Endocrine Flashcards
Diabetes
Type 1 vs Type 2
Insulin release
Insulin action
Autoimmune destruction of pancreatic islet cells leading to reduced insulin
Hypersecretion of insulin by depleted beta cell mass. Increasing insulin resistance
Alpha cells: glucagon, beta cells: insulin
Glucose -> beta cell. Enters via GLUT-2. Increases ATP. ATP closes K+ channels which depolarise cell. VgCa channels open Ca to cell. Insulin released.
To peripheral muscle. Binds insulin receptor. Mobilises GLUT-4 to membrane. Glucose able to enter cell.
Increase glucose -> increased insulin
Increase uptake liver (200g) and muscles (150g) as glycogen
Suppresses gluconeogenesis, lipolysis, proteolysis, ketogenesis
Type 1 DM
Aetiology
Presentation
Complications
Genetic predisposition and autoimmune process (insulin/islet cell autoantibodies)
Family history of other autoimmune conditions HLA DR3/4
Polyuria, polydipsia, weight loss, lethargy, DKA problems… (dehydration, breathing, abdo pain)…
DKA
Type 2 DM
Who
RF
Pres
30+ obese, low physical activity
Obesity (trunk i.e. metabolic), lack of activity, PCOS, metabolic syndrome, family Hx (x2.4 > than T1DM), south Asian, pre-diabetes (impaired glucose tolerance/fasting glucose)
Polyuria, polydipsia, lethargy, prolonged/frequent/recurrent infections (e.g. vaginal thrush)
DM
Ix
Diagnosis criteria
Complication screening (3)
Urine dip, FPG, RPG, OGTT, HbA1c (n.b. this won’t be accurate in anaemic patients)
Symtomatic + one elevated FPG (≥7.0) or RPG (≥11.1)
Asymptomatic + two elevated FPG or RPG
HbA1c ≥48mmol/mol or 6.5%
Urine dip for protein
BP for HTN
Fasting lipid for hyperlipidaemia
Diabetic foot
Presentation (2)
Risk factors
Ulcers (neuropathic painless and punched out or arterial), loss of pulses
Charcot foot - Bone and joint degeneration -> deformity - Rockerbottom sole, claw toes, loss of transverse arch
Peripheral neuropathy, callus smoking, HTN, hypercholesterolaemia
Diabetic eye problems
Types
Process
Features (5)
Cataracts, retinopathy, maculopathy, glaucoma
Microvascular occlusion -> retinal ischaemia -> neovascularisation
Pericyte loss -> leakage -> haemorrhages or diffuse oedema
Microaneurysm - from physical weakness
Hard exudates - lipoproteins from leakage
Haemorrhages - rupture of weakened capillaries small dots, blots or flame
Cotton wool spots - build up of axonal debris
Neovascularisation
Diabetic eye problems
Presentation
Management
Emergency referrals (3)
Painless, gradual reduction of central vision
Haemorrhage - sudden onset dark, painless floater
Optimise glycaemic control Blood pressure control Lipid control Laser photocoagulation Or intravitreal steroids
Sudden LOV
Red eye
Retinal detachment
Annual review criteria (10)
Educate + modifiable RFs Check BMI Check complications: hypos, HOHS, DKA Assess CVS: BP, pulses, bruits Inspect injection sites - lipodystrophy Foot check - neuropathy and pulses Urine dip - protein, nitrites, ketones Check eyes - acuity and ophthalmoscopy -> refer opthalmology Ask erectile dysfunction Bloods: HbA1c and home capillary monitoring results, random lipids
Type II DM management
Single drug therapy ideally metformin
Target is 6.5%
Gradually increase over weeks to reduce GI SE
Dual drug therapy *only if HbA1c > 58mmol/mol or 7.5%
Target is 7% (53mmol/mol)
Sulfonylurea or pioglitazone
Still not 58/7.5%
Metformin + sulfonylurea + pioglitazone
Metformin + sulfonylurea + gliptin
Start insulin
Insulin
Metformin Class Pharmacology Contraindications SE
Biguanide
Increases insulin sensitivity (GLUT 4), decreases gluconeogenesis
CKD, eGFR < 30
GI upset: nausea, anorexia, diarrhoea - 20% intolerable
Sulfonylurea Class Pharmacology CI SE
Oral hypoglycaemics
Increase panc insulin secretion
Pregnancy
*Hypo, weight gain
Piaglitazone Class Pharmacology CI SE
Oral hypoglycaemics
Increases insulin sensitivity
Heart failure and osteoporosis
Weight gain, fluid retention and osteoporosis
Insulin regimes (4)
Once-daily - Long or int at bedtime - only suitable T2DM
Twice-daily - Pre breakfast/evening meal
Basal-bolus - Long or int at bedtime with rapid/short to cover meals
Continuous subcut or insulin pump- If very poor control
Sickness and Diabetes
Stress response to illness -> increased cortisol
Cortisol increases blood sugars and decreases insulin
If oral meds - Seek help if glucose >13mmol/l
If insulin meds - Seek help if signs of DKA (Kussmaul, vomiting, drowsy/confused, can’t eat)
DKA
Causes
Presentation (7)
Reduced insulin levels caused by - missed insulin, infection, intoxication, ischaemia, infarction
Abdominal pain + vomiting Polyuria, polydipsia, dehydration Kussmaul respiration (deep hyperventilation to correct acidosis) Acetone breath (pear drop) (Fat -> Ketones)
DKA Ix (4)
Plasma glucose: high >11 or known DM
Plasma ketones: high >3mmol/l
ABG: metabolic acidosis pH < 7.3
Urine dip: ketones (++) and glucose
DKA management
ABCDE sats etc… + catheterise
Volume depletion: IV NaCl (1L/hour or maintenance)
*switch to 5% dex when glucose <12
Hyperglycaemia: IV insulin - will drop the potassium…
*Fixed rate IV infusion: 0.1U/kg/hr add glucose when drops
Hypokalaemia (as a result of fluids and insulin): K+in fluids
>5.5 = nil
3.5-5.5 = 40mmol/L infusion solution
<3.5 = senior review
Acidaemia: IV bicarbonate
Hyperosmolar hyperglycaemic state
What
Causes
Mechanisms
Often very high blood glucose >40 + v.high serum osmolality. (DKA equivalent for type II DM)
Infection, MI, dehydration, inability to take normal meds, thiazides + loop, poor control
Hyperglycaemia -> osmotic diuresis -> hyperosmolarity leading to fluid shift of water into intravascular compartment -> severe dehydration
No ketosis as enough insulin to suppress ketogenesis
Hypovolaemia
Marked hyperglycaemia (>30) without hyperketonaemia or acidosis
Osmolality > 320 mosmol/kg (concentration of blood)
N.b. osmolality = /kg, osmolarity = /L
Extreme dehydration + altered mental state ± seizures ± delirium
HHS Ix (6)
Urinalysis: glycosuria +++. Ketonuria + Capillary glucose > 30 Serum osmolarity > 320mmol/L U+E -> AKI ABG -> normal Blood cultures -> rule out sepsis
HHS management
Treat cause
Safely normalise osmolality - replace fluid and electrolytes
Normalise blood glucose
ABCDE
IV access, ECG, SaO2, BP
Calculate osmolality frequently (2Na + gluc + urea)
-IV 0.9% NaCl -> aim for fall of Na by 10mmol/24 hours, glucose 5mmol/hr
-Aim for 3-6 litres +ve by 12 hours
IV insulin (0.05U/kg/hr) if glucose no longer falling
Rapid correction of Na
Cerebral oedema, central pontine myelinosis
Metabolic syndrome
Cluster of common abnormalities including insulin resistance, impaired glucose tol, reduced HDL, elevated triglycerides and HTN
BMI classification
≤18.5 underweight 18.5-24.9 optimal 25-29.9 overweight 30-34.9 obese I 35-39.9 obese II ≥40 obese III - weight is imminent threat
Other causes of obesity
Drugs: Glitazone, sulfonylurea, antipsychotics , antidepressants: tricyclics and mirtazapine, lithium, progesterone only contraception, BB, corticosteroids
Conditions: Hypothyroid, PCOS, Cushing’s, hypogonadism
NICE recommended calorie decrease for weight loss
600kcal
Gynaecomastia
Physiology
Causes
Oestrogens stimulate, androgens inhibit therefore ratio is important
Conditions raising oestrogen
Conditions dropping testosterone/androgen resistance
Conditions causing increased conversion of androgens to oestrogen - aromatase (in increased adiposity)
Path (low test) - androgen resistance, Klinefelter’s, viral orchitis (mumps), renal disease
High oestrogen - Neoplasms secreting HCG (e.g. seminoma), RCC, adrenal tumour (oestrogen), *liver disease - increased prod androstenedione and aromatisation to oestrogen), obesity, hyperthyroid.
Drugs
Drugs causing gyneacomastia (4)
Digoxin - oestrogen like effect (enhanced with liver failure)
Increase prolactin - antipsychotics, TCA, metoclopramide
Spironolactone - inhibit testosterone synthesis
Anabolic steroids - androgens cause high oestrogens
T3 & T4
Which active
Where activated
T3
80% @ liver, 20% @ thyroid
Hypothyroid
Most common cause
Associations
Other causes (3)
Hashimoto’s thyroiditis
AI disease: T1DM, Addison’s, pernicious anaemia: 5x in women
Iatrogenic: surgery or radioiodine treatment
Drugs: lithium, amiodarone (*iodine rich may become hypo or hyper)
Iodine deficiency most common in developing world
Hypothyroid symptoms (8)
Tired + lethargic Intolerant to cold Slow intellectual: poor memory and difficulty concentrating Constipation Weight gain + decreased appetite Deep hoarse voice Menorrhagia Reduced libido, depression
Signs of hypothyroid (7)
Dry coarse skin/hair Puffy face/hands/feet (myxoedema) Bradycardia Goitre Delayed tendon reflex Carpal tunnel Serous cavity effusions: pericarditis/pleural effusions
Myxoedema
Features (6)
Severe cases
Treatment
Due to build up of mucopolysaccharide in tissues.
Expressionless face with peri-orbital fullness
Pale cool skin with rough - doughy texture
Enlarged heart
Megacolon
Cerebellar ataxia
Psychosis + encephalopathy -> myxoedema coma
Severe cases - Hypo features + seizures + hypothermia + decreased consciousness + hypoventilation + hypoglygaemia/natremia
IV levothyroxine + IV hydrocortisone (after blood cortisone) + resp support
Management of hypothyroid
Levothyroxine (T4) for life
Initial dose: 50-100 mcg, step up by 25-50 depending on TFT every 3-4 weeks
Annual TFT when stable
Hyperthyroid
Main cause
Other causes
Grave’s disease (assoc thyroid eye disease) - 75%
Toxic multinodular goitre - more common in >60 from high iodine (amiodarone or derbyshire)
Toxic nodule/adenoma
Drugs: amiodarone
Exogenous thyroid hormone excess: treatment
Ectopic thyroid tissue: metastatic follicular carcinoma or ovarian teratoma
TSH secreting pituitary adenoma (secondary)
Symptoms and Signs of hyperthyroid (5 each)
Weight loss and increased appetite Irritable + weak Sweating, tremor Diarrhoea Mental illness: anxiety to psychosis Heat intolerant Loss of libido Oligomenorrhoea
Sweaty/warm palms Fine tremor Tachycardia ± AF Hair thinning Goitre *Proximal myopathy (wasting and weakness) Gynaecomastia Brisk reflexes Urticaria/pruritus + thyroid acropachy + pretibial myxoedema
Graves disease
Antibody
Pathophysiology
Thyroid eye disease features (10)
Anti-TSH receptor (Abs may react with orbital antigens)
AAb stimulate TSH receptor leading to excess secretion of thyroid hormones and hyperplasia of follicular cells -> diffuse goitre
Lid lag, lid retraction, ophthalmoplegia, exophthalmos, gritty eyes, diplopia, loss of colour vision, conjunctival oedema, papilloedema
Nb. Worsened by radio-iodine + smoking
Management of Hyperthyroid
Beta-blockers - propanolol
Lubricating eye drops
Antithyroid drugs
-Carbimazole: start 10-20mg/day titrate based on TFT (monthly)
-Propylthiouracil - causes liver fail: reserve for pregnancy and thyroid storm
Radioactive iodine (CI at pregnancy/breast feeding)
Relapsed Grave’s or toxic nodular (worsens eye disease in Grave’s)
Surgery
Warning with antithyroid drugs
myelosuppression - agranulocytosis + neutropenia sepsis
Usually presents as a sore throat
Thyroid storm
Happens in
Features
Cause
Grave’s or TMNG
Hyperpyrexia > 41 CVS: HR > 140, hypotension, AF, CHF GI: Nausea, jaundice, vomiting, diarrhoea, abdominal pain NEURO: Confusion, agitation, delirium Infection
Resus: O2, IV fluids, NG tube if vomiting
- Oral carbimazole or propylthiouracil
- @4 hours - Lugol’s solution - aqueous iodine to block TH
IV propanolol
IV hydrocortisone (treats possible relative adrenal insufficiency)
PTH physiology
Released in response to low ionised Ca
Actions
-To bone: increase osteoclastic activity - release Ca and PO4
-To kidney: 25-OH-D to 1,25-OH2-D (1-alpha hydroxylase) - increases Ca absorption gut
Increases reabs Ca, decreases reabs PO4 (increases PO4 in urine, decreases Ca)
-Net effect - increased Ca, decreased PO4
Calcitonin
Produced by para-follicular (medullary) C cells of thyroid inhibits osteoclast activity - reduces Ca and PO4
Primary hyperparathyroid
Who
Cause
Presentation
Occur in postmenopausal women
85% are solitary adenoma
10% are 4 gland hypertrophy
80% are asymptomatic and diagnosis when hyperCa found
Excess Ca absorption from bone: osteopenia and osteoporosis if extreme
Excessive renal Ca excretion: calculi
Mild symptoms of hypercalcaemia: fatigue, weakness, muscle pain
*Bones, stones, abdominal moans, thrones, psychic overtones
Gynaecomastia
Physiology
Causes
Oestrogens stimulate, androgens inhibit therefore ratio is important
Conditions raising oestrogen
Conditions dropping testosterone/androgen resistance
Conditions causing increased conversion of androgens to oestrogen - aromatase (in increased adiposity)
Path (low test) - androgen resistance, Klinefelter’s, viral orchitis (mumps), renal disease
High oestrogen - Neoplasms secreting HCG (e.g. seminoma), RCC, adrenal tumour (oestrogen), *liver disease - increased prod androstenedione and aromatisation to oestrogen), obesity, hyperthyroid.
Drugs
Drugs causing gyneacomastia (4)
Digoxin - oestrogen like effect (enhanced with liver failure)
Increase prolactin - antipsychotics, TCA, metoclopramide
Spironolactone - inhibit testosterone synthesis
Anabolic steroids - androgens cause high oestrogens
T3 & T4
Which active
Where activated
T3
80% @ liver, 20% @ thyroid
Hypothyroid
Most common cause
Associations
Other causes (3)
Hashimoto’s thyroiditis
AI disease: T1DM, Addison’s, pernicious anaemia: 5x in women
Iatrogenic: surgery or radioiodine treatment
Drugs: lithium, amiodarone (*iodine rich may become hypo or hyper)
Iodine deficiency most common in developing world
Hypothyroid symptoms (8)
Tired + lethargic Intolerant to cold Slow intellectual: poos memory and difficulty concentrating Constipation Weight gain + decreased appetite Deep hoarse voice Menorrhagia Reduced libido, depression
Signs of hypothyroid (7)
Dry coarse skin/hair Puffy face/hands/feet (myxoedema) Bradycardia Goitre Delayed tendon reflex Carpal tunnel Serous cavity effusions: pericarditis/pleural effusions
Myxoedema
Features (6)
Severe cases
Treatment
Due to build up of mucopolysaccharide in tissues.
Expressionless face with peri-orbital fullness
Pale cool skin with rough - doughy texture
Enlarged heart
Megacolon
Cerebellar ataxia
Psychosis + encephalopathy -> myxoedema coma
Severe cases - Hypo features + seizures + hypothermia + decreased consciousness + hypoventilation + hypoglygaemia/natremia
IV levothyroxine + IV hydrocortisone (after blood cortisone) + resp support
Management of hypothyroid
Levothyroxine (T4) for life
Initial dose: 50-100 mcg, step up by 25-50 depending on TFT every 3-4 weeks
Annual TFT when stable
Hyperthyroid
Main cause
Other causes
Grave’s disease (assoc thyroid eye disease) - 75%
Toxic multinodular goitre - more common in >60 from high iodine (amiodarone or derbyshire)
Toxic nodule/adenoma
Drugs: amiodarone
Exogenous thyroid hormone excess: treatment
Ectopic thyroid tissue: metastatic follicular carcinoma or ovarian teratoma
TSH secreting pituitary adenoma (secondary)
Symptoms and Signs of hyperthyroid (5 each)
Weight loss and increased appetite Irritable + weak Sweating, tremor Diarrhoea Mental illness: anxiety to psychosis Heat intolerant Loss of libido Oligomenorrhoea
Sweaty/warm palms Fine tremor Tachycardia ± AF Hair thinning Goitre *Proximal myopathy (wasting and weakness) Gynaecomastia Brisk reflexes Urticaria/pruritus + thyroid acropachy + pretibial myxoedema
Graves disease
Antibody
Pathophysiology
Thyroid eye disease features (10)
Anti-TSH receptor (Abs may react with orbital antigens)
AAb stimulate TSH receptor leading to excess secretion of thyroid hormones and hyperplasia of follicular cells -> diffuse goitre
Lid lag, lid retraction, ophthalmoplegia, exophthalmos, gritty eyes, diplopia, loss of colour vision, conjunctival oedema, papilloedema
Nb. Worsened by radio-iodine + smoking
Management of Hyperthyroid
Beta-blockers - propanolol
Lubricating eye drops
Antithyroid drugs
-Carbimazole: start 10-20mg/day titrate based on TFT (monthly)
-Propylthiouracil - causes liver fail: reserve for pregnancy and thyroid storm
Radioactive iodine (CI at pregnancy/breast feeding)
Relapsed Grave’s or toxic nodular (worsens eye disease in Grave’s)
Surgery
Warning with antithyroid drugs
myelosuppression - agranulocytosis + neutropenia sepsis
Usually presents as a sore throat
Thyroid storm
Happens in
Features
Cause
Grave’s or TMNG
Hyperpyrexia > 41 CVS: HR > 140, hypotension, AF, CHF GI: Nausea, jaundice, vomiting, diarrhoea, abdominal pain NEURO: Confusion, agitation, delirium Infection
Resus: O2, IV fluids, NG tube if vomiting
- Oral carbimazole or propylthiouracil
- @4 hours - Lugol’s solution - aqueous iodine to block TH
IV propanolol
IV hydrocortisone (treats possible relative adrenal insufficiency)
PTH physiology
Released in response to low ionised Ca
Actions
-To bone: increase osteoclastic activity - release Ca and PO4
-To kidney: 25-OH-D to 1,25-OH2-D (1-alpha hydroxylase) - increases Ca absorption gut
Increases reabs Ca, decreases reabs PO4 (increases PO4 in urine, decreases Ca)
-Net effect - increased Ca, decreased PO4
Calcitonin
Produced by para-follicular (medullary) C cells of thyroid inhibits osteoclast activity - reduces Ca and PO4
Primary hyperparathyroid
Who
Cause
Presentation
Occur in postmenopausal women
85% are solitary adenoma
10% are 4 gland hypertrophy
80% are asymptomatic and diagnosis when hyperCa found
Excess Ca absorption from bone: osteopenia and osteoporosis if extreme
Excessive renal Ca excretion: calculi
Mild symptoms of hypercalcaemia: fatigue, weakness, muscle pain
*Bones, stones, abdominal moans, thrones, psychic overtones
Management of hyperparathyroid
Mild hypercalcaemia + minimal kidney stones - surveillance
-Check creatinine and Ca 6 months
-DEXA yearly
Vitamin D *suppresses PTH
Avoid dehydration, thiazide diuretics - increase fluids
Surgery if symptomatic
Bisphosphonates (alendronate)
Cinacalcet (calcimimetic) reduces serum Ca and PTH levels and raises PO4 (no effect on bone turnover
Types of hyperparathyroid, cause & PHT/Ca/PO4 levels
Primary - solitary adenoma at PTH glands (85%) postmenopausal women - High PTH, high Ca, low phosphate
Secondary - as a result of low calcium - PT gland hyperplasia, *almost always associated with kidney, liver or bowel disease - High PTH, low Ca, high phosphate, low vitamin D
Tertiary - ongoing hyperplasia of PT glands after correction of underlying renal disorder CKD . i.e. after prolonged secondary hyperplasia of all 4 glands - High PTH, high Ca, high phosphate, normal vitamin D, high alk phos (separates from primary)
Types of hypoparathyroid
Primary hypothyroidism
-Congenital - DiGeorge, defect in PTH gene, defect in Calcium sensing
Acquired - Neck surgery, neck irradiation, alcohol, iron deposition (haemochromatosis), copper (Wilson’s), magnesium deficiency or excess
Pseudohypoparathyrodism - defect in PTH action and end-organ resistance to PTH
Low IQ, short stature, short 4th and 5th metacarpals
Low Ca, high PO4, high PTH (but fail action)
Pseudopseudohypoparathyroidism
Similar phenotype to above but normal biochemistry
Hypoparathyroid Ix
Low Ca, high PO4, low PTH, normal alk phos (@ pseudohypoparathyroidism = low Ca, high PO4, high PTH)
U+E - to exclude CKD
25-hydroxyvitamin D3 to exclude vitamin D deficiency as cause of hypocalcaemia
ECG - prolonged QT (hypocalcaemia)
Hypoparathyroid treatment
If tetany - urgent IV Ca
Diet: rich in Ca and vit D
Calcium and vit D
Anterior vs posterior pituitary
GH: stimulates liver to produce IGF-1 and counteracts insulin
Prolactin: promotes growth of mammary glands and reproductive organs
FSH: stimulates release of sex steroids
LH: stimulates release of sex steroids
ACTH: adrenocorticotropic hormone: stimulates adrenal cortex to release glucocorticoids and androgens
TSH
Vasopressin - Role in water re absorption.
Oxytocin - Social bonding, sexual reproduction, and ejection of breast milk
Nerves in the cavernous sinus
Local effects of pituitary masses (3)
Cavernous sinus = CN 3, 4, 5a, 5b, 6
Optic chiasm - Visual field defect: bitemporal hemianopia
Headaches: retro-orbital and bilateral worse on waking
Ocular nerve palsies - squint
Presentation of hypopituitary
LH/FSH - Infertility/oligomenorrhoea, erectile dysfunction, loss of libido
GH - Short stature in kids
Prolactin - Inappropriate milk secretion
Long standing - loss of muscle bulk and body hair
Craniopharyngioma
Benign and cystic growth of pituitary gland (grows down = lose bottom half vision) most common childhood IC neoplasm. Headache + visual field defects + hypopituitarism
Syndromes associated with hypopituitism (3)
Kallmans - Deficiency in GnRH - Associated with anosmia
Sheehans syndrome - Pituitary infarction in post partum haemorrhage
Pituitary apoplexy - Rapid enlargement due to bleed into tumour -> mass effect, CV collapse and acute hypopituitarism
Pituitary apoplexy
Ix
Management
Serum cortisol, LH/FSH, IGF Prolactin, TSH, testosterone/oestradiol.
FBC, clotting, U&E
Visual fields
MRI
Fluids to ensure heamodynamically stable
Hydrocortisone IV
Surgery
Effects of prolactin
Women
Men
Women - inhibits GNRH -> reduced gonadotropin (FSH + LH) secretion -> menstrual dysfunction + galactorrhoea -> low oestrogen
Men - direct reversible response on hypothalamus -> secondary hypogonadism -> decreased libido and ED
Causes of hyperprolacinameia
Prolactinoma - benign MICROadenoma
Hypothyroid -> raises TSH -> stimulates release of PRL
Other endocrine = Cushing’s syndrome
Antipsychotics -> block dopamine -> raise PRL
-Dopamine receptor antag: domperidone, metoclopramide, neuroleptics
-Dopamine depleting: methyldopa
-Antidepressants: e.g. TCA, MAOI, SRI
Physiological - pregnancy, puerperium, stress, exercise
Head injury
Hyperprolacinameia presentation
Women: oligomenorrhoea, amenorrhoea, galactorrhoea, infertility, hirsutism
Men: slower pres, reduced libido, reduced beard growth, ED
Children: growth failure and delayed puberty
Hyperprolacinameia teatment
Side effects
Dopamine agonist - Bromocriptine
SE: sleepiness, hypotension, cardiac/retroperitoneal/pulmonary fibrosis - monitor
Acromegaly vs Giantism
Cause
Acromegaly = overgrowth of all organ systems bones, joints and soft tissues by IGF1 Giantism = excess GH or IGF1 before closure of epiphyseal plates
Usualy MACROadenoma - Hence visual defects.
Nb. IGF1 is main tissue mediator of GH
Acromegaly presentation
Due to size: headaches (55%), visual field defect (bitemporal hemianopia)
Excess GH:
Change in appearance: enlarge hands and feet (ring and shoe size), frontal bossing, thickened nose, coarsening facial features
Change in mouth: macroglossia - OSA and snoring
Change in skin: dark thick oily skin + sweating (65%)
Articular overgrowth: arthralgia, osteoarthritis, jaw pain
Nerve compression: bilateral carpal tunnel (50%) - IGF mediated hypertrophy, acroparasthesia (extremities)
Visceral hypertrophy: cardio/hepatomegaly
Cardiac features: HTN, arrhythmia, LVH
T2DM and glucose intolerance due to insulin resistance
Features of hyperprolacinaemia - Amenorrhea, Galactorrhea, poor libedo
GH inhibited by?
High glucose levels & somatostatin
Ix in acromegaly
Serum IGF1 - raised, correlates with GH, long half life, stable serum -> therefore choice, may be affected by liver disease
OGTT to confirm a raised IGF
-75g glucose load
-Failure to suppress to < 0.4mcg/L
Management of acromegaly
First line: transsphenoidal surgery
Second line: SS analogues: Ocreotide/lanreotide: SE abdominal cramps
Third line: dopamine agonists, cabergoline (safe at preg), bromocriptine
Complications of acromegaly
Cardiac complications: 40%
-LVH, arrhythmia - monitor with ECG and echo
-HTN
Sleep apnoea
Diabetes
Carpal tunnel: improves with Rx of acromegaly
Increased risk colon cancer: monitor every 3-5 years
Adrenal secretions
The deeper you get the sweeter it gets - Salt, Sugar, Sex
Zona glomerulosa - mineralocorticoids - aldosterone
Zona fasciculata - glucocorticoids - cortisol
Zona reticularis - androgens - DHEA - dehydroepiandrosterone
Effects of Cortisol (5)
Diurnal variation?
RIDGE Suppression of reproduction Suppression of immunity Suppression of digestion Suppression of growth Mobilisation of energy -> elevated sugars
Diurnal variation - highest at morning, lowest at midnight
Cushings SYNDROME
What
Types
Prolonged exposure to exogenous or endogenous glucocorticoids with clinical state of increased free cortisol and loss of negative feedback
ACTH independent
-Adrenal adenoma/adrenal carcinoma/excess glucocorticoids
ACTH dependent
-Excessive ACTH pit (Cushing’s disease), ectopic ACTH producing tumours (due to lung cancer, small cell)
Cushings syndrome features (8)
Truncal obesity, buffalo hump, weight gain
Facial fullness, moon face
Proximal muscle wasting
Diabetes or impaired GT: polyuria, polydipsia
Hypertension
Osteoporosis
Infection prone and poor healing
Mood change: depression, lethargy, irritable, psychosis
Skin: atrophy, purple striae, easy bruising, hirsutism, acne, pigmentation, acne
Cushings syndrome Ix
Serum glucose: elevated
First line: 1mg overnight dexamethasone suppression test, measure cortisol 8am - Failure to suppress to <50nmol/L = +ve
24 hour urinary free cortisol: high (x3) should be high in 2/3 samples
Second line: 48 hour 2mg dexamethasone suppression test, failure to suppress to <50nmol/L
Localisation - Plasma ACTH
if low = adrenal = CT adrenal
If high = likely pituitary.
Cushings syndrome complications (4)
CV disease: main cause of death: HTN, DM, dyslipidemia
Metabolic syndrome, HTN, T2DM
Impaired immunity
Osteoporosis
Addisons
What
Types
Antibody
Destruction of adrenal cortex and subsequent reduction in output of adrenal hormones: glucocorticoids (cortisol), and mineralocorticoids (aldosterone)
Primary: Addison’s - inability of adrenal glands to produce steroid - autoimmune
Addison’s 85%
Surgical
Metabolic failure: CAH e.g. 21-hydroxylase deficiency
Secondary: Inadequate pituitary stimulation of adrenal glands, exogenous steroids
Steroids suppress axis
CRH deficiency
Anti-21 hydroxylase (85%)
Addisons Symtoms (5Ts) Signs
Chronic: thin, tanned, tired, tearful and tumbling
Fatigue and weakness
GI: Anorexia, nausea, vomiting, weight loss
Cravings for salt and salty food
Muscle cramps
Faintness due to hypotension
Mood: confusion, personality change, irritable
Signs: pigmental palmar crease and buccal mucosa, hypotension, postural hypotension
Addisons Ix
Confimation test
Sodium - low, potassium - high (by low aldosterone, low ENaC and ROMK)
Glucose - low in children (low cortisol)
Cortisol levels - highest @ 8am, if 100-150nmol/L = further investigation, <100 = urgent admission
ACTH levels - for differentiate primary or secondary
High = primary, low = secondary
Renin and aldosterone (high renin and low aldosterone in Addison’s)
Anti 21-hydroxylase (n.b. @ CAH = 21 hydroxylase deficiency)
Short synacthen test:
Take cortisol level
Give 250 mcg synacthen IM (synth ACTH). In 30 mins retake cortisol
If cortisol rises then exclude Addison’s >500nmol/L
Addisons management
Glucocorticoid: hydrocortisone - TDS, highest dose at morning 15-30mg
- In illness may increase x 3, double in intercurrent illness
Mineralocorticoid: Fludrocortisone: 50-300 mcg/day will correct postural hypotension and electrolyte imbalance
Addisonian crisis What Precipiants Symptoms Signs Management
Acute deficiency of glucocorticoid cortisol and mineralocorticoid
Major or minor infx, commonly vom/diarrhoea, injury, surgery, pregnancy
Malaise, fatigue, nausea/vomiting, low-grade fever, muscle cramps, confusion
Dehydration: hypotension and hypovolaemic shock
Low Na, high K, Cr raised, hypoglycaemia, bloods for cortisol and ACTH
IV/IM hydrocortisone (*100mg adult) n.b. At high dose hydrocortisone has mineralocorticoid effect
Rehydration - fluids
Further hydrocortisone + glucose: 100mg in 5% over 24 hours
Continuous cardiac and electrolyte monitoring (ECG, reg U+E)
Treatment of infx (IV ABX)
Conns
What
Causes
Excess production of aldosterone independent of RAAS system due to adrenal adenoma - > renin is suppressed
Primary
-Adrenal adenoma in 80%
-Bilateral adrenal hyperplasia in 20%
Secondary - due to high renin from decreased renal perfusion in renal artery stenosis
Conns presentation
Oedema
Hypertension
Hypokalaemia - weakness, cramps, parasthesia
Metabolic alkalosis - secretion of H+ in exchange for K+ (more K+ in urine) in intercalated cells
Conns Ix
U+E: hypernatraemia, hypokalaemia BP: high *Aldosterone: renin ratio (high ald, low renin - normal renin exludes Dx) >800 = imaging required ECG for arrhythmia CT/MRI for adrenal adenoma
Conns magement
Medical management prior to surgery: 4 weeks spironolactone (aldosterone antagonist) Laparoscopic adrenalectomy (only if unilateral) BAH: aldosterone antagonists Spironolactone (blocks aldosterone and testosterone = may lead to gynaecomastia, ED and menstrual problems)
Phaeochromocytoma What Main complications Presentation (4) Signs
Catecholamine producing adrenal tumour @ adrenal medulla. Secrete autonomously from SNS
Life threatening HTN, cardiac arrhythmia
Episodic headache + sweating + palpitations + tremor
Hypertension, postural hypotension, tremor, flushing, tachycardia
Phaeochromocytoma
Ix
Management
24 hour urine catecholamines, metanephrines, VMA
Raised serum metanephrines
Abdominal CT/MRI
Phentolamine or IV nitroprusside
Definitive is sugery
Adrenergic receptors blockade A1 A2 B1 B2
SM @ BV = reduces BP, SM contraction @ bladder neck = increased peeing
Inhibit insulin release @ pancreas = more insulin
Tachycardia + increased contractility -> decrease HR + CO
Increased renin release -> decreased renin
Bronchodilation -> bronchoconstriction
Carcinoid
What
Presentation
Which tumours more likely
Tumour of enterochromaffin cell secreting serotonin, other vasoactive peptides
Flushing and diarrhoea
Wheeze, palpitations, telangiectasia, abdominal pain
30% of gut, 5% of bronchial
Diabetes insipidus
Types
What
Value
Nephrogenic or cranial
Passage of large amounts of dilute urine due to hyposecretion or resistance to ADH/vasopressin (same thing) and inability to concentrate urine
3l of <300mOsm/kg
Causes of DI
Cranial
Nephrogenic
Damage to hypothalamus
Acquired: idiopathic, tumour (e.g. craniopharyngioma), intracranial surgery, head injury, granulomatous disease (sarcoid, TB, GPA), infection (men, enceph)
Inherited: AD vasopressin gene
Acquired: hypokalaemia, CKD, lithium, RTA, hypercalcaemia
Inherited: X linked mut V2 ADH receptor gene, AR AQP2 gene
DI Ix (5)
24 hour urine collection >3l
Urine osmolality <300mOsm/kg (2[Na+K] + urea + glucose)
Serum osmolality: normal or high (normal/high sodium, calcium, potassium)
Urine dip: -ve for glucose
*Water deprivation test with *desmopressin response
DI Mx
Cranial: desmopressin replacement (Overdose = hyponatraemia)
Nephrogenic: ensure drink adequate fluid in response to thirst, stop causative drugs, treat underlying disease e.g. hypoK, hyperCa
Low sodium: either dietary or with thiazide + NSAID
SIADH
What
Causes
Complications
Hyponatremia and hypo-osmolality resulting from inappropriate, continued secretion or action of the antidiuretic hormone arginine vasopressin
Pulmonary processes: pneumonia, lung cancer (esp small cell)
CNS disorders: infection, trauma, MS, haemorrhage, malignancy
Malignancy: lung, GI, GU, lymphoma
Drugs: SSRIs, NSAIDs, chemo drugs
Central pontine myelinolysis
Ix for SIADH
Na - low < 135 & Urine Na high
Serum osmolality - low <280 proportional to hyponatraemia
Urine osmolality - >100mOsm/kg - typically higher than plasma
Indicate elevated AVP
Normal renal and adrenal function
Serum sodium will not respond to normal saline infusion
Mx of SIADH
Acute (<48) + severe (<125)
IV hypertonic saline (3%) and check Na every 2 hours
Aim to increase 1-2 per hour until neurological symptoms resolve
+ treat cause + furosemide if risk of fluid overload
Chronic + severe
IV hypertonic saline
Vasopressin receptor antagonist tolvaptan + cause + furosemide
