Endocrinology (2)

Question 1

Define multiple endocrine neoplasia

Answer 1

An autosomal dominant inherited syndrome characterised by tumours of the endocrine organs.

Question 2

Summarise the aetiology of multiple endocrine neoplasia

Answer 2

Genetically inherited autosomal dominant

MEN1 gene mutation - mutation of tumour supressor gene
Causes MEN type 1

RET gene mutation - mutation of proto-oncogene
Causes MEN type 2A and 2B

MEN 1:
Parathyroid adenoma
Pituitary adenoma
Pancreatic cancer - most often gastrinoma
Facial angiofibromas and collagenomas

MEN 2A:
Thyroid medullary cancer
Phaeochromocytoma
Parathyroid adenoma

MEN 2B:
Thyroid medullary cancer
Phaechromocytoma
Multiple neuromas
Marfanoid habitus

Question 3

Summarise the epidemiology of multiple endocrine neoplasia

Answer 3

Very rare

MEN 1 diagnosis usually made in 4th decade of life, however tumours develop in teenage years

Question 4

What are the presenting symptoms and signs on physical examination of multiple endocrine neoplasia?

Answer 4

MEN1:
Parathyroid adenoma - hypercalcaemia
Abdominal pain and tenderness
Constipation
Confusion
Symptoms of nephrolithiasis - loin to groin pain

Pancreatic gastrinoma - Zollinger-Ellison syndrome:
Abdominal pain
Dysphagia
Gastro-oesophageal reflux
Vomiting

Pancreatic insulinoma - hypoglycaemia - dizziness, hunger

Pancreatic glucagonoma - hyperglycaemia

Prolactinoma - galactorrhoea, gynaecomastia, amenorrhoea, headaches, bilateral hemianopia
Hypersomtatotrophinaemia - acromegaly, headaches, bilateral hemianopia

MEN 2A:
Thyroid medullary cancer - hoarseness, coughing, trouble swallowing, sweating, hypertension, pruritic skin lesions, lump in the neck, diarrhoea, palpable thyroid nodules
Phaeochromocytoma - hypertension, sweating, tremor, tachycardia, palpitations, headaches
Parathyroid adenoma

MEN 2B:
Thyroid medullary cancer
Phaechromocytoma
Multiple neuroma 
Marfanoid habitus - long limbs, long fingers, high arched palate

Question 5

What are the appropriate investigations for multiple endocrine neoplasia?

Answer 5

MEN 1:
Hormone hypersecretion blood tests - PTH, gastrin, insulin, glucagon, prolactin, GH, IGF-1
Serum calcium
DNA testing for genetic abnormality
MRI head to look for pituitary adenoma

MEN 2:
24hr urine metanephrines for phaechromocytoma
MRI/CT adrenals
Serum calcitonin - elevated in Medullary thyroid cancer
FNA of thyroid nodules
Thyroid ultrasound
Parathyroid adenoma - elevated calcium and PTH

Question 6

Define primary hyperaldosteronism

Answer 6

Increased autonomous production of aldosterone by the adrenal glands due to a problem with the adrenals, resulting in suppression of plasma renin activity.

Question 7

Summarise the aetiology of primary hyperaldosteronism

Answer 7

Conn’s syndrome - adrenal adenoma secreting aldosterone (most common - 70%)
Adrenal carcinoma - RARE
Adrenal cortex hyperplasia - 30% of cases
Familial hyperaldosteronism - dominant inheritance,
Idiopathic

Question 8

Summarise the epidemiology of primary hyperaldosteronism

Answer 8

1-2% of hypertensive patients
Conn’s syndrome is more common in WOMEN and YOUNG patients
Bilateral adrenal hyperplasia is more common in MEN and presents at an older age

Question 9

What are the presenting symptoms of primary hyperaldosteronism?

Answer 9

Usually asymptomatic and found incidentally on bloods

Hypertension symptoms:
Headaches
Flushing

Hypokalaemia symptoms:
Polydipsia and polyuria (due to nephrogenic DI)
Nocturia
Constipation
Weakness
Fatigue
Numbness
Tingling
Tetany

Question 10

What are the signs on physical examination of primary hyperaldosteronism?

Answer 10

Hypertension

Complications of hypertension eg hypertensive retinopathy

Question 11

What are the appropriate investigations for pulmonary hyperaldosteronism?

Answer 11

Serum aldosterone - high
Serum renin - low
Serum potassium - may be hypokalaemic
Serum sodium - may be hypernatraemic
Serum magnesium - may be hypomagnesiumaemic
Urine potassium - high
Aldosterone:renin activity ratio: elevated
CT adrenals - may show adrenal adenoma or carcinoma
Genetic testing for familial hyperaldosteronism

Confirmatory Tests
Salt Loading: failure of aldosterone suppression following salt load confirms Conn’s

Postural Test: Measure plasma aldosterone, renin activity and cortisol when patient lies down at 8am, and measure again after 4 hours of the patient being upright.
Aldosterone-producing adenoma: aldosterone secretion decreases between 8am and noon
Bilateral adrenal hyperplasia: adrenals respond causing increase renin leading to increased aldosterone

Question 12

What is the management of primary hyperaldosteronism?

Answer 12

Bilateral Adrenal Hyperplasia:
Spironolactone (aldosterone receptor antagonist)
Eplerenone if spironolactone side-effects are intolerable
Amiloride (potassium-sparing diuretic)
Monitor serum K+, creatinine and BP
ACE inhibitors and CCBs may also be added

Aldosterone Producing Adenomas: Adrenalectomy

Adrenal Carcinoma: Surgery and post-operative mitotane (antineoplastic)

Question 13

What are the possible complications of primary hyperaldosteronism?

Answer 13

Hypokalaemia
Metabolic alkalosis
Hypertension
Stroke
MI
AF
Heart failure
Impaired renal function
Complications of hypertension

Question 14

Summarise the prognosis of primary hyperaldosteronism

Answer 14

Surgery may cure the hypertension or make the hypertension easier to manage
Hypertension improved by management in all forms

Question 15

Define osteoporosis

Answer 15

A metabolic bone disorder characterised by a decrease in bone mineral density and altered bone architecture, resulting in increased bone fragility and susceptibility to fracture. Bone mineralisation is normal

Question 16

Summarise the aetiology of osteoporosis

Answer 16

Mainly post-menopausal or senile osteoporosis
Secondarily seen with drugs or systemic conditions

Other causes:
Low oestrogen eg postmenopausal leading to loss of bone matrix
Age related - osteoblast senescense
Iatrogenic - glucocorticoids, heparin, L-thyroxine
Malignancy – myeloma, metastatic carcinoma
Rheumatological – rheumatoid arthritis, ankylosing spondylitis
Gastrointestinal – malabsorption, liver disease, anorexia
Hypogonadism (in young men and women) – sex hormones inhibit bone resorption
Endocrine - Cushing’s, hyperthyroidism, primary hyperthyroidism

Question 17

What are the risk factors of osteoporosis?

Answer 17

Post-menopause
Age
Family history
Low BMI
Low calcium intake/serum calcium
Smoking
Lack of physical exercise
Low exposure to sunlight
Alcohol abuse
Late menarche
Early menopause
Hypogonadism
Glucocorticoid use

Question 18

Summarise the epidemiology of osteoporosis

Answer 18

Predominently white post-menopausal women
Can affect any sex, age and ethnicity
In the UK, osteoporosis causes fractures in 50% of women and 20% of men aged >50 years

Question 19

What are the presenting symptoms of osteoporosis

Answer 19

Asymptomatic until a pathologic fracture occurs
Most often vertebral fracture which results in back pain, height loss and hunched posture
Can also have distal radius and femoral neck fractures often in post-menopausal

Question 20

What are the signs on physical examination of osteoporosis?

Answer 20

There are often no signs until complications develop

When vertebral fractures occur:
Tenderness on percussion
Thoracic kyphosis (due to multiple vertebral fractures)

Neck of femur fracture:
Severe pain when hip flexed and externally rotated

Question 21

What are the appropriate investigations for osteoporosis?

Answer 21

DEXA Scan - compares bone density to that of normal individual to develop t-score. T score compares to healthy 25 year old female at peak bone mass.
T score -1 is normal

Quantitative ultrasound/CT scan/x-ray of the heel to detect reduced bone mineral density
X-rays to diagnose fractures
Biochemical markers of bone resorption and formation (urinary deoxypyridinoline)

Serum albumin - may be decreased
Serum alkaline phosphatase - normal, osteomalacia if raised
Serum calcium - normal. If low, osteomalacia. If high, hyperparathyroidism.
Serum creatinine, phosphate, vitamin D
Thyroid function tests and serum parathyroid hormone

Question 22

Define polycystic ovarian syndrome

Answer 22

A condition characterised by 2 of the three:
Hyperandrogenism
Oligo/anovulation
Polycystic ovaries on USS

It also shows oligo/amenorrhoea, hirsuitism, obesity, insulin resistance and can be associated with diabetes mellitus and dyslipidaemia.

Question 23

Summarise the aetiology of polycystic ovarian syndrome

Answer 23

Increased secretion of LH by the anterior pituitary gland
Aetiology is unknown
Environmental factors
Genetic variants

Hyperinsulinaemia results in increased ovarian androgen synthesis and reduced hepatic sex hormone binding globulin (SHBG) synthesis - causes increase in free androgens (which gives rise to the symptoms)

Question 24

Summarise the epidemiology of polycystic ovarian syndrome

Answer 24

Most common endocrine disorder of females of reproductive age
Accounts for 80-90% of causes of hyperandrogenism in women
Affects 6-8% of women
Most common cause of infertility in women

Question 25

What are the presenting symptoms of polycystic ovarian syndrome?

Answer 25

Symptoms of hyperandrogenism: Acne on face, back, chest Hisutism - facial hair on chin, upper lip chest and back Male pattern hair loss Obesity Oligomenorrhoea or amenorrhoea Dysfunctional uterine bleeding Infertility

Question 26

What are the signs on physical examination of polycystic ovarian syndrome?

Answer 26

``` Hirsutism Acne Obesity Male pattern hair loss Ancanthosis nigricans - dark velvety thickened, hyperpigmented patches in creases on neck, groin, underarm - sign of insulin resistance ```

Question 27

What are the appropriate investigations for polycystic ovarian syndrome?

Answer 27

``` Bloods: LH - elevated LH:FSH - elevated >3:1 Elevated androgens - testosterone, androstenedione, DHEA Low FSH and sex hormone binding globulin ``` USS pelvis - may show follicles on ovaries and increase in ovarian volume ``` Rule out: Hyperprolactinaemia Hypo/hyperthyroidism Cushing’s syndrome Congenital adrenal hyperplasia (check 17OH-progesterone levels) ``` Look for impaired glucose tolerance/T2DM: Fasting blood glucose, HbA1c Fasting lipid profile

Question 28

Define Paget's disease of bone

Answer 28

A chronic bone remodelling disorder characterised by excessive osteoclastic breakdown and excessive osteoblastic formation, resulting in abnormal mosaic organised, weak bone

Question 29

Summarise the aetiology of Paget's disease of bone

Answer 29

Aetiology is unknown Genetic component - may be autosomal dominant pattern. SQSTM1 mutation Prior virus infection eg measles Environmental component

Question 30

Summarise the epidemiology of Paget's disease of bone

Answer 30

2nd most common chronic bone remodelling disorder after osteoporosis More common in men Mean age of onset is 55 years old Polyostotic in 75% of cases Paget’s disease prevalence is highest in the UK, North America, Australia and New Zealand.

Question 31

What are the presenting symptoms of Paget's disease of bone?

Answer 31

``` Can often be asymptomatic Bone pain, particularly deep hip pain - insidious onset, aggravated by weight bearing and movement Bowing of the legs Increasing shoe or hat size Hearing loss as bone growth compresses auditory nerve Visual loss Lion face Lower limb muscle weakness Arthritis Microfractures Headaches Radiculopathy due to nerve compression ```

Question 32

What are the signs on physical examination of Paget's disease of bone?

Answer 32

Skull, thoracolumbar spine, pelvis, femur and tibia most commonly affected Arthritis Bone pain and deformity (enlarged skull, sabre tibia) Increasing skull size Bitemporal skull enlargement with frontal bossing (prominent, protruding forehead) Sensorineural deafness (due to compression of vestibulocochlear nerve) Increased local temperature Tibial, femur or forearm bowing Pathological fractures Leontiasis Kyphosis

Question 33

What are the appropriate investigations for Paget's disease of bone?

Answer 33

Serum calcium - normal Serum PTH - normal Serum phosphate - normal Serum ALP - isolated large increase X-Ray: Lytic lesions early on Late: thickened cortical bone, sclerotic changes Osteoporosis circumscripta Trabeculae are coarsened inside (particularly at femoral head/neck) Bone is bent Enlarged, deformed bones Skull changes: cotton wool appearance, enlargement of frontal and occipital areas Bone biopsy - abnormal disorganised bone with mosaic pattern of lamellar bone, osteoclasts with multiple nuclei, wide canaliculi with disorganised matrix Bone scan: areas of dense uptake in Paget's bone Raised serum alkaline phosphatase, urinary hydroxyproline, pyridinoline cross-links

Question 34

Define thyroid nodules

Answer 34

Abnormal growth of the thyroid cells, forming a lump in the thyroid gland.

Question 35

Summarise the aetiology of thyroid nodules

Answer 35

The vast majority of thyroid nodules are BENIGN, but a small proportion can lead to thyroid cancer Most thyroid nodules are adenomatous, and most are multiple The nodules are usually non-functioning

Question 36

Summarise the epidemiology of thyroid nodules

Answer 36

40% of the general population have a single nodule or multiple nodules More common in WOMEN Very small proportion of thyroid nodules will be malignant

Question 37

What are the presenting symptoms of thyroid nodules?

Answer 37

Most are ASYMPTOMATIC - usually found on self-examination or clinical examination Lump on thyroid gland A single isolated nodule is more likely to be malignant They can sometimes cause pain and will rarely compress the trachea or cause dysphagia Usually non-functional, if functional there will be symptoms of hyperthyroidism

Question 38

What are the signs on physical examination of a thyroid nodule?

Answer 38

Lump in the neck Moves up and down neck when swallowing Check for lymphadenopathy - indicative of malignancy If functional, will find signs on hyperthyroidism

Question 39

What are the appropriate investigations of thyroid nodules?

Answer 39

TFTs - usually non-functioning, therefore normal. If functioning, high T3/4, low TSH USS thyroid - visualise nodules Radioiodine isotope scan - if functional, shows hot nodule and if non-functional, cold nodule FNA of nodule

Question 40

Define osteomalacia

Answer 40

A metabolic bone disease in which there is decreased mineralisation of newly formed osteoid bone in adults (after fusion of the epiphyseal plates), often due to vitamin D deficiency, leading to soft bones which are prone to fracture.

Question 41

Summarise the aetiology of osteomalacia

Answer 41

``` The main cause is vitamin D deficiency Inadequate exposure to sunlight Inadequate intake Malabsorption Chronic kidney disease or liver failure: decreased activation of vit D ``` Hypophosphataemia - acquired and X linked hypophosphataemia Long term use of anticonvulsants eg phenytoin Mesenchymal tumours

Question 42

Summarise the epidemiology of osteomalacia

Answer 42

Incidence decreasing in Western world due to fortification on food with vitamin D

Question 43

What are the presenting symptoms and signs on physical examination of osteomalacia?

Answer 43

``` Early, mild osteomalacia - asymptomatic Bone pain Muscle weakness Soft bones Increased fractures from low impact Joint pain Spjnal tenderness to percussion Muscle pasms - hands and feet Waddling gait Fatiguability and malaise Proximal myopathy Bone tenderness ```

Question 44

What are the appropriate investigations for osteomalacia?

Answer 44

``` Bloods: Vitamin D - low Calcium - low Phosphate - low PTH - elevated ALP - elevated Serum urea and creatinine - elevated if due to CKD ``` X-ray: Osteopenia Looser zones (psuedofractures, transverse lucency with sclerotic margins) Bone biopsy: Increased unmineralised osteoid volume, increased width of osteoid seam, no new bone mineralisation Tetracycline labelling: Tetracycline antibiotic can detect and examine bone mineralisation in the living patient. The tetracycline is related to a fluorescent stain. Contraindicated in children

Question 45

What is the management of osteomalacia?

Answer 45

Oral vitamin D supplements Calcium replacement Treat underlying cause Patients with normal renal function: Give 25-hydroxycholecalciferol Patient converts this to 1,25-dihydroxy-vitamin D via 1-alpha hydroxylase (kidney) Given as ergocalciferol (25-hydroxy vitamin D2) or cholecalciferol (25-hydroxy vitamin D3) In patients with renal failure: Can’t activate 25-hydroxy vitamin D preparations Give alfa calcidiol - 1-alpha hydroxycholecalciferol - this is active vitamin D

Question 46

What are the possible complications of osteomalacia?

Answer 46

``` Secondary hyperparathyroidism Insufficiency fractures Hypercalcaemia Hypercalciuria and renal stones Metastatic calcification in renal failure ```

Question 47

Summarise the prognosis of osteomalacia

Answer 47

Depends on underlying cause and compliance with therapies

Question 48

Define hypogonadism

Answer 48

A condition in which there is reduced or absent secretion of hormones, or other physiological activity of the gonads (ovaries in females, testes in males). Males = decreased testosterone production, sperm production or both. Females = decreased oestrogen production and impairment of ovarian function Primary hypogonadism/Hypergonadotropic hypogonadism: Gonads fail Loss of negative feedback of sex steroids Increased secretion of GnRH, FSH and LH Secondary hypogonadism/Hypogonadotropic hypogonadism: Hypothalamic or pituitary failure Deficiency in GnRH or FSH/LH secretion Hypogonadism entails infertility and an increased risk of developing osteoporosis

Question 49

Define the aetiology of hypogonadism

Answer 49

Primary hypogonadism: Radiotherapy Chemotherapy Trauma to gonads Male: Klinefelter syndrome Acquired: testicular necrosis (torsion, trauma, radiation), infection Female: Turner's syndrome (45X) Acquired ovarian failure - premature, ovariectomy, PCOS Secondary hypogonadism: Stress, weight loss, excessive exercise, eating disorder Pituitary tumour Hypothalamic tumour Infiltrative disease of pituitary or hypothalamus Kallmann’s syndrome (isolated GnRH deficiency) Hyperprolactinaemia (due to a prolactinoma)

Question 50

Summarise the epidemiology of hypogonadism

Answer 50

Female: Prevalence increases with age. Secondary hypogonadism is a more common cause of anovulation and amenorrhoea. Turner’s syndrome occurs in around 1.5% of conceptions. Male: Prevalence increases with age Primary hypogonadism accounts for 30-40% of male infertility (most common cause is Klinefelter’s syndrome). Secondary hypogonadism accounts for 1-2%.

Question 51

What are the presenting symptoms and signs on physical examination of hypogonadism?

Answer 51

``` Female: Amenorrhoea Absent breast development or breast atrophy Decreased body hair Decreased libido Infertility Short stature Oestrogen deficiency: night sweats, hot flushes, dyspareunia ``` Turner's: short stature, wide-spaced nipples, wide carrying angle, low hairline, infertility, high arched palate ``` Male: Infertility Decreased libido Delayed puberty - small penis, undescended or small testes, high pitched voice Impotence Loss of body hair ``` Klinefelter's - decreased IQ, tall, poor muscle tone If due to pituitary tumour: Headache Visual disturbance Seizures Kallmann's syndrome: Ansomia

Question 52

What are the appropriate investigations for hypogonadism?

Answer 52

Serum GnRH - high in primary hypogonadism, low in secondary hypogonadism Serum LSH and FH - high in primary hypogonadism, low in secondary hypogonadism Serum testosterone - low Serum oestrogen/estradiol - low Serum prolactin - elevated if prolactinoma TFTs - hypothyroidism can cause secondary hypogonadism MRI head - view pituitary tumour Karyotyping - assess for genetic condition as a cause Female: Pelvic imaging (US/MRI) – check for structural defects (e.g. androgen insensitivity) Turner’s syndrome: periodic echocardiography, renal ultrasound Autoimmune oophoritis: check autoimmune adrenal insufficiency

Question 53

What are the appropriate investigations for hypogonadism?

Answer 53

Serum GnRH - high in primary hypogonadism, low in secondary hypogonadism Serum LSH and FH - high in primary hypogonadism, low in secondary hypogonadism Serum testosterone - low Serum oestrogen/estradiol - low Serum prolactin - elevated if prolactinoma TFTs - hypothyroidism can cause secondary hypogonadism MRI head - view pituitary tumour Karyotyping - assess for genetic condition as a cause Female: Pelvic imaging (US/MRI) – check for structural defects (e.g. androgen insensitivity) Turner’s syndrome: periodic echocardiography, renal ultrasound Autoimmune oophoritis: check autoimmune adrenal insufficiency

Question 54

Define thyroiditis

Answer 54

Autoimmune-mediated lymphocytic inflammation of the thyroid gland leading to a destructive thyroiditis. This causes release of thyroid hormones, leading to a transient hyperthyroidism, followed by hypothyroidism, and finally full recovery.

Question 55

Summarise the aetiology of thyroiditis

Answer 55

Hashimoto's thyroiditis: autoimmune condition with autoantibodies against thyroglobulin, thyroid peroxidase and anti-microsomal The most common cause of hypothyroidism in the UK. de Quervain's thyroiditis - following viral upper respiratory tract infection Postpartum thyroiditis - increased immune system after pregnancy aggravates underlying mild autoimmune thyroiditis Drug-induced thyroiditis Acute or infectious thyroiditis Riedel's thyroiditis - fibrous tissue replaces

Question 56

Summarise the epidemiology of thyroiditis

Answer 56

15-20 times more likely in women Occurs 30-50 years old Hashimoto's thyroiditis is most common cause of hypothyroidism in developed world where there are sufficient amounts of iodine

Question 57

What are the signs and symptoms of thyroiditis?

Answer 57

``` Hyperthyroid phase: Palpitations Sweating Weight loss Tachycardia Diarrhoea ``` ``` Hypothyroid phase: Fatigue Constipation Dry skin Weight gain Cold intolerance Menstrual irregularities Depression Hair loss ``` Enlarged thyroid gland/goitre Painless mostly, painful in de Quervain's thyroiditis Symptoms of compression from goitre - dysphagia, dyspnoea, hoarseness

Question 58

What are the appropriate investigations for thyroiditis?

Answer 58

TFTs: Hyperthyroid phase: elevated T3/T4, low TSH Hypothyroid phase: low T3/T4, elevated TSH Autoantibodies: Anti-thyroid peroxidase Anti-thyroglobulin Anti-microsomal antibodies Thyroid ultrasound Radionuclide isotope scanning (very low radioiodine uptake) Histology: diffuse lymphocytic and plasma cell infiltration, formation of lymphoid follicles

Question 59

What is the appropriate management of thyroiditis?

Answer 59

Often self-limiting 1st line - observation and monitoring with beta blockers and CCBs for symptom management 2nd line if non-resolving - oral levothyroxine sodium If goitre causing symptoms - surgery

Question 60

What are the possible complications of thyroiditis?

Answer 60

Thyroid hormone over-replacement causing bone loss + tachycardia Hyperlipidaemia Hashimoto's encephalopathy Myxoedema coma

Question 61

Define diabetes mellitus

Answer 61

Type 1: Autoimmune disease characterised by beta cell destruction, leading to hyperglycaemia due to an insulin insufficiency. Type 2: Insulin resistance leading to chronic hyperglycaemia which is not ketosis prone and often seen in older obese patients.

Question 62

Summarise the aetiology of diabetes mellitus

Answer 62

Type 1: Autoimmune destruction of beta cells in Islets of Langerhans Due to anti-glutamic acid decarboxylase and anti-islet cell cytoplasmic antibodies Causes decreased insulin secretion HLA-DR3 and HLA-DR4 associated with increased risk Type 2: Lots of insulin is secreted however the patient is insulin resistant. Eventually the beta cells are exhausted and there is hypothropy and hypoplasia Obesity Hypertension Sedentery lifestyle Genetics

Question 63

Summarise the epidemiology of diabetes mellitus

Answer 63

Type 1 accounts for 10% of diabetes. It is more common in younger patients. Most patients present before 30 years old Type 2 accounts for 90% of cases. More common in those over 40, obese etc. Increasing incidence with increasing obesity incidence

Question 64

What are the presenting symptoms and signs on physical examination of diabetes mellitus?

Answer 64

``` Polyphagia Polydipsia Polyuria Glycosuria Fatigue Nocturia Thrush and other yeast infections ``` Type 1: Onset under 30 years old Weight loss Often presents as DKA - diffuse abdominal pain, nausea and vomiting, altered mental state, Kussmaul's respiration, ketotic sweet smelling breath, coma, confusion Signs of associated autoimmune conditions eg vitiligo, Addison's, autoimmune thyroiditis Blurred vision - due to diabetic retinopathy Type 2: Infections Ulcers Diabetic nephropathy - loss of sensation in stocking and glove distribution Blurred vision May present with hyperosmolar hyperglycaemic state - confusion, coma, hyperglycaemia Overweight Diabetic foot: dry skin, reduced SC tissue, ulceration, gangrene, Charcot’s arthropathy Skin changes: necrobiosis lipoidica diabeticorum, granuloma annulare, diabetic dermopathy, acanthosis nigricans

Question 65

What are the appropriate investigations for diabetes mellitus?

Answer 65

Fasting blood glucose: 5.6-6.9mmol/L = prediabetes >7mmol/L / >126mg/dL = diabetes Oral glucose tolerance test - >200mg/dL 2 hours after eating HbA1c: 5.7 - 6.4% = prediabetes >6.5% = diabetes Random plasma glucose: >11.1mmol/L = diabetes Urinalysis - glycosuria, ketonuria in DKA, proteinuria if diabetic nephropathy, urine albumin:creatinine ratio shows microalbuminuria Antibodies for T1DM: Anti-glutamic acid decarboxylase Anti-islet cell Insulin antibodies Fundoscopy - signs of retinopathy - cotton wool spots, microaneurysms, flare haemorrhages DKA: ABG - metabolic acidosis, ketonaemia U+Es - hyperkalaemia

Question 66

What is the management of diabetes mellitus?

Answer 66

Type 1: Insulin - short-acting (lispro, aspart, glulisine) insulin analogues 3x daily and long-acting (glargine, determir, degludec) insulin analogues 1x daily Type 2: 1st line = lifestyle factors - weight loss, exercise, diet, management of hypertension 2nd line = metformin 3rd line = additional anti-diabetics eg sulphonylureas, gliptins etc If 3 antidiabetics therapy does not work, insulin therapy may be used DKA = IV fluids, insulin and electrolyte replacement eg potassium

Question 67

What are the possible complications of diabetes mellitus?

Answer 67

Increased risk of infection Hypoglycaemia - mood change, fits, confusion, coma, pallor, sweating, tremor, tachycardia Type 1: DKA Type 2: Hyperosmolar hyperglycaemic state: Causes severe dehydration, hypernatraemia, high osmolality Macrovascular complications - MI, stroke, peripheral vascular disease, ischaemic heart disease ``` Microvascular complications: Neuropathy: Distal symmetrical sensory neuropathy Painful neuropathy Carpal tunnel syndrome Diabetic amyotrophy Mononeuritis Autonomic neuropathy Gastroparesis (abdominal pain, nausea, vomiting) Impotence and urinary retention ``` ``` Nephropathy: Microalbuminuria and proteinuria Renal failure Prone to UTI Renal papillary necrosis ``` Retinopathy: Background leading to pre-proliferative leading to proliferative maculopathy Prone to glaucoma, cataracts and transient visual loss

Question 68

Summarise the prognosis of diabetes mellitus

Answer 68

Type 1: Prognosis depends on early diagnosis, good glycaemic control and compliance with treatment and screening Vascular disease and renal failure are the main causes of increased morbidity and mortality Type 2: Good prognosis with good control