Endo Flashcards
Hypothalamus neurons
Anterior pituitary: parvocellular
Posterior pituitary: magnocellular
Excess growth hormone disorders
Gigantism
Acromegaly
Acromegaly symptoms
Sweating Headache Macroglossia Increased hand and feet size Hypertension and impaired glucose tolerance
Acromegaly diagnosis
Oral glucose tolerance test
Paradoxical IGF-1 increase
Acromegaly treatment
Trans sphenoidal pituitary surgery
Pre operative somatostatin analogue (octreotide)
Pre operative dopamine agonist (cabergaline)
Prolactinoma effects
Prolactin binds to kisspeptin receptors
Kisspeptin release inhibited
Downstream inhibition of GnRH/FSH/LH
Low libido, oligomenorrhoea, osteoporosis
Causes of high serum prolactin
Prolactinoma
Macroprolactin(false positive)
Stress of venepuncture(false positive): cannulated prolactin series
Prolactinoma treatment
Dopamine receptor agonist(cabergoline)
Effects of TSH on follicular cell
Thyroid peroxidase(TPO) and thyroglobulin(TG) synthesis
Enzyme to convert T4 to T3
Deiodinase
Proteins which transport T3/T4 in blood
Thyroid binding globulin
Albumin
Prealbumin
Regulation of T3/T4 porduction
T3 &T4 have -ve feedback on hypothalamus and ant. pituitary
I- has -ve feedback on thyroid gland
Test for infants to check for thyroid disorder
Heel prick test to check for hypothyroidism, TSH will be high
Hashimoto’s thyroiditis pathophysiology
Primary hypothyroidism
Autoimmune disorder with anti-TPO antibodies
Hashimoto’s symptoms
Fatigue Bradycardia Dry skin Weight gain Constipation Depression maybe
Hashimoto’s treatment
Levothyroxine(T4)
Hyperthyroidism causes
Graves disease
Plummer’s disease
Viral(de Quervain) thyroiditis
Grave’s disease pathophysiology
Primary hyperthyroidism
Anti TSH receptor antibodies
Grave’s disease symptoms
Smooth goitre
Bilateral exophthalmos(bulging eyes)
Pretibial myxoedema
Plummer’s disease pathophysiology
Toxic nodular goitre
Benign adenoma that overproduces T4
Causes lumpy goitre
Viral thyroiditis symptoms
Painful dysphagia Pyrexia Thyroid inflammation Thyroid no visible on radioiodine scan Hyperthyroidism followed by hypothyroidism
Hyperthyroidism symptoms
Weight loss Tachycardia Palpitations Sweating Heat intolerance
Hyperthyroid treatment
Thionamides: propylthiouracil(PTU), carbimazole(CBZ) inhibit TPO
Potassium iodide: before surgery by inhibiting TPO, H2O2 and iodination
Beta blockers: propanolol
Surgery: beware of recurrent laryngeal nerve and parathyroid glands
Radioiodine: permanently reduces T4, can cause hypothyroidism
Layers of adrenal gland
Zona glomerulosa(aldosterone) Zona fasciculata(cortisol) Zona reticularis(sex steroids) Adrenal medulla(adrenaline)
Aldosterone action
Na reabsorption, K and H secretion in DCT and collecting duct
Increases blood volume
Aldosterone regulation
Low renal perfusion pressure High renal sympathetic activity(JGA) Low Na at macula densa Renin secretion by JGA Renin->AT1->AT2->aldosterone synthesis
Cortisol levels thoughout the day
Highest in the morning
Lowest at midnight(must be asleep)
Addison’s disease pathophysiology
Autoimmune disorder(UK) Tuberculosis of adrenal gland(worldwide)
High ACTH and MSH due to POMC
Addison’s disease symptoms
Hyperpigmentation Low bp GI problems Hypoglycaemia Hyponatraemia Hyperkalaemia
Addison’s diagnosis
Low 9am cortisol
High ACTH
SynACTHen test
Addison’s treatment
Saline(bp) Dextrose(hypoglycaemia) Hydrocortisone(cortisol) Prednisolone(cortisol) Fludrocortisone(aldosterone)
Cushing’s syndrome causes
Steroids taken by mouth
Cushing’s disease(pituitary adenoma)
Primary adrenal adenoma
Ectopic ACTH (lung cancer)
Cushing’s symptoms
Weight gain Thin skin Proximal myopathy High bp Diabetes Red cheeks
Cushing’s syndrome diagnosis
Low dose dexamethasone suppression test
Cushing’s treatment
Metyrapone(11 hydroxylase i): causes hypertension and hirsutism
Ketoconazole(17 hydroxylase i): causes liver damage
Pituitary surgery is Cushing’s disease
Uni/bilateral adrenectomy
Conn’s syndrome pathophysiology and symptoms
Benign adrenal cortical tumour
Excess aldosterone causing hypertension and hypokalaemia
Conn’s syndrome treatment
Spironolactone, epleronone: mineral corticoid receptor antagonist
Spironolactone can cause gynaecomastia and menstrual irregularities
Epleronone has milder side effects and similar affinity
Phaeochromocytoma pathophysiology and symptoms
Adrenal medulla tumour causing excess adrenaline and noradrenaline
Hypertension and episodic severe hypertension
Can cause ventricular fibrillation & death
Phaeochromocytoma treatment
Surgery with careful preparation
Alpha blockers(noradrenaline) to treat high bp
Beta blockers(adrenaline) to treat high bp and heart
21 hydroxylase deficiency
Aldosterone and cortisol deficiency
Sex steroid excess->girls have ambiguous genitalia
11 hydroxylase deficiency
Aldosterone and cortisol deficiency
11 deoxycorticosterone acts like aldosterone
Excess sex steroids, testosterone and 11-deoxycorticosterone
High bp, low K+, virilisation
17 hydroxylase deficiency
Cortisol and sex steroid deficiency
Excess aldosterone
Hypertension
Hypokalaemia
Low glucose
Low sex steroids
Hormones in calcium and phosphate regulation
PTH
Calcitriol
FGF23
Calcitonin
Calcitriol synthesis
Vit D3/D2->25(OH)cholecalciferol-> 1,25(OH)2cholecalciferol by 1-alpha hydroxylase
Calcitriol effects
Bone:
Increase osteoblast activity
Gut:
Increase calcium absorption
Increase phosphate absorption
Kidney:
Increase calcium reabsorption
Increase phosphate reabsorption(PCT)
PTH synthesis
Chief cells in parathyroid gland
Level of PTH is inversely proportional to calcium conc.
PTH effects
Bone:
Calcium mobilisation
Gut(via calcitriol):
Increase calcium absorption
Increase phosphate absorption
Kidney:
Calcium reabsorption
Phosphate secretion(PCT)
1-alpha hydroxylase activity
PTH regulation
Serum Ca has -ve feedback
Calcitriol has -ve feedback
Calcitonin effects
Bone:
Reduce osteoclast activity
Kidney:
Increase Ca excretion
FGF23 function
Inhibit calcitriol
PTH and FGF23 both bind to Na/PO4 cotransporter in PCT->low reabsorption
Hypercalcaemia symptoms
Stones(nephrocalcinosis)
Abdominal moans(anorexia, constipation, pancreatitis)
Psychic groans(fatigue, depression, coma)
Primary hyperparathyroidism pathophysiology
Parathyroid adenoma
High serum Ca but no -ve feedback
PTH will be high
Low phosphate
Primary hyperparathyroidism treatment
Parathyroidectomy
Bisphosphonate
Shockwave lithotripsy
IV fluids
Secondary hyperparathyroidism pathophysiology
Normal physiological response to hypocalcaemia
Low calcium
High PTH
Commonly vit D deficiency
Secondary hyperparathyroidism treatment
Vit D replacement:
Normal renal function-> ergocalciferol(D2) or cholecalciferol(D3)
Impaired renal function->alfacalcidol as there is no 1-alpha hydroxylase
Tertiary hyperparathyroidism signs and treatment
Chronic renal failure so no calcitriol
High PTH
Enlarged parathyroid glands
Hypercalcaemia
Parathyroidectomy
Hormone that reduces glucagon and insulin secretion
Somatostatin
Measure of serum insulin level
C-peptide
GI incretin effect
More insulin is secreted when glucose passes through the gut
GLP1 stimulates insulin, suppresses glucagon
GLUT2 vs GLUT4
GLUT2 is not insulin sensitive, found in beta cells->ATP used to inhibit K diffusion as K activates Ca channel, causing insulin release
GLUT4 is insulin sensitive, found in myocytes/adipocytes
Diabetes mellitus diagnosis
HbA1c > 48mmol/mol
Fasting glucose >7mmol/L
Fed glucose >11mmol/L
T1DM symptoms and test
Weight loss Hyperglycaemia Glycosuria, polyuria, polydipsia, nocturia Ketones in blood/urine Blurred vision Fatigue
Antibodies
Low c-peptide
Ketone presence
T1DM management
Short acting insulin
Long acting insulin
Technology: real time glucose sensor, insulin pumo therapy
Transplant: islet cell/pancreas+kidney but needs life long immunosuppression
T2DM risk factors
Age Ethnicity Obesity Family history PCOS
T2DM complications (micro and macro)
Microvascular:
Retinopathy
Neuropathy
Nephropathy
Macrovascular:
Ischaemic heart disease
Cerebrovascular disease
Peripheral vascular disease
T2DM treatment
Metformin (biguanide)
Sulphonylurea (gliclazide)
DPP4 inhibitor (sitagliptin)
SGLT2 inhibitor (dapagliflozin)
GLP1 agonist (semaglutide)
Pioglitazone
Alpha glucosidase inhibitor
Manage hypertension and cholesterol
Male gonad cells and function
Sertoli: FSH receptor, spermatogenesis, synthesise inhibin, activin, AMH
Leydig: LH receptor, synthesise androgens
Female gonad cells and function
Granulosa: FSH receptor, converts androgen to oestrogen, produces progesterone after ovulation
Theca: LH receptor, androgen synthesis, support growing follicle
Folliculogenesis stages
Primordial follicle Primary follicle Secondary follicle Mature follicle Corpus luteum
Menstrual cycle hormone changes
High FSH to stimulate follicle maturation
Oestrogen stimulates LH receptor synthesis
FSH lower from -ve feedback
High oestrogen->LH surge(ovulation)
High progesterone and oestrogen to maintain endometrium
Capacitation of sperm
Oestrogen and Ca dependent
Sperm binds to ZP3
Sperm secretes hyaluronidase&protease
Sperm penetrates zona pellucida
Implantation mediators
Leukaemia inhibitory factor(LIF)
IL-11
Oxytocin function
Uterine contraction
Cervical dilation
Milk ejection
Tanner staging(puberty)
Thelarche
Genitalia
Pubarche
Enzyme to convert testosterone to oestrogen
Aromatase
Enzyme to convert testosterone to dihydrotestosterone
5 alpha reductase
Hypogonadism hormone levels
Primary: High FSH/LH Low E2/testosterone Men: cancer, trauma, infection Women: menopause
Secondary: Low FSH/LH Low E2/testosterone Pituitary tumour High prolactin
Menopause symptoms
Osteoporosis Dry skin/thin hair Mood disturbance Weight gain Sexual dysfunction
Menopause treatment
Oestrogen replacement
Progesterone to prevent endometrial hyperplasia
Early menopause(premature ovarian insufficiency) causes and diagnosis
Autoimmune
Genetic e.g. Turner’s syndrome/fragile X
Cancer therapy
High FSH(>25iU/L) twice, 4 weeks apart
Sheehan’s syndrome pathophysiology
Post partum hypopituitarism secondary to hypotension
Anterior pituitary enlarges during pregnancy->post partum haemorrhage-> pituitary infarction
Sheehan’s syndrome symptoms
Lethargy(TSH) Weight loss(ACTH) Anorexia(ACTH) Failure of lactation(prolactin) Failure to resume menses(FSH/LH) Posterior pituitary usually unaffected
Pituitary apoplexy pathophysiology
Intra pituitary haemorrhage
Can be caused by anti coagulants
Pituitary apoplexy symptoms
Severe onset headache
Bitemporal hemianopia
Cavernous sinus involvement: diplopia(CNIV,VI), ptosis(CNIII)
Fertile hypogonadism men treatment
Gonadotrophin injection, can give hCG as well which acts on LH receptors
Non fertile hypogonadism men treatment
Replace testosterone
Daily gel
3 weekly injection
3 monthly injection
Fertile hypogonadism female treatment
Induce ovulation: FSH injection Weight loss, metformin, lifestyle Letrozole(aromatase inhibitor) Clomiphene(oestradiol receptor antagonist)
IVF: GnRH antagonist(short) -> day 6 GnRH agonist(long) -> day -7
Causes of male infertility
Pretesticular: Klinefelter’s
Testicular: cryptorchidism
Posttesticular: ED, congenital
Causes of female infertility
Endometriosis: functioning endometrial tissue outside uterus
Fibroids: benign tumours of myometrium
PCOS: hyperandrogenism,oligo/anovulation, polycystic ovaries(US)
Endometriosis and fibroids treatment
Progesterone
Hysterectomy
Laparoscopic ablation, salpingo-oopherectomy(endometriosis)
PCOS treatment
Diet/lifestyle Metformin Oral contraceptive pill Anti androgen Progesterone
AVP function
Binds to V2 receptor in kidney
More aquaporin 2 expression on collecting duct
AVP regulation
Osmotic:
Osmolarity sensed by osmoreceptors in organum vasculosum and subfornical organ
Non-osmotic:
Atrial pressure sensed by atrial stretch receptor(right atrium)
Diabetes insipidus symptoms
Polyuria
Polydipsia
Nocturia
Types of diabetes insipidus
Cranial DI: AVP insufficiency
Nephorgenic DI: AVP resistance
Diabetes insipidus diagnosis
Water deprivation test:
Urine volume drop->psychogenic polydipsia
Give ddAVP->urine volume drop->CDI
Urine volume still high->NDI
> 3% weight loss-> risk of dehydration
Diabetes insipidus treatment
CDI: desmopressin
NDI: thiazide diuretics
Syndrome of inappropriate ADH(SIADH) causes and treatment
Too much AVP
Water retention, low urine output
High urine osmolarity, low plasma osmolarity
Causes: head injury, pulmonary disease, malignancy, drugs, idiopathic
Treatment:
Fluid restrict
AVP antagonist but expensive
Hormone replacement therapy risks
Venous thromboembolism(oestrogen)
Hormone sensitive cancers: give progesterone to prevent endometrial dysplasia
Stroke
Transgender therapy
Men:
Testosterone injection/gel
Progesterone to prevent menstrual bleeding
Women:
Oestrogen oral/injection/transdermal
Testosterone reduction(GnRH agonist/anti-androgen)
Target HbA1c for diabetics to prevent microvascular complications
53 mmol/mol
Diabetic retinopathy stages
Background: hard exudates, microaneurysms, dot haemorrhages
Preproliferative: soft exudates
Proliferative: new vessels
Maculopathy: hard exudates near macula
Retinopathy and maculopathy treatment
Panretinal photocoagulation
Anti-VEGF injection (maculopathy)
What is diabetic nephropathy
Hyperglycaemia & hypertension->glomerular hypertension->fibrosis->low GFR->renal failure
Diabetic neuropathy distribution and pathology
Glove and stocking Small vessels(vasa nervorum) supplying small nerves get blocked
Diabetic foot management
Annual assessment:
Foot deformity, ulceration
Sensation
Foot pulse
Good footwear
Antibiotics if infected
Amputation last resort
