Endocrinology Flashcards
(213 cards)
1
Q
What does endocrine mean? What does exocrine mean? Endocrine hormone action? Paracrine? Autocrine?
A
Glands ‘pour’ secretions into bloodstream (thyroid, adrenal, beta cells of pancreas)
‘Pour’ secretions through duct to site of action (pancreas- amylase, lipase)
Blood-borne, acting on distant sites
Acting on adjacent cells
Feedback on same cell that secreted hormone
2
Q
Peptides/ monoamine hormones stored where? Steroids synthesised when? Features of peptide hormones?
A
In vesicles
Synthesised on demand
Vary in length
Linear/ ring structures, two chain and may bind to carbs, stored in secretory granules, hydrophilic, water soluble, released in pulses/ bursts, cleared by tissue or circulating enzymes
3
Q
Prephormone turned into what? Prohormone packaged into what? Stored and secreted as what?
A
Prohormone
Hormone
As a hormone
4
Q
Amine hormones bind to what receptors? Stimulate what NS? Iodothyronines are not what? % protein bound? % of T3 in circulation secreted directly by thyroid?
A
Alpha and beta adrenoceptors, sympathetic nervous system
Water soluble
99%
20%
5
Q
Secretory cells secrete thyroglobulin into where? Acts as base for what synthesis? Incorporation of iodine onto what form iodothyronines? Conjugation of these form what which is colloid bound to what? TSH stimulates movement of colloid into where?
A
Colloid Thyroid hormone synthesis Tyrosine molecules T3 and T4 Thyroglobulin Secretory cell- T3 and T4 cleaved from thyroglobulin
6
Q
Hormone receptor locations x3? Vitamin D is a what hormone? Soluble where and transported by what?
A
Cell membrane= peptide, cytoplasm= steroid, nucleus= thyroid
Fat soluble- enters cell directly to nucleus to stimulate mRNA production
Vitamin D binding protein
7
Q
Adrenocortical and gonadal steroids % protein bound? Pass to where and do what? Not rapid inactivation where?
A
95%
Enter cell to nucleus, altered to active metabolite, bind to cytoplasmic receptor
In liver by reduction and oxidation, or conjugation to glucuronide and sulfate groups
8
Q
Stages of testosterone formation?
A
Cholesterol–> pregnenolone–> progesterone–> testes= androstenedione–> testosterone–> ovaries= oestradiol- secreted by follicles of ovaries
In adrenals= cortisol from adrenal cortex
9
Q
Steroid hormone action? Forms of hormone secretion? Dopamine inhibits what hormone? 2 hormones affecting GH?
A
Through membrane and binds to receptor–> receptor- hormone complex enters nucleus–> binds to GRE, initiates transcription of gene–> mRNA= protein synthesis
Basal secretion- continuously or pulsatile
Superadded rhythms- day-night cycle= ACTH, prolactin, GH and TSH
Prolactin
GHRH and somatostatin
10
Q
Diurnal rhythm meaning? Cortisol, testosterone and prolactin levels? Increased hormone metabolism reduces what? FSH can induced what in follicle? Hormones in large quantity can cause what?
A
Of/ during the day
Initially= high cortisol, reduce to lower in day
Testosterone= similar, prolactin= night mainly
Hormone function
LH receptors
Down regulation of its target receptors
11
Q
What is synergism? What is antagonism? 2 nuclei in posterior pituitary? Oxytocin and ADH from hypothalamic neurones through what to posterior pituitary?
A
Combined effects of 2 hormones amplified- glucagon with epinephrine
One hormone opposing another
Paraventricular and supraoptic
Axons of hypothalamic- hypophyseal tract, stored in axon terminals in posterior pituitary
12
Q
ADH release controlled by what 2 things? Hormones from anterior pituitary? TSH to where? ACTH? FSH and LH? GH? Prolactin?
A
Blood volume and osmolality GHRH, GHIH, CRH, TRH, GnRH, dopamine Thyroid Adrenal cortex Testes/ ovaries Entire body Mammary glands
13
Q
Hypothalamus secretes what which stimulates GH production? GH does what- directly and indirectly?
A
GHRH and GHIH (somatostatin)
Increases fat breakdown and release and increased blood glucose and other anti-insulin effects
Liver and other tissue= IGFs- increased cartilage formation and skeletal growth, extraskeletal= increased protein synthesis and cell growth and proliferation
14
Q
Hypothalamus releases what which stimulates anterior to produce what? Thyroid hormone functions?
A
TRH–> TSH–> thyroid produces thyroid hormones
Accelerates food metabolism, increased protein synthesis, stimulate of carb metabolism, enhances fat met, increase in vent rate, increase in CO and HR, brain develop during foetal life and postnatal development, growth rate up
15
Q
Sequence for cortisol release? e.g. of mineralocorticoids? Glucocorticoids? Androgens? DHEA?
A
Hypothalamus= CRH--> anterior pituitary= ACTH--> adrenal cortex= cortisol--> negative feedback Aldosterone Cortisol androgens Androstenedione Dihydroepiandrosterone
16
Q
Hormones from adrenal medulla? Short term stress sends nerve impulses to where? Causes what? This causes what to happen?
A
Epinephrine, norepinephrine
Spinal cord through preganglionic fibres
Adrenal medulla to secrete amino acid-based hormones–> catecholamines (epinephrine and norepinephrine)
Heart rate and BP to increase, bronchioles to dilate, liver converts glycogen to glucose, blood flow changes, reduces digestive system activity and urine output, metabolic rate increases
17
Q
Prolonged stress causes what to be released? Kidneys do what and what rises? What else happens?
A
CRH from hypothalamus, ACTH from anterior pituitary, adrenal cortex= steroid hormones
Kidneys retain sodium and water- blood volume and blood pressure rise, proteins and fats into glucose/ broken down, blood glucose increases
Immune system suppressed
18
Q
LH causes what cell to turn cholesterol into androgen? Androgen into oestrogen using what? FSH causes this in what cell? LH causes Leydig cells to produce what? This causes what cell to produce sperm?
A
Theca cell Aromatase Granuloma cell Testosterone Sertoli cell
19
Q
Hormones produced by other organs in body?
A
Heart = atrial natriuretic peptide, liver= IGF-I, kidney= erythropoietin, GI tract= gastrin, incretin, lung= hormone metabolism, blood vessel= prostanoids, nitric oxide, endothelin
20
Q
What is satiety? Risks of obesity?
A
Feeling of fullness Type II diabetes, hypertension, CHD, stroke, osteoarthritis, obstructive sleep apnoea, carcinoma- breast, endometrium, prostate, colon Especially abdominal (visceral) rather than subcutaneous fat
21
Q
Underweight, obese and morbidly obese BMI values? 3 organs controlling appetite regulation? What happens with increased food intake?
A
<18.5= underweight, 30+= obese, >40= morbidly obese
Brain, GI tract, adipose tissue
Increased fat stores, insulin and leptin released
22
Q
What is the hunger centre called in the hypothalamus? The satiety centre? Leptin is released from where? Goes where? Able to sample what and stimulate what? What also stops us eating?
A
Lateral hypothalamus Ventromedial hypothalamic nucleus Fat cells in adipose tissue Into BBB and arcuate nucleus Peripheral hormones, stimulate CART CCK
23
Q
What hormone secreted by neuroendocrine cells in ileum, pancreas and colon reduces appetite and gastric motility? Similar to what? How many amino acids?
A
Peptide YY
NPY
36- also inhibits gastric motility
24
Q
CCK does what? Where is ghrelin expressed? What does this stimulate? What is it known as? High when what? Fall when? Levels lower when?
A
Delays gastric emptying, gall bladder contraction and insulin release via vagus nerve In the stomach GH release and appetite Orexigenic Fasting When re-feeding After gastric bypass surgery
25
No POMC=what deficiency? Adrenal insufficiency means what?
ACTH deficiency, not pigmented
| No cortisol- obese
26
Leptin and insulin stimulate what neurones? This increases levels of what 2 things? They inhibit what 2 things? This does what?
POMC/ CART neurones--> CART and alpha-MSH levels increased
NPY/ AgRP neurons--> reduced NPY and AgRP
Increased satiety and reduced appetite
27
Ghrelin stimulates what 2 things? What reduces NPY and AgRP secretion? In long term, which 3 things regulate satiety and hence energy balance?
NPY / AgRP secretion --> increased appetite
PYY 3-36
Leptin, nutrients and temperature
28
4 reasons for diabetes being a public health issue? 3 reasons for type 2 diabetes?
Mortality
Disability
Co-morbidity
Reduced quality of life
Increase in prevalence, lack of effective global/ national/ local policy, major inequalities in prevalence and outcome- higher prev in BME communities, poorer outcomes in deprived communities
29
Prevention of diabetes depends on what 3 things? 4 steps of diabetes approach?
Primary prevention: incidence of condition
Secondary prevention: % of incident cases diagnosed
Tertiary: survival from diagnosis
Identifying who is at risk, preventing diabetes, diagnosing diabetes earlier, supporting self-care for diabetes
30
Features of identifying those at risk of diabetes?
Sedentary lifestyle, obesogenic environment
Knowledge, prejudice, physiology= ineffective brakes
Vicious cycles of mechanical dysfunction, psychological impact, ineffective dieting, low socioeconomic status= accelerators
31
3 categories of things maintaining being overweight?
Physical/ physiological- more weight= more difficult to exercise and dieting--> metabolic response
Psychological- low self-esteem and guilt, comfort eating
Socioeconomic- reduced opportunities, employment, relationships, social mobility
32
Clinical record increasing diabetes risk?
Age, sex, ethnicity, family history, weight BMI, waist circumference, history of gestational diabetes, hypertension or vascular disease
Impaired glucose tolerance (IGT) or impaired fasting tolerance (IFG)
33
Screening tests for diabetes?
Same for pre-diabetes and diabetes
Preventing/ postponing= effective, likely to be cost effective
HbA1c, random capillary blood glucose, fasting venous blood glucose, oral glucose tolerance test- 2 hours after oral glucose load
34
3 ways of preventing diabetes? 3 ways of diagnosing diabetes earlier?
Sustained increase in exercise, change in diet and weight loss
Raising awareness in community and in health professionals
Using clinical records to identify those at risk and/ or using blood tests to screen before symptoms develop
35
Other methods for diagnosing diabetes earlier? % adults at risk population may have blood glucose measurement even without systematic screening?
Screen as part of CHD prevention every 5 years from 40-74 years
Screening at review of hypertension management
Other risk groups may be screened
30%
36
Ways of supporting self-care for diabetes?
Self- monitoring, diet, exercise, drugs, education, peer support
37
What leads to PTH release? Effects of this? Production of what increases? Normal Ca2+ level?
Decreased sCa2+
Increased osteoclast activity releasing Ca2+ and PO43- from bones, increased Ca2+ absorption in gut using vitamin D, increased Ca2+ and reduced PO34- absorption in kidney
Active 1,25 dihydroxy-vitamin D3
1.1mmol/ l
38
Calcium and PTH relationship? Ca2+, PO34- and PTH in primary hyperparathyroidism? Secondary hyperparathyroidism? Tertiary?
Small changes in serum calcium--> big changes in PTH
Increased Ca2+, decreased PO34- and increased PTH
Decreased Ca2+, increased PTH
Increased Ca2+, big increase in PTH
39
Causes of primary hyperparathyroidism? Presentation? Tests? Treatment? Complications?
80% solitary adenoma, 20% hyperplasia of all glands, <0.5% parathyroid cancer
Asymptomatic, increased Ca2+
Weak, tired, depressed, thirsty, dehydrated, polyuric, osteopenia/ porosis, increased BP
Increased Ca2+ and PTH, decreased PO34-, increased 24h urinary Ca2+
Imaging: osteitis fibrosa cystica, may show as subperiosteal erosions
DEXA for osteoporosis
Increase fluid intake, avoid thiazides and high Ca2+ and vit D intake, excision of adenoma
Hypoparathyroidism, recurrent laryngeal nerve damage (thus hoarse,) symptomatic Ca2+ decrease
40
Causes and treatment of secondary hyperparathyroidism? Causes of tertiary?
Decreased vit D intake, chronic renal failure
Correct causes, phosphate binders; vit D
After prolonged secondary hyperparathyroidism- glands act autonomously after hyperplastic or adenomatous change--> increased Ca2+ from big increase in PTH unlimited by feedback control
41
Ca2+, PTH and PO34- levels in primary hypothyroidism? Due to what? Causes, signs, tests and treatment?
Low PTH, low Ca2+and high phosphate
Gland failure, autoimmune; congenital (Di George syndrome)
Hypocalcaemia and autoimmune comorbidities
Decreased Ca2+, increased PO43- or normal alk phos
Ca2+ supplements and calcitriol
42
Causes of secondary hypoparathyroidism?
Radiation, surgery (thyroidectomy, parathyroidectomy,) hypomagnesaemia (needed for PTH secretion)
43
What is pseudohypoparathyroidism? Ca2+, PTH and PO43- levels? Signs, tests and treatment?
```
Failure of target cell response to PTH
Low Ca2+, PTH high, high phosphate
Short metacarpals (esp. 4th and 5th,) round face, short stature, calcified basal ganglia, decreased IQ
Decreased Ca2+, increased PTH/ alk phos
Ca2+ supplements and calcitriol
```
44
What is pseudopseudohypothyroidism?
Morphological features of pseudopseudohypothyroidism but with normal biochemistry
Cause for both= genetic
Normal Ca2+ metabolism
45
Vit D deficiency causes what PTH, Ca2+ and phosphate levels? For hypercalcaemia malignancy?
Increased PTH, decreased Ca2+, decreased phosphate (secondary hyperparathyroidism)
High calcium, low PTH, normal phosphate
46
Symptoms of hypercalcaemia? Causes?
Thirst, polyuria, nausea, constipation, confusion--> coma, renal stones, ECG abnormalities
Malignancy, primary hyperparathyroidism= 90%
Also thiazides, thyrotoxocosis, sarcoidosis, familial hypocalciuric, immobolisation, milk-alkali- overdosing of calcium, adrenal insufficiency, phaeochromocytoma
47
Causes of hypocalcaemia? How is vit D metabolised? How is corrected calcium calculated?
Vit D deficiency- 25 hydrolysed in liver then 1 hydrolysed in kidney
Total serum calcium + 0.02*(40-serum albumin)
48
Consequences of hypocalcaemia? 2x tests?
Parasthesia, muscle spasm- hands and feet, larynx, premature labour, seizures, basal ganglia calcification, cataracts, ECG abnormalities
Chvostek's- tap over facial nerve, look for spasm of facial muscles
Trousseau's signs- inflate BP cuff to 20mm Hg above systolic for 5 mins
49
In fasting state, all glucose comes from where? % glucose to liver and periphery after ingested? High insulin and glucose suppresses what?
The liver- glycogen breakdown, gluconeogenesis- lactate, alanine and glycerol used--> insulin independent tissues- brain and RBCs
40%--> liver, 60%--> periphery, mostly muscle
Lipolysis and levels of NEFA or FFA fall
50
Glucose--> cells through what? Need ATP for what channels? What modulates release of insulin from Beta cells? Glucose entering cell causes what? Insulin--> receptor causes what?
GLUT2 transporter
Potassium channels
Ca2+
Closes K channels--> Ca2+ into cell--> insulin from secretory granules released
GLUT vesicles to membrane--> glucose into tissues
51
Other counterregulatory hormones to insulin? Acute hyerglycaemia can lead to what 2 things? Chronic leads to what?
Adrenaline, cortisol, GH, similar to glucagon
Diabetic ketoacidosis, hyperosmolar coma
Micro and macrovascular complications
Treatment can--> hypoglycaemia
52
Triglycerides are broken down into what and used for what? FFA used by what?
Into FFA and glycerol in adipose tissue- used by liver to produce insulin
Heart as a fuel source
53
Types of diabetes?
Gestational and medication induced diabetes
Maturity onset diabetes of youth (MODY)= monozygotic diabetes
Pancreatic
Endocrine diabetes (acromegaly/ cushings), malnutrition related diabetes
54
Biochemical def of diabetes? Pathogenesis of type 1 diabetes? Leads to what things in the body?
Symptoms and random plasma glucose> 11 mmol/l
Fasting> 7 mmol/l
Loss of beta cells due to autoimmune destruction- only 10% B cells remain
Continued breakdown of glycogen in liver, unrestrained lipolysis, skeletal muscle breakdown, increase in hepatic glucose output, increased urinary glucose losses, increase in circulating glucagon, perceived stress--> increased cortisol and adrenaline, increasing ketone levels
55
Low insulin levels leads to what? What isn't there with type 2 diabetes? Presenting features of diabetes?
Prevents muscle catabolism and excessive ketogenesis
Ketonuria
Thirst, polyuria, weight loss and fatigue, hunger, pruritis vulvae and balanitis, blurred vision
56
Suggestive features of type 1 diabetes?
Onset in childhood/ adolescence, lean body habitus, acute onset of osmtic symptoms, prone to ketoacidosis, high levels of islet autoantibodies
1) Weight loss 2) Short history of severe symptoms 3) Moderate/ large urinary ketones-- any 2 of these 3 features
57
Suggestive features of type 2 diabetes? Type 1 or 2?
Usually in over 30s, gradual onset, FH is often positive, almost 100% concordance in identical twins
If in doubt- treat with insulin
58
% chance of type 1 diabetes if mother has it, father, both parents, brother/ sister, non-identical and identical twin? Antibodies associated with type 1 diabetes? Other autoimmune diseases also associated?
Mother= 2%, father= 8%, parents= 30%, brother/ sister= 10%, 15%= non-identical twin, 40%= identical twin
Anti-GAD, pancreatic islet cell Ab, islet antigen-2 Ab
Hypothyroidism, Addisons, coeliac disease
59
Ketoacidosis can lead to what? FFA impairs what and transported to where for what?
Falling circulating blood volume, anorexia and vomiting, dehydration, hyperglycaemia and increasing acidosis--> circulatory collapse and death
To liver, energy for gluconeogenesis and oxidised--> ketone bodies (beta hydroxyl butyrate, acetoacetate and acetone)
60
Signs and symptoms of diabetic ketoacidosis?
Hyperventilation, dehydration, hypotension, tachycardia, coma
Over days, polyuria, polydipsia, nausea and vomiting, weight loss, weakness, abdominal pain, drowsiness/ confusion
61
Biochemical diagnosis of DKA?
Hyperglycaemia, K+ high on presentation despite total body K+ deficit, fall with insulin and rehydration, anticipate fall in K+
HCO3-< 15 mmol/l, urea and creatinine= raised due to pre-renal failure
Urinary ketones dipstix> 2+ ketones, blood ketones> 3.0
62
Management of DKA? Complications?
If systolic BP<90, then give saline then start insulin infusion
Cerebral oedema, aspiration pneumonia, hypokalaemia, hypomagnesaemia, hypophosphataemia, thromboembolism- venous and arterial
63
Cause of type 1 diabetes? % concordance in identical twins? How many genes important? What is LADA?
Insulin deficiency from autoimmune destruction of insulin-secreting pancreatic B cells
30% concordance in identical twins, indicating environmental influence
4x genes- one (6q) determines islet sensitivity to damage e.g. from viruses, cross-reactivity from cows' milk-induced antibodies
Form of type 1 DM- with slower progression to insulin dependence in later life
64
Type 1 diabetes treatment?
2x daily mix of short/ medium acting insulin
Basal bolus- once/ twice daily medium acting plus pre meal quick acting insulin
Ability to judge CHO intake
65
Symptoms of hypoglycaemia due to high insulin?
Sweating, tremors, palpitations, loss of conc, hunger
Acute deprivation in brain-->cerebral dysfunction
Higher glucose targets= reduces risk, but increases risk of diabetic complications
66
What can type 2 diabetes be? Low levels of insulin prevent what? Causes?
Impaired secretion or insulin resistance which leads to impaired glucose tolerance which causes T2 DM and progressive hyperglycaemia and high FFA
Muscle catabolism and ketogenesis, muscle breakdown and gluconeogenesis are restrained- not ketonuria
Obesity, lack of exercise, calorie and alcohol excess, progresses from IGT or IFG, >80% concordance in identical twins
67
Presentation and treatment of type 2 diabetes?
Asymptomatic or complications
Metformin (oral)- to increase insulin sensitivity and help weight
Sulfonylurea (oral)- added if glucose still not controleld
Insulin SC- isophane insulin bd or long-acting analogue
68
What diabetic type are more at risk of hyperosmolar hyperglycaemic non ketotic coma? Due to what? What are a danger? Treatment?
With type 2 DM
Marked dehydration and very high glucose levels, acidosis= absent
Occlusive events- focal CNS signs, chorea, DIC, leg ischaemia/ rhabomyolysis, DVT
LMWH prophylaxis to all unless contraindication
Rehydrate slowly with 0.9% saline IVI over 48h
Replace K+ when urine starts to flow
Only insulin if blood glucose not falling by 5mmol/L/h with rehydration
Look for cause, e.g. MI, drugs or bowel infarct
69
Complications of diabetes? Stages of retinopathy? New vessels in eyes can proliferate, bleed, fibrose and detach the retina known as what?
Injection site infections, vascular disease (MI, stroke, HTN)
Nephropathy, diabetic feet
Cataracts, rubeoisis iridis- can lead to glaucoma, diabetic retinopathy
Dots and blots= (background,) small infarcts and haemorrhages (pre-proliferative)--> vascular leak, microaneurysms, capillary occlusion, local hypoxia and ischaemia--> new vessels (proliferative)
Maculopathy
70
E.g. of long-acting basal insulin? E.g. of fast-acting prandial insulins?
NPH insulin, insulin glargine, insulin detemir, insulin degludec, lente insulin series, pumped series
Insulin lispro, insulin glulisine, EDTA/ citrate human insulin, faster-acting insulin aspart
71
What does basal insulin control?
Controls blood glucose in between meals and particularly during night
Basal= adjusted to maintain fasting blood glucose between 5-7 mmol/l
72
NPH insulin has onset, peak action and duration of what? Aspart, lispro and glulisine?
Onset of 90 mins, peak action 2-4 hours, duration of up to 24 hours
10-20 mins, peak action= 30-90 mins, duration of 2-5 hours
73
Human premixed humulin M3 has onset, peak action and duration of what?
30 mins, peak action= 2-8 hours, duration of up to 24 hours
74
Pros and cons of basal insulin?
Simple, based on fasting glucose, less risk of hypoglycaemia at night
Doesn't cover meals, best used with long-acting which considered expensive
75
Pros and cons of pre-mixed (basal and prandial) insulin?
Can cover requirements of day
Not physiological, requires consistent meal and exercise pattern, cannot separately titrate individual insulin components
Increased risk of nocturnal hypoglycaemia
Increased risk for fasting hyperglycaemia if basal not last long enough
76
Neuroglycopenic meaning? Low blood glucose level? Treatment for hypoglycaemia?
Difficulty concentrating, confusion, weakness, drowsiness, dizziness, vision changes, difficulty speaking
<3.9mmol/ l
Carbohydrate
77
Risk factors for hypoglycaemia?
History of severe episodes, long duration of diabetes, renal impairment, extremes of age
Type 2: advancing age, cognitive impairment, aggressive treatment of glycaemia, impaired awareness of hypoglycaemia
78
Glucose targets in type 1 and 2?
Lowest not with freq hypo
Relax in advanced disease, complications/ limited life expectancy
Aim for lowest not associated with hypo, <7.0% usually appropriate
May need to relax targets
79
T4 converted to T3 using what? Symptoms of pituitary- gonadal axis not working?
Deiodinases
| Lack periods, infertility, decreased sexual function, erectile dysfunction
80
If cortisol levels low due to HPA axis, can get what?
From infection/ trauma--> cardiovascular collapse
81
3 categories of pituitary disease?
Pressure on local structure, pressure on normal pituitary- hypopituitarism, functioning tumour- prolactinoma, acromegaly, Cushing's disease
82
What does hypopituitarism look like in a man?
Lack of ACTH- lack of pigment
| Deficient in testosterone and GH= obese, no hair
83
What is Cushing's syndrome? Causes?
Chronic, excessive and inappropriate elevated levels of circulating plasma glucocorticoids (cortisol)
Pituitary tumour, ectopic (lung), adrenal tumour, oral steroids
84
What is Cushing's disease? Most often result of what? Peak age? Low-dose dexamethasone test leads to what?
A cause of Cushing's syndrome- increased ACTH from anterior pituitary
Of pituitaryadenoma/ due to excess production of hypothalamus CRH stimulating cortisol from adrenals
No change in plasma cortisol, but 8mg may be enough to more than 1/2 morning cortisol
85
Features of ectopic ACTH production- especially small cell lung cancer and carcinoid tumours? Rare causes of ectopic CRH production?
```
Pigmentation, hypokalaemic metabolic alkalosis, weight loss, hyperglycaemia, classical features= often absent
Dexamethasone even in high doses fails to suppress cortisol production
Some thyroid (medullary) and prostate cancers
```
86
ACTH independent causes of Cushing's syndrome?
Adrenal adenoma/ cancer- may cause abdo pain plus/ minus virilisation in women- because tumour is autonomous, dexamethasone in any dose won't suppress cortisol
Adrenal nodular hyperplasia
Iatrogenic- pharmacological doses of steroids (common)
87
Symptoms of Cushing's disease? Signs?
Weight gain, mood change, proximal weakness, gonadal dysfunction, acne, recurrent Achilles tendon rupture
Central obesity, plethoric, moon face, buffalo neck hump, supraclavicular fat distribution, skin and muscle atrophy, bruises, purple abdominal striae, osteoporosis, BP/ glucose increase; infection- prone; poor healing.
88
Tests and treatment for Cushing's syndrome?
MRI= detects only 70% of pituitary tumours causing Cushing's
Overnight dexamethasone suppression test- given at midnight, serum cortisol is measured at 8am
Stop meds if possible, removal of adenoma, bilateral adrenalectomy if source unlocatable, surgery if tumour is located and hasn't spread
89
What is Conn's syndrome? 2 main causes of Conn's syndrome?
Causes an excess of aldosterone- more Na+ and water retention, greater potassium excretion, decreased renin release
Unilateral adenoma in renal tissue- removal of one gland removing adenoma with aim of curing
Bilateral adrenal hyperplasia- removing could cause Addisons disease, given something to block action aldosterone e.g. spironolactone- also binds to sex hormone receptors so SEs can be unpleasant
90
What is acromegaly? Causes liver to produce what? Enlargement of what?
Increased GH secretion from pituitary tumour (99%) or hyperplasia e.g. ectopic GH-releasing hormone from carcinoid tumour
IGF-I
Much of body- hands, increased height if get acromegaly prior to fusion of hypopheses, microglomia?
91
Symptoms of acromegaly? Signs? What happens if acromegaly before bony epiphyses (rare)?
Acroparasthesia, amenorrhoea, decreased libido, headache, increased sweating, snoring, arthralgia, backache, insulin- resistant diabetes
Increased growth in hands, jaw and feet, coarsening face, wide nose, big tongue, widely spaced teeth, puffy lips, eyelids and skin, scalp folds, skin darkening
Obstructive sleep apnoea, goitre, proximal weakness and arthropathy, carpal tunnel= 50%
Gigantism
92
Complications of acromegaly?
Impaired glucose tolerance, DM, vascular: BP increase, left ventricular hypertrophy, cardiomyopathy, arrhythmias, increased risk of IHD and stroke, colon cancer risk increase
Sub-fertility is common, pregnancy may be normal; signs and chemistry may remit, monitor glucose
93
Tests for acromegaly? Glucose tolerance test is needed if basal serum GH is over what? If lowest is above what value, acromegaly is confirmed?
Increased glucose, Ca2+ and PO43-, GH: also increased in: stress, sleep, puberty and pregnancy
Serum IGF1 is raised
Normally GH secretion= inhibited by high glucose and GH= hardly detectable
In acromegaly GH release fails to suppress
0.4 micrograms/L
If above 1 micrograms/ L
94
Treatment for acromegaly? What if surgery fails? Side effects?
Reduce GH and IGF-I levels to at least <2 micrograms/ L
Aim to correct tumour compression by excising lesion
Transsphenoidal surgery= often 1st-line
Somatostatin analogues (SSA) and/ or radiotherapy
Pain at infection site, gastrointestinal: abdominal cramps, flatulence, loose stools, increased gallstones, impaired glucose tolerance
95
What is prolactinoma? What is microprolactinoma? Macroprolactinoma? It can be either what or what?
Lactotroph cell tumour of the pituitary
Macro= >5000mu/l, micro= stays small
Non-functioning pituitary tumour w/ compression of the pituitary stalk or due to antidopaminergic drugs
96
Local effect of prolactinoma tumour? Effect of prolactin? Management?
Headache, visual field defects (bi-temporal hemianopia,) CSF leak
Effect of prolactin- amenorrhoea or irregular periods, infertility, galactorrhoea, low libido, low testosterone in men
Given dopamine agonists- cabergoline, bromocriptine, quinagolide
97
Cortisol levels in morning? Peak when? What is Addison's disease? Causes?
Low levels in the morning, peak when first get up in the morning
Glucocorticoid and mineralocorticoid deficiency
80%= autoimmunity, TB, adrenal metastases, lymphoma, opportinistic infections in HIV, adrenal haemorrhage, congenital
98
Symptoms of adrenal insufficiency?
Often diagnosed late: tanned, tired, tearful, weakness, anoerxia, dizzy, faints, flu-like myalgias
Depression, psychosis, low self-esteem
Nausea/ vomiting, abdo pain, diarrhoea
99
Tests for adrenal insufficiency?
Decreased Na+ and increased K+, glucose decreased, uraemia, increased Ca2+, eosinophilia, anaemia
100
Diagnosing adrenal sufficiency?
Short ACTH stimulation test (synacthen): do plasma cortisol before and 1/2 hr after tetracosactide IM
Addison's excluded if 30 min cortisol> 550nmol/L
ACTH: 9am ACTH is high, it is low in secondary causes
21-hydroxylase adrenal autoantibodies: +ve in autoimmune disease in >80%
Plasma renin and aldosterone
AXR/ CXR
101
Treatment for adrenal insufficiency?
Replace steroids: hydrocortisone daily, in 2-3 doses
| Mineralocorticoids to correct postural hypotension, Na+/ K+ adjust both on clinical grounds
102
Commonest cause of secondary adrenal insufficiency?
Iatrogenic, due to long-term steroid therapy leading to suppression of pituitary- adrenal axis
Only apparent on withdrawal of steroids
103
Most common presentation of thyroid disease? Thyroid hormone does what?
Goitre- enlargement which is palpable and visible
| Develops the nervous system, metabolic rate, fight or flight by increasing synthesis of beta receptors (sympathetic NS)
104
Thyroglobulin and thyroid peroxidase antibodies are found in almost all patients with what? Present in what % of Grave's patients? Low levels present in healthy individuals at risk of?
Autoimmune hypothyroidism
75%
Thyroid or other autoimmune disease
105
Most common cause of hyperthyroidism? Often results in what? Typical age? Due to what?
Graves disease
Enlarged thyroid
40-60 years (younger if maternal family history)
Circulating IgG autoantibodies binding to and activating G-protein-coupled thyrotropin receptors--> increased hormone production
106
What binds to TSH receptors in Graves disease? What is neonatal graves'?
Thyroid stimulating antibodies- some do not stimulate but block effects of TSH
Receptor antibodies cross the placenta
107
Triggers of Graves disease? Associated with what other autoimmune diseases? There are what 2 factors?
Stress, infection, childbirth
Vitiligo, type 1 DM, Addison's, pernicious anaemia, coeliac, RA, SLE, Sjogren's, myasthenia gravis
Genetic and environmental factors
108
Signs and symptoms of hyperthyroidism? Other symptoms? Graves' ophthalmology can cause what? Treatment of Graves' disease?
Irritability, muscle weakness, sleeping problems, fast heartbeat, poor tolerance of heat, diarrhoea and weight loss
Thickening of skin on the shins- 'aspretibial myxedema'
Eye problems such as bulging- 'Graves' ophthalmology'= swelling of extraocular muscles
Diplopoa
Anti thyroid drugs, thyroidectomy, methyl prednisolone
109
What is thyrotoxicosis? Hyperthyroidism is when these elevated levels is due to what?
Elevated T3 and T4 due to the thyroid or due to the diet or other glands
The thyroid
110
3 mechanisms for increased levels of thyroid hormones?
Overproduction of thyroid hormone, leakage of preformed hormone from follicular cells, ingestion of excess thyroid hormone, perticious hyperthyroidism
111
Common causes of hyperthyroidism? Other causes?
Graves disease, adenoma, toxic multinodular goitre
Congenital (neonatal hyperthyroidism)
Iodine induces hyperthyroidism, drug induced: iodine, amiodarone- prevents iodine uptake and prevents conversion of T3 to T4, lithium
112
Clinical features and signs of hyperthyroidism?
Weight loss, tachycardia, palpitations, hyperphagia, anxiety, tremor, heat intolerance, sweating, diarrhoea, lip lag and stare, menstrual disturbance
Graves: goitre, eye disease
Adenoma: solitary nodules
113
Investigations for hyperthyroidism? Treatment of hyperthyroidism?
Thyroid function test (increased T3 and T4 supressed TSH in primary, elevated TSH in secondary)
Diagnose underlying cause, antibodies: TPO, TRAb Tg, isotope uptake scan
Antithyroid drugs: thionamised (carbimazole this decreases synthesis of new thyroid hormones)
Radioactive I131 (I transported into thyroid with I/Na symporter)
This emits beta particle which causes ionisation of thyroid cell- may exacerbate thyroid eye disease
Surgery- near total thyroidectomy for Graves and MNG and toxic adenoma
114
3 types of hypothyroidism?
Primary- >99% absence/ dysfunction thyroid gland, most cases due to Hashimoto's thyroiditis
Secondary
Tertiary- pituitary/ hypothalamic dysfunction
115
Primary causes of hypothyroidism?
Primary atropic hypothyroidism- lymphocytic infiltration of thyroid--> atrophy, no goitre, T cell mediated
Hashimoto's thyroiditis- goitre due to lymphocytic and plasma cell infiltration, commoner in women 60-70 years old, autoantibody titres are very high
Iodine deficiency, post-thyroidectomy or radioiodine treatment
Anti-thyroid drugs, amiodarone, lithium, iodine, post-partum thyroiditis
116
Secondary/ tertiary causes of hypothyroidism?
Pituitary or hypothalamic disease- not enough TSH, very rare
117
Signs of hypothyroidism?
Bradycardic, reflexes relax slowly, ataxia (cerebellar,) dry thin hair/ skin, yawning/ drowsy/ coma; cold hands plus/ minus decreased T, ascites plus/ minus non-pitting oedema (lids; hands; feet) plus/ minus pericardial or pleural effusion; round puffy face/ double chin/ obese; defeated demeanour; immobile plus/ minus ileus; CCF
Neuropathy, myopathy, goitre
118
Symptoms of hypothyroidism?
Tired; sleepy, lethargic; decreased mood; cold-disliking; weight gain; constipation; menorrhagia, hoarse voice; decreased memory/ cognition; dementia; myalgia; cramps; weakness
119
Diagnosis of hypothyroidism? Treatment?
TSH increased; T4 decrease
Cholesterol and triglyceride increase; macrocytosis (enlarged RBC)
Levothyroxine (T4)-lower in patients with IHD
120
Metabolic changes during pregnancy?
Increased erythropoetin, cortisol, noradrenaline
High CO, plasma volume expansion, high cholesterol and triglycerides, pro thrombotic and inflammatory state, insulin resistance
121
Gestational syndromes?
Pre-eclampsia- hypertension in pregnancy associated with seizures, common, very serious and threaten foetus
Gestational diabetes- increase in maternal age and diabetes
Obstetric cholestasis- liver function
Gestational thyrotoxicosis
Transient diabetes insipidus
Postnatal depression, postpartum thyroiditis, postnatal autoimmune disease
122
Foetal thyroid synthesis from what week? Axis for foetus maturing at what week? Maternal T4 at what week regulates neurogenesis, migration and differentiation then foetal T4?
From 10 weeks
At 15-20 weeks
0-12 weeks
123
Glycoprotein hormones like TSH, LH, FSH and hcG have what subunits? Hypothyroidism in pregnancy can have what effects?
Alpha and beta subunit
Gestational hypertension, placental abruption, post partum haemorrhage
Untreated: low birth weight, preterm delivery, neonatal goitre, neonatal resp distress
124
Hyperthyroidism in pregnancy? Management?
IUGR, low birth weight, pre-eclampsia, preterm delivery, risk of stillbirth, risk of miscarriage
Beta blockers, anti-thyroid medication, carbimazole, RAI= contraindicated during pregnancy
125
When are TSH-R antibodies measured? Foetal thyrotoxicosis associations?
At 22-26 weeks- if raised 2-3 fold, surveillance is needed
| Foetal goitre, foetal tachycardia, fetal hydrops, preterm delivery, foetal demise
126
Prevalence of post partum thyroiditis? High risk women are who?
7%
| Type 1 diabetes, Graves disease in remission, chronic viral hepatitis, measure TSH 3 months post partum
127
What is diabetes insipidus? Due to what 2 things?
Passage of large volumes of dilute urine due to impaired water resorption by kidney
Reduced ADH from posterior pituitary (cranial DI) or impaired response of kidney to ADH (nephrogenic DI)
128
% of body is water? Extracellular what fraction, split into what? Intracellular fluid? Ions in ECF? ICF?
```
60%
1/3= Intravascular and interstitial fluid
2/3
Na+, Cl- and HCO3-
K+, Mg2+ and phosphate ions
```
129
Excretion by kidney conducted by what? Vasopressin and oxytocin made where and transported where? ADH binds to what? What receptor on basolateral membrane of renal collecting ducts?
GFR and vasopressin
PVN and SON--> posterior pituitary in axoplasm of neurons
G-protein coupled 7 transmembrane domain receptors
V2 receptors
130
What is osmolality and what is it measured in? Similar to what but why slightly different? What is and isn't important when measuring? As osmolality increases, so does what?
Conc in plasma= mOsmol/ kg
Osmolarity, 6%= lipids and protein
Size= not important, but number is
AVP release
131
What is SIADH? Improper response to ADH may be due to what?
```
Too much vasopressin release when should not be released, also from ectopic source
Electrolyte imbalance (hypercalcaemia, hypokalaemia,) kidney disease, chronic lithium ingestion
Can be genetic (X-linked if V2 receptor defect or AR if AQ2 defect)
```
132
Symptoms of diabetes insipidus? Causes of cranial DI?
Polyuria, polydipsia, dehydration, symptoms of hypernatraemia
Idiopathic (<50%), congenital- ADH gene defects
Tumour: craniopharyngioma, metastases, pituitary tumour
Trauma
Hypophysectomy
Autoimmune hypophysitis
Infiltration: histiocytosis, sarcoidosis
Vascular: haemorrhage
Infection: meningoencephalitis
133
Causes of nephrogenic DI?
Inherited, metabolic: low K+, high Ca2+, drugs: lithium, demeclocycline
Chronic renal disease
Post-obstructive uropathy
134
Diagnosing diabetes insipidus? Investigation of DI?
Measure urine volume, DI unlikely if urine volume<3 L/day, check renal function and serum calcium
Water deprivation test- hypertonic saline infusion and measurement of AVP an alternative, tests the ability of the kidneys to concentrate urine for DI diagnosis and then to localise the cause
135
Treatment of cranial and nephrogenic DI?
Cranial= find the cause- MRI (head); test anterior pituitary function
Give desmopressin, synthetic analogue of ADH- high activity at V2 receptor
Nephrogenic: treat the cause
136
What is an important, but over-diagnosed cause of hyponatraemia? Hyponatraemia most often caused by what? Symptoms?
Syndrome of inappropriate secretion of ADH
Excess water rather than salt loss- Na+< 135 mmol/l
Headache, irritability, nausea/ vomiting, mental slowing, unstable gait, confusion, disorientation
Acute/ chronic= stupor/ coma, convulsions, resp arrest
137
Causes of SIADH?
Malignancy: lung small-cell, pancreas, prostate, thymus or lymphoma
CNS disorders: meningoencephalitis, abscess, stroke, subarachnoid or subdural haemorrhage, head injury, neurosurgery
Chest disease: TB, pneumonia, abscess, aspergillosis, small-cell lung cancer
Endocrine disease: hypothyroidism- due to excess ADH from carotid sinus baroreceptors
Drugs: opiates, psychotropics, SSRIs, cytotoxics
138
Treatment of SIADH? SIADH what % of all hyponatraemia? What is secreted?
Treat the cause and restrict fluid, consider salt plus/ minus loop diuretic if severe, identify and stop any causative drug (if possible)
25%
Too much AVP when should not be being secreted
139
What is osmotic demyelination syndrome? Risk factors? Management?
White areas in middle of pons, massive demyelination of descending axons, may take up to 2 weeks to manifest
Serum Na+< 105 mmol/L, hypokalaemia, chronic excess alcohol, malnutrition, advanced liver disease
Selective V2 receptor oral antagonist- 'tolvaptan', competitive antagonist to AVP, cause a profound aquaresis
140
Anterior lobe of pituitary is what % of total weight? E.g. of non-functioning pituitary tumours?
75%
Non-functioning pituitary adenomas, endocrine active pituitary adenomas, malignant pituitary: functional and non-functional pituitary carcinoma
Metastases in pituitary (breast, lung, stomach, kidney)
Pituitary cysts
Developmental abnormalities, primary tumours of the CNS
Vascular tumours
Malignant systemic diseases
Granulomatous diseases
Vascular aneurysms
141
Where do craniopharyngiomas come from? Features? Causes what?
Squamous epithelial remnants of Rathke's pouch
Solid, cystic, mixed, extends into suprasellar region
Raised ICP, visual disturbances, growth failure, pituitary, hormone deficiency, weight increase
142
Rathke's cyst from what? What is it? Present with what?
Remnants of Rathke's pouch
Single layer of epithelial cells with mucoid, cellular or serous components in cyst fluid
Mostly intrasellar component, may extend into parasellar area
Mostly asymptomatic and small
Headache and amenorrhoea, hypopituitarism and hydrocephalus
143
Meningioma is commonest after what? Complication of what? Associated with? Usually present with what?
Pituitary adenoma
Radiotherapy
Visual disturbance and endocrine dysfunction
Loss of visual acuity and visual field defects
144
What is lymphocytic hypophysitis? Examples? Commoner in who?
Inflammation of pituitary gland due to autoimmune reaction
Adenohypophysitis, infindibuloneurohypophysitis, panhypophysitis
Women
145
Non-functioning pituitary adenomas account for what % of primary intracranial tumours? What % cases are diagnosed between 20-60 years of age? What % of pituitary macroadenomas? What % of macroadenomas cause visual disturbances and headaches? Signs of aggressiveness?
```
10-15%
78%
50%
50% and 50%
Large size, cavernous sinus invasion, lobulated suprasellar margins
```
146
Signs and investigations of pituitary dysfunction? Local mass effects?
Tumour mass effects, hormone excess, hormone deficiency
Hormonal tests, if abnormal- perform MRI pituitary
Cranial nerve palsy and temporal lobe epilepsy, headaches, visual field defects, CSF rhinorrhoea
147
Tests and treatment of non-functioning tumours?
No specific tests, but absence of hormone secretion
Test normal pituitary function
Trans-sphenoidal surgery if threatening eyesight/ progressively increasing in size
148
Why is testing pituitary function so complex? Pituitary is working if what is working normally?
Because many hormones: GH, LH/ FSH, ACTH, TSH and ADH
| The peripheral target organ
149
TSH and Ft4 in primary hypothyroidism? In hypopituitary? Graves disease? In TSHoma? Hormone resistance?
```
Raised TSH, low Ft4
Low Ft4 with normal/ low TSH
Suppressed TSH, high Ft4
High Ft4 with normal/ high TSH
High Ft4 with normal/ high TSH
```
150
Testosterone and LH/FSH levels in primary hypogonadism? Hypopituitary? Anabolic use? Measure what in pituitary disease?
Low T, raised LH/ FSH
Low T, normal/ low LH/ FSH
Low T and suppressed LH
0900h fasted T and LH/FSH
151
Hormone levels in females before puberty? What increases in puberty? Hormone levels post-menarche? Primary ovarian failure? Hypopituitary?
Oestradiol very low/ undetectable with low LH and FSH although FSH slightly higher than LH
Pulsatile LH and oestradiol
Monthly menstrual cycle with LH/ FSH, mid-cycle surge in LH and FSH and levels of oestradiol increases through cycle
High LH and FSH with FSH greater than LH and low oestradiol
Oligo/ amenorrhoea with low oestradiol and normal or low LH and FSH
152
Testing the HPA axis? Cortisol, ACTH and synacthen response in primary adrenal insufficiency? Hypopituitarism?
Measure 0900hr cortisol and synacthen
Low cortisol, high ACTH, poor response
Low cortisol, low or normal ACTH, poor response
153
How is GH secreted throughout the day? Levels fall with what and are low when? Testing GH/ IGF1 axis?
In pulses with greatest pulse at night and low/ undetectable levels between pulses
With age, low in obesity
IGF-I and GH stimulation test, insulin stress test, glucagon test, other
154
How would prolactin be measured? May be raised due to what?
3 samples over an hour to exclude stress of venupuncture
| Stress, drugs, antipsychotics, stalk pressure, prolactinoma
155
When may dynamic testing be useful? Dexamethasone suppression testing for what disease? Oral glucose GH suppression test for what? CRH stimulation for what? TRH stimulation for what? GnRH stimulation for what? Insulin- induced hypoglycaemia for what deficiency? Glucagon test for what deficiency?
```
In select cases to further evaluate pituitary reserve and/ or for pituitary hyperfunction
Cushing's
Acromegaly
Cushing's
TSHoma
Gonadotropin deficiency
GH/ ACTH deficiency
GH deficiency
```
156
Preferred imaging study for pituitary? What do T1 images show you? Show up as what? T2 images?
MRI- better visualisation of soft tissues and vascular structures than CT, no exposure to ionising radiation
Produce high-signal intensity images of fat, fatty marrow and orbital fat- show up as bright images
High intensity signals of structures with high water content such as CSF and cystic lesions
157
What are CT scans better for? Better at determining what? May be useful when? Cons of CT?
Body structures and calcifications within soft tissues
Diagnosis of tumours with calcification e.g. germinomas, craniopharyngiomas and meningiomas
When MRI is contraindicated such as in patients with pacemakers or metallic implants in brain/ eyes
Less optimal soft tissue imaging compared to MRI, use of IV contrast media, exposure to radiation
158
Signs and treatment for GH deficiency? LH/ FSH deficiency? TSH?
Short stature, abnormal body composition, reduced muscle mass, poor quality of life
Rx: GH
Hypogonadism, reduced sperm count, infertility, menstruation problems
Rx: testosterone in males, oestradiol + or - progesterone in females
Hypothyroidism- Rx: levothyroxine
159
ACTH deficiency signs and treatment? ADH?
Adrenal failure, decreased pigment- Rx: hydrocortisone
| Diabetes insipidus, polyuria- Rx: DDAVP
160
The challenge of modified- release HC? Solution? Dose of levothyroxine? Aim to achieve what level? Higher doses in who? Check level when?
Gut length and transit time
Microparticulates
1.6mg/kg/day
Mid to upper half of reference range level
In patients on oestrogens or in pregnancy
Check level before dose
161
Dose of GH in GH replacement? Aim for what IGF1 level? Measure IGF1 how many weeks after dose start? Improves what 3 things?
<60 years- start 0.2-0.4 mg/ day
>60 years- start 0.1-0.2 mg/day
Measure IGF1 6 weeks after dose start
Lipid profiles, body composition and bone mineral density
162
Forms of testosterone replacement? Follow levels of what 3 things? Improves what things?
Gels, injections, oral
Testosterone, FBC, PSA
Bone mineral density, libido, function, energy levels and sense of wellbeing, muscle mass and reduces fat
163
Formulations of oestrogen replacement? Pros of this? HRT in 40-49 year olds not associated with what?
Oral/ combined with progesterone
Alleviates flushes and night sweats; improves vaginal atrophy, reduces cardio disease risk, osteoporosis and mortality
Breast cancer
164
Formulations of desmopressin? Monitor what level?
Subcutaneously, orally, intra-nasally, sub-lingually, adjust according to symptoms
Sodium levels
165
Monogenic causes of diabetes? Inherited how? Diagnosed when? Single gene altering what? Tend to be what?
```
Maturity- onset diabetes of the young= MODY- commonest type
Autosomal dominant
<25 years
Non- insulin dependent
Altering beta cell function
Non- obese
```
166
What mutation type alters insulin secretion and reduces beta cell proliferation? What mutation is very sensitive to sulfonylurea treatment? HNF4A causes what?
Hepatic nuclear factor (HNF)
HNF1A
FH, young age of onset, non-obese, Sus and macrosomia (>4.4kg at birth)
Neonatal hypoglycaemia
167
What is the glucose- sensor of beta cells and rate-determining step in glucose metabolism? MODY is typically diagnosed as what? Patients that might be MODY?
GCK
Type 1 or young-onset type 2
Parent affected, absence of islet autoantibodies, evidence of non- insulin dependence- good control on low dose insulin, no ketosis, measurable C-peptide, sensitive sulfonylurea
168
C-peptide in type 1 and 2/ MODY diabetes? Signs and diagnosis of permanent neonatal diabetes? Mutations of Kir6.2 and SUR1 subunits of beta cell ATP sensitive K+ channel prevents what?
Negative within 5 years due to complete autoimmune beta cell destruction in type 1
Type 2 and MODY= C-peptide persists
Small babies, epilepsy, muscle weakness, <6 months
Prevents closure of channel- beta cells unable to secrete insulin
169
Maternally inherited diabetes and deafness (MIDD) mutation in what? Features?
In mitochondrial DNA, loss of beta cell mass, similar presentation to type 2, wide phenotype
170
What is lipodystrophy? Associated with what?
Selective loss of adipose tissue
| Insulin resistance, dyslipidaemia, hepatic steatosis, hyperandrogenism, PCOS
171
Acute disease of pancreas? Chronic?
Usually transient hyperglycaemia, due to increased glucagon secretion
Alcohol, alters secretions, formation of proteinaceous plugs that block ducts and act as foci for calculi formation
Stop alcohol, treat with insulin
172
How is hereditary hemochromatosis inherited? Triad of what? Excess iron where? Most need what? 2x deposition diseases?
Autosomal recessive
Cirrhosis, diabetes, bronzed hyperpigmentation
Liver, pancreas, pituitary, heart and parathyroids
Insulin
Amyloidosis/ cystinosis
173
How does excessive GH secretion causes diabetes? How does Cushings syndrome causes diabetes? Pheochromocytoma? What drug can increase insulin resistance?
Similar to type 2- insulin resistance rises, impairing insulin action in liver and peripheral tissues
Increased insulin resistance, reduced glucose uptake, gluconeogenesis from liver stimulated via increased substrates
Catecholamine (predominantly epinephrine)--> decreased glucose uptake, increased gluconeogenesis
Glucocorticoids
Thiazides/ protease inhibitors, antipsychotics- mechanisms not clearly understood
174
What fraction of adults, 2-10 YOs and 11-15 YOs are overweight/ obese? Morbidities associated? Factors contributing to weight maintenance?
2/3, 1/4 and 1/3
HTN, high cholesterol, T2 DM, CHD, stroke, OA, obstructive sleep apnoea, carcinoma (breast, endometrium, prostate, colon)
Energy intake, type of food intake, appetite, mood, activity, metabolic rate, genes, drugs
175
What is nonexercise activity thermogenesis?
Spontaneous physical activity (twitching, fidgeting)= familial trait
Marked individual differences in contribution to daily energy expenditure
May be significant contributor to maintaining leanness
176
Metabolic syndrome causes what? High waist circumference with two of what features? Adipocytes are highly active endocrine glands that secrete what? These exert marked influences on metabolic function and cardio risk in number of what in body? Can increase risk of what?
Abdominal obesity
High triglycerides, high HDL cholesterol, BP consistently above 140, diabetes
Important hormones, cytokines, vasoactive substances and other peptides
Organ systems
T2 DM, HTN, inflammation, atherosclerosis/ thrombosis
177
What does obesity assessment explore?
Person's view of their weight and diagnosis and possible reasons for weight gain, eating patterns and physical activity, beliefs about eating, physical activity and weight gain, ethnic/ socioeconomic influences on beliefs, what has been tried and success, readiness to change and confidence in making changes
178
4 components of multi component intervention in obesity?
Activity- set own goals and referred to Activity Sheffield, individualised dietary advice from dietician, behavioural strategies- goal setting, support, rewards
positive feedback
179
Individual level interventions?
Exercise- fits easily into people's lives e.g. walking, cycling, dancing
Prescribe exercise
Diet- healthy diet, low calorie diets, very low calorie diets- <1000 kcal/day, may be used for max 12 weeks or 2-4 days a week e.g. by obese reaching plateau in weight loss
<600kcal/day with clinical supervision
Behaviour change strategies- self-monitoring, relaxation, hypnotherapy, commercial programmes, only use if adhere to best practice e.g weekly loss of 0.5-1 kg, uses balanced healthy eating approach, multi-component, on-going support
180
4 methods of wider-level intervention in obesity?
Food supply- altering composition and manufacture of food products by reducing energy-dense ingredients, increased access/ availability of healthy food
Society- media campaigns, changing media portrayal of body image, changing social norms
Environment- changes in transport infrastructure, changes in urban design
Reshaping public policy- subsidise prices, raise prices e.g. sugar tax, minimum price for alcohol unit
legislation
181
What can doctors do to combat obesity?
Education, brief interventions, signpost to programmes, prescribe exercise, prescribe medications, refer to surgery, lobby for policy changes
182
Barriers to tackling obesity?
We like easily available energy, don't like expending energy unnecessarily, most interventions will only impact in long-term
Industry profits from making us fat
National economy that needs an industry?, unrealistic pricing of energy?
Adults underestimate theirs and kids weights, the media tend to use extreme images of obesity and GPs underestimate pt BMI
183
Additional factors contributing to weight loss? Best predictors of clinically significant weight loss at 1 year?
Medication with appropriate counselling and support, diabetes management, hypo advice, support, hard work
>2.5kg during 4 week dietary run
>5% wt loss after 12 weeks
Patients in this 'responder' group achieve an average of 16.4% wt loss
184
VLCDs are accompanied by improvements in what? Weight loss typically achieved? Most regain 1/3 weight or all when? Average adult gains what a day/ decade?
Glycaemic control, lipids and BP
5-15 kg
1/3 in 1 year or all in 3-5 years
1g/ day, 3 kg/ decade
185
Successful weight maintainers tend to do what?
Stick to a low calorie, low fat diet, eat breakfast every day, eat same amounts through week, weekend and holidays, restrict variety of foods esp fatty foods, highly active, lower scores of depression, eating excess, bingeing from outset, self monitoring- weight, food intake and activity levels
186
What is puberty? What is adrenarche? How many years before gonadarche?
Physical changes through which a child's body matures into an adult body capable of sexual reproduction to enable fertilisation.
Adrenal maturation= increased adrenal androgens
2 years
187
What is gonadarche? What is menarche? Pubarche? Thelarche?
Gonadal maturation secondary to increased GnRH activity= sex steroid activity= growth spurt, development of external genitalia and pubic hair, increase in uterus/ ovary size and spermatogenesis, menarche/ voice deepening
Period starting
Pubic hair
Breast development
188
What is thelarche induced by? Completed in how many years? What happens to the breasts? Other hormones involved in breast development?
Oestrogen- 3 years
Duct proliferation, site specific adipose deposition, enlargement of areola and nipple
Prolactin, glucocorticoids, insulin
189
At right age, what hormone provides permissive signal to start adrenarche? What marker from the adrenals? What from adrenals/ gonads? What age does this start?
Leptin
DHEAS
Androstenedione, testosterone
6/ 7 years
190
At what age does gonadarche take place? What does precocious mean? & female? Most caused by what? What hormone inhibits FSH?
8 or 9 years old
Early puberty before 8/9
90%- idiopathic
Inhibin
191
FSH affects what cells in males and females? LH?
Sertoli--> sperm, granulosa
| Leydig cells= testosterone, Theca internal cells
192
Factors affecting puberty?
Genetics, environment- nutrition, psych, anorexia, stress, maternal deprivation
Fat: higher BMI= early menarche
Adipocytes- leptin secreted, hypothalamus, glutamate, GnRH, goes to gonadotropins in anterior pituitary to stimulate
193
What is gynaecomastia? Rx?
Breast development in men (oestrogen related)
| GnRH analogues= down regulator of receptor
194
Delayed puberty is what? Cause of gonadotropin deficiency? What is isolated gonadotropin deficiency known as? Symptoms? Defect in what gene and protein? What does this protein modulate?
Idiopathic
Delayed activation of hypothalamic pulse generator
Tumours of hypothalamus/ pituitary
Hypohypothyroidism: Kallmann''s syndrome
Hyposmia/ anosmia- can't smell
Undescended testes, poor development of genitalia
KAL1 gene, ANOSMIN1 protein
Migration of GnRH neurones in early development, also olfactory dysfunction
195
What is primary gonadal failure also known as, also in men and women?
Hyperhypothyroidism
Men= Klinefelter's
Women= Turners syndrome
196
Chronic complications of hyperglycaemia include what 2 issues? Some diabetic complications?
Macrovascular and microvascular
Leading cause of blindness in working age adults, diabetic retinopathy, peripheral vascular disease, stroke, cardiovascular disease, leading cause of mortality
197
3 forms of consequences of diabetic neuropathy?
Pain- burning, paraesthesia, hyperaesthesia, allodynia, nocturnal- exacerbation
Autonomic- orthostatic hypotension, cardiac AN, gastroparesis, diarrhoea, constipation, incontinence, erectile dysfunction
Insensitivity- foot ulceration, infection, amputations, falls, Charcot foot ---> reduced quality of life
198
Features of diabetic peripheral neuropathy? Association with what? Microvascular complications are preventable by what?
Typical 'glove and stocking' sensory loss, significant motor deficit is not common, painful symptoms= 30%, pathogenesis of pain not known, peripheral vs central involvement
CVD
Rigorous glycemic control
199
Treatment of diabetic painful neuropathy? Screening tests?
Good glycemic control, tricyclic antidepressants, anticonvulsants, opioids, IV lignocaine, capsaicin, transcutaneous nerve stimulation/ acupuncture, spinal cord stimulators, psychological interventions/ hypnosis
Test sensation, vibration perception, ankle reflexes
200
Flow chart of diabetic amputation?
Neuropathy/ vascular--> trauma--> ulcer---> failure to heal---> infection----> amputation
201
Within peripheral vascular disease, decreased perfusion due to what? Sites? How many times more likely to have lower limb amputation? Clinical presentation?
Microvascular disease
More distal
15-40 times more likely
Intermittent claudication, rest pain
202
Signs of vascular disease? Non-invasive evaluation?
Diminished or absent pedal pulses, coolness of the feet and toes, poor skin and nails, absence of hair on feet and legs
Doppler pressure studies- pressure at brachial, pedal and toe arteries, duplex arterial imaging, rationale- identify and confirm disease, predict healing or determine need for surgical intervention
203
Treatment of peripheral vascular disease?
Quit smoking, walk through pain, surgical intervention
204
Greatest risk of diabetic retinopathy in what people? Eligibility for diabetic retinopathy screening programme? Pathogenesis of micro-aneurysms? Pathogenesis of leakage?
Long duration diabetes, poor glycemic control, hypertensive, on insulin treatment, pregnancy
>11 years old
Pericyte loss and smooth muscle cell loss
Basement membrane thickening, pericyte loss, reduces junctional contact with endothelial cells
205
Pathogenesis of ischaemia/ occlusion in the eyes?
Pericyte loss, endothelial cells respond by increasing turnover--> thickening--> ischaemia
Glial cells grow down capillaries--> occlusion
Ischaemia/ occlusion--> proliferation
206
Different stages of diabetic retinopathy grading? Only proven treatment for DR?
R0: none, R1: background, R2: pre-proliferative, R3: proliferative, M: maculopathy, P: photocoagulation, U: unclassifiable
Laser therapy, benefits outweigh the risks, aim is to stabilise changes, treatment does not always improve sight
207
Risks and success of laser treatment?
Over half notice difficulty with night vision, 1/5 lose peripheral vision, 3% stop driving because of tunnel vision, may notice drop in acuity if intensive laser
Very effective- over 90% of severe sight loss prevented by laser proliferative retinopathy, over 90% severe sight loss prevented by laser for early proliferative retinopathy
208
Hallmark of diabetic nephropathy? Followed by progressive decline in what? Major risk factor for what?
Development of proteinuria, renal function
| For CVD, risk factors= poor BP and BG control
209
Pathophysiology of nephropathy? Treatment?
Glomerulus changes, increase of injury glomerular, filtration of proteins---> diabetic nephropathy
BP and glycemic control, ARB/ ACEi, proteinuria control, cholesterol control
210
What can delay onset/ prevent type 2 diabetes? Including use of what 2 things? Issues?
Intensive diet and exercise programmes
Metformin and TZDs
Difficult to maintain over long term and costly
Unwanted side effects of medications
211
What are incretins? How do incretins influence glucose homeostasis? What drugs inactivate the incretin hormones GIP and GLP-1? Effects?
Hormones secreted by intestinal endocrine cells in response to nutrient intake
Via multiple actions including glucose-dependent insulin secretion, postprandial glucagon suppression and slowing of gastric emptying
DPP-4 inhibitors- competitive antagonists of DPP-4 enzyme which inactivate incretin hormones, orally available
Little effect on gastric emptying, do not cause nausea/ vomiting, no effect on weight, effects are mediated by multiple receptors
212
GLP-analogues induce what? How consumed? TZD effective what? Positive effects on what? Contraindicated in who?
Delay in gastric emptying, nausea/ vomiting, weight loss, mediated by GLP-1 receptor, injectable only
Glucose lowering agents, on metabolic syndrome
In CCF, high risk of fractures, macula oedema
213
Factors promoting insulin resistance? Impaired insulin action leads to what?
Obesity, physical inactivity- inflammation, free fatty acids, hormones (adiponectin), visceral fat and ectopic fat
Reduced muscle and fat uptake after eating, failure to suppress lipolysis and high circulating FFAs, abnormally high glucose output after meal
