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CBL endocrine
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- 1"young F with rceent dramatic weight loss, no menstruation for 3 months, acute abdo pain and vomiting, fast breathing, glucose and ketones in urine" What is the immediate concern? Admission?Immediate concern is of new onset Type 1 Diabetes Mellitus with Diabetic Ketoacidosis.
Patients who are unwell, very hyperglycaemic (glucose >30mmol/L), moderate to large ketones in urine, vomiting with dehydration and vomiting require admission to hospital.
Patients who have no evidence of acidosis or ketosis may be initiated on Insulin treatment as an out-patient. - 2Relevance of family hx of autoimmune diseaseTFT’s and possibly a short synACTHen test may be indicated.
- 3presentation of T1DM- Onset is typically in childhood/adolescence
- They are usually lean
- Ketosis prone – can either test for blood ketones or more usually the presence of urinary ketones
- Presence of auto antibodies
- C peptide is low or undetectable.
- Presentation is typically acute with severe symptoms – polyuria, polydipsia and weight loss. - 4Why polyuria in T1DM?when renal threshold of plasma glucose of 10 mmol/L has been reached
- 5auto-antibodies in T1DMislet cell, insulin, Glutamic Acid Decarboxylase (GAD) Antibodies.
- 6risk of T1DM if family hx0.4% in normal population
• 1-2 % if your mother has it
• 3-6% if your father has it
• Siblings 6% risk
• Monozygotic twins have a 36% concordance - 7Autoimmune Polyendocrine Syndrome Type 2 - what -who - genetics• Triad of Addison’s, AI thyroiditis and T1DM
• More common in females, Presents in adulthood
• Polygenic
– HLA DQ + DR allele association
– DR3 DQB1*0201 DR 4 DQB1*0302 - 8associations of Autoimmune Polyendocrine Syndrome– Pernicious Anaemia
Coeliac Disease
– Primary hypogonadism
Alopecia
– Myasthenia Gravis
Stiff Man Syndrome - 9Triad of diabetic ketoacidosisHyperglycaemia with Glucose of 30 mmol/L (>11.1mmol/L),
Acidosis with Bicarbonate of 6 mmol/L (Bic <15mmol/L)
Ketonuria (Urine dipstick positive for ketones ++++) - 10clinical signs of diabetic ketoacidosis- abdo pain
- Kussmaul's breathing/air hunger
- smell of ketones/nail varnish - 11What are the diagnostic definitions of Diabetes Mellitus, Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT) as endorsed by the World Health Organisation in 2006?
- 12HbA1c cut-off for diabetes (if without symptoms?)48mmol/mol (6.5%)
a value <48mmol/mol (6.5%) does not exclude diabetes diagnosed using glucose tests.
Finger prick HbA1c tests must be confirmed by laboratory venous HbA1c in all patients.
In patients without symptoms of diabetes the laboratory venous HbA1c should be repeated. If the second sample is <48mmol/mol (6.5%) the person should be treated as at high risk of diabetes and the test should be repeated in 6 months or sooner if symptoms develop. - 13What to do in absence of unequivocal hyperglycaemia with acute metabolic decompensation?one of the three glucose tests should be repeated on a different day to confirm the diagnosis.
- 14How does insulin deficiency lead to diabetic ketoacidosis?insulin deficiency, and counter regulatory catabolic hormone excess (glucagon)
insulin deficiency causes excess mobilisation of FREE FATTY ACIDS from adipose tissue which provides the substrate for ketone production in the liver
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Ketones (β hydroxyl butyrate, acetoacetate, acetone) are excreted by the kidneys and buffered in the blood initially but eventually this system fails and acidosis develops.
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Hyperglyceamia also occurs as the liver produces glucose from lactate and alanine which are generated by muscle proteinolysis.
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Reduced peripheral glucose utilisation associated with Insulin deficiency exacerbates hyperglycaemia.
The osmotic diuresis produced by hyperglycaemia and ketonuria causes hypovolaemia - 15Possible causes of diabetic ketoacidosis• new presentation of T1DM
• Non compliance with Insulin
• Inappropriate alterations in Insulin
• Infection
• Myocardial infarction
• Pregnancy - 16management of acute diabetic ketoacidosis- insulin
- potassium (+other electrolytes)
- fluids (sodium chloride 0.9%)
consider and treat precipitant - 17typical losses in DKA• 6-8 litres of water
• Average Losses (mmol)
– Sodium 500-1000
– Chloride 350
– Potassium 300-1000
– Calcium 50-100
– Phosphate 50-100
– Magnesium 25-50 - 18What methods of determining glycaemic control are available?Short term: Home Blood Glucose Monitoring
Long Term: Haemoglobin A1c – glycosylated Hb allows a long term guide to determining glycaemic control. - 19target HbA1c in T1DMTarget HbA1c in T1DM is 53 mmol/mol (7%.) Stricter control is associated with a lower risk of complications.
- 20What elements do you consider to be key to an education package prior to discharge of a new T1DM?1 Never stop Insulin – it is required for survival
2 Use of Insulin device, injection technique, injection sites, rotation of injection sites
3 Out line of the basics of the chosen Insulin regimen
4 Sick day rules – how to manage acute illness with potentially increased Insulin requirements, monitoring of BMs and urine ketones
5 Hypoglycaemia – recognising symptoms – precipitants and how to adjust insulin
6 Smoking
7 Alcohol
8 Driving regulations and informing the DVLA
9 Exercise
10 Diabetes U.K. – local contacts and website address
11 Contact with Diabetes Nurse Specialist and follow up
12 Principals of long term control – the association of good glycaemic control with lower risks of microvascular and macrovsacular complications.
13 Planning a pregnancy. - 21typical features of T2DM• Usually occurs in over 30’s
• Gradual Onset
• Diagnosis often missed
• 25-30% have retinopathy at presentation
• Typically overweight or obese
• Not usually associated with ketoacidosis
• Autoimmune markers tend to be negative - 22What is T2DM?Type 2 diabetes is a chronic, progressive metabolic disorder characterised by Insulin resistance and impaired secretion (beta cell failure)
- 23What lifestyle advice should be provided at diagnosis of T2DM?• Diet including advice on weight loss
• Exercise – increase in activity level should be encouraged, exercise improves
insulin sensitivity
• Lifestyle - especially on advice on how to stop smoking - 24Describe the value of glucose lowering in preventing the risk of macrovascular and microvascular complicationsreduced albuminuria/retinopathy/microvascular disease/myocardial infarction/other
1% reduction in HbA1c gives 25% risk reduction for microvascualr disease - 25Management of diabetic cardiovascular diseaseRISK FACTOR MODIFICATION is key (smoking, dyslipidaemia, hypertension, hyperglycaemia)
CVD is most pronounced in young people with T1DM and exacerbated by spcopeconomic deprivation. - 26Ethnicity with increased prevalence of CV with diabetesSouth Asian individuals
- 27BP lowering in T2DMHypertension in people with diabetes should be treated aggressively with lifestyle modification and drug therapy.
Target diastolic blood pressure in people with diabetes is ≤80 mm Hg.
Target systolic blood pressure in people with diabetes is ≤130 mm Hg.
antihypertensives for diabetics:
• an ACE inhibitor (ARB if ACE inhibitor intolerant), or
• a calcium channel blocker, or
• a thiazide diuretic.
Beta blockers and alpha blockers should not normally be used in the initial management of blood pressure in patients with diabetes. - 28aspirin in diabetesLow-dose aspirin is not recommended for primary prevention of vascular disease in patients with diabetes.
- 29How would you help this patient in the case manage her diabetes in order to prevent hypoglycaemia?1) Hypoglycaemia: Including treatment of hypoglycaemia and definition – differentiating between mild (self treated) and severe (requiring external aid)
2) Occupation
3) Insulin regimen: problems of:
a) Type of regimen: premixed BD regimen
b) Insulin distribution is loaded towards the evening dose
In this lady’s case a basal bolus regimen +/- carbohydrate counting (Maths teacher) would be helpful. - 30important questions to ask when consulting about changing insulin regime• Ensure optimal compliance
• What are her hobbies? Exercise increases the risk of hypoglycaemia
• ensure that she is rotating her injection sites
• ensure she is abiding to driving regulations
• Could she be pregnant? - 31Driving and DVLA regulationspatients with DM who are on Insulin or hypoglycaemic treatment have a responsibility to inform the DVLA, and to comply with driving regulations
- 32MDT for DM- diabetic nurse specialist
- dietician
- opthalmologist
- podiatrist - 33risk factors for gestational diabetes1. BMI >30 kg/m2
2. Previous macrosomic baby weighing 4.5 kg or more
3. Previous GDM
4. Family history of diabetes (first degree relative)
5. Minority ethnic origin with high prevalence of diabetes (South Asian, black Caribbean, Middle Eastern).
NICE recommend that women with any of the above risk factors be offered OGTT at 24-28 weeks of gestation. - 34diagnosis of GDMusing 75 g OGTT is recommended:
• fasting venous plasma glucose ≥5.1mmol/L or
• two hours after OGTT ≥8.5 mmol/L - 35management strategies fo gestational diabetesPatients are managed with diet, self monitoring of blood glucose and, if required, metformin or Insulin.
- 36symptoms of thyrotoxicosisWeight Loss
Increased appetite
Tremor
Oligomenorrhoea
Polyuria
Weakness, fatigue
Diarrhoea
Insomnia, anxiety
Change in heat preference – cold not hot. - 37most significant indicator of thyroid functionTSH
Cannot be used in patients with pituitary disease, since they do not produce TSH - 38What to do if TFTs are not in agreement with clinical findings?assay interference should be suspected (heterophile antibodies, anti T4 or anti T3 antibodies
- 39sick euthyroidismIn very unwell patients, e.g. in Intensive care, a pattern of ‘sick euthyroidism’ is often seen with low TSH levels, low free T3 and sometimes low fT4 levels
- 40Amiodarone and TFTs1) inhibits T4→T3 conversion – which in the pituitary results in a mild raise in TSH
2) can induce hypothyroidism- usually in the first year of treatment
3) can induce hyperthyroidism – either by the Jod Basedow* effect in patients with a multi nodular goitre or by a destructive thyroiditis in an other wise healthy gland
In brief patients on amiodarone have elevated/high normal fT4, low normal fT3 and initially a high TSH – which returns to normal within a few months. - 41How to define hyperthyroidism and thyrotoxicosis?Thyrotoxicosis is the syndrome resulting from excessive free thyroxine (fT4) and or free tri-iodothyronine (fT3).
Hyperthyroidism refers to thyroid over activity resulting in thyrotoxicosis.
Thyrotoxicosis can thus occur without hyperthyroidism – e.g. when stored hormone is released from a damaged gland (e.g. sub acute thyroiditis) or when excess hormone replacement is prescribed. - 42causes of thyrotoxicosisPrimary – i.e. driven by the thyroid
1. Graves’ disease – due to thyroid stimulating immunoglobulin antibodies – TSH receptor antibodies that bind to and stimulate the TSH receptor.
2. Toxic Multinodular Goitre
3. Toxic Adenoma
4. Rarer Causes (metastatic thyroid cancer, ectopic thyroid tissue)
Secondary (1 and 3 are rare!)
1. TSH secreting pituitary adenoma – ‘TSHoma’ TSH remains detectable or high, despite high fT4 or fT3
2. Gestational Thyrotoxicosis – see below high levels of human chorionic gonadotrophin in 1st trimester
3. Thyroid Hormone Resistance Syndrome – pattern of elevated fT4 and fT3 due to peripheral resistance to action with detectable TSH. - 43What investigations can help delineate the substrate of thyrotoxicosis?Antibodies +/- nuclear medicine scan
- 44thyroid autoantibodies (pregnancy?)Markers of autoimmune thyroid disease
Anti TPO antibodies. Antithyroid microsomal antibodies have been identified as antithyroid peroxidise (Anti TPO) antibodies. Present in 45-80% of Graves’ disease and 80-95% of Hashimoto’s disease/atrophic thyroiditis.
Anti TSH Receptor antibodies (TRABs) are difficult to measure – but are the most reliable test for diagnosing Graves’ disease (cause!) They are important in 2 situations in pregnancy
1) To determine the cause of thyroid disease in pregnancy – βhCG causes specificity spillover at the TSH receptor due to homology with TSH and when βhCG levels are high causes a transient gestational thyrotoxicosis
2) To assess the risk of neonatal thyrotoxicosis. - 45nuclear imaging for thyrotoxicosisThyroid scintigraphy scanning with technetium-99m or Iodine -131 is useful when antibody testing is negative, a nodule is palpable, or thyrotoxicosis without hyperthyroidism is suspected.
Important patterns –
1) Diffuse uptake with suppression of background activity = Graves’
2) Irregular Uptake – Multi Nodular Goitre
3) Hot Nodule – Toxic Adenoma
4) Reduced uptake- thyroiditis eg viral. - 46Why is nuclear imaging useful in multnodular goitre or hot nodules?This is an important investigation in that patients with multinodular goitre or hot nodules are less likely than those with Grave’s to have a sustained remission with anti thyroid drugs alone.
- 47effectiveness of anti-thyroid drugsPharmacological treatment of Graves’ will induce a sustained remission in 40-50% - the remainder will require a further course of treatment or definitive therapy
- 48symptoms improvement in hyperthyroid whilst anti-thyroid medication becomes effectivebeta blockers
- 49Anti-thyroid drugsCarbimazole and Propylthiouracil (PTU) inhibit iodide organification by thyroid peroxidise reducing T3 and T4 production. They also reduce TSH receptor stimulating antibody levels.
Carbimazole usually used, PTU if pregnancy planned or pregnant.
Patients should always be warned about the symptoms of infections and rashes. - 50anti-thyroid drugs and symptoms warranting an urgent FBC checkFever, mouth ulcers or a sore throat may herald incipient agranulocytosis and hence patients must know to stop treatment and have an urgent FBC checked.
- 512 regimens of anti-thyroid drugs1) A reducing regimen where higher doses are started at initiation of treatment (e.g. 40 mg of Carbimazole) then as the patient becomes euthyroid the dose is reduced, maintaining a euthyroid state.
2) Block and Replace – Commence with blocking medication e.g. 40mg of Carbimazole – then when patient is euthyroid add in Thyroxine. Smoother biochemical control, ideal where there is concern of hypothyroidism with thyroid eye disease. Avoid in pregnancy. - 52Radioactive iodine - contraindications - SEs - for whatContraindicated in pregnancy, lactation, and in patients with active thyroid eye disease. May be socially unacceptable eg to mothers due to the restrictions on prolonged close contact with small children afterwards.
131I acts slowly – may induce hypothyroidism requiring life long thyroxine therapy. Can induce a transient thyroiditis.
Treatment of choice for toxic MNG – except large MNG or those with significant retrosternal extension causing obstructive symptoms, who may require surgery.
Also often used in patients who have remission after a course of medical therapy. - 53surgery for hyperthyroid - when - complicationsSubtotal/total thyroidectomy – Is indicated where 131I is contraindicated or unacceptable to the patient or where there is a large goitre as above. Hypothyroidism, hypocalcaemia, recurrent laryngeal nerve palsy are important considerations.
- 54features of thyroid eye diseaseExophthalmos – in 30-50%
Lid lag and lid retraction are the result of excess sympathetic activity and are not specific to Graves’ disease.
Graves eye signs
1) Grittiness and redness
2) Conjunctival oedema (=chemosis)
3) Periorbital oedema
4) Proptosis and exophthalmos
5) Ophthalmoplegia- this is due to an orbital lymphocytic infiltration of the orbit causing diplopia and can involve numerous ocular muscles.
Ophthalmopathy affects up to 60% clinically but 90% can have changes evident on CT or MRI. Also euthyroid or even hypothyroid Graves’ disease are recognised, both with ophthalmopathy. - 55What factors increase the risk of developing Graves opthalmopathy?Smoking Sarah should stop smoking!
Male Sex
Age
Radioactive iodine treatment - 56examination of thyroid eye diseaselid retraction (upper sclera visible)
exopthalmos (lower sclera visible)
proptosis: protusion of eyeball, seen from above (stand behind patient)
opthalmoplegia
chemosis: needs an examination with
fluorescein to look for corneal ulceration
lid lag: move finger downards fast to elicit lid lag, while keeping the head still - 57Which thyroid patients need urgent eye referral?Poor vision, blurred vision, recent or rapid change in vision or poor colour vision - ? optic neuropathy?
Severe conjunctival pain may indicate corneal ulceration. - 58tretament of Graves opthalmopathyGrittiness – artificial tears
Eyelid – tape eyelids at night to avoid corneal damage, surgery if risk of exposure keratopathy
Proptosis – steroids, radiotherapy may need orbital decompression
Optic neuropathy - steroids, radiotherapy may need orbital decompression
Ophthalmoplegia – prisms in the acute phase, orbital decompression, orbital muscle surgery. - 59differential diagnosis of fatigue, weight gain, constipation and tearfulnesshypothyroidism, anaemia, depression and even hypoadrenalism
- 60symptoms of hypothyroidismtiredness,
weight gain,
feeling cold with a preference for warmth,
constipation,
myalgia,
carpal tunnel syndrome
menorrhagia - 61signs of hypothyroidismexcess weight,
thick coarse facial features,
dry skin,
fine,
brittle hair
loss of the outer eyebrows.
There may be delayed relaxation of ankle and other deep tendon reflexes. - 62Possible causes of hypothyroidism• Autoimmune Hashimoto’s thyroiditis
• Destructive thyroiditis
• Secondary to hypothalamic or pituitary failure
• Idiopathic atrophic hypothyroidism
• Iodine deficiency
• Following treatment for thyrotoxicosis - 63TFTs for hypothyroidelevated TSH, with reduced fT4. (Measuring T3 is unhelpful because of increased conversion of T4 to T3.)
Pituitary driven hypothyroidism, e.g. due to a macroadenoma, panhypopituitarism or following surgery is associated with a low TSH.
positive antibodies to thyroid peroxidise are in keeping with Hashimoto’s thyroiditis. - 64treatment of hypothyroidismThyroid hormone replacement!
Levothyroxine usually starting at 50-100mcg (lower where there is a concern of ischaemic heart disease) and titrating in 25mcg increments aiming for a normal TSH.
There may be a time lag from TSH being in the normal range to clinical improvement. - 65What is myxoedema?Myxoedema is severe hypothyroidism. There is accumulation of hydrophilic MUCOPOLYSACCHARIDES in the ground substance of the dermis and other tissues leading to the thickened facial features and doughy induration of the skin.
In myxoedema:
- Dull, expressionless face, sparse hair, periorbital puffiness, macroglossia
- Pale, cool, skin - rough and doughy
- Pericardial effusion
- Megacolon/ intestinal obstruction
- cerebellar ataxia
- Prolonged relaxation phase of deep tendon reflexes
- Peripheral neuropathy - 66What is myxoedema coma?Uncommon, REDUCED CONSCIOUSNESS and HYPOTHERMIA common – not necessarily with coma.
Heart failure, hypotension, hyponatraemia and hypoventilation also occur. Treatment is supportive with intravenous fluids, slow rewarming, ventilation and intravenous T3 followed by oral or nasogastric T4 once improving. - 67subclinical thyroid conditionssubclinical hyperthyroid: low TSH and normal T4
subclinical TSH: high TSH and normal T4
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- Endocrinology Fichas sobre CBL endocrine, creado por Ellie Britt el 22/01/2018.
- Creado por
- Ellie Britt · ene 2018
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- 7 abr 2018
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