expressed preference by patient (patient preference)

F = follow up/surveillance not a good option

AND all symptomatic patients

Answer 67

A

bilateral neck exploration - visualise all 4 parathyroid glands and remove 1 or more abnormal glands
- indications:
  - surgeon preference/training
  - failure of focussed operation
  - known or intraoperative identified parathyroid hyperplasia
  - high suspicion of multigland disease (secondary or tertiarl HPTism, lithium-induced HPTism, familial HPTism)
  - discordant or negative preoperative localisation studies
- if all 4 glands abnormal, subtotal parathyroidectomy - remove 3 glands + part of 4th, leave a remnant 1-2x a normal gland or ≥30g PT gland (if devasc, reimplant)
- or total parathyroidectomy if definitely not transplant candidate
- thymectomy also performed - thymus most common location for supranumerary gland
- consider intraop PTH
focused/targeted/minimally invasive parathyroidectomy
- only if localised adenoma on imaging & stilly only 80% chance of cure bc may still ahve hyperplasia
- advantages: smaller incision, shorter op time, dissection limited to left side of neck, lower rates transient hypocalcaemia

Answer 68

A

secondary hyperparathyroidism occurs due to the physiological secretion of PTH by PT glands in response to hypocalcaemia
most common causes = CKD and vit D deficiency, also intestinal malabsorption
in CKD: have high PO4 (stimulates PT glands) and also decreased activated vit D, so less Ca absorption from the gut –> feeds back to stimulate PT gland
- decreased PO4 clearance –> hyperphosphataemia
- PO4 directly stimulates PT glands
- PO4 binds with calcium and decreases level so free serum calcium reduced and calcium release from bone also reduced –> low calcium levels stimulate PTs
- stimulation of FGF-23 –> severe inhibition of 1-alpha-hydroxylase and reduced renal activation of vit D
  - this leads to reduced gut absorption of Ca, downregulation of vit D receptors on PT glands (ie vit D resistance)
- net effect of hyperphosphataemia & low levels of biologically active form of vit D = chronic hypocalcaemia, which causes
  - downregulation of CaSR on PT cell & shift in Ca set point
  - downreg of vit D receptors on PT cells
  - alterations in cell cycle regulation –> PTH hypersecretion, PT cell proliferation, PT gland hyperplasia
- further exacerbation of hypocalcaemia from Ca-poor renal diasylates
- aluminium toxicity from renal failure meds can cause osteomalacia
vit D deficiency - incl Rickett’s and osteomalasia
malabsorption syndromes incl coeliac disease, CT, short gut, bariatric procedures
meds - lithium, diuretics
metabolic abnormalities - hypermagnesaemia, hyperphosphataemia

Answer 69

A

asymptomatic - found on tets
osseous lesions
- bone pain secondary to increased remodelling
- compression fractures (adults) or growth retardation (kids)
- osteitis fibrosis cystica (30% dialysis pts) –> increased bone resorption & formation leading to chaotic matrix depositoin & ‘woven bone’ appearance, weaker
- also osteomalacia, pepperpot skull, long bone fractures
pruritis
metastatic calcification eg vasculature, heart valves, kidneys, GI tract, others
calciphlaxis - soft tissue & vasc calcs, may lead to tissue necrosis

Answer 70

A

normalise Ca and PO4: decrease dietary phosphate, phosphate binders, calcium & vit D supplementation, IV vit D, aluminium binders, dialysis
calcimimetic - alters sensitivity of CaSR of PT cells and reduced PTH secretion, helps restore Ca-PO4 homeostasis
parathyroidectomy if medically refractory or complicated

Answer 71

A

occurs when pts w chronic renal failure & pre-existing HPTism have resolution of their renal dysfunction (usu after transplant) and have developed autonomous parathyorid function with continued production of PTH w/o normal feedback inhibition
majority resolve spontaneously (85% within first 6mo, in 95% after 6mo)
localisation studies worth doing (often 1 gland will be culprit)
options: medical therapy with cinacalcet or parathyroidectomy
profound post-op hypocalcaemia = common after parathyroidectomy for renal HPT - attributed to renal osteodystrophy - hungry bone syndrome - and occurs due to sudden reduction in PTH after surgery –> surge in bone uptake of Ca as a result of remineralisation
- usu 3-5days postop admission for IV calcium & oral ca & calcitriol
- also Mg replacement
- pre-op calcitriol loading 5/7 preop = decreased postop IV Va requirement and 50% reduction in LOS

Answer 72

A

Common - 60% of pts w hyperparathryoidism also have vit D deficiency. Typically elevated PTH with decreased or normal calcium. Give 3000-5000IU per day for 1 month.

Should be corrected in all patient’s with hyperparathyroidism; doesn’t exacerbate hypercalcaemia and reduces PTH levels & bone turnover`1

Answer 73

A

Commonly used adjunct which guides surgeon on when to stop PT exploration. Improves cure rates in pts w PHTPism and well-localised disease undergoing MIP from 96% w/o IOPTH to 97-99%. Based on the principle that PTH level is expected to drop after pathologic gland(s) excised due to short halflife of PTH (3-5mins)

PTH is drawn at:

preincision (at a date prior to surgery or prior to starting op on day of surgery)
preexcision (after exposing an abnormal gland but prior to ligating blood supply to gland)
5mins after gland removal
10mins after gland removal

>50% decline in PTH at 10mins after PT gland removal compared to highest baseline level (either preincision or preexcision) AND a final PTH that is within the normal range suggests cure & procedure can be terminated.

Answer 74

A

superior parathyroid gland
- most commonly on posterior surface of upper pole, posterior and superior to RLN; 80% found in expected location ~1cm superior to junction of inf thyroid artery and RLN at level of cricoid cartilage where RLN enters larynx
  - ~22% subcapsular
- if abnormal, tends to migrate posteriorly & downwards (and the lower it goes, the more posterior it becomes; check
  - tracheoesophageal groove, behind oesophagus or pharynx, in posterior mediastinum & intrathyroidal (0.2%)
inferior parathyroid gland
- most commonly inferior to junction of inf thyroid artery & RLN, anterior and medial to RLN on posterolateral aspect to inf pole of thyroid lobe (50%)
  - less often subcapsular
- more often ectopic: can be found anywhere from angle of mandible to pericardium
  - within thymus/thyrothymic ligament = most common ectopic location (30%)
  - others include: lateral to the inferior pole, anterior superior mediastinum, aortopulmonary window, carotid sheath, intrathyroidal & undescended in a submandibular location
NB superior/inferior designation not based on relative cranial to caudal position of gland and parathyroid VI can actually lie caudal to parathyroid III
- what is more consistent is that inf PT lie anterior to RLN & superior PTs lie posterior to RLN
- this holds true for low-lying glands; descended superior glands found posteriorly in the mediastinum & descended inf glands found in anterior mediastinum

Answer 75

A

hypothalamus releases TRH into hypothalamic-hypophyseal portal system
TRH travels to ant pit
ant pit releases TSH
TSH travels in bloodstreawm to thyroid gland
TSH binds to TSH receptor (thyroid-releasing hormone receptor)
thyroid hormone is released into bloodstream
- important for growth, metabolism and many other functions
- thyroid hormone negatively feeds back on hypothalamus

Answer 76

A

5 step process for formation of thyroid hormone - highly dependent on iodine (trace element absorbed in SB)

thyroid histo: made up of circular follicles lined by cuboidal follicular ells; centre is colloid (where thyroid hromones are stored); outside follicles = praafollicular C cells, secrete calcitonin

Synthesis of thyroglobulin
- follicular cells create this; a precursor protein which doesn’t contain iodide and is stored in colloid
- produced in ER –> Golgi apparatus pack into vesicles which are pushed out into follicle lumen by exocytosis
Uptake of iodine
- upregulated by protein kinase A activation/phosphorylation which is end result of TSH binding to its receptor
- protein kinase A phosphorylation causes upregulation of sodium-iodide transporter so iodine uptake is increased, diffuses into cells & is transported into colloid
Coupling
- phosphorylation also activates the enzyme thyroid peroxidase (TPO); this has 3 functions which go about coupling the iodide & thyroglobulin to create thyroid hormone
  - oxidation of iodide –> iodine
  - organification - the linking of thyroglobulin to iodine; generates mono-iodine-tyrosine and di-iodine-tyrosine
  - coupling reactions - TPO then combines MIT/DIT to form T3 & T4
Storage
- T3 and T4 then bound to thyroglobulin and stored in colloid
Release
- thyroid hormone released into circulation
- thyrocytes/follicular cells uptake iodinated thyroglobulin via endocytosis
- in the cell lysosomes fuse with an endosome containing iodinated thyroglobulin and proteolytic enzymes cleave off thyroglobulin into T3 and T4 and some of the MIT & DIT molecules are also cleaved off –> can be put back into the follicles therefore salvaging some for furture use
- more T4 released than T3; T4 converted to T3 in periphery (active form of hormone)

Answer 77

A

laryngeal complex = innervated by branches of vagus nerve
vagus arises from medulla in brainstem & exits skull base via jugular foramen
then enters carotid sheath & lies posterior to, and between, int jugular vein adn int carotid artery
as main trunk of vagus descends from skull base into chest, 2 branches of relevance for thyroid surgery
- SLN
- RLN
SLN
- separates from vagus at base of skull –> descends toward superior pole of thyroid medial to carotid csheath
- at level of cornu of hyoid, ~2-3cm above superior pole of thyroid, divides into 2 branches
- larger internal branch penetrates thyrohyoid membrane, provides sensory innervation to larynx cranial to vocal folds
- smaller external branch continues along lat surface of inferior pharyngeal constrictor muscle, descends anteriorly and medially along w superior thyroid artery
  - courses from carotid sheath to cricothyroid muscle, runs medial to upper pole to supply cricothyroid & comes close to junctio of upper poel and upper pole vessel
  - within 1cm of entrance of superior thyroid artery into thyroid capsule, nerve generally takes medial course & enters cricothyroid muscle which it innervates
  - Cernia classification: type 1 = nerve crosses superior thyroid vessels >1cm above superior pole; type 2 = nerve crosses suprior thyroid vessels <1cm above (type2a) or below (type tb) the superior pole
- damage = loss of voice quality or strength
RLN
- as they approach medial surface of gland from below, erves lie in or in front of TOG
- on right: RLN originates from vagus as it crosses anterior to subclavian artery
  - passes inf then post to R subclavian artery & ascneds lateral to trachea along tracheoesophageal groove
  - during thyroidectomy, at level of lowe rborder of thyroid, right RLN can usu be found within 1cm lateral to or within TOG
  - compared to left side, course less predictable in lower portions of field of thyroid surgery & follows more oblique course
  - by midportion of thyroid in TOG, usually immediately ant or post to a main arterial trunk of inf thyroid artery
- on left: RLN separates from vagus as it passes anterior to arch of aorta
  - passes inf & posteromedial to aorta at ligamentum arteriosum & ascends towards larynx
  - enters TOG as it ascends to level of lower pole of thyroid
  - cf right, more predictably directly within TOG in lower portions of surgical field for thyroidectomy
- both RLNs consistently found within TOG when within 2.5cm of entrance into larynx
  - either pass ant or post to a branch of inf thyroid arteyr & enter larynx at level of cricothyroid articulation on caudal border of cricothyroid muscle
  - right nerve passes ant or post to inf thyroid artery or between its branches
  - left lies posterior (occasionally ant) to inf thyroid artery
- in the last 1-2cm of its extralaryngeal course, the RLN is juxtaposed between lateral side of lig of Berry & medial side of TZ, plastered in place by an overlying fascia containing the tertiary branches of the inf thyroid artery
  - is here, just before entering larynx under cover of cricopharyngeus mscle, that RLN is most constant in position & also most prone to injury during thyroid surgery due to difficulty freeing it from structures enveloping it
  - nerve is essentially tethered as it dives beneath cricothyroid & can be stretched by overly vigorous dissection
  - nerve may be contained wtihin the ligament of Berry which may further exacerbate this issue/lead to traction injury with medial retraction of thyroid
- in up to 72% of pts, bilateral RLNs branch before their insertion into the larynx (2 or more branches)
  - when there is branching, the more anterior of the branches carries most of motor fibres, therefore anterior most important branch to preserve
anatomic variants
- non-recurrent R laryngeal nerve 0.5-1.5% - R inf laryngeal nerve arises directly from vagus & courses medially into larynx following course of superior thyroid artery or inferior thyroid artery
  - occurs in setting of arterial anomalies, most commonly aberrant R subclavian artery arises as a separate branch from aortic arch, distal to left subclavian, and passes from L to right, posterior to oesophagus
- can also have a right RLN and a nonrecurrent right laryngeal nerve - normally would join in a position beneath lower border of thyroid
- non-recurrent L laryngeal nerve = quite rare, assoc w more extensive and less common arch/great vessel anomalies than nonrecurrent right laryngeal nerve
RLN has mixed motor, sensory and autonomic functions, innervates intrinsic laryngeal muscles

Answer 78

A

epithelial malignant tumour of thyroid gland which originates from thyroid follicular cells
diagnosis can be made on FNA because diagnostic features are mainly in the nuclei
nuclei have clear/ground glass appearance, irregular nuclear contours with nuclear grooves and pseudo-inclusions, fragments of papillae, psammoma bodies (laminated calcifications), orphan Annie eyes (clearing of nuclei in centre)
histologically well differentiated with retained follicular cell differentiation, with papillary growth pattern (finger-like (papillary) columnar epithelium projections
multifocality in up to 80%
lymphatic spread common
histopath variants:
- microcarcinoma (PTC ≤1cm) - excellent prognosis
- classic PTC
- follicular variant of PTC (10%) - difficult to differentiate from FTC but prognosis simlar to classic PTC cf FTC
- encapsulated follicular variant = excellent prognosis
- aggressive subtypes = tall cell, columnar, hobtail
- solid variant, diffuse sclerosing variants = less clear prognostic implications but likley more aggressive than classic PTC

Answer 79

A

well differentiated malignant tumour of follicular cells that shows transcapsular and/or vascular invasion
- can have a wide range of microscopic changes ranging from virtually normal follicular architecture and function to severely altered cellular architecture
lacks diagnostic nuclear features of papillary carcinoma
- aspirates: hypercellular w microfollicular pattern and scant colloid suggests follicular neoplasm (adenoma or carcinoma)
histological diagnosis depends on demonstration of follicular cells occupying abnormal positions, incl capsular or vascular invasion; cells may not demonstrate nuclear atypia but when present, marked nuclear atypia is assoc w worse prognosis
- if finding of abnormal position not present, diagnosis is benign follicular adenoma
traditionally subdivided into:
- minimally invasive (encapsulated)
  - fully encapsulated tumours w microscopically identified foci of capsular or vascular invasion
  - encapsulated tumours with capsular invasion and no vascular invasion are highly indolent tumours w mortality <5%
- widely invasive
  - extensive vascular and/or extrathyroidal invasion
  - mortality 5-30%
lymph node involvement unusual (<10%)
haematogenous spread - mets 10-15% (lung and bone)

Oncocytic (Hurthle cell) follicular carcinoma shows follicular growth pattern but is composed of cells with abundant granular eosinophilic cytoplasm, which has this appearance bc of accumulation of innumerable mitochondria

consists of >75% oxyphilic/oncocytic cells that are enlarged w granular eosinophilic cytoplasm
currently designated by WHO as a histopathologic variant of follicular carcinoma, but differences in biologic behaviour eg ability to metastasise to LNs (up to 30%) and possibly higher rate or recurrence & tumour-related mortality
moreover, growing body of genetic evidence suggests that oncocytic tumours develop via unique mechanisms and therefore represent a distinct type of well-diff thyroid ca

Answer 80

A

Clinical suspicion of advanced disease, incl invasive primary tumour, or clinically apparent multiple or bulky LN involvement

Answer 81

A

remove primary tumour, disease that has extended beyond thyroid capsule and clinically significant LN mets
minimise risk of disease recurrence & metastatic spread
facilitate post-op treatment with RAI where appropriate
permit accurate staging and risk stratification of disease
permit accurate long-term surveillance for disease recurrence
minimise treatment-related morbidity

Answer 82

A

Cancer >4cm, T4 (gross extrathyroidal extension) or clinically apparent metastatic disease to nodes (cN1) or distant sites (clinical M1) - total thyroidectomy & gross removal of all primary tumour unless contraindications
Cancer 1-4cm w/o extrathyroidal extension or clinical evidence of LN mets  total thyroidectomy or hemithyroidectomy
- Hemi may be sufficient for low-risk papillary & follicular carcinomas (ie ATA low risk group)
- Consider total if older (>45yrs), contralateral thyroid nodules, personal hx of radiation therapy to H&N, familial DTC – bc of plans for RAI therapy or to facilitate f/u strategies or address suspicions of bilateral disease (or pt preference)
Cancer <1cm w/o extrathyroidal extension, cN0 - initially thyroid lobectomy unless clear indications to remove contralat node
- Total if prior head & neck radiation, familial thyroid ca or clinically detectable cervical nodal mets

Answer 83

A

Predicts survival but not recurrence accurately

T1 ≤2cm limited to thyroid (T1a ≤1cm, T1b 1-2cm)
T2 2-4cm limited to thyroid
T3a >4cm limited to thyroid, T3b extrathyroidal extension involving only strap muscles from a tumour of any size
T4a gross extrathyroidal extension invading subcut soft tissues, larynx, trachea, oesophagus or RLN from tumour of any size
T4b gross extrathyoridal extension invading prevertebral fascia or encasing carotid artery or mediastinal vessels from tumour of any size
N0a = one or more cytologically or histologically confirmed benign LNs
N0b = no radiological or clinical evidence of locoregional LN mets
N1a = met to level VI or VII (uni or bilateral)
N1b = mets to unilateral, bilateral or contralateral laterl neck LNs or retropharyngeal LNs
M0 or M1

Answer 84

A

AJCC staging - predicts survival (not recurrence accurately)
ATA prognostic groups - predict recurrence
MACIS, AGES, AMES - mainly about DSS
AMES clinical scoring system (age, distant mets, extent, size of primary tumour)
AGES (age, pathological grade, extent, size of primary)
Low risk = <40yrs, female, no local extension/intrathyroidal/no capsular invasion, no mets, <2cm, well differentiated
High risk = >40yrs, male, capsular invasion/extrathyroidal extension, regional or distant mets, >4cm, poorly differentiated
Most important prognostic factor in DTC = age at dx; <40 = excellent survival, w age benefit extended to 50 in women
Impact of lymph node mets on prognosis also depends on age – smaller effect on overall survival (used to think no effect) if <45; if >45, increased risk of death by 46%
Most recurrences of DTC occur within 5yrs but may occur many/decades later espec in PTC
Papillary
- Usu excellent; 10yr survival >95% for most favourable stages
Follicular
- Prognosis not as good as papillary
- Age also most important predictor of survival; 95% 10yr survival in pts <40yrs & 80% 10yr survival in pts 40-60yrs
- Prognosis best in young pts w limited capsular or vasc invasion
- Age = most important predictor of survival
- Size also important re prognosis but even small are important (unlike PTC)
- Hurthle cell – more aggressive, local recurrence more common & less avid to absorb RAI

Answer 85

A

originates in parafollicular/C cells (neural crest origin)
RET mutation –> constitutive phosphorylation of tyrosine kinase receptor –> increased intracellular messaging and unreg cellular proliferation –> C cell hyperplasia, a precursor to carcinoma in pts w RET mutations
histopath appearance quite variable; most MTCs show +ve calcitonin staining + CEA, chromogranin A, synaptophysin (ie characteristic histopath supplemented by IHC showing calcitonin positivity)
surgical specimens from pts w MTC show spindle-shaped and frequently pleomorphic cells w/o follicle development bc these cells originate from the calcitonin-producing parafollicular C cells of the thyroid
in pts w palpable disease at dx, 2/3 have ipsilateral cervical nodes, 1/3 contralateral nodes
up to 50% have mets at presentation - lungs/bone/liver

Answer 86

A

rule out phaeo - adrenalectomy first if have phaeo
if pre-op dx or syndromic predisposition, at least total thyroidectomy and prophylactic bilateral central neck dissection
if lateral disease clinically, radiologically or on biopsy, ipsilat LLND (some advocate for prophylactic unilateral neck if known level VI disease on that side, but not universally recommended)
if distant metastatic disease identified pre-op: palliative total thyroidectomy and CLND to reduce borden of local mass effect, or debulking op if curative resection not possilbe, leaving functionally important structures e.g. RLN & PTs
if MTC dx post-op in pt who had less tha a total thyroidectomy, do completion unless sporadic and unifocal, no C cell hyperplasia, otherwise normal USS of neck, neg surgical margins and normal serum calcitonin all confirmed
autograft any resected/devascularised PTs but if RET neg / MEN2B / FMTC - autograft in neck; MEN2A - heterotopic site e.g. brachioradialis (in case of future PT pathology)
re germline RET mutations, traditionally:
- MEN2B RET mutation = prophylactic ttx within 1st year of life or at time of diagnosis
- other pts w germline RET mutation - prophylactic ttx before age 5
- level VI nodal dissection can be omitted if done before these time cut-offs unless thyroid nodules >5mm, elevated calcitonin or evidence of LN mets
- now timing of prophylactic surgery is based on which inherited ET mutation

Answer 87

A

Primary alterations within gland - most common
- Graves disease/diffuse toxic goitre - most common
- toxic multinodular goitre
- toxic thyroid adenoma
- thyroiditis (early stage) - Hashimoto’s, De Quervain’s, post-partum
- thyroid malignancy w overproduction thyroid hormone (v rare)
CNS disorders & increased TSH-produced stimulation of thyroid
- TSH-secreting tumour of pituitary
O&G causes
- molar pregnancy with increased release of hCG (rare) - choriocarcinoma
- struma ovari (ovarian goitre) = ovarian teratoma containing mainly thyroid tissue
Drugs/poisons etc
- overdose of thyroid hormone (iatrogenic)
- amiodarone toxicity
- iodine-induced (Jod-Basedow effect)
  - hyperthyroidism following admin of either iodine/iodide dietary supplement or contrast medium
  - typcially presents in a pt w pre-existing nodular goitre or someone w endemic goitre who then relocates to an iodine-abundant geographical area

Answer 88

A

GIT: wt loss despite increased appetite; diarrhoea
CVS: palpitations, SOB, angina/chest pain, arrhythmias, ankle swelling
MSK: fatigue, muscle weakness (esp proximal), tremor, increased linear growth in children
GU: oligo/amenorrhoea, increased thirst, frequency
Skin: hair loss, pruritis, vitiligo, pretibial myxedema
Psych/CNS: irritability, nervousness, insomnia, sweating, heat intolerance
more severe signs of thyrotoxicosis - high-output cardiac failure, arrhythmias e.g. VT & AF
thyroid storm: hypermetabolic state w high fever, tachycardia, N&V, tremulous/agitated/psychosis
Graves’ specific - eye signs

Answer 89

A

NB (¹²³I – useful for dx; ¹³¹I – has longer t1/2 & radiation, useful for scanning for residual CA & ablation; can also use technetium)
Graves - diffusely increased
TA/hyperfunctioning nodule - focal uptake w suppression of surrounding thyroid & contralateral lobe
TMNG: patchy uptake (areas of intense & suppressed uptake)
decreased uptake: thyroiditis, autonomous thyroid tissue w iodine load (eg amiodarone/interferon), excessive exogenous intake, ectopic thyroid production - e.g. Struma ovarii, thyroid mets
*

Answer 90

A

thionamide class - includes MTU, methimazole, carbimazole
block synthesis of thyroid hormone via inhibition of iodination/organification of tyrosine + coupling of iodotyrosine molecules to form T3 and T4
PTU also blocks peripheral conversion of T4 to T3, making it useful for Rx of thyroid storm
- less placental & breast milk transfer cf carbimazole so used in pregnancy/breastfeeding though increased risk of hepatotoxicity & some guidelines recommend to change back to carbimazole in third trimester
S/Es of thionamides: agranulocytosis (warn to stop if developing sore throat or fever & check neutrophil count before restarting), rash, arthralgia, neuritis, birth defects incl embryopathy, choanal & oesophageal atresia (less of an issue in PTU), also hepatotixicity in PTU
carbimazole - usu respond within 2wks, check TFTs in 4-6wks
methimazole - metabolite of carbimazole
in Graves, T4 suppression –> decreased size 10%, stability 40%, growth 50%
- inhibit gland fx w/o destroying tissue, so increased incidence of subsequent hypothyroidism (cf surgery/RAI)
- good for reliable pts w small goitres

Answer 91

A

primary most common (thyroid doesn’t produce enough hormone)
- iodine deficiency most common overall - low dietary intake in developing countries
developed countries:
- thyroiditis (Hashimotos > post-partum)
- RAI
- surgical removal
- drugs
small % secondary (inadequate TSH from pituitary) or tertiary (inadeqaute TRH from hypothalamus)
also states of limited activity or resistance to thyroid hormone in perphery - v rare

Answer 92

A

a presumed reduction in thyroid hormone levels caused by ingestion of a large amount of iodine
an autoregulatory phenomenon that transiently inhibits iodide organification in the thyroid gland, the formation of thyroid hormones inside the thyroid follicle and the release of thyroid hormones into the bloodstream
- this becomes evident secondary to elevated levels of circulating iodide
an effective means of rejecting a large quantity of imbibed iodide, and therefore preventing the thyroid from synthesising large quantities of thyroid hormone
the effect lasts around 10 days, after which it is followed by an ‘escape phenomenon’ with resumption of normal organification of iodine and normal thyroid peroxidase function
- believed to occur bc of decreased inorganic iodine conc inside thyroid follicle below a critical threshold secondary to down-regulation of sodium-iodide symporter on the basolateral membrane of thyroid follicular cell
- in patients with underlying autoimmune thyroid disease, the suppressive action of high iodide may persist
Wolff-Chaikoff effect used to treat thyroid storm by suppressing thyroid gland
explains hypothyroidism produced in some patients by amiodarone
part of the mechanism for use of potassium iodide in nuclear emergencies
differs from the Plummer effect which is where a high iodine conc inhibits the proteolysis of thyroglobulin and the release of pre-formed thyroid hormones from thyroid follicles
Plummer effect lasts about 7-10 days but isn’t subject to an escape phenomenon

Answer 93

A

amiodarone-induced thyrotoxicosis occurs more frequently in pops that are iodine-deplete at baseline, whereas in areas of higher iodine uptake, hypothyroidism predominates
mechanisms of hypothyroidism include
- inability to escape from Wolf-Chaikoff effect from drugs’ high iodine content
- inhibition of thyroid hormone entry into periphery
- direct cytotoxic thyroiditis
presentation of amiodarone-induced thyrotoxicity often atypical & may present w exacerbation of cardiac disease being greated by amiodarone

Answer 94

A

hyperthyroidism following administration of iodine or iodide, either as a dietary supplement, iodinated contrast medical imaging, or as a medication (mainly amiodarone)
typically presents in a patient with endemic goitre (due to iodine deficiency) who reclocate to an iodine-abundant geographical area
also, people who have Graves disease, TMNG or various types of thyroid adenoma are also at risk of Jod-Basedow effect when receiving iodine, bc the thyroid won’t then respond to the negative feedback from increased thyroid hormones
the hyperthyroidism usu develops over 2-12 weeks following iodine admin

Answer 95

A

acute pyogenic infection of thyroid gland
most common underlying cause = infection of congenital piriform sinus fistula which tracks and communicates w thyroid
most common orgs = staph species incl MRSA & strep species, or fungal
can lead to thyroid abscess formation; rarely more serious sequelae e.g. retropharyngeal abscess, tracheal obstruction, mediastinitis & jugular venous thrombosis
clinical presentation = fever, severe unilateral pain & swelling of thyroid gland (typically left-sided) and cervical lymphadenopathy
Ix: TFTs rarely useful. Raised inflam markers. USS & aspiration for dx/culture
Mx: antibiotics +/- perc drainage
usually no long-term sequelae

Answer 96

A

aka subacute granulomatous thyroiditis
a self-limiting, painful, inflammatory thyroiditis thought to be secondary to viral infection - most cases have an upper respiratory infection before onset
following a viral prodrome, progress to granulomatous inflammation of thyroid gland - enlarged follicles which become infiltrated w mononuclear cells, lymphocytes, neutrophils & later multinucleated giant cells, consistent w granulomatous inflammation
natural history involves 4 phases (time course typically 2-5mo)
- acute, painful hyperthyroid phase (pain & swelling in thyroid region, with low-grade fevers, dysphagia, severe fatigue, weight loss)
- euthyroid phase
- mild hypothyroid phase
- recovery to euthyroid phase
Ix: TFTs as above, cyto from FNA (multinucleated giant cell granulomas)
Self-limiting; majority of pts return to euthyroid state spontaneously
- if pain - NSAIDs, or if more severe steroids
- +/- temporary thyroxine

Answer 97

A

2nd most common type of autoimmune thyroiditis - 10% of women within 2-12mo of postpartum period
similarities to Hashimoto’s - hypothyroidism may be preceded by a short thyrotoxic state, and often assoc w circulating TPOAb
- 10x increased risk of ultimately developing Hashimoto thyroiditis
typically short-lived with resolution in 2-4mo
short course of thyroxine may be necessary

Answer 98

A

autoimmune-mediated destruction of thyrocytes
F>M, up to 10:1, most common cause of hypothyroidism in iodine-replete populations
aetiology/pathogenesis
- circulating autoantibodies to thyroid antigens (TgAb & TPOAb) –> chronic autoimmune destructive process involving formation of immune complexes & complement in basement membrane of follicular cells –> leads to infiltration of lymphocytes into thyroid follicles & eventually fibrosis, which decreases effective number of follicles needed to produce thyroid hormones
- may have short thyrotoxic state prior to hypothyroidism
- strong hereditary component - family members have 9fold increase of also developing
- associated w other autoimmune disease (eg pernicious anaemia, gastritis, vitiligo, DM, Addisons) & w increased risk of NHL = thyroid B-cell lymphoma
clinical
- gland increases in size, sometimes nodular
- +/- intermittent pain & fluctuation in size
- initial thyrotoxicosis then eventually (+/- subclinical) hypothyroidism
investigations
- TFTs
- TgAb in 60%, TPOAb in 95%; if euthryoid or subclinically hypothyroid w elevated autoantibody titres, greater risk of progressing to overt hypothyroidism
- imaging not required but sonographic appearances: coarse, heterogeneous & hypoechoic parenchymal echotexture w increased vascularity, often w appearance that can sometimes be confused w discrete thyroid nodules
  - size ranges from diffusely or focally enlarged to small & atrophic
  - may be mildly enlarged & more numerous perithyroidal LNs from autoimmune inflammatory process
- cytology: moderately cellular specimen w aggregates of follicular cells w oncocytic/Hurthle cell changes, minimal colloid & infiltration of mature lymphocytes
  - giant cells, plasma cells, macrophages, histiocytes, eosinophils may also be seen
- path: diffuse infiltration by lymphocytes, plasma cells & development of lymphoid nodules
  - gland gradually increases in size & its nodular nature may make it difficult to discern from a simple MNG
management
- thyroxine to achieve euthyroid state & suppress TSH secretion –> leads to gland shrinkage & relief from compressive sx if present
- sometimes surgery if compressive sx

Answer 99

A

aka chronic fibrous thyroiditis
poorly understood inflammatory process causing diffuse destruction & fibrosis of thyroid gland
rare, age 30-60
aetiology/pathogenesis
- chronic inflammatory process/fibrosis
- primary theories = either an autoimmune process or a specific fibrotic disorder related to multifocal fibrosclerosis
- associated w other diseases e.g. retroperitoneal & mediastinal fibrosis
- fibrotic reaction may extend out of glandular capsule & involve surrounding structures e.g. aerodigestive tract & RLN
- no evidence to suggest increased risk of malignancy
clinical
- may develop v suddenly - extremely firm & constricting gland that can be v uncomfortable for pts
- can cause clinically significant airway obstruction, dysphagia, dysphonia
- unilateral sx may suggest malignancy & lead to surgical intervention - findings at surgery can be impressive bc process can extend into trachea & oesophagus, w obliteration of anatomic planes & landmarks
investigations
- dx usu made clinically? w observation of woody thyroid gland
- biochemical hypothyroidism
- USS - diffusely hypoechoic gland w ill-defined borders
- FNA cyto: dense fibrotic changes but can’t be reliably distinguished from fibrotic changes often assoc w anaplastic thyroid ca
management
- to treat inflammatory component - traditionally corticosteroids or tamoxifen; mycophenolate & rituximab also been used
- thyroxine
- surgery - no consensus but in general only the constricting portion of thyroid removed (wedge resection of isthmus most common) for relief of tracheal compression

Answer 100

A

angiotensinogen –(renin)–> angiotensin I –(ACE)–> angiotensin II –> aldosterone
aldosterone release from zona glomerulosa principally regulated by angiotensin II and the blood potassium level
R-A-A axis is responsive to sodium delivery to DCT of kidney; low sodium delivery (in hypovolaemia, shock, renal artery vasoconstriction, hyponatraemia and increases in sympathetic output) –> renin released from JGA
renin cleaves prohormone angiotensinogen, made in liver, to inactive angiotensin I
angiotensin I cleaved by ACE in lungs & elsewhere –> angiotensin II (a potent vasoconstrictor & stimulator of aldosterone release)
hypokalaemia decreases aldosterone release by suppressing renin secretion & also by acting directly at zona glomerulosa; hyperkalaemia has opposite effect
ACTH also stimulates aldosterone secretion
aldosterone regulates circlating fluid volume & electrolyte balance by promoting sodium & chloride retention by the distal tubule
- potassium & hydrogen ions = secreted into the urine
- expands ECF volume & increases BP
negative feedback occurs primarily through increase in sodium delivery to distal tubule, suppressing renin release

Answer 101

A

CRF (corticotrophin-releasing factor) released into hypothalamic-pituitary-portal system by hypothalamic neurons –> ACTH secretion by ant pit
ACTH binds to a GPCR on adrenocortical cell surface –> stimulates glucocorticoid secretion
- ACTH released in pulsatile fashion, usu w circadian rhythm; highest levels of ACTH & thus cortisol generally detected on waking & levels gradually decline through day to nadir in early evening
- cortisol regulates its own secretion via neg feedback on hypothalamus & pit
main glucocorticoids = cortisol & corticosterone
- in general, generate a catabolic state that characterises body’s response to stress
- cause alterations in carb, protein & lipid metabolism –> net effect of increased blood glucose concs
  - liver: upreg of gluconeogenesis & glycogenolysis; net glycogen deposition occurs
  - peripheral tissues: glucose uptake inhibited
  - adipose tissue: lipolysis of fat –> release of FFAs into circulation
  - general state of insulin resistance induced, resulting in protein catabolism
  - FAs & amino acids serve as energy sources & substrates for gluconeogenesis
- cardiovasc system: glucocorticoids exert a permissive & enhancing effect on catecholamine signaling by sensitising arterial smooth muscle cells to beta-adrenergic stimulation & increasing catecholamine concs in neuromuscular junctions
  - cardiac contractility & peripheral vasc tone thus maintained
  - why haemodynamic collapse w acute adrenal insufficiency can be remedied by glucocorticoid administration
  - also have weak mineralocorticoid effects
- immune system: glucocorticoids are potent anti-inflam & immunosuppressive agents
  - acutely, reduce circulating lymphocyte & eosinophil counts while increasing neutrophil counts
  - lymphocyte apoptosis is promoted, cytokine and immunoglobulin production is decreased & histamine release suppressed
  - decreased prostaglandin synthesis through inhibition of phospholipase A2
- skeletal system: decreased intestinal absorption & increasing urinary excretion of calcium –> osteoporosis

Answer 102

A

ACTH & other incompletely understood mechanisms regulate secretion of adrenal androgens androstenedione, DHEA & DHEA-S (androstenedione = produced in smallest quantities)
physiologic effects of adrenal sex steroids are generally weak in comparison to the gonadal sex steroids, particularly in males
in females, peripheral conversion of DHEA & DHEA-S via aromatase enzyme system to more potent androgens, incl androstenedione, testosterone & dihydrotestosterone (?also oestradiol) supports normal pubic & axillary hair growth & may play a role in maintaining libido & a sense of well-being

Answer 103

A

phaeo: plasma free metanephrines (high sens but mod spec, useful rule out)
Conn’s: K+, aldosterone:renin ratio (>25-30)
Cushing’s: 24hr urinary free cortisol
Sex steroids: serum DHEAS & 17-hydroxyprogesterone

Answer 104

A

adrenal cysts, myelolipoma & haemorrhage have characteristic features on CT enabling diagnosis
- myelolipoma = low attenuation on non-con (-20 to -30HU), presence of a pseudocapsule between mass & surrounding retroperitoneal fat, calcs in up to 20%
adrenal adenomas
- most lipid rich & low-density/attenuation (<10HU on non-con CT), homogeneous w regular outline, low degree of vascularity with rapid washout of >60% in 15mins / <30HU at 10mins
- incidentaloma <4cm in size w these features & attenuation value of <10HU requires no further dx imaging
malignant lesions, phaeo (& up to 30% of adenomas) = lipid poor with high attenuation on unenhanced CT
- other features: rapid contrast enhancement & <60% washout in 15mins (high vascularity), heterogeneity, irregular outline, size >4cm, necrosis, internal calcs or haemorrhage

Answer 105

A

glucocorticoids & mineralocorticoids required indefinitely
hydrocortisone 10mg BD
fludrocortisone - start on 0.1mg PO

Answer 106

A

suspect:
- classic: headaches, palpitations, sweating
- HTN
- phaeo crisis - CHF/CVA in young person w/o cause
screen:
- plasma free metanephrines - high sens but moderate spec - good initial screening, useful to rule out
confirm:
- 24hr urine metanephrines & catecholamines (combined)
- clonidine suppression test
localise
- CT/MRI
- MIBG
- ?dotate PET
treat
- pre-op alpha +/- beta blockade
  - start phenoxybenzamine (non-selective alpha blocker) at 10-20mg BD & increase by 10mg increments q2-3days til postural hypotension or max dose of 40mg TDS
  - helps achieve relative ciruclating volume expansion & allows cardiomyopathy secondary to chronic hypertension to resolve
  - period of pre-op conditioning should last at least 2wks to allow adequate reversal of alpha-blocker downregulation
    - this restores sensitivity to vasopressor agents, which can then be used to treat the patient post-op
    - may need longer in cases of severe cardiomyopathy
  - CCB can be added if still inadequate BP control
  - beta-blocker if persistent tachycardia/arrhythmia - but don’t start til alpha blockade complete bc a decrease in peripheral vasodilatory beta receptor stimulation –> unopposed alpha-adrenergic stimulation that may cause hypertensive crisis, CHF & pulmonary oedema (propanolol 10mg tds)
- pre-op volume expansion with fluids - less important when aggressive pre-op alpha blockade achieved bc increase in venous capacitance restores euvolaemia gradually by stimulating thirst
- Mg - inhibits catecholamine release from adrenal medulla & directly antagonises adrenergic receptors to produce arteriolar vasodilation
- post-op hypotension may be profound bc state of hypovolaemia is created by presence of excess circulating catecholamines then sudden withdrawal of this stimulus after tumour removal –> peripheral arteriolar vasodilatatoin & a dramatic increase in venous capacitance –> together may precipitate cardiovasc collapse
- monitor glucose - can get hypoglycaemia from sudden withdrawal of lipolytic, glycolytic and glycogenolytic effects of catecholamines that were induced by the phaeo

Answer 107

A

suspect:
- HTN, particularly if hypokalaemia, severe/treatment resistant HTN, <40yrs
- hypokalaemia absent in majority (muscle weakness, cramps, paraesthesias, palpitations, polyuria
screen:
- K+
- aldosterone:renin ratio (>25-30)
confirm:
- saline suppression test (2-3L IV saline w plasma aldosterone checked before and after - looking for failure to suppress)
- oral salt-loading (5000mg saline daily for 3days, then 24hr urine aldosterone)
- fludrocortisone suppression test (some centres give high dose fludrocort during oral salt loading to increase specificity of suppression testing)
- pts <30yrs who test +ve should be genetically screened for familial glucocorticoid-remediable aldosteronism, espec if they have fhx of early-onset HTN
localise
- CT/MRI
- adrenal venous sampling (some use routinely, others selectively e.g. if cross-sectional imaigng fails or if ≥40yrs bc more likley to have nonfunctioning adrenal cortical adenoma)
  - risk of adrenal vein rupture 1% and unsuccessful in 40-80% mostly bc of inability to cannulate R adrenal vein
  - relies on simultaneous measurement of cortisol & aldosterone & renin levels in peripheral circulation and left & right adrenal veins +/- with ACTH stimulation - looking for >4x aldosterone:cortisol ratio on one side
  - helps distinguish unilateral from bilateral disease
treat
- spironolactone for at least 2 wks pre-op
- correct HTN & hypokalaemia prior to surgery
- post-op watch for renal impairment - glomerular hyperfiltration caused by hyperaldosteronism can artifically raise creatinine clearance & mask renal insufficiency
  - after adrenalectomy, decreased aldosterone levels can lower glomerular filtration & unmask true degree of CKD
- also watch for hyperkalaemia due to transient suppression of contralat gland - occurs within 1-3wks so monitor w weekly bloods for 1mo post resection

Answer 108

A

suspect
- Cushingoid features
screen
- 24hr urinary free cortisol (2x); >3x normal = prob Cushing
- if 1-3x normal, do 2x late evening salivary cortisol
confirm
- low-dose (1-2mg) overnight dex suppression test
- for ACTH dependent vs independent:
  - ACTH (check on more than one occasion; suppressed if ACTH independent; in ACTH dependent usually higher in ectopic ACTH disease cf pit disease)
  - high-dose overnight dex suppression test if suspect ACTH-dependent
    - pit tumour usu retain some neg-feedback control that is totally lost in pts w ectopic source of ACTH
    - if cortisol drops to <50% baseline after single dose of 8mg dex suggests pit-driven disease
  - ?CRH
localise
- CT/MRI
- +/- pituitary MRI if suspect ACTH-dependent
- bilateral inferior petrosal sinus ACTH sampling w CRH stimulation
- CT/MRI of NCAP to look for cause when ectopic ACTH suspected +/- octreoscan
treat
- ketoconazole as a bridge to definitive surgery (inhibits cotisol synthesis)
- peri-op stress dose steroids, then physiologic replacement levels for several weeks but variable - some >1yr
- VTE prophylaxis - hypercoagulable

Answer 109

A

A catecholamine-secreting tumour derived from chromaffin cells of neural crest origin arising in either the adrenal medulla (phaeochromocytoma) or extra-adrenal autonomic ganglia (paraganglioma)
10% extra-adrenal
10% bilateral (hereditary cases more likely to be bilateral)
10% malignant (higher for extra-adrenal sites - 38% SDHB phaeos malignant, 10% NF1 phaeos malignant; otherwise malignancy rare in syndromic phaeos)
up to 1/3 carry germ-line. mutations in pre-disposing genes (eg RET, VHL, NF1, SDHB & D)
- familial cases manifest at earlier age & more likely to be multifocal

Answer 110

A

group of AR disorders characterised by deficiency in end steroid production & overproduction of steroid intermediaries due to enzyme deficiency in the steroid synthetic pathway from cholesterol
failure of neg feedback on pit –> increase in plasma ACTH levels & adrenal hyperplasia
21-hydroxylase deficiency accounts for majority (>90%) –> results in glucocorticoid & mineralocorticoid deficiency w overproduction of adrenal androgens –> ambiguous genitalia in females, salt loss & hyperkalaemia
medical mx of CAH includes replacement of steroid behind teh enzyme block which restores the neg feedback loop, so reducing ACTH & adrenal androgen levels
pts in whom med tx fails to control hyperandrogenism, or iatrogenic hypercortisolism occurs may benefit from bilat lap adrenalectomy - can decrease androgens and improve control of signs & sx of hypercortisolism (esp obesity)

Answer 111

A

rare
57% functional
- multiple 35%
- cortisol 30%
- androgens 20%
- oestrogens 10%
- aldosterone 2%
most sporadic but may be assoc w MEN1, Beckwith-Wiedemann, Li-Fraumeni
tend to be large at presentation (mean 9-13cm)
only absolute criterion for dx of ACC = presence of extensive invasion or local structures or mets
- Weiss criteria to help distinguish between benign & malignant histo
- Ki67 may also help

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