Endocrinology Flashcards
What does endocrine mean? What does exocrine mean? Endocrine hormone action? Paracrine? Autocrine?
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
Peptides/ monoamine hormones stored where? Steroids synthesised when? Features of peptide hormones?
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
Prephormone turned into what? Prohormone packaged into what? Stored and secreted as what?
Prohormone
Hormone
As a hormone
Amine hormones bind to what receptors? Stimulate what NS? Iodothyronines are not what? % protein bound? % of T3 in circulation secreted directly by thyroid?
Alpha and beta adrenoceptors, sympathetic nervous system
Water soluble
99%
20%
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?
Colloid Thyroid hormone synthesis Tyrosine molecules T3 and T4 Thyroglobulin Secretory cell- T3 and T4 cleaved from thyroglobulin
Hormone receptor locations x3? Vitamin D is a what hormone? Soluble where and transported by what?
Cell membrane= peptide, cytoplasm= steroid, nucleus= thyroid
Fat soluble- enters cell directly to nucleus to stimulate mRNA production
Vitamin D binding protein
Adrenocortical and gonadal steroids % protein bound? Pass to where and do what? Not rapid inactivation where?
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
Stages of testosterone formation?
Cholesterol–> pregnenolone–> progesterone–> testes= androstenedione–> testosterone–> ovaries= oestradiol- secreted by follicles of ovaries
In adrenals= cortisol from adrenal cortex
Steroid hormone action? Forms of hormone secretion? Dopamine inhibits what hormone? 2 hormones affecting GH?
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
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?
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
What is synergism? What is antagonism? 2 nuclei in posterior pituitary? Oxytocin and ADH from hypothalamic neurones through what to posterior pituitary?
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
ADH release controlled by what 2 things? Hormones from anterior pituitary? TSH to where? ACTH? FSH and LH? GH? Prolactin?
Blood volume and osmolality GHRH, GHIH, CRH, TRH, GnRH, dopamine Thyroid Adrenal cortex Testes/ ovaries Entire body Mammary glands
Hypothalamus secretes what which stimulates GH production? GH does what- directly and indirectly?
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
Hypothalamus releases what which stimulates anterior to produce what? Thyroid hormone functions?
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
Sequence for cortisol release? e.g. of mineralocorticoids? Glucocorticoids? Androgens? DHEA?
Hypothalamus= CRH--> anterior pituitary= ACTH--> adrenal cortex= cortisol--> negative feedback Aldosterone Cortisol androgens Androstenedione Dihydroepiandrosterone
Hormones from adrenal medulla? Short term stress sends nerve impulses to where? Causes what? This causes what to happen?
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
Prolonged stress causes what to be released? Kidneys do what and what rises? What else happens?
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
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?
Theca cell Aromatase Granuloma cell Testosterone Sertoli cell
Hormones produced by other organs in body?
Heart = atrial natriuretic peptide, liver= IGF-I, kidney= erythropoietin, GI tract= gastrin, incretin, lung= hormone metabolism, blood vessel= prostanoids, nitric oxide, endothelin
What is satiety? Risks of obesity?
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
Underweight, obese and morbidly obese BMI values? 3 organs controlling appetite regulation? What happens with increased food intake?
<18.5= underweight, 30+= obese, >40= morbidly obese
Brain, GI tract, adipose tissue
Increased fat stores, insulin and leptin released
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?
Lateral hypothalamus Ventromedial hypothalamic nucleus Fat cells in adipose tissue Into BBB and arcuate nucleus Peripheral hormones, stimulate CART CCK
What hormone secreted by neuroendocrine cells in ileum, pancreas and colon reduces appetite and gastric motility? Similar to what? How many amino acids?
Peptide YY
NPY
36- also inhibits gastric motility
CCK does what? Where is ghrelin expressed? What does this stimulate? What is it known as? High when what? Fall when? Levels lower when?
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
No POMC=what deficiency? Adrenal insufficiency means what?
ACTH deficiency, not pigmented
No cortisol- obese
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
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
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
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
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
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
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)
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
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
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%
Ways of supporting self-care for diabetes?
Self- monitoring, diet, exercise, drugs, education, peer support
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
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
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
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
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
Causes of secondary hypoparathyroidism?
Radiation, surgery (thyroidectomy, parathyroidectomy,) hypomagnesaemia (needed for PTH secretion)
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
What is pseudopseudohypothyroidism?
Morphological features of pseudopseudohypothyroidism but with normal biochemistry
Cause for both= genetic
Normal Ca2+ metabolism
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
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
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)
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
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
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
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
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
Types of diabetes?
Gestational and medication induced diabetes
Maturity onset diabetes of youth (MODY)= monozygotic diabetes
Pancreatic
Endocrine diabetes (acromegaly/ cushings), malnutrition related diabetes
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
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
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
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
% 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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Neuroglycopenic meaning? Low blood glucose level? Treatment for hypoglycaemia?
Difficulty concentrating, confusion, weakness, drowsiness, dizziness, vision changes, difficulty speaking
<3.9mmol/ l
Carbohydrate
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
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
T4 converted to T3 using what? Symptoms of pituitary- gonadal axis not working?
Deiodinases
Lack periods, infertility, decreased sexual function, erectile dysfunction
If cortisol levels low due to HPA axis, can get what?
From infection/ trauma–> cardiovascular collapse
3 categories of pituitary disease?
Pressure on local structure, pressure on normal pituitary- hypopituitarism, functioning tumour- prolactinoma, acromegaly, Cushing’s disease
What does hypopituitarism look like in a man?
Lack of ACTH- lack of pigment
Deficient in testosterone and GH= obese, no hair
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
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
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
