Endocrinology (Thyroid) Flashcards
Hyperthyroidism
describes the excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is a term used to describe the clinical manifestations of excess circulating thyroid hormones due to any cause, including hyperthyroidism.
Thyroid Physiology
- The hypothalamus releases thyrotropin-releasing hormone (TRH) which acts on the anterior pituitary, causing it to release thyroid-stimulating hormone (TSH).
- The TSH acts on the thyroid gland to produce thyroxine (T4) and triiodothyronine (T3).
- T4 is inactive and is converted to T3 peripherally.
- T3 and T4 exert negative feedback on the hypothalamus and pituitary.
causes of hyperthyroidism
- Graves’ disease
- Toxic multinodular goitre
- Toxic thyroid adenoma
- Hashimoto’s thyroiditis (acute phase)
- Subacute (de Quervain’s) thyroiditis (acute phase)
- Drugs (e.g. amiodarone)
- Post-partum thyroiditis (acute phase)
presentation of hyperthyroidism
- weight loss
- increased appetite
- restlessness
- heat intolerance
- tachycardia
- palpitations
- diarrhoea
- sweating
- tremor
- anxiety - psychosis
- oligomenorrhoea
signs of hyperthyroidism
- Sweaty and warm palms
- Palmar erythema
- Fine tremor
- Tachycardia – can be atrial fibrillation:
- Hair thinning/loss
- Brisk reflexes
- Goitre (swelling of the neck due to enlargement of the thyroid gland)
- Proximal myopathy
- Lid lag
- Thyroid acropachy (nail clubbing)
investigations for hyperthyroidism
- TFT : TSH, T3, T4
- thyroid autoantibodies
- thyroid US
- Radioactive iodine uptake testing (thyroid scintigraphy)
TFT results for hyperthyroidism
TSH: low
T3: raised
T4: raised
Thyroid autoantibodies:
- TSH receptor antibodies (TRAb): positive in Graves’ disease
- Thyroid peroxidase antibodies (TPOAb): positive in Hashimoto’s thyroiditis
Graves’ disease
is an autoimmune condition characterised by the presence of TSH receptor antibodies (TRAb) binding to the TSH receptor, stimulating the thyroid gland to increase secretion of T3 and T4 leading to hyperthyroidism. Since more T3 and T4 are made, negative feedback reduces the release of TSH from the anterior pituitary gland.
RF for graves disease
Smoking
Family history
Female sex
signs of graves
1) Eye signs:
- Exophthalmos – bulging/protruding eyeballs
- Ophthalmoplegia – paralysis/weakness of one or more extraocular muscles
2) Pretibial myxoedema:
3) Non-pitting oedema
Eye signs usually precede pretibial myxoedema
investigations for graves
TFTs:
- Increased T3 and T4
- Reduced TSH
Thyroid autoantibodies:
- TSH receptor antibodies (TRAb): positive in 90% of patients
Radioactive iodine uptake testing:
- Uptake is increased, diffuse, and homogenous (consistent throughout the thyroid gland)
management of Graves in primary care i.e. before referral to secondary care
- 1st-line: propranolol for symptomatic relief + referral to endocrinology
- If symptoms are troublesome while awaiting referral: offer carbimazole
management of Graves in secondary care:
- 1st-line: carbimazole
- 2nd-line: propylthiouracil
- Consider radioiodine treatment
thyroid eye disease
an autoimmune condition resulting in inflammation and swelling of the extraocular muscles, fatty tissue and connective tissue within the orbit.
Pathophysiology:
Closely correlating with Graves’ disease, patients with TED have been found to have elevated levels of antibodies against thyroid-stimulating hormone (TSH) receptors, which are expressed in orbital fat and connective tissue.
Studies also attribute increased fibroblast activity as well as the accumulation of collagen and hyaluronic acid to the enlargement and fibrosis of the extraocular muscles.2
management of thryoid eye disease
- correct hyperthyroidims
- smoking cessation!!
- artificial tears and tapes
- steroids in severe cases e.g. IV methylprednisolone as first line form compressive optic neuropathy
- surgical decompression and lid surgery
Toxic multinodular goitre (TMNG)
is characterised by thyroid nodules that secrete excess T3 and T4 autonomously (without the need for TSH to stimulate them) leading to hyperthyroidism.
Risk Factors for Toxic multinodular goitre
- Iodine deficiency – more common in developing countries
- Head and neck irradiation
- Female sex
investigations for toxic multinodular goitre
TFTs:
* Increased T3 and T4
* Reduced TSH
Thyroid autoantibodies:
* None are present
Radioactive iodine uptake testing:
* Uptake is patchy
management of toxic multinodular goitre
radioactive iodine
radioactive iodine side effect
hypothyroidism
toxic thyroid adenoma
A toxic adenoma is a singular thyroid nodule that releases thyroid hormones autonomously. They are almost always benign.
Investigations for toxic thyroid adenoma
TFTs:
* Increased T3 and T4
* Reduced TSH
Thyroid autoantibodies:
* None are present
Radioactive iodine uptake testing:
* Uptake is in a focal area
managemnt of toxic thyroid adenoma
radioactive iodine or surgery
Hashimoto’s thyroiditis:
- This can cause hyperthyroidism initially (in the acute phase), followed by hypothyroidism.
Subacute (de Quervain’s) thyroiditis:
Can cause hyperthyroidism initially (in acute phase), followed by hypothyroidism.
Post–partum thyroiditis:
Can cause hyperthyroidism initially (in acute phase), followed by hypothyroidism.
A thyrotoxic crisis
is a potentially life-threatening complication of hyperthyroidism. It can lead to hyperthermia, cardiac arrhythmias heat failure, multiple organ failure, and sepsis.
causes of thytrotoxic crisis
- Infection
- Trauma or surgery
- Withdrawal/non-compliance with antithyroid medication
- Myocardial infraction or stroke
- Pulmonary embolism
- Childbirth
- Overdose of levothyroxine
- Diabetic ketoacidosis, hyperosmolar hyperglycaemic state
- Hypoglycaemia
Presentation of thyrotoxic crisis
Patients generally present with sudden-onset severe hyperthyroidism:
- Hyperpyrexia (>41.0ºC)
- Tachycardia >140 bpm
- Arrhythmias (e.g. atrial fibrillation)
- Nausea
- Diarrhoea
- Confusion
- Psychosis
- Seizures
- Coma
Investigations for thyrotoxicosis
TFTs:
- Elevated T3 and T4
- Reduced TSH
ECG
Chest x-ray
ABGs
management of thyrotoxic crisis
- 1st-line: beta-blockers, propylthiouracil, and hydrocortisone
- High levels of thyroid hormone can increase the breakdown of cortisol, increasing the risk of adrenal insufficiency. Hydrocortisone is given to mitigate this risk
what is subclinical hyperthyroidism
- suppressed TSH below the normal ref range but T3/T4 are within normal ref range
most common cause of subclinical hyperthyroidism is
toxic multinodular goitre
- more common i elderly
investigations for subclinical hyperthyroidism
Thyroid function tests (TFTs) show low TSH and normal FT4 and FT3. These should be repeated 3 months after to exclude other causes of transient TSH suppression. If after at least 3 months of repeat testing, TSH is still low but FT4 and FT3 are normal, subclinical hyperthyroidism is diagnosed.
Referral for subclinical hyperthyroidism
1) Urgently refer to secondary care via a suspected cancer pathway if:
- Goitre, nodule, or structural change is present or if malignancy is suspected
- TFTs are generally normal in people with thyroid cancer
2) Refer to an endocrinologist if:
- Subclinical hyperthyroidism is diagnosed as above and there is evidence of thyroid disease (e.g. goitre, positive autoantibodies, or symptoms of hyperthyroidism)
types of thyroid cancer
- Papillary thyroid carcinoma (most common)
- Follicular thyroid carcinoma (second most common)
- Medullary thyroid cancer(MEN 2A or 2B)
- Anaplastic thyroid cancer
- Thyroid lymphoma
Papillary thyroid carcinoma:
- Most common form of thyroid cancer – around 70%
- More common in women aged 35-40 years
- Metastases tend to spread locally in the neck
- The prognosis is excellent
Follicular thyroid carcinoma:
- Second most common form of thyroid cancer – around 10%
- May infiltrate the neck but tends to metastasise to the lung and bones
- More common in women aged 30-60 years
Medullary thyroid cancer:
- Cancer of parafollicular calcitonin-producing C cells of the thyroid
- Can be sporadic, but can be inherited as part of multiple endocrine neoplasia (MEN) 2A or 2B
- Serum calcitonin is often raised
Anaplastic thyroid cancer:
- One of the most aggressive cancers in humans
- Most common in people aged 55-65 years of age
- Usually infiltrates the neck leading to compression (cough, vocal cord paralysis, dysphagia, dyspnoea etc.)
- Mean survival is often <6 months, regardless of treatments given
Thyroid lymphoma:
Associated with Hashimoto’s thyroiditis
More common in women around the age of 65 years
Usually a rapidly growing mass in the neck which can lead to symptoms due to compression
investigations for thyroid cancer
TFTs:
- Usually normal
Neck ultrasound:
- Shows masses/nodules
- Features seen include macrocalcifications, irregular borders, intramodular blood flow, and peripheral halo
Fine-needle aspiration cytology (FNAC):
- Allows for histological diagnosis
Radioactive iodine uptake testing:
- ‘Cold areas’ are areas of abnormally low uptake and are seen in thyroid cancer
management of thyroid cancer
Options involve a total thyroidectomy, radioactive iodine, and radiotherapy.
Hypothyroidism
describes the inadequate production of thyroid hormones by the thyroid gland. It may also be referred to as an underactive thyroid.
most common cause of hypothyroidism in the UK
- hashimotos thyroiditis
- iodine deficiency in the developing world
hypothyroidism can be
primary
secondary
Primary hypothyroidism
- Hashimoto’s thyroiditis
- Iatrogenic (e.g. radiotherapy to the neck, radioactive iodine treatment)
- Iodine deficiency
- Some drugs (e.g. amiodarone and lithium)
- Infiltrative causes (e.g. sarcoidosis or haemochromatosis)
- Congenital (e.g. dysgenesis)
- Postpartum thyroiditis
Secondary hypothyroidism
- Any cause of hypopituitarism (e.g. neoplasm, trauma, infection, radiotherapy)
- Any cause of hypothalamic dysfunction (e.g. neoplasm, trauma)
presentation of hypothyroidism
- Fatigue
- Lethargy
- Cold intolerance:
- Dry skin
- Hair loss
- Constipation
- Decreased appetite with weight gain
- Poor memory
- Difficulty with concentration
- Reduced libido
- Menorrhagia
signs of hypothyroidism
- Dry and coarse skin
- Cold peripheries
- Myxoedema:
- Non-pitting oedema of the face, hands, and feet
- Bradycardia
- Decreased tendon reflexes
- Carpal tunnel syndrome
investigations for hypothyroidism
Thyroid function tests (TFTs):
- These measure TSH, T3, and T4
- TSH: elevated
- T3: reduced
- T4: reduced
Thyroid autoantibodies:
- Thyroid peroxidase antibodies (TPOAb): positive in Hashimoto’s thyroiditis
Thyroid ultrasound:
- Considered if a goitre is detected
Radioactive iodine uptake testing (thyroid scintigraphy):
- Helps distinguish between different causes of goitre
- More findings are discussed in each cause below
Hashimoto’s thyroiditis
is an autoimmune condition characterised by the destruction of the thyroid gland cells. Although it causes hypothyroidism, there can be hyperthyroidism in the acute phase.
rf for hashimotos
The presence of another autoimmune disease (e.g. type 1 diabetes)
management of Hashimotos
- 1st-line: lifelong thyroid hormone replacement (levothyroxine)
- Surgery for goitres may be considered (e.g. if there are obstructive symptoms)
Adverse effects of thyroid hormone replacement therapy
Adverse effects of thyroid hormone replacement therapy can be due to over-treatment, which can lead to features of hyperthyroidism such as:
- Weight loss
- Osteoporosis
- Arrhythmia (atrial fibrillation)
Subacute (de Quervain’s) thyroiditis
inflammation of the thyroid gland leading to a triphasic presentation of hyperthyroidism, then hypothyroidism, then a return to euthyroidism.
It is thought to be due to a viral infection.
- Hyperthyroid phase – 4-6 weeks in length
- Hypothyroid phase – 2-6 months in length
- Euthyroid phase
management of subacute (de Quervains) thyroiditis
- 1st-line: supportive management (e.g. NSAIDs for thyroid pain)
- In some severe cases, corticosteroids may be used.
*
drugs which can cause hypothyroidism
- Lithium – reduces the activity of thyroid hormone.
- Amiodarone – is structurally similar to thyroid hormones and contains iodine, meaning it can lead to both hyper- and hypothyroidism.
Subclinical hypothyroidism:
TSH: high
T3 and T4: normal
investigations for subclinical hypothyroidism
Thyroid function tests (TFTs) show elevated TSH and normal FT4 and FT3. These should be repeated after 3 months to exclude other causes of transiently raised TSH.
Thyroid peroxidase antibody (TPOAb) testing may be considered. If positive, this can predict progression to overt hypothyroidism.
management of subclinical hypothyroidism
- TSH >10 mU/L: consider offering levothyroxine
- TSH 5.5 – 10 mU/L:
* If <65 years old and symptoms of hypothyroidism: 6-month trial of levothyroxine
* In older people: watch and wait
* If asymptomatic: observe and repeat TFTs in 6 months
Myxoedema coma
is an extreme, decompensated form of hypothyroidism. In this case, decompensation describes the inability of the body to adapt to untreated hypothyroidism.
risk factors for Myxoedema coma
Risk Factors
- Being elderly
- Hypothermia
- Infection (e.g. pneumonia)
- Some drugs (amiodarone, beta-blockers, anaesthesia, lithium)
- Hypoglycaemia
- Stroke
- Surgery or trauma
- Burns
- Hypoxia
Myxoedema coma presentation
- Acute mental state changes (e.g. confusion) – common
- Hypothermia (<35.5°C often)
- Generalised swelling and puffiness due to oedema
- Coarse hair
- Dry skin
- Bradycardia
- Bradypnoea
- Hypoxia
investigations for myxoedemic coma
TFTs:
* TSH: usually raised
* T3 and T4: usually reduced
FBC:
* May show signs of infection (e.g. raised white cell count)
U&Es:
* May show hyponatraemia
Blood glucose:
* May be reduced
Serum cortisol:
- To rule out adrenal insufficiency which may co-exist with hypothyroidism in hypopituitarism
ABGs:
- May show hypoxia, hypercapnia, and respiratory acidosis
ECG:
* May show bradycardia
management of myxoedemic coma
- 1st-line: IV fluids + IV thyroid hormone replacement + IV hydrocortisone (until the possibility of coexisting adrenal insufficiency has been ruled out)
- Correct hypoglycaemia and electrolyte disturbances
- Consider non-invasive ventilation or intubation and ventilation
sick euthyroid syndrome
low free T3 (FT3), free T4 (FT4), and low/normal thyroid-stimulating hormone (TSH).
It is generally seen in patients after critical illness, starvation, or intensive care. It is thought to occur due to changes in the hypothalamus-pituitary-thyroid axis.
Patients generally do not have symptoms and changes are reversible upon recovery. No treatment is generally needed.
Hyperparathyroidism (HPT)
is characterised by an increased level of parathyroid hormone (PTH) in the blood. Increased levels of PTH cause serum calcium levels to increase and phosphate levels to fall.
HPT types
Primary HPT:
- The disorder is from within the parathyroid glands themselves
Secondary HPT:
- The disorder is from somewhere else outside the parathyroid glands
- This is usually in response to low calcium secondary to kidney, liver, or bowel disease
Tertiary HPT:
- Usually seen in those with long-term secondary HPT. Eventually, this leads to parathyroid hyperplasia and autonomous PTH secretion
Calcium and phosphate homeostasis
- PTH normally stimulates bone resorption, along with stimulating the kidneys to reabsorb calcium and convert 25-hydroxyvitamin D3 to its active form 1,25-hydroxyvitamin D3, which is responsible for the intestinal absorption of calcium.
- Low serum calcium stimulates PTH secretion, whereas high calcium levels suppress PTH secretion.
- PTH reduces the reabsorption of phosphate from the proximal tubules in the kidneys, leading to more phosphate excretion in the urine.
- Calcitonin is a hormone that opposes the effects of PTH and reduces serum calcium. It is released by thyroid parafollicular cells.
Chronic kidney disease and secondary HPT
Patients with chronic kidney disease (CKD) excrete less phosphate due to dysfunction of the kidneys. This leads to the removal of calcium ions from the circulation as they are deposited in the insoluble salt calcium phosphate. This leads to hypocalcaemia and an increased level of potassium ions in the circulation, leading to secondary hyperparathyroidism.
Primary hyperparathyroidism
- Solitary parathyroid adenoma – 80% of cases
- Parathyroid hyperplasia
- Multiple parathyroid adenomas
- Parathyroid malignancy
Secondary hyperparathyroidism
- Chronic kidney disease
- Calcium loss/increased calcium demand
Presentation: Primary hyperparathyroidism
The features of primary HPT and hypercalcaemia can be remembered using the mnemonic:
- Bones – bone pain and fractures
- Stones – renal stones
- Abdominal groans – anorexia, nausea
- Psychiatric moans – depression, insomnia, impaired memory
- Thrones – constipation
- An ECG may show QT interval shortening
Presentation: Secondary hyperparathyroidism
- Features of hypercalcaemia (mentioned above)
- Features of chronic kidney disease
- Features of malabsorption (e.g. coeliac disease, Crohn’s disease, chronic pancreatitis)
- Features of osteomalacia (e.g. bone pain, fractures, or bowed legs in children)
- Features of hypocalcaemia
Investigations for hyperparathyroidism
Serum calcium:
- Findings vary depending on the type of HPT
Serum phosphate:
- Findings vary depending on the type of HPT
Parathyroid hormone:
- Findings vary depending on the type of HPT
Alkaline phosphatase (ALP):
- Generally raised
X-ray:
- May show **pepper pot skull **(salt and pepper sign) in the skull – these are multiple small well-defined areas of lucency in the skull cap
investigation findings for primary HPT
- elevated calcium
- reduced phosphate
- PTH: raised or inappropriately normal despite raised calcium
- ALP: increased
investigation findings for secondary HPT
when the glands are fine but a condition, like kidney failure, lowers calcium levels and causes the body to react by producing extra parathyroid hormone
- reduced calcium
- elevated phosphate
- PTH: raised
- ALP: increased
investigation findings for tertiary HPT
- normal/elevated calcium
- reduced phosphate
- PTH: raised
- ALP: increased
Primary hyperparathyroidism management
- 1st-line: total parathyroidectomy
- If unsuitable for/declines surgery: manage medically with calcimimetic (e.g. cinacalcet)
- Cinacalcet binds to calcium-sensing receptors leading to the reduction of serum calcium and PTH – it mimics the effects of calcium
management of secondary hyperparathyroidism
1st-line: manage underlying cause (e.g. offer vitamin D and calcium supplements for a patient with CKD)
management of tertiary hyperparathyroidism
1st-line: watch and wait + consider partial/total parathyroidectomy
complications of hyperparathyroidism
Complications
- Osteoporosis
- Bone fractures
- Renal stones
- Features of hypercalcaemia (e.g. depression, constipation, nausea)
Complications of surgery:
- Hypocalcaemia
- Recurrent laryngeal nerve palsy
- Haematoma formation and airway obstruction
