Endocrinology Flashcards
What abnormalities would you expect on TFTs in a patient with Hypothyroidism?
High TSH
Low T4
What abnormalities would you expect on TFTs in a patient with Sub-clinical Hypothyroidism?
High TSH
Normal T4
What abnormalities would you expect on TFTs in a patient with Hyperthyroidism?
Low TSH
High T4/T3
What abnormalities would you expect on TFTs in a patient with Thyrotropinoma?
High TSH
High T4
What abnormalities would you expect on TFTs in a patient with Sick Euthyroid/pituitary issues?
Low TSH
Low T3/T4
What are the symptoms of thyrotoxicosis?
HIGH SYMPATHETIC OUTPUT
Weight loss
Diarrhoea
Weakness
Irritability
Tremor
Heat intolerance
Tachycardia
Brisk reflexes
Proximal weakness
What investigations should be performed in suspected thyrotoxicosis?
TFTs - low TSH, high T4/T3
Thyroid autoAb
Isotope scan - if unclear cause
How should thyrotoxicosis be managed?
B-blockers for sx
Block
-Carbimazole (1st line)
-Propylthiouracil
Replace
-Levothyroxine
Thyroidectomy/131-Thyroid
What are the side effects of Carbimazole?
Rash
Pruritis
Hypothyroidism
TERATOGENESIS - fetal goitre
AGRANULOCYTOSIS
What are the features of Thyroid Storm?
SUDDEN ONSET SEVERE HYPERTHYROIDISM
Hyperpyrexia, Dehydration
Tachycardia, Hypotension
Abdo pain, N&V, diarrhoea
Altered mental state
In which patient groups is Thyroid Storm typically seen?
Underlying Grave’s/TMN goitre
Precipitated by illness, trauma, emergency surgery, contrast
What is the management of Thyroid Storm?
IVI
Carbimazole
Hydrocort/Dex
Digoxin/BB for arrhythmias
Treat underlying cause
What are the features of Grave’s disease?
DIFFUSE goitre
Associated w/ autoimmune disease
GAG deposition
-exophthalmos
Pretibial myxoedema
Thyroid acropachy
By what mechanism does Grave’s disease cause hyperthyroidism?
Circulating IgG TSHR stimulating autoantibodies
What is the major pregnancy related complication of Grave’s disease and how should it be treated?
Fetal thyrotoxicosis
Treat w/ PTU (crosses placenta less)
How should exophthalmos associated w/ Grave’s disease be managed?
Stop smoking
Prism (lenses)
High-dose steroids
Decompression
Orbital XRT
What are the features of toxic multinodular goitre?
NODULAR goitre
Mass effect (e.g. compression of airway in retrosternal goitre)
Typically euthyroid –> suddenly thyrotoxic as nodules develop
By what mechanism does toxic multinodular goitre cause hyperthyroidism?
TSH independent nodules developing
How is toxic multinodular goitre managed?
Thyroidectomy
What is a toxic adenoma?
Solitary T3/T4 producing nodule
-appears ‘hot’ on isotope scan
What is subacute (de Quervain’s thyroiditis)?
Self-limiting PAINFUL goitre post viral illness
-‘cold’ on isotope scan
What is subacute (de Quervain’s thyroiditis) treated?
NSAIDs
How should Amiodarone be monitored and why?
Can cause hypo/hyperthyroidism
TFTs every 6/12
What are the clinical features of hypothyroidism?
LOW SYMPATHETIC OUTPUT + COARSE FACE
-fatigue/lethargy
-cold intolerance
-constipation
-weight gain
-bradycardia
-delayed reflex response
-myxoedema (+/- effusions)
-poor memory/difficulty concentrating
What investigations should be performed in suspected hypothyroidism?
TFTs - high TSH, low T4
Thyroid autoAb
FBC - macrocytic anaemia
High cholesterol
What are the common causes of hypothyroidism?
PRIMARY
-Deficiency - worldwide most common
-Autoimmune (Hashimoto’s) - UK most common
-Riedel’s fibrosing thyroiditis
-Iatrogenic (post rx, Amiodarone, Lithium)
SECONDARY
-hypopituitarism (rare)
What sort of goitre does Hashimoto’s present with?
Diffuse
By what mechanism does Hashimoto’s cause hypothyroidism?
TPO autoAb
What is the potential complication of Hashimoto’s?
Conversion to marginal zone B-cell lymphoma
By what mechanism does Riedel’s fibrosing thyroiditis cause hypothyroidism?
IgG4 disease
-replaces normal tissue w/ fibrosis
What are the features of Riedel’s fibrosing thyroidits?
HARD GOITRE FIXED TO NECK
Chronic
Can mimic anaplastic ca
Signs of other IgG4 disease
-retroperitoneal fibrosis
-liver disease
How is Riedel’s fibrosing thyroiditis managed?
Steroids
Thyroidectomy
What is a myxoedematous coma?
Extreme presentation of severe hypothyroidism
What are the clinical features of myxoedematous coma?
Hypothermia
Hyporeflexia
Hypoglycaemia
Bradycardia
Pancreatitis
Psychosis/seizures –> coma
What are the common precipitants of myxoedematous coma?
Recent radioiodine/thyroidectomy/pituitary surgery
Infections
Physiological stressors
What is the management of myxoedematous coma?
Ventilation (as required)
Replace (T3, glucose, warm)
Treat underlying cause
What are the distinguishing features of a pharyngeal pouch?
Older males
Dysphagia
Halitosis
Regurgitation –> aspiration
What are the distinguishing features of a thyroglossal cyst?
Midline b/w thyroid isthmus and hyoid bone
Moves w/ tongue protrusion
What are the distinguishing features of a branchial cyst?
TEENS
Oval, mobile cyst b/w SCM and pharynx
Increases in size post URTI
What are the distinguishing features of a cystic hygroma?
<2 y/o
LEFT sided
Large
Transilluminates
What are the red flag sx suggestive of thyroid ca?
Stridor
Persistent cough
Hoarseness
Haemoptysis
Lymphadenopathy
Rapid growth
Painless
Fixed/hard lump
How should thyroid ca be investigated?
Step 1 - TFTs & clinical exam
Step 2 (if euthyroid +/- lymphadenopathy) - FNA (not USS)
What are the different types of thyroid ca?
Papillary (60%)
Follicular (~25%)
Medullary (5%)
Lymphoma (5%)
Anaplastic (rare)
In which patients does papillary thyroid ca typically present?
Younger patients
-better prognosis if young/female
How does papillary thyroid ca spread?
LOCALLY
-LN
-Lung
How is papillary thyroid ca treated?
Total thyroidectomy +/- node excision +/- 131-Iodine
What are the features of follicular thyroid ca?
Presents in middle age
Spreads early via blood (bone, lungs)
Well differentiated
How is follicular thyroid ca treated?
Total thyroidectomy + T4 suppression + radioiodine ablation
In which patients does medullary thyroid ca typically present?
Sporadic (80%)
MEN2 syndromes
Which investigations should be performed when ix medullary thyroid ca?
Phaeochromocytoma screen
RET genetic screening
Calcitonin
-may be raised as tumour marker
-biopsy to exclude localised amyloidosis
How is medullary thyroid ca treated?
Total thyroidectomy + node clearance +/- external beam XRT
In which patients does thyroid lymphoma present?
W:M 3:1
How does thyroid lymphoma present?
Stridor
Dysphagia
How should thyroid lymphoma be ix?
Full lymphoma staging pre-treatment
Assess histology for MALT origin
-medullary associated lymphoma thyroid
-good prognosis
How is thyroid lymphoma treated?
ChemoXRT
In which patients does anaplastic thyroid ca present?
W:M=3:1
Elderly
What are the features of anaplastic thyroid ca?
Rapidly growing, hard, invasive
SOB
Dysphagia
Hoarse voice
How is anaplastic thyroid ca treated?
Poor response to ANY treatment
Resection OR excision + XRT to palliate
-protect airway
What are the causes of primary hyperparathyroidism?
Adenoma (80%)
Hyperplasia (>19%)
Cancer (<1%)
How does 1o hyperparathyroidism present?
Asymptomatic
Hypercalcaemic sx - bones, stones, groans, psychic moans
HTN
What clinical syndromes are associated w/ 1o hyperparathyroidism?
MEN-1
MEN-2a
Hyperparathyroid-jaw tumour syndrome
Describe MEN-1
Autosomal dominant
MEN1 tumour suppressor gene abnormality
Tumours
-parathyroid adenoma/hyperplasia
-pituitary adenoma
-pancreas tumour
-carcinoid/adrenal tumours
Describe MEN-2a
Autosomal dominant
RET proto-oncogene mutation
Tumours
-parathyroid hyperplasia (80%)
-thyroid medullary ca (100%)
-phaeochromocytoma (50%)
Describe hyperparathyroid-jaw tumour syndrome?
Autosomal dominant
Triad of:
-jaw fibromas
-pituitary adenoma
-GU tumours
Describe MEN-2b
Autosomal dominant
RET proto-oncogene mutation
Tumours
-thyroid medullary ca
-phaeochromocytoma
-mucosal neuromas
Marfanoid appearance
What are the causes of 2o hyperparathyroidism?
Vitamin D deficiency
CKD
What is the treatment of 2o hyperparathyroidism?
Treat underlying cause
PO4 binders
Vit D replacement
What is the management of 2o hyperparathyroidism?
Treat underlying cause
PO4 binders
Vit D replacement
Cinacalcet (rarely)
-if high PTH & parathyroidectomy difficult
What are the biochemical findings in 1o hyperparathyroidism?
High Ca
Low PO4
High/high normal PTH
High ALP
What are the biochemical findings in 2o hyperparathyroidism?
Low/normal Ca
High PO4
High PTH
High ALP
What is the management of 1o hyperparathyroidism?
Mild - fluids, avoid thiazides
Mod - excision
What are the complications of parathyroid excision?
HypoPTH - can save 1x gland
RLN damage - hoarse voice
Hungry bone syndrome
What is hungry bone syndrome?
Rapid hypocalcaemia due to bone remodelling after PTH suddenly suppressed
-check ca for 2/52 post PTH excision
What is the cause of 3o hyperparathyroidism?
Adaptation of autonomous parathyroid glands after prolonged 2o hyperparathyroidism
e.g. chronic renal failure AFTER transplant
What are the biochemical findings in 3o hyperparathyroidism?
High Ca
Very high PTH
What are the 1o causes of hypoparathyroidism?
Reduced PTH scretion from gland failure
-autoimmune
-surgical resection
-hereditary
What are the biochemical findings of hypoparathyroidism?
Low Ca
High PO4
Low PTH
NORMAL ALP
What are the presenting features of hypoparathyroidism?
Hypocalcaemia (SPASMODIC)
-spasms
-perioral paraesthesia
-anxiety
-seizures
-muscle tone high (colic, wheezing, dysphagia)
-orientation impaired (confusion)
-dermatitis
-impetigo herpetiformis (pustules in pregnancy)
-Chvostek’s/chorea/cataracts/cardiomyopathy/long QTc
What is Trousseau’s sign?
Carpopedal spasm on inflating BP cuff
-sign of latent tetany
What is Chvostek’s sign?
Facial muscle spasm elicited by tapping CN VII near the tragus
What syndromes are associated w/ 1o hypoparathyroidism?
DiGeorge
Autoimmune polyendocrinopathy
-addison’s/hypoPTH
-candidiasis
-ectodermal dysplasia
What are the features of DiGeorge syndrome?
CATCH 22
-cardiac
-abnormal facies
-thymic hypoplasia
-cleft palate
-hypoCa
-chromosome 22
What is the treatment for 1o hypoparathyroidism?
Alfacalcidol
Ca gluconate if v. low
What is Albright’s osteodystrophy?
GNAS1 mutation causing pseudohypoparathyroidism
How does Albright’s osteodystrophy present?
SHORT 4th/5th fingers
Round face
Dental hypoplasia
Short height
Low IQ
What are the biochemical findings of Albright’s osteodystrophy?
Low Ca
High PO4
High PTH
Normal/high ALP
What is familial hypocalciuric hypercalcaemia?
Autosomal recessive defect in Ca SR
Leads to excess Ca reabsorption –> high serum Ca
What are the biochemical findings of familial hypocalciuric hypercalcaemia?
Ca/Cr ratio <1/100
Ca slightly elevated
What is the treatment for familial hypocalciuric hypercalcaemia?
No treatment needed
What are the different types of pitutiary tumour, and from what cell line do they arise?
Acdiophilic tumours - GHoma, prolactinoma
Basophilic tumours - ACTHoma
Chromophobe tumours - non-secretory
What are the pressure effects of pituitary tumours?
Headache
Bilateral temporal hemianopia
Diabetes insipidus
Hypothalamic effects - temperature control, sleep, appetite
CSF rhinorrhoea - erosion to sella
What is the most common pituitary tumour?
Prolactinoma
What is the relationship between Dopamine and Prolactin?
NEGATIVE FEEDBACK
Prolactin stimulates dopamine release from the hypothalamus
Dopamine inhibits prolactin release
What are the causes of hyperprolactinaemia?
Physiological - stress, pregnancy, breastfeeding
Dopamine antagonists (metoclopramide, haloperidol, risperidone)
Oestrogen
Prolactinoma
Hypothalamic disease
Trauma/surgery (stalk damage)
What are the presenting features of hyperprolactinaemia?
Galactorrhoea + amenorrhoea (females)
Erectile dysfunction + reduced facial hair (males)
Late features - mass effects, osteoporosis
What investigations should be performed in suspected hyperprolactinaemia?
Pregnancy test (ddx amenorrhoea)
Basal prolactin
MRI head
How can prolactinomas be classified?
Microprolactioma <1cm
Macroprolactinoma >1cm
How are microprolactinomas treated?
Dopamine agonist (e.g. bromocriptine, carbegoline)
What are the s/e of dopamine agonists?
Depression
Postural hypotension (give at night)
Nausea
Cause cardiac fibrosis (rarely)
How are macroprolactinomas treated?
Surgery +/- XRT
How does an ACTHoma present?
Cushing’s syndrome
How does a GHoma present?
Acromegaly
How does an FSHoma present?
Macro-orchidism
What is Sheehan syndrome?
Pituitary apoplexy/infarct 2o post-partum blood loss
What are the sx of hypopituitarism?
Addison’s
Hypo’s
SOB (GH loss)
Absent lactation
Amenorrhoea
Infertility + impotence
Hypothyroidism
Osteoporosis (late)
What is the treatment for hypopituitarism?
Hydrocortisone
Thyroxine
Somatotroping
Testosterone/Oestrogen/Gonadotrophin
What is Kallmann syndrome?
Congenital hypogonadotrophic hypogonadism + midline defect (anosmia + colour blindness)
What are the sx of acromegaly?
Acroparaesthesia
Amenorrhoea
Low libido
Headache
Sweating
OSA
Arthralgia/backache
Weight gain
Prognathism, malocclusion
Curly hair
What are the clinical signs of acromegaly?
Large hands/jaw/feet
Corasened facies
Supraorbital ridges
Macroglossia
Thickened/darkened skin
Acanthosis nigricans
Goitre
Proximal weakness
Carpal tunnel
What are the complications of acromgealy?
Impaired glucose tolerance (40%, DM in 15%)
Vascular - HTN, LVH, cardiomyopathy, arrhythmias, IHD
Colorectal ca
How should suspected acromegaly be investigated?
BM
OGTT w/ GH levels (failure to supress)
Ca/PO4 (high)
IGF-1 (gold standard)
GH (serial levels)
MRI
ECG, echo
What is the treatment for acroemgaly?
1st line - Transphenoidal surgery
2nd line - Somatostatin analogues (octreotide)/XRT
How are the causes of hyponatraemia classified?
By volume status
-hypovolaemic
-euvolaemic
-hypervolaemic
What are the hypovolaemic causes of hyponatraemia?
Diuretics
Inherited kidney disorders
GI loss (D/V)
Skin loss (burns/sweat)
Mineralocorticoid deficiencies
What are the euvolaemic causes of hyponatraemia?
SIADH
Hypothyroidism
Short-term diuretics
2o adrenal insufficiency
What are the hypervolaemic causes of hyponatraemia?
Heart failure
Renal failure (+ nephrotic syndrome)
Liver failure
What is SIADH?
Syndrome of ADH excess = concentration of urine
Inappropriately high urine Na >20
High urine Osm >100
What are the causes of SIADH?
Small cell lung ca
Prostate ca/lymphoma
TB, amyloidosis
Surgery
CNS (stroke, infections)
Drugs - SSRIs, opiates, psychotropics, cytotoxines
What is the treatment for SIADH?
Fluid restriction
Demelocycline
-tetracycline that inhibits ADH production
What is diabetes insipidus?
Syndrome of polyuria + polydipsia caused by hyposecretion/insensitivity to ADH
What are the three types of diabetes insipidus?
Nephrogenic DI
Cranial DI
Psychogenic/primary polydipsia
-1o deficit in regulation of osmoregulation of thirst
What are the causes of nephrogenic DI?
Impaired ADH response by kidney
-lithium
-democyclcine
-CKD
-low K
-high Ca
-post-obstructive uropathy
What are the causes of cranial DI?
Reduced ADH secretion from post pituitary gland
-idiopathic (MCC)
-congenital (Wolfram’s)
-brain tumours/bleed/infection
-sarcoidosis
How should suspected diabetes insipidus be investigated?
BMs (DDx DM)
Water deprivation test (8hr)
Urine Osm (<600 in DI)
Desmopressin IM & repeat
-CDI Urine Osm >600 (kidneys respond)
-NDI (no increase)
How should diabetes insipidus be treated?
CDI
-IM Desmopressin
NDI
-Thiazides
-NSAIDs
-treat underlying cause
What is Cushing’s Syndrome?
State of chronic glucocorticoid excess
What are the causes of Cushing’s Syndrome?
ACTH dependent
-Cushing disease (ACTH secreting pituitary adenoma)
-ectopic ACTH producing tumour
-ectopic CRF producing tumour
ACTH independent
-iatrogenic (steroids)
-adrenal adenoma
What are the presenting features of Cushing’s Syndrome?
Proximal weakness
Recurrent Achilles tendon rupture
Mood changes
Acne
Sexual dysfunction (hirsutism, irregular menses, virilisation)
Truncal obesity w/ thin limbs
Supraclavicular fat pad, moon facies
Osteoporosis, HTN, insulin resistance
How can the ACTH dependent and ACTH independent causes of Cushing’s syndrome be differentiated clinically?
ACTH productio ncauses pigmentation
What are the electrolyte abnormalities present in untreated Cushing’s syndrome?
Low K+
High Na
Hyperglycaemia
Metabolic alkalosis
How should Cushing’s Syndrome be investigated?
1st line
-overnight Dex suppression test (failure to suppress)
-high 24hr urine cortisol
2nd line
-48hr low-dose Dex (failure to suppress cortisol)
-48hr high-dose Dex (pituitary causes suppressed)
CT adrenals
MRI pituitary
What are the investigative findings of Cushing’s Disease?
ACTH producing tumour
ACTH - high
Low-dose Dex - not suppressed
High-dose Dex - suppression >50%
CT - bilateral adrenal hyperplasia
MRI - pituitary adenoma
What are the investigative findings of an ectopic ACTH producing tumour?
Paraneoplastic (small cell lung ca, carcinoid)
ACTH - high
Low-dose Dex - not suppressed
High-dose Dex - not suppressed
CT - bilateral adrenal hyperplasia
What are the investigative findings of 1o adrenal adenoma/ca?
Cortisol - high
ACTH - high
Low-dose Dex - not suppressed
High-dose Dex - not suppressed
CT - bilateral adrenal atrophy
What is the treatment for Cushing’s Disease?
Transphenoidal resection of pituitary adenoma
Bilateral adrenalectomy if unable to find source
What is the treatment for an ectopic ACTH producing tumour?
Resection of tumour
AZOLE drugs/mifepristone if tumour not yet located
What is the treatment for a 1o adrenal adenoma/ca?
Adrenalectomy
What is the treatment for excess exogenous steroids?
Taper off steroids
What is Nelson’s syndrome?
Bilateral adrenalectomy performed before treating pituitary adenoma
-leads to disinhibition of that tumour
-aggressive ACTH secretion
-hyperpigmentation, VF defect/opthalmoplegia
-Paradoxical worsening Cushing’s
What is Addison’s disease?
State of low mineralocorticoid and glucocorticoid
What are the causes of Addison’s disease?
Primary (destruction of cortex)
-autoimmune (80%)
-secondary (TB, lymphoma, mets, haemorrhage)
Secondary
-iatrogenic due to acute steroid withdrawal
What is Waterhouse-Friderichsen Syndrome?
Addison’s syndrome 2o haemorrhagic destruction of adrenal cortex
How does Addison’s Syndrome present?
Vague constitutional sx
Unexplained N&V + abdo pain + diarrhoea + dizziness
Acute vascular collapse/coma (crisis)
Hyperpigmentation
Psych - depression, psychosis, anorexia
What are the electrolyte abnormalities of Addison’s Syndrome?
High K
Low Na
Metabolic acidosis
Hypoglycaemia
(Hypotension)
How should suspected Addison’s Syndrome be investigated?
Short synACTHen stimulation test
9am plasma cortisol w/ serial measurements
-no rise in Addison’s
AutoAb
CT adrenals
How should Addison’s Syndrome be treated?
ACUTE crisis - glucose, IVF, hydrocort +/- fludrocort
Non-acute - steroid replacement +/- mineralocrticoid if postural hypotension
What is Conn’s syndrome?
1o hyperaldosteronism
-2/3 due to aldosterone producing adrenal adenoma
-1/3 due to bilateral hyperplasia
How does Conn’s syndrome present?
Triad of
-hypokalaemia
-metabolic acidosis
-HTN
How should suspected Conn’s syndrome be investigated?
Renin (low)
Aldosterone (high)
CT/MRI - localisation
-if unilateral adenoma seen –> adrenal vv sampling
How should Conn’s Syndrome be treated?
Lap adrenalectomy + spironolactone
What is a phaeochromocytoma?
A catecholamine secreting tumour derived from chromaffin cells in the adrenal cortex
How do phaeochromocytomas present?
Triad of
-headache
-sweating
-tachycardia (sense of impending doom)
Where are phaeochromocytomas found?
Rule of 10s
-10% extra-adrenal
-10% malignant
-10% bilateral
-10% FHx
What conditions are commonly associated with phaeochromocytoma?
MEN2A/2B
NF1
Von Hippel Lindau
Sturge-Weber Syndrome
What investigations are indicated in suspected phaeochromocytoma?
24hr urinary metanephrines
Localisation - CT/MRI, isotope scan
How should phaeochromocytoma be treated?
Surgery
Pre-op blockade
-alpha block THEN b-block
How does T1DM typically present?
Symptomatic younger pts
Sudden polyuria/polydipsia
Recurrent UTIs
Thrush
Weight loss
DKA
How does T2DM typically present?
Asymptomatic
Gradual onset
Older pts
What is the underling mechanism of T1DM?
Insulin-dependent autoimmune disease
Low C-peptide
What is the underlying mechanism of T2DM?
Non-insulin dependent due to end-organ insulin resistance
Initially normal C-peptide
What are the diagnostic criteria for DM?
HbA1c >47
OGTT 2hr >11.1
Fasting BM >7.0
Random BM >11.1
Symptomatic pts need 1x abnormal reading
Asymptomatic pts need 2x abnormal readings
What are the two pre-diabetic conditions?
Impaired glucose tolerance
-7.8-11.1 and normal fasting glucose
Impaired fasting glucose
-5.5-7.0 and normal OGTT
What investigations can be performed when there is diagnostic uncertainty in DM?
GADA
B-islet cell Ab
Low C-peptide
high Ketones - Type 1
What is LADA?
Latent autoimmune diabetes in adult
-T1DM that presents in adults
-C-peptide undetectable
What is MODY?
Maturity onset diabetes of young
-autosomal dominant T2DM
-presents <25 y/o
-C-peptide detectable
What is Wolfram Syndrome?
DIDMOAD
-diabetes insipidus
-diabetes mellitus
-optic atrophy
-deafness (sensorineural)
-<16 y/o
-urogenital tract malformations
-neurology (ataxia, seizures, neuropathies)
What is DKA?
Diabetic Ketoacidosis
-acidaemia (pH <7.3/HCO3- <15)
-hyperglycaemia (BM >11 or known DM)
-ketonaemia >3 or ketonuria > ++
How does DKA present?
Acute onset in T1DM
Vomiting
Abdo pain
Dehydration
Polyuria/polydipsia
Fatigue/drowsiness/coma
Ketone breath
Kussmaul resp
How should DKA be treated?
Fixed rate insulin (0.1 unit/kg/hr)
IVI
-including K/dextrose
What is HHS?
Hyperglycaemic Hyperosmolar State
-hypovolaemia
-marked hyperglycaemia >30
-no ketonaemia (<3) or acidosis
-Osm >320
How does HHS present?
Insidious onset
Precipitant (infection/cardiovascular)
Polyuria/polydipsia over weeks - dehydration
Neurological signs
-FND
-visual acuity changes
-confusion –> coma
How should HHS be treated?
Fixed rate insulin (0.05 units/kg/hr)
IVI
-including K+/dextrose
What are the potential complications of DKA/HHS?
Cerebral oedema (replace fluid deficit slowly)
Aspiration pneumonia
VTE
Dehydration
Hypo K/Mg/Po4
How do hypoglycaemic episodes present?
BM <4
Autonomic sx - sweating, anxiety/agitation, tremor, palpitations, dizziness, hunger
Neuroglycopenic sx - drowsy/confusion, visual issues, seizure, coma
How should hypoglycaemic episodes be treated?
Conscious - oral replacement
Drowsy/uncooperative - buccal glucose gel
Unconscious/refractory - 10% dextrose/glucagon gel
What is the DVLA advice for hypoglycaemic episodes?
Stop car safely & switch engine off
Fast-acting carbohydrate
Wait 45mins before resuming
Snack regularly
What are the cardiovascular complications of DM?
Atherosclerosis –> higher MI risk (silent)
Peripheral neuropathy
Retinopathy
Nephropathy
How should blood pressure be managed in DM?
Lower BP target
-T1DM <135/85
-T2DM <140/80
-if end organ damage <130/80
ACEi preferable (except afro-carribean)
How does diabetic Amyotrophy present?
Aymotrophy
-proximal motor neuropathy
-painful progressive weakness w/ wasting
-usually unilateral
-absent knee reflexes
How does diabetic polyneuropathy present?
Glove/stocking distribution of paraesthesia
How does mononeuritis multiplex present?
Acute mononeuropathy (sensory AND motor loss) of non-contiguous nerves
-asymmetrical
How does autonomic neuropathy present?
Postural sx
Gustatory sweating
Impotence
Visual blurring
Gastroparesis
Which antiemetic is first line for gastroparesis?
Metoclopramide (prokinetic)
Which skin changes can present in diabetes?
Lipidoca diabeticorum
-shiny, yellowish area on shin w/ vessel growth
Acanthosis nigricnas
Granuloma annulare
What are the treatment aims for diabetes?
HbA1c <48
HbA1c <53 if hypoglycaemic risk (Sulphonylurea)
What is the first line treatment for T2DM?
Metformin (biguanide)
What are the key features of Metformin?
Stops weight gain
No hypoglycaemic risk
Held/stopped if eGFR <30/Cr>150
What are the s/e of Metformin?
GI upset (try MR)
Lactic acidosis (v. rare)
What is the method of action of Gliclazide?
KATP channel inhibitor = increase insulin secretion
What are the s/e of Gliclazide?
Hepatic cholestasis
Blood dyscrasias
Allergic skin reactions
Weight gain/hypos
What is the method of action of Gliptins?
DPP4 inhibitors increase insulin secretion
What is the method of action of Metformin?
Insulin sensitisation
-only effective if residual islet cells left
What are the s/e of Gliptins?
Headaches
N&V
Heart failure
Pancreatitis/pancreatic ca risk
Arthralgia
What is the method of action of Glitazones?
PPAR-gamma activator –> increase insulin secretion + sensitivity
What are the key features of Glitazones?
Weight gain
Use if insulin resistant/NAFLD
What are the s/e of Glitazones?
Fluid retention (CCF)
Hepatotoxic
Osteoporosis/#
Bladder ca
Drug interactions
What monitoring is required for Glitazones?
LFTs every 2/12 for 1 year
Monitor and stop in 3-6/12 if ineffective
What is the method of action of Gliflozins?
SGLT2 inhibitor –> blocks glucose reabsorption by kidneys –> excess glycosuria
-only effective if eGFR <60
What are the key features of Gliflozins?
Reduced mortality in patients w/ CVD/heart failure
Weight loss
What are the s/e of Gliflozins?
Normoglycaemic DKA
UTIs/thrush/diuresis (glycosuria)
Hyperkalaemia
What is the method of action of Exenatide/Liraglutide?
GLP analogues/mimetics –> augment insulin release/slow gastric emptying
What are the key features of Exenatide/Liraglutide?
Weight loss
No hypos when used alone
What are the indications for Exenatide/Liraglutide?
BMI >35 + psych/medical problems associated w/ obesity OR
BMI <35 + insulin posing occupational implication OR
weight loss may benefit obesity comorbidities
What are the s/e of Exenatide/Liraglutide?
TDS injections
GI s/e
Pancreatitis/pancreatic ca risk
Worsens gastroparesis
C/i if eGFR <30
What is the method of action of Repaglinide/Nateglinide?
Secretogogues/sulphonylurea receptor binders –> increase insulin release
What are the s/e of Repaglinide/Nateglinide?
Rash
GI upset
Hypos
Hepatptoxic
What is the method of action of Acarbose?
Intestinal a-glucosidase inhibitor = less absorption of glucose
What are the key features of Acarbose?
Weight neutral
Reduces post-prandial hyperglycaemia
Used in DUMPING SYNDROME
What are the s/e of Acarbose?
Flatulence + abdo discomfort
Osmotic diarrhoea
What is the method of action of Orlistat?
Inhibits pancreatic/gastric lipases –> steatorrhoea and weight loss
What are the common types of Insulin?
Ultra-fast acting - Novorapid, Humalog
Short-acting soluble - Actrapid, Humulin S
Intermediate-acting - Humulin I, Insulatard
Long-acting - Lantus, Levemir
Tuojeo - v. concentrated
Degludec - v. long acting
Pre-mixed - NovoMix
What insulin regimens are commonly prescribed?
Biphasic
-good for T2DM
Basal-bolus
-QDS insulin
What is the Dawn phenomenon?
Physiologically high BM in the early am
No nocturnal hypos
How should insulin generally be titrated?
Increase dose prior to high BMs by 10%
What is the Somogyi effect?
High rebound BM in the morning due to insufficient night-time insulin delivery in T1DM
What are the sick day rules?
Check BM QDS
Check Ketonuria
Increase insulin dose if BM rising
GP to consider ultra-fast acting insulin
Admit if vomiting, dehydrated, ketotic, children or pregnant
What is the DVLA advice re. diabetic medications?
Notify if on insulin/sulphonylureas AND >1 hypo in last 1/12
HGV drivers
-no hypos last 1/12
-full hypo awareness
-self monitoring at least BD/times of driving
What are the indications for bariatric surgery?
BMI >35 + 1x comorbidity responding to weight loss
BMI 30-34.9 and recent onset T2DM
Consider for Asian pts w/ recent onset T2DM and BM <30
What is Dumping Syndrome and how does it present?
Excess insulin secretion post fundoplication
Presents with
-flushing
-dizziness
-post-prandial hypos
What are the indications for islet cell transplant?
T1DM + >2 severe hypos in 2 years + impaired hypo awareness
What are the contraindications to islet cell transplant?
Obesity
>50U insulin/day
Poor renal function
What is a glucagonoma and how does it present?
Glucagon secreting pancreatic tumour
Presents with
-flushes + diarrhoea
-diabetes
-DVT
-depression
-NME rash
-hyperglycaemia
-weight loss
What is hypoglycaemic hyperinsulinaemia and what are its causes?
Excess insulin causing low BM
Causes
-insulinoma
-fictitious disease/exogenous insulin poisoning/sulphonylurea overdose