Endocrinology Flashcards
What is the role of LH?
Interacts with theca interna cells which results in androgen production
What is the role of FSH?
Stimulates aromatase synthesis which catalyses formation of oestrogens
Stimulates ovum and follicle development
What is sex hormone binding globulin?
B globulin that transports testosterone, dihydrotestosterone and oestradiol in plasma
Where is sex hormone binding globulin produced?
Liver
What might cause a decrease in sex hormone binding globulin levels?
Androgenic things Obesity Hypothyroidism Androgen use Nephrotic syndrome Cushings disease Acromegaly PCOS
What can cause and increase in sex hormone binding globulin levels?
Oestrogenic states Hepatic cirrhosis Hyperthyroidism Oestrogen use Pregnancy Oral contraceptives Anorexia
What can cause pseudohyponatraemia?
Severe hyperlipidaemia
Paraproteinaemia
Iso osmotic non sodium containing fluids to extracellular space - sorbitol/glycine flushing solutions used in urology
What is pseudohyponatraemia?
Low measured serum sodium
Normal serum osmolality
What is Kallmann syndrome?
Congenital disorder of hypothalamic function and reduced pituitary gonadotropic activity
What are the main features of kallmann syndrome?
Hypogonadism
Eunuchoidism
Anosmia
In what disease do you find autoantibodies to glutamic acid decarboxylase?
Diabetes mellitus
What can cause adrenal hypertension?
Primary aldosteronism
Cushing’s syndrome
Phaechromocytoma
What are features of haemochromatosis?
New diagnosis diabetes Hypogonadism Deranged liver function Pigmentation Elevated serum ferritin
A 32 year old lady with BMI of 34 attends clinic complaining of two month history of amenorrhoea. She is noted to have glycosuria and fasting plasma glucose of 12.5. Her oestrogen and prolactin levels are high while LH and FSH concentrations are low. What is the likely diagnosis?
Pregnancy
A 42 year old man with a history of cholecystitis and recurrent abdo pain develops diabetes mellitus. What is the underlying diagnosis?
Chronic pancreatitis
What is the most useful test for assessing the appropriateness of thyroid hormone replacement in primary hypothyroidism?
TSH
What are characteristics of active acromegaly?
Increased sweating
Glucose intolerance
Hypertension
What hormone levels are typical of PCOS?
Elevated testosterone
High LH
What are the Rotterdam criteria for diagnosis of PCOS?
Diagnosis if 2/3:
Oligomenorrhoea or anovulation
Clinical and/or biochemical evidence of hyperandrogenism
Polycystic ovaries on ultrasonography
A 50 year old male with T2DM has a spot urinary albumin:creatinine ratio of 3.4mg/mmol Which drug class should be used to retard progression of his renal disease? Why?
ACE inhibitor
Urinary ACR over 2.5 in man suggests microalbuminuria
First manifestation of diabetic nephropathy and predicts development of overt nephropathy
On which chromosome is the problem in neurofibromatosis type 1?
17
What are characteristics of neurofibromatosis type 1?
Cafe au lait spots Axillary freckling Dermal neurofibromas Nodular neurofibromas Lisch nodules on iris
What are complications of neurofibromatosis?
Nerve compression
Phaechromocytoma
Mild learning disability
Epilepsy
What are features of neurofibromatosis type 2?
Cafe au lait spots
Vestibular schwannomas
Premature cataract
If there is a goitre over which there is a bruit, what is the diagnosis? Why?
Graves’ disease
Associated with angiogenesis and thyroid follicular hypertrophy
What are Graves eye signs?
Conjunctival oedema (chemosis) Exopthalmos Proptosis Lid retraction Lid lag Periorbital puffiness
What is a dermatological manifestation of Graves’ disease?
Pretibial myxoedema
What are biochemical features of conns syndrome?
Hypokalaemia
Alkalosis
Low renin
HTN
What are causes of conns syndrome?
Adrenal adenoma
Bilateral adrenal hyperplasia
What are some causes of SIADH?
Hypothyroidism Bronchial Ca Pneumonia Head injury Subarachnoid haemorrhage
How do you calculate plasma osmolality?
(2 [sodium + potassium] + glucose + urea)
What problems are associated with GH therapy?
Pituitary derived GH: CJD
Recombinant GH: IIH
How is a diagnosis of Addison’s disease made?
Demonstrating low cortisol levels without diurnal variation with a raised ACTH
Synacthen test shows failure of cortisol secretion following subcutaneous admin of ACTH
A 62 year old is reviewed complaining of lethargy and fatigue. He smokes 10 cigarettes a day and drinks 15 units of alcohol a week. His blood tests show a hyponatraemia of 128. What are 2 appropriate investigations for this patient? Why?
Chest X-ray - bronchial Ca with SIADH
TFTs - hypothyroidism
A 59 year old male attends clinic for his first annual review of type 2 diabetes. Most recently he had problems with OA affecting hips and 2nd/3rd metacarpophalangeal joints. Currently he takes aspirin and metformin. When his LFTs are checked prior to commencing a statin, he is found to have AST 78, ALT 88, ALP 210, bilirubin 10. He doesn’t drink, his BMI is 24, he is negative for hep B and C, he is negative for ANA, ASMA, LKM and AMA. His caeruloplasmin is normal. What is the likely cause?
Haemochromatosis
Where is leptin produced?
Adipocyte
Where are receptors for leptin located? What is it’s effect?
Arcuate nucleus in the hypothalamus
Produces satiety
What are clinical features of acromegaly?
Spade like hands Prominent supraorbital ridge Prognathism Macroglossia Carpal tunnel syndrome Oily skin Paraesthesia Visual field disturbance Hypopituitarism
What are complications of acromegaly?
Hypertension
Cardiomyopathy
Hyperglycaemia/diabetes mellitus
Bowel tumours
What is whipples triad?
Diagnosis of hypoglycaemia requires:
Evidence of plasma hypoglycaemia <3
Associated symptomatology
Resolution of sequelae with correction of hypo
What is the management of hypoglycaemia in an inpatient who has reduced consciousness?
100ml 20% dextrose IV
What causes of hypoglycaemia should be investigated if the episode cannot be explained?
EXPLAIN EXogenous insulin administration Pituitary insufficiency Liver failure Alcohol/autoimmune/Addisons Insulinoma Neoplasia
What can cause Thyrotoxicosis?
Graves’ disease
Multinodular goitre
Drug induced - Amiodarone
A 13 year old girl starting wetting the bed after being dry from the age of 3. Mother notices she is drinking large volumes of fluids. Two days later she has difficulty breathing and loses consciousness. What is going on?
Diabetes mellitus
May initially present as enuresis
An 8 month old infant boy is failing to thrive. He is vomiting, dehydrated, polyuric and is irritable. His blood sugars are normal and he doesn’t have a UTI. What’s going on?
X linked recessive nephrogenic diabetes insipidus
What conditions make up sipple syndrome?
MEN2A
Bilateral medullary carcinoma of thyroid or C cell hyperplasia
Phaeochromocytoma
Hyperparathyroidism
At what HbA1c level should you add in a second antidiabetic drug after Metformin has been titrated?
58 (7.5%) and above
What is the target HbA1c for patients with diabetes using lifestyle changes alone or lifestyle and Metformin?
48 (6.5%)
What is the target HbA1c for patients with diabetes using any drug which may cause hypoglycaemia?
53 (7%)
What drugs can be added in if Metformin is not adequately controlling diabetes and HbA1c remains above 58?
Gliptin
Sulfonylurea
Pioglitazone
SGLT2 inhibitor
What is the therapy of choice if triple therapy (Metformin plus 2 others) are not effective, not tolerated or contraindicated and the patient has a BMI of over 35?
Metformin and sulfonylurea and GLP1 mimetic (exanatide)
What risk factor modifications are important in diabetes?
Blood pressure target <140/80 or <130 if end organ damage present. ACEi first line
Antiplatelets only if existing CV disease
Statin if QRISK2 score >10%
What are diagnostic criteria for diabetes?
If symptomatic:
Fasting glucose 7 or more
Random glucose/OGTT 11.1 or more
Asymptomatic: same but on two separate occasions
In what conditions can HbA1c not be used for diagnosis?
Haemaglobinopathies Haemolytic anaemia Untreated Iron deficiency anaemia Suspected gestational diabetes Children HIV CKD
What HbA1c value is diagnostic of diabetes?
48 or more
How do you diagnose impaired fasting glucose?
Fasting glucose 6.1 or more but less than 7
How do you diagnose impaired glucose tolerance?
Fasting plasma glucose less than 7
OGTT 7.8 or more, less than 11.1
What is McCune Albright syndrome? What are features?
Genetic condition affecting bone, skin and endocrine systems
Early puberty in girls, bone fractures, gigantism, cafe au lait spots
What are features of an Addisonian crisis?
Hyponatraemia
Hyperkalaemia
Hypoglycaemia
What can cause an Addisonian crisis?
Sepsis or surgery causing an acute exacerbation of chronic insufficiency
Adrenal haemorrhage (Waterhouse friderichsen syndrome)
Steroid withdrawal
What is the management of Addisonian crisis?
Hydrocortisone 100mg IM or IV
1L normal saline infused over 30-60 mins, with dextrose if hypoglycaemic
Continue hydrocortisone every 6h until stable
Oral replacement may begin after 24h and reduce to maintenance over 3-4 days
What are some causes of Gynaecomastia?
Physiological: normal in puberty
Syndromes with androgen deficiency: Kallman’s, Klinefelter’s
Testicular failure: e.g. mumps
Liver disease
Testicular cancer e.g. seminoma secreting hCG
Ectopic tumour secretion
Hyperthyroidism
Haemodialysis
Drugs: spironolactone, cimetidine, digoxin, cannabis, finasteride, gonadorelin analogues e.g. Goserelin, buserelin, oestrogens, anabolic steroids
What are some contraindications for Metformin use?
Chronic kidney disease: NICE recommend dose should be reviewed if creatinine is > 130 micromol/l (or eGFR < 45 ml/min) and stopped if the creatinine is > 150 micromol/l (or eGFR < 30 ml/min)
Metformin may cause lactic acidosis if taken during a period where there is tissue hypoxia - recent MI, sepsis, AKI and severe dehydration
Iodine-containing x-ray contrast media: peripheral arterial angiography, coronary angiography, intravenous pyelography (IVP); there is an increasing risk of provoking renal impairment due to contrast nephropathy; metformin should be discontinued on the day of the procedure and for 48 hours thereafter
Alcohol abuse is a relative contraindication
Why does refeeding syndrome occur? What changes are seen?
Exogenously administered glucose results in insulin release and therefore rapid uptake of glucose, potassium, phosphate and magnesium into cells. Fluid is also retained into the extracellular space.
Abnormal fluid balance, vitamin deficiency, hypophosphataemia, hypomagnesaemia, hypokalaemia
What are the most common causes of hypercalcaemia?
Malignancy: bone mets, myeloma, PTHrP
Primary hyperparathyroidism
What are some less common causes of hypercalcaemia to consider beside malignancy and hyperpararhyroidism?
Sarcoidosis TB Vitamin D intoxication Acromegaly Thyrotoxicosis Milk alkali syndrome Thiazides Calcium containing antacids Dehydration Addison's disease Paget's disease of bone
How is Addison’s disease likely to present?
Weight loss
Abdominal pain
Lethargy
Nausea and vomiting
What are causes of hyoadrenal crisis?
Addison's disease TB HIV Adrenal haemorrhage Anterior pituitary disease
What biochemical changes will you see with Addison’s disease?
Hypoglycaemia
Hyponatraemia
Hyperkalaemia
Why is Addison’s disease associated with pigmentation?
Excess ACTH and therefore MSH (melanocyte stimulating hormone)
What effect does the administration of GnRH have on levels of oestrogen and how is this beneficial in endometriosis?
Induce a state of hypogonadotrophic hypogonadism or psuedomenopause with low circulating levels of oestrogen
What is the management for hypoadrenal crisis due to Addison’s disease?
Fluid resuscitation
Urgent cortisol measurement
Steroid administration
Search for occult infection
What are the most common causes of hypertriglyceridaemia?
Obesity Alcohol intake Hypothyroidism Insulin resistance Poorly controlled diabetes Pregnancy Familial hypertriglyceridaemia
At what level of GFR should liraglutide (GLP1 agonist) be avoided?
If GFR <60
At what level of GFR should saxagliptin (DPP4 inhibitor) be prescribed at half dose?
<50
What are some causes of SIADH?
Malignancy: small cell lung cancer, pancreas, prostate
Neuro: stroke, SAH, subdural, meningitis
Infections: TB, pneumonia
Drugs: sulfonylureas, SSRI, TCA, carbamazepine, vincristine, cyclophosphamide
PEEP
Porphyria
How is SIADH managed?
Correction slowly to avoid central pontine myelinolysis
Fluid restriction
Demeclocycline
Vasopressin antagonist
How is Addison’s disease managed?
Hydrocortisone: 20-30mg/day, majority in morning dose
Fludrocortisone
Education on importance of not missing doses
MedicAlert bracelet/steroid card
Intercurrent illness, dose should be doubled
What are causes of an Addisonian crisis?
Sepsis or surgery causing acute exacerbation of chronic insufficiency
Ardrenal haemorrhage (waterhouse friderichsen syndrome)
Steroid withdrawal
What is management for an Addisonian crisis?
Hydrocortisone 100mg IM or IV
1L normal saline infused over 30-60 mins, or dextrose if hypoglycaemic
Continue hydrocortisone 6h until patient is stable
Oral replacement after 24h and reduce to maintenance over 3-4 days
What is maturity onset diabetes of the young?
Development of type 2 diabetes in patients under 25
Autosomal dominant condition
Usually responsive to sulfonylureas
What are the 3 Ds of pellagra (niacin deficiency)?
Dementia
Diarrhoea
Dermatitis
What are causes of hypercalciuria?
Vitamin D excess
High rates of skeletal turnover eg hyperparathyroidism
Renal tubular acidosis
Treatment with loop diuretic
Why is skin pigmentation seen with primary adrenal failure but not with secondary insufficiency?
Primary: problem in adrenal gland, lack of cortisol so compensatory increase in ACTH. This is made from POMC precursor which also is broken down to MST. This stimulates melanocytes so giving hyperpigmentation
Secondary: hypopituitarism and so lack of ACTH
What is thyroid acropachy?
Clubbing of fingers Painless Periosteal bone formation Periosteal proliferation Soft tissue swelling, pigmented and hyperkeratotic
What is pre tibial myxoedema?
Slightly raised pinkish indurated patches usually on fronts of shins or dorsum of foot
Associated with Graves’ disease
What are some features of diabetic autonomic neuropathy?
Tachycardia Constipation Impotence Urinary retention Gastroparesis Anhydrosis
What is the most appropriate treatment for diabetic gastroparesis?
Metoclopramide
Which anti diabetic mediation is associated with fluid retention and weight gain?
Pioglitazone
Why should metformin not be prescribed in patients with renal, hepatic or heart failure?
Lactic acidosis risk
What can form at the injection site of insulin?
Lipodystrophy
What is a problem with using porcine insulin?
Development of anti insulin antibodies
Which disease processes can cause salivary/parotid enlargement?
Lymphoma Sarcoidosis Parotid tumour Calculi Virus: mumps Alcohol excess Anorexia nervosa/ bulimia
Deficiency of which other electrolyte can result in treatment unresponsive hypocalcaemia?
Magnesium as it is required for action of PTH
What are causes of raised prolactin?
Pregnancy Prolactinoma Physiological PCOS Primary hypothyroidism Phenothiazines, metoclopramide, domperidone
What are causes of peripheral neuropathy?
Diabetes Alcohol Vitamins (B) Infection (Guillain Barre) Drugs: amiodarone, anticonvulsants, isoniazid, nitrofurantoin
What are complications of pagets?
Hypercalcaemia High output failure Pathological fractures Platybasia (malformed relationship between occipital bone and cervical spine) Sarcoma
What is the most common cause of hirsutism in women?
PCOS
What is hitsutism?
Androgen dependent hair growth in women
What are causes of hirsutism?
PCOS Cushing's syndrome Congenital adrenal hyperplasia Androgen therapy Obesity (peripheral conversion oestrogen to androgen) Adrenal tumour Androgen secreting ovarian tumour Phenytoin
What is the Ferriman-Gallwey scoring system?
Assessment of hirsutism
9 body areas assigned a score 0-4. Score >15 indicates moderate to severe
What is the management of hirsutism?
Weight loss
Waxing/bleaching
COCP - dianette or Yasmin
Facial: topical eflornithine (not in preg or breast feeding)
What are risk factors for scurvy?
Elderly patients particularly if live alone Patients in developing world Alcohol dependent Smokers Unbalanced diet Peritoneal dialysis or haemodialysis
What is the appropriate test for suspected phaeochromocytoma?
24 hour urinary vanillymandelic acid measurement (VMA)
Which is the most appropriate test for suspected Addisons?
Synacthen test
What are appropriate screening tests for Cushing’s syndrome?
1mg overnight dexamethasone suppression test (given at 11pm and cortisol measured at 9am)
24 hour urine free cortisol collection
Why does a VIPoma lead to hypokalaemic acidosis?
Loss of alkaline secretions
Why does thyrotoxicosis lead to hypercalciuria and elevated alk phos?
Increased bone turnover
What are features of vitamin A deficiency?
Night blindness Dry skin Dry conjunctiva Xerophthalmia Bitots spots (white plaques of keratinised epithelial cells in conjunctiva)
How does vitamin C deficiency present?
Bleeding gums
Muscle pain
Periosteal and perifollicular haemorrhages
What are clinical features of osteomalacia?
Bone pain
Waddling gait due to proximal myopathy
Fractures
What are features of pellagra?
Diarrhoea Dementia Dermatitis Neuropathy Ataxia Fits
What is pellagra?
Lack of nicotinic acid
Which hormones are released from the adrenal gland?
Mineralocorticoids
Glucocorticoids
Androgrens
Stress hormones
What is the role of glucocorticoids in the body?
Facilitates hepatic gluconeogenesis
Inhibition of glucose uptake in muscle
Inhibition of protein synthesis
Reduces inflammatory processes
Which zones of the adrenal gland are responsible for making each hormone?
Zona glomerulosa: mineralocorticoids
Zona fasciculata: glucocorticoids
Zona reticularis: androgens
Medulla: catecholamines
What controls CRH release from the hypothalamus?
Circadian rhythm
Stress
What are the biochemical abnormalities seen with Addison’s disease?
Hyponatraemia
Hyperkalaemia
Hypoglycaemia
How is a diagnosis of Addisons made?
Short Synacthen Test (SST): IV or IM injection of synthetic ACTH (tetracosactide), If cortisol level after 30 mins fails to rise above 550nmol/L = adrenal insufficiency
What is the management for addisons?
Long-term corticosteroid and mineralocorticoid replacement
Hydrocortisone: 20mg daily – 10mg on waking, then 10mg mid-afternoon or 5mg midday and 5mg mid-late afternoon
Replaces circadian rhythm
Fludrocortisone: Longer acting therefore only require 100 microgram OD
Patients entirely dependent on tablet replacement
Sick day rules
Steroid card
What are signs and symptoms of Cushing’s?
Hyperglycaemia Moon face Gynaecomastia Fat deposit on face and back of shoulders Osteoporosis Sodium and fluid retention Amenorrhoea Hirsutism Thin skin Purple striae Bruises
How do you diagnose Cushing’s?
Dexamethasone suppression test - potent synthetic glucocorticoid that inhibits normal ACTH production
Low-dose dexamethasone suppression test: Defines glucocorticoid excess, Single 1mg dose at midnight, Failure to suppress 9am serum cortisol (<50nmol/L) = Cushing syndrome
High-dose dexamethasone suppression test: Localises glucocorticoid excess, 2mg x 8 doses 6hrly ending at midnight, >50% suppression at 9am of cortisol = Anterior pituitary source, <50% suppression at 9am = Extrapituitary ‘ectopic’ source
What is the management of Cushing’s?
Surgical: Adrenal adenoma = adrenalectomy, Pituitary adenomas = transsphenoidal surgery
Rapid removal of cause can cause relative adrenal insufficiency so may need hydrocortisone cover until return to normal
Not fit for surgery: Radiotherapy, Metryrapone – inhibit glucocorticoid secretion
What are causes of conns syndrome?
Discrete adenoma - tumour of the zona glomerulosa
Bilateral hyperplasia
What are signs and symptoms of conns syndrome?
Hypokalaemia: Muscle fatigue, Tiredness
Hypertension: Headaches, Visual disturbances
How is a diagnosis of conns made?
Evidence of features suggestive: Severe hypertension BP >180/100 mmHg, Difficult to control HTN despite use of multiple anti-hypertensive agents, Hypertension at a young age, Hypertension with spontaneous or diuretic induced hypokalaemia
Hypertension in patients with coexisting adrenal adenoma or hyperplasia
Calculation of the aldosterone:renin ratio – increased in disease
Confirmation of adrenal tumour on CT
What are some side effects of treatment with recombinant human growth hormone?
Raised ICP with normal MRI: results from antidiuretic effect, most common in those with impaired renal function SUFE Malignancy Gynaecomastia Impaired glucose metabolism
Which test is most appropriate for diagnosing acromegaly?
Oral glucose tolerance test
What is the gold standard test for assessment of dynamic pituitary function including cortisol and growth hormone secretory capacity?
Insulin tolerance test
What is diabetic nephropathy?
Persistent albuminuria >300 mg/day or >200 micrograms/min
Confirmed on at least 2 occasions 3-6 months apart
Relentless decline in GFR
Elevated BP
What are signs of hyperprolactinaemia?
Reduced libido and arousal Gynaecomastia Menstrual irregularities Amenorrhoea Galactorrhoea
What are features of acromegaly?
Coarse facial appearance Spade hands Increase shoe size Large tongue Prognathism Interdental spaces Excessive sweating and oily skin Hypopituitarism Headaches Bitemporal hemianopia Galactorrhoea
What are complications of acromegaly?
HTN
Diabetes
Cardiomyopathy
Colorectal cancer
What is the management of conns syndrome?
Surgical management: Unilateral adrenalectomy in presence of adenoma
Medical management: Spironolactone – mineralocorticoid receptor antagonist, Will result in rapid fall in refractory high blood pressure
What is Phaeochromocytoma?
Tumour of the adrenal medulla secreting excessive catecholamines: Adrenaline / noradrenaline / dopamine
What are signs and symptoms of Phaeochromocytoma?
Intermittent due to paroxysmal release Anxiety / headache Palpitations / tachycardia Hypertension Sweating
How is a diagnosis of Phaeochromocytoma made?
Urine collections of catecholamines or metabolites
24-hour urine metadrenaline and normetadrenaline collection due to variable production of catecholamines throughout day
Total urinary levels elevated in phaeochromocytoma
Plasma tests for metabolites higher sensitivity
What is the management of Phaeochromocytoma?
Prevention of hypertensive crisis
Stabilise on medical therapy prior to any definitive surgical intervention
Medical: Blockade of alpha-adrenoceptors (doxazosin), Control peripheral vasoconstriction and hypertension, Control blood pressure
Followed by beta-adrenoceptor blockade (bisoprolol), Control pulse rate
Surgical removal of tumour
What percentage weight loss should a patient be aiming for if they are put on orlistat?
5% weight loss in 3 months
What levels of HBA1c are diagnostic for diabetes?
One off reading 48 if symptomatic
If no symptoms, 2 readings of 48 or more 3 months apart
How often should women who have gestational diabetes be screened post partum?
Check initially post partum then repeat annually
What should the HbA1c target of a diabetic controlled with diet alone be?
48
What should the HbA1c target be for a diabetic patient on any drugs which may cause hypoglycaemia?
53
Why should metformin be stopped in a patient with an MI?
Risk of lactic acidosis
How does diabetic amyotrophy present?
Asymmetrical painful wasting of quadriceps and areflexia
What are some manifestations of autonomic neuropathy?
Postural hypotension
Impotence
Gastroparesis
Neuropathic bladder
What is the treatment for acromegaly?
Somatostatin analogues
Surgery
What is the treatment for a prolactin secreting tumour?
Bromocriptine or cabergoline (dopamine agonists)
Surgery
In a patient presenting with cushingoid features, what does a lack of suppression of cortisol levels with high dose dexamethasone suggest?
Ectopic source of ACTH for example from a small cell lung cancer
What are the features of metabolic syndrome?
Increased waist circumference: >94cm men, 80cm women. Or BMI over 30 Raised triglycerides: >1.7 Reduced HDL: <1.03, <1.29 in women Raised BP: >130/85 or treated HTN Raised fasting plasma glucose: >5.6
Why does a hydatidiform mole lead to high levels of thyroxine?
Beta HCG is very similar in structure to LH, FSH and TSH so high levels can lead to production of T4 and T3
Which diabetic patients should be offered statin therapy?
Type 1 who do not have established CVD risk factors but are:
Older than 40
Have had diabetes for more than 10 years
Have established nephropathy
Have other CVD risk factors such as obesity and HTN
What are some causes of predominantly hypercholesterolaemia as opposed to hypertriglceridaemia?
Nephrotic syndrome
Cholestasis
Hypothyroidism
Which antibodies are likely to be present in type 1 diabetes?
Islet cell
Glutamic acid decarboxylase
What are features of diabetic autonomic neuropathy?
Impotence Postural hypotension Gastroparesis Steatorrhoea (bacterial overgrowth) Atonic distended bladder
What features confirm hyperosmolar hyperglycaemic state?
Dehydration
Osmolality >320
Hyperglycaemia >30 with pH >7.30, bicarbonate >15 and no significant ketonaemia <3
What 2 differentials account for 90% of hypercalcaemia cases?
Primary hyperparathyroidism
Malignancy
In which condition are Kimmelstiel Wilson nodules seen in the kidney?
Diabetic nephropathy
What are 3 ways of monitoring glucose control over time?
HbA1c
Fructosamine
Log book of blood sugar levels
What does dexa stand for?
Dual energy X-ray absorptiometry
What is maturity onset diabetes of the young?
Development of type 2 diabetes mellitus in patients under 25
Inherited as autosomal dominant
What is the most common presentation of men 1?
Hypercalcaemia
Which gene causes men 2?
RET oncogene
At what level of HbA1c does an additional medication need to be added for glycaemic control?
58
What biochemical abnormalities are seen in congenital adrenal hyperplasia?
Increased plasma 17 hydroxyprogesterone
Increased plasma 21 deoxycortisol
Increased urinary adrenocorticosteroid metabolites
What is congenital adrenal hyperplasia?
Autosomal recessive inherited condition
Deficiency of 21 hydroxlase enzyme which is responsible for synthesis of aldosterone and cortisol
How does congenital adrenal hyperplasia present?
Due to inadequate mineralocorticoids: vomiting due to salt-wasting leading to dehydration and death
Due to excess androgens: azoospermia, ambiguous genitalia in some females, such that it can be difficult to identify external genitalia as male or female, early pubic hair and rapid growth in childhood, precocious puberty or failure of puberty to occur, excessive facial hair, virilization, and/or menstrual irregularity in adolescence, infertility due to anovulation, clitoromegaly, enlarged clitoris and shallow vagina
Due to insufficient androgens and estrogens: Undervirilization in XY males with female external genitalia, In females, hypogonadism, sexual infantilism or abnormal pubertal development, infertility
What are causes of hirsutism?
PCOS Cushings CAH Androgen therapy Obesity Adrenal tumour Androgen secreting ovarian tumour Phenytoin
What scoring system is used to assess hirsutism?
Ferriman Gallwey score: 9 body areas assigned a score 0-4
Score >15 is moderate to severe hirsutism
What is the management of hirsutism?
Advise weight loss if overweight
Cosmetic techniques: waxing/bleaching
Dianette (co-cyprindiol) or Yasmin (drospirenone)
Facial: topical eflornithine
What are causes of hypertrichosis?
Drugs: minoxidil, ciclosporin, diazoxide
Congenital hypertrichosis lanuginosa
Anorexia nervosa
Porphyria cutanea tarda
What is nelsons syndrome?
Rapid enlargement of a pituitary corticotroph adenoma that occurs after removal of both adrenal glands
What investigation should be done for suspected phaeochromocytoma?
24 hr urinary collection of metanephrines
What are sick day rules for diabetics?
Increase frequency of glucose monitoring to 4 hourly or more frequently
Encourage fluid intake aiming for at least 3 litres in 24 hours
If unable to eat, sugary drinks to maintain carb intake
Continue to take meds even if not eating much
What is the management of Hyperosmolar hyperglycaemic state?
Slow rehydration with IV infusion of 0.9% saline over 2 days
What are risk factors for diabetes?
Modifiable: Obesity, Deprivation, Diet, Physical Activity, Smoking
Non modifiable: Age, Sex, Ethnicity, FH of Diabetes, Gestational Diabetes
How does diabetes present?
Thirst Frequency Polyuria Weight Loss Tired all the time
What are benefits of Metformin?
Reduces CVD risk
Optimises control
Weight loss
What are important side effects and complications of Metformin?
Lactic Acidosis with low eGFR
Gastric upset
What is target HbA1c for a patient on a sulfonylurea?
53
What are side effects and risks of DPP4 inhibitors?
Acute Pancreatitis
Derangement of LFTs
Which DPP4 inhibitors can be used for diabetes?
Alogliptin (first line CCG recommendation)
Linagliptin safe in renal impairment
What are problems with pioglitazone?
Associated with bladder cancer
Do not use in heart failure
What is the mechanism of action of Metformin?
Decreased hepatic gluconeogenesis by inhibition of mitochondrial respiratory chain complex 1
Increases insulin sensitivity to enhance peripheral glucose uptake by GLUT4
Decrease glucose absorption from GI tract
What is the dose of Metformin?
500mg BD
What are contraindications to use of Metformin?
Impaired renal function: stop if GFR <30 Cardiac or respiratory insufficiency Liver disease, alcohol abuse History of metabolic acidosis Severe sepsis Use of IV contrast media: stop couple of days before to prevent AKI
What are adverse effects of Metformin?
Lactic acidosis: very rare, 0.03 cases / 1000 patient years, 50% mortality
GI symptoms
B12 malabsorption
What is the mechanism of action of sulfonylureas?
Bind to and close ATP sensitive K channels on pancreatic beta cells which depolarises cell leading to opening of voltage gated Ca channels leading to increased fusion of insulin granules with cell membrane and therefore increased secretion of proinsulin
What are adverse effects of sulfonylureas?
Hypoglycaemia Weight gain: 1-4 kg in 6 months Gastrointestinal symptoms in 3% Allergic rash Bone marrow suppression
What is the mechanism of action of acarbose?
Alpha glucosidase inhibitor
Prevent digestion of carbohydrates
What does nice recommend on use of acarbose as an oral hypoglycaemic drug?
Use only in individuals intolerant of other OHDs
What is the mechanism of action of Thiazolidinediones (glitazones)?
PPAR-gamma agonist
Nuclear receptor which leads to transcription of insulin sensitive genes: lipoprotein lipase, GLUT4, fatty acid transport protein
What are contraindications to glitazones?
Oedema
Anaemia
Impaired liver function
Can worsen macular oedema
What are adverse effects of glitazones?
Fluid retention : oedema , heart failure , anaemia
Weight gain : 1 – 4 kg in 6 months
Hypoglycaemia in combination with other oral agents
Increased risk of distal fractures
Unforeseen chronic effects
Can induce ovulation - increasd risk of pregnancy
What are examples of GLP1 agonists?
Exenatide
Liraglutide
Lixisenatide
Dulaglutide
What are examples of DPP4 (Dipeptidyl peptidase-4) inhibitors?
Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, Alogliptin
What is the mechanism of action of GLP1 agonists?
Incretin mimetics Increase insulin sensitivity Decrease hepatic glucose production Decrease gastric emptying and GI motility Decrease appetite, increase satiety
What is the mechanism of action of DPP4 inhibitors?
DPP4 enzyme inactivates GLP1 so inhibit this to increase GLP1 levels
What are advantages of GLP1 agonists?
Improves glycemic control – 0.5 to 1%
Promote weight loss
Low risk of hypo on its own
Improves lipid profile
What are side effects of GLP1 agonists?
GI symptoms
Rare risk of pancreatitis due to islet cell hyperplasia
Risk of hypo when used with insulin or SU
What are advantages of gliptins (DPP4 inhibitors)?
No weight loss, hypos or slowing of gastric emptying
Adverse events comparable to placebo
When should DPP4 inhibitors be prescribed?
Consider as 2nd line instead of SFU if : Hypos may be a problem, SFU contraindicated or intolerant
Use as 3rd line therapy
May be preferable to glitazone if : Weight gain may be a problem, Glitazone contraindicated or not tolerated
Stop if A1c reduction at 6 months < 0.5%
What is the mechanism of action of dapagliflozin?
Selectively inhibits SGLT2 in the renal proximal tubule so blocks reabsorption of glucose back into blood
What are complications of dapagliflozin?
Vulvovaginitis, balanitis and related genital infections - thrush
What are examples of fast acting insulin?
Novorapid
Humalog
Apidra
What are examples of long acting insulins?
Glargine
Levemir
Degludec
Toujeo
What are examples of pre mixed insulins?
Novomix 30
Humalog Mix
What are examples of different insulin regimes?
Once-daily regimen: Long acting or intermediate acting insulin administered at bedtime
Twice-daily regimen: A biphasic insulin is injected twice a day (pre-breakfast and pre-evening meal)
Basal-bolus regimen: Intermediate- or long-acting insulin is administered at night, plus short acting insulin at meal times. This regimen provides tight glycaemic control but requires more frequent injections
What is the alphabet strategy for improving diabetic health?
Advice: Smoking , diet , exercise Blood pressure: < 140/80 Cholesterol: TC 4 or less , LDL : HDL 2 or less Diabetes control: HbA1c 7% or less Eye examination: Annual examination Feet examination: Annual examination Guardian drugs: Aspirin, ACEI, statins
What are criteria for use of GLP1 mimetics?
BMI > 35 and weight related co-morbidities/psychological issues
BMI < 35 and insulin has occupational implications, or weight loss likely to help co-morbidities
What are eye signs of Graves’ disease?
Proptosis, lid lag, lid retraction, chemosis, Grittiness Optic neuropathy (colour vision), Ophthalmoplegia
What investigations should be done for a person with suspected Graves’ disease?
TFTs ECG Thyroid autoantibodies Thyroid USS Radio-iodine uptake scan: If unsure about etiology - graves increased uptake. Thyroiditis decreased
What are possible treatments for Graves’ disease?
Carbimazole Propylthiouracil: use in pregnancy Beta-blocker: symptomatic relief Radioiodine: not in pregnancy or thyroid eye disease Thyroidectomy
What changes with thyroid disease in pregnancy?
FT4 falls in early pregnancy (increased TBG)
FT3 remains stable
TSH also falls in first trimester
Graves’ disease usually improves, but relapses post-partum
Hypothyroid patients need 50% more thyroxine
Hyperemesis can cause transient mild hyperthyroidism
What gamma GT result would be inkeeping with acromegaly?
Failure of suppression of gh on GTT
What investigations should be done for acromegaly?
GTT – growth hormone, IGF1
MRI pituitary
Formal visual fields
Pituitary function test
What are features of acromegaly?
Acanthosis nigricans Blood pressure Carpal tunnel Diabetes Enlarged organs Field defect IGF high
What is the management of acromegaly?
Surgical – trans-sphenoidal: Potentially curative (70% micro, 50% macro), Risk of impaired pituitary function
Medical: Somatostatin analogues (octreotide), pegvisomant, dopamine
agonists (bromocriptine), Can result in tumour regression, Primary therapy in some cases, Control of GH secretion after debulking large tumours
Radiotherapy: If GH levels not controlled
What investigations should be done for Addison’s?
U and ES- 40% might have normal k BONE- 10% have high calcium Hypoglycemia Random cortisol B12, folate, TFTS, Iron studies, antibodies Short synacthen test ACTH RENIN ALDOSTERONE
What is the short synacthen test?
ACTH stimulation test 250 mcg ACTH (Synacthen) I.M /I.V 0 and 30 min plasma cortisol 0 min for ACTH Normal subjects plasma cortisol > 460nmol/l either at baseline or at 30 min
What is the management of Addison’s?
Hydrocortisone 15-25mg/day e.g 15mg morning, 5mg evening
Fludrocortisone - in a single dose of 50-200 microg/day
Sick day rules - double dose hydrocortisone
Why do steroids worsen diabetic control?
Causes insulin resistance in skeletal muscle by directly inhibiting translocation of GLUT4 to plasma membrane
Sensitivity of glycogen synthesis and glucose oxidation decreased
What is autoimmune polyglandular syndrome type 1?
Autosomal recessive Adrenal insufficiency Hypoparathyroidism Chronic mucocutaneous candidiasis Primary gonadal failure Primary hypothyroidism Malabsorption Pernicious anaemia Chronic active hepatitis Vitiligo
What is the investigation of choice for haemochromatosis?
Serum ferritin raised Transferrin saturation (serum iron/total iron binding capacity) raised HFE genetic testing
What is a short synacthen test?
Serum cortisol measured before and 30 mins after 250 micrograms synthetic ACTH
If insufficient response, Addison’s/ atrophy or destruction of adrenal glands
What is the PPAR gamma receptor? How is it used in treating diabetes?
Intracellular nuclear receptor
Natural ligands are free fatty acids
Controls adipocyte differentiation and function
Thiazolidinediones are agonists at receptor and reduce peripheral insulin resistance
What are features of hyperosmolar hyperglycaemic state?
Severe hyperglycaemia
Dehydration and renal failure
Mild/absent ketonuria
What causes mortality in HHS?
Rhabdomyolysis VTE Lactic acidosis Hypertriglyceridaemia Renal failure Stroke Cerebral oedema
What are precipitants of HHS?
New diagnosis T2DM Infection High dose steroids MI Vomiting Stroke VTE Poor treatment compliance
What is first line management of diabetic neuropathy pain?
Amitriptyline
Duloxetine
Gabapentin
Pregabalin
What are management options for gastroparesis?
Metoclopramide
Domperidone
Erythromycin
All prokinetic agents
What is subacute thyroiditis?
Associated with viral infections
Characterised by transient hyperthyroidism and high ESR
What is the most common variety of congenital adrenal hyperplasia?
21 hydroxylase deficiency
What is the function of 21 hydroxylase?
Conversion of 17 hydroxyprogesterone to cortisol and aldosterone
How can virilisation be prevented in congenital adrenal hyperplasia?
Early treatment, in vivo treatment with steroids for mother
How can adrenal crisis present in a neonate?
Hyponatraemia
Hypotension
Hypoglycaemia
What is the most appropriate initial investigation for Cushing’s syndrome?
24 hour urine free cortisol concentration
What are the rules on driving if a patient has a hypoglycaemic episode?
Stop car, treat hypoglycaemia, move out of drivers seat and wait 45 mins after blood glucose has risen above 4
What are rules on driving a HGV if insulin dependent diabetic?
Can drive if:
No severe episodes hypo in previous 12 months
Has full hypo awareness
Must show adequate control of condition by regular monitoring (at least twice daily)
Must demonstrate understanding of risks
No other debarring complications of diabetes
What are rules for non insulin dependent diabetics on driving?
2 episodes of hypo needing third party assistance in 12 months or lacking hypoawareness or have has disabling hypos while driving must inform DVLA
What are signs of hypothyroidism on examination?
Dry skin/hair Loss of lateral 1/3 eyebrows Goitre Bradycardia Ataxia Mental slowness Carpal tunnel Slow reflexes Peaches and cream complexion Peripheral neuropathy
What are causes of hypothyroidism?
Drugs: amiodarone, lithium Autoimmune Cancer Radiotherapy Infection Hypopituitarism
What are signs of hyperthyroidism on examination?
Tachycardia Fast AF Warm peripheries Goitre Opthalmoplegia Pretibial myxoedema Thyroid acropatchy Palmar erythema Thinning of hair Brisk reflexes Lid lag Exophthalmos
What are non diabetic causes of hypoglycaemia?
Liver failure Addison’s Insulinoma Alcohol excess Pituitary insufficiency
