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.
Complications of total thyroidectomy?
Immediately get RLN damage, hypoparathyroidism (check calcium), wound infection. Late is hypothyroidism (have to be on L-thyroxine for rest of life).
What is it called if have suppressed TSH but normal fT4/3?
Called subclinical hyperthyroidism; misnomer because based on lab values. Most common cause is taking too much thyroxine, early stage of nodules/Graves. Important because of link with CVD/osteoporosis/AF; if have no risk factors may just observe.
Causes of subnormal TSH?
Subclinical hyperthyroidism, hyperthyroidism, pituitary/hypothalamic insufficiency, drugs e.g. amiodarone. First one more likely if fT4/3 are near the top of normal.
Treating primary hypothyroidism?
If <60 and no Hx of IHD start on therapeutic dose. If older or higher risk, start low and go slow. Guided by TSH in normal range.
What is T3 toxicosis?
Low TSH, high fT3, normal fT4. Usually due to an autonomous nodule.
Sick euthyroid?
Low T4 and T3, with TSH inappropriately normal or suppressed. Often seen in severe illness; thyroxine treatment not indicated
Investigating thyroid disease?
- Autoantibodies. Graves = TRab (>90%) [stimulating]. AI hypo = anti TPO (<95%).
- US = not routinely recommended for goitre; better for non functioning nodules. Can do FNA.
- Radioisotope uptake scan. Can detect retrosternal goitre.
Investigating Graves’ if antibody negative?
Thyroid uptake scan!
Pathway in Ix thyroid?
If find goitre, do TFTs, then either US or uptake scan (non-functioning vs functioning).
What does it mean if high dose dex suppresses cortisol?
Probably pituitary cause (high ACTH); if not then ectopic ACTH or adrenal pathology so do ACTH to differentiate.
Treating Cushing’s caused by adrenals?
If resect adenoma, might be that contralateral adenoma has atrophied so need steroid cover.
Investigating primary adrenal insufficiency?
Bloods: hyponatraemia, high urea, hyperkalaemia.
Cortisol: 9am cortisol low, ACTH high. Undetectable cortisol is diagnostic.
Short synacthen: poor response. Can be done at any time whereas baseline cortisol should be morning.
Considerations in primary adrenal insufficiency?
Education/emergency card and bracelet. Give gluco and mineralo replacement, and monitor treatment by symptom response.
Measuring plasma renin in Addisons?
Do to monitor; if high then suggests insufficient fludrocortisone,
Investigating Conn’s?
- Present with HTN. Aim is to show lack of aldosterone suppression. Do A:R; higher ratio = more likely.
- Dynamic testing to suppress aldosterone; e.g. saline infusion test (2L) and see if aldosterone suppressed.
- If not suppressed, image adrenals to see if have mass.
- However, hyperaldosteronism and nodule not enough as “incidentaloma” very common; do adrenal venous sampling to identify unilateral disease.
What must be done before doing aldosterone:renin in Conn’s?
Normalise potassium (low assoc. with FN), stop diuretics and other medications. B-blockers, NSAIDs can suppress renin (FP); ACE/ARB/diuretics give FN.
Difference between primary and secondary aldosteronism?
Primary is detached from RAAS; secondary is normal function of RAAS.
Causes of primary hyperaldosteronism?
Conn’s (adenoma), adrenal hyperplasia (most common), adrenal carcinoma (poor prognosis).
Causes of secondary hyperaldosteronism?
Renal artery stenosis, renal hypoperfusion, cirrhosis, CCF, renin-secreting tumour!
Treating hyperaldosteronism?
Conn’s with lap. adrenalectomy. Can do medical treatment (spironolactone/epleronon) i.e. aldosterone antag.
Testing for diabetes insipidus?
Must be passing at least 3L urine a day. Think have shortage so try to stimulate ADH. Water deprivation test: allows plasma osmolality to rise, and urine should rise too; If not, then inappropriate diuresis.
Comparison of cranial DI, nephrogenic DI and primary polydipsia for urine osm?
C & N DI Urine osm <300 (very dilute); primary polydipsia >800 and >800 after given vasopressin because is appropriate. Cranial DI rises to >800, nephrogenic doesn’t change.
Treatment for cranial diabetes insipidus?
Desmopressin. Longer t1/2 than ADH. Give ~BD. Monitor serum sodium and osmolality.
Causes of testicular failure?
Primary (cryptorchidism, syndromic [XXY]), iatrogenic (therapy, anabolic steroids), secondary (Kallman syndrome, absent gonadotrophin drive).
Recombinant growth hormone deficiency in adults?
Reserved for those with severe GH deficiency, impaired quality of life and on treatment for other pituitary deficiencies
Testosterone replacement?
Usually not above >12; probably good <8. Depends on symptoms.
1. 12 week depot injection
2. Daily gels (can virilise partner).
Monitor PSA, FBC, LFT. Needed because haematocrit may rise too much.
Testosterone replacement for those with secondary gonadal failure?
Will not restore fertility! Will need exogenous gonadotrophin to initiate spermatogenesis. (Will not respond to this in primary hypogonadism). Same principle in women.
Primary and secondary ovarian failure?
Primary = gonadal dysgenesis (X), premature menopause. Secondary = LH/FSH deficiency.
PCOS features?
Irregular menses, unwanted body hair, sub fertility, weight gain, CV risk factors (IR, dyslipidaemia)
Treating premature ovarian failure?
Need HRT until at least 50! Exogenous oestrogens reduce very high risk of osteoporosis; need additional progesterone if not had hysterectomy
Notes on phaeo?
Potentially fatal HTN crisis, reversible after surgical removal, adrenomedullary, lack of long term medical treatments and associated with endocrine syndromes [MEN2]. CAN’T TREAT MEDICALLY
Features of phaeo?
HTN very labile and episodic, get sweating, flushing, sense of impending doom, pyrexia, headache, palpitations, chest pain, SOB, postural HYPOTENSION
Ix phaeo?
Plasma mets; metabolites of catecholamines (T1/2 too short) or in urine (24 hr mets collection). Then image: CT or I-MIBG (can exclude multiple tumours). Make sure not on drugs or coffee!
Rule of ‘10’s in phae?
<10% malig, 10% extra-adrenal (PARAGANGLIOMA), 10% bilateral. Also very vascular and prone to haemorrhage causing HTN crisis.
Treating phaeochromocytoma?
- Medical. alpha blockers key! [phenoybenzamine]. If give these people a B-blocker can get HTN crisis.
- Also high salt and fluid diet to rehydrate (HTN but volume deplete because HTN inhibits RAAS!)
- Surgery. Need experienced team.
- Prognosis: good if benign, less if malignant.
Considering endocrine causes of HTN?
- Catecholamine: family history of phaeo, paroxysmal, syndromic features.
- MR: sustained, resistant HTN, hypokalaemia, adrenal mass, FHx HTN/CVA.
- Other: accelerated, resistant HTN, deterioration in renal function with ACEI, children/AYA with HTN.
Thyroid disease and HTN?
Hypo via increased resistance, hyper via increased metabolic rate.
Three action sites of PTH?
- Renal tubule (reabsorb more calcium from urine) [minutes]
- Bone (release calcium, stimulates osteoclasts) [hours]
- Activates Vit D; can then act on gut!
PTH has very short half life!
Three main components of bone?
- Inert mineral (calcium hydroxyapatite)
- Osteoid (collagen and chondroitin)
- Cellular component (osteobloasts, clasts and osteocytes & haematopoietic tissue [living component])
Primary hyperparathyroidism?
Common. 3:1 F:M; 50-70. Mostly benign solitary parathyroid adenoma; some ‘4-gland’ parathyroid hyperplasia; occasionally parathyroid carcinoma (much higher calcium and PTH, may have palpable mass)
Biochemistry of primary hyperparathyroidism?
High calcium and low PO42-, raised or inappropriately normal PTH, elevated bony ALP, urinary calcium high/high-normal. Mild metabolic acidosis.
Complications of primary hyperparathyroidism?
Kidney stones, renal impairment. Osteoporosis at wrist and hip, osteitis fibrosa cystica, brown tumours of bone, corneal calcification, HTN.
Management of primary hyperparathyroidism?
- Surgical neck exploration. Only do if have symptoms or complications (as surgery has risks). 75% of mild primary hyperparathyroidism will have no symptoms or complications in the next ten years.
- Conservative with monitoring (if asymptomatic)
- Calcimimetic drugs cinacalcet if surgery not possible/failed
Low calcium diet in primary hyperparathyroidism?
Actually makes things worse
Malignant hypercalcaemia?
Median LE 6 weeks.
- 80% humoral hypercalcaemia of malignancy (PTH-RP)
- 20% bone erosion (diffuse bony disease [myeloma] or focal bony mets)
Cancers causing HHM?
Squamous cell carcinomas (lung, breast, oesophagus etc.) Normally clinically obvious tumour mass. Tumour cells make PTHrp so low PTH and 1,25 Vit D. NOT at high risk of pathological fractures.
Myeloma and calcium?
30% of myeloma patients get hypercalcaemia; diffuse osteolysis due to cytokine release. Often have renal impairment due to light chains so get high phosphate! However, hypercalcaemia is steroid responsive so prognosis okay.
Focal osteolytic mets and calcium?
Lung, breast, prostate, thyroid, RCC; local pain and high risk of pathological fracture.
Management of severe hypercalcaemia?
Baseline PTH if first presentation; helps for aetiology.
Treat hydration (0.9% NaCL) then bisphosphonates.
May normalise in 2-3 days.
Causes of hypocalcaemia?
Vit D def (eventually become hypocalcaemia)
Hypoparathyroidism
Drugs (phosphate, bisphosphonates, chemo)
Hypomagnasaemia (inhibits PTH release, and peripheral action)
Renal failure (can’t activate Vit D)
May be false positive if hypoalbuminaemic.
Symptoms of hypocalcaemia?
Parathesiae of mouth and fingers, muscular twitching and leg cramps, carpopedal spasm (tetani), seizures, laryngeal stridor. See Trousseau’s sign and Chvostek’s sign.
Aetiology of hypoparathyroidism?
Much less common than hyper
Post-surgical (thyroidectomy) most common, congenital absence (DiGeorge), AI, infiltration, pseudohypoparathyroidism (tissue resistance)
Biochemistry of hypoparathyroidism?
Low calcium, high serum PO42-, low/undetectable PTH, normal renal function, low urine calcium excretion
Important thing to check in hypocalcaemia?
Magnesium!
Renal failure and hypocalcaemia?
Firstly because vit D inactive so can’t absorb, and have high phosphate which reduces calcium because can’t excrete phosphate
Classic fragility fractures?
Neck of femur, vertebral collapse, wrist. Also see dorsal kyphosis (this sign alone is enough to treat)
Bone in osteoporosis?
Reduced mass, normal biochemistry (unlike osteomalacia)
Defining osteoporosis?
Clinically with presence of low-impact fractures, or radiographically (BMD criteria); can be BMD criteria or established if have had #)
Osteoporosis vs osteomalacia?
Osteoporosis; living component takes up more space, equal reduction in mineral and osteoid. Osteomalcia has more osteoid to living; mineral the same.
Measuring BMD?
DXA of hip and lumbar spine. Measures area (g/cm2). -2.5 is osteoporosis; -1 to -2.5 is osteopenia (from T score). At age 80, 100% of population have osteopenia.
T and Z score?
T is SD from young adult; Z is age-matched. Use T score for diagnosis.
BMD as a child?
Quite low! Peak in late 20s/early 30s (becausing gaining muscle which means more force going through bone).
Some factors affecting bone mass?
Exercise, genetics, calcium intake, menopause, drugs, disease, immobility.
Independent risk factors for fracture?
Low weight, tall height (>5’7) smoking, alcohol, medications (steroids), premature menopause, hypogonadism, calcium intake, family history, ethnic background (Afro-Carribean best BMD, South Asian lowest BMD)
Secondary osteoporosis?
- Malabsorption, hepatic or renal disease
- Endocrine problem (hypogonadism, thyrotoxicosis, hyperparathyroidism, Cushings)
- Drugs (steroids, AEDs, heparin)
- Others (RA, osteogenesis imperfecta, systemic mastocytosis, immobilisation, weightlessness).
Treating osteoporosis?
Calcium intake, vitamin D intake, lifestyle e.g. weight-bearing exercise, bisphosphonates, SERM, HRT, strontium ranelate (higher chance of MI), PTH injections, denosumab (anti-RANKL mAb). Need to risk stratify ie FRAX
What does FRAX score give results for?
10 year probability of any osteoporotic fracture, and score of hip fracture alone. Treat any over 10%. Without BMD, get red/amber/green; only do BMD for amber (though can do for red because can monitor treatment).
Osteomalacia and Rickets?
Low Vit D; failure to mineralise bone. Elevated PTH to compensate, high ALP, hypocalcaemia and hypophosphataemic (unless caused by renal osteodystrophy)
Causes of osteomalacia and Rickets?
Lack of sunlight/dietary vit D, drugs, renal/hepatic disease, dietary lack of Ca2+/PO42-. Essentially poor bone metabolism due to shortage in an ‘ingredient’.
Symptoms of osteomalacia?
Weakness, myalgia, bone pain. See bowing if occurs while growing, knock knees, craniotabes!
Key difference between osteomalacia and renal osteodystrophy?
Phosphate high in renal!
Diagnosing diabetes?
Symptoms + random glucose >11, fasting >7 or OGTT >11, or no symptoms or two values meeting these. Or HbA1c >48.
When not to use HbA1c?
All children and young people, suspected GDM, acutely unwell, recently started relevant drugs, acute pancreatic damage, renal failure
Features of T2 DM?
FHx, obese, habitual activity, race (South Asian, indigenous), history of GDM, PCOS, socio-economic (more in urban areas)
What causes T2DM?
Decreased B cell function means decreased insulin response to food; meanwhile have decreased insulin action in muscle and liver (insulin resistance) leading to increased liver glucose output and decreased storage. Could be fat accumulation in liver and pancreas alone.
Diagnosing T1?
Typically have one + of: hyperglycaemia, ketosis, rapid weight loss, personal family history of AI, BMI <25, age of onset below 50. Do not discount if BMI >25 or age >50!
Glucokinase MODY?
Need higher levels of glucose to trigger insulin release. Don’t need treatment except in pregnancy. No real assoc. cx (e.g. microvascular). Often presents incidentally in children or at pregnancy (i.e. mostly asymptomatic). Non-obese, persistently raised FBG, may be FHx, no extra-pancreatic features
TF MODY: HNF-1a/4a?
Normoglycaemic in childhood, develop DM 12-30 worsening glycaemia with age. May be misdiagnosed at TI DM. Poor control does lead to complications, unlike glucokinase MODY. May be FHx.
Very sensitive to low dose sulfonylureas (gliclazide). Insulin can be stopped if have T1 diagnosis.
1a is most common MODY.
TF MODY: HNF-1B?
Have renal disease (cysts and impaired renal function). DM alone unusual. Usually need insulin and not as responsive to gliclazide.
Why do genetic testing for MODY?
Makes diagnosis, differentiates from T1, helps prognosis, family counselling, guide treatment i.e. stop insulin. If glucokinase, can leave off treatment; just oral treatment for 1a/4a. However, testing is expensive so need high risk patients (strong FHx, atypical feature).
Insulin resistance syndromes?
Acanthosis nigricans, persistent hyperglycaemia (despite large insulin doses), PCOS.
Lipodystrophy?
Genetic (can be congenital or familial) or acquired. Classified by anatomical distribution of lipodystrophy. May have complete absence of peripheral fat (all stored in organs), may be partial. Often more apparent in women. IR usually a feature. Clinical diagnosis.
HIV and DM?
Higher incidence in men treated with HAART. HIV itself may cause DM.
Causes of goitre?
- Diffuse (simple, thyroiditis, iodine deficiency, AI)
- Nodular (MNG, solitary toxic nodule [not really a goitre], cysts, fibrotic)
- Miscellaneous (sarcoidosis, Tb)
- Tumours (benign adenoma, carcinoma (pap[great prognosis]/fol/med/anaplastic [awful prognosis]), lymphoma, mets).
Goitre in Graves?
Smooth, rubbery goitre as whole gland turned on.
Grave’s eye disease?
Grittiness, eye discomfort, chemosis (swollen conjunctiva), periorbital oedema, proptosis (sclera visible), extraocular muscle involvement and cornea involvement. If cannot close eyes at risk of ulcer etc. so medical emergency. NB: lid lag/retraction can occur with any form of thyrotoxicosis (SNS activity).
First investigation in thyroid nodule?
TFTs! If TSH normal, do US guided FNA. If suppressed, and have nodule do uptake scan. If hot, ablate/resect/medical. If cold/indeterminate, do US guided FNA!
FNA thyroid classification?
1-5; 5 is diagnostic of malignancy. Just cytology so may need hemithyroidectomy if suspicious. If malignancy not aggressive then may not need to remove the other half and therefore may not need thyroxine!
Pseudocushing’s?
Can occur if have protease inhibitor and inhaled steroids; cortisol assay only picks up endogenous. Fluticasone has very high first pass metabolism; oral medications that prevent this get systemic effects quite quickly and has long t1/2 a
Drugs affecting inhaled steroid metabolism?
Antiretroviral, antibiotics, antifungals! Can get Cushing’s.
Fractured NOF and sodium?
At risk of volume depletion so get “appropriate” ADH released and reduced free water excretion; however, if already salt deplete (on diuretics etc.) then sodium levels drop
Central salt wasting?
Often follows brain injury. Get increased adrenergic response from vasculature; BP rises; get release of naturetic peptides from ventrcles; get fluid loss caused by increased sodium excretion; body then releases ADH appropriately and get hyponatraemic.
Dosage for Addisonian crisis?
IV hydrocortisone 100mg IV stat, repeat every six hours. Addison’s disease, antirejection therapy, inflammatory diseases; often happens with any illness because need more cortisol or may miss dosage.
Cortisol and stress?
Goes up in minute to stress (physical, psychological, physiological); raises blood glucose, catabolic effect on protein, enhances activation of other hormones e.g. catecholamines and therefore have vital role in vascular resistance (key if ill). Do not worry about anti-inflammatory effects if septic because hypoperfusion will kill
De Quervain’s thyroiditis?
Aka subacute thyroiditis. Virus implicated. F:M 3:1. Initial phase of destruction (thyrotoxicosis) then depletion of stores typically het phase of hypo. Complete resolution expected. Expect high inflammatory markers early, along with high fT4 and low TSH
Uptake scan in early subacute thyroiditis?
Reduced uptake because have had destruction and release of thyroid hormones, where Graves’ will show diffuse increased uptake.
Goitre in Hashimoto’?
Often initial firm goitre; marked lymphocytic infiltration.
Silent thyroiditis?
Similar to subacute but no pain; happens quite often post-partum (5% women) so termed post-partum thyroiditis. Usually hypothyroid for some time after
Main cause of drug-related thyroiditis?
Amiodarone
Three regulators of aldosterone secretion?
- Main is RAAS
- Secondary is potassium ion directly (independent of RAAS); hence why must normalise potassium before doing aldosterone:renin ratio.
- ACTH has minor role
Cortisol and MR receptor?
Cortisol has high affinity for MR receptor so get aldosterone biochemistry in Cushing’s; saturates 11BHSD enzyme which normally converts it to inactive cortisone. Liquorice inhibits enzyme; can be at risk of HTN.
Three main causes of hypernatraemia?
- Pure water loss (renal = DI; extra-renal = insensible/skin/resp)
- Hypotonic water loss (GI = diarrhoea, secretions; burns, sweating)
- Sodium gain (hypervolaemia) e.g. primary aldosteronism, Cushing’s, salt tablets, hypertonic dialysis
?malignancy and increased uptake on thyroid scan?
Increased uptake = almost never malignant.
Results of thyroid FNA?
70% benign, 20% non-diagnostic, 10% malignant (and usually very treatable).
Why acidotic in Addisonian crisis?
Na+ left in urine so H+ retained to balance charge (as is K+) hence hyperkalaemia
