Endocrine Flashcards
What is acromegaly?
Excessive secretion of growth hormone
What is the main cause of acromegaly?
Excess growth hormone secondary to a pituitary adenoma (95%)
What can also cause acromegaly?
Ectopic growth hormone releasing hormone (GHRH) or growth hormone producing tumours e.g. pancreatic
What is excess GH in childhood also known as?
Gigantism
What are the features of acromegaly?
- Coarse facial appearance
- Spade-like hands
- Interdental spaces
- Increase in shoe size
- Large tongue
- Prognathism (protrusion of the jaw)
- Excessive sweating and oily skin (sweat gland hypertrophy)
What other features of acromegaly may be seen on examination?
Pituitary tumour features:
1. Hypopituitarism
2. Headaches
3. Bilateral hemianopia
1/3 rd of people will have raised prolactin and so galactorrhoea
What are the investigations for acromegaly?
- Serum IGF-1 levels
- Oral glucose tolerance test (used as confirmation)
- MRI may demonstrate a pituitary tumour
What are the Endocrine Society guidelines for diagnosis of acromegaly?
- Measure IGF-1 levels in patient with typical clinical manifestations of acromegaly
- In patients with elevated or equivocal serum IGF-1, confirm diagnosis by finding a lack of suppression of GH to < 1μg/L following hyperglycaemia during an OGTT
What would the findings of an OGTT be for acromegaly?
- Normal = GH is suppressed to < 2 mu/L with hyperglycaemia
- Acromegaly = no suppression
- May also demonstrate impaired glucose tolerance
Which test can be used to monitor disease progression in acromegaly?
Serum IGF-1 levels
What is the first line management options for acromegaly?
Trans-sphenoidal surgery
What medical management is available if surgery is not successful/ inoperable in acromegaly?
- Somatostatin analogue, e.g. octreotide. Directly inhibits release of GH
- Pegvisomant: GH receptor antagonist, once daily s/c, very effective, does not reduce tumour volume so may still need surgery to reduce mass effect
- Dopamine agonists, e.g. bromocriptine, only effective in a minority of patients
What are the complications of acromegaly?
Hypertension
Diabetes (>10%)
Cardiomyopathy
Colorectal cancer
Obstructive sleep apnoea
What are some of the side effects of somatostatin analogues used for acromegaly?
Abdominal pain
Steatorrhoea
Gallstones
What is the prognosis for acromegaly?
Associated with serious complications and premature death if not treated
Physical changes are irreversible
What is adrenal insufficiency?
Deficiency of adrenal cortical hormones (mineralocorticoids, glucocorticoids and androgens)
What is the aetiology of adrenal insufficiency?
Primary (Addisons disease): Autoimmune (>70%)
Secondary: Pituitary or hypothalamic disease.
Surgical: After bilateral adrenalectomy.
Medical: (iatrogenic) sudden cessation of long-term steroid therapy
What are the risk factors for adrenal insufficiency?
4Is:
1. Infections: Tuberculosis, meningococcal septicaemia (Waterhouse–Friderichsen syndrome), Cytomegalovirus (HIV patients)
2. Infiltration: Metastasis (lung, breast, melanoma), lymphomas, amyloidosis
3. Infarction: Secondary to thrombophilia
4. Inherited: Adrenoleukodystrophy 1, ACTH receptor mutation
What are the 4Is for risk factors for adrenal insufficiency?
- Infections
- Infiltration
- Infarction
- Inherited
What is the most common cause of adrenal insufficiency?
Most common cause is iatrogenic- sudden cessation in long term steroid therapy
Primary causes are rare
What are the presenting symptoms of acute adrenal insufficiency?
(Addisonian crisis)
Acute adrenal insufficiency with major haemodynamic collapse often precipitated by stress (e.g. infection or surgery)
What are the presenting symptoms of chronic adrenal insufficiency?
Non-specific vague symptoms such as dizziness, anorexia, weight loss, diarrhoea, vomiting, abdominal pain, lethargy, weakness, depression
What are the clinical features of adrenal insufficiency?
- Postural hypotension
- Increased pigmentation: more noticeable on buccal mucosa, scars, skin creases, nails, pressure points (resulting from melanocytes being stimulated by increased ACTH levels)
- Loss of body hair in women (androgen deficiency)
- Associated autoimmune conditions: e.g. vitiligo
What are the clinical features of an Addisonian crisis?
Hypotensive shock
Tachycardia
Pale
Cold and clammy
Oliguria
What are the appropriate investigations for adrenal insufficiency?
Definite investigation is ACTH stimulation (synACTHen) test
9am serum cortisol may also be helpful
What results would be seen in Addison’s disease on a synACTHen test/ 9am serum cortisol test?
> 500 nmol/l makes Addison’s very unlikely
< 100 nmol/l is definitely abnormal
100-500 nmol/l should prompt a ACTH stimulation test to be performed
ACTH stimulation test should show an increase in plasma cortisol levels 30 minutes after giving Synacthen 250ug IM
What are the appropriate investigations for an Addisonian crisis?
1a. Bloods- Haematology (FBC for neutrophilic, CRP and ESR for infection)
1b. Biochemistry (U&Es for hyperkalaemia, hyponatraemia, hypoglycaemia and metabolic acidosis)
1c. Microbiology (blood cultures)
2. Urine- MCS
What are the causes of an Addisonian crisis?
- Sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s, Hypopituitarism)
- Adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
- Steroid withdrawal
What is the management for Addisonian crisis?
- Hydrocortisone 100 mg im or iv
- 1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
- Continue hydrocortisone 6 hourly until the patient is stable (no fludrocortisone is required because high cortisol exerts weak mineralocorticoid action)
- Oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
- Treat the underlying cause e.g. Abx for sepsis
What is the management plan for adrenal insufficiency?
Replacement therapy of glucocorticoid and mineralocorticoid
Combination of:
1.Hydrocortisone (usually given in 2 or 3 divided doses, 20-30 mg per day, with the majority given in the first half of the day)
2.Fludrocortisone
Patient education: importance of not missing doses, MedicAlert bracelets, hydrocortisone injection for crisis
Management of intercurrent illness: glucocorticoid dose should be doubled with fludrocortisone staying the same
What precaution must be taken in a patient with adrenal insufficiency and hypothyroidism?
Give hydrocortisone before thyroxine to avoid precipitating an Addisonian crisis
What are the possible complications of adrenal insufficiency?
Hyperkalaemia
Death during an Addisonian crisis
What is the prognosis for patients with adrenal insufficiency?
Adrenal function rarely recovers, but normal life expectancy can be expected if treated
What are carcinoid tumours?
A slow growing type of neuroendocrine tumour originating in the cells of the neuroendocrine system, but can metastasise
What is carcinoid syndrome?
- Usually occurs when metastases are present in the liver and release serotonin into the systemic circulation
- May also occur with lung carcinoid as mediators are not ‘cleared’ by the liver
How can carcinoid tumours be classified?
Fore, mid or hindgut tumours
What are the features of carcinoid tumours?
- Flushing (often earliest symptom)
- Diarrhoea
- Bronchospasm
- Hypotension
- Right heart valvular stenosis
What also might be secreted in carcinoid tumours alongside serotonin?
ACTH and GHRH
What are the investigations for carcinoid tumours?
- Urinary 5-HiAA
- Plasma chromogranin A y
- Radiolabelled octreotide scans to detect carcinoid tumours as they express somatostatin receptors
What is the management of carcinoid tumours?
- Somatostatin analogues e.g. octreotide
- Diarrhoea: cyproheptadine may help
What is Cushing’s syndrome?
The clinical manifestation of pathological hypercortisolism (chronic inappropriate elevation of free circulating cortisol) from any cause
What is the aetiology of Cushing’s syndrome?
Can be divided into exogenous and endogenous: exogenous causes of Cushing’s syndrome (e.g. glucocorticoid therapy) are far more common than endogenous ones
What are the endogenous causes of Cushing’s syndrome?
- ACTH-dependent (80%):
a. Excess ACTH secreted from a pituitary adenoma: Cushing’s disease (80%).
b. ACTH secreted from an ectopic source, e.g. small-cell lung carcinomas, pulmonary carcinoid tumours (20%) - ACTH-independent (20%):
a. Excess cortisol secreted from a benign adrenal adenoma (60%)
b. RARE: 1% of Cushing’s syndrome cases are caused by adrenal carcinoma BUT of this 1%, adrenal overproduction of cortisol is seen in 30% to 40% of adrenal carcinomas
What is the epidemiology of Cushing’s syndrome?
- Relatively uncommon
- Exogenous Cushing’s is more common than endogenous
- Endogenous Cushing’s is more common in women (x4)
- Peak incidence is 20–40 years, although it can occur at any age
What are the presenting symptoms of Cushing’s syndrome?
- Weight gain and fatigue
- Muscle weakness, myalgia
- Thin skin
- Easy bruising
- Poor wound healing
- Fractures (resulting from osteoporosis)
- Hirsutism
- Acne
- Frontal balding
- Oligo- or amenorrhoea
- Depression or psychosis
What are the signs of Cushing’s syndrome on physical examination?
Specific features:
1. Facial plethora: increased perfusion, redness, one of the earliest features of Cushing’s syndrome
2. Proximal muscle weakness
3. Bruises
Other signs:
1. Facial fullness
2. Interscapular fat pad
3. Thin skin
4.Central obesity
5. Pink/purple striae on abdomen, breast, thighs
6. Kyphosis (due to vertebral fracture)
7. Poorly healing wounds
8. Hirsutism, acne, frontal balding.
9. Hypertension
10. Ankle oedema (salt and water retention as a result of mineralocorticoid effect of excess cortisol)
11. Pigmentation in ACTH-dependent cases
What are the two most common investigations for Cushing’s syndrome?
- Overnight dexamethasone suppression test:
a. most sensitive test and is now used first-line
b. Patients with Cushing’s syndrome do not have their morning cortisol spike suppressed - 24 hr urinary free cortisol
What are the possible findings of a dexamethasone suppression test for Cushing’s syndrome?
If ACTH is suppressed then a non-ACTH dependent cause is likely such as an adrenal adenoma
What is the role of a ‘high-dose’ dexamethasone suppression test in Cushing’s syndrome?
Used to localise the pathology resulting in Cushing’s syndrome: Cushing’s disease and ectopic ACTH secretion
What are the possible findings of a high dose dexamethasone test for cushing’s syndrome?
Cushing’s syndrome due to other causes (e.g. adrenal adenomas):
a. Cortisol: Not suppressed
b. ACTH Suppressed
Cushing’s disease (i.e. pituitary adenoma → ACTH secretion):
a. Cortisol: Suppressed
b. Cortisol: Suppressed
Ectopic ACTH syndrome:
a. Cortisol: Not suppressed
b. ACTH: Not suppressed
What is the management of iatrogenic Cushing’s syndrome?
Discontinue administration, lower steroid dose or use an alternative steroid-sparing agent if possible
What is the medical management of Cushing’s syndrome?
Indication: Pre-operative or if unfit for surgery
1. Inhibition of cortisol synthesis with:
a. metyrapone (competitive inhibitor of 11β-hydroxylation in the adrenal cortex inhibiting cortisol production) or
b. ketoconazole (potent inhibitor of cortisol and aldosterone synthesis)
2. Treat osteoporosis and provide physiotherapy for muscle weakness
What is the surgical management of Cushing’s syndrome?
- Pituitary adenomas, also known as Cushing’s disease:
a. Trans-sphenoidal adenoma resection
b. Hydrocortisone replaced until
pituitary function recovers - Adrenal adenoma/carcinoma: Surgical removal of tumour (plus adjuvant therapy with mitotane for adrenal carcinoma)
What is the management of ectopic ACTH Cushing’s syndrome?
Investigate lung tumour: chest x-ray, bronchoscopy, CT
Treatment is directed at the tumour
What are some general findings in Cushing’s syndrome?
A hypokalaemic metabolic alkalosis may be seen, along with impaired glucose tolerance
What are the complications of Cushing’s syndrome?
- Diabetes
- Osteoporosis
- Hypertension
- Pre-disposition to infections
- Adrenal insufficiency secondary to adrenal suppression
- Complications of surgery: CSF leakage, meningitis, sphenoid sinusitis, hypopituitarism
What is the prognosis of Cushing’s syndrome?
In the untreated, 5-year survival rate is 50%, mortality is mainly from cardiovascular disease
Depression usually persists for many years following successful treatment
What is diabetes insipidus?
Characterised by either a decreased secretion of antidiuretic hormone (ADH) from the pituitary (cranial DI) or an insensitivity to antidiuretic hormone (nephrogenic DI)
What is the consequence of diabetes insipidus?
Hypotonic polyuria (production of large quantities of dilute urine)
What are the causes of cranial DI (decreased secretion of ADH)?
- Idiopathic
- Post head injury
- Pituitary surgery
- Craniopharyngiomas
- Infiltrative: e.g. Sarcoidosis
- Haemochromatosis
- DIDMOAD: association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram’s syndrome)
What are the causes of nephrogenic DI (insensitivity of ADH)?
- Genetic:
a. More common form affects the vasopression (ADH) receptor
b. Less common form results from a mutation in the gene that encodes the aquaporin 2 channel - Electrolytes:
a. Hypercalcaemia
b. Hypokalaemia - Lithium: desensitizes the kidney’s ability to respond to ADH in the collecting ducts
- Tubulo-interstitial disease: e.g. obstruction, sickle-cell, pyelonephritis
What are the two main features of diabetes insipidus?
- Polyuria
- Polydipsia
What is the pathophysiology of both forms of DI?
- Both mechanisms result in the failure of activation of aquaporins channels and the luminal membrane of the collecting duct remains impermeable to water
- This results in large volume hypotonic urine and polydipsia
What is an additional feature of DI in children?
Nocturia ± enuresis (involuntary urination) and sleep disturbances
What are the possible signs of DI on examination?
- Few signs if patients drink adequate fluids
- Urine output is often >3 L/24 h
- If fluid intake < fluid output: signs of dehydration may be present e.g. tachycardia, reduced tissue turgor, postural hypotension, dry mucous membranes
- Signs of the cause: e.g. visual field defect bitemporal hemianopia from pituitary tumour
What are the investigations for diabetes insipidus?
- Bloods and urine analysis: high plasma osmolality, low urine osmolality (if urine osmolality of >700 mOsm/kg excludes DI)
- Water deprivation test:
- Water is restricted for 8 h
- Plasma and urine osmolality are measured every hour over the 8 h
- Weigh the patient (hourly) to monitor the level of dehydration (stop the test if the fall in body weight is >3%)
- Desmopressin (2 mg IM) is given after 8 h and urine osmolality is measured
What are the findings of the water deprivation test for normal patients (without DI)?
- Water restriction causes a rise in plasma osmolality and increase in ADH secretion
- This leads to increased water reabsorption in the collecting ducts
- Urine is concentrated: (Urine osmolality > 600 mosmol/kg)
What are the findings of the water deprivation test for Diabetes Insipidus?
- Lack of ADH activity means that urine is unable to be concentrated by the collecting ducts (Urine osmolality < 400 mosmol/kg)
- Cranial: Urine osmolality rises by >50%, following administration of desmopressin (due to deficiency in vasopressin)
- Nephrogenic: Urine osmolality rises by <45%, following administration of desmopressin (resistance to vasopressin)
What is the main difference in the water deprivation test findings for the two types of DI?
With desmopressin administration, there will be an increase in urine osmolality in patients with cranial DI (not in nephrogenic because are insensitive to it)
What is the management of DI?
Cranial DI: desmopressin
Nephrogenic DI: thiazides and a low salt/protein diet
What are the complications of DI?
Hypernatraemic dehydration:
1. Mild to moderate hypernatraemia may present with irritability, restlessness, lethargy, muscle twitching, spasticity, or hyper-reflexia
3. Severe hypernatraemia may present with delirium, seizures, or coma
Excess desmopressin therapy may cause hyponatraemia
What is the prognosis of Diabetes Insipidus?
Variable depending on cause:
1. While DI is often a lifelong condition cranial DI may be transient following head trauma
2. Cure of cranial or nephrogenic diabetes insipidus may be possible on removal of cause, e.g. tumour resection, drug discontinuation
What is Diabetes Mellitus?
A chronic condition characterised by abnormally raised levels of blood glucose
What is Type 1 DM?
- Autoimmune disorder where the insulin-producing beta cells of the islets of Langerhans in the pancreas are destroyed by the immune system
- This leads to an absolute deficiency of insulin resulting in raised glucose levels
What is the epidemiology of Type 1 DM?
Tends to develop in childhood/early adult life and typically present unwell, possibly in diabetic ketoacidosis
What is Type 2 DM?
- Caused by a relative deficiency of insulin due to an excess of adipose tissue
- In simple terms there isn’t enough insulin to ‘go around’ all the excess fatty tissue, leading to blood glucose creeping up
What is the epidemiology of Type 2 DM?
The most common cause of diabetes in the developed world
What are the other types of diabetes mellitus?
- Prediabetes: used for patients who don’t yet meet the criteria for a formal diagnosis of T2DM to be made but are likely to develop the condition over the next few years (require monitoring and advice)
- Gestational: raised glucose levels during pregnancy (important to detect)
- MODY: Maturity onset diabetes of the young, group of inherited genetic disorders affecting the production of insulin, results in younger patients developing symptoms similar to those with T2DM
- Latent autoimmune diabetes of adults (LADA): a small group of patients who develop autoimmune diabetes later in life
What are typical presenting symptoms of Type 1 DM?
- Weight loss
- Polyuria
- Polydipsia
- DKA:
a. Abdominal pain
b. Vomiting
c. Reduced consciousness
What are the presenting symptoms of Type 2 DM?
- Often picked up incidentally on routine blood tests
- Polydipsia
- Polyuria
What are the investigations for Type 1 DM?
- Urine: dip for glucose (and ketones)
- Fasting glucose and random glucose
- C-peptide levels are typically low in patients with T1DM
- Antibody testing: e.g. Antibodies to glutamic acid decarboxylase (anti-GAD), Islet cell antibodies, Insulin antibodies
What is the diagnostic criteria for Type 1 DM if the patient is symptomatic?
- Fasting glucose greater than or equal to 7.0 mmol/l
- Random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
What is the diagnostic criteria for Type 1 DM if the patient is asymptomatic?
Must be demonstrated on two separate occassions:
1. Fasting glucose greater than or equal to 7.0 mmol/l
2. Random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
What additional tests should be performed in adults with suspected Type 1 DM but atypical features?
Atypical features e.g. age 50 years or above, BMI of 25 kg/m² or above, slow evolution of hyperglycaemia or long prodrome: measurement of C‑peptide and/or diabetes‑specific autoantibody titres
What are the investigations for Type 2 DM?
Diagnosis can be made from either a plasma glucose or a HbA1c sample
What is the diagnostic criteria for Type 2 DM if the patient is symptomatic?
- Fasting glucose greater than or equal to 7.0 mmol/l
- Random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
What is the diagnostic criteria for Type 2 DM if the patient is asymptomatic?
Demonstrated on two separate occasions:
1. Fasting glucose greater than or equal to 7.0 mmol/l
2. Random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
What is the HbA1c criteria for Type 2 DM?
Greater than or equal to 48 mmol/mol (6.5%) is diagnostic of diabetes mellitus
What is important to consider when using HbA1c in the diagnosis of Type 2 DM?
- A HbAlc value of less than 48 mmol/mol (6.5%) does not exclude diabetes
- In patients without symptoms, the test must be repeated to confirm the diagnosis
- It should be remembered that misleading HbA1c results can be caused by increased red cell turnover e.g.:
a. haemoglobinopathies
b. haemolytic anaemia
c. untreated iron deficiency anaemia
d. CKD
e. HIV
f. Children
g. People taking medication that may cause hyperglycaemia (e.g. corticosteroids)
What is the HbA1c criteria for prediabetes?
42-47 mmol/mol
(Or fasting glucose 6.1 -6.9 mmol/l)
What is the difference between impaired fasting glucose and impaired glucose tolerance?
- Impaired fasting glucose = a fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies
- Impaired glucose tolerance = fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
What are the major differences in Type 1 and Type 2 DM?
Type 1:
1. Typically presents < 20 years
2. Presents more acutely (hours-days)
3. Recent weight loss is typical
4. Features of DKA
Type 2:
1. Typically presents > 40 years (can present in younger, obese patients)
2. Presents more slowly (weeks to months)
3. Obesity is a strong RF
4. Milder symptoms e.g. polyuria, polydipsia
5. Ketonuria is rare
What is the management of Type 1 DM?
- Patients always require insulin to control the blood sugar levels
- This is because there is an absolute deficiency of insulin with no pancreatic tissue left to stimulate with drugs
- Different types of insulin are available according to their duration of action: short, immediate and long acting
How is insulin given in patients with Type 1 DM?
Subcutaneous: direct replacement for endogenous insulin
What are the main side effects of insulin?
- Hypoglycaemia
- Weight gain
- Lipodystrophy
What is the management of Type 2 DM?
- Majority of patients are controlled using oral medication (after lifestyle advice)
- First-line drug for the vast majority of patients is Metformin
- Second-line drugs include sulfonylureas, gliptins and pioglitazone
- If oral medication is not controlling the blood glucose to a sufficient degree then insulin is used
What is Metformin in the management of Type 2 DM?
- Oral medication
- Increases insulin sensitivity and decreases hepatic gluconeogenesis
- First line medication
- Not to be used in patients with an eGFR < 30ml/min
What are the side effects of Metformin?
- Gastrointestinal upset: should be slowly titrated up to minimise this
- Lactic acidosis
*If standard-release metformin is not tolerated then modified-release metformin should be trialled
What are the second line medications for Type 2 DM?
1st: Metformin + SGLT-2 inhibitor (first line for patients with CVD/HF)
Then: Metformin + gliptin/ sulphonylurea
(only add a second drug if HbA1c > 58mmol/mol)
What is DPP-4 inhibitors?
- Oral medication, end in -gliptin
- Increases incretin levels which inhibit glucagon secretion
- Generally well tolerated, increased risk of pancreatitis
- Good for patients with CKD
What are sulfonylureas?
- Oral medication
- Stimulate pancreatic beta cells to secrete insulin
- E.g. gliclazide and glimepiride
- SE: Hypoglycaemia, weight gain, hyponatraemia
What are SGLT-2 inhibitors (-gliflozins)?
- Oral medication
- Inhibits reabsorption of glucose in the kidney
- Typically results in weight loss
- SE: UTI
What is the third line medical management of Type 2 DM?
Triple therapy: Metformin + sulfonylurea + gliptin/ SGLT-2 inhibitors
What can be added before triple therapy in some patients in the management of Type 2 DM?
Insulin
What is the fourth line management if triple therapy is not effective/ tolerated and BMI > 35 in Type 2 DM?
Metformin + sulfonylurea + GLP-1
What are GLP-1 agonists?
- SC medication in Type 2 DM
- Incretin mimetic which inhibits glucagon secretion
- Typically results in weight loss
- SEs: Nausea and vomiting, pancreatitis
When is SGLT-2 monotherapy used in the management of Type 2 DM?
If Metformin in contraindicated and there is a risk of CVD/ HF
How often should HbA1c be checked in the management of Type 2 DM?
- Individual targets should be agreed with patients to encourage motivation
- HbA1c should be checked every 3-6 months until stable, then 6 monthly
What are the HbA1c targets for the different management options of Type 2 DM?
- Lifestyle alone: 48 mmol/mol (6.5%)
- Lifestyle and metformin: 48 mmol/mol (6.5%)
- Lifestyle and any drug that could lead to hypoglycaemia e.g. sulfonylurea: 53 mmol/mol (7.0%)
What is the HbA1c target for patients already on treatment (on one drug)?
53 mmol/mol (7.0%)
What lifestyle advice should be given to all patients with Type 2 DM?
- Ecourage high fibre, low glycaemic index sources of carbohydrates
- Control the intake of foods containing saturated fats and trans fatty acids
- Discourage the use of foods marketed specifically at people with diabetes
- Initial target weight loss in an overweight person is 5-10%
What advice should be given to patients with Type 2 DM regarding sick days?
If they become unwell:
1. Increase frequency of blood glucose monitoring to four hourly or more frequently
2. Encourage fluid intake aiming for at least 3 litres in 24hrs
3. If struggling to eat they may need sugary drinks to maintain carbohydrate intake
4. It is useful to educate patients so that they have a box of ‘sick day supplies’ that they can access if they become unwell
5. Access to a mobile phone has been shown to reduce progression of ketosis to diabetic ketoacidosis
6. If a patient is taking oral hypoglycaemic medication, they should be advised to continue taking their medication even if they are not eating much
Which medication should be stopped for Type 2 DM patients if they become ill?
Insulin, due to risk of DKA
What medications should be stopped for Type 2 DM patients if they become dehydrated?
Metformin due to potential impact on renal function
What are the features of hypoglycaemia in patients with DM?
Depends on the blood glucose level
What are the features of hypogylcaemia when blood glucose concentrations are <3.3 mmol/L?
Autonomic symptoms due to the release of glucagon and adrenaline:
1. Sweating
2. Shaking
3. Hunger
4. Anxiety
5. Nausea
What are the features of hypoglycaemia when blood glucose concentrations are below <2.8 mmol/L?
Neuroglycopenic symptoms due to inadequate glucose supply to the brain:
1. Weakness
2. Vision changes
3. Confusion
4. Dizziness
What are the more severe but rarer symptoms of hypoglycaemia?
Convulsions and coma
What is the management of hypoglycaemia in the community?
- Initially, oral glucose 10-20g should be given in liquid, gel or tablet form
- Alternatively, a propriety quick-acting carbohydrate may be given: GlucoGel or Dextrogel.
- A ‘HypoKit’ may be prescribed which contains a syringe and vial of glucagon for IM or SC injection at home
What is the management of hypoglycaemia in a hospital setting?
- If the patient is alert, a quick-acting carbohydrate may be given e.g. GlucoGel
- If the patient is unconscious or unable to swallow, SC or IM glucagon may be given
- Alternatively, intravenous 20% glucose solution may be given through a large vein
What is the DVLA guidance for patient with DM?
- There has not been any severe hypoglycaemic event in the previous 12 months
- The driver has full hypoglycaemic awareness
- The driver must show adequate control of the condition by regular blood glucose monitoring (memory function monitors), at least twice daily and at times relevant to driving
- The driver must demonstrate an understanding of the risks of hypoglycaemia
- There are no other debarring complications of diabetes
What is the management of hypertension and DM?
ACE inhibitors are first line with a blood pressure target of < 140/90 mmHg for type 2 diabetics
What is Hyperosmolar hyperglycaemic state?
- Due to insulin deficiency, as is diabetic ketoacidosis, but patients are usually old and may be presenting for the first time
- History is longer (e.g. 1 week)
- There is marked dehydration, high Na + , high glucose (>35 mmol/ L), high osmolality (>340 mosmol/kg), BUT no acidosis and no ketones
How are the complications for DM divided?
- Microvascular:
a. Neuropathy
b. Nephropathy
c. Retinopathy - Macrovascular:
a. Ischaemic heart disease
b. Stroke
c. Peripheral vascular disease
What is diabetic neuropathy?
- Diabetes typically leads to sensory loss and not motor loss
- Sensory loss typically results in a ‘glove and stocking’ distribution, with the lower legs affected first due to the length of the sensory neurons supplying this area
What is the management of diabetic neuropathy?
- First-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin
- If the first-line drug treatment does not work try one of the other 3 drugs
- Tramadol may be used as ‘rescue therapy’ for exacerbations of neuropathic pain
What are the different types of gastrointestinal autonomic neuropathy?
- Gastroparesis:
a. Symptoms include erratic blood glucose control, bloating and vomiting
b. Management: metoclopramide, domperidone or erythromycin (prokinetic agents) - Chronic diarrhoea: often at night
- GORD: decreased lower esophageal sphincter (LES) pressure
What is diabetic foot disease?
An important complication of diabetes mellitus which should be screen for on a regular basis
What are the two main factors contributing to diabetic foot?
- Neuropathy: resulting in loss of protective sensation (e.g. not noticing a stone in the shoe), Charcot’s arthropathy, dry skin
- Peripheral arterial disease: diabetes is a risk factor for both macro and microvascular ischaemia
What are the common presentations of diabetic foot?
- Neuropathy: loss of sensation
- Ischaemia: absent foot pulses, reduced ankle-brachial pressure index (ABPI), intermittent claudication
- Complications: calluses, ulceration, Charcot’s arthropathy, cellulitis, osteomyelitis, gangrene
What is the screening programme for diabetic foot disease?
All diabetic patients on at least an annual basis:
1. Screening for ischaemia: done by palpating for both the dorsalis pedis pulse and posterial tibial artery pulse
2. Screening for neuropathy: a 10 g monofilament is used on various parts of the sole of the foot
How are patients with diabetic foot disease risk stratified?
- Low risk: no risk factors except a callus alone
- Moderate risk: deformity or neuropathy or non-critical limb ischaemia
- High risk: (should be followed up regularly)
a. previous ulceration or
b. previous amputation or
c. on renal replacement therapy or
d. neuropathy and non-critical limb ischaemia together or
e. neuropathy in combination with callus and/or deformity or
f. non-critical limb ischaemia in combination with callus and/or deformity
What is diabetic nephropathy?
Common complication of diabetes mellitus, all patient should be screened annually:
1. Using urinary albumin:creatinine ratio (ACR)
2. Should be an early morning specimen
3. ACR > 2.5 = microalbuminuria
What is the management of diabetic nephropathy?
- Dietary protein restriction
- Tight glycaemic control
- BP control: aim for < 130/80 mmHg
- ACE inhibitor or angiotensin-II receptor antagonist (not both) should be started if urinary ACR of 3 mg/mmol or more
- Control dyslipidaemia with statins
What is diabetic ketoacidosis (DKA)?
A serious complication or first presentation of type 1 diabetes mellitus (rarely type 2)
What is the pathophysiology of DKA?
- Uncontrolled lipolysis which results in the excess production of free fatty acids
- These are ultimately converted to ketone bodies
What is type 1 diabetes mellitus?
- Autoimmune disorder
- Insulin producing beta-cells in the in the Islet of Langerhans in the pancreas are destroyed
- Results in an absolute deficiency of insulin resulting in raised glucose levels
What are the features of DKA?
- Abdominal pain
- Of type 1: polyuria, polydipsia, dehydration
- Kussmaul breathing: deep hyperventilation
- Acetone-smelling breathing
- Low GCS
What are the precipitating factors for DKA?
- Infection
- Missed insulin doses
- Myocardial infarction
What are the investigations for DKA?
- A to E approach
- Key investigations include VBG (pH, glucose) bloods for ketones, U&Es
- Urine dip
What is the diagnostic criteria for DKA?
- Glucose > 11 mmol/L or known DM
- pH < 7.3
- Bicarbonate < 15 mmol/L
- Presence of ketones:
a. Ketones > 3mmol/L
b. Urine ketones ++ on dipstick
What are the management principles of DKA?
MEDICAL EMERGENCY: A to E approach
1. Fluid resuscitation
2. Insulin
3. Correction of electrolyte disturbance
4. Long-term management e.g. insulin
What is the fluid replacement management in DKA?
- Most patients with DKA will be deplete of 5-8 L
- Isotonic saline is used initially (0.9% sodium chloride)
- Bolus of 500ml over 10-15 minutes
- Then replacement fluids: 100 ml/kg/day for the first 10kg, 50 ml/kg/day for the next 10kg, 20 ml/kg/day for weight over 20kg
- Plus maintenance fluids
What is the greatest risk in fluid resuscitation in children in the management of DKA?
Cerebral oedema:
1. Children and young adults are particularly vulnerable
2. Slower infusion rates may be indicated
3. Presents with headache, irritability, visual disturbance, focal neurology
4. If suspicion: CT head and senior review
What is the insulin management of DKA?
- Start an IV infusion at 0.1unit/kg/hour
- Once the blood glucose has been bought down to < 14mmol/L, continue the IV insulin and add 10% dextrose
- Infusion of 10% dextrose should be started at 125 mls/hr in addition to the 0.9% sodium chloride regime
How are electrolyte disturbances corrected in the management of DKA?
- Serum potassium levels fall after the administration of insulin
- Therefore may need to add potassium to the fluids
- Of the rate of potassium infusion is > 20 mmol/hour then cardiac monitoring may be required
What is DKA resolution?
- pH > 7.3
- Blood ketones < 0.6 mmol/L
- Bicarbonate > 15 mmol/L
If the patient is eating and drinking at this point = switch to S/C insulin
What must happen before a patient is discharged for an admission of DKA?
The patient must be reviewed by a diabetes specialist nurse
How quickly should ketonaemia and acidosis resolve in the management of DKA?
- Should resolve within 24 hours
- If not, requires senior review from endocrinologist
What are the complications of a DKA?
Can be from DKA or the management of it:
1. Gastric stasis
2. VTE
3. Arrhythmias secondary to hyperkalaemia
4. Incorrect fluid therapy: cerebral oedema, hypokalaemia, hypoglycaemia
5. ARDS
6. AKI
What is the prognosis of DKA?
Although a serious condition, mortality has decreased significantly due to improved understanding of pathophysiology and close monitoring of electrolytes
What is Dyslipidaemia?
Classified as serum Total cholesterol, LDL-C, triglycerides, apolipoprotein B, or lipoprotein(a) concentrations above the 90th percentile for the general population
What is the aetiology of Dyslipidaemia?
- Primary causes: due to single or multiple gene mutations, resulting in a disturbance of LDL and triglyceride production or clearance (most commonly seen in children and young adults)
- Secondary causes: caused by lifestyle factors or disorders that interfere with blood lipid levels over time such as obesity, CKD
What is the epidemiology of Dyslipidaemia?
- Common, particularly in developing countries
- Strong correlation between body mass index and coronary heart disease
- Primary causes are common in children and young adults whereas secondary is seen more in adults
What are the presenting symptoms of Dyslipidaemia?
- Excess body weight
- PMH Diabetes Mellitus Type 2 or cardiovascular disease
- Consumption of saturated fats
- FH of early onset of coronary heart disease or Dyslipidaemia
What are the signs of Dyslipidaemia on physical examination?
- Xanthelasmas: Yellow plaques that occur most commonly near the inner canthus of the eyelid
- Tendinous xanthomas: Slowly enlarging subcutaneous nodules (on tendons or ligaments)
What are the appropriate investigations for Dyslipidaemia?
Lipid profile:
1. Total cholesterol (TC) >5.18 mmol/L (>200 mg/dL)
2. LDL-cholesterol >2.59 mmol/L (>100 mg/dL)
3. triglycerides >1.7 mmol/L (>150 mg/dL)
4. Fasting (12h) triglycerides: ≥2.3 mmol/L (200 mg/dL)
Can also offer TFTs
What is the management of dyslipidaemia divided into?
Primary prevention: 20mg atorvastatin
1. 10-year cardiovascular risk > 10%
2. Type 1 DM
3. CKD, eGFR < 60ml/min
Secondary prevention: 80mg atorvastatin
1. Known ischaemic heart disease
2. Cerebrovascular disease
3. Peripheral arterial disease
What are the management principles of dyslipidaemia?
Combination of lifestyle changes to diet and exercise, medications, and dietary supplements
1. Lifestyle changes: dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise
2. Drug therapy: Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a key enzyme in cholesterol synthesis, which leads to up-regulation of LDL receptors and increased LDL clearance
What are the complications of dyslipidaemia?
Due to atherosclerosis:
1. Ischaemic heart disease
2. Peripheral vascular disease
3. Acute coronary syndrome
4. Stroke
5. Erectile dysfunction (endothelial dysfunction)
What is the prognosis of dyslipidaemia?
The rate of adverse outcomes has been significantly reduced with the use of statins
What is Graves’ Disease?
- An autoimmune thyroid condition associated with hyperthyroidism caused by TSH (thyroid-stimulating hormone) receptor antibodies
- The most common cause of thyrotoxicosis
What is the epidemiology of Grave’s disease?
Typically seen in women aged 30-50 years
What is the aetiology of Graves’ Disease?
Autoantibodies:
1. TSH receptor stimulating antibodies (90%)
2. Anti-thyroid peroxidase antibodies (75%)
These lead to stimulation of the thyroid and overproduction of thyroxine
What are the features specific to Grave’s disease?
- Eye signs (30% of patients)
a. exophthalmos
b. ophthalmoplegia - Pretibial myxoedema
- Thyroid acropachy, a triad of:
a. digital clubbing
b. soft tissue swelling of the hands and feet
c. periosteal new bone formation
What are the signs of Grave’s disease on examination?
- Diffuse, smooth enlarged goitre
- Exophthalmos - bulging of the eye anteriorly
- Signs of thyrotoxicosis