Endocrinology 2 Flashcards
what is hyperosmolar hyperglycaemic state?
it is a medical emergency where hyperglycaemia results in osmotic diuresis, severe dehydration and electrolyte deficiencies
It typically occurs in elderly with T2DM but it can be the initial presentation of T2DM
what is the pathophysiology of hyperosmolar hyperglycaemic state?
Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium
Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood.
Despite these severe electrolyte losses and total body volume depletion, the typical patient with HHS, may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume.
what are the clinical features of hyperosmolar hyperglycaemic state?
General: fatigue, lethargy, nausea and vomiting
Neurological: altered level of consciousness, headaches, papilloedema, weakness
Haematological: hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis)
Cardiovascular: dehydration, hypotension, tachycardia
what are the complications of hyperosmolar hyperglycaemic state ?
MI stoke peripheral arterial thrombosis seizures cerebral oedema treatment
how is hyperosmolar hyperglycaemic state diagnosed?
- Hypovolaemia
- Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis
- Significantly raised serum osmolarity (> 320 mosmol/kg)
Note: A precise definition of HHS does not exist, however the above 3 criteria are helpful in distinguishing between HHS and DKA. It is also important to remember that a mixed HHS / DKA picture can occur.
how is hyperosmolar hyperglycaemic state managed?
- Normalise the osmolality (gradually)
- Replace fluid and electrolyte losses
- Normalise blood glucose (gradually)
Fluid replacement - IV 0.9% NaCl should be first line
*rapid changes in the osmolality (to which glucose and sodium are the main contributors) are dangerous and can result in CV collapse and central pontine myelinolysis
Rapid changes must be avoided. A safe rate of fall of plasma glucose of between 4 and 6 mmol/hr is recommended. The rate of fall of plasma sodium should not exceed 10 mmol/L in 24 hours.
a target blood glucose should be between 10 and 15mmol/L
a complete normalisation of electrolytes and osmolality may take up to 72 hours to correct
*** if there is not significant ketonaemia then DO NOT start insulin - you should always start fluids before giving insulin in hyperglycaemic hyperosmolar state
Replace their potassium depending on their levels
what is the cellular structure f the thyroid gland?
Thyroid epithelia form follicles filled with colloid – a protein-rich reservoir of the materials needed for thyroid hormone production.
In the spaces between the follicles, parafollicular cells can be found. These cells secrete calcitonin, which is involved in the regulation of calcium metabolism in the body.
what is the function of the thyroid gland?
it is one of the largest endocrine glands in the body
it is one of the main regulators of metabolism
metabolic processes increased by thyroid hormone include:
Basal Metabolic Rate
Gluconeogenesis
Glycogenolysis
Protein synthesis
Lipogenesis
Thermogenesis
it produces thyroxine (T4) and triiodothyronine (T3), the two main thyroid hormones. These then act on a wide variety of tissues, helping to regulate the use of energy sources, protein synthesis, and controls the body’s sensitivity to other hormones.
what causes thyroid hormones to be released?
The Hypothalamus detects a low plasma concentration of thyroid hormone and releases Thyrotropin-Releasing Hormone (TRH) into the hypophyseal portal system.
TRH binds to receptors found on thyrotrophic cells of the anterior pituitary gland, causing them to release Thyroid Stimulating Hormone (TSH) into the systemic circulation. TSH binds to TSH receptors on the basolateral membrane of thyroid follicular cells and induces the synthesis and release of thyroid hormone.
what is hyperthyroidism also known as?
thyrotoxicosis
Hyperthyroidism is where there is over-production of thyroid hormone by the thyroid gland. Thyrotoxicosis refers to an abnormal and excessive quantity of thyroid hormone in the body.
how is hypothyroidism classified?
primary hypothyroidism: there is a problem with the thyroid gland itself, for example an autoimmune disorder affecting thyroid tissue (see below)
secondary hypothyroidism: usually due to a disorder with the pituitary gland (e.g.pituitary apoplexy) or a lesion compressing the pituitary gland
congenital hypothyroidism: due to a problem with thyroid dysgenesis or thyroid dyshormonogenesis
what is the most common cause of hypothyroidism?
Hashimoto’s thyroiditis
what is the most common cause of thyrotoxicosis?
Graves disease
what are the symptoms of hypothyroidism?
weight gain lethargy cold intolerance dry, cold, yellowish skin not-pitting oedema (in hands and face) dry, coarse scalp hair, loss of lateral aspects of eyebrows constipation menorrhagia decreased tendon reflexes carpal tunnel syndrome
what are the symptoms of hyperthyroidism?
weight loss manic restlessness heat inolerance palpitations - may provoke arrhythmias increased sweating Pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli Thyroid acropachy: clubbing diarrhoea oligomenorrhe anxiety tremor
what are the different types of hyperthyoidism?
Primary Hyperthyroidism is due to thyroid pathology. It is the thyroid itself that is behaving abnormally and producing excessive thyroid hormone.
Secondary hyperthyroidism is the condition where the thyroid is producing excessive thyroid hormone as a result of overstimulation by thyroid stimulating hormone. The pathology is in the hypothalamus or pituitary.
Grave’s Disease is an autoimmune condition where TSH receptor antibodies cause a primary hyperthyroidism. These TSH receptor antibodies are abnormal antibodies produced by the immune system that mimic TSH and stimulate the TSH receptors on the thyroid. This is the most common cause of hyperthyroidism.
Toxic Multinodular Goitre (also known as Plummer’s disease) is a condition where nodules develop on the thyroid gland that act independently of the normal feedback system and continuously produce excessive thyroid hormone.
other causes of hyperthyroidism:
Solitary toxic thyroid nodule
Thyroiditis (e.g. De Quervain’s, Hashimoto’s, postpartum and drug-induced thyroiditis)
what are unique features of graves disease?
These features all relate to the presence of TSH receptor antibodies.
Diffuse Goitre (without nodules)
Graves Eye Disease
Bilateral Exopthalmos
Pretibial Myxoedema
what are the unique features of toxic multinodular goitre?
Goitre with firm nodules
Most patients are aged over 50
Second most common cause of thyrotoxicosis (after Grave’s)
what is solitary toxic thyroid nodule?
This is where a single abnormal thyroid nodule is acting alone to release thyroid hormone. The nodules are usually benign adenomas. They are treated with surgical removal of the nodule.
what is De Quervain’s Thyroiditis?
De Quervain’s Thyroiditis describes the presentation of a viral infection with fever, neck pain and tenderness, dysphagia and features of hyperthyroidism. There is a hyperthyroid phase followed by hypothyroid phase as the TSH level falls due to negative feedback. It is a self-limiting condition and supportive treatment with NSAIDs for pain and inflammation and beta blockers for symptomatic relief of hyperthyroidism is usually all that is necessary.
There are typically 4 phases; phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR phase 2 (1-3 weeks): euthyroid phase 3 (weeks - months): hypothyroidism phase 4: thyroid structure and function goes back to normal
Investigations
thyroid scintigraphy: globally reduced uptake of iodine-131
what is thyroid storm?
aka thyrotoxic crisis
It is a more severe presentation of hyperthyroidism with pyrexia, tachycardia and delirium.
it requires admission for monitoring - it will be treated the same way as any other thyrotoxicosis, although supportive care with fluid resuscitation, anti-arrhythmic medications and beta blockers.
how is hyperthyroidism managed?
Carbimazole - is the first line anti-thyroid drug (the drug can either be carefully titrated to maintain normal levels (titration block regimen) or the dose is given high enough to block all production and the patient takes levothyroxine titrated to effect (block and replace regimen)
Often Complete remission and the ability to stop taking carbimazole is usually achieved within 18 months of treatment
Propylthiouracil is second line
if this doesn’t work then it can be treated with radioactive iodine - this involves drinking a single dose of radioactive iodine. This is taken up by the thyroid gland and the emitted radiation destroys a proportion of the thyroid cells. This reduction in functioning cells results in a decrease of thyroid hormone production and thus remission from the hyperthyroidism. Remission can take 6 months and patients can be left hypothyroid afterwards and require levothyroxine replacement. (patients must not be pregnant, must avoid close contact with children and pregnant woman for 3 days and limit contact with anyone three days after receiving dose.
Beta-blockers - for symptomatic relief as they block adrenaline related symptoms - propanolol is a good choice as it is a non-selective block on adrenergic activity (other selective beta blockers just work on the heart) they are particularly useful in those patients with thyroid storm
surgery is definitive option but they would require levothyroxine replacement for life
what is Riedel’s thyroiditis?
Riedel’s thyroiditis is a rare cause of hypothyroidism characterised by dense fibrous tissue replacing the normal thyroid parenchyma. On examination a hard, fixed, painless goitre is noted. It is usually seen in middle-aged women. It is associated with retroperitoneal fibrosis.
what are the different causes of hypothyroid?
- hashimotos’s thyroiditis
- iodine deficiency
- secondary treatment of hyperthyroidism
- medications (lithium and amioderone)
- central causes - This is where the pituitary gland is failing to produce enough TSH. This is often associated with a lack of other pituitary hormones such as ACTH. This is called hypopituitarism and has many causes: Tumours, Infection, Vascular (e.g. Sheehan Syndrome), Radiation
what is hashimoto’s?
This is the most common causes of hypothyroidism in the developed world. It is caused by autoimmune inflammation of the thyroid gland. It is associated with antithyroid peroxidase (anti-TPO) antibodies and antithyroglobulin antibodies. Initially it causes a goitre after which there is atrophy of the thyroid gland.
how is hypothyroidism managed?
Replacement of thyroid hormone with oral levothyroxine is the treatment of hypothyroidism. Levothyroxine is synthetic T4, and metabolises to T3 in the body. The dose is titrated until TSH levels are normal.
what is subclinical hyperthyroidism?
it is defined as
- normal serum free T3 and T4 levels
- with TSH below the normal range
what are causes of subclinical hyperthyroidism?
multinodular goitre, particularly in elderly females
excessive thyroxine may give a similar biochemical picture
why is it important to recognise subclinical hyperthyroidism?
The importance in recognising subclinical hyperthyroidism lies in the potential effect on the cardiovascular system (atrial fibrillation) and bone metabolism (osteoporosis). It may also impact on quality of life and increase the likelihood of dementia
how is subclinical hyperthyroidism managed?
TSH levels often revert to normal - therefore levels must be persistently low to warrant intervention
a reasonable treatment option is a therapeutic trial of low-dose antithyroid agents for approximately 6 months in an effort to induce a remission
what is subclinical hypothyroidism?
TSH raised but T3, T4 normal
no obvious symptoms
*risk of progressing to overt hypothyroidism is 2-5% per year (higher in men)
risk increased by the presence of thyroid autoantibodies
how is subclinical hypothyroidism managed?
Not all patients require treatment.
TSH is between 4 - 10mU/L and the free thyroxine level is within the normal range
if < 65 years with symptoms suggestive of hypothyroidism, give a trial of levothyroxine. If there is no improvement in symptoms, stop levothyroxine
‘in older people (especially those aged over 80 years) follow a ‘watch and wait’ strategy, generally avoiding hormonal treatment’
if asymptomatic people, observe and repeat thyroid function in 6 months
TSH is > 10mU/L and the free thyroxine level is within the normal range start treatment (even if asymptomatic) with levothyroxine if <= 70 years 'in older people (especially those aged over 80 years) follow a 'watch and wait' strategy, generally avoiding hormonal treatment'
what would TFTs show in thyrotoxicosis e.g. Grave’s disease?
TSH - low
T4 - high
* in T3 thyrotoxicosis the free T4 will be normal
what would TFTs show in primary hypothyroidism?
TSH - high
T4 - low
what would TFT’s show in secondary hypothyroidism?
TSH - low
T4 - low
*replacement steroid therapy is required prior to thyroxine
what antibodies can you test for in thyroid disease?
Antithyroid Peroxidase (anti-TPO) Antibodies are antibodies against the thyroid gland itself. They are the most relevant thyroid autoantibody in autoimmune thyroid disease. They are usually present in Grave’s Disease and Hashimoto’s Thyroiditis.
Antithyroglobulin Antibodies are antibodies against thyroglobulin, a protein produced and extensively present in the thyroid gland. Measuring them is of limited use as they can be present in normal individuals. They are are usually present in Grave’s Disease, Hashimoto’s Thyroiditis and thyroid cancer.
TSH Receptor Antibodies are autoantibodies that mimic TSH, bind to the TSH receptor and stimulate thyroid hormone release. They are the cause of Grave’s Disease and so will be present in this condition.
what scans can be used for thyroid disease?
Ultrasound of the thyroid gland is useful in diagnosing thyroid nodules and distinguishing between cystic (fluid filled) and solid nodules. Ultrasound can also be used to guide biopsy of a thyroid lesion.
Radioisotope scans are used to investigate hyperthyroidism and thyroid cancers. Radioactive iodine is given orally or intravenously and travels to the thyroid where it is taken up by the cells. Iodine is normally used by thyroid cells to produce thyroid hormones. The more active the thyroid cells, the faster the radioactive iodine is taken up. A gamma camera is used to detect gamma rays emitted from the radioactive iodine. The more gamma rays that are emitted from an area the more radioactive iodine has been taken up. This gives really useful functional information about the thyroid gland:
Diffuse high uptake is found in Grave’s Disease
Focal high uptake is found in toxic multinodular goitre and adenomas
“Cold” areas (i.e. abnormally low uptake) can indicate thyroid cancer
how does thyroid cancer usually present?
Features of hyperthyroidism or hypothyroidism are not commonly seen in patients with thyroid malignancies as they rarely secrete thyroid hormones
Most commonly presents as an asymptomatic thyroid nodule detected by palpation or ultrasound in a woman in her 30s or 40s.
what are the different types of thyroid cancer?
Papillary carcinoma - (70%) often young females
Follicular adenoma - (20%)
Medullary - (5%) - cancer of parafollicular (C) cels, secrete calcitonin
Anaplastic - (1%) - not responsive to treatment, can cause pressure symptoms, most common in elderly females, local invasion is common
Lymphoma - rare - associated with hashimoto’s thyroiditis
what investigations would you perform for thyroid cancer?
TSH - will usually be normal
USS neck - nodules - suspicious features include micro-calcifications, a more-tall-than-wide shape, hypervascularity, marked hypoechogenicity, or irregular margins
fine needle biopsy and cytology
Laryngoscopy - paralysed vocal cord is highly suggestive of malignancy
what can hyponatremia be caused by?
hypovolaemic - Na+ lost and water follows
- this loss can be from kidneys - due to diuretics, addison’s disease ( increased potassium), kidney injury or osmotic diuresis)
- this can be caused by loss from elsewhere - D+V, fistula, burns
Euvolaemic - water gained - normal Na+ quantity
- the water can be gained from the kidneys - SIADH, hypothyroidism, glucocorticoid insufficiency
- the water gained from elsewhere - water intoxication
** Water excess (patient often hypervolaemic and oedematous)
secondary hyperaldosteronism: heart failure, liver cirrhosis
nephrotic syndrome
IV dextrose
psychogenic polydipsia
