Disease Profiles: Thyroid Disorders Flashcards
How would you manage hyperthyroidism in pregnancy?
Graves may settle as pregnancy suppresses autoimmunity
β-blockers if needed
LOW DOSE antithyroid drugs (wait as late as possible due to side effects on foetus) - propylthiouracil 1st trimester, carbimazole 2/3rd trimester
Describe the genetic factors linked to Graves disease
Increased incidence in family members
Susceptibility associated with certain HLA haplotypes, as well as polymorphisms in genes associated with immune regulation
Describe the management of acute severe hypercalcaemia
Fluids - rehydrate with 0.9% saline 4-6L in 24 hours
Consider loop diuretics once rehydrated (avoid thiazides)
Bisphosphonates - single dose will lower Ca2+ over 2-3 days, max. effect at 1 week
Describe the histology of minimally invasive follicular carcinoma
Follicular architecture well differentiated, may have part surrounding capsule, difficult to distinguish from adenoma
How would you differentiate between hyperemesis gravidarim and hyperthyroidism in pregnancy?
Hyperemesis gravidarim - ↑hCG, ↓TSH, no antibodies
HG should resolve by 20 weeks gestation
Which genetic syndrome results in patients who almost always develop a parathyroid adenoma with hypercalcaemia at a young age?
MEN1 and 2
Which forms of hyperparathyroidism can result in hypercalcaemia?
Primary and tertiary
Why is smoking cessation very important in a patient with Graves disease?
Graves eye disease is associated with smoking
Which type of differentiated thyroid cancer has a propensity for haematogenous spread?
Follicular carcinoma
What is pretibial myxoedema?
Infiltrative dermopathy caused by the accumulation of excess mucopolysaccharides, associated with Graves disease and occasionally seen in Hashimoto’s thyroiditis
Describe the management of thyroid lymphoma
Chemotherapy (R-CHOP), radiotherapy or steroids
(Does not respond to RAI)
Describe the pathophysiology of Graves disease
Involves auto-antibodies to TSH receptor, thyroid peroxisomes and thyroglobulin
The anti-TSH receptor antibodies stimulate the thyroid resulting in increased function
Some antibodies can inhibit function - may explain paradoxical episodes of hypofunction which can occur
Describe the clinical presentation of medullary thyroid carcinoma
Neck mass with local effects - dysphagia, hoarseness, airway compromise
Paraneoplastic syndromes - diarrhoea, Cushing’s
When would you treat subclinical hyperthyroidism?
If TSH <0.1%, or if co-existing osteoporosis/fracture or AF
What are β-blockers used for in the management of Graves disease?
Useful for immediate symptomatic relief of thyrotoxic symptoms
PTH increases urinary _____ excretion
Phosphate
Name 3 causes of hypocalcaemia
Chronic kidney disease, congenital absence (DiGeorge syndrome), destruction (surgery, radiotherapy, malignancy)
___ production by a medullary thyroid carcinoma causes diarrhoea
VIP
______ cases of medullary thyroid carcinoma result in a solitary nodule
Sporadic
Describe the management of hypercalcaemia secondary to malignancy
Treat underlying malignancy
Chemotherapy may reduce calcium in e.g. myeloma
Name two drugs which can cause hypercalcaemia
Vit. D, thiazides
Describe the management of advanced medullary thyroid carcinoma
May involve tyrosine kinase inhibitors
Why are patients with differentiated thyroid cancer after initial treatment given suppressive doses of levothroxane?
Aim is to suppress TSH below the normal range to minimise risk of recurrence
Describe the clinical presentation of thyroid lymphoma
Rapid onset mass in thyroid
Which genetic syndrome results in patients who develop an adenoma resulting in primary hyperparathyroidism?
Familial isolated hyperparathyroidism
Describe the clinical presentation of a differentiated thyroid cancer
Majority present with palpable nodules
Small percentage are chance findings on histological section of thyroidectomy tissue
Approx. 5% present with local or disseminated metastases
Local effects e.g. hoarseness, dysphagia, cough suggest advanced disease
What is fibrosa cystica?
Osteoporosis, brown tumours and osteitis caused by overproduction of PTH and continued osteoclasis in hyperparathyroidism
Why should you alert neonatologist if you find TRAb antibodies in a pregnant woman?
TRAb antibodies can cross the placenta and cause neonatal transient hyperthyroidism
Which investigations would you perform in suspected differentiated thyroid cancer?
US scan, TSH
Confirm with US-FNA, may need excisional biopsy of lymph node
Pre-operative laryngoscopy if vocal cord palsy suspected clinically
Describe the pathophysiology of a goitre
Reduced T3/T3 production causes a rise in TSH, stimulating gland enlargement
May maintain euthyroid state or if compensation fails there will be goitrous hypothyroidism
What is scintiscan used for in investigating a patient with hyperthyroidism?
Used in patients who are antibody negative to look for toxic nodular disease
How would you manage a ‘low risk’ thyroid cancer?
Thyroid lobectomy + biopsy, thyroidectomy following biopsy results if needed
What is pseudo-pseudohypoparathyroidism?
Describes the phenotypic defects of pseudohypoparathyroidism (Albright’s herditary osteodystrophy) but without any abnormalities in calcium metabolism
Describe the chronic clinical features of hypercalcaemia
Myopathy
Fractures
Osteopenia
Depression
Pancreatitis
Duodenal ulcers
Hypertension
Renal calculi
Which differentiated thyroid cancer has been associated with activation of the MAP kinase pathway, rearrangements of RET or NTKR1, activating point mutation in BRAF and ras mutations?
Papillary carcinoma
How would you be able to tell if a nodule on the throat is in the thyroid?
Moves on swallowing - invested in pretracheal fascia
___ production by a medullary thyroid carcinoma causes Cushing’s
ACTH
Name three causes of medullary thyroid carcinoma
Adults - sporadic, familial non-MEN
Children - MEN2a
Name 3 causes of thyrotoxicosis not associated with hyperthyroidism
Thyroiditis e.g. drug-induced
Exogenous thyroid hormones
Ectopic thyroid tissue
Name the three components of fibrosa cystica
Osteoporosis, brown tumours and osteitis
How would you investigate a follicular adenoma?
US scan, FNA, serum TSH, thyroid surgery + biopsy
How would you monitor a patient with differentiated thyroid cancer after initial treatment?
Measure TSH and Tg every 6 months for first 5 years, then annually for next 5 years, consider discharge after 5 years if low risk
What is a diffuse goitre?
Diffusely enlarged thyroid
Describe the clinical presentation of post-partum thyroiditis
Small, diffuse, nontender goitre
Hyperthyroid then hypothyroid
Describe histology of papillary carcinoma
Can be multifocal
Often cystic
May be calcified - psammoma bodies
What is a follicular adenoma?
Benign encapsulated tumour of the thyroid gland that is surrounded by a thin fibrous capsule
What causes primary hyperparathyroidism?
Due to a benign adenoma, hyperplasia or rarely a malignant neoplasia within the parathyroid glands
How can hypomagnesaemia cause hypocalcaemia?
Calcium release from cells is dependent on magnesium - in magnesium deficiency intracellular calcium is high so PTH release will be inhibited
Describe the management of primary hyperparathyroidism
Parathyroidectomy if indicated
Cinacalcet (calcium mimetic) - can be useful if need treatment but unfit for surgery
What is a multi-nodular goitre?
Irregular enlarged thyroid due to nodule formation
Which patient group is most likely to develop a sporadic diffuse goitre?
Females, usually occurs in puberty/YA
What is the first line antithyroid drug in the management of Graves disease?
Carbimazole
How would a brown tumour appear on x-ray?
Lytic lesion
Name two conditions associated with subclinical hyperthyroidism
Osteoporosis and atrial fibrillation
Describe the clinical presentation of pseudohypoparathyroidism
Bone abnormalities (McCune Albright)
Obesity
Subcutaneous calcification
Learning disability
Brachydactyly (shortened 4th metacarpal)
What is subclinical hyperthyroidism?
↓TSH, normal fT4/3
Describe the clinical presentation of a multi-nodular goitre
Multiple nodules - thyroid feels bumpy on palpation
Mass effects
Can be inactive or toxic
If a patient has a solitary thyroid nodule which is firm, hard and immobile with cervical lymphadenopathy and associated hoarseness, is it more likely to be benign or malignant?
Malignant
Describe the management of anaplastic thyroid carcinoma
Total thyroidectomy if resectable +/- adjuvant radiochemotherapy as needed
(Do not respond to RAI)
Describe the management of a diffuse goitre
Treat underlying cause if appropriate
Usually no further treatment needed (unless causing obstructive symptoms - surgery)
How are thyroid nodules which have undergone USS-FNA classified?
FNA Bethesda classification - Thy1-5
How would you manage a hypothyroid patient who becomes pregnant?
Increase thyroxine dose by 25mcg as soon as pregnancy suspected, check TFTs regularly and increase thyroxine appropriately
Name two classes of disease which can cause hyperparathyroidism
Granulomatous disease e.g. sarcoid, TB
Disease of high turnover e.g. thyrotoxic, Pagets (especially if bedridden)
How would you investigate a multi-nodular goitre?
As for thyroid nodule - thyroid function test, US, FNA, thyroid isotope scan
CT scan may detect retrosternal extension and tracheal compression in patients with a very large goitre or clinical symptoms
Flow volume loops if considering other potential causes of breathlessness
What is a toxic thyroid nodule?
Thyroid gland contains autonomously functioning thyroid nodule(s), with resulting hyperthyroidism
Describe the prognosis of anaplastic thyroid carcinoma
Rapid growth and involvement of neck structures and death
What causes a sporadic diffuse goitre?
Most cases have no clear cause
Some associated with ingestion of substances limiting T3/T4 production or dyshormonogenesis
Describe the biochemistry usually seen in primary hyperparathyroidism
High calcium, usually high serum PTH, normal or low phosphate
Name an autoimmune disease associated with the development of papillary carcinoma
Hashimotos
Describe the clinical presentation of primary hyperparathyroidism
Hypercalcaemia - fatigue, depression, bone pain, myalgia, nausea, thirst, polyuria, renal stones, osteoporosis
Describe the management of a thyroid storm
High dose carbimazole
β-blockers (propranolol)
Potassium iodide
Hydrocortisone
IV fluids +/- inotropes
Treat precipitating cause e.g. MI, infection, PE
What is pseudohypoparathyroidism?
Genetic defect of the Gs⍺-protein causing end organ resistance to PTH → hypocalcaemia
Which patient group is most likely to develop follicular carcinoma?
Higher incidence in female, higher incidence at 40-50 years
Incidence slightly higher in regions of iodine deficiency
Describe the clinical presentation of anaplastic thyroid carcinoma
Thyroid nodule
Features of local infiltration/compression
Cervical lymphadenopathy
Signs of distant metastases
Name a genetic mutation associated with medullary thyroid carcinoma
Germline RET mutations
Name the 4 types of benign thyroid nodule
Cyst
Colloid nodule
Benign follicular adenoma
Hyperplastic nodule
Define thyrotoxicosis
The clinical, physiological, and biochemical state arising when the tissues are exposed to excess thyroid hormone