Thyroid ca/parathyroid

disease
Nangammbi RJ
29/09/23
A historic perspective

• In 1791, Pierre Joseph Desault achieved a landmark in thyroid surgery by performing the 1st partial
thyroidectomy.

• Surgeons like Dupuytren in 1808, William Blizard in 1811 or Henry Earle in 1823 followed him closely.

• In the late 19th century William Stewart Halsted described thyroid cancer.
Introduction con’t

• Thyroid cancer has a wide spectrum of morphologies and behaviors that include the most
common and indolent tumours as well as the most aggressive and rapidly lethal malignancies.

• The importance of pathology in the identification, diagnosis, and prognostication of thyroid

cancer cannot be underestimated.
 Thyroid cancer is the most common endocrine malignancy.

1% of all malignancies

Sex ratio is 3:1 (F/M)

Peak incidence after age 30

5-yr relative survival rate for all stages

Incidence
Incidence of thyroid cancer in US and worldwide has increased 300%
over the past three decades.

Obesity trends may play a role, but the underlying biological

pathways are not well-characterized.
History

•Several risk factors are associated with

carcinoma and require consideration
when evaluating patients with a thyroid
mass.
Examination

• Nodules that are >4cm, hard, gritty or fixed to surrounding structures such as
trachea or strap muscles are more likely to malignant.

• Cervical chain of nodes should be assessed – both anterior and posterior triangles.

• Examination for the Delphian and pyramidal lobe situated just above the thyroid
isthmus and cricoid cartilage is important.

• Assessment for recurrent laryngeal nerve paralysis by means of indirect

laryngoscopy should also be undertaken.
•Classification of primary thyroid neoplasms of follicular cell de
Investigations

Investigations can be divided into laboratory, imaging and sampling.

Laboratory:
1. TSH
• Is the only test that is necessary to detect abnormalities in thyroid function.
• The levels reflect the ability of the anterior pituitary to detect free T4 levels,
therefore is the most sensitive and specific test for the diagnosis of hyper and
hypothyroidism and for optimizing T4 replacement and suppressive therapy.
• The initial step in evaluating a patient with a thyroid nodule should include a TSH
hormone level (95% of all nodules are hypofunctional and are considered cold).
Interpretation of TSH results

TSH level The nodule is hypo functioning and thyroid hormone replacement should be
initiated and FNAC performed when the patient is considered euthyroid.
is high:

The nodule is hyper functioning and should be evaluated with a thyroid scan.
TSH level
is low: These lesions have a low likelihood of malignancy.

FNAC can be performed immediately either by palpation or under ultrasound

TSH level guidance.
is normal: T3 and T4 are not used for detecting abnormalities of thyroid function unless
TSH is abnormal.
Laborator 2. Thyroid antibodies 3. Serum thyroglobulin

y con’t • Antibodies such as anti- The most important use for

thyroglobulin (Anti-Tg) and it is in monitoring patients
anti-thyroid peroxidase (Anti with differentiated thyroid
–TPO) elevation in these cancer for recurrence after
indicate an auto-immune total thyroidectomy and
thyroiditis. radioactive iodine ablation.
4. Calcitonin

• Patients with MTC may have c-cell hyperplasia and elevated serum
calcitonin levels therefore patients with family history of medullary ca
or MEN II should have routine calcitonin level measurements.

• Routine calcitonin measurements as part of a thyroid nodule workup

in patients without family history or without MEN II is not
recommended.
U/S

• Is the most widely used imaging technique for the evaluation of thyroid
nodules.

• It is cheap, safe, non-invasive, portable and has no radiation emissions.

• It can detect solid nodules of 3mm and cystic nodules of 2mm.

• It can distinguish nodular growth from intranodular haemorrhage.

• It can with no absolute certainty show suspicion of malignancy.

Imaging: U/S

• Preoperative U/S can now be accurately used to stage

patients and identify metastatic lymph nodes that physical
examination fails to detect in 30% to 50% of patients.

• By detecting abnormal LN, ultrasound provides the surgeon

with preoperative map of lymphadenopathy, often
impacting on the type oof operative procedure performed.

• The reliability of U/S is now such that the surgical decision

to add a lateral neck dissection to a thyroidectomy may be
based on the sonographic findings.
Radionuclide imaging:

• Iodine 123 (I123) emits low radiation, has a half-life of 12 hours and is used to image lingual

thyroids or goitres.

• Iodine 131 (I131) emits high radiation, has a half-life of 10 days and is used to screen and treat

patients with differentiated thyroid cancers.

• However, its use is very limited now as compared to the past.

• It provides size, shape and functional activity of the gland.

• Areas that trap more radioactivity are termed hot lesions and areas that trap less radioactivity are

termed cold lesions.

• The risk of malignancy in cold lesions is 15 to 20% and in hot lesions less than 5%.

• Technetium-99(Tc99) emits low radiation, has a short half-life and is sensitive for nodal metastases.
CT/MRI scan
• Limited role in the initial management of a thyroid nodule.

• It is more useful in detecting thyroid tissue in retrosternal and retroclavicular regions and
allows for the assessment of mediastinal involvement and cervical lymphadenopathy.

• MRI and CT scan allow excellent soft tissue evaluation for findings such as oesophageal
invasion.

• Unfortunately, CT scan requires iodinated contrast agents that may delay the use of RAI
postoperatively for 4-6 weeks.

• MRI ( which does not require iodinated contrast) is more expensive than CT or ultrasound
but demonstrates exquisite soft tissue details and vascularity.

• This allows identification of extraglandular invasion and involvement of the great vessels.
Sampling
Fine needle aspiration (FNA):

• FNA biopsy of thyroid nodules is an accurate and cost-effective method for distinguishing
benign from malignant nodules.

• Most centres using this procedure have achieved a 35% to 75% reduction in the number of
patients requiring surgery, while still doubling or tripling the malignancy yield at
thyroidectomy.

• FNA is preferred to thyroid scanning or ultrasonography as the initial diagnostic test for
evaluating patients with thyroid nodules.

• Since FNA became popular, the number of thyroid surgical procedures has decreased by 50%
whereas the percent yield of cancers for patients undergoing surgery for thyroid nodules has
increased from 10-15% to 20-50%.
Method for FNA
• The area of aspiration is cleaned.

• Local anaesthetic may or may not be administered depending on doctor and patient
preference.

• A 23-gauge needle attached to a 10cc syringe is inserted into the nodule either by palpation or
ultrasound guidance.

• Constant aspiration on the syringe is applied with care of not slipping out of the nodule while
several passes are made within the nodule.

• Suction is released before removal of the needle.

• Cells are placed on a dry glass slide and fixed and observed under the microscope.

• If blood is aspirated, use a finer gauge needle (25-30) and repeat FNA in an upright position.
Bethesda classification system of thyroid cytopathology
Core biopsy

• Is not necessary for the diagnosis or staging of thyroid cancer except for large
tumours which FNA could not provide a reliable diagnosis and for lymphoma.

• In these cases, an 18-gauge cutting needle instead of a 14-gauge core biopsy needle
should be used to minimize the risk of bleeding.
Prognostic factors • A total of 17 risk stratification systems have been developed
for differentiated around the world in an effort to better predict the outcomes
thyroid carcinoma in patients who have differentiated thyroid cancer.
Management
1. Papillary thyroid carcinoma

Surgical treatment either involves:

• A lobectomy - removal of entire lobe and isthmus

• A total thyroidectomy - removal of the entire thyroid gland including both lobes and the isthmus.

• A near total thyroidectomy - Leaving behind some thyroid tissue <2g in order to preserve the blood

supply to the parathyroids and recurrent laryngeal nerve.

A consensus has been reached for certain subgroups of patients:

• For high-risk patients, such as those who have bilateral tumours, distant metastases, extrathyroidal

extension, lymphadenopathy, more aggressive histology – TOTAL THYRIODECTOMY is advocated.

• For low-risk patients, such as those with occult/ micropapillary thyroid cancer, solitary
tumour less than 1-1,5cm or no lymphadenopathy – LOBECTOMY is favoured.

• However, the debate centres around low to moderate risk patients, on whether to
perform a lobectomy or total thyroidectomy.

2. Follicular carcinoma

Surgical treatment:

• If preoperative FNA shows a follicular lesion → lobectomy (because 80% of patients

will have benign adenomas).

• If preoperative FNA shows follicular lesion in older patient with >4cm lesion especially
if male → total thyroidectomy (because 50% of patients will have a cancer).
NB: Intraoperative frozen section evaluation is rarely diagnostic and
therefore is generally not done.

• If cancer diagnosed pre-operatively → total thyroidectomy

• If diagnostic lobectomy shows angioinvasion or invasive carcinoma →

completion thyroidectomy (so that I131 can be used to detect and
ablate metastatic disease).
 Surgery:

2 forms of surgery exist :

1. Prophylactic surgery for prevention of MTC.

2. Treatment surgery for patients with confirmed MTC.

The minimum treatment for patients with MTC is total thyroidectomy

3. Medullary and routine central compartment LND.

thyroid
carcinoma Prophylactic surgery for prevention of MTC

• Prophylactic surgery removes an organ destined for malignant

transformation before the cancer develops.

• This form of surgery is important in MTC because patients at risk of

these cancers can be picked up by genetic screening and due to the

fact that the tumour is incurable after it has progressed beyond the

confines of the thyroid capsule.

4. Anaplastic carcinoma

• Too aggressive and invasive when it is diagnosed therefore not many patients can undergo surgery.

• If it presents as a respectable mass, thyroidectomy with combination radiotherapy and chemotherapy may
improve survival.

• Tracheostomy or isthmusectomy may be needed to alleviate airway obstruction.

• Radical neck dissection for advanced disease offer no survival advantage over less aggressive surgical approaches.

PROGNOSIS

• Is very poor. Most aggressive of the thyroid malignancies. Most patients die within 6 months of diagnosis.
5. Thyroid Lymphoma

• Patients respond rapidly to chemotherapy: C – cyclophosphamide, H –

doxorubicin, O – vincristine, P – prednisone.

• Combined treatment with radiotherapy and chemotherapy is recommended.

• Previous the standard of the care for TL was radical resection, because the
disease was thought to be a form of anaplastic thyroid cancer, but as the benefit
of chemo and radiotherapy over surgery became evident, the need for surgical
intervention was diminished.
Pregnancy
in patients
treated
for thyroid
ca
 • 4 small glands embedded on

Parathyroid posterior surface of thyroid

gland.
• Size of a grain of rice.

disease • Secret PTH.

• Regulates calcium and
phosphate.
Hyperparathyroidism

• Disease is characterized by excessive PTH secretion.

• The offending parathyroid gland is usually large: In 1/3 a tumour is

palpable in the neck before surgery.

• Uncontrolled PTH secretion> hypercalcemia, polyuria, dehydration,

and reduced renal function, which worsens the hypercalcemia.
Effects of PTH
To increase plasma calcium concentrations by:

• Increasing release of Calcium and Phospate from bone matrix

• Increased Calcium reabsorption by the kidney.

• Increased renal production of 1,25 dihydroxy Vit D (Calcitriol)> increased GIT absorption of
Calcium.

• Will also increase renal excretion of Phosphate.

• Thus, overproduction of PTH> Increased plasma Calcium concentration and

phosphaturia>decreased serum Phosphate levels.
Primary hyperparathyroidism
Hyperfunction of parathyroid glands themselves
Most patients have:
• Serum calcium concentrations within 0.25-0.375 mmol/L above the
upper limit of normal
• Majority are women over age 50 years who are asymptomatic
Not completely autonomous: still somewhat suppressed by high
calcium, thus calcium levels not as high as it could be:
Oversecrection of PTH due to:
• Adenoma, hyperplasia or rarely carcinoma
Aetiology
• A history of irradiation to the head and neck, on average 20 to 40 years prior (not necessarily
multi gland disease).

• Radioactive iodine therapy

• Chronically low calcium intake: case reports

• May occur as part of MEN1 (mutation in MEN 1 gene) or MEN2a (mutation in RET gene).

• Patients on long-term Lithium (e.g. Bipolar mood disorder) at high risk.

• HRPT2 gene — Germ-line inactivating HRPT2 mutations have been described in a type of familial
hyperparathyroidism, the hyperparathyroidism-jaw tumour syndrome, that is associated with an
increased risk of parathyroid cancer.
Secondary hyperparathyroidism
• Due to physiological secretion of parathyroid hormone in response to hypocalcaemia

Most commonly due to:

• Vitamin D deficiency (from GIT)> drive for Calcium absorption from bone

• Chronic renal failure>failure to convert Vit D to 1,25(OH)2D3: Bone disease in renal

failure=renal osteodystrophy.

• Clinical features often that of renal failure

• If due to Vit D deficiency, presentation due to bone loss>osteomalacia, fracture risk and
myopathy.
Tertiary hyperparathyroidism

• Seen in patients with long-term secondary

hyperparathyroidism>hyperplasia of parathyroid glands and loss of
response to serum calcium concentrations: autonomous activity

• Mostly seen in chronic renal failure

Work-up
Initial investigations of choice:

• Serum PTH, Calcium & Phosphate

ALP:

• Increased due to increased bone resorption

Urine calcium:

• Increased in primary hyperparathyroidism

Measurement of 24-hour urine calcium excretion:

• Helps distinguishing PHPT from familial hypocalciuric hypercalcemia (FHH): elevated levels exclude FHH

• Identifies asymptomatic patients with renal disease requiring intervention

Vitamin D levels:

• Important to identify patients with PHPT and vitamin D deficiency, who require vitamin D
repletion.

• Differentiates secondary hyperparathyroidism due to vitamin D deficiency

GFR

Bone density scan

Lumbar X-rays:

• Exclude occult fractures if symptomatic

Renal imaging:

• Rules out renal stones if clinically indicated

U/S Neck

Safe and widely used

Localizes abnormal glands

Operator dependent

Sonographic characteristics of parathyroid adenomas:

• Homogeneous hypoechogenicity

• Presence of extrathyroidal feeding vessel with peripheral vascularity seen on

colour Doppler imaging.
• Sestamibi scan
• Subtraction thyroid scan
• CT scan
• MRI
Management

Primary hyperparathyroidism:
Preventative measures for patients who do not undergo surgery
• Avoid thiazides and lithium
• Avoid volume depletion and immobility
• Avoid consumption of >1g Calcium per day (do not give low Calcium diet,
may increase PTH secondarily)
• Encourage hydration to minimize nephrolithiasis
• Maintain moderate vitamin D intake (400 to 800 IU daily)
Management

Primary hyperparathyroidism:
Managing acute hypercalcemia
• IV fluids: Normal saline + Furosemide IV once volume is restored
• Calcitonin and Bisphosphonates temporarily decreases calcium prior to surgery
Medical treatment in patients unfit for surgery:
• Adequate Vit D intake
• Calcium intake 800-1000mg per day
• Weight bearing exercise
• Bisphosphonates in patients with low bone mineral density
Surgical management

Surgical excision of abnormal parathyroid gland only permanent curative treatment

Surgery indicated in all patients with:

• Symptomatic disease who are fit for surgery with a reasonable life expectancy

• Selected asymptomatic patients (unlikely to be completely asymptomatic):

• Patient <50 years

• Serum Calcium >1g above normal likely to become symptomatic (or >0.25 mmol/L
above upper limit in normal)
• Poor GFR <60 mL/min
• Bone density: >2.5 SD below peak bone mass
• 24-hour urinary calcium >400 mg/day
 • Correct Vit D deficiency
• Control chronic renal failure
• Dietary phosphate restriction
Management of
secondary • Phosphate binders if phosphate
hyperparathyroi remains high despite dietary
restriction
dism
• Limit calcium supplements to <2 g
per day
• Supplement Vit D
Surgical management

• 3.5 gland parathyroidectomy or total parathyroidectomy and auto

transplantation.
Indications: Includes the following despite best medical therapy:
• Bone pain or pathological fractures
• Pruritis
• Calciphylaxis
Tertiary hyperparathyroidism

• Total parathyroidectomy and auto-transplantation or subtotal

parathyroidectomy
Parathyroid carcinoma

• Rare cause of hyperparathyroidism: 1-2%

• Benign hyperparathyroidism more common in females.
• Carcinoma of the parathyroid equal gender incidence.
• Predilection for single inferior gland.
• Multiglandular parathyroid carcinoma very rare.
Clinical presentation
• Mean age mid 40 to 50s
• Symptomatic hypercalcemia>parathyroid crisis
• Neck mass
• Bone, renal disease and pancreatitis
• 1/3 have nodal metastases at presentation
• 1/3 have distant metastases at presentation: mostly to bone and liver.
• When PTH levels are less than 4 times normal and lesion mass is <1,9g the odds of having
carcinoma very low.
Diagnosis
Interpretation difficult in differentiating adenoma from
carcinoma.
Definitive diagnosis made on:
• Local invasion of contiguous structures
• Lymph node or distant metastases
Management

Surgery:

• Mainstay of therapy

• Previously aggressive surgery with wide removal of tissue including thyroid lobectomy advocated.

• Now parathyroidectomy of involved lesion en-bloc resection of any involved adjacent tissue

( centres recommend ipsilateral lymph node dissection.

• Important to avoid capsular violation or tumour spillage.

• Some authors recommend re-operation to remove ipsilateral thyroid lobe if histology comes back

malignant, but re-operation to remove all tumorous tissue recommended by all.

Reference

1. Callender, G.G., Carling, T., Christison-Lagay, E. and Udelsman, R., 2014. Surgery
for thyroid cancer. Endocrinology and Metabolism Clinics, 43(2), pp.443-458.

2. Miller, M.C., 2010. The patient with a thyroid nodule. Medical Clinics, 94(5),
pp.1003-1015.

3. Melany, M. and Chen, S., 2017. Thyroid cancer: ultrasound imaging and fine-
needle aspiration biopsy. Endocrinology and Metabolism Clinics, 46(3), pp.691-
711.