Endocrinology Flashcards
1
Q
What is the definition, aetiology and epidemiology of Acromegaly?
A
Acromegaly is the constellation signs and symptoms that are caused by hypersecretion of growth hormone (GH) in adults (if this happens before puberty it is known as gigantism). It is rare, incidence is 5 in 1,000,000.
Most commonly caused by GH-secreting pituitary adenoma. Rarely caused by GHRH (growth hormone releasing hormone) secretion, leading to somatotroph (cells in anterior pituitary that produce GH) hyperplasia, by hypothalamic ganglioneuroma, bronchial carcinoid or pancreatic tumours.
2
Q
What are the symptoms of Acromegaly?
A
Patient may present with a very gradual onset of symptoms (often only detectable on serial photographs).
• Patient may complain of rings and shoes becoming tight
• ↑sweating, headache and carpel tunnel syndrome
• Coarsening of facial features, soft tissue and skin changes.
• Joint pain and dysfunction
• Snoring
Other symptoms include:
• Hypoprolactinaemia (oligomenorrhoea, decreased libido, impotence)
• Fatigue (common)
• Hypertension and arrhythmias (common)
• Increased appetite, polyuria/polydypsia
More uncommon symptoms include:
• Symptoms of hypopituitarism due to compression of the adenohypophysis
• Visual field defects due to compression of optic chiasm
3
Q
What are the examination findings of Acromegaly?
A
Hands and feet are enlarged, with thick greasy skin.
Signs of carpal tunnel syndrome may be found.
Face looks characteristic, with prominent eyebrow ridge and cheeks, thick lips, gaps between teeth, large tongue and husky voice.
4
Q
What are the potential complications of Acromegaly?
A
CVS: Cardiomyopathy, hypertension
GI: Colonic polyps
Reproductive: hyperprolactinaemia
Metabolic: hypercalcaemia, hyperphosophataemia, renal stones, diabetes mellitus, hypertiglyceridaemia.
5
Q
How can Acromegaly be investigated?
A
A serum IGF-1 test (Insulin-like Growth Factor is secreted due to GH stimulation) will show elevated levels of IGF-1.
Oral glucose tolerance test can also be done; glucose suppresses GH release, if GH is still elevated, this confirms a diagnosis of acromegaly.
A pituitary CT or MRI can also be done to confirm the presence of a pituitary adenoma. If this is normal, can measure GHRH (Growth Hormone Releasing Hormone) - if elevated, points to a ectopic GH-releasing source.
6
Q
How is Acromegaly managed?
A
Surgical removal is the only curative treatment (trans-sphenoidal hypophysectomy). Radiation can be an adjunct to surgery.
If surgery cannot be performed or fails, a somatostatin analogue (such as octreotide) is indicated to suppress GH release.
Dopamine agonists (bromocriptine or cabergoline) also reduce GH secretion, and can be used in treatment. Has an important side-effect profile.
GH receptor antagonist can be used if developed resistance to somatostatin analogues.
7
Q
What is the definition of Adrenal Insufficiency?
A
Adrenal insufficiency is the deficiency of adrenocortical hormones (mineralocorticoids, glucocorticoids and androgens).
8
Q
What is the aetiology of Adrenal Insufficiency?
A
Primary causes (problem with endocrine organ itself) - called Addison’s disease include:
• Autoimmune destruction of the adrenal cortex (>70% of cases)
• Infections such as tuberculosis, meningococcal septicaemia, CMV (HIV patients), histoplasmosis
• Can be caused by infarction, and congenital (adrenoleukodystrophy)
Secondary causes include due to pituitary or hypothalamic disease.
The most common cause is iatrogenic - where cortisol production is suppressed due to long-term steroid use, leading to negative feedback on hypothalamic-pituitary-axis. This results in decreased CRH (corticotrophin releasing hormone) and decreased ACTH production.
9
Q
What are the clinical features of Adrenal Insufficiency?
A
Chronically presents with non-specific symptoms: dizziness, anorexia (causing weight loss), diarrhoea and vomiting (unknown reason), abdominal pain, lethargy, weakness and depression.
On examination:
• Postural hypotension
• Increased pigmentation (more noticeable in buccal mucosa, scars, skin creases, nails and pressure points) - this is absent in secondary causes (iatrogenic) as ACTH production is also dampened.
• Loss of body hair in women (due to androgen deficiency)
Can present with other autoimmune conditions such as vitiligo.
10
Q
What are the clinical features of Addisonian crisis?
A
Acute presentation (Addisonian crisis): Acute adrenal insufficiency with major haemodynamic collapse often precipitated by stress (e.g. infection or surgery). On examination: tachycardia, pale, cold, clammy, oliguria.
11
Q
What are the potential complications of Adrenal Insufficiency?
A
- Hyperkalaemia
* Death during Addisonian crisis.
12
Q
How can Adrenal insufficiency be investigated?
A
Start with a 9am serum cortisol test. If <110 nanomol/L, likely adrenal failure. If >550, likely normal response. If between, do a short synACTHen test.
Identify the cause:
• Autoantibodies (against 21-hydroxylase).
• Abdominal CT or MRI
Addisonian crisis:
• FBC (neutropenia)
• U&Es (↑urea, ↓Na+, ↑K+)
• ↑ESR and CRP
CXR can be used to identify cause.
13
Q
How is Adrenal insufficiency managed?
A
Chronic: Glucocorticoid replacement with hydrocortisone (three times a day) and mineralocorticoids with fludrocortisone. Hydrocortisone needs to be increased during acute illness or stress.
Give them a steroid warning card (says patient is on steroids), Medic-alert bracelet, emergency hydrocortisone ampule and patient education.
14
Q
What is the definition and epidemiology of carcinoid syndrome?
A
Carcinoid syndrome is a constellation of symptoms produced by the systemic release of humoral factors (biogenic amines, polypeptides, prostaglandins) from carcinoid tumours. They are very rare: annual incidence is 1 in 1,000,000. Asymptomatic carcinoid tumours are more likely, and are usually found after rectal biopsy or appendectomy.
15
Q
What are the clinical features of carcinoid syndrome?
A
A history of paroxysmal flushing, diarrhoea, crampy abdominal pain, wheeze, sweating and palpitations.
On examination: Note facial flushing, telangiectasia, and wheeze.
Cardiac murmurs such as Tricuspid stenosis and regurgitation or pulmonary stenosis is common because of serotonin and kinins leading to fibrosis of right-sided heart valves.
16
Q
How can Carcinoid syndrome be investigated?
A
Investigations
• 24-h urine collection: 5-HIAA levels (a metabolite of serotonin, false positive with high intake of certain fruits e.g. bananas and avocados)
• Blood: plasma chromogranin A and B
• Radioisotope scan: radiolabeled somatostatin analogue helps localise the tumour
17
Q
What is the definition and epidemiology of Cushing’s Syndrome?
A
Cushing’s syndrome is the syndrome associated with abnormally elevated levels of cortisol in the body. Cushing’s syndrome is very rare, affecting 2-4/1million. However, exogenous Cushing’s syndrome (due to excess steroid intake) is much more common.
18
Q
What is the aetiology of Cushing syndrome?
A
Causes can be broken down into ACTH dependent (80%) or independent (20%). ACTH dependent causes include:
• ACTH secreting Pituitary Adenoma (80%) - Cushing’s disease
• ACTH secreted from an ectopic tumour such as small-cell lung carcinoma (20%)
ACTH independent causes include:
• Adrenal adenoma (60%)
•Adrenal carcinoma (40%)
Exogenous Cushing’s syndrome due to excess steroid intake is much more common.
19
Q
What are the clinical features of Cushing’s Syndrome?
A
Patients present with increasing weight, fatigue muscle weakness, myalgia, easy bruising and poor wound healing. Oligo/amenorrhoea is a common complaint. Patient may also complain of depression or psychosis.
You may also notice that patient has glucose intolerance.
On examination:
• Red cheeks, moon face, intrascapular fat pads,
• Bruising, thin skin with red striae on abdomen.
• General thin arms and legs (lemon on sticks) with central obesity.
• Kyphosis
• Hirsutism, acne and frontal bolding.
• Hypertension and ankle oedema (due to excess mineralocorticoids)
• Pigmentation in ACTH-dependent cases.
20
Q
What are the potential complications of Cushing’s Syndrome?
A
Complications: Diabetes, osteoporosis, hypertension. Predisposition to infections.
21
Q
How is Cushing’s Syndrome investigated?
A
Women of child-baring age should have a pregnancy test when investigating hypercortisolism.
Blood tests may show hyperkalaemia or ↑glucose (due to glucose intolerance).
Urinary free cortisol (measured by 24h urine collection) and late-night salivary cortisol would be elevated. A Low-dose/overnight dexamethasone suppression test would suppress cortisol in a healthy patient, but not in a Cushing’s patient.
To discriminate between ACTH dependent or independent, measure plasma ACTH. If ↓, then CT or MRI the adrenal glands. If ↑ then perform a pituitary MRI. Also can perform inferior petrosal sinus sampling (if central:peripheral ACTH > 2:1, then confirmed pituitary is source). If lung cancer is suspected, then CXR, sputum cytology, bronchoscopy, CT scan.
22
Q
How is Cushing’s Syndrome managed?
A
In iatrogenic cases, discontinue or lower steroid use. Use steroid-sparing agent if possible.
Medical treatment is for pre-operative or if patient is unfit for surgery. Inhibit cortisol synthesis with metyrapone or ketaconazole.
Surgical treatments are gold-standard. A trans-sphenoidal adenoma resection for a pituitary adenoma. Adrenalectomy for adrenal adenoma/carcinoma. Remove ectopic tumour if possible.
23
Q
What is the prognosis of Cushing’s Syndrome?
A
If untreated, 5-year survival is 50%. Depression usually continues after successful treatment.
24
Q
What is the definition and epidemiology of Diabetes Insipidus?
A
Diabetes Insipidus is a disorder of inadequate secretion of, or insensitivity to vasopressin (ADH) leading to hypotonic polyuria. DI is fairly uncommon, and median age of onset is 24 years.
25
What is the aetiology and risk factors of Diabetes Insipidus?
It can either be cranial/central where the posterior pituitary fails to secrete the hormone, or nephrogenic where the collecting tubes are insensitive to vasopressin. This leads to less aquaporins inserted into the collecting tubes, and thus less water is retained, resulting in large volumes of hypoosmolar urine and polydipsia.
Risk Factors: Strong risk factors for central DI are any injury to posterior pituitary such as from surgery, tumour or trauma. For nephrogenic DI, lithium and AVP pathway mutations are strong risk factors.
26
What are the clinical features of Diabetes Insipidus?
Patient typically presents with polyuria, nocturia and polydipsia. Patient may also have non-specific signs of hypernatraemia such as restlessness, lethargy, spasticity and hyper-reflexia.
On examination, patient may have signs of dehydration such as dry mucous membranes, postural hypotension, reduced tissue turgor and tachycardia.
The patient may also present with signs of the cause, such as visual field defects.
27
How can Diabetes Insipidus be investigated?
A urine osmolarity test will show osmolarity is low (<300 mosmol/kg). Blood tests can show increased omsolarity of the blood, increased Na+ and Ca+. There may be decreased K+ in chronic nephrogenic DI.
A urine dipstick can be used to rule out diabetes mellitus.
A water deprivation test where water is restricted for 8 hours and plasma and urine osmolarity is measured over the 8h. Weigh the patient to monitor level of dehydration. Patients with DI will still have hypoosmolar urine.
Desmopressin (AVP) can be administered to differentiate between nephrogenic and central DI. Those with central DI will see a >50% increase in urine osmolarity, those with nephrongenic a <45% increase.
28
How is Diabetes Insipidus managed?
Central DI: Treat with desmopressin (a vasopressin analogue).
Nephrogenic DI: Try to treat the cause (i.e stop medication); Sodium restriction and protein restriction may help polyuria. Thiazide diuretics can help.
29
What is the prognosis of Diabetes Insipidus?
Variable depending on cause. Cranial DI may be transient following head trauma. Cure may be possible if cause is treated, such as removal of drugs, or tumour resection.
30
What are the causes of hyperthyroidism?
* Primary (abnormal thyroid) - Graves' Disease (75% of cases), Toxic multinodular goitre (2nd biggest cause), toxic thyroid nodule (adenoma), and drugs.
* Secondary (excess TSH) - pituitary adenoma secreting TSH, high HcG can also stimulate thyroid, thyroid hormone resistance syndrome (very rare) where pituitary is resistant to t3/t4.
* Subclinical - This is where, although TSH is suppressed, FT3 + FT4 is in normal range.
* Thyrotoxicosis without hyperthyroidism - due to large doses of levothyroxine or thyroiditis.
31
What is the definition and epidemiology of Graves' Disease?
Graves disease is an autoimmune condition resulting in hyperthyroidism. It is relatively common affecting 0.8/1000 women a year, with negligible incidence in men. It is the most common cause of hyperthyroidism in many countries.
32
What is the aetiology of Graves' Disease?
Thyroid hormone overproduction is a result of stimulation of TSH receptors in thyroid by TSH receptor antibodies. This causes an increased basal metabolic rate, and increased protein, carbohydrate and fat metabolism.
33
What are the symptoms of Grave's Disease?
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Patient's present with heat intolerance, sweating, palpitations, anxiety, irritability and a tremor.
Weight loss (despite a good appetite), diarrhoea and pruritus are also common.
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Females complain of menstrual abnormalities and reduced libido. Males complain of impotence.
Grave's orbitopathy is present in 25% of cases, with tobacco use being a strong risk factor. Patient's complain of blurred vision, diplopia, eye grittiness and eye protrusion.
34
What are the examination features of Graves' Disease?
The patient may be underweight, restless, sweaty, and have signs of other autoimmune diseases. Also notice pretibial myxoedema (raised pigmented orange-peel textured nodules or plaques on shins) and symmetrically enlarged smooth goitre.
Hands: Tremor, warm, moist, rapid or irregular pulse, onycholysis (nails dethatch from nailbed), clubbing and palmar erythema.
Eyes: May notice lid lag and lid retraction
35
What are the potential complications of Graves' Disease?
Thyrotoxic crisis, heart failure, osteoporosis, infertility.
36
How can Hyperthyroidism be investigated?
As with primary hyperthyroidism, blood tests will show supressed TSH, and elevated T3 and T4.
To differentiate between the causes of primary hyperparathyroidism (Plummer's disease [Toxic nodular goitre], Viral thyroiditis) perform radioactive iodine uptake test. In Grave's disease, notice elevated DIFFUSE uptake.
TSH receptor antibodies can also be detected, but is an expensive test.
37
How is Graves' Disease managed?
All patients with primary hyperthyroidism should be told about the three options:
1. Medical: Prolonged antithyroid drug (ATD) therapy, involving carbimazole/thiamazole or propylthiouracil (all work by inhibiting thyroid peroxidase and hormone synthesis). Block and replace regimens are when ATDs are prescribed as well as levothyroxine. Symptomatic therapy by beta-blockers such as propranolol or atenolol can be used to treat tremor, palpitations, tachycardia and anxiety. Patients told to look out for sore throat, fever etc. as agranulocytosis is an important side-effect.
2. Radioactive iodine: Must avoid pregnant women and young children for 4 months.
3. Surgery: Reserved for patients with large goitres causing upper-airway obstruction, and those who cannot take ATD, and are either pregnant or cannot take radioiodine due to exophthalmos. Complicated by: left recurrent laryngeal nerve, which if cut can cause speech difficulty; hypothyroidism and hypoparathyroidism.
38
What is the definition of Hyperparathyroidism?
Hyperparathyroidism is when there is increased PTH secretion unrelated to the plasma calcium concentration.
39
What is the aetiology of hyperparathyroidism?
Primary hyperparathyroidism is caused by adenomas or hyperplasia (98%), rarely parathyroid carcinomas (2%).
Secondary hyperparathyroidism is when there is increased secretion of PTH secondary to hypocalcaemia. Often caused by chronic renal failure or vitamin D deficiency.
Tertiary is autonomous PTH secretion following chronic secondary hyperparathyroidism.
40
What are the clinical features of hyperparathyroidism?
Primary: Many patients have mild hypercalcaemia and are asymptomatic. A history of osteoporosis or osteopenia is common, as well as nephrolithiasis (as most kidney stones are of calcium phosphate).
Other symptoms of hypercalcaemia can be remembered with: Stones, Bones, Groans, Psychic Moans and Thrones. Stones = kidney stones. Bones = bone pain and osteoporosis. Groans = Abdominal pain, nausea, constipation. Psychic moans = depression, lethargy, fatigue, confusion, anxiety. Thrones = polyuria and polydipsia.
Secondary: May present with symptoms and signs of hypocalcaemia - see Osteomalacia and/or the underlying cause (chronic renal failure, or vitamin D deficiency).
41
What are the potential complications of hyperparathyroidism?
Hypercalcaemia. Osteitis fibrosis cystica in secondary hyperparathyroidism due to renal failure.
42
How can hyperparathyroidism be investigated?
Bloods:
• Serum calcium is ↑ in primary and ↓ in secondary.
• A serum PTH can be measured with immunochemical assays, which will be elevated.
• Vitamin D may be low in someone with secondary hyperparathyroidism.
• ↑ Alkaline Phosphatase due to increase bone turnover.
Patient may also have hyperchloremic due to PTH inhibition of bicarbonate reabsorption.
A renal ultrasound can be used to look at renal calculi. A DXA of (lumbar spine, hip and forearm) should be completed to assess extent of disease.
43
How is hyperparathyroidism managed?
Acute hypercalcaemia: I.V fluids.
Primary hyperparathyroidism: 1st line treatment is a parathyroidectomy (subtotal, or rarely total) which tends to be curative. Monitor serum calcium and creatinine. Bisphosphonate can be given if osteoporosis is present.
Secondary hyperparathyroidism: Treat underlying renal failure or vitamin D supplements.
44
What is the definition of female hypogonadism?
Female hypogonadism is characterised by ovarian failure or impairment of function.
45
What is the aetiology of female hypogonadism?
Primary hypogonadism is due to gonadal dysgenesis (Turner's syndrome, FMR1 mutation and other chromosomal abnormalities) or gonadal damage (Autoimmune or iatrogenic causes such as radiation, surgery, chemotherapy).
Secondary hypogonadism can be due to problems with:
• Function: stress, weight loss, excessive exercise, and eating disorders.
• Pituitary/hypothalamic lesions: Pituitary adenoma, craniopharyngeomas, heamochromatosis.
• Hyperprolactinaemia: Prolactinomas or tumours causing pituitary stalk compression.
• Congenital GnRH deficiency: Kallman's syndrome, idiopathic.
• PCOS? (not sure if PCOS is a cause of hypogonadism, and if so primary or secondary)
46
What are the symptoms of female hypogonadism?
Symptoms of oestrogen deficiency include night sweats, hot flushes, vaginal dryness, and dyspaeunia (painful intercourse), decreased libido, infertility.
Patient would also have symptoms of underlying cause e.g. headaches, or weight changes.
47
What may be the examination features of female hypogonadism?
On examination:
• If pre-pubertal: delayed puberty (primary amenorrhoea, absent breast development, no secondary sexual characteristics). Also may have eunuchoid proportions (long legs and arms for height span).
• Regression of secondary sexual characteristics (loss of pubic hair, breast atrophy)
• Signs of underlying cause such as visual fields defect (pituitary), anosmia (Kleinfelter's), and other autoimmune conditions.
48
What are the potential complications of female hypogonadism?
Infertility. Osteoporosis. Ischaemic heart disease.
49
How can female hypogonadism be investigated?
Bloods:
• ↓ oestradiol
• ↑ FSH and LH in primary (due to decreased negative feedback as no oestradiol or inhibin produced by ovaries), but ↓ in secondary (definition of secondary).
Investigate the aetiology for primary:
• Karyotype (to look for chromosomal abnormalities).
• Pelvic imaging (US or MRI) in patients with primary amenorrhoea, to demonstrate the presence or absence of the uterus and vagina or absence of obstruction.
• Screening for mutations such as the FMRI1 gene.
Or Investigate the aetiology for secondary:
• Pituitary function tests (9 a.m. cortisol, TFTs, prolactin, visual field testing, hypothalamic-pituitary MRI, smell tests for anosmia)
• For Turner's and autoimmune assays.
50
What is the definition of male hypogonadism?
Male hypogonadism is a syndrome of reduced testosterone production, sperm production or both.
51
What is the aetiology of male hypogonadism?
Primary hypogonadism can be caused by:
• Gonadal dysgenesis - Klinefelter's syndrome (XXY), cryptorchidism (undescended testes).
• Gonadal damage - Infection (e.g. mumps), torsion, trauma, autoimmune and iatrogenic (chemotherapy, surgery, radiation).
• Defects in enzymes involved in testosterone synthesis or myotonic dystrophy.
Secondary hypogonadism can be caused by:
• Pituitary/hypothalamic lesions
• GnRH deficiency (Kallmann's syndrome or idiopathic)
• Hyperprolactinaemia
• Systemic/chronic diseases
• Genetic mutations
• Prader-Willi syndrome and Laurence-Moon-Biedl syndrome.
52
What are the symptoms of male hypogonadism?
Children may present with delayed puberty.
Adolescents and adults tend to present with decreased libido, impotence and infertility. A loss of spontaneous morning erections is strongly indicative of testosterone deficiency.
Patient may also present with symptoms of underlying cause such as those from Klinefelter's syndrome: intellectual dysfunction and social behavioural problems.
53
What are the examination features of male hypogonadism?
Pre-pubertal hypogonadism presents with signs of delayed puberty: high-pitched voice, decreased pubic/axillary/facial hair, small or undescended testes (measure using Prader's orchidometer), gynaecomastia, eunuchoid proportions (arm span > height).
Post-pubertal hypogonadism commonly presents with gynaecomastia and decreased pubic/axillary/facial hair, and less commonly with soft and small testes, and micropenis.
Also may notice features of underlying condition such as anosmia in Kallmann's syndrome, visual field defects due to pituitary tumour etc.
54
What are the potential complications of male hypogonadism?
Infertility, osteoporosis and range of others if due to chromosomal abnormalities.
55
How can male hypogonadism be investigated?
Begin with serum total testosterone to diagnose hypogonadism. A FBC also may show normocytic anaemia (as testosterone promotes erythropoiesis). Also measure LH and FSH to differentiate between primary and secondary (↑ LH/FSH in primary, ↓ in secondary).
Investigating primary: Karyotyping to confirm Klinefelter's Syndrome.
Investigating secondary: Pituitary function tests (9 a.m. cortisol, TFTs, prolactin), MRI of hypothalamic pituitary area.
56
What is the definition and epidemiology of hypothyroidism?
Hypothyroidism is the clinical syndrome resulting from the insufficient secretion of thyroid hormones. Affects up to 2% of adults and women more than men (6:1) .
57
What is the aetiology of hypothyroidism?
Primary causes (95%) include:
• Autoimmune (Hashimoto's) thyroiditis (most common cause, affecting women up to 9x more).
• Iatrogenic (post-surgery, radioiodine, medication for hyperthyroidism)
• Severe iodine deficiency (most common cause worldwide) or iodine excess (Wolff-Chaikoff effect)
• Thyroiditis (De Quervain's)
• Congenital: thyroid dysgenesis
• Inherited defects in thyroid hormone biosynthesis
Secondary (5%) causes are pituitary or hypothalamic disease e.g. tumours.
58
What are the symptoms of hypothyroidism?
A history of thyroid surgery or radioiodine surgery strongly points to hypothyroidism.
Onset is usually insidious. Patients complain of cold intolerance, lethargy, weight gain, constipation, dry skin, hair loss, hoarse voice. Can also complain of mental slowness, depression, dementia, cramps, ataxia and paraesthesia.
Females may experience menstrual disturbances (irregular cycles, menorrhagia).
Personal or family history of other autoimmune conditions can point to Hashimoto's.
59
What are the examination features of hypothyroidism?
Note bradycardia and cold hands. Pale puffy face, goitre, oedema, dry skin, vitiligo. Also notice pericardial or pleural effusions. The patient may also have ascites, and have slow relaxation of reflexes, and signs of carpal tunnel syndrome.
60
What are the potential 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).
61
How can hypothyroidism be investigated?
Blood: TFTs (Thyroid Function Test) - Primary: ↓ T4/T3 and ↑ TSH. Secondary: ↓ T4/T3 and ↓ or inappropriately normal TSH.
FBC may show normocytic anaemia
U&Es may show ↓ Na.
Cholesterol may be increased.
In suspected secondary cases: pituitary function tests, MRI and visual field testing.
62
What is the management of hypothyroidism?
Chronic: Levothyroxine (synthetic T4) 20-200ug a day. Rule out adrenal insufficiency and treat before starting thyroid hormone replacement to avoid Addisonian crisis.
Myxoedema coma: Give oxygen, rewarming, rehydration, I.V liothyroxine or T4, IV hydrocortisone (in case hypothyroidism is secondary to hypopituitarism). After stable, treat the underlying disorder e.g. infection. Myxoedema coma has a mortality of up to 80%.
63
Define osteoporosis
Osteoporosis is defined by a reduced bone density of <2.5 standard deviations below peak bone mass by healthy adults (T-score), resulting in bone fragility and increased fracture risk. It is common. In >50 year olds, 1/3 of women and 1/12 of men have osteoporosis. It is more common in caucasians than afro-carribeans.
64
What is the aetiology of osteoporosis?
Primary causes include: idiopathic (<50 years), and post-menopausal.
Secondary causes include:
• Malignancy: myeloma, metastatic carcinoma
• Endocrine: Cushing's, thyrotoxicosis, primary hyperparathyroidism, hypogonadism.
• Drugs: corticosteroids, heparin.
• Rheumatologic: Rheumatoid arthritis, ankylosing spondylitis.
• Gastrointestinal: Malabsorption syndromes, liver disease, anorexia.
65
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.
66
What are the clinical features of osteoporosis?
* Femoral neck fractures (commonly after minimal trauma) - severe pain with leg shortened and externally rotated.
* Vertebral fractures (on examination loss of height, kyphosis, vertebral tenderness)
* Colle's fracture (from falling on outstretched hand).
* May also complain of back pain.
67
How can osteoporosis be investigated?
DXA scan (tends to be of hip), producing a T-score of 30% loss in density is needed before it shows as radiolucency. However, may find biconcave vertebrae and crush fractures.
68
What is the definition, epidemiology and aetiology of Paget's Disease?
Is a disease characterised by excessive bone remodelling at one or more sites, resulting in bone that is structurally disorganised. It is common in older age, affecting 3% of all >50 year-olds.
Unknown aetiology. Genetic factors and viral infection may play a role.
69
What are the clinical features of Paget's Disease?
A family history is strongly associated with the condition. Most of the time, patients are asymptomatic.
Patient may also complain of insidious onset pain aggravated by weight bearing and movement. Headaches, deafness and increasing skull size.
On examination:
• You may find bitemporal enlargement of the skull with frontal bossing.
• Spinal kyphosis
• Anterolateral bowing of the femur, tibia or forearm.
• Skin over bone may be warm (as a result of increased vascularity).
• Sensorineural deafness (due to compression of Vestibulocochlear nerve).
70
How can Paget's Disease be investigated?
* Bloods: ↑ Alkaline Phosphate, normal Ca2+ and PO43-.
* Bone radiographs show enlarged, deformed bones with mixed lytic/sclerotic appearance.
* Bone scan may reveal areas involved.
* Bone reabsorption markers such as urine hydoxyproline.
71
What is the definition and epidemiology of pheochromocytoma?
A pheochromocytoma is a catecholamine-producing tumour that usually arises from chromaffin cells of the adrenal medulla, but are extra-adrenal in about 10% of cases (paragangliomas). 10% are bilateral and 10% are malignant. In general they are quite rare.
72
What is the aetiology of a pheochromocytoma?
Cause of sporadic cases unknown. May be familial in 30% of patients.
73
What are the clinical features of a pheochromocytoma?
Patient presents with paroxysmal episodes of headaches, sweating.
Cardiovascular symptoms include: palpitations, chest pain, dyspnoea.
GI symptoms: epigastric pain, nausea, constipation.
Neuro/psychiatric: Weakness, tremor, anxiety.
Patient is likely to have hypertension. Also postural hypotension (due to loss of plasma volume). Pallor, tachycardia, fever and weight loss.
74
How can a pheochromocytoma be investigated?
* 24-hr urine collection for measurement of catecholamines (adrenaline, noradrenaline and dopamine), fractionated metanephrines and creatinine (to ensure adequate collection).
* Serum free metanephrines and normetanephrines (breakdown products of adrenaline and noradrenaline) is offered to patients with a high risk (familial cases) or positive urine collection, as is very sensitive, but not very specific (still 85%, but as to not misdiagnose).
Genetic testing may be appropriate, looking for familial diseases or genetic disorders such as neurofibromatosis.
Tumour can be localised with CT or MRI scan.
75
What is the definition and epidemiology of T1DM?
T1DM is a metabolic hyperglycaemic condition caused by absolute insufficiency of insulin production. It is one of the most common chronic diseases in childhood, with a prevalence of 0.25% in the UK. There is considerable Geographic variation in the incidence.
76
What is the aetiology of T1DM?
Interactions between genes imparting susceptibility and environmental triggers leads to the autoimmune damage of β-cells. There is a role of T-cells in the pathogenesis of T1DM. Over time, effector cells increases, but regulatory cells decrease - leading to the destruction of β-cells. Although many genes are responsible for the risk of T1DM, the HLA-DR3 and DR4 alleles pose a significant risk, while DR2 is protective.
77
What are the symptoms of T1DM?
Often of juvenile onset (<30 years). Polyuria/nocturia, polydipsia, tiredness and weight loss are key features. Frequent thrush or UTIs may be a sign of DM.
Signs include dehydration, cachexia, hyperventilation due to metabolic acidosis, smelling of ketones, glycosuria and ketonuria.
A patient who has history of other autoimmune conditions, is more likely to suffer from Type 1 DM.
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How should you examine someone with T1DM?
Perform a fundoscopy to look for diabetic retinopathy, examine the feet for neuropathy, and measure blood pressure.
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What are the potential complications of T1DM?
* Diabetic Ketoacidosis
* Microvascular complications: retinopathy, neuropathy and nephropathy.
* Macrovascular complications: Peripheral vascular disease, Ischaemic heart disease, Stroke/TIA.
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How can T1DM be investigated?
Bloods:
• A fasting blood glucose >7mmol/l or a random blood glucose >11mmol/l is indicative of DM. Two positive results are needed before diagnosis.
• HbA1c indicates glycaemic levels over the previous 2-3 months.
Urine: Ketones in the presence of hyperglycaemia points to Type 1 DM.
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How is T1DM managed?
Aim of management in T1DM patient is glycaemic control. This is achieved by:
• Patient education - involve diabetic nurse specialist and dieticians.
• Basal-bolus insulin: Provide one long-acting insulin (isophane, glargine, detemir) for injection once daily. And provide short-acting insulin (Lispro, aspart, glulisine) for injection three times daily before each meal.
• Insulin pumps may give slightly better glycaemic control. However, they are costly and cumbersome and if malfunctioning can cause DKA.
• Motivated patients can attend DAFNE courses (Dose Adjustment For Normal Eating) to learn how to calculate their carbohydrate intake.
• Monitoring their symptoms and glucose levels with regular finger prick tests by the patient. Also by monitoring their HbA1c levels.
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How is a hypoglycaemic event treated?
A major worry for patients is the prospect of hypoglycaemic events. There can be treated by:
• If conscious: 50g oral glucose (e.g. in form of Lucozade or dextrose tablets) followed by a startchy snack. Advised against driving for 45 minutes.
• If unconscious: 50ml of 50% glucose IV or 1 mg glucagon IM.
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What is the prognosis of T1DM?
Depends on early detection, and compliance with regimen and screening. Vascular disease and renal failure are major causes of increased morbidity and mortality.
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What is the definition and epidemiology of T2DM?
Diabetes Mellitus Type 2 is a disease characterised by peripheral resistance to insulin with impaired insulin secretion leading to a state of chronic hyperglycaemia. It affects 5-10% of the population. People of Asian, African and Hispanic descent are at greater risk. The incidence has increased over the last 20 years, alongside the incidence of obesity.
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What is the aetiology of T2DM?
It is a multi-factorial disease caused by genetic interactions with intrauterine and adult environment.
• Genetic: Monozygotic twins have a 90% concordance rate. Life-time risk for first-degree relative of diabetes to is 5-10x higher.
• Obesity: Increased plasma free fatty acid levels and adipokines secreted by adipocytes contribute to insulin resistance.
• Secondary diabetes due to pancreatic diseases, endocrinopthies and drugs (e.g. corticosteroids, atypical antipsychotics, protease inhibitors)
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What are the clinical features of T2DM?
Type 2 Diabetes Mellitus can often be asymptomatic and only detected incidentally.
Patients commonly visit their doctors for candidal infections, skin infections (cellulitis) and urinary tract infections. Diabetes is diagnosed because the patient has strong risk factors (obesity, ethnicity etc.) and a blood test is done.
Patients also commonly present with fatigue, blurred vision and paraesthesias. Uncommonly polyuria and polydipsia, nocturia, polyphagia.
On examination, may be obese (BMI >30)
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How should you examine a patient with T2DM?
* Measure BMI, waist circumference and blood pressure.
* Look for signs of Diabetic foot: Ischaemic and neuropathic signs (Dry skin, reduced subcutaneous tissue, corns and calluses, ulceration, gangrene.
* Look for skin changes (rare) such as Necrobiosis lipoidica diabticorum (well-demarcated plaques on the shins or arms with shiny atrophic surface and red-brown edges) and Acanthosis nigricans.
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What are the potential complications of T2DM?
* Hyperosmolar Hyperglycaemic State
* Microvascular complications: retinopathy, neuropathy and nephropathy.
* Macrovascular complications: Peripheral vascular disease, Ischaemic heart disease, Stroke/TIA.
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How can T2DM be investigated?
* A fasting blood glucose >7mmol/l or a random blood glucose >11mmol/l is indicative of DM. Two positive results are needed before diagnosis.
* Monitor HbA1c, U&Es, lipid profile, estimated GFR and spot urine albumin : creatinine ratio (to detect microalbuminuria)
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What are the four aspects of T2DM management?
There are four aspects of T2DM that need to be treated and monitored:
1. Blood Pressure
2. Dyslipidaemia
3. Weight
4. Glycaemic control
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How is T2DM managed apart from glycaemic control?
Blood Pressure
Patients with diabetes are 2x as likely to die of stroke or MI than those without. See Blood Pressure? Combination treatment is often required to reach BP goals. Thiazide diuretics, calcium-channel blocker, an ACE-inhibitors or angiotensin-II receptor antagonist.
Lipid Control
Prescribe statins such as simvastatin. Also lifestyle and dietary changes can be beneficial for lipid profile.
Weight
Weight can be controlled or reduced with changes in diet as well as lifestyle changes such as increased physical activity. Drugs such as Orlistat or Rimonabant may be used.
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How is glycaemic control T2DM obtained?
1. Start with lifestyle measures and put patient on metformin. If HbA1c is not at goal by three months:
2. Add sulphonylurea such as glicazide and glimepride (insulin seragogues which block the ATP sensitive potassium channel on β-cells. This leads to depolarisation of the cell before insulin is released. It is used in lean patients where diet alone has not succeeded. Hypoglycaemia and weight gain are side effects). If HbA1c not at target after three months:
3. Replace sulphonylurea with basal insulin (glargine, detemir). If HbA1c is not improved by 3 months:
4. Add premeal rapid-acting insulin
If weight loss is a major concern, replace sulphonylurea with GLP-1 agonist such as exanatide.
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What complication screening measures need to be done for a patient with T2DM?
* Retinopathy: regular digital retinal photography
* Nephropathy: monitor U&Es and estimated GFR using MDRD calculator, spot urine analysis, BP control, ACEi, monitor K+.
* Neuropathy: regular examination and inspection of feet, joint vibration, foot hygiene.
* Vascular disease: regular examination of foot pulses.
* Diabetic foot: educate to examine feet regularly. Diabetic footwear.
* Cardiovascular risk factors: Lose weight, exercise, stop smoking, BP control.
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What is the prognosis of T2DM?
Diabetes increases the likelihood of major cardiovascular events and death, but the increased risk is variable across patients depending on age at diabetes onset, glucose control, BP control, lipid control, tobacco control, renal function, and other factors. When diabetes is diagnosed at age 40, men lose an average of 5.8 years of life, and women lose an average of 6.8 years of life.
The United Kingdom Prospective Diabetes Study (UKPDS) showed that intensive therapy to achieve lower levels of glycaemia decreased the risk of development and progression of diabetic microvascular complications. The 10-year post-trial monitoring data from the UKPDS show that early intensive glucose control, decreased the risk for myocardial infarction and all-cause mortality.
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Define Diabetic Keto-Acidosis
Diabetic ketoacidosis (DKA) is 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. DKA involves a triad of hyperglycaemia, ketosis and acidosis. It is the most common acute complication of diabetes mellitus.
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What are the clinical features of DKA?
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Symptoms of DKA include:
• Excessive thirst and frequent urination
• Weakness
• Nausea and vomiting
• Abdominal pain
• Confusion
```
On examination, may notice signs of volume depletion such as poor skin turgor, dry mucous membranes, tachycardia and hypotension. Also may notice Kussmaul breathing (rapid and deep due to acidosis) as well as fruity breath and altered mental status.
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How can DKA be investigated?
Patients with suspected DKA:
• Plasma glucose usually>13.9mmol/L
• ABG showing metabolic acidosis with high anion gap.
• Urinalysis positive for glucose and ketones.
• Serum urea and creatinine usually increased from dehydration
• CXR to look for infections
• ECG to look for ischaemic changes.
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What is the definition and epidemiology of Hyperosmolar Hyperglycaemic Syndrome?
HHS is characterised by profound hyperglycaemia and hyperosmolar serum in the absence of significant ketoacidosis. HHS is seen more commonly in older people, and predominantly affecting people with type 2 diabetes.
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What is the aetiology of HHS?
Infections (commonly UTIs or pneumonias) are a major precipitating factor. The trigger can also be an acute illness such as a cerebrovascular incident or myocardial infarction.
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What are the clinical features of HHS?
Patients present with confusion or altered mental status, coma is rare. Patients also present with polyuria and polydipsia, as well as weight loss and weakness and seizures.
On emanation patient has signs of extreme dehydration such as dry mucous membranes, pour skin turgor, tachycardia, and hypotension.
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How can HHS be differentiated from DKA?
Main differential is with DKA.
• In DKA, patients are often younger and have type 1 diabetes, where as in HHS, patients are often older and have type 2 diabetes.
• Abdominal pain is not a feature of HHS but is a common complain in DKA
• In DKA, the patient is acidotic with a pH of <7.3, while in HHS, they are not usually acidotic.
• In DKA, there is an anion gap as well as ketones in urine, this is not a feature of HHS because there is enough insulin to prevent ketogenesis.
On the other hand, HHS and DKA are similar in that they cause an increased serum osmolarity due to hyperglycaemia.
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What is the definition and epidemiology of PCOS?
Polycystic Ovarian Syndrome includes symptoms of hyperandrogenism, oligomenorrhoea/amenorrhoea and polycystic ovarian morphology on ultrasound. PCOS is the most common cause of infertility (and hirsutism) in women, affecting 6-8% of women.
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What is the aetiology of PCOS?
Caused by environmental factors (e.g. related to diet and the development of obesity) and genetic variants (genes regulating gonadotrophin, insulin, and androgen synthesis and action, weight and energy regulation) may influence development of PCOS.
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What are the clinical features of PCOS?
Symptoms start at the time of puberty, however may be masked if on contraceptive pill. These symptoms include:
• Menstrual irregularity (oligomenorrhoea, and amenorrhoea), dysfunctional urine bleeding, infertility.
• Hyperandrogenism which presents as hirsutism, male-pattern hair loss and acne.
On examination: Notice hirsutism, male pattern hair-loss and acne. Many patients also tend to be obese. As insulin resistance and hyperinsulinaemia is a strongly associated condition, patient may show Acanthosis nigricans and have hypertension.
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How can PCOS be investigated?
Bloods:
• Serum free testosterone, androstenedione and DHEA-S are increased.
• ↑LH and ↑LH:FSH ratio (>3)
• ↓ SHBG (Sex Hormone Binding Globulin)
• A glucose tolerance test or HbA1c or fasting glucose test may show abnormalities in line with T2DM.
Tests for exclusion:
• Serum prolactin (as hyperprolactinaemia presents with oligo/amenorrhoea)
• TFT (as hyper/hypothyroidism can also present with menstrual abnormalities)
• Serum 17OH-Progesterone which is elevated in congenital adrenal hyperplasia (21-hydroxylase deficiency) which is a rare but more serious cause of virilisation and hirsutism.
Transvaginal Ultrasound may show (75% of PCOS patients, but also abnormal in 25% of non-PCOS patients): ≥12 follicles in each ovary, measuring 2-9mm and/or ↑ovarian volume >10ml.
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What is the definition and epidemiology of Primary Hyperaldosteronism?
Characterised by autonomous aldosterone overproduction from the adrenal gland with subsequent suppression of renin-angiotensin system. Not common, only 1-2% of hypertensive patients have it.
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What is the aetiology of Primary Hyperaldosteronism?
Excess aldosterone due to adrenal adenoma (70%) is called Conn's syndrome. Other causes include hyperplasia of adrenal cortex (30%) and rarely glucocorticoid-suppressible hyperaldosteronism or aldosterone producing adrenal carcinoma.
[Excess aldosterone results in ↑Na and water retention causing hypertension; ↑K loss and hypokalaemia, and suppression of renin because of NaCl retention.]
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What are the clinical features of Primary Hyperaldosteronism?
Patient is usually asymptomatic but has hypertension and may have a family history of primary hyperaldosteronism or early hypertension.
Patient may also have symptoms of hypokalaemia:
• Muscle weakness
• Polyuria and polydipsia (nephrogenic diabetes insipidus secondary to hypokalaemia)
• Paraesthesia
• Tetany
On examination: Patient may have signs of hypertension and complications of hypertension (e.g. retinopathy).
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How can Primary Hyperaldosteronism be investigated?
Routine blood tests show ↓K (or normal) in serum with normal Na+ in serum (due to parallel ↑ of water in blood).
Blood tests will also show ↑plasma aldosterone : plasma renin ratio. Antihypertensive must be stopped for test (6 weeks for spironolactone, 2 weeks for others).
Other tests:
• Oral salt loading: Failure of aldosterone suppression following a sodium load confirms primary hyperaldosteronism.
• Postural test: Plasma aldosterone, renin activity and cortisol are measured with patient lying down at 8 a.m. The tests are repeated after 4h of being upright (at 12 noon). In adenomas (which are mostly ACTH-sensitive) aldosterone secretion decreases from 8-12. In bilateral adrenal hyperplasia, adrenals respond to standing posture by increased renin and this aldosterone secretion.
• CT or MRI of the abdomen to visualise the adrenals.
• Bilateral adrenal vein catheterization allows distinction between Conn's syndrome and bilateral adrenal hyperplasia by measuring adrenal vein aldosterone levels.
Radio-labelled cholesterol scanning: Unilateral uptake in adrenal adenomas and bilateral in bilateral adrenal hyperplasia's.
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How is Primary Hyperaldosteronism managed?
Bilateral adrenal hyperplasia: Spironolactone (an aldosterone receptor antagonist). Change to eplerenone or amiloride if needed. Monitor serum potassium and creatinine, and BP. ACEi and calcium channel blockers may be needed to be added. It can take 4-8 weeks for the hypertension to respond.
Conn's Syndrome: Adrenalectomy (laparoscopically for best results).
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What is the prognosis of Primary Hyperaldosteronism?
Surgery usually cures hypertension in younger patients (50%), and makes treatment for amenable in those not cured (usually elderly or with long-standing hypertension).
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What is the definition and epidemiology of SIADH?
Syndrome of Inappropriate ADH is a syndrome characterised by continued secretion of ADH despite absence of normal stimuli (i.e. ↑serum osmolarity or blood volume). Hyponatreamia is the most common electrolyte imbalance seen in hospitals. <50% of all severe hyponatraemia are due to SIADH.
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What are the causes of SIADH?
* Brain: haemorrhage/thrombosis, meningitis, abscess, trauma, tumour, Guillain-Barré syndrome (these cause neurohypophysial dysfunction)
* Lungs: pneumonia, TB, abscess, aspergillosis, small cell carcinoma.
* Tumours: Small cell lung cancer, lymphoma, leukaemia, pancreatic, prostate, mesothelioma, sarcoma, thyoma. It may be caused by ectopic ADH secretion.
* Drugs: Vincristine, opiates, carbamazepine, chlorpropamide.
* Metabolic: Porphyria, alcohol withdrawal.
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What are the clinical features of SIADH?
Patients present with symptoms of hyponatraemia:
• Mild hyponatraemia may be asymptomatic
• May present with headache, nausea/vomiting, muscle cramps/weakness, irritability, confusion, drowsiness, convulsions and coma.
May also have symptoms of underlying cause.
On examination: Severe hyponatraemia may elicit ↓reflexes and extensor plantar reflexes.
Importantly hyponatraemia in SIAD is not due to ↓Na, but instead of ↑body water. This means there needs to be absence of hypovolemia signs. Patients with tachycardia, orthostatic hypotension, dry mucous membranes, and poor skin turgor are likely to have other causes hyponatraemia.
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How can SIADH be investigated?
Bloods:
• Serum Na will be decreased as well as Serum osmolarity.
• Creatinine (to assess renal function), glucose and lipids and proteins should be measured (to exclude psuedohyponatraemia seen with ↑proteins or lipids). TFTs to exclude hypothyroidism) and short synACHTen test to exclude adrenal insufficiency
Urine: A ↑urine osmolarity with ↑Na in urine coupled with ↓plasma osmolarity and Na, in the absence of hypovolaemia/hypotension, oedema, renal failure, adrenal insufficiency and hypothyroidism is needed in the diagnosis of SIADH.
Investigations to identify underlying cause: CXR, CT chest/abdomen/pelvis, MRI/CT head.
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How is SIADH managed?
Treat the underlying cause.
Water restriction (0.5-1L /day). If ineffective, give demeclocycline (decreases responsiveness of collecting tubules to ADH). Vasopressin (V2) receptor antagonists such as tolvaptan are likely to be useful in moderate chronic hyponatraemia and if water restriction is insufficient.
In severe cases (seizures and reduced consciousness), give slow IV hypertonic 3% saline to increase Na.
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What is the prognosis of SIADH?
High mortality and morbidity with [Na+] <110mmol/L.
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What are the different types of thyroid cancer?
Thyroid cancer is the most common endocrinology malignancy and can be (in order of incidence):
1. Papillary (60%) - differentiated follicular cells. Often in younger patients. Can spread to lymph nodes and lung.
2. Follicular (<25%) - differentiated follicular cells. Occur in middle-age and spreads early via blood (bone, lungs). Tends to be well differentiated.
3. Medullary (5%) - parafollicular cells. Sporadic or part of MEN syndrome. May produce calcitonin which can be used as a tumour marker.
4. Anaplastic (rare) - undifferentiated follicular cells. Occurs in elderly and poor response to treatment.
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What are the risk factors for thyroid cancer?
radiation exposure (e.g. from treatment of previous malignancy) and female sex, as well as certain genetic conditions.
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What are the clinical features of thyroid cancer?
A thyroid tumour tends to be fairly asymptomatic, but noticed as a lump on the neck which has grown over time. Uncommonly, the patient may complain of:
• Hoarseness (due to laryngeal nerve involvement)
• Dysphagia (due to oesophageal pressure)
• Dyspnoea (due to tracheal pressure)/
On examination: Notice a palpable thyroid nodule that may not be easy to move?. This may be a single nodule, or may be part of a multinodular goitre.
You may also note cervical lymphadenopathy which suggests neck metastasis.
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How can thyroid cancer be investigated?
1st order investigations:
• TSH screening. A normal (unsuppressed) result alongside a nodule indicates cancer. A malignancy in a hyperfunctioning nodule is very rare.
○ If abnormal, measure T4 and T3 to see if nodule is causing hyperthyroidism.
• Fine-needle biopsy may show histological features that confirm malignancy.
A neck ultrasound can be used to ascertain the characteristics of the nodule e.g. size, solid/cystic components.
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What are the definitions and epidemiology of Osteomalacia and Rickets?
Osteomalacia is a disorder of bone matrix mineralisation (decreased ratio of bone mineral to matrix). Rickets is a disorder of defective mineralisation of cartilage in the epiphyseal growth plates of children. They are now uncommon in industrialised countries, but affect females more.
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What is the aetiology of Osteomalacia/Rickets?
They are caused by vitamin D deficiency (which leads to reduced phosphate absorption), which can be secondary to:
• Reduced sunlight exposure (most common cause in western world)
• Dietary deficiency or malabsorption (small bowel disease e.g. coeliac, IBD, extensive surgery etc.)
• Reduced 25-hydroxylation of vitamin D due to liver disease or anticonvulsants.
• Reduced 1α-hydroxylation due to chronic kidney disease, hypoparathyroidism and genetic mutations.
• Vitamin D resistance due to mutations in the vitamin D receptor gene.
or renal phosphate wasting, which can be secondary to:
• Fanconi's syndrome (phosphaturia, glycosuria, amino aciduria)
• Renal tubular acidosis (type 2)
• Hereditary hypophosphataemic rickets
• Tumour-induced osteomalacia.
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What are the symptoms of Osteomalacia/Rickets?
Osteomalacia commonly presents with diffuse bone pain (especially axial skeleton), weakness (tends to be in proximal muscles) and malaise.
Rickets presents with hypotonia, growth retardation and skeletal abnormalities.
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What are the examination features of Osteomalacia/Rickets?
May find patient has proximal muscle weakness, bone tenderness and uncommonly waddling gait (occurs in patients with severe bone pain and proximal myopathy).
May also elicit Trousseau's sign (caused by hypocalcaemia) and Chvostek's sign (elicited by tapping over the facial nerve, causing twitching of ipsilateral facial muscles).
Rickets is often noticeable by bossing of frontal and parietal bones and swelling of costochondral junctions (rickety rosary). Bow legs in early childhood, 'knock knees' in later childhood. Short stature.
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What are the potential complications of Osteomalacia/Rickets?
Bone deformities, hypocalcaemia may cause epileptic seizures, cardiac arrhythmias, hypocalcaemic tetany and depression.
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How can Osteomalacia/Rickets be investigated?
Bloods:
• Normal or ↓Ca, ↓phosphate, ↑AlkPhos, ↓25(OH) vitamin D.
• May also have ↑PTH causing secondary hyperparathyroidism.
• Check U&Es and ABGs (Patients with renal tubular acidosis have normal anion gap hyperchloraemic metabolic acidosis).
Radiographs: May appear normal or show osteopenia. Looser's zones or pseudofractures (radiolucent bands) in ribs, scapula, pubic rami or upper femur.
Note: Osteomalacia presents as osteoporosis in 70% of DXA scans, so they cannot be used to distinguish between the two.
A bone biopsy with double tetracycline labelling shows reduced distance between tetracycline bands.
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What is the management of Osteomalacia/Rickets?
Treatment is vitamin D and calcium replacement. Monitor 24h urinary calcium, serum calcium, phosphate, Alk Phos, PTH and Vitamin D.
Treat underlying cause (e.g. advice on diet and sunlight exposure).
For inherited or acquired disorders of phosphate wasting, or oncogenic osteomalacia, give Vitamin D, calcium and oral phosphate.
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What is the definition and epidemiology of hypopituitarism?
Hypopituitarism is a deficiency of one or more of the hormones secreted by the anterior pituitary. Panhypopituitarism is deficiency of all pituitary hormones. Prevalence of pituitary adenomas are 9 in 100,000.
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What is the aetiology of hypopituitarism?
* Pituitary masses, most commonly adenomas.
* Pituitary trauma, such as radiation, surgery or skull base fracture.
* Hypothalamus (functional): anorexia, starvation or over-exercise.
* Infiltration: tuberculosis, sarcoidosis, haemochromatosis, histiocysis X
* Vascular: pituitary apoplexy, Sheehan's syndrome.
* Infection: meningitis, encephalitis, syphilis (rare), and fungal abscesses.
* Genetic mutations: Pit-1 and Prop-1 genes.
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How can hypopituitarism be investigated?
* Basal pituitary function tests: 9 a.m. cortisol, LH, FSH, testosterone, oestrodiol, IGF-1, prolactin, free T4 and TSH
* Dynamic tests (rarely perfome): Insulin-induced hypoglycaemia
* Short synachten test
MRI or CT of brain.
Visual field testing.
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What is the definition and epidemiology of Multiple Endocrine Neoplasia?
Multiple endocrine neoplasia syndromes are hereditary conditions characterised by the development of multiple endocrine tumours. MEN syndromes are relatively rare.
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What is the aetiology of Multiple Endocrine Neoplasia?
MEN1 and MEN2 are caused by autosomal dominant gene mutations, that are inherited or can develop sporadically.
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What are the different types of Multiple Endocrine Neoplasia syndromes?
The different syndromes are associated with different constellation of neoplasias. These can be remembered by the mnemonic:
• MEN I (3 Ps) - Pituitary, Parathyroid, Pancreatic.
• MEN IIa (2Ps, 1M) - Pheochromocytoma, Parathyroid, Medullary Thyroid Cancer
• MEN IIb (1P, 2Ms) - Pheochromocytoma, Medullary Thyroid Cancer, Marfanoid habitus/mucosal neuroma
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What are the common clinical features of all/most MEN syndromes?
Presents in young age, and commonly in someone with a family history.
Weight changes is a common feature (either gain or loss). Hypertension due to pheochromocytoma or hypercortisolism and abdominal pain (due to peptic ulceration) is also common. Clinical signs of kidney stones (hyperparathyroidism --> hypercalcaemia --> nephrolithiasis) can also be a feature.
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Define obesity
Obesity can be defined as a chronic adverse condition due to an excess amount of body fat. The most widely used method to determine obesity is through the BMI ([weight in kg]/[height in m]^2). Currently if BMI is >30 for caucasians, they are considered obese.
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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).
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What is the aetiology of obesity?
"Common" obesity is caused by the interplay between our genes and the obesogenic environment as well as behavioural choices.
Causes of genetic obesity are rare, but include Prader-Willi syndrome, Bardet–Biedl syndrome, Cohen syndrome, and MOMO syndrome.
Hormonal causes include Cushing's syndrome, hypothyroidism, insulinoma. Eating disorders and mental health disorders can also cause obesity.
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What is the definition and epidemiology of Prolactinomas?
Prolactinomas are benign lactotroph ademomas expressing and secreting prolactin. Prolactinomas are the most common type pf pituitary adenomas. They are commonly seen in women of child-bearing age, with a peak incidence between second and third decades of life. (After the fifth decade, there is no difference in the incidences between women and men).
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What is the aetiology of a prolactinoma?
Majority occur sporadically, a small proportion may have MEN1.
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What are the types of prolactinomas?
They can either be microadenomas (most common) which are <10 mm in diameter and tend to stay stable in size, or macroadenomas which are usually locally invasive.
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What are the clinical features of a prolactinoma?
Patients complain of:
• Oligomenorrhoea/amenorrhoea
• Infertility
• Galactorrhoea (sometimes identified only on examination)
• Loss of libido
• Erectile dysfunction
• Visual deterioration is also common, with patients complaining of bitemporal hemianopia.
Patient may also have osteoporosis due to low oestradiol and testosterone levels. Patient can also uncommonly present with headaches, or opthalmoplegia (paralysis of the muscles within or surrounding the eye).
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How can a prolactinoma be investigated?
These are very simple:
• Serum prolactin levels are elevated
• A pituitary MRI can show characteristic features of a pituitary adenoma
• A computerised visual-field examination may reveal unilateral or bitemporal hemianopia.
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How are prolactinomas managed?
The treatment for asymptomatic patients with microadenomas is just observation.
For patients with symptomatic microadenomas, they can be treated with:
1. Dopamine agonists (Cabergoline or Bromocriptine) are the first line therapy. Shown to be safe for pregnancy.
2. Oral contraceptive pill if patient does not want dopamine agonist, and only has menstrual abnormalities and do not desire pregnancy.
3. Trans-sphenoidal surgery for patients who cannot tolerate drugs.
4. Sellar radiotherapy
For patients with macroadenomas, dopamine agonists and trans-sphenoidal surgery is also recommended.
