Endocrine Flashcards

1
Q

Diabetes
Type 1 vs Type 2
Insulin release
Insulin action

A

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

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2
Q

Type 1 DM
Aetiology
Presentation
Complications

A

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

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3
Q

Type 2 DM
Who
RF
Pres

A

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)

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4
Q

DM
Ix
Diagnosis criteria
Complication screening (3)

A

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

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5
Q

Diabetic foot
Presentation (2)
Risk factors

A

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

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6
Q

Diabetic eye problems
Types
Process
Features (5)

A

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

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7
Q

Diabetic eye problems
Presentation
Management
Emergency referrals (3)

A

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

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8
Q

Annual review criteria (10)

A
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
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9
Q

Type II DM management

A

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

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10
Q
Metformin
Class
Pharmacology
Contraindications
SE
A

Biguanide

Increases insulin sensitivity (GLUT 4), decreases gluconeogenesis

CKD, eGFR < 30

GI upset: nausea, anorexia, diarrhoea - 20% intolerable

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11
Q
Sulfonylurea
Class
Pharmacology
CI
SE
A

Oral hypoglycaemics

Increase panc insulin secretion

Pregnancy

*Hypo, weight gain

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12
Q
Piaglitazone
Class
Pharmacology
CI
SE
A

Oral hypoglycaemics

Increases insulin sensitivity

Heart failure and osteoporosis

Weight gain, fluid retention and osteoporosis

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13
Q

Insulin regimes (4)

A

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

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14
Q

Sickness and Diabetes

A

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)

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15
Q

DKA
Causes
Presentation (7)

A

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)
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16
Q

DKA Ix (4)

A

Plasma glucose: high >11 or known DM
Plasma ketones: high >3mmol/l
ABG: metabolic acidosis pH < 7.3
Urine dip: ketones (++) and glucose

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17
Q

DKA management

A

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

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18
Q

Hyperosmolar hyperglycaemic state
What
Causes
Mechanisms

A

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

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19
Q

HHS Ix (6)

A
Urinalysis: glycosuria +++. Ketonuria +
Capillary glucose > 30
Serum osmolarity > 320mmol/L
U+E -> AKI
ABG -> normal
Blood cultures -> rule out sepsis
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20
Q

HHS management

A

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

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21
Q

Rapid correction of Na

A

Cerebral oedema, central pontine myelinosis

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22
Q

Metabolic syndrome

A

Cluster of common abnormalities including insulin resistance, impaired glucose tol, reduced HDL, elevated triglycerides and HTN

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23
Q

BMI classification

A
≤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
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24
Q

Other causes of obesity

A

Drugs: Glitazone, sulfonylurea, antipsychotics , antidepressants: tricyclics and mirtazapine, lithium, progesterone only contraception, BB, corticosteroids

Conditions: Hypothyroid, PCOS, Cushing’s, hypogonadism

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25
NICE recommended calorie decrease for weight loss
600kcal
26
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
27
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
28
T3 & T4 Which active Where activated
T3 80% @ liver, 20% @ thyroid
29
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
30
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 ```
31
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 ```
32
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
33
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
34
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)
35
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 ```
36
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
37
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
38
Warning with antithyroid drugs
myelosuppression - agranulocytosis + neutropenia sepsis Usually presents as a sore throat
39
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)
40
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
41
Calcitonin
Produced by para-follicular (medullary) C cells of thyroid inhibits osteoclast activity - reduces Ca and PO4
42
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
43
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
44
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
45
T3 & T4 Which active Where activated
T3 80% @ liver, 20% @ thyroid
46
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
47
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 ```
48
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 ```
49
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
50
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
51
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)
52
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 ```
53
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
54
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
55
Warning with antithyroid drugs
myelosuppression - agranulocytosis + neutropenia sepsis Usually presents as a sore throat
56
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)
57
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
58
Calcitonin
Produced by para-follicular (medullary) C cells of thyroid inhibits osteoclast activity - reduces Ca and PO4
59
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
60
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
61
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)
62
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
63
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)
64
Hypoparathyroid treatment
If tetany - urgent IV Ca Diet: rich in Ca and vit D Calcium and vit D
65
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
66
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
67
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
68
Craniopharyngioma
Benign and cystic growth of pituitary gland (grows down = lose bottom half vision) most common childhood IC neoplasm. Headache + visual field defects + hypopituitarism
69
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
70
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
71
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
72
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
73
Hyperprolacinameia presentation
Women: oligomenorrhoea, amenorrhoea, galactorrhoea, infertility, hirsutism Men: slower pres, reduced libido, reduced beard growth, ED Children: growth failure and delayed puberty
74
Hyperprolacinameia teatment | Side effects
Dopamine agonist - Bromocriptine | SE: sleepiness, hypotension, cardiac/retroperitoneal/pulmonary fibrosis - monitor
75
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
76
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
77
GH inhibited by?
High glucose levels & somatostatin
78
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
79
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
80
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
81
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
82
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
83
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)
84
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
85
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.
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Cushings syndrome complications (4)
CV disease: main cause of death: HTN, DM, dyslipidemia Metabolic syndrome, HTN, T2DM Impaired immunity Osteoporosis
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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%)
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``` 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
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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
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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
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``` 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)
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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
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Conns presentation
Oedema Hypertension Hypokalaemia - weakness, cramps, parasthesia Metabolic alkalosis - secretion of H+ in exchange for K+ (more K+ in urine) in intercalated cells
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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 ```
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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) ```
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``` 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
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Phaeochromocytoma Ix Management
24 hour urine catecholamines, metanephrines, VMA Raised serum metanephrines Abdominal CT/MRI Phentolamine or IV nitroprusside Definitive is sugery
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``` 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
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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
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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
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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
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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
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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
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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
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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
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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