Endocrinology Flashcards

Question

What is DI? | How many types are there?

Answer 1

5 types of DI Basis is a failure to concentrate urine resulting in polydipsia and polyuria. ``` -Central DI is due to an ADH deficiency ages of 10 and 20 and occurs in males and females = Idiopathic Tumours cranial surgery or HI ``` - Nephrogenic DI is due to ADH insensitivity - Dipsogenic DI is due to abnormal thirst mechanisms in the hypothalamus -Gestational DI occurs only during pregnancy. Placenta produces vessopressinase - breaks down arginine vassopressin If excessive can lead to DI Treat with desmopressin - not vassopressin as this will be broken down Also caused by gestational Toxemias - imparied hepatic clearance of normal vessopressinase therefore less active ADH and more urine produced and excreted -Psychogenic polydipsia may also manifest as DI but unlike DI will respond to a water deprivation test Diagnosis: Serum and urine osm Urine Na water deprivation test - measure urine output over 24 hours + remeasure urine and serum osm to see if urine is concentrated. In central and nephrogenic, gestational it will not. Dipsogenic and psychogenic it will. Typically the urine will be very dilute (low urine osm compared to serum osm) and production can exceeed 20L/day Mx: Central and Gestational = ADH replacement - vassopressin Gestational: desmopressin Nephrogenic - treat underlying cause or use indapamide / bendroflumethiazide

Answer 2

Used to diagnose and distinguish the forms of Diabetes Insipidus and rule out primary polydipsia 1L fluid restriction put in place for 24 hours - measure the changes in body weight, urine output, and urine composition when fluids are withheld to induce dehydration. - The body's normal response to dehydration is to conserve water by concentrating the urine. Those with DI continue to urinate large amounts of dilute urine in spite of water deprivation. I - In primary polydipsia, the urine osmolality should increase and stabilize at above 280 Osm/kg with fluid restriction, while a stabilization at a lower level indicates diabetes insipidus. - Stabilization = increase in urine osmolality is less than 30 Osm/kg per hour for at least three hours.[ Desmopressin stimulation - drink fluids or water only when thirsty to avoid cerebral oedema - If desmopressin reduces urine output and increases urine osmolarity, the hypothalamic production of ADH is deficient, and the kidney responds normally to exogenous vasopressin (desmopressin). - If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity (since the endogenous vasopressin levels are already high).

Answer 3

TYPICAL: HTN + Paroxysms of headache + palpitations + sweating MEN2A and MEN2B Also less commonly - Acute heart failure -cateholaine induced cardiomyopathy Most commonly: Adrenal medullary tumour Often bilateral If not - preganglionic often If cannot be located on CT = 131 MIBG scan to localise source of metanephrin production ``` ALSO: Acute heart failure Flushing Tachycardia syncopal / pre-syncopal hypotensive / hypertensive confusion ``` MX: 24 hour urinary catecholamines / metanephrins adrenal androgens renin:aldosterone ratio for HTN RX: Surgery Alpha blockade first - PHENOXYBENZAMINE If b blockade first can be sent into hypertensive crisis

Answer 4

Cause: 2 hit hypoth - genetic and somatic in MEN1 gene Transcripts found in all body systems MEN1 patients usually have a family history of MEN1. Inheritance is autosomal dominant Carcinoid tumours are also associated ``` MEN I (3 Ps) - Pituitary, Pancreatic, Parathyroid, MEN IIa (2Ps, 1M) - Pheochromocytoma, Medullary Thyroid Ca + Parathyroid MEN IIb (1P, 2Ms) - Pheochromocytoma, Medullary Thyroid Ca, Marfanoid habitus/mucosal neuroma ```

Answer 5

``` Thyroxine does not cross the placental barrier Other will be experiencing symptoms of GD - hypertension - palpitations - headache - flushing and anxiety - sweating - thyroid acropatchy - exophthalmos - smooth goitre - painless ``` MX: Abs = ANTI-THYROID ANTIBODY POSITIVE Thyroid receptor stimulating antibodies TSH neg RX: No need to block and replace Instead block and monitor T4 levels aiming to keep in upper 2/3 of normal range USE CARBIMAZOLE LATE - LESS HEPATOTOXICITY IN PREGNANCY PROPYLTHIOURACIL CAN BE USED IN EARLY PREGNANCY BUT NOT IN LATE

Answer 6

Paget's disease is described in four stages 1 - Increased Osteoclastic activity VIA RANK-L - loss lamellar bone 2 - Mixed osteoclastic – osteoblastic activity 3 - Osteoblastic activity - lay down trabecular bone - weak - and replace marrow with highly vascularised trabecullar bone Eventually the whole struture becomes decellularised = BURNED OUT PAGETS 4 - Malignant degeneration - 1% osteosarcoma Overall this leads to 1) lytic lesions / wedge fractures / spont fractures / osteolytica circumspecta of the skull 2) MSCC / hip fractures 3) malignant osteosarcoma in a minority 4) pancytopenia ``` MX: BONE SCAN SKELETAL SURVEY BISPHOSPHONATES 6 MONTHLY ALP LEVELS ``` Goal of therapy is to normalise bone turnover and ALP is a marker of this typical bloods at presentation NORMAL CALCIUM and PHOSPHATE RAISED ALP NORMAL LFTS OTHERWISE without history of ALD / hepatitis / psc / pbc and no jaundice

Answer 7

The functions of the adrenal gland can be split into 3 anatomically distinct regions of the cortex ``` 1. Zona glomerulosa = ALDOSTERONE REABSORB SALT AND EXCRETE POTASSIUM reduces renin production (initial stimulus) 2. Zona fasciculata = CORTISOL GLUCOSE / METABOLISM / INFLAMMATION 3. Zona reticularis = TESTOSTERONE FERTILITY / LIBIDO Peripheral tissues Testosterone to DIHYDROTESTOSTERON via 5a reductase Testosterone to oestrogen via AROMATASE ```

Answer 8

Principally Conn and Liddle are very similar Both result in the effects of hyperactivation of the NA/K DCT exchanger HYPERTENSION HYPOKALAEMIA HYPERNATRAEMIA / NORMAL / NORMAL HIGH METABOLIC ALKALOSIS HOWEVER CONN = HYPERSECRETION OF ALDOSTERONE -Renin suppressed -High Aldosterone -acidified urine - activation of Na+/H+ exchanger -metabolic alkalosis =Primary hyporeninaemic hyperaldosteronism Constant secretion of aldosterone from zona glomerulosa of adrenal cortex either due to a ZG hyperplasia or adenoma = Hyporeninaemic hyperaldosteronism with hypernatremic, hypokalemic, metabolic alkalosis. ``` LIDDLE = HYPERACTIVATION OF DCT SODIUM/K+ EXCHANGER -Renin and Aldosterone suppressed -urine acidified -metabolic alkalosis ``` Actions: DCT and CD = sodium absorption / K+ excretion DCT H+ / Na+ exchanger = acidifies urine / absorbs sodium CONSEQUENCES: Plasma volume expansion results due to osmosis BP rise = > Atrial stretch + JMA reduces renin ANP = natriuretic and decreases sodium reabsorption - no effect on K+ channels JMA = reduces renin = reduces ang1/ang2 Result = correction of hypernatraemia - high normal hyporeninism hypokalaemia metabolic alkalosis (loss of H+) DIAGNOSIS: HYPOKALAEMIA - esp if occurs while on ACEi -Normally ACEi would reduce ANG II and so reduce aldosterone production leading to retention of potassium rather than a low potassium -renin:alodesterone ratio MX: SPIRONOLACTONE / EPILERONONE FOR CONNS Salt restricted diet AMILORIDE FOR LIDDLE -spiro has no effect as defect is with the channel itself - not the upstream receptor

Answer 9

3 types of AUTOIMMUNE polyglandular syndromes HYPOS of EVERYTHING ``` 1) PGS 1 = WHITAKER SYNDROME AIRE GENE MUTATION - aut recessive addisons hypoparathyroidism -candidiasis ``` ``` 2)PGS 2 = SCHMIDTS - most common PGS (HLA-DQ2, HLA-DQ8 and HLA-DR4 linked) addisons hypothyroid DM1 +/- coeliac and myaesthenia / graves and hashimotos - low sodium (no aldosterone) - low T4 / high TSH - elevated FG >7 / random >11 ``` 3) X linked PGS 3 - FOXP3 mutation - loss of tolerance AI thyroiditis and other assorted AI conditions

Answer 10

Whitaker syndrome AIRE mutation ADDISONS HYPOPARATHYROID CANDIDA

Answer 11

SCHMIDTS syndrome HLA linked DM1 ADDISONS HYPOTHYROID COELIAC / MYAESTHENIA / pernicious anaemia

Answer 12

X linked IPEX syndrome = mutation in FOXP3 Responsible for T cell tolerance mechanisms multiple AI pathologies arise due to lack of screening in thymus / lack of Il-10 and tgfb secretion by CD25+ Tregs

Answer 13

Causes hyperthyroidism and low TSH TSH R ab +VE TPO ab +ve follows similar course to deQuervains thyrotox-->euthyroid -->hypothyroid (may be permanent)

Answer 14

Fasting for 15hrs C peptide and pro-insulin titre measured glucose measured Normal response is insulin suppressed and normal glucose levels maintained due to glucagon and glycogenolysis Glucose <2.5 and insulin >5 (majority is proinsulin) = insulinoma 72hr fast = 98% sensitivity ALL MEN Associations: MEN I (3 Ps) - Pituitary, Pancreatic Insulinomas or glucagonoma, Parathyroid, MEN IIa (2Ps, 1M) - Pheochromocytoma, Medullary Thyroid Ca + Parathyroid MEN IIb (1P, 2Ms) - Pheochromocytoma, Medullary Thyroid Ca, Marfanoid habitus/mucosal neuromaMEN 1 = classic 3 Ps - phaeo / pancreatic insulinoma or glucagonoma / parathyroid cancer

Answer 15

What does it do? - SYNTHETIC GASTRIN stimulates gastrin / gastric acid / calcitonin and intrinsic factor release binds CCK-R Used to diagnose 1. Carcinoid syndrome to induce flushing / drive serotonin response in borderline individuals 2. diagnose meckels 3. diagnose medullary thyroid cancer = Men 2a and Men 2b typically a hard mass is found on the neck and may be associated with signs of phaeochromocytoma PENTAGASTRIN - CALCITONIN STIMULATION TEST Pentagastrin given -cause calcitonin levels to rise significantly above the normal or basal range -calcitonin normally inhibits PTH - thus in MTC expect low calcium levels. -After a total thyroidectomy for medullary thyroid carcinoma, the pentagastrin-stimulated calcitonin release can be used to detect residual parafollicular cell C-cells.

Answer 16

Malignancy of calcitonin parafocllicular C cells - secreting cells of thyroid and associated with raised calcitonin levels

Answer 17

``` Rotterdam criteria - need 2/3 Oligo / amenorrhoea hyperandrogenism - raised DHT / low oestrogen - coarse hair / facial hair cysts on USS - >12 follicles in each or 1 ovary over 2mm ``` Associated: adrenal hyperplasia, hypothyroidism, and hyperprolactinemia. ``` Present: weight gain irregular menstruation - heavy / oligo / amen hirsutism polydipsia / polyurea if early DM2 infertility ```

Answer 18

60:40 globulins combine all binding globulins / immunoglobulins / enzymes in plasma

Answer 19

Hypercalcaemia WITHOUT hypophosphataemia - bone pain - low mood and depression - renal stones - abdominal pain and constipation + spontaenous fracture + proetinureia Diagnosis: Serum free K and L light chain electrophoresis will be either IgM / IgA / IgG dominant process B cell myeloma Mx: Steroid - pred 40 pamidronate chemotherapy

Answer 20

Bind to hydroxyapetite and inhibit osteoclast activity Can rapidly correct hypercalcaemia from bone turnover in myeloma risk of AVN

Answer 21

Associated with DM1 and may repdate onset - 0.3-1% incidence Characterised by area of skin atrophy and ulceration with pigmentation Nona trophied areas should be treated with topical steroid

Answer 22

Haemangioblastoma Renal cell cancer Phaeochromocytoma Syndrome characterised by cyst formation, -Haemangioblastomas - cns ataxia / retina / spinal cord RCC - polycythaemia due to secondary increase in EPO

Answer 23

Insulin requirement whilst in hyperosmolar hyperglycaemic state will be greater than normal 24 hr requirement Therefore count sum fo insluin over 24 hours on sliding scale prescribe 2/3 dose split bd mix 30

Answer 24

``` Postural drops Gastroparesis peripheral sensory neuropathy proprioceptive feedback loss - charcot's joints achalasia ``` DDX: AXR = dilated stomach isotope motility study - assess gastric emptying RX: bed head elevation / compression stockings / education re: sitting up - FLUDROCORTISONE 50MCG start and titrate to max 400mcg /24 hr Erythromycin 50 qds / metoclop / domperidone senna

Answer 25

Accumulation of lipid laden foam macrophages reflecting lipid metabolism The defect makes the body unable to remove low density lipoprotein = ACCELERATED ATHEROMATOUS DISEASE ``` FAMILIAL HYPERCHOLESTEROLAEMIA = 1/500 Tendon Xantholamata + high cholesterol = PATHOGNEMONIC - Other causes of tendon deposition are very rare Achilles tendon Knuckles extensor hallucis longus triceps tendon tibial tubersotity Cholesterol >7.5mmol/l ``` Heterozygotes - CAD in 30s and MI 60s Homozygotes - CAD in teens and MI 30s - Cholesterol >16 Treatment: 1. atorvastatin - reduce LDL - promote HDL - improve TG clearance 2. ezetimibe statin dual therapy or if statin not tolerated 3. add in fibrate to reduce TG absorption

Answer 26

Associated with diabetes 0.3-1% may predate / post date atrophic skin changes associated with multifocal necrotic uclers with that are slow to heal

Answer 27

Gout and Pseudo gout characterised by uric acid crystals and calcium pyrophosphate crystals within the joint space respectively

Answer 28

Alpha blocker - highly potent - non selective irreversible used in treatment of phaeochromocytoma prior to b-blockade Dose 10mg bd increased to 20mg qds. - 3 days continuous treatment before surgical intervention to ensure complete alpha blockade

Answer 29

autosomal dominant mutation of TSG NF1 Chr 17 NIH criteria need >2 - >6 Cafe au Lait spots >15mm - >2 neurofibromas or one plexiform lesion - bag of worms. Neurofibromas are tumors of the peripheral nerves - Axillary or Inguinal freckling - Lisch nodules - iris brown hamartomas >2 - Optic Glioma (MOST COMMON TUMOUR) - FMH - pseudarthrosis - previous non healed fracture forms pseudojoint - SCOLIOSIS optic gliomas are treated with chemo Associated with HTN Renal Artery Stenosis Phaeochromocytoma Aortic Coarctation RARE - SCHWANNOMA / MENINGIOMA normal LE

Answer 30

Chr 22 Differs considerable from NF1 - mainly schwanomas - scanty neurofibromas - S/C gliomas / schwannomas instead - very scanty cafe au lait- <6 - NO Crowe's sign - axillary freckling - NO LISCH nodules on iris (hamartomas) LEARNING DIFFICULTIES ACOUSTIC NEUROMAS + SN DEAFNESS - BILATERAL ATAXIA NIH Diagnosis: A) Bilateral acoustin neuromas on CN VIII on Ct or MRI or 2 of: -unilateral acoustic neuroma -glioma / schwanomma / meningioma/neurofibroma -FMH Associated HTN: phaeochromocytoma Renal artery stenosis Aortic Coarctation Reduced LE due to compressive CNS lesions

Answer 31

Mutations in a G protein coupled receptor found in multiple body systems - hyperactivation of many endocrine processes - cafe au lait pigmentation whcih does not cross the midline - cafe au lait spots that follow developmental lines =nape of neck and crease of buttocks Path fractures ``` Precocious puberty: Commonest - estrogen-producing cysts =early menarch / rapid growth / early breast development BUT Less common in males = macroorchidism ``` Hyperthyroidism: 33% Growth Hormone Excess: GNAS mutation ant.pit. Cushing's Syndrome: rare + in infancy

Answer 32

Low testosterone high FSH high LH High GnRH e.g. Kleinfelter XXY = gonadal failure - HIGH FSH / HIGH LH AND LOW TESTOSTERONE DIff to Kallman where LH and testosterone are low (Gonadotrophin deficiency)

Answer 33

HYPERTENSION HYPOKALAEMIA METABOLIC ALKALOSIS

Answer 34

Conns is primary hyperaldosteronism - can be blocked with spironolactone Liddle is constitutive activation of the aldosterone receptor target channel - NA/K+ exchanger. Spironolactone will have no effect but amiloride will block the channel

Answer 35

Aut Recessive mutation in thiazide-sensitive sodium-chloride symporter in DCT = transports K+ / Na / CL / Cal / Mag Constitutively inactive ``` Results: -hypokalaemia -hypomagnesia -hypocalcaemia - METABOLIC ALKALOSIS The high lumenal K+ results in compensatory ativation of H+/K+ exchanger and net loss of H+ ```

Answer 36

Aut Recessive mutation in furosemide sensitive thick ascending limb of th eloop of henle affecting the loop diuretic transporter Na+ 2cl- / K+ transporter hypokalemia, metabolic alkalosis, and normal to low blood pressure and secondary hypomagnesia / hypocalcaemia Normally works through active transport of Na+ and Cl-into medulla. Water follows. lumen osm increases. Diffusion of K+ back into nephron further increasing osm and +Ve charge Mg2+ and Ca2+ transport relies on maintaining +ve charge in lumen i.e Mg2+ Ca2+ moves down ion gradient into cell from lumen Therefore dysfunction of Na / K / CL transporter results in - HYPOTENSION (NO H20 MOVEMENT) -HYPOKALAEMIA -HYPOMAG -HYPOCAL - METABOLIC ALKALOSIS The high lumenal K+ results in compensatory ativation of H+/K+ exchanger and net loss of H+

Answer 37

ALP 6 monthly skeletal survey limited evidence bisphosphonates slow progression

Answer 38

SIADH - Thirst - Dilutional Hypontraemia - dilute serum osm - Can lead to salt wasting syndrome as well due to secondry renal medulla washout - urinary sodium >20 - responds to fluid restriction Ectopic ACTH - cortisol - glycusouria and impaired FG / OGTT - aldosterone - hypokalaemia + corrected hypernatraemia - metabolic alkalosis - HTN hyporeninemic hyperaldosteronism - will fail dexamethasone suppression test

Answer 39

prolactin is elevated in hypothyroidism It is suppressed by dopamine - e.g. bromocriptine / cabergoline / percolide

Answer 40

Aldosterone resistance Also lead poisoning interstitial nephritis also headaches abdo pain glycosuria aminoacid uria Mx: penicillamine DMSA calcium disodium edetate

Answer 41

Rare skin = NECROLYTIC MIGRATORY ERYTHEMA impaired FG and OGTT lethargy weight loss glycosuria

Answer 42

ADH causes urinary concentration in the colelcting ducts via AQ2 It causes a net movement of water ``` Therefore EXPECT: Low serum osm (being diluted) <280 high urine osm (being concentrated >300 Dilutional hyponatraemia - becomes salt wasting Stable BP ``` worsened by given salt fluids treat: tolvaptan fluid restriction

Answer 43

CKD insufficient a1 hydroxylase in kidney = less 25oh vit D therefore less calcium absorbed from guy greater calcium urinary losses activation of PTH. Remains elevated as vit D conversion correction pathway is irreperable treat with calcium supplementation vit d supplementation calcitonin

Answer 44

Post viral thyroiditis - over release Vs over production inflammatory attack of thyroid gland leading to degranulation of T3 and T4 No rise in TSH - suppressed typical features of hyperthyroid May then appear hypothyroid may recover - may not MX: nsaid - pred if pain not improving conservative replacement if not recovering

Answer 45

Radioiodine uptake into nodules increased uptake seen on isotope scan

Answer 46

Low dose Dexamethasone suppression test Aim is to suppress ACTH production and therefore Cortisol production. Successful suppression results in cortisol <50 and rules it out >50 = cushings disease Progress to MRI pituitary ?ACTH secreting adenoma In this case high ACTH would suggest pituitary Low ACTH would suggest adrenal cushings

Answer 47

Differentiate Cushings disease from ectopic ACTH production i.e.

Answer 48

botulinum toxin if failed anti-muscarinics (oxybutynin)

Answer 49

Co-amoxiclav - 2 weeks | MRI to rile out osteomyelitis if deep ulceration

Answer 50

Androgen effects - anti-androgen or oestrogens COCP co-cyprindrol help to re-establish menstrual regularity reduce hirsutism metformin can help regularise periods Liraglutide - weight loss + glycaemic control GLP-1 agonist inhibits glucagon secretion increases insulin production increases satiety and promotes weight loss takes up to 6 months to see an effect ovaarian drilling

Answer 51

bisphosphonates alendronate / risedronate etc Anti-Rank L denosumab

Answer 52

low vit D = High PTH = high turnover to restore calcium homeostasis Fractures proximal weakness malaise Treat with high dose cholecalciferol

Answer 53

Eye disease may manifest before thyrotoxicosis and smooth goitre Caused by deposition of hydrophillic glycosaminoglycans in retro-orbital tissue leading to exophthalmos typically causes opthalmoplegia and vision loss over time MAnagement: high dose steroids retuximab extra orbital radiation - limited evidence surgical decompression once disease quiescent

Answer 54

``` Parkinsonism MND SACD DM1 autonomic neuropathy Addisons pituitary failure alcohol induced neuropathy ``` 1. compression stockings 2. permanent head tilt of bed 3. fludricortisone 4. pyridostigmine

Answer 55

subclincial hypothyroid and asymptomatic TPO negative Repeat TFTs in 3 years subclincial hypothyroid TPO positive Annual TFTs Subclinical hypothyroidism IF symptomatic -Start 50mcg Clinical hypothyroidism and symptomatic - start 100mcg

Answer 56

Somatostatin analogues - (primary therapy or while awaiting surgery) Dopamine agonists - cabergoline / l doppa / bromocriptine / silegiline -(particularly for prolactin cosecretion) Pituitary Surgery Post-operative radiotherapy Stereotactic ‘gamma knife’ radiotherapy for recurrence GH receptor antagonists for recurrence -Pegvisomant is an analogue of human growth hormone that has been genetically modified to be a growth hormone receptor antagonist. • It binds to growth receptors on cell surfaces, where it blocks growth hormone binding and decreases IGF-1. • Licensed for use in patients with acromegaly who have had an inadequate response to surgery and/or radiation therapy and in whom an appropriate medical treatment with somatostatin analogues did not normalise IGF-1 concentrations or was not tolerated. annual colonoscopic surveillance - RR adenocarcinoma

Answer 57

Ramipiril recommended esp if proteinurea present bendroflumethiazide not recommended due to adverse effects on glucose - use amlodipine if already on ramipril

Answer 58

Depending on what type of gene mutation RET = MEN 2 - moderate risk screen from age 5 with calcitonin levels / uss / thyroid exam