Endocrine 2.28-36 Flashcards
Which hormones are released by the hypothalamus to inhibit TSH production? i.e. opposite of TRH?
Somatostatin, dopamine.
What is congenital adrenal hyperplasia?
Umbrella term but vast majority is 21-hydroxylase deficiency. Most frequent cause of virilisation in 46XX females; get clitoromegaly and labial fusion; males appear normal because most sex hormones come from testes. Occurs because enzyme is needed for aldosterone/cortisol pathways; instead drive androgen production. If have complete (salt-wasting) form then have life threatening minerol/gluco deficiency
Cretinism?
Mental developmental delay and growth restriction in children for iodine deficient regions who are not treated in early childhood; thyroid very efficiently extracts iodide from blood. Oversupply of iodine associated with AI thyroid disease.
Things that affect T4 to T3 conversion?
Systemic illness, acute trauma, fasting, drugs e.g. amiodarone, proplthiouracil, propranolol, glucocorticoids.
Testosterone production in males?
95% from testicular secretion; rest is from direct adrenal secretion or peripheral conversion of androstenedione to testosterone.
Marijuana and testosterone?
Causes reduced GnRH secretion, leading to decreased testosterone. Anabolic steroids can have the same effect as endogenous production is suppressed
Biochemical features of ectopic ACTH production e.g. SCLC?
Hypernatraemia, hypokalaemia, metabolic alkalosis, hyperglycaemia, lung malignancy. May not see typical features of Cushing’s.
Confirming Cushing’s syndrome?
Take history inc. exogenous steroids!
- Overnight dex. suppression test shows no suppression can also do 48 hour low dose dex suppression. Measure at 9am after 1mg at midnight. <50 = Cushing’s unlikely
- Urinary free cortisol (24 hours); can have false negatives.
Localising Cushing’s syndrome?
- Do overnight dex suppression and 24 hr UFC to confirm diagnosis.
- Plasma ACTH; if very high (>300) likely to be ectopic; undetectable may be adrenal tumour/hyperplasia
- If undetectable, CT adrenals; if no mass do adrenal vein sampling.
- If detectable, do high dose dex suppression; if cortisol suppressed (>50%) may be pituitary. Alternatively, do CRH test; will cause rise in pituitary disease, not in ectopic.
- Then either do high contrast CT C/A/P to find tumour, or MRI if suspect pituitary.
- K+ likely to be low in ectopic.
Criteria for SIADH?
Need hyponatraemia, urine osmolarity >100 and urine Na >20. When plasma is dilute, urine should be maximally dilute therefore low osm. Need absence of cofounders!
Potential cofounders in SIADH diagnosis?
Non-osmotic AVP release (pain, surgery, nausea),
Why is hyponatraemia with surgery a real concern?
Release ADH with any surgery; usually given fluids; if given to excess can die. Get dilutional hyponatraemia and cerebral oedema. If going to fluid restrict, must stop oral and IV!
Over-rapid correction of hyponatraemia?
May have patient with chronically low Na+; falls further and present, given hypertonic saline as acutely unwell (correctly). Then fluid restricted to prevent ascites as had ALD. Given further hypertonic saline inappropriately. Get osmotic demyelination syndrome! Key is only give enough to resolve acute problem and no more than 10mmol/L in 24 hrs.
What is osmotic demyelination syndrome?
Correct hyponatraemia too quickly; get demyelination and necrosis. Can get quadriplegia, opthalmoplegia, pseudubulbar palsy, coma. Also called central pontine myelinolysis.
Management algorithm in hyponatraemia?
Rule out hyperglycaemia/lipids/protein first (pseudohyponatraemia). Then, are they acutely unwell (coma, seizures); if yes treat with hypertonic saline (slowly); if not check urine osmolality! Begins on diagnostic pathway as treatment is cause-specific.
Diagnostic algorithm in hyponatraemia?
Exclude pseudo, check urine osmolality, if low then primary polydipsia, inappropriate VT, low solute intake. If high (>100), check urine Na. If <30 then are retaining it appropriately (HF/LF/RF/GI loss); if >30 then on diuretics/ACE? If not then may be SIADH, hypoadrenalism, AVP like drugs.
Causes of hypernatraemia?
Too little water or too much salt. Dehydration (elderly, terminal illness, water loss > intake), or excess Na+ in IV therapy (i.e. too much normal saline). Think are you “filling a hole” or “keeping a hole full” [maintenance]. Replacement must match requirements!
Cardiac effects of hyperkalaemia and hypokalaemia?
Tenting of T waves, broad QRS, sine wave appearance pre-arrest. Hypokalaemia; gives flattened T waves and broad QRS.
K+ distribution?
96% IC so measuring not representative. Higher in renal failure. Comes in via Na/K exchanger, leaves via K+ channel. Flux affected by pH, hormones etc. If pH falls, too many hydrogen ions, try to get rid of them IC so K+ comes out to replace charge and get hyperkalaemia in ECF. Can get it in rhabdomyolysis (trauma, extreme exercise).
Where is K+ actually stored?
IC - mostly in muscles, liver and red cells.
Things causing K+ efflux into ECF and therefore hyperkalaemia?
Acidosis, A-adrenergic agonists, strenuous exercise/trauma.
Things causing K+ influx into cells and therefore hypokalaemia?
Alkalosis, B-adrenergic agonists (hence salbutamol used in acute hyperkalaemia), insulin (same reason). These methods are a “sticking plaster” as total body potassium remains the same.
Problem with continuous K+ efflux?
Measuring K+ seems high, but actual body stores low.
Renal K+ handling?
Most reabsorbed in PCT and thick ascending limb; actual control is in DCT.
What happens if there is increased K+ delivery to DCT?
Get aldosterone release.
What causes increased renal excretion of potassium?
Aldosterone, increased flow, alkalosis, (increased K+ intake)
What causes increased renal reabsorption of K+?
K+ loss, acidosis (exchange it for H+)
Causes of hypokalaemia?
GI causes (low intake, GI losses e.g. D&V), renal causes (alkalosis, diuretics, mineralo/glucocorticoids, tubular disorders (Liddles’). Get apparent K+ loss with insulin effects, alkalosis, salbutamol but really just stored IC.
Conn’s?
Primary hyperaldosteronism; tetany, paraesthesia, weakness, polyuria and dipsia. See hypokalaemia(high HCO3) alkalosis, hypernatraemia, reduced free water excretion, increased urinary aldosterone. HTN. Renin low, aldosterone high/normal. Can be adenoma, hyperplasia, FHI/II
Barrter’s syndrome?
Transporter defect. Impairs reabsorption of Na+/K+/CL- in kidneys; high levels of urinary electrolytes, become volume deplete, causing aldosterone release so get low potassium. Also get alkalosis and low-to-normal BP.
Gitelman’s syndrome?
Defect on thiazie-sensitive co-transporter (Na+/CL- transporter) that normally reabsorbs. Means instead get constant use of Na/K exchanger to normalise K+, giving hypokalaemia.
Causes of hyperkalaemia?
- Decreased excretion (renal failure, ACE/ARB), Addisons/hyperaldosteronism, acidosis)
- Increased release from cells (acidosis, tissue damage (rhabdo, TLS), vigorous exericse)
- Increased extraneous load (KCL, transfusion of stored blood [K+ released from IC])
Management of hyperkalaemia?
ECG, stabilise myocardium (calcium gluconate), IV insulin/dextrose, salbutamol nebs), dialysis if no response. Remember to stop all K+ sparing/containing mediations.
Causes of pituitary deficiency?
- Congenital
- Acquired far more common. Mostly SoL (adenoma/mets), iatrogenic (surgery/radiotherapy), trauma, infection, infiltritative/inflammatory conditions).
What is it called when all pituitary hormones are down?
Panhypopituitarism
Causes of pituitary excess?
Usually due to functioning benign adenomas. May produce more than one hormone; can be ectopic e.g. ACTH from SCLC or carcinoid tumours.
Mass effect in pituitary disease?
Sits in bony area; if have large adenoma get pressure symptoms (headache, nausea), and visual disturbances (bitemporal hemianopia)
Pituitary adenomas and hormone levels?
May be functioning or non-functioning; if functioning may produce more than 1 hormone. Can also compress normal pituitary and cause deficiency i.e. mixed picture!
Classical pattern of pituitary hormone loss in pituitary mass effect?
GH, then LH, FSH, TSH, ACTH, prolactin. Usually become symptomatic in the middle.
Presentation of hypoadrenalism?
Malaise, weight loss, N&V, abdominal pain, postural hypotension (primary = aldosterone down; otherwise because cortisol and vasopressin have synergistic effect), hypoglycaemia (anti-insulin), low Na+, high K+ (primary only), and ADRENAL CRISIS
Difference between primary and secondary adrenal deficiency?
- Primary = high ACTH, high renin (tries to stimulate). Subnormal synacthen response. Pigmented (buccal mucosa, joints), salt cravings (MR deficiency). High K+, low Na+, high urea, low morning cortisol, synacthen response low.
- Secondary = decreased/inapp. normal ACTH, normal renin (RAAS working), ALSO have subnormal synacthen (atrophied adrenals) but eventually will recover. Non-pigmented!
Treating adrenal crisis?
(Do ACTH/cortisol if possible), and do aggressive fluid resuscitation, IV hydrocortisone, and correct hypoglycaemia.
Cortisol and ACTH in different causes of Cushing’s syndrome?
- Cushing’s disease = high/inapp. normal ACTH, high cortisol
- Exogenous steroids = low ACTH, variable cortisol
- Adrenal tumours (adenomas, carcinomas) are low ACTH, high cortisol
- Ectopic ACTH/CRH = very high ACTH, high cortisol
Diagnosing Cushing’s disease specifically?
- History (exogenous steroids), confirm high cortisol (24hr UFC/elevated midnight cortisol (trough time)
- Demonstrate raised ACTH
- High dose dex suppression should suppress
- Imaging/inferior petrosal sinus sampling should localise
Hyperaldosteronism?
Often asymptomatic, HTN main sign. Hypokalaemia, rarely hypernatraemia!, hypomagnasaemia, met. alkalosis. Think of this constellation along with stubborn HTN!
Primary causes of hyperaldosteronism?
Aldosterone producing adrenal adenoma (Conn’s), bilateral adrenal hyperplasia, adrenal carcinoma
Secondary causes of hyperaldosteronism?
Anything causing RAAS activation e.g. HF/LF/nephrotic syndrome, anti-HTN meds (compensatory rise), renal artery stenosis, very rarely renin-producing tumours.
Causes of primary hypothyroidism?
Rarely congenital, mostly acquired (AI/surgery/radiotherapy/radioiodine). Get high TSH, low fT4, low/normal fT3. In secondary get low/normal TSH, low fT4,low/normal fT3. Anti-TPO in Hashimotos.
Symptoms of hypothyroid?
Mostly asymptomatic, weight gain/hard to lose weight, dry skin and hair, cold intolerance, lethargy, sleepiness, constipation, menorrHAGIA, bradycardia, most severe is myxoedema coma.
Treatment guides in hypothyroidism?
L-thyroxine. If primary, can use TSH to guide replacement (aim for middle of TSH); if secondary then cannot use TSH so aim for fT4 in upper normal and normal fT3. Odd TFTs on L-thyroxine are usually due to poor medication management rather than pituitary problem!!!
Primary hyperthyroidism?
AI (Graves’ = anti-TSH), toxic nodule, MNG. Low TSH, increased fT4/3.
Secondary hyperthyroidism?
TSH excess and high fT4/3; TSH-oma. Odd TFTs. Elevated alpha subunit.
Graves’ specific signs?
Orbitopathy, thyroid acropachy, thyroid associated dermopathy.
Managing TSH-oma?
Render euthyroid with somatostatin analogues, then remove TSHoma (transphenoidal surgery).
Primary hypogonadism?
Gonadal failure (ovaries, testes). High LH/FSH, low sex steroids. Can be congenital (XXY, X) or acquired (infection (mumps), AI (premature ovarian failure), medication (chemo), infiltrative (haemochromatosis)
Secondary hypogonadism?
Reduced gonadotropins and sex steroids.
Features of hypogonadism?
Women: amenorrhoea, infertility, loss of libido, osteopenia, osteoporosis.
Men: erectile dysfunction, loss of body/facial hair, loss of libido, osteopenia/osteoporis, central adiposity e.g. seen in XXY. Treat cause and replace sex steroids (COC/patch in F; M is testosterone replacement (pill/gel/IM). These will however stop infertility so may need gonadotropins too.
Prolactin regulation?
TRH increases, dopamine decreases, oestrogen increases (at pituitary). Dopamine key; means if isolated pituitary would constitutively produce prolactin.
Pathological causes of high prolactin?
Anything interfering with dopamine e.g. APS, metoclopramide. Prolactin secreting pituitary adenomas (macro/micro), stalk hyperprolactinaemia. Also reduced clearance (ESRD, cirrhosis).
Features of hyperprolactinaemia?
Women present EARLY with galactorrhoea, menstrual irreg, infertility. Men present LATE; rarely galactorrhoea, ED, visual field defects, headaches, osteopenia/osteoporosis.
Treatment of prolactinomas?
Dopamine agonists! Very responsive
GH regulation?
GHRH +ve; somatostatin -ve. Acts mainly on liver, produces IGF-1 which has end-organ effect
Features of acromegaly?
Frontal bossing, coarse facial features, increased interdental spacing, enlarged hands and feet, sweating, organomegaly, CTS, hyperglycaemia, HTN, visual field defects, OSA, CVD.
Diagnosing acromegaly?
Elevated IGF-1 and failure of GH to suppress with OGTT! NB: GH also stimulated by hypoglycaemia. Then MRI for pitutiary adenoma. Surgery; if fails give somatostatin analogues, radiotherapy.
Diabetes insipidus?
Failure of ADH (production or action).
- Central can be congenital, acquired (idiopathic, head injury, surgery, infections of CNS)
- Nephrogenic
Clinical features of DI?
Polyuria, nocturia, polydipsia, thirst, dehydration. May be hypernatraemic but often can compensate remarkably well by drinking huge amounts; if interrupted e.g. ill then suddenly get high sodium and dehydration.
Treating DI?
Desmopressin (synthetic ADH without vascular effect unlike terlopression). Aim to control polyuria and maintain normal sodium. Essential that desmopressin is not stopped.
Treating primary hyperthyroidisim?
- Initial symptom control (propanolol)
- Graves disease; block and replace (carbimazole then L-thyroxine weeks later) or dose titration regimen (titrate carbimazole dose; needs more monitoring). Treat for at least one year; if relapse then definitive treatment.
- MNG; recommended treatmetn is radioactive iodine, or surgery. Can give antithyroid drugs
Key side effect of antithyroid drugs?
Agranulocytosis; if get sore throat must present. More commonly get rash and urticaria; don’t usually need drug withdrawal.
Definitive treatment in hyperthyroid?
- Radioiodine; contra in preg/lactation. Avoid close contact with other people particularly young children
- Total thyroidectomy (if cannot avoid children, severe Graves’ eye disease, locally compressive symptoms). Gives rapid control.