Endocrine Flashcards
What is Acromegaly?
A chronic, progressive, multi-systemic disease associated with significant morbidity and increased mortality
It is caused by excessive secretion of growth hormone, usually due to a pituitary somatotroph adenoma
Gigantism occurs with disease onset in childhood (before puberty)
What is the aetiology of Acromegaly?
Due to a pituitary somatotroph adenoma in about 95% to 99% of cases
Prolactin is als secreted in 25% to 30% of cases
What is the epidemiology of Acromegaly?
Rare- annual incidence of five in 1 000 000
Age at diagnosis: 40–50 years
What are the presenting symptoms of Acromegaly?
Very gradual progression of symptoms over many years (often only detectable on serial photographs)
Coarsening of facial features
Patients may complain of rings and shoes becoming tight
Increased sweating, headache, carpal tunnel syndrome
Symptoms of hypopituitarism:
-hypogonadism
-hypothyroidism
-hypoadrenalism)
Visual disturbances (caused by optic chiasm compression)
Hyperprolactinaemia (irregular periods, reduced libido, impotence)
What are the signs of Acromegaly on physical examination?
Hands:
-Enlarged spade-like hands with thick greasy skin
Signs of carpal tunnel syndrome
Pre-mature osteoarthritis (arthritis also affects other large joints, temporomandibular joint)
Face:
-Prominent eyebrow ridge (frontal bossing) and cheeks
-Broad nose bridge
-Prominent nasolabial folds
-Thick lips
-Increased gap between teeth
-Large tongue
-Prognathism: protrusion of the lower jaw
-Husky resonant voice (thickening vocal cords)
Visual field loss:
-Bitemporal superior quadrantanopia progressing to *bitemporal hemianopia (caused by pituitary tumour compressing the optic chiasm)
Neck: Multi-nodular goitre
Feet: Enlarged
What are the appropriate investigations for Acromegaly?
Serum IGF-1: Useful screening test
-GH stimulates liver IGF-1 (insulin-like growth factor) secretion (IGF-1 varies with age of patient and increases during pregnancy and puberty)
*Oral glucose tolerance test:
Failure of suppression of GH after 75 g oral glucose load (false- positive results are seen in anorexia nervosa, Wilsons disease, opiate addiction)
Pituitary function tests: (to test for hypopituitarism)
-9 a.m. cortisol
-Free T4 and TSH
-LH and FSH
-Testosterone (in men)
-Prolactin
MRI of the brain:
To image the pituitary tumour and effect on the optic chiasm
What is the management for Acromegaly?
*Surgical: Trans-sphenoidal hypophysectomy is the only curative treatment
Radiotherapy: Adjunctive treatment to surgery
Medical: If surgery is contra-indicated or refused:
-SC somatostatin analogues (octreotide, lanreotide)
-Side-effects: abdominal pain, steatorrhoea glucose intolerance, gallstones, irritation at the injection site
-Oral dopamine agonists (bromocriptine, cabergoline) for high prolactin
-Side-effects: nausea, vomiting, constipation, postural hypotension (increase dose gradually and take it during meals), psychosis (rare)
-GH antagonist (pegvisomant)
Monitor:
-GH and IGF1 levels can be used to monitor disease control
-Pituitary function tests, echocardiography, regular colonoscopy and blood glucose
What are the complications of Acromegaly?
CVS: Cardiomyopathy, hypertension Respiratory: Obstructive sleep apnoea Gl: Colonic polyps Reproductive: Hyperprolactinaemia (30%) therefore GnH suppression Metabolic: -Hypercalcaemia -Hyperphosphataemia -Renal stones -Diabetes mellitus -Hypertriglyceridaemia -Osteoarticular complications: articular cartilage hypertrophy, bone enlargement Psychological: -Depression -Psychosis (resulting from dopamine agonist therapy) Complications of surgery: -Nasoseptal perforation -Hypopituitarism -Adenoma recurrence -CSF leak, -Infection (meninges, sphenoid sinus)
What is the prognosis for Acromegaly?
Associated with serious complications and premature death
Prognosis has improved due to modern surgical and pharmacological treatment, with early diagnosis and treatment, although physical changes are irreversible
What is adrenal insufficiency?
Deficiency of adrenal cortical hormones (mineralocorticoids, glucocorticoids and androgens)
What is the aetiology / risk factors 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
4Is:
- Infections: Tuberculosis, meningococcal septicaemia (Waterhouse–Friderichsen syndrome), Cytomegalovirus (HIV patients)
- Infiltration: Metastasis (lung, breast, melanoma), lymphomas, amyloidosis
- Infarction: Secondary to thrombophilia
- Inherited: Adrenoleukodystrophy 1, ACTH receptor mutation
What is the epidemiology of adrenal insufficiency?
Most common cause is iatrogenic. Primary causes are rare
What are the presenting symptoms of adrenal insufficiency?
Chronic presentation:
Non-specific vague symptoms such as dizziness, anorexia, weight loss, diarrhoea, vomiting, abdominal pain, lethargy, weakness, depression
Acute presentation: (Addisonian crisis)
Acute adrenal insufficiency with major haemody-
namic collapse often precipitated by stress (e.g. infection or surgery)
What are the signs of adrenal insufficiency on physical examination?
Postural hypotension
Increased pigmentation: Generalised but 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
Addisonian crisis: Hypotensive shock, tachycardia, pale, cold, clammy, oliguria
What are the appropriate investigations for adrenal insufficiency? Interpret the results
Confirm the diagnosis:
9a. m. serum cortisol <100nmol/L is diagnostic of adrenal insufficiency.
- If 9 a.m. cortisol > 550 nmol/L: adrenal insufficiency is unlikely.
- Patients with 9 a.m. cortisol of between 100 and 550 nmol/L should have a short ACTH stimulation test (short SynACTHen test)
- Serum cortisol <550 nmol/L at 30 min indicates adrenal failure (primary)
Addisonian crisis:
Bloods- Haematology (FBC for neutrophilic, ESR for infection), Biochemistry (U&Es for raised urea and potassium, low sodium, CRP for infection), Microbiology (blood cultures)
Urine- MCS
What is the management for addisonian crisis?
- Rapid IV fluid rehydration (0.9% saline, 1 L over 30–60 min, 2–4 L in 12–24 h)
- 50ml of 50 % dextrose to correct hypoglycaemia.
- IV 200 mg hydrocortisone bolus followed by 100 mg 6 hourly (until BP is stable).
- Treat the precipitating cause (e.g. antibiotics for infection)
- Monitor temperature, pulse, respiratory rate, BP, sat O2 and urine output.
What is the management plan for adrenal insufficiency?
Chronic:
Replacement of glucocorticoids with hydrocortisone (three times/day) and mineralocorticoids with fludrocortisone
Hydrocortisone dosage needs to be increased during acute illness or stress
If associated with hypothyroidism, give hydrocortisone before thyroxine (to avoid precipitating an Addisonian crisis)
Advice: Steroid warning card, Medic-alert bracelet, emergency hydrocortisone ampoule, patient education
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 is Carcinoid Syndrome?
Constellation of symptoms caused by systemic release of serotonin (5-hydroxytryptamine) and other vasoactive peptides from a carcinoid tumour
What is a Carcinoid tumour?
A slow growing type of neuroendocrine tumour originating in the cells of the neuroendocrine system, but can metastasise
Can be classified into fore-, mid- or hindgut tumours
What is the aetiology of Carcinoid Syndrome?
Carcinoid tumours are slow-growing neuroendocrine tumours mostly derived from serotonin-producing enterochromaffin cells
They produce secretory products such as serotonin, histamine, tachykinins, kallikrein and prostaglandin
75–80% of patients with the carcinoid syndrome have small bowel carcinoids
Common sites for carcinoid tumours include appendix and rectum, where they are often benign and non-secretory
Hormones released into the portal circulation are metabolized in the liver and so symptoms typically do not appear until there are hepatic metastases (resulting in the secretion of tumour products into the hepatic veins)
Symptoms can also appear when hormones are released into the systemic circulation from bronchial or extensive retroperitoneal tumours
What is the epidemiology of Carcinoid Syndrome?
RARE, asymptomatic carcinoid tumours are more common and may be an incidental finding after rectal biopsy or appendectomy
10% of patients with multiple endocrine neoplasia (MEN) type 1 have carcinoid tumours
What are the presenting symptoms of Carcinoid Syndrome?
Diarrhoea Paroxysmal flushing Palpitations Abdominal cramps Wheeze Sweating
What are the signs of Carcinoid Syndrome on physical examination?
Facial flushing Telangiectasia Wheeze Right-sided heart murmurs: -Tricuspid stenosis, regurgitation or pulmonary stenosis Nodular hepatomegaly in cases of metastatic disease Carcinoid crisis: -Profound flushing -Bronchospasm -Tachycardia -Fluctuating blood pressure
What are the appropriate investigations for Carcinoid Syndrome?
24-h urine collection:
-5-HIAA levels (a metabolite of serotonin, false positive with high intake of certain fruit/drugs e.g. bananas and avocados, caffeine, paracetamol)
Bloods:
-Plasma chromogranin A and B, fasting gut hormones: elevated
-Metabolic profile: elevated creatinine if dehydrated from diarrhoea
-LFTs: changes depending on location of tumour/presence of metastases
CT or MRI scan: To localise the primary tumour and detect live metastases (routine every 4-6 months)
Endoscopy/bronchoscopy: localise tumour
Radioisotope scan:
-Radiolabelled somatostatin analogue (e.g. indium-111 octreotide) helps localize tumour
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?
Exogenous corticosteroid exposure is the most common cause
Endogenous:
ACTH-dependent (80%):
-Excess ACTH secreted from a pituitary adenoma: Cushing’s disease (80%).
-ACTH secreted from an ectopic source, e.g. small-cell lung carcinomas, pulmonary carcinoid tumours (20%)
ACTH-independent (20%):
- Excess cortisol secreted from a benign adrenal adenoma (60%)
- 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?
Cushing’s syndrome is relatively uncommon in the general population
Exogenous Cushing’s syndrome is the most common cause
Endogenous Cushing’s syndrome is more common in females (x4)
Peak incidence is 20–40 years, although it can occur at any age
What are the presenting symptoms of Cushing’s syndrome?
Increasing weight 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:
- Facial plethora: increased perfusion, redness, one of the earliest features of Cushing’s syndrome
- Proximal muscle weakness
- Bruises
Other signs:
- Facial fullness
- Interscapular fat pad
- Thin skin
- Central obesity
- Pink/purple striae on abdomen, breast, thighs
- Kyphosis (due to vertebral fracture)
- Poorly healing wounds
- Hirsutism, acne, frontal balding.
- Hypertension
- Ankle oedema (salt and water retention as a result of mineralocorticoid effect of excess cortisol)
- Pigmentation in ACTH-dependent cases
What are the appropriate investigations for Cushing’s syndrome?
Initial high-sensitivity tests:
- Urinary free cortisol (two or three 24 h urine collections) -Late-night salivary cortisol
- Overnight dexamethasone suppression test
- Low dose dexamethasone suppression test, involves giving 0.5mg dexamethasone orally every 6h for 48h
- In Cushings syndrome, serum cortisol measured 48 h after the first dose of dexamethasone fails to suppress below 50 nmol/L (morning cortisol)
Tests to determine the underlying cause:
-ACTH-independent (adrenal adenoma/carcinoma): low Plasma ACTH, CT or MRI of adrenals
-ACTH-dependent (pituitary adenoma): High Plasma ACTH, Pituitary MRI. High-dose dexamethasone suppression test (DOES NOT SUPPRESS)
?Inferior petrosal sinus sampling: Central: peripheral ratio of venous ACTH > 2:1 (or >3:1 after CRH administration) in Cushings disease
ACTH-dependent (ectopic):
- If lung cancer is suspected: CXR, sputum cytology, bronchoscopy, CT scan
- Radiolabelled octreotide scans to detect carcinoid tumours as they express somatostatin receptors.
Others:
- Urine pregnancy test
- Serum glucose: elevated, Cushing’s syndrome commonly leads to diabetes and glucose intolerance
- Non-specific changes include hypokalaemia (particularly in ectopic Cushings)
What is the management of Cushing’s syndrome?
In iatrogenic cases, discontinue administration, lower steroid dose or use an alternative steroid-sparing agent if possible
Medical:
- Pre-operative or if unfit for surgery
- Inhibition of cortisol synthesis with metyrapone (competitive inhibitor of 11β-hydroxylation in the adrenal cortex inhibiting cortisol production) or ketoconazole (potent inhibitor of cortisol and aldosterone synthesis)
- Treat osteoporosis and provide physiotherapy for muscle weakness
Surgical:
-Pituitary adenomas(Cushing’s disease): Trans-sphenoidal adenoma resection (hydrocortisone replaced until
pituitary function recovers)
-Adrenal adenoma/carcinoma: Surgical removal of tumour (plus adjuvant therapy with mitotane for adrenal carcinoma)
Ectopic ACTH production: Treatment is directed at the tumour.
*In refractory cases of Cushings disease, bilateral adrenalectomy may be performed
What are the complications for 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
Complications of radiotherapy:
Hypopituitarism, radionecrosis, small increased risk of second intracranial tumours and stroke
Bilateral adrenalectomy may rarely be complicated by development of Nelsons syndrome
(locally aggressive pituitary tumour causing skin pigmentation due to excessive ACTH secretion)
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?
A disorder of inadequate secretion of or insensitivity to vasopressin (ADH) leading to hypotonic polyuria (production of large quantities of dilute urine)
What is the aetiology of Diabetes Insipidus?
DI may be central in origin, resulting from an absolute or relative deficiency of vasopressin (ADH); or it may be nephrogenic in origin, resulting from a renal insensitivity or resistance of the collecting duct to vasopressin
Both mechanisms result in the failure of activation of Water channels (aquaporins) and the luminal membrane of the collecting duct remains impermeable to water
This results in large volume hypotonic urine and polydipsia
What are the causes of Centra/Cranial Diabetes Insipidus?
Idiopathic *Tumours (e.g. pituitary tumours) Infilitrative (e.g. sarcoidosis) Infection (e.g. meningitis) Vascular (e.g. aneurysms, Sheehan syndrome) Trauma (e.g. head injury, neurosurgery)
What are the causes of Nephrogenic Diabetes Insipidus?
Idiopathic *Drugs (e.g. lithium) Post-obstructive uropathy Pyelonephritis Pregnancy Osmotic diuresis (e.g. diabetes mellitus)
What is the epidemiology of Diabetes Insipidus?
DI is uncommon
No differences in prevalence between sexes or among ethnic groups but median age of onset is 24 years
What are the presenting symptoms of Diabetes Insipidus?
Polyuria
Nocturia
Polydipsia (excessive thirst)
Enuresis (involuntary urination) and sleep disturbances in children
What are the signs of Diabetes Insipidus on physical examination?
Cranial diabetes insipidus has 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 appropriate investigations for Diabetes Insipidus?
Blood:
-U&Es: HIGH Plasma osmolality LOW Urine osmolality
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 Diabetes Insipidus?
Normal:
-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)
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 management of Diabetes Insipidus?
Treat the identified cause if possible
Cranial diabetes insipidus:
-Desmopressin (DDAVP), a vasopressin analogue, can be given 10 mg/day, intranasally (parenteral DDAVP is 5 to 20 times more potent)
Nephrogenic diabetes insipidus:
-Sodium and/or protein restriction may help polyuria
-Thiazide diuretics
What are the complications of Diabetes Insipidus?
Hypernatraemic dehydration:
-Mild to moderate hypernatraemia may present with irritability, restlessness, lethargy, muscle twitching, spasticity, or hyper-reflexia
-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
While DI is often a lifelong condition cranial DI may be transient following head trauma
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 common chronic syndrome of impaired carbohydrate, protein, and fat metabolism owing to insufficient secretion of insulin and/or target-tissue insulin resistance
What is Diabetes Mellitus- Type 1?
A metabolic disorder characterised by hyperglycaemia due to absolute insulin deficiency
The condition develops due to destruction of pancreatic beta cells, mostly by immune-mediated mechanisms
What is the aetiology of Diabetes Mellitus- Type 1?
Caused by destruction of the pancreatic insulin-producing b-cells, resulting in absolute insulin deficiency The b -cell destruction is caused by an autoimmune process in 90% of patients
Likely to occur in genetically susceptible patients and is probably triggered by environmental agents
What is the epidemiology of Diabetes Mellitus- Type 1?
Type 1 diabetes accounts for about 5% to 10% of all patients with diabetes
It is the most commonly diagnosed diabetes of youth (under 20 years of age) and is one of the most common chronic diseases in childhood
HLA DR3 and 4 carry a significant link
What are the presenting symptoms and signs of Diabetes Mellitus- Type 1 on physical examination?
*Often of juvenile onset (<30 years)
Polyuria/nocturia
Polydipsia (thirst)
Non-specific symptoms: tiredness, weight loss
Symptoms of complications e.g. Diabetic ketoacidosis:
-Nausea and vomiting
-Abdominal pain
-Drowsiness, confusion, coma
-Kussmaul breathing (deep and rapid)
-Ketotic breath
-Signs of dehydration (e.g. dry mucous membranes, reduced tissue turgor)
Signs of complications e.g. diabetic retinopathy, neuropathy
What are the appropriate investigations for Diabetes Mellitus- Type 1?
*Blood glucose:
-Fasting blood glucose >7mmol/L
-Random blood glucose >11 mmol/L
*Two positive results are needed before diagnosis
Others:
HbA1C: Estimates overall blood glucose levels in past 2–3 months
-FBC, U&Es: Monitor for nephropathy and hyperkalaemia caused by ACE inhibitors
-Lipid profile
-Urine albumin creatinine ratio (to detect microalbuminuria- nephropathy)
-Urine: Glycosuria, elevated ketones, MSU (microscopy, culture)
-CXR: To exclude any infection.
-ECG: To look for acute ischaemic changes
Patients presenting with suspected DKA:
-Bloods: FBC (raised WCC even without infection), U&Es (raised urea and creatinine from dehydration), LFT, CRP, glucose, amylase, blood cultures, ABG (metabolic acidosis with high anion gap), blood/urinary ketones
What is the management for Diabetes Mellitus- Type 1?
In the short term, insulin is life-saving because it prevents diabetic ketoacidosis
The long-term goal of insulin treatment is the prevention of chronic complications by maintaining blood glucose levels as close to normal as possible
Monitoring: control of symptoms (e.g. thirst, tiredness), regular finger prick tests by the patient, monitoring HbA1c levels (target <7%) every 3–6 months
Good glycaemic control in type 1 diabetes requires attention to diet, exercise, and insulin therapy-all three components should be co-ordinated for ideal control with Diabetes nurse specialists and dietitians
*Self-monitoring of blood glucose (SMBG) is a core component of good glycaemic control
Insulin:
SC insulin: Short- acting insulin (e.g. Lispro, aspart, glulisine) three times daily before each meal and one long-acting insulin (isophane, glargine, detemir) injection once daily
Injection sites should be rotated
Insulin pumps may give slightly better glycaemic control
What is the management of hypoglycaemia in Diabetes Mellitus -Type 1?
If reduced consciousness:
-50 ml of 50% glucose IV or 1 mg glucagon IM
If conscious and cooperative:
-50 g oral glucose (e.g. in the form of Lucozade! , milk,
sugar or 3 dextrose tablets)
-Followed with a starchy snack
Should not drive for 45 min
*Screening and management cardiovascular risk factors
What are the possible complications of Diabetes Mellitus -Type 1?
Diabetic ketoacidosis, may be precipitated by infection or errors in management
Microvascular: Retinopathy, nephropathy, neuropathy
Macrovascular: Peripheral vascular disease, ischaemic heart disease, stroke/TIA. Susceptible to infections (especially on feet)
Complications of insulin treatment: Weight gain, fat hypertrophy at insulin injection sites
What are the features of hypoglycaemia in Diabetes Mellitus -Type 1?
- Caused my missing a meal or overdosage of insulin Meuroglycopenic and adrenergic signs:
- Personality change
- Fits, confusion, coma
- Pallor
- Sweating
- Tremor, tachycardia, palpitations
- Dizziness
- Hunger
- Focal neurological symptoms
- Hypoglycaemic symptoms may be masked by autonomic neuropathy, b-blockers and brain adapting to recurrent episodes
What is the prognosis of Diabetes Mellitus -Type 1?
Depends on early diagnosis, good glycaemic control and compliance with screening and treatment
Vascular disease and renal failure are major causes of increased morbidity and mortality
What is Diabetes Mellitus- Type 2?
A progressive disorder defined by increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output
What is the aetiology of Diabetes Mellitus- Type 2?
Often presents on a background genetic predisposition (HLA DR3/4) and is characterised by insulin resistance and relative insulin deficiency
Insulin resistance is aggravated by ageing, physical inactivity, and overweight (BMI 25-29.9 kg/m²) or obesity (BMI >30 kg/m²)
What is the epidemiology of Diabetes Mellitus- Type 2?
Prevalence in the UK: 5–10%
People of Asian, African and Hispanic descent are at greater risk
The incidence has increased in parallel with increased prevalence of obesity ad being overweight worldwide
What are the risk factors for Diabetes Mellitus- Type 2?
Obesity/overweight Older age Gestational diabetes (50% of women will go on to develop DM within 10 years of delivery) *Significant genetic link (HLA DR3/4) Physical inactivity Polycystic ovary syndrome Hypertension Dyslipidaemia Cardiovascular disease
What are the presenting symptoms of Diabetes Mellitus- Type 2?
May be incidental finding due to being asymptomatic
Polyuria
Polydypsia
Tiredness
Patients may present with hyperosmolar hyperglycaemic state (also known as hyperosmolar non-ketotic state) Infections (infected foot ulcers, candidiasis, balanitis or pruritus vulvae)
Assess for other cardiovascular risk factors: e.g. hypertension, hyperlipidaemia and smoking
What are the signs of Diabetes Mellitus- Type 2 on physical examination?
BMI: weight(kg)/ height(m)2), waist circumference
Hypertension
Look for signs of complications (retinopathy, nephropathy, neuropathy)
Diabetic foot:
-Both ischaemic and neuropathic signs
-Dry skin, reduced subcutaneous tissue, corns and calluses, ulceration, gangrene
-Signs of peripheral neuropathy: foot pulses are diminished in ischaemic foot
-Skin changes (rare)
What are the appropriate investigations for Diabetes Mellitus- Type 2?
Diabetes mellitus is diagnosed if one or more of the following are present:
-Symptoms of diabetes and a random plasma glucose 11.1 mmol/L.
-Fasting plasma glucose 7.0 mmol/L (after an overnight fast of at least 8 h).
-Two-hour plasma glucose 11.1 mmol/L after a 75 g oral glucose tolerance test
Monitor:
-HbA1C: 48 mmol/mol (6.5%) or greater
-U&Es, lipid profile, estimated glomerular filtration rate (GFR) using the MDRD calculator
-Spot urine albumin: Creatinine ratio (to detect microalbuminuria)
What is MODY?
Mature onset diabetes of the young: a rare cause of type 2 diabetes due to mutations transmitted in an autosomal dominant manner
What is the management of Diabetes Mellitus- Type 2?
FIRST: lifestyle modifications (diet and exercise) and Metformin
If HbA1C ≥ 7% after 3 months:
2. Lifestyle + metformin + sulphonylurea*
If HbA1C ≥ 7% after 3 months:
3. Lifestyle + metformin + basal insulin
If HbA1C≥7% after 3 months and fasting blood glucose >7mmol/L:
4. Add premeal rapid-acting insulin
What are the medical therapies for Diabetes Mellitus- Type 2 and how do they work?
Metformin: -Biguanide, Insulin sensitiser -Inhibits hepatic gluconeogenesis, hence GI side effects Sulphonylureas: -e.g. gliclazide -block ATP-sensitive K+ channels in b cells, stimulating insulin release Acarbose: -Alpha glucosidase inhibitor -Prolongs absorption of oligosaccharides -Allows insulin secretion to cope Thiazolidinediones: -e.g. Pioglitazone -Insulin sensitizer, mainly peripheral Glucagon-like peptide-1 (GLP-1): -Secreted in response to nutrients in gut -Stimulates insulin, suppresses glucagon -Increases satiety -Restores B cell glucose sensitivity Gliptins: -Given alongside GLP-1 to increase half life
What is Hyperosmolar hyperglycaemic state?
This is due to insulin deficiency, as 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), no acidosis
What are the microvascular complications of Diabetes Mellitus?
Neuropathy:
-Distal symmetrical sensory neuropathy
-Painful neuropathy
-Carpal tunnel syndrome
-Diabetic amyotrophy (asymmetrical wasting of proximal muscle)
-Mononeuritis (e.g. III nerve palsy with preservation of pupillary response, VI nerve)
-Autonomic neuropathy (e.g. postural hypotension), gastroparesis (abdominal pain, nausea, vomiting), impotence, urinary retention
Nephropathy:
-Microalbuminuria, proteinuria and, eventually, renal failure
-Prone to UTIs and renal papillary necrosis
Retinopathy:
-Background: Dot and blot haemorrhages, hard exudates
-Pre-proliferative: Cotton wool spots, venous beading
-Proliferative: New vessels on the disc and elsewhere
-Maculopathy: Macular oedema, exudates within 1 disc diameter of the centre of fovea, haemorrhage
-Also prone to glaucoma, cataracts, transient visual loss
What are the macrovascular complications of Diabetes Mellitus?
Ischaemic heart disease
Stroke
Peripheral vascular disease
What is the prognosis of Diabetes Mellitus- Type 2?
Diabetes increases the likelihood of major cardiovascular events and death, but the increased risk is variable across patients depending on: -age at diabetes onset -duration of diabetes -glucose control -blood pressure control -lipid control -tobacco control -renal function* -microvascular complication status Mortality can be attenuated by cardiovascular risk factor control
What is Diabetic Ketoacidosis?
An acute metabolic complication of diabetes that is potentially fatal and requires prompt medical attention for successful treatment
It is characterised by absolute insulin deficiency and is the most common acute hyperglycaemic complication of type 1 diabetes mellitus
What is the aetiology of Diabetic Ketoacidosis?
Reduced Insulin and increased counter-regulatory hormones result in increased hepatic gluconeogenesis and reduced peripheral glucose utilization. Renal reabsorptive capacity of glucose is exceeded causing glycosuria, osmotic diuresis and dehydration. Increased lipolysis leads to ketogenesis and metabolic acidosis
The two most common precipitating events are:
- Infection
- Discontinuation of, or inadequate, insulin therapy
Underlying medical conditions, such as myocardial infarction or pancreatitis, that provoke the release of counter-regulatory hormones are also likely to result in DKA in patients with diabetes
What is the epidemiology of Diabetic Ketoacidosis?
The incidence of hospital admissions for DKA among adults with Type 1 AND type 2 diabetes mellitus has increased
What are the presenting symptoms of Diabetic Ketoacidosis?
PMH of DM Nausea and vomiting Abdominal pain Dehydrated Hyperventilation Acetone smell on breath Confusion
What are the signs of Diabetic Ketoacidosis on physical examination?
Signs of dehydration: -Dry mucous membranes -Decreased skin turgor or skin wrinkling -Slow capillary refill -Tachycardia with a weak pulse -Hypotension Polyuria Polydipsia Kussmaul breathing (deep and rapid) Ketotic breath Coma
What are the appropriate investigations for Diabetic Ketoacidosis?
Venous blood gas:
-Metabolic acidosis (pH can determine the severity of DKA)
-pH ≥7.0 indicates mild or moderate DKA
-pH <7.0 indicates severe DKA (critical care)
-Hyperkalaemia is common
-Plasma osmolality is high (>320 mmol/kg) in DKA and is an indication of dehydration
Blood ketones: ketonaemia (ketones ≥3.0 mmol/L)
Blood glucose: hyperglycaemia (blood glucose >11.1 mmol/L)
U&Es: Hyponatraemia and Hyperkalaemia are common in DKA, but hypokalaemia is an indicator of severe
FBC: Leukocytosis is common in DKA and correlates with blood ketone levels
Urinalysis: ketones, leukocytes
ECG: look for cardiac precipitates for DKA such as MI (and check cardiac enzymes)
Pregnancy test
Amylase and lipase: for pancreatitis
Creatinine kinase: elevated with rhabdomyolysis (breakdown of damaged skeletal muscle)
CXR: if low oxygen sats
Blood cultures: if infection suspected
What is the management of Diabetic Ketoacidosis?
URGENT: Start intravenous fluids as soon as DKA is confirmed (fluid bolus of 500 mL of normal saline), repeat if SBP remains low (<90mmHg)
Start a fixed-rate intravenous insulin infusion
Ensure continuous cardiac monitoring
Identify and treat any precipitating acute illness e.g. MI, sepsis, pancreatitis
What are the complications of Diabetic Ketoacidosis?
Cerebral oedema/brain injury most common cause of mortality in DKA
Arterial or venous thromboembolic events: Standard prophylactic low-dose heparin
SE of high insulin dose therapy: hypokalaemia, hypoglycaemia
Pulmonary oedema/ARDS: rare but significant complications of treatment for DKA (fluid overload)
What is the prognosis for Diabetic Ketoacidosis?
Improved understanding of the pathophysiology of DKA, together with close monitoring and correction of electrolytes, has resulted in a significant reduction in the overall mortality rate from this life-threatening condition
Death is rarely caused by the metabolic complications of hyperglycaemia or ketoacidosis but rather relates to the underlying illness
*The prognosis is substantially worsened at the extremes of age and in the presence of coma and hypotension
What is Dyslipidaemia?
Dyslipidaemia is 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 low-density lipoprotein (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, chronic renal insufficiency, abdominal obesity, diabetes mellitus and hypothyroidism
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:
-total cholesterol (TC) >5.18 mmol/L (>200 mg/dL)
-LDL-cholesterol >2.59 mmol/L (>100 mg/dL)
-triglycerides >1.7 mmol/L (>150 mg/dL)
Fasting (12h) triglycerides: ≥2.3 mmol/L (200 mg/dL)
Thyroid stimulating hormone: elevated in primary hypothyroidism
Lipoprotein (a): values >50 mg/dL or >125 nmol/L are considered high
What is the management of Dyslipidaemia?
Combination of lifestyle changes to diet and exercise, medications, and dietary supplements
Lifestyle changes: dietary reduction in total and saturated fat, weight loss in overweight patients, aerobic exercise
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?
Atherosclerosis: Ischaemic heart disease Peripheral vascular disease Acute coronary syndrome Stroke Erectile dysfunction (endothelial dysfunction)
What is the prognosis of Dyslipidaemia?
The rate of adverse outcomes has been significantly reduced with the use of statins
Useful in the rid reduction of coronary heart disease
What is Hypertriglyceridaemia?
Having a fasting plasma triglyceride level of ≥2.3 mmol/L (≥200 mg/dL)
What is an exclusive sign of Hypertriglyceridaemia on physical examination?
Eruptive xanthomas: Small yellowish papules, frequently surrounded by an erythematous base, that appear predominantly on the buttocks, elbows, and other pressure-sensitive areas
What is Graves’ Disease?
An autoimmune thyroid condition associated with hyperthyroidism caused by TSH (thyroid-stimulating hormone) receptor antibodies
What is the aetiology of Graves’ Disease?
Graves’ disease is an autoimmune condition
The aetiology of thyroid hormone overproduction is stimulation of the thyroid by TSH receptor antibodies
What is the epidemiology of Graves’ Disease?
Graves’ disease is the most common form of hyperthyroidism in most areas of the world (other cause is toxic multinodular goitre)
What are the presenting symptoms of Graves’ Disease?
Features of hyperthyroidism: -Heat intolerance -Palpitations -Sweating -Weight loss -Tremor Neck lump
What are the signs of Graves’ Disease on physical examination?
*Diffuse goitre (smooth)
Tremor
Exophthalmos - bulging of the eye anteriorly
The presence of upper eyelid retraction with thyroid dysfunction, exophthalmos/optic neuropathy, and/or extraocular muscle involvement is diagnostic of Graves’ orbitopathy (25% of patients)
Menstrual disturbances e.g. oligomenorrhoea
What are the appropriate investigations for Graves’ Disease?
Thyroid function tests:
-Suppressed/low TSH
-Serum free/total T3 or T4: elevated
Calculation of T3/T4 ratio: high compared to in thyroiditis
Radioactive iodine uptake test: elevated
Thyroid isotope scan: diffuse uptake (rather than patchy in multi nodular goitre)
TSH receptor antibodies: POSITIVE
Colour-flow Doppler Ultrasound: may help to distinguish Graves’ from painless thyroiditis; highly vascular; diffuse; enlarged thyroid
Others:
-CT/MRI of orbit: may show muscle thickening
-Skin biopsy: may confirm thyroid dermopathy
What is Hyperparathyroidism?
Primary: Increased secretion of parathyroid hormone (PTH) unrelated to the plasma calcium concentration
Secondary: Increased secretion of PTH secondary to hypocalcaemia
Tertiary: Autonomous PTH secretion following chronic secondary hyperparathyroidism
What is the aetiology of Hyperparathyroidism?
Primary:
-Parathyroid gland adenoma(s) (80%)or hyperplasia (18% hyperplasia/multiple adenomas)
-Rarely, parathyroid carcinoma (2%)
-May be associated with multiple endocrine neoplasia (MEN)
Secondary:
-Chronic renal failure
-Vitamin D deficiency
What is the epidemiology of Hyperparathyroidism?
Primary: relatively common disorder, annual incidence is five in 100,000
Twice as common in females
Peak incidence 40–60 years
*Vitamin D deficiency is the most common cause of elevated serum parathyroid hormone levels
