Endocrinology: Thyroid dysfunction Flashcards
What are the 2 mechanisms behind diabetes insipidus?
1) A lack of ADH (cranial diabetes insipidus)
2) A lack of response to ADH (nephrogenic diabetes insipidus)
What is diabetes insipidus caused by a lack of ADH also known as?
cranial diabetes insipidus
What is diabetes insipidus caused by a lack of response to ADH also known as?
nephrogenic diabetes insipidus
Where is ADH produced?
Hypothalamus
Where is ADH stored?
Posterior pituitary gland
What is ADH also known as?
Vasopressin
Function of ADH?
ADH stimulates water reabsorption from the collecting ducts in the kidneys.
Pathophysiology in diabetes insipidus?
1) Lack of ADH/lack of response to ADH
2) Kidneys unable to reabsorb water and conentrate the urine
3) Leads to polyuria and polydipsia
What is primary polydipsia?
Is this the same as diabetes insipidus?
Primary polydipsia is when the patient has a normally functioning ADH system but drinks excessive amounts of water, leading to excessive urine production (polyuria).
This is not diabetes insipidus.
What happens in Nephrogenic diabetes insipidus?
when the collecting ducts of the kidneys do not respond to ADH
Causes of nephrogenic diabetes insipidus?
1) Idiopathic
2) Medications, particularly lithium
3) Genetic mutations in the ADH receptor gene (X-linked recessive inheritance)
4) Hypercalcaemia
5) Hypokalaemia
6) Kidney disease (e.g. polycystic kidney disease)
What medication is most likely to cause nephrogenic diabetes insipidus?
Lithium
What happens in cranial diabetes insipidus?
Cranial diabetes insipidus is when the hypothalamus does not produce ADH for the pituitary gland to secrete.
Causes of cranial diabetic insipidus?
1) Idiopathic
2) Brain tumours
3) Brain surgery
4) Brain infections e.g. meningitis, encephalitis
5) Genetic mutations in the ADH gene (autosomal dominant inheritance)
6) Wolfram syndrome
What is Wolfram syndrome?
A genetic condition causing cranial diabetes insipidus, optic atrophy, deafness and diabetes mellitus.
Describe the inheritance pattern for genetic mutations in the ADH receptor gene causing:
a) cranial diabetes insipidus
b) nephrogenic diabetes inspidus
a) autosomal dominant
b) x-linked recessive
What type of diabetes insipidus can hypercalcaemia cause?
Nephrogenic
What type of diabetes insipidus can hypokalaemia cause?
Nephrogenic
What are the presenting features of diabetes inspidus?
- Polyuria (>3 litres of urine per day)
- Polydipsia
- Dehydration
- Postural hypotension
What are the 2 lab findings in diabetes insipidus?
1) Low urine osmolality (lots of water diluting the urine)
2) High/normal serum osmolality (water loss may be balanced by increased intake)
Also more than 3 litres on a 24-hour urine collection
What is the test of choice for diagnosing diabetes insipidus?
Water deprivation test (also known as the desmopressin stimulation test)
Describe the water deprivation test/desmopressin stimulation test
1) The patient avoids all fluids for up to 8 hours before the test (water deprivation).
2) After water deprivation, urine osmolality is measured.
3) If the urine osmolality is low, synthetic ADH (desmopressin) is given.
4) Urine osmolality is measured over the 2-4 hours following desmopressin.
In primary polydipsia, how will water deprivation affect urine osmolality?
Water deprivation will cause urine osmolality to be high (urine more conc).
Therefore, desmopressin does not need to be given.
In cranial diabetes insipidus, how will water deprivation affect urine osmolality?
What happens after desmopressin is given?
In cranial diabetes insipidus, the patient lacks ADH. The kidneys are still capable of responding to ADH.
1) Initially, the urine osmolality remains low as it continues to be diluted by the excessive water lost in the urine.
2) After desmopressin is given, the kidneys respond by reabsorbing water and concentrating the urine.
3) The urine osmolality will be high.
In nephrogenic diabetes insipidus, how will water deprivation affect urine osmolality?
What happens after desmopressin is given?
In nephrogenic diabetes insipidus, the patient is unable to respond to ADH.
The urine osmolality will be low both before and after the desmopressin is given.
Describe Urine Osmolality After Water Deprivation in:
a) primary polydipsia
b) cranial diabetes insipidus
c) nephrogenic diabetes insipidus
a) high
b) low
c) low
Describe Urine Osmolality After desmopressin in:
a) primary polydipsia
b) cranial diabetes insipidus
c) nephrogenic diabetes insipidus
a) not required
b) high
c) low
Management of diabetes insipidus?
1) Treat underlying cause e.g. stop lithium
2) Mild cases may be managed conservatively
3) Desmopressin (synthetic ADH) can be used in cranial diabetes insipidus
Desmopressin can be used in the management of which type of diabetes insipidus?
Cranial (to replace absent ADH)
What needs to be monitored during treatment of cranial diabetes insipidus with desmopressin?
Sodium –> there is a risk of hyponatraemia (due to increased water retention and dilution of blood)
Mangement of Nephrogenic diabetes insipidus?
Nephrogenic diabetes insipidus is less straightforward to treat. Management options include:
- Ensuring access to plenty of water
- High-dose desmopressin
- Thiazide diuretics
- NSAIDs
Define thyrotoxicosis
Thyrotoxicosis refers to the effects of an abnormal and excessive quantity of thyroid hormones in the body.
Location of pathology in 1ary vs 2ary hyperthyroidism?
1ary –> due to thyroid pathology (thyroid is behaving abnormally and producing excessive thyroid hormone.)
2ary –> due to pathology in the hypothalamus or pituitary (e.g. pituitary gland produces too much thyroid-stimulating hormone, stimulating the thyroid gland to produce excessive thyroid hormones)
Define subclinical hyperthyroidism
Describe T3/T4 levles and TSH levels
Thyroid hormones (T3/T4) –> normal
TSH –> supressed (low)
There may be mild or absent symptoms.
What is Grave’s diseas?
An autoimmune condition where TSH receptor antibodies cause primary hyperthyroidism.
What antibodies are seen in Grave’s disease?
TSH receptor antibodies
How do TSH receptor antibodies cause hyperthyroidism in Grave’s disease?
TSH receptor antibodies, produced by the immune system, stimulate TSH receptors on the thyroid.
Does Grave’s disease cause 1ary or 2ary hyperthyroidism
1ary
What is the most common cause of hyperthyroidism?
Grave’s disease
What is toxic multinodular goitre also known as?
Plummer’s disease
What is toxic multinodular goitre?
A condition where nodules develop on the thyroid gland, which are unregulated by the thyroid axis and continuously produce excessive thyroid hormones.
Who is toxic multinodular goitre most common in?
People aged >50 y/o
Presentation of hyperthyroidism
General:
- Weight loss
- Restlessness
- Heat intolerance
- Insomnia
- Fatigue
Neuro:
- Anxiety & irritability
- Tremor
- Brisk reflexes on exam
Cardiac:
- Palpitations (may even provoke arrythmias e.g. AF)
- Tachycardia
Skin:
- Increased sweating
GI:
- Diarrhoea/frequent loose stooles
Gynae:
- Oligomenorrhoea
- Sexual dysfunction
Graves’ disease has additional specific features relating to the presence of TSH receptor antibodies.
What are these?
- Grave’s eye disease, including exopthalmos
- Pretibial myoxedema
- Thyroid acropachy (hand swelling and finger clubbing)
- Diffuse goitre (without nodules)
What is exopthalmos?
Exophthalmos (also known as proptosis) describes the bulging of the eyes caused by Graves’ disease.
Inflammation, swelling and hypertrophy of the tissue behind the eyeballs force them forward, causing them to bulge out of the sockets.
What is pretibial myoxedema?
A skin condition caused by deposits of glycosaminoglycans under the skin on the anterior aspect of the leg (the pre-tibial area).
It gives the skin a discoloured, waxy, oedematous appearance over this area. It is specific to Grave’s disease and is a reaction to TSH receptor antibodies.
What is a goitre?
Goitre refers to the neck lump caused by swelling of the thyroid gland.
Describe the goitre in patients with toxic multinodular goitre.
Nodules may be palpable within a swollen thyroid gland (goitre)
What are the 4 main causes of hyperthyroidism?
GIST
G – Graves’ disease
I – Inflammation (thyroiditis)
S – Solitary toxic thyroid nodule
T – Toxic multinodular goitre
How does thyroiditis affect thyroid levels?
Thyroiditis (thyroid gland inflammation) often causes an initial period of hyperthyroidism, followed by under-activity of the thyroid gland (hypothyroidism).
What are the 4 main causes of thyroiditis?
1) De Quervain’s thyroiditis
2) Hashimoto’s thyroiditis
3) Postpartum thyroiditis
4) Drug-induced thyroiditis
What drugs can cause hyperthyroidism?
Amiodarone
What is a solitary toxic thyroid nodule?
A solitary toxic thyroid nodule is where a single abnormal thyroid nodule acts alone to release excessive thyroid hormone.
The nodules are usually benign adenomas.
Management of a solitary thyroid nodule?
Surgical removal of the nodule.
What is De Quervain’s thyroiditis?
Also known as subacute thyroiditis. It is a condition causing temporary inflammation of the thyroid gland.
There are 3 phases:
1) Thyrotoxicosis
2) Hypothyroidism
3) Return to normal
Management of De Quervain’s thyroiditis?
It is a self-limiting condition, and supportive treatment is usually all that is necessary. This may involve:
- NSAIDs for symptoms of pain and inflammation
- Beta blockers for the symptoms of hyperthyroidism
- Levothyroxine for the symptoms of hypothyroidism
A small number (under 10%) remain hypothyroid long-term.
What is a thyroid storm?
Thyroid storm is a rare presentation of hyperthyroidism. It is also known as thyrotoxic crisis.
It is a rare and more severe presentation of hyperthyroidism with fever, tachycardia and delirium.
What triad of symptoms can be seen in a thyroid storm?
1) Fever
2) Tachycardia
3) Delirium
Management of a thyroid storm?
It can be life-threatening and requires admission for monitoring.
It is treated the same way as any other presentation of thyrotoxicosis, although they may need additional supportive care with fluid resuscitation, anti-arrhythmic medication and beta blockers.
1st line medical management of hyperthyroidism?
Carbimazole (usually taken for 12 to 18 months)
Once a patient taking carbimazole for hyperthyroidism has normal thyroid hormone levels (usually within 4-8 weeks), they continue on maintenance carbimazole.
How is this maintenance managed?
1) Titration block –> The carbimazole dose is titrated to maintain normal levels
2) Block and replace –> A higher dose blocks all production, and levothyroxine is added and titrated to effect (known as block and replace)
Key potential side effect of carbimazole?
1) Acute pancreatitis –> In your exams, look out for a patient on carbimazole presenting with symptoms of pancreatitis (e.g., severe epigastric pain radiating to the back).
2) Agranuglocytosis
2nd line drug used in hyperthyroidism?
Propylthiouracil
Key risk of Propylthiouracil?
1) There is a small risk of severe liver reactions, including death, which is why carbimazole is preferred.
2) Agranulocytosis
What is a key presenting feature of agranulocytosis?
Sore throat
In your exams, if you see a patient with a sore throat on carbimazole or propylthiouracil, the cause is likely agranulocytosis. They need an urgent full blood count and aggressive treatment of any infections.
Treatment options in hyperthyroidism?
1) Carbimazole
2) Propylthiouracil
3) Radioactive iodine
4) Beta blockers
5) Surgery
How is radioactive iodine used in hyperthyroidism?
1) Drinking a single dose of radioactive iodine.
2) The thyroid gland takes this up, and the emitted radiation destroys a proportion of the thyroid cells.
3) The reduction in the number of cells results in a decrease in thyroid hormone production.
4) Remission can take 6 months, after which the thyroid is often underactive, requiring long-term levothyroxine.
What is required for long term management if radioactive iodine treatment used in hyperthyroidism?
Levothyroxine - as thyroid gland has been destroyed
What are the strict rules surrouning treatment with radioactive iodine treatment?
1) Women must not be pregnant or breastfeeding and must not get pregnant within 6 months of treatment
2) Men must not father children within 4 months of treatment
3) Limit contact with people after the dose, particularly children and pregnant women
following treatment with radioactive iodine, how long must women not get pregnant?
Within 6 months
following treatment with radioactive iodine, how long must men not father children?
4 months
How are beta blockers used in hyperthyroidism?
Beta blockers are used to block the adrenalin-related SYMPTOMS of hyperthyroidism.
Do not treat the underlying problem but control the symptoms, while definitive treatment takes time.
They are particularly useful in patients with thyroid storm.
Beta blocker of choice in hyperthyroidism?
Propanolol (non-selectively blocks adrenergic activity)
Surgical options for hyperthyroidism?
- Thyroidectomy (removing the whole gland)
- Removing the toxic nodules
Patients will be hypothyroid after a thyroidectomy, requiring life-long levothyroxine.
Mechnanism of carbimazole?
Anti-thyroid agent:
Converted to its active form of methimazole which then inhibits thyroid peroxidase (TPO)
(TPO normally catalyses the iodination of tyrosine residues in thyroglobulin and the oxidative coupling of iodinated tyrosine)
Contraindications of carbimazole?
- Pregnancy
- Breastfeeding
- Severe blood disorders
Side effets of carbimazole?
- Bone marrow disorders
- Haemolytic anaemia
- Agranulocytosis
- Acute pancreatitis
Site of pathology, TSH, T3 and T4 levels in 1ary hypothyroidism
Site - thyroid gland
TSH - high (due to lack of negative feedback)
T3&T4 - low
Site of pathology, TSH, T3 and T4 levels in 2ary hypothyroidism
Site - pituitary gland
TSH - low
T3&T4 - low
What is the most common cause of hypothyroidism in the developed world?
Hashimoto’s thyroiditis
What is the most common cause of hypothyroidism in the developing world?
Iodine deficiency
What is Hashimoto’s thyroiditis?
It is an autoimmune condition causing inflammation of the thyroid gland. It is associated with anti-thyroid peroxidase (anti-TPO) antibodies and anti-thyroglobulin (anti-Tg) antibodies.
What antibodies are seen in Hashimoto’s?
1) Anti-TPO
2) Anti-Tg
In which food products is iodine normally found?
Iodine is particularly found in dairy products and may be added to non-dairy milk alternatives (e.g., soya milk).
Give some causes of hypothyroidism
- Hashimoto’s
- Iodine deficiency
- Treatments for hyperthyroidism
- Lithium
- Amiodarone
How can amiodarone affect the thyroid?
Amiodarone interferes with thyroid hormone production and metabolism, usually causing hypothyroidism but can also cause thyrotoxicosis.
What treatments for hyperthyroidism have the potential to cause hypothyroidism?
- Carbimazole
- Propylthiouracil
- Radioactive iodine
- Thyroid surgery
How does lithium affect the thyroid?
Lithium inhibits the production of thyroid hormones in the thyroid gland and can cause a goitre and HYPOthyroidism.
What is 2ary hypothyroidism associated with?
Secondary hypothyroidism is often associated with a lack of other pituitary hormones, such as ACTH (referred to as hypopituitarism)
Causes of 2ary hypothyroidism?
- Tumours (e.g., pituitary adenomas)
- Surgery to the pituitary
- Radiotherapy
- Sheehan’s syndrome (where major post-partum haemorrhage causes avascular necrosis of the pituitary gland)
- Trauma
What is Sheehan’s syndrome?
Occurs when the anterior pituitary gland is damaged (avascular necrosis) due to significant blood loss.
Typically occurs after major post-partum haemorrhage
Presentation of hypothyriodism?
General:
- Weight gain
- Fatigue
- Cold intolerance
Skin & hair:
- Dry skin (anhydrosis)
- Cold, yellowish skin
- Coarse hair and hair loss (loss of lateral aspect of eyebrows)
- Non-pitting oedema (e.g. swollen hands, face0
Gynae:
- Heavy or irregular periods
GI:
- Constipation
Neuro:
- Decreased deep tendon reflexes
- Carpal tunnel syndrome
Which causes of hypothyrodism can cause a goitre?
1) Iodine deficiency
2) Hashimoto’s thyroiditis can initially cause a goitre, after which there is atrophy (wasting) of the thyroid gland.
Describe changes in thyroid gland in Hashimoto’s
Initially –> goitre
After –> atrophy
Medical management of hypothyroidism?
Levothyroxine
Mechanism of levothyroxine?
Levothyroxine is a synthetic version of T4 and metabolises to T3 in the body.
How is the dose of levothyroxine titrated?
The dose is titrated based on the TSH level, initially every 4 weeks.
In patients on levothyroxine, what would a high TSH result indicate?
Levothyroxine dose is too low –> increase dose
In patients on levothyroxine, what would a low TSH result indicate?
Levothyroxine dose is too high –> reduce dose
Where levothyroxine is not tolerated, what can be used instead?
Liothyronine sodium (a synthetic version of T3)
What 2 electrolyte abnormalities can cause nephrogenic diabetes insipidus?
1) Hypercalcaemia
2) Hypokalaemia
