1
Q
What is acromegaly?
A
Constellation of signs and symptoms caused by hypersecretion of GH in adults (Excess GH before puberty results in gigantism)
2
Q
What is the aetiology of acromegaly?
A
- Most cases are a result of GH-secreting pituitary adenoma
- Rarely: Excess GHRH causing somatotroph hyperplasia from hypothalamic ganglioneuroma, bronchial carcinoid or pancreatic tumours
3
Q
What is the epidemiology of acromegaly?
A
- Rare
- Age at diagnosis: 40-50
4
Q
What are the presenting symptoms of acromegaly?
A
- Very gradual progression of symptoms over many years
- 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 chiasmm compression
- Hyperprolactinaemia (irregular periods, reduced libido, impotence)
5
Q
What are the signs of acromegaly on examination?
A
- Hands: Enlarged spade-like hands with thick greasy skin. Signs of carpal tunnel syndrome. Premature oesteoarthritis (which 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, progathism, 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
6
Q
What are the investigations for acromegaly?
A
- Serum IGF-1: GH stimulates liver IGF-1 secretion
- Oral glucose tolerance test: Failure of suppression of GH after 75h oral glucose load (false positive results seen in anorexia nervosa, Wilson’s disease, opiate addiction
- Pituitary function tests: 9am cortisol, free T4 and TSH, LH, FSH, testosterone (in men) and prolactin (to test for hypopituitarism
- MRI of the brain: to image the pituitary tumour and effect on the optic chiasm
7
Q
How is acromegaly managed?
A
- Surgical: Trans-spenoidal hypophysectomy is the only curative treatment
- Radiotherapy: Adjunctive treatment to surgery
- Medical: If surgery is contra-indicated or reduced
- SC somatostatin analogues (octreotide, lanreotide) Side effects: abdo pain, steatorrhoea glucose intolerance, gallstones, irritation at injection site
- Oral dopamine agonists (bromocriptine, cabergoline) SE: nausea, vomiting, constipation, postural hypotension (raised dose gradually and take it during meals) psychosis
- GH antagonist (pegvisomant)
- Monitor: GH and IGF1 levels can be used to monitor disease control. Pituitary function tests, echocardiography, regular colonoscopy and blood glucose
8
Q
What are the possible complications of acromegaly?
A
- CVS: cardiomyopathy, hypertension
- Respiratory: Obstructive sleep apnoea
- GI: colonic polyps
- Reproductive: Hyperprolactinaemia
- Metabolic: Hypercalcaemia, Hyperphosphataemia, renal stones, diabetes mellitus, Hypertriglyceridaemia
- Psychological: Depression, psychosis (resulting from dopamine agonist therapy)
- Complications of surgery: Nasoseptal perforation, hypopituitarism, adenoma recurrence, CSF leak, infection (meninges, sphenoid sinus)
9
Q
What is the prognosis for acromegaly?
A
Good with early diagnosis and treatment, although physical changes are irreversible
10
Q
What is adrenal insufficiency?
A
Deficiency of the adrenal cortical hormones (e.g. mineralocorticoids, glucocorticoids and androgens)
11
Q
What is the aetiology of adrenal insufficiency?
A
- Primary (Addison’s disease): Autoimmune
- Infections: Tuberculosis, meningococcal septicaemia (Waterhouse-Friderischen syndrome), CMV (HIV patients), histoplasmosis
- Infiltration: Metastasis (e.g. lung, breast, melanoma), lymphoma, amyloidosis
- Infarction: Secondary to thrombophilia
- Inherited: Adrenoleukodystrophy, ACTH receptor mutation
- Surgical: After bilateral adrenalectomy
- Secondary: Pituitary or hypothalamic disease
- Iatrogenic: Sudden cessation of long-term steroid therapy
12
Q
What is the epidemiology of adrenal insufficiency?
A
Most common cause is iatrogenic
- Primary causes are rare
13
Q
What are the presenting symptoms of adrenal insufficiency?
A
- Chronic presentation: Non-specific symptoms such as dizziness, anorexia, weight loss, diarrhoea, vomiting, abdominal pain, lethargy, weakness, depression
- Acute presentation (Addisonian crisis): Acute adrenal insufficiency with major haemodynamic collapse often precipitated by stress (e.g. infection or surgery)
14
Q
What are the signs of adrenal insufficiency on examination?
A
- Postural hypotension
- Increased pigmentation: Generalised but more noticeable on buccal mucosa, scars, skin creases, nail, pressure points (resulting from melanocytes being stimulated by raised ACTH level)
- Loss of body hair in women (androgen deficiency)
- Associated autoimmune conditions: e.g. vitiligo
- Addisonian crisis: Hypotensive shock, tachycardia, pale, cold, clammy, oliguria
15
Q
What are the investigations for adrenal insufficiency?
A
- Confirm the diagnosis: 9am serum cortisol less than 100nmol/L is diagnostic of adrenal insufficiency.
- Identify the level of defect ACTH: Raised in primary disease, decreased in secondary. Long Synacthen test
- Identify the cause: Autoantibodies (against 21-hydroxylase). Abdominal CT or MRI. Other tests e.g. adrenal biopsy for microscopy, culture, PCR, depending on the suspected causes
Check TFTs - Investigations in ‘Addisonian crisis’: FBC
16
Q
How is adrenal insufficiency managed?
A
- Addisonian crisis: Rapid IV fluid rehydration. 50ml of 50% dextrose to correct hypoglycaemia. IV 200mg hydrocortisone bolus followed by 100mg 6 hourly (until BP stable). Treat the precipitating cause (e.g. antibiotics for infection). Monitor temperature, pulse, respiratory rate, BP, sat 02 and urine output
- 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 Addisonian crisis)
- Advice: Steroid warning card, Medic-alert bracelet, emergency hydrocortisone ampoule, patient education
17
Q
What are the possible complications of adrenal insufficiency?
A
Hyperkaelaemia
Death during Addisonian crisis
18
Q
What is the prognosis of adrenal insufficiency?
A
- Adrenal function rarely recovers, but normal life expectancy can be expected if treated
- Type I (autosomal recessive disorder caused by mutation in the AIRE gene which encodes a nuclear transcription factor): Addison’s disease, chronic mucocutaneous candidiasis, hypoparathyroidism
- Type II: Addison’s disease, diabetes mellitus Type I, hypothyroidism, hypogonadism
19
Q
What is carcinoid syndrome?
A
Constellation of symptoms caused by systemic release of humoral factors (biogenic amines, polypeptides, prostaglandins) from carcinoid tumours
20
Q
What is the aetiology of carcinoid syndrome?
A
- 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
- May be classified into fore-,mid-, hind-gut tumours, 75-80% tumours include appendix and rectum, where they are often benign and non-secretory
- Also found in other parts of large intestine, stomach, thymus, bronchus and other organs
- Hormones released into the portal circulation are metabolised in the liver
- Thus symptoms typically do not appear until there are hepatic metastases (resulting in the secretion of tumour products into the hepatic veins) or release into the systemic circulation from bronchial or extensive retroperitoneal tumours
21
Q
What is the epidemiology of carcinoid syndrome?
A
- 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
22
Q
What are the presenting symptoms of carcinoid syndrome?
A
- Paroxysmal flushing
- Diarrhoea
- Crampy abdominal pain
- Wheeze
- Sweating
- Palpitations
23
Q
What are the signs of carcinoid syndrome on examination?
A
- 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 and fluctuating blood pressure
24
Q
What are the investigations for carcinoid syndrome?
A
- 24h 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
- Blood: Plasma chromogranin A & B, fasting gut hormones
- CT or MRI scan: To localises the tumour
- Radioisotope scan: Radiolabelled somatostatin analogue (e.g. indum-111 octreotide) helps localise tumour
- Investigations for MEN-1
25
What is Cushing's syndrome?
Syndrome associated with chronic inappropriate elevation of free circulating cortisol
26
What is the aetiology of Cushing's syndrome?
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%)
- Excess cortisol secreted from an adrenal carcinoma (40%)
Rare: ACTH-independent micro- or macronodular adrenal hyperplasia
27
What is the epidemiology of Cushing's syndrome?
Endogenous Cushing's syndrome is more common in females
| - Peak incidence is 20-40 years
28
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
29
What are the signs of Cushing's syndrome on examination?
- Facial fullness, facial plethora, interscapular fat pad
- Proximal muscle weakness, thin skin, bruises
- 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 a result of mineralocorticoid effect of excess cortisol)
- Pigmentation in ACTH dependent cases
30
What are the investigations for Cushing's syndrome?
Must only be performed in patients with a high pre-test probability
- Blood: Non-specific changes include hypokalaemia (particularly in ectopic Cushing's) raised glucose
- Initial high sensitivity tests: Urinary free cortisol (2 or 3 24h urine collections) Late night salivary cortisol. Overnight dexamethasone suppression test.
- Tests to determine the underlying cause: ACTH independent: Reduced Plasma ACTH. CT or MRI of adrenal. ACTH dependent (adenoma): Raised Plasma ACTH, pituitary MRI
ACTH dependent (ectopic): If lung cancer suspected, CXR, sputum cytology, broncoscopy CT scan. Radiolabelled octreotide scans to detect carcinoid tumours as they express somatostatin receptors
31
How is Cushing's syndrome managed?
- 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 metyropone or ketonazole. Treat osteoporosis and provide physiotherapy for muscle weakness
- Surgical: Pituitary adenomas: Trans-sphenoidal adenoma resection (hydrocortisone replaced until pituitary function recovers)
- Adrenal adenoma/carcinoma: Surgical removal of tumour (+ adjuvant therapy with mitotane for adrenal carcinoma
- Ectopic ACTH production: Treatment is directed at the tumour
- Radiotherapy: In those who are not cured and have persistent hypercortilosaemia after trans-spenoidal resection of the tumour
- In refractory cases of Cushing's disease, bilateral adrenalectomy may be performed
32
What are the possible complications of Cushing's syndrome?
- Diabetes, osteoporosis, hypertension. Pre-disposition to infections
- Complications of surgery: CSF leakage, meningitis, sphenoid sinusitis, hypopituitarism.
Bilateral adrenalectomy may be rarely be complicated by development of Nelson's syndrome (locally agressive pituitary tumour causing skin pigmentation due to excessive ACTH secretion
33
What is the prognosis of Cushing's syndrome?
- In the untreated, 5-year survival rate is 50%
| - Depression usually persists for many years following successful treatment
34
What is diabetes insipidus?
A disorder of inadequate secretion of a or insensitivity to vasopressin (ADH) leading to hypotonic polyuria
35
What is the aetiology of diabetes insipidus?
- Failure of ADH secretion by the posterior pituitary (central/cranial) or insensitivity of the collecting duct to ADH (nephrogenic)
- Water channels (aquaporins) fails to activate and the luminal membrane of the collecting duct remained impermeable to water
- This results in large volume hypotonic urine and polydypsia
36
What causes central diabetes insipidus?
- Idiopathic
- Tumours e.g. pituitary tumours
- Infiltrative e.g. sarcoidosis
- Infection e.g. meningitis
- Vascular e.g. aneurysms, Sheehan syndrome
- Trauma (e.g. head injury, neurosurgery, DIDMOAD
37
What causes nephrogenic diabetes insipidus?
- Idiopathic
- Drugs e.g. lithium
- Post-obstructive uropathy
- Pyelonephritis
- Pregnancy
- Osmotic diuresis (e.g. diabetes mellitus)
38
What is the epidemiology of diabetes insipidus?
- Depends on aetiology, but median age of onset is 24 yrs
39
What are the presenting symptoms of diabetes insipidus?
- Polyuria, nocturia and polydipsia (excessive thirst)
- Enuresis and sleep disturbances in children
- Other symptoms depend on the aetiology
40
What are the signs of diabetes insipidus on examination?
- Cranial diabetes insipidus has few signs if patients drink adequate fluids
- Urine output is often more than 3L/24h
- If fluid intake is less than 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)
41
What are the investigations for diabetes insipidus
- Blood: U&E and Ca++ (Na+ may be rise secondary to dehydration) Raised plasma osmolality. Decreased urine osmolality
- Water deprivation test: Water is restricted for 8h. Plasma and urine osmolality are measured every hour over the 8h. Weigh the patient hourly to monitor the level of dehydration; stop the test if the fall in body weight more than 3%. Desmopressin is given after 8h and urine osmolality is measured
42
How is diabetes insipidus managed?
- Treat the identified cause if possible
- Cranial diabetes insipidus: Desmopressin (DDAVP), a vasopressin analogue, can be given to potentiate effects of residual vasopressin
- Nephorogenic diabetes insipidus: Sodium and/or protein restriction may help polyuria. Thiazine diuretics
43
What are the complications of diabetes insipidus?
- Hypernatraemicd dehydration
| - Excess desmopressin therapy may cause hyponatraemia
44
What is the prognosis of diabetes insipidus?
- Variable depending on cause
- Cranial diabetes insipidus may be transient following head trauma
- Cure of cranial or nephrogenic insipidus may be possible on removal of cause e.g. tumour resection, drug discontinuation
45
What is type 1 diabetes mellitus?
Metabolic hyperglycaemic condition caused by absolute insufficiency of pancreatic insulin production
46
What is the aetiology of type diabetes mellitus?
- 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 subjects and is probably triggered by environmental agents. Polymorphisms of a number of genes may influence the risk of type 1 diabetes. These include the gene encoding preproinsulin and a number of genes related to immune system function
- Pancreatic B cell autoantigens may play a role in the initiation or progression of autoimmune islet injury. These include gluatmic acid decarboxylase (GAD) insulin, insulinoma associated protein 2 and cation efflux zinc transporter (ZnT8)
47
What is the epidemiology of type 1 diabetes mellitus?
- On of the most common chronic diseases in childhood with a prevalence of 0.25% in UK
- Considerable geographic variation in incidence
48
What are the presenting symptoms of type 1 diabetes mellitus?
- Often of juvenile onset (under 30yrs). Polyuria/nocturia (osmotic diureses caused by glycosuria), polydipsia (thirst), tiredness, weight loss. Symptoms of complications. Diabetes ketoacidosis: Nausea, vomiting, abdominal pain, polyuria, polydipsia, drowsiness, confusion, coma, Kussmaul breathing (deep and rapid) ketotic breath, signs of dehydration (e.g. dry mucous membranes & reduced tissue turgor)
- Signs of complications: examination of feed, test for neuropathy
- Signs of associated autoimmune conditions e.g. vitiligo, Addison's disease, autoimmune thyroid disease
49
What are the investigations for type 1 diabetes mellitus?
Blood glucose: Fasting blood glucose over 7mmol/L or random blood glucose over 11 mmol. 2 pos results needed before diagnosis
HbA1C: Estimates overall blood glucose levels in past 2-3 months
FBC: MCV, reticulolytes ( raised erythrocyte turnover causes misleading HbA1c levels)
U&E: Monitor for nephropathy and hyperkalaemia caused by ACE inhibitors
Lipid profile
Urine albumin creatinine ratio
CXR: exclude infection
ECG: Look for ischaemic changes
50
How is type 1 diabetes mellitus managed?
Diabetes keoacidosis consider HDU/ICU input, central line, arterial line and urinary catheter if severe acidosis, hypotensive or oliguric
- Insulin
- Fluids
- Potassium replacement
- Monitor blood glucose
- Broad spectrum antibiotics if infection suspected
- NBM for at least 6h (gastroparesis is common)
- NG tube: If GCS is reduced to prevent vomiting and aspiration
- Refer to diabetes team for patients education
51
What does glycaemic control involve in type 1 diabetes mellitus?
- Advice and patient education: Diabetes nurse specialist dietitians. SC insulin: Short acting insulin (e.g. Lispro, aspart, glusine) three times daily before each meal and one long-acting insulin. Injection sites should be rotated
- Insulin pumps slightly better glycaemic control but are costly and cumbersome for some patients and ketoacidosis may occur if pump malfunction
- Monitor: control of symptoms, regular finger prick tests by patient, monitoring HbA1c levels
- Screening and management of complications
Treatment of hypoglycaemia
52
What are the possible complications of type 1 diabetes mellitus?
- Diabetic ketoacidosis: reduced insulin and increased counter-regulatory hormones result in raised hepatic gluconeogenesis and decreased peipheral glucose utilisation.
- Microvascular: Retinopathy, nephropathy, neuropathy
- Macrovascular: Peripheral vascular disease, ischaemic heart disease, stroke (TIA)
- Complications of insulin treatment: Weight gain, fat hypertrophy at insulin injection sites
- Hypoglycaemia caused by missed a meal r overdosage of insuline
53
What is the prognosis of type 1 diabetes mellitus?
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
54
What is type 2 diabetes mellitus?
Characterised by increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output
55
What is the aetiology of type 2 diabetes mellitus?
- Multi-factoiral ( fenetic and environmental
- Obesity: raised plasma free fatty acid levels and adipokines secreted by adipocytes (e.g. leptin, adinonectin, TNF-a, resistin) contribute to peripheral insulin resistance. Chronic hyperglycaemia can have a toxic effect on B cells
- Secondary diabetes: Pancreatic diseases (chronic pancreatitis, hereditary haemochromatosis, pancreatic cancer, surgical removal of pancreas), Endocrinopathies (Cushings), Drugs (eg. corticosteroids
56
What is the epidemiology of type 2 diabetes mellitus?
People of Asian, African and Hispanic descent are at greater risk. Incidence has increased over last 20 years, in parallel with increased obesity worldwise
57
What are the presenting symptoms of type 2 diabetes mellitus?
- May be incidental finding
- Polyuria, polydipsia, tiredness. Patients may present with hyperosmolar hyperglycaemic state (also known as hyperosmolar, non ketotic state). Infections
- Assess for other cardiovascular risk factors: hypertension, hyperlipidaemia and smoking
58
What are the signs of type 2 diabetes mellitus on examination?
- Measure weight and height, weight circumference, blood pressure
- Look for signs of complications
- Diabetic foot: both ischaemic and neuropathic signs. Dry skin, reduced subcutaneous tissue, corns and calluses, ulceration, gangrene
- Charcot's arthropathy and signs of peripheral neuropathy, foot pulses are decreased in ischaemic foot
- Skin changes: aNecrobiosis lipoidica diabeticorum (well-dermacated plaques on the shins or arm with shiny atrophic surface and red-brown edges), granuloma annulare (flesh coloured paplules coalescing in rings on the back of hands and fingers), diabetic dermopathy (depressed pigmented scars on shins)
59
What are the investigations for type 2 diabetes mellitus?
Diagnosed if one or more of the following are present
- Symptoms of diabetes and random plasma glucose over 11.1mmol/L
- Fasting plasma glucose over 7mmol
- Two hour plasma glucose over 11.mmol after a 75g oral glucose tolerance test
Monitor: HbA1c, U&Es, lipid profile, estimated glomerular filtration rate using MDRD calculator
- Spot urine albumin. Creatinine ratio (to detect microalbuminaria)
60
How is type 2 diabetes mellitus managed?
- Glycaemic control
- Sulphonylureas (gliclazide) block ATP-sensitive K channels in B cells, stimulating insulin release. Metformin inhibits hepatic gluconeogenesis. Plioglitazone activate PPAR gamma & reduced peipheral insulin resistance
- Retinopathy: Regular digital retinal photography, ophthomology referral and laser photo-coagulation if necessary
- Nephropathy: Monitor U&Es and estimated GFR using MDRD calculator, spot urine analysis
- Neuropathy: Regular examination and inspection of the feet for ulcers, 10g monofilament testing, joint vibration, foot hygeine, amitriptuline
- Vascular disease: Regular examination of foot pulses
- Diabetic foot: Educate to examine foot regularly. Diabetic footwear. Podiatry assessment. For infections, clean and dress regularly, swan for culture and sensitivity
- Screen for and test cardiovascular risks: Lose weight, exercise, stop smoking, BP control, all diabetics patients should be started on a statin. Aspirin in patients with diabetes and additional cardiovascular risk factor
61
What does glycaemic control in type 2 diabetes mellitus involve?
- At diagnosis: Lifestyle & metformin
- If HbA1c more than 7% after 3 months: Lifestyle & metformin & sulphonurea
- If HbA1c more than 7% after 3 months: Lifestyle & metformin % basal insulin
- If HbA1c more than 7% and fasting blood glucose less than 7mmol/L: Add premeal rapid acting insulin
- Sulphonurea may be given as monotherapy in patients who cannot tolerate metformin
62
What advice and patient education should be given to type 2 diabetics?
INFORM PT
- Information: Diabetic nurses, leaflets, websites etc, explaining diabetes control, complications
- Nutrition: Optimizing meal plans, diet
- Foot care: Regular inspection, appropriate footwear, role of chiropodist
- Organisations: Local and national support groups
- Recognition and treatment of hypoglycaemia
- Monitoring capillary blood glucose and charting it. Monitoring for ketones during intercurrent illness
- Pregnancy: Strict glycaemic control and planning of conception
- Treatment: Action, duration and administration, technique for insulin, change the site of injection, explain the need to plan exercise
63
What are the possible complications of type 2 diabetes mellitus?
- Hyperosmolar hyperglycaemic state: Due to insulin deficiency as diabeteic ketoacidosis but patient is usually old and may be presenting for the first time, history is longer (e.g. 1 week). Distal symmetrical sensory neuropathy, painful neuropathy, carpal tunnel syndrome, diabetic amyotrophy, mononeuritis, autonomic neuropathy, gastroparesis, impotence, urinary retention.
Nephropathy: Microambinuria, proteinuria and eventually renal failure.
- Retinopathy: Backgroun: 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 the fovea, haemorrhage within 1 disc diameter of centre of the fovea associated with reduced visual acuity.
Also prone to glaucoma, cataracts, transient visual loss
- Macrovascular: ischaemic heart disease, stroke, pvd
64
What is the prognosis of type 2 diabetes mellitus?
- Intensive therapy to achieve lower levels of glycaemia, lowers the risk of development and progression of diabetic microvascular complications
65
What is Grave's disease?
Autoimmune thyroid condition associated with hyperthyroidism
66
What is the aetiology of Grave's disease?
- Autoimmune
- Stimulation of thyroid by TSH receptor antibodies causing thyroid hormone overproduction
- Genetic (80%) and environmental (20%) factors
67
What is the epidemiology of Grave's disease?
- Most common form of hyperthyroidism in most areas of world
68
What are the presenting symptoms of Grave's disease?
- Heat intolerance
- Sweating
- Weight loss
- Palpitations
- Tremor
- Irritability
69
What are the signs of Grave's disease on examination?
- Wide pulse pressure
- Diffuse goitre
- Tachycardia
- Orbitopathy
- Scalp hair loss
- Moist, velvety skin
- Cardiac flow murmir
- Thyroid bruit
- Oncholysis
- Vitiligo
- Pretibial myoedema
- Acropachy
70
What are the investigations for Grave's disease?
- TSH: suppressed
- Serum free T4: Elevated, except in T3 toxicosis or subclinical disease
- Serum free or total T2: elevated, except in subclinical disease
71
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
72
What is the aetiology of hyperparathyroidism?
Primary: Parathyroid gland adenomas or hyperplasia. Rarely, parathyroid carcinoma. May be associated with multiple endocrine neoplasia (MEN)
Secondary: Chronic renal failure, vitamin D deficiency
73
What is the epidemiology of hyperparathyroidism?
Primary: Annual incidence if 5 in 100,000. Twice as common in females. Peak incidence 40-60 years
74
What are the presenting symptoms of hyperparathyroidism and its signs on examination?
- Primary: Many patients have mild hypercalcaemia and are asymptomatic
- Hypercalcaemia may present with: polyuria, polydipsia, renal calculi, bone pain, abdominal pain, nausea, constipation, psychological depression and lethargy
- Secondary: May present with symptoms and signs of hypocalcaemia and/or the underlying cause (chronic renal failure, vit D deficiency)
75
What are the investigations for hyperparathyroidism?
- U&E's, serum calcium (raised in primary and tertiary, decreased or normal in secondary), Phosphate (low in 1&2, raised in 3), raised alkaline phosphatase, vit D (low in 2)
- Primary: hyperchloraemic acidosis (normal anion gap) caused by PTH inhibition of renal tubular reabsorption of bicarbonate
- Urine: Differential diagnosis of primary hyperparathyroidism includes familial hypocalciuric hypercalcaemia
- Renal ultrasound at baseline to look for renal calculi
- Radiographs
- Preoperative localisation
76
How is primary hyperparathyroidism managed?
- Acute hypercalcaemia: IV fluids. Conservative management: In patients who do not meet surgical criteria, avoid factors that can exacerabate hypercalcaemia including thiazide diuretics. Maintain adequate hydration (at least 6-8 glasses water per day). Moderate calcium & vit D intake
- Surgical: Subtotal parathyroidectomy, total parathyroidectomy (in MEN1). Indications: symptomatic patients or asymptomatic patients with
Age= over 50
Bone mineral density= T score less than 2.5
Creatinine clearance= reduced by 30%
Difficult to do follow up periodically
Elevated serum calcium
77
How is secondary hyperparathyroidism managed?
Treat underlying renal failure
| Calcium and vitamin D supplements
78
What are the possible complications of hyperparathyroidism?
- Primary: Raised PTH results in more bone resorption, raised renal tubular calcium reabsorption, 1a-hydroxylation of vit D and intestinal calcium absorption, leading to hypercalcaemia
- Secondary: Increased stimulation of osteoclasts and bone turnover leading to osteitis fibrosa cystica
- Complications of surgery: Hypocalcaemia, recurrent laryngeal nerve palsy
79
What is the prognosis for hyperparathyroidism?
- Primary: surgery is curative for benign disease in most cases
- Secondary or tertiary: As for chronic renal failure
80
What is female hypogonadism?
Characterised by impairment of ovarian function
81
What is the aetiology of female hypogonadism?
Primary hypogonadism (hypergonadotrophic)
- Gonadal dysgenesis: Chromosomal abnormalities (e.g. Turner's syndrome), FMR1 gene pre-mutation carriers (CGG repeats between 55&200)
- Gonadal damage: Autoimmune, iatrogenic (chemotherapy, radiation, surgery)
- Secondary hypogonadism (hypogonadotrophic)
- Functional: Stress, weight loss, excessive exercise, eating disorders (anorexia nervosa, bulimia)
- Pituitary/hypothalamic tumours and infiltrative lesions: Pituitary adenomas, craniopharyngiomas, haemochromatosis
- Hyperprolactinaemia: Prolactinomas or tumours causing pituitary stalk compression
- Congenital GnRH deficiency: Kallmann's syndrome, idiopathic
82
What is the epidemiology of female hypogonadism?
Symptoms of oestrogen deficiency
- Night sweats, hot flush, vaginal dryness and dyspareunia
- Reduced libido, infertility
- Symptoms of underlying cause
83
What are the signs of female hypogonadism on examination?
Pre-pubertal hypogonadism:
- Delayed puberty (primary amenorrhoea, absent breast development, no secondary sexual characteristics)
- Eunuchoid proportions (e.g. long legs, increased arm span for height)
Post-pubertal hypogonadism:
- Regression of secondary sexual characteristics (loss of secondary sexual hair, breast atrophy). Perioral and periorbital fine facial wrinkles
- Signs of underlying cause/ associated symptoms
- Hypothalamic/pituitary disease: Visual field defects
- Kallmann's syndrome: Anosmia
- Turner's syndrome: Short stature, low posterior hairline, high arches palate, widely spaced nipples, wide carrying angle, short fourth and fifth metacarpals, congenital lymphoedema
- Patient's with autoimmune primary ovarian failure: Signs of autoimmune disease e.g. hyperpigmentation in Addison's disease or vitiligo
84
What are the investigations for female hypogonadism?
- Reduced serum oestradiol. Serum FSH & LH: Raised in primary (due to decreased feedback inhibition by ovarian oestradiol and inhibin). Reduced or inappropriately normal FSH/LH in secondary hypogonadism
- Investigation to determine the aetiology
- Primary: Karyotype (to look for chromosomal abnormalities: complete or partial deletion of the X chromosome in Turner's syndrome or presence of Y chromsome. Pelvic imagine: in pts with primary amenorrhoea, to demonstrate presence or absence of uterus and vagina and vaginal or cervical outlet obstruction (Mullerian agenesis, androgen insensitivity, transverse vaginal septum, imperforate hymen
- In unexplained pre-mature ovarian failure: screening for pre-mutation in FMR1 gene after appropriate genetic counselling and informed consent
- Secondary: Pituitary function tests (9am cortisol, TFTs, prolactin), visual field testing, hypothalamic-pituitary MRI, smell tests for anosmia. Serum transferrin saturation if hereditary haemochromatosis is suspected
- Turner's: Periodic echo and cardio follow-up. Renal USS
- Autoimmune oophoritis: Evaluate for autoimmune adrenal insufficiency
85
What is male hypogonadism?
A syndrome of reduced testosterone production, sperm production or both
86
What is the aetiology of primary male hypogonadism?
- Gonadal dysgensis: Klinefelter's syndrome (XXY), undescended testes (cryptochidism)
- Gonadal damage: Infection (e.g. mumps), torsion, trauma, autoimmune, iatrogenic (chemotherapy, surgery, radiation)
- Rare causes: Defects in enzymes involved in testosterone synthesis, myotonic dystrophy
87
What is the aetiology of secondary male hypogonadism?
- Pituitary/hypothalamic lesions
- GnRH deficiency: Kallmann's syndrome (associated with anosmia), idiopathic
- Hyperprolactinaemia
- Systemic/chronic diseases
- Rare causes: Genetic mutation. Secondary hypogonadism may be seen in a number of are syndromes
- Prader-Willi syndrome: Loss of critical region on chromosome 15 causing obesity and short stature, small hands, almond-shaped eyes, learning difficulty/postnatal hypotonia
- Laurence-Moon-Biedl syndrome: Obesity, polydactyly, retinitis pigmentosa, learning difficulty
88
What is the epidemiology of male hypogonadism?
- Primary accounts for 30-40% of male infertility, secondary accounts for 1-2%
- Most common cause of primary hypogonadism is Klinefelter's syndrome
89
What are the presenting symptoms of male hypogonadism?
- Delayed puberty ( f the onset is before puberty)
- Reduced libido, impotence, infertility
- Symptoms of underlying cause e.g. Klinefelter's syndrome: intellectual dysfunction and behavioural abnormalities which cause difficulty in social interactins
90
What are the signs of male hypogonadism on examination?
- Measure testicular volume using Prader's orchidometer (ellipsoids of different sizes) Normal adult testicular volume: 15-25 ml
Pre-pubertal hypogonadism:
- Signs of delayed puberty (high pitched voice, reduced pubic/axillary/facial hair, small or undescended testes, small phallus), gynaecomastia, eunuchoid proportions, arm span more than height, lower segment larger than upper segment ( delayed fusion of epiphyses and continued growth of bones)
- Features of underlying cause e.g. cryptochidism, anosmia in Kallmann's
Postpubertal hypogonadism:
- Reduced pubic/axillar/facial hair, soft and small tests, gynaecomastia, fine perioral wrinkles. Features of the underlying cause e.g. visual field defects due to pituitary tumour, signs of systemic chronic illness
91
What are the investigations for male hypogonadism?
- Serum total testosterone, SHB and albumin, LH & FSH
- Primary: Reduced testosterone, raised LH and FSH (neg feedback)
- Secondary: Reduced testosterone, reduced or inappropriately normal LH/FSH
Determine level of defect:
- Primary: karyotype (exclude Klinefelter's)
- Secondary: Pituitary function tests, MRI of hypothalamic pituitary area, visual field testing, smell tests for anosmia. Iron studies if hereditary haemochromatosis suspected
- Bone age: In boys with delayed puberty: determined by comparison of radiograph of patient's bones in left hand and wrist with bones of a standard atlas (allows assessment of skeletal maturation and potential for future skeletal growth
92
What is hypopituitarism?
Deficiency of one or more of the hormones secreted by the anterior pituitary
- Panhypopituitarism is deficiency of all pituitary hormones
93
What is the aetiology of hypopituitarism?
- Pituitary masses: Most commonly adenomas. Other parapituitary tumours (e.g. craniopharyngioma, meningioma, glioma, metastases), cysts (arachnoid cyst, Rathke's cleft cyst)
- Pituitary trauma: Radiation, surgery or skull case fracture
- Hypothalamus (functional): Anorexia, starvation, over-exercise
- Infiltration: Tuberculosis, sarcoidosis, haemochromatosis, histicytosis X
- Vascular: Pituitary apoplexy, Sheehan's syndrome
- Infection: Meningitis, encephalitis, syphilis, fungal abscess
- Genetic mutations: Pit-1 and Prop-1 genes
94
What is the aetiology of hypopituitarism?
Annual incidence and prevalence of pituitary adenoma: 1 in 100,000 and 9 in 100,000, respectively
95
What are signs and symptoms of hypopituitarism with GH deficient?
- Children: Short stature (less than 3rd centile/not in keeping with parental height)
- Adults: Low mood, fatigue, reduced exercise capacity, muscle strength, increased abdominal fat mass
96
What are the signs and symptoms of hypopituitarism with LH/FSH deficient?
Delayed puberty
- Females: Loss of secondary sexual hair, breast atrophy, menstrual irregularities, dyspareunia, decreased libido, infertility
- Males: Loss of secondary sexual hair, gynaecomastia, small or soft testes, reduced libido, impotence
97
What are the signs and symptoms of hypopituitarism with prolactin deficient?
Absence of lactation
| - in Sheehan's syndrome
98
What are the signs and symptoms of pituitary apoplexy?
Life-threatening hypopituitarism with headache, visual loss and cranial nerve palsies
99
What are the investigations for hypopituitarism?
Pituitary function tests
- Basal tests: 9am cortisol, LH, FSH, testosterone, oestradiol, IGF-1, prolactin, free T4 and TSH
- Dynamic tests: insulin-induced hypoglycaemia (contraindicated in pts with epilepsy, IHD, hypoadrenalism) Give 0.15 U/kg IV insulin. In hypopituitarism, peak GH and cortisol response to insulin-induced hypoglycaemia are less than20 U/L and less than 550 nmol/L respectively
- Short Synacthen test
- MRI or CT of brain
- Visual field testing
100
How is hypopituitarism managed?
Hormone replacement:
- Hydrocortisone: Should be provided with Medicalert bracelet and steroid card
- L-thyroxine: Take after hydrocortisone to avoid Addisonian crisis
- Sex hormones: Testosterone in males. Oestrogen with/or progesterone in females
- Growth hormones: children require specialist supervision
- Posterior pituitary deficiency: Desmopressin
101
What are the complications of hypopituitarism?
- Adrenal cris, hypoglycaemia, myxoedema coma, infertility/
- Osteoporosis, dwarfism (children)
- Complications of pituitary mass: optic chiasm compression, hydrocephalus (third ventricular compression), temporal lobe epilepsy
102
What is the prognosis of hypopituitarism?
Good with lifelong hormone replacement
103
What is hypothyroidism?
Clinical syndrome resulting from insufficient secretion of thyroid hormones
104
What is the aetiology of primary hypothyroidism?
Reduced thyroid hormone production:
Acquired:
- Autoimmune (Hashimoto's) thyroiditis (cellular and antibody-mediated
- Iatrogenic (post-surgery, radioiodine, medication for hyperthyroidism)
- Severe iodine deficiency or iodine excess (Wolff-Chaikoff effect)
Thyroiditis
- Congenital: Thyroid dysgenesis
105
What is the aetiology of secondary hypothyroidism?
Pituitary or hypothalamic disease (e.g. tumours) resulting in reduced TSH or TRH and reduced stimulation of thyroid hormone production
106
What is the epidemiology of hypothyroidism?
Females to males: 6:1
Age of onset commonly over 40 years, but can occur at any age
Iodine deficiency is seen in mountainous areas e.g. Alps, Himalayas
107
What are the presenting symptoms of hypothyroidism?
- Onset is usually insidious
- Cold intolerance, lethargy, weight gain, constipation, dry skin hair loss, hoarse voice,
- Mental slowness, depression, dementia, cramps, ataxia, paraesthesia
- Menstrual disturbances (irregular cycles, menorrhagia) in females
- History of surgery or radioiodine therapy for hyperthyroidism
- Personal or family history of other autoiumme conditions e.g. Addison's disease, T1DM, pernicious anaemia and pre-mature ovarian failure
- Myxoedema coma (severe hypothyroidism usually seen in the elderly): Hypothermia, hypoventilation, hyponoatreamia, heart failure, confusion and coma
108
What are the signs of hypothyroidism on examination?
- Hands: Bradycardia, cold hands
- Head/neck/skin: Pale puffy face, goitre, oedema, hair loss, dry skin, vitiligo
- Abdomen: Ascites
- Neurological: Slow relaxation of reflexes, signs of carpal tunnel syndrome
109
What are the investigations for hypothyroidism?
- Blood: TFT: Primary: Reduced T4/T3 and raised TSH (due to reduced negative feedback) Secondary: Reduced T3/T3 and reduced and inappropriately normal TSH
(Subclinical hypothyroidism is characterised by normal serum free T3/T4 and raised TSH)
- FBC: Normocytic anaemia
- U&E's: May show reduced Na+
- Cholesterol: May be raised
- In suspected secondary cases: Pituitary function tests, pituitary MRI and visual field testing
110
How is hypothyroidism managed?
- Chronic: Levothyroxine. Rule out underlying adrenal insufficiency and treat before starting thyroid hormone replacement to avoid Addisonian crisis. Adjust dosage depending on TFT and clinical picture. In patients with ischaemic heart disease, start at low dose and gradually increase at 6 week intervals if ischaemic symptoms do not deteriorate
- Myxoedema coma: Oxygen, rewarming, rehydration, IV T4/T3, IV hydrocortisone (in case hypothyroidism is secondary to hypopituitarism), treat the underlying disorder e.g. infection
111
What are the possible complications of hypothyroidism?
Myxoedema coma, myxoedema madness (psychosis with delusions and hallucinations or dementia) in severe hypothyroidism (may be seen in the elderly after starting levothyroxine treatment
112
What is the prognosis of hypothyroidism?
Lifelong levothyroxine replacement therapy required. Myxoedema coma has a mortality of up to 80%
113
What is multiple endocrine neoplasia?
Hereditary tumour syndromes of variable neoplastic patterns and characterised by the development of multiple endocrine tumours
- Tumours can include parathyroid adenomas, pituitary adenomas, enteropancreatic neuroendocrine tumours, phaeochromocytomas
114
What is the aetiology of multiple endocrine neoplasia?
- MEN1 & MEN2 are caused by autosomal-dominant mutations that can be inherited or occur sporadically
- MEN1 gene mutations responsible for 80-90% of MEN1 cases
- RET proto-oncogene mutations responsible for almost all MEN 2 cases
115
What is the epidemiology of multiple endocrine neoplasia?
- Relatively rare
MEN 1:
- Prolactinomas most common MEN1 pituitary adenoma
- 90% pts develop primary hyperparathyroidism by 50
MEN2
- Most cases are MEN2A
- Medullar thyroid cancer presents in nearly all genetic carriers of MEN2 by adulthood if not treated with prophylactic thyroidectomy, and is the commonest present feature of MEN2
116
What are the presenting symptoms of multiple endocrine neoplasia?
- Young age
- Positive family history
- Episodic triad of sweating, palpitation, and headache (MEN2)
- Visual changes (MEN1)
- Unexplained flushing (MEN2)
- Weight changes
- Abdominal pain
- Headache
117
What are the signs of multiple endocrine neoplasia on examination?
- Clinical features of kidney stones
- Facil angiofibromas or collagenomas (MEN1)
- Mucosal neuromas (MEN2B)
- Arm span and upper-to-lower-body-segment ratio (MEN2B)
- Palpable thyroid nodule (MEN2)
- Hypertension
118
What are the investigations for multiple endocrine neoplasia?
- Serum calcitonin (MEN2): raised
- Serum carcinoembryonic antigen (MEN2): Raised
- Serum parathyroid hormone and calcium: raised
- Fasting serum gastrin (MEN1): raised
- Serum prolactin (MEN1): raised
- 24 hour urine urine calcium: low,normal or raised
- Thyroid biopsy (MEN2): atypical cells or medullary thyroid cancer
119
What is obesity?
Chronic adverse condition due to an excess amount of body fat
120
What is the aetiology of obesity?
- Caloric intake that, over time, is greater than caloric expenditure
- Factors that are associated with this energy imbalance in western society includes genetic predisposition, behavioural dynamics, hormonal disturbances, cultural influences and environmental circumstances as described below. These categories overlap and typically, more than 1 factor is present in a given person
- Hormonal causes can include hypothyroidism, hypercortisolism, insulinoma
121
What is the epidemiology of obesity
In 2008, 24% of men and 25% of women aged 16 years or over in England were classified as obese (BMI ≥30 kg/m^2
122
What are the presenting symptoms of obesity?
- Height
- Weight
- Work out BI
123
What are the signs of obesity on examination?
- Hypothyroidism, hypercortisolism, corticosteroid therapy
- Waist circumference
- Hip circumference
- Comorbid conditions
- MMI 30.0 to 39.9 kg/m^2; morbid obesity: BMI ≥40.0 kg/m^2
124
What are the investigations for obesity?
- Clinical exam
- FBC: normal, may show anaemia
- Serum transaminases, normal, may be elevated if liver dysfunction
- ECG: normal: may show abnormalities associated with heart disease
125
What is osteoporosis?
Reduced bone density (defined as less than 2.5 standard deviations below peak bone mass achieved by healthy adults i.e. T score less than 2.5) resulting in bone fragility and increased fracture risk
- Osteopenia is defined as a T-score between -1 and -2.5
126
What is the aetiology of osteoporosis?
Primary: Idiopathic (under 50 yrs), post-menopausal
Secondary:
- Malignancy: Myeloma, metastatic carcinoma
- Endocrine: Cushing's disease, thyrotoxicosis, primary hyperarathyroidism, hypogonadism
- Drugs: Corticosteroids, heparin
- Rheumatological: Rheumatoid arhritis, ankylosing spondylitis
- Gastrointestinal: Malabsorption syndromes (e.g. coeliac disease, partial gastrectomy), liver disease (primary biliary cirrhosis), anorexia
127
What are the risk factors for osteoporosis?
- Age
- Family history
- Low BMI
- Low calcium intake
- Smoking
- Lack of physical exercise
- Low exposure to sunlight
- Alcohol abuse
- Late menarche
- Early menopause
- Hypogonadism
128
What is the epidemiology of osteoporosis?
- Common
- In over 50 yr olds, 1/3 of women, 1/12 of men
- More common in caucasians than in afro-carribbeans
129
What are the presenting symptoms of osteoporosis?
- Often asymptomatic until characteristic fractures occur
- Femoral neck fractures (commonly after minimal trauma). Vertebral fractures (loss of height or stooped posture or acute back pain are lifting)
- Colle's fracture of the distal radius after fall onto outstretched hand
130
What are the signs of osteoporosis on examination?
Often no signs until complications develop
- Tenderness on percussion (over vertebral fractures
- Thoracic kyphosis (if multiple vertebral fractures); and
- Severe pain with leg shortened and externally rotated (in femoral neck fracture)
131
What are the investigations for osteoporosis?
- Blood: Ca++, P043- and AlkPhos are normal in primary (unless due to secondary causes
- X-Ray: Usually diagnose fractures when symptomatic. Often normal (More than 30% loss in density before showing radiolucency, abnormal trabeculae or cortical thinning evident), biconcave vertebrae, crush fractures
- Isotope bon scan: highlight microfractures
- Bone densitometrey: for obtaining T & Z scores
132
What is a T score?
Number of standard deviations the bone mineral density measurement is above or below the young normal mean bone mineral density
- Used to define osteoporosis
133
What is a Z score?
Number of standard deviations the measurement is above or below the age-matched mean bone mineral density
- May be helpful in identifying patient who may need a work-up for secondary causes of osteoporosis
134
What is Paget's disease of bone?
Characterised by excessive bone remodelling at one (monostotic) or more (polyostotic) sites resulting in bone that is structurally disorganised
135
What is the the aetiology of Paget's disease of bone?
- Unknown
- Genetic factors and viral infection may play a role as suggested by familial and pathological studies
- Excessive bone resorption by abnormally large osteoclasts is followed by increased bone formation by osteoblasts in a disorganised fashion. This results in an abnormal ('mosaic') pattern of lamellar bone. The marrow spaces are filled by an excess of fibrous tissue with a marked increase in blood vessels
136
What is the epidemiology of Paget's disease of bone?
- Common older age
| - Men and women are equally affected
137
What are the presenting symptoms of Paget's disease of bone?
- May be asymptomatic
- May present with insidious onset pain, aggravated by weight bearing and movement (may be caused by Pagetic process, associated degenerative join disease or stress fractures), headaches, deafness, increasing skull size
138
What are the signs of Paget's disease of bone on examination?
- Bitemporal skull enlargement with frontal bossing
- Spinal kyphosis
- Anterolateral bowing of femur, tibia or forearm
- Skin over involved bone may warm (as result of increased vascularity
- Sensorineural deafness (compression of vestibulocochlear nerve)
139
What are the investigations for Paget's disease of bone?
- Bloods: Raised AlkPhos, but Ca+ and P043- normal (except if immobilised
- Bone radiographs: Enlarged, deformed bone with mixed lytic/sclerotic appearance, lack of distinction between cortex and medulle skull: osteoporosis circumscripta, enlargement of frontal and occipital areas, associated with a 'cotton wool' appearance
- Bone scan: To assess extent of skeletal involvement, but is not specific for diagnosis. Pagetic bone lesions are seen as focal areas of markedly increased uptake (hot spots)
- Resoprtion markers: Urinary hydroproline
140
What is phaeochromocytoma?
Catecholamine-producing tumours that usually arise from chromaffin cells of the adrenal medulla but are extra-adrenal in about 10% of cases.
- 10% are bilateral and 10% are malignant
- Extra-adrenal phaeochromocytomas are referred to as 'paragagnliomas'
141
What is the aetiology of phaeochromocytoma?
- Cause of sporadic cases unknown
- May be familial in up to 30%
- Familial cases may be seen in patients with: MEN2a, von Hippel-Lindau (VHL) syndrome, neurofibromatosis type 1 (NF1) and mutations in genes encoding subunits of the mitochorndrial enzyme succinate dehydrogenase: SDHB, SDHD, SDHC
142
What is the epidemiology of phaeochromocytoma?
- Rare
| - Less than 0.2% of hypertensive patients
143
What are the presenting syntoms of phaeochromocytoma?
- Paroxysmal episodes of headache, sweating
- Cardio/respiratory: Palpitations, chest pain, dyspnoea
- GI: Epigastric pain, nausea, constipation
- Neuro/psychiatric: weakness, tremor, anxiety
144
What are the signs of phaeochromocytoma on examination?
- Hypertension: 2/3 sustained, 1/3 paroxysmal
- Postural hypotension: Secondary to decrease in plasma volume.
- Pallor, tachycardia, fever, weight loss
145
What are the investigations for phaeochromocytoma?
- 24h urine collections (in acid containing bottle): for measurement of catecholamines (adrenaline, noradrenaline, dopamine) & if available fractionated metanephrines. Urinary creatinine should be measured to verify an adequate collection. Certain drugs may increase measured catecholamines e.g. tricyclic antidepressants, levodopa.
- Plasma free metanephrines: In patients at high risk
- Tumour localisation: CT or MRI scan
- 123I-MIBG scintigraphy: For large (10cm and above) phaeochromocytomas ("risk of malignancy) or
paraganglioma ("risk of multiple tumours and malignancy), or if CT or MRI is negative, but
diagnosis considered likely due to clinical and biochemical evidence.
- Screen for associated conditions
- VHL: Ophthalmoscopy, MRI posterior fossa & renal USS
- NF1: Clinical exam for neurofibromas, cafe-au-lait spots and axillary freckling
- Genetic testing and counselling
146
What is a non-functioning pituitary tumour?
- Pituitary adenomas are third most common intra-cranial neoplasm in adults
- Do not cause characteristic hormone hypersecretion syndrome
- Clinically non-functional adenoma (CNFPA)
147
What is the aetiology of a non-functioning pituitary tumour?
- Unknown
| - Monoclonal in origin, suggests intrinsic genetic alterations as initiating events
148
What is the epidemiology of a non-functional pituitary tumour?
Pituitary adenomas are the third most common intracranial neoplasms (behind meningiomas and astrocytomas), accounting for about 10% of all intracranial tumours in adults. There is no known gender or racial difference in prevalence.
149
What are the presenting symptoms of a non-functional pituitary tumour?
- Presence of risk factors (MEN1, FIPA, Carney complex)
- Long-standing and progressing symptoms
- Headaches
- Erectile dysfunction
- Soft small testicles
- Gynaecomastia
- Amenorrhoea
Loss of libido
- Weight gain
- Fatigue
- Vomiting
- Weakness
- Hot flushes
150
What are the signs of non-functional pituitary tumour on examination?
- Infertility
- Breast atrophy
- Diaphoresis
- Decreased visual acuity
- Bitemporal hemianopia
- Pituitary apoplexy
151
What are the investigations for a non-functional pituitary tumour?
- Prolactin: May be elevated
- Growth hormone stimulation test
- IGF-1: low or normal
- LH. FSH
- Alpa subunit of human pituitary glycoprotein hormones: Normal or elevated
152
What is polycystic ovary syndrome (PCOS)?
Characterised by oligomenorrhoea/amenorrhoea and hyperandrogenism (clinical or biochemical)
- Frequently associated with obesity, insulin resistance, type 2 diabetes and dyslipidaemia
153
What is the aetiology of PCOS?
- Environmental factors (e.g. related to diet and the development of obesity) & genetic variants (e.g. genes regulating gonadotrophins, insulin, androgen synethsis etc) may influence development of PCOS
- Hyperinsulinaemia results in increased ovarian androgen synthesis and reduced hepatic SHBG synthesis (resulting in increased free androgens)
154
What is the epidemiology of PCOS?
- Most common cause of infertility in women
| - Affects 6-8% of women
155
What are the presenting symptoms of PCOS?
- Menstrual irregularities (oligomenorrhoea or amenorrhoea)
- Dysfunctional uterine bleeding, infertility
- Symptoms of hyperandrogenism: Hirsutism, male-pattern hair loss, acne
156
What are the signs of PCOS one examination?
- Hirsutism, male pattern hair loss & acne
- Acanthosis nigricans (signs of severe insulin resistance): velvety thickening and hyperpigmentation of the skin of axillae or neck
157
What are the investigations for PCOS?
- Blood: Raised LH, LH:FSH ration (over 3). Raised testosterone, androstenedione and DHEA-S. Lowered SHBG
- Tests to exclude hyperprolactinaemia (serum prolactin, hypo/hyperthyroidism (thyroid function tests), congenital adrenal hyperplasia (17OH-progesterone), and Cushing's syndrome
- Look for impaired glucose tolerance/ T2DM: fasting glucose, HbA1c
- Fasting lipid profile
- Transvaginal USS: 12 or more follicles in each ovary, measuring 2-9mm and/or increased ovarian volume more than 10mL
158
What is primary hyperaldosteronism?
Aldosterone production exceeds the body's requirements and is relatively autonomous with regard to its normal chronic regulator, the renin-angiotensin II system
- Results in excessive sodium reabsorption via amiloride-sensitive epithelial sodium channels within distal nephron, leading to HTN and suppression of renin-angiotensin II
159
What is the aetiology of primary hyperaldosteronism?
- Unknown
| - Occurrence within families keeping with genetic bases
160
What is the epidemiology of primary hyperaldosteronism?
In the UK there were 316 inpatient admissions with hyperaldosteronism in the 1-year period 2013 to 2014, predominantly in the 15 to 59 year age group (215 cases)
161
What are the presenting symptoms of primary hyperaldosteronism?
- Age 20-70
- Family history
- Family history of early onset HTN and/pr stroke
- Nocturia, polyuria
- Lethargy
- Mood disturbance (irritability, anxiety, depression)
- Difficulty concentrating
162
What are the signs of primary hyperaldosteronism on examination?
- HTN
| - Presence of risk factors
163
What are the investigations for primary hyperaldosteronism?
- Fludrocortisone supression test: failure of upright (10 a.m.) plasma aldosterone to suppress to <166 picomol/L
- Saline infusion testing: plasma aldosterone regarded as diagnostic
- Oral salt loading
- Adrenal CT: detection of adrenal mass lesion
- Adrenal venous sampling: Aldosterone production lateralises to one adrenal in unilateral forms
164
How is primary hyperaldosteronism managed?
- Unilateral laparoscopic adrenalectomy
| - Aldosterone antagonists
165
What are the possible complications of primary hyperaldosteronism?
- Perioperative complications: Bleeding, infection, wound hernia, cardiovascular events)
- Stroke
- MI
- Heart failure
- Aldosterone antagonist- or mineralocorticoid receptor antagonist-induced hyperkalaemia
166
What is the prognosis of primary hyperaldosteronism?
- PTs undergoing unilateral adrenalectomy for unilateral PA: Leads of cure in 50-60%
- Pts undergoing treatment with aldosterone antagonists: HTN improved and controlled in majority
167
What is prolactinoma?
Benign lactotroph adenomas expressing and secreting prolactin
168
What is the aetiology of prolactinomas?
- Monoclonal in origin suggesting that pituitary tumours arise from proliferation of single, mutated pituitary cells, where somatic cell mutations stimulate cellular growth rate.
- Majority occur sporadically
- Small percentage of pts have MEN1 of FIPA
169
What is the epidemiology of prolactinomas?
- Most common type of pituitary adenoma= 40% of these tumours
- More frequent in women, mainly during child-bearing years. Peak incidence between 2nd & 3rd decades of life
- 10:1 women:men
170
What are the presenting symptoms of prolactinomas?
- Presence of risk factors (female, 20-50yrs)
- Amenorrhoea, oligomenorrhoea
- Loss of libido
- Erectile dysfunction
171
What are the signs of prolactinomas on examination?
- Galactorrhoea
- Visual deterioration (e.g. temporal hemianopia)
- Osteoporosis
172
What are the investigations for prolactinomas?
- Serum prolactin: Elevated
- Pituitary MRI: characteristic features of pituitary adenoma
- Computerised visual-field examination: May reveal unilateral or bi-temporal hemianopia
173
How are prolactinomas managed?
- Observation
- Dopamine agonist
- Combined oral contraceptive
- Transphenoidal surgery
- Sellar radiotherapy
174
What are the possible complications of prolactinomas?
- Visual field impairment
- Anterior pituitary failure and/or diabetes insipidus
- Hypopituitarism associated with radiotherapy
175
What is the prognosis for prolactinomas?
- Benign disease follows progressive improving course while medically treated
176
What is SIADH?
Characterised by continued secretion of ADH, despite the absence of normal stimuli for secretion (i.e. increased serum osmolality or decreased blood volume)
177
What is the aetiology of SIADH?
- Brain: Haemorrhage/thrombosis, meningitis, abscess, trauma, tumour, Guillain-Barre syndrome
- Lung: Pneumonia, TB, abscess, aspergillosis, small cell carcinoma
- Tumours: Small cell lung cancer, lymphoma, leukaemia, pancreas, prostate, mesothelioma, sarcoma, thymoma. May be caused by ectopic ADH secretion
- Drugs: Vincristine, opiates, carbamazepine, chlorpropamide
- Metabolic: Porphyria, alcohol withdrawal
178
What is the epidemiology of SIADH?
- Hyponatreamia is most common electrolyte imbalance seen in hospitals
- More than 50% of all severe hyponatraemia is due to SIADH
179
What are the presenting symptoms of SIADH?
- Mild hyponatraemia: may be asymptomatic
- Headache, nausea/vomiting, muscle cramp/weakness, irritability, confusion, drowsiness, convulsions and coma
- Symptoms of underlying cause
180
What are the signs of SIADH on examination?
- Mild hyponatraemia: no signs
- Severe: Decreased reflexes, extensor plantar reflexes
- Signs of underlying cause
- The hyponatraemia in SIADH is dilutional from increased body water and non decreased total Na+
181
What are the investigations for SIADH?
- Reduced Na+, creatinine (renal function), glucose, serum protein and lipids (to exclude pseudohyponatraemia seen with raised protein or lipids)
- Free T4 and TSH (exlcude hypothyroidism), short ACTH stimulation test (exclude renal insufficiency)
- SIADH diagnosis: Reduced plasma osmolality and increased urine osmolality. Presence of above and absence of hypovalaemia/hypotension, oedema, renal failure, adrenal insufficiency and hypothyroidism are required for diansosi
- Ix for identifying cause: CXR, CT chest/abdomen/pelvis, MRI/CT head
182
How is SIADH managed?
- Treat underlying cause
- Water restriction (0.5-1L/day). If infective, give demeclocycline (reduced responsiveness of the collecting tubule cells to ADH)
- Vasopressin (V2) receptor antagonist e.g. tolvaptan are likely to be useful in moderate chronic hyponatraemia if water restriction is insufficient
- In severe cases (seizures and reduced consciousness) give slow IV hypertonic 3% (and furosemide) saline with close monitoring. Change in Na+ should not excess 10mmol/L in first 24h and 18mmol/L in first 48h. Rapid correction can result in central pontine-myelinolysis
183
What are the possible complications of SIADH?
- Convulsions, coma, death
| - Central pontine myelinolysos quadreparesis, respiratory arrest, fits) occurs with rapid correction of hyponatraemia
184
What is the prognosis of SIADH?
- Depends on underlying cause
- High morbidity and mortality with [Na+] less than 110mmol/L
- Up the 50% mortality with central pontine myelinolysis
185
What is thyroid cancer?
Four types account for more than 98% of thyroid malignancies:
- Follicular
- Papillary
- Anaplastic
- Medullary
186
What is the aetiology of thyroid cancer?
- Genetic alterations thought to underlie thyroid cancers
- Papillary thyroid carcinomas often harbour mutations (e.g., BRAF mutations) that activate effector signalling through a mitogen-activated protein kinase. Follicular thyroid carcinomas often have a chromosomal translocation that fuses the paired box gene 8 with the peroxisome proliferator-activated receptor (PPAR) gamma gene. This in turn acts as an oncogene.
187
What is the epidemiology of thyroid cancer?
- Most common endocrinological malignancy
- More common in women than in men
- Median age at diagnosis: 40-45
188
What are the presenting symptoms of thyroid cancer?
- Presence of risk factors (head and neck irradiation, female sex)
- Hoarseness
- Dyspnoea
- Dysphagia
189
What are the signs of thyroid cancer on examination?
- Palpable thyroid nodule
- Tracheal deviation
- Cervical lymphadenopathy
- Rapid leck enlargment
190
What are the investigations for thyroid cancer?
- TSH: normall
- Fine-needle biopsy: cytology suggests histological features
- Ultrasound, neck: nodule number/characteristics
- Laryngoscopy: May show ipsilateral paralysed vocal cord
191
What is a thyroid nodule?
An abnormal growth of thyroid cells that forms a lump within the thyroid gland.
- Vast majority are benign, small proportion do contain thyroid cancer
192
What is the aetiology of a thyroid nodule?
- Hashimoto's disease
- Hypothyroidism
- Thyroid Cancer
193
What is the epidemiology of a thyroid nodule?
- Common
| - By 60, 1/2 of all people have a thyroid nodule that can be found either through examination or with imaging
194
What are the presenting symptoms of a thyroid nodule?
- Often asymptomatic
- Patients may find thyroid nodules by noticing lump in neck while looking in mirror, buttoning collar.
- Neck, jaw, ear pain
- Difficulty breathing, swallowing or cause 'a tickle in the throat' if nodule large enough to compress windpipe
- Hoarseness- if nodule irritates laryngeal nerve
195
What are the signs of a thyroid nodule on examination?
- Thyroid gland and nodules within it move upon swallowing, masses external to thyroid do not
- Note size and presence of other palpable nodules
- Consistency must be noted- firmer the nodule, greater the concern for carcinoma
- Fixation suggests cellular invasion and malignancy
196
What are the investigations for a thyroid nodule?
- Thyroid ultrasound
- Thyroid fine needle aspiration biopsy
- Nuclear thyroid scans
- Molecular diagnostics
197
What is thyroiditis?
- General term that refers to inflammation of thyroid gland
198
What is the aetiology of thyroiditis?
- Caused by attack on thyroid, causing inflammation and damage to the thyroid cells
- Antibodies that attack the thyroid cause most types of thyroiditis
- Can be caused by infection
- Drugs such as interferon, amiodarone can damage cause thyroiditis by damaging thyroid cells
199
What is the epidemiology of thyroiditis?
- 25% of adults with T1DM have thyroiditis, about one half of whom have hypothyroidism
- Disease more common in children with Down syndrome or Turner syndrome
200
What are different types of thyroiditis?
- Hashimoto's thyroiditis
- de Quervain's or subacute thyroiditis
- Post-partum thyroiditis
- Silent or painless thyroiditis
- Drug-induced thyroiditis
- Radiation-induced thyroiditis
- Acute or infections thyroiditis
201
What are the presenting symptoms of thyroiditis Hashimoto's thyroiditis?
- Fatigue
- Weight gain
- Constipation
- Dry skin
- Depression
- Goitre
202
What are the presenting symptoms of de Quervain's thyroiditis?
- Anxiety
- Insomnia
- Heart palpitation
- Weight loss
- Irritability
203
What are the signs of Hashimoto's thyroiditis on examination?
- Puffy face and periorbital oedema typical of hypothyroid faces
- Cold, dry skin which may be round and scaly
- Peripheral oedema of hands and feet, typically nonpitting
- Thickened and brittle nails
- Hair loss involving the scalp, the lateral third of the eyebrows, possibly skin, genital and facial hair
- Bradycardia
- Elevated blood pressure
- Macroglossia
- Slow speech
- Ataxia
204
What are the investigations for thyroiditis?
- Lab tests to evaluate pt for elevated ESR, elevated thyroglobulin levels and depressed radioactive iodine intake
- Blood tests to determine kid of thyroiditis
- Biopsy
205
How is thyroiditis managed?
```
- Depends on type
Hashimoto's:
- Immediately start hormone replacement
- Bed rest
- NSAIDs
- Beta blockers to lower heart rate and reduce tremors
```
206
What are the possible complication of thyroiditis?
Increases risk of:
- Grave's
- Addison's
- T1DM
- Premature ovarian failure
- Lupus erythematosus
- Rheumatoid arthritis
207
What is the prognosis of thyroiditis?
- Transient periods of thyrotoxicosis can occur
| - Rarely, illness may progress to hyperthyroid Grave's disease
208
What is osteomalacia and rickets?
- Osteomalacia is a disorder of mineralisation of bone matrix ('osteoid')
- Rickets is a disorder of defective mineralisation of cartilage in the epiphyseal growth plates of children
209
What is the aetiology of osteomalacia?
Vitamin D deficiency:
- Lack of sunlight exposure. Dietary deficiency or malabsorption (small bowel disease e.g. coeliac disease/IBD, extensive bowel surgery, gastrectomy, pancreatic insufficiency) Decreased 25-hydroxylation of vitamin D (liver disease, anticonvulsants). Decreased 1a-hydroxylation (chronic kidney disease, hypoparathyroidism, mutations in the gene encoding (1a-hydroxylase) Vitamin D resistance (mutations int the vitamin D receptor gene)
Renal phosphate wasting:
- Fanconi's syndrome (phosphaturia, glycosuria, aminoa aciduria). Renal tubular acidosis (type 2). Hereditary hypophosphataemic rickets (X-linked or autosomal dominant). Tumour-induced osteomalacia
210
What is the epidemiology of osteomalacia?
Now uncommon in industrialised countries
| - More common in females
211
What are the presenting symptoms of osteomalacia?
- Bone pain (especially axial skeleton)
- Weakness
- Malaise
212
What are the signs of osteomalacia on examination?
- Bone tenderness
- Proximal muscle weakness
- Waddling gait
Signs of hypocalcaemia may be present:
- Troussaeu's sign: Inflamtion of sphygmomanometer cuff to above the systolic pressure for more than 3min causes the tetanic spasm of wrist and fingers
- Chvostek's sign: tapping over the facial nerve causes twitching of the ipsilateral facial muscles
213
What are the investigations for osteomalacia?
- Blood: reduced or normal Ca++, decreased phosphate, raised AlkPhos, decreased 25(OH)vitD, raised PTH, Check U&E's, ABG (pts with renal tubular acidosis have normal anion gap hyperchloraemic metabolic acidosis. Raised phosphate excretion
- Radiographs: may appear normal or show osteopenia. Looser's zones or pseudofractures in ribs, scapula, pubic rami or upper femur
- Bone biopsy after double tetracycline labelling: Tetracycline is deposited at the mineralisation front as a band. After 2 courses of tetracycline, the distance between bands is reduced in osteomalacia.
214
How is osteomalacia managed?
- Vit D and calcium replacement. Monitor 24h urinary calcium, serum calcium, phosphate, AlkPhos, PTH and vitamin D
- Treat the underlying cause (e.g. advice on diet and sunlight exposure
- X-link hypophosphataemia: Oral phosphate and 1,25 (Oh)2 vitamind D
215
What are the possible complications of osteomalacia?
- Bone deformities
- Hypocalcaemia may cause epileptic seizures
- Cardiac arrhythmias
- Hypocalcaemic tetany
- Depression
216
What is the prognosis of osteomalacia?
- Symptoms and radiological appearances improve with vitamin D treatment
- Bone deformities in children tend to be permanent
Year 3 SOFIA CONDITIONS
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