endo2 Flashcards

Question

What skin condition may be associated with Addison disease?

Answer 1

- hypotensive and orthostatic - most have systolic BP less than 110

Answer 2

Adrenoleukodystrophy Very long chain fatty acid levels - they'll be really high

Answer 3

A diagnosis of primary adrenal insufficiency is confirmed by the combination of: 1. a positive short Synacthen test (ie an absent or severely blunted plasma cortisol response to tetracosactrin 30 to 60 minutes after injection) 2. elevated adrenocorticotrophic hormone (ACTH) 3. elevated plasma renin (measured by direct concentration or plasma renin activity). Measuring diurnal (morning and afternoon) plasma or serum cortisol concentrations is not useful for evaluating adrenal insufficiency.

Answer 4

Heralds an Addisonian crises

Answer 5

Fasting blood glucose is low because there is no cortisol to help glycogenolysis

Answer 6

Hydrocortisone must not be given for at least 8 hours prior. Other corticosteroids do not interfere with the assay and can be given.

Answer 7

Androstenedione is the common precursor of male and female sex hormones

Answer 8

It transforms androstenedione to estrone and testosterone to estradiol. Estradiol is the primary premenopausal oestrogen and is made in the ovary from testosterone. Estrone is in postmenopausal women and is made in adipose tissue.

Answer 9

Suppressed in Addison disease Normal or elevated excludes Low level not diagnostic because some of the population have low levels.

Answer 10

Ambiguous genitalia Elevated 17-OH progesterone

Answer 11

- indicated intravascular volume depletion and need for higher doses of fludricortisone

Answer 12

Low Not enough cortisol required to induce the PNMT enzyme in the adrenal medulla which synthesies adrenalin from noradrenalin

Answer 13

- anti-adrenal antibodies in 50% - antibodies to thyroid in 45%

Answer 14

If not clearly autoimmune --\> CXR to look for TB, fungal infection or cancer CT abdo will show small noncalcified adrenals in autoimmune addisons (calcified if TB or other causes) Enlarged if metastatic or granulomatous causes.

Answer 15

- secondary (hypopituitarism) - but lack ACTH and have normal skin pigmentation - ACTH deficiency --\> normal mineralocorticoid production and do not develop hyperkalemia. - Haemochromatosis can cause skin pigmentation. Can also cause Addison, hypoPTHism and diabetes - AIDS can cause hypocortisolism and frank adrenal insufficiency - CAH - but will have features of androgen excess

Answer 16

Drosperinone. Progestin component of Yaz/Yazmin.

Answer 17

Myotonic dystrophy Aldosterone synthase deficiency 17 hydroxylase deficiency (salt wasting CAH)

Answer 18

due to decreased angiotensin 2 production as well as intra-adrenal dysfunction ACEIs and NSAIDs RTA Type IV Diabetic nephropathy Hypertensive nephrosclerosis Tubulointerstitial disease AIDS

Answer 19

Hydrocortisone is the drug of choice - 15-30mg daily in 2 divided doses. Fludrocortisone **_retains sodium_**. Used in presence of hyponatraemia, postural hypotension or hyperkalemia (gets exchanged for sodium). Titrate to postural BP, serum K+ and plasma renin (increase if renin elevated) DHEA - improved sexual function in women and sense of general wellbeing in both, may increase lean body mass and bone density but not confirmed and replacement is _not routine_.

Answer 20

- better symptom control when they receive routine mineralocorticoid therapy as well as gluco corticoid - allows good control at a lower glucocorticoid dose, minimising side effects - no need to adjust dose in times of stress

Answer 21

Normal Blood pressure, sodium and potassium Plasma renin at upper end of normal range. Limited by plasma renin as increasing fludrocort causes oedema and hypokalemia.

Answer 22

Reasonably normal Increased all-cause mortality, mainly from cardiovascular disease, malignancy and infection May have ongoing chronic low-grade fatigue.

Answer 23

Central obesity Muscle wasting Thin skin Hirstutism Purple striae Psych changes Osteoporosis Hypertension Poor wound healing

Answer 24

Hyperglycaemia and glycosuria Leukocytosis Lymphocytopaenia Hypokalaemia Elevated serum cortisol and urinary free cortisol without suppression by dexamethasone

Answer 25

Exogenous Only rarely due to excessive corticosteroids produced by adrenal cortex

Answer 26

ACTH hypersecretion by the pituitary. Usually a benign pituitary adenoma that is \<5mm and located in the anterior pituitary. 3x more common in women

Answer 27

Autonomous adrenal secretion independent of ACTH which is low, usually due to a unilateral adrenal tumour. Nonpituitary ACTH secreting neoplasms (i.e. SCLC) that produce excessive ectopic ACTH. Usually hypokalaemic and hyperpigmented. Masses are usually large. 15% of cases are of unknown origin.

Answer 28

Avascular necrosis.

Answer 29

Erectile dysfunction in men Amenorrhoea or oligomenorrhea in women.

Answer 30

Due to increased free water clearance - diabetes with glycosuria may worsen it.

Answer 31

- the patient requires control of hypercortisolism preoperatively - the source of ACTH excess is unclear - surgical resection has been unsuccessful. Ketoconazole is the treatment of choice

Answer 32

Dex suppression test - 1mg given at 11pm then morning cortisol performed. Low morning cortisol excludes Cushing - HOWEVER if still clinically expected, need to test further as this is only a screening test.

Answer 33

24 hour urine collection for free cortisol and creatinine - abnormally high free cortisol or cortisol/creatinine ration confirms hypercortisolism. Creatinine is secreted constantly while cortisol is under diurnal control. Having the creatinine there makes sure enough urine was collected.

Answer 34

Cortisol lowest at midnight (normally) Even in Cushing's, morning serum cortisol may be normal, an elevated midnight cortisol can distinguish it form other conditions that cause a high urine free cortisol (pseudo-Cushings). A later night salivary version can be done too which is sensitive and specific.

Answer 35

Phenytoin and rifampicin accelerate dexamethasone metabolism, meaning that cortisol doesn't get suppressed. Estrogens i.e. in pregnancy or OCP can also stop suppression by dexamethasone.

Answer 36

Depression Anorexia nervosa Alcoholism Familial cortisol resistance

Answer 37

Hypercortisolism due to the adrenal cortex' cells abnormal stimulation by hormones such as caetcholamines, vasopressin, serotonin, HCG or GIP When stimulated by GIP (gastric inhibitory polypeptide) --\> cortisolism will be intermittent and food dependentent, ACTH may not be completely suppressed.

Answer 38

Serum ACTH - low = probable adrenal tumor - high = pituitary or ACTH secreting tumor

Answer 39

Usually a benign adrenal adenoma

Answer 40

- diameter \>4cm - nodule growth - atypical imaging ie density on noncon CT - \>10 Hounsfield units or high CT contrast washout

Answer 41

Tissue differentiation on CT. Zero is water Greater than 10 tends to be organ or tissue (i.e kidney, blood, muscle, brain) Greater than 100 tends to be soft tissue Greater than 700 is bone. Less than zero is fat down to -500, then lung, then air (1000)

Answer 42

MRI - will demonstrate pituitary lesion in 50% of cases often with premature cerebral atrophy - if less than 5mm, further investigation (inferior petrosal venous sinus sampling) is required

Answer 43

When equivocal on MRI but evidence of ACTH secretion If more than twice peripheral venous ACTH levels, this is indicative of pituitary Cushing's disease. Can be done during CRH administration which will cause inf. petrosal sinus levels to b 3x greater than peripheral ACTH when the pituitary is the source.

Answer 44

Chest CT/Abdo looking for carcinoid or SCLC. Also look at the thymus, pancreas and adrenals. - must biopsy a chest mass as more risk of infection and may be infection rather than ACTH secreting mass. If CT scanning fails - in octreaotide scan may help. FDG-PET is not useful. If unable to be found, bilateral adrenalectomy with ongoing investigation with imaging as the ectopic source may become detectable later.

Answer 45

Both will have abnormal dex suppression test but urine free cortisol and diurnal variation of cortisol usually normal in the obese.

Answer 46

Rapid enlargement of a pituitary adenoma following bilateral adrenalectomy (this is done v rarely now). Can cause visual field defect and hyperpigmentation

Answer 47

Transphenoidal resection of the pituitary adenoma Pituitary corticotrophs remained suppressed for up to 3 years - may need hydrocort or pred replacement in the meantime Recurrence managed with cabergoline. Lap adrenalectomy if unresponsive

Answer 48

Pasireotide - a somastatin analog that targets multiple receptors

Answer 49

a somastatin analog that targets multiple receptors

Answer 50

- symptom control and reduction of GH and IGF-1 in acromegaly, inc where surg/rtx/dopamine agonist treatment has failed. - Acromegaly when unable to undergo surgery or awaiting tx effect of RTx - symptomatic relief of carcinoid and VIPomas (but NOT curative) - reduction of pancreatic surgery complications

Answer 51

Happens in patients successfully treated for Cushings, even with replacement steroids - hypotension, nausea, fatigue, arthalgia and flaking skin - increase hydrocort can improve the sx.

Answer 52

Residual MCI, muscle weakness and OP Good survival May get relapse if growth of an adrenal remnant post bilateral adrenalectomy

Answer 53

- Autosomal dominant functional disorder of the ovaries - adrenal and ovarian androgen hypersecretion - elevated serum testosterone or free

Answer 54

For a diagnosis of PCOS, two of the following criteria must apply—menstrual irregularity, hyperandrogenism and polycystic appearance of the ovaries (which are not necessarily always present in PCOS)

Answer 55

Excessive LH release by the anterior pituitary, causing the ovaries to produce excess testosterone High insulin levels increase GnRh pulse frequency, which further forces LH over FSH dominance.

Answer 56

Both adrenal and ovarian androgen hypersecretion. Testosterone is best measure.

Answer 57

Goal is to restore predictable uterine bleeding and effective endometrial shedding. Combined OCP is most effective way to regulate menses and does not cause insulin resistance Metformin can be used when COCP and OCP (progestin) aren't tolerated and can improve menstrual frequence, although not as well.

Answer 58

Without corticosteroid, they will become virilized due to their ambiguous genitalia.

Answer 59

- increased hair (chin, upper lip, abdomen and chest) - acne - Menstrual irregularity - defeminization - loss of breast, hips - virilization - frontal balding, muscularity, clitoromegaly, voice deepening

Answer 60

Serum or free testosterone If elevated --\> pelvic exam and ultrasound If negative --\> adrenal CT scan Elevated androstenedione --\> ovarian or adrenal neoplasm Elevated DHEAs - adrenal source as this only produced by the adrenal gland. Usually due to adrenal hyperplasia --\> do a CT Elevated 17-hydroprogesterone in CAH (because 21 is missing)

Answer 61

Ovarian failure LH:FSH ratio \>2

Answer 62

Lap bilateral oophorectomy if CT adrenals is normal since small hilar cell tumors of the ovary may not be visible. Also for salt-wasting and infertility CAH, or treatment resistant hyperandrogenism. Spironolactone Finasteride (inhibits 5-alpha reductase) improves hirtsutism but spironolactone is better Flutamide suppresses testosterone and lowers corticosteroid dose required for CAH.

Answer 63

When used with OCP, aside from improving lipid profile, greater decreases in hirsutism and serum free testosterone levels

Answer 64

Clomiphene

Answer 65

Clomifene inhibits estrogen receptors in the hypothalamus, inhibiting negative feedback of estrogen on gonadotropin release, leading to up-regulation of the hypothalamic–pituitary–gonadal axis. It is a selective oestrogen receptor modulator (SERM)

Answer 66

Resistant hypertension Hypokalaemia Elevated plasma and urine aldosterone levels and low plasma renin that does not correct with sodium loading.

Answer 67

Increased sodium retention Suppressed plasma renin Increased renal potassium excretion --\> hypokalemia Increased cardiovascular events (moreso than essential HTN)

Answer 68

- Aldosterone producing adrenal adenoma (Conn syndrome), 40% of which have a mutation potassium channel gene - Unilateral or bilateral adrenal hyperplasia - Bilateral form may be corticosteroid suppressible due to an autosomal dominant genetic defect allowing ACTH stimulation of aldosterone production

Answer 69

Moderate hypertension or isolated diastolic hypertension Hypokalaemia --\> muscle weakness Parasthesia, tetany, headache Polyuria and polydipsia

Answer 70

_Usually Hypertensive_ Renovascular disease (atherosclerotic, fibromuscular hyperplasia) Coarctation of the aorta Renin-secreting tumors _Usually Normo- or Hypotensive_ _Reduced Circulating Blood Volume:_ Gitelman’s Syndrome Bartter’s Syndrome Pseudohypoaldosteronism Type I Diuretic Use (surreptitious or prescribed therapy) _Reduced ‘Effective’ Circulating Blood Volume:_ Congestive Heart Failure Hepatic cirrhosis Nephrotic Syndrome

Answer 71

- Plasma renin, plasma aldosterone plus ratio. If elevated, test further - Hypokalemia helpful _but normal in 50%_ - may have metabolic alkalosis with increased HCO3 - further ix with sodium loading and morning plasma renin, with aldosterone measured as well. Normal or elevated makes primary aldosteronism unlikely. - dx confirmed with 24 hour urine collection of aldosterone, free cortiisol and creatine. Low plasma renin plus high urine aldosterone = primary aldosteronism.

Answer 72

Stop diuretics for 3 weeks Stop dihydropyridine CCBs as can normal aldosterone secretion Stop b-blockers as they suppress renin in essential htn Useable anti-HTs are ACEIs, alpha blockers, verapamil, and hydralazine

Answer 73

Occurs in many with with essential hypertension

Answer 74

Not diagnostic - need to confirm with 24 hour urine The two tests use different units and measurements

Answer 75

Adrenal vein sampling - gold standard Only to direct surgeon to correct adrenal and should only be performed if surgery is being considered Good test if not hypokalemic, over 40 or have an adrenal adenoma \<1cm. Right adrenal vein hard to catheterise. Samples are assayed for both aldosterone and cortisol during a synacthen infusion to ensure that sampking has got both.

Answer 76

All patients with biochemically confirmed primary aldosteronism gets a thin section CT scan of the adrenals to screen for a rare adrenal carcinoma. In the absence of a large mass, cannot distinguish between unilateral and bilat excess.

Answer 77

Trial of spironolactone or eplerenone if no carcinoma or obvious source on adrenal CT and not for surgery

Answer 78

Spironolactone --\> antiandrogen activity resulting in breast tenderness, gynecomastia and reduced libido Eplerenone --\> better for men since does not have anti-androgenic effects

Answer 79

antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone dependent sodium potassium exchange site in the distal convoluted renal tubule

Answer 80

BP \>160/100 Drug resistant hypertension Hypertension with spontaneous or diuretic induced hypokalemia? Hypertension with adrenal incidentaloma Hypertension with an FHx of early onset hypretension or stroke before age 40 Hypertension and a first degree relative with primary aldosteronism

Answer 81

- chronic intravascular depletion or renal vascular disease (but will have high renin) - excessive ingestion of licorice can cause hypertension and hypokalemia as it contains a metabolite tha inhibits adrenal 11b hydroxysteroid dehydrogenase type 2 that normally inactivates cortisol in the renal tubule - high renal tubular cortisol activates aldosterone receptors --\> absorption of sodium and excretion of potassium - excessive corticosteroid secretion will also cause hypertension with hypokalemia (i.e. CAH 17-hydroxylase deficiency)

Answer 82

Higher rate of CVS complications than essential hypertension Following unilateral adrenalectomy for Conn syndrome, suppression of the contralateral adrenal may result in temporary postop hypoaldosteronism --\> hyperkalemia and hypotension

Answer 83

Conns (unilateral adenoma) --\> lap adrenalectomy or long term spiro/eplerenone Bilateral adrenal hyerplasia --\> long term spironolactone or eplerenone Need to monitor BP daily as will get a significant BP drop when added to other anti-HTs Reversible in about 2/3rds of cases

Answer 84

- attacks of headache, perspiration, palpitation and anxiety - paroxysmal hypertension esp during surgery or delivery - elevated urinary catecholamines or their metabolites - normal serum T4 and TSH

Answer 85

Phaeo: Adrenaline and noradrenaline secreting tumour of the adrenal medulla Para: sympathetic paraganglia tumor that often metastasises and secretes norad or is nonsecretory. May be in the adrenals or along the sympathetic chain

Answer 86

Adrenaline: Tachyarrythmia Norad: Hypertension

Answer 87

Type 2 VHL MEN 2A and 2B Recklinghausen Neurofibromatosis Type 1 (NF-1) Familial paraganglioma

Answer 88

100% These account for about 25% of patients with phaeos.

Answer 89

Catastrophic hypertensive crisis Fatal cardiac arrhythmia

Answer 90

Hypertension, headache, sweating, palpitations and anxiety

Answer 91

IV contrast Glucagon Needle biopsy / surgery Anaesthesia Exercise, bending, lifting or emotional stress Certain drugs

Answer 92

MAO-Is Caffeine & nicotine Decongestants Amphetamines Cocaine IV contrast Adrenalin

Answer 93

Vasospasm due to excess adrenalin release.

Answer 94

Plasma free metanephrines. Normal levels rule it out. Not diagnostic as physical/emotional stress, sleep apnoea and MAO-Is (amongst others will elevated). You need to do a 24 hour urine for fractionated metanephrines and creatinine which will confirm most phaeos. 97% sensitive.

Answer 95

- serum chromogranin A is elevated in 90% and correlate with tumor size, higher in metastatic disease - but elevated in azotemia, hypergastrinemia, exogenous steroids and PPIs. - neuron specific enolase is positive and implicate a malignant phaeo, normal levels are unhelpful. Often a tumor marker for SCLC Mild hyperglycemia and leukocytosis Elevated plasma renin activity

Answer 96

VHL, ret proto-oncogene and SDHB/SDHD mutations

Answer 97

MEN2a and 2b

Answer 98

- performed when biochemically or genetically suspected - non-contrast thin section adrenal CT followed by a contrast using **nonionic** contrast which reduces the risk of catecholamine release --\> hypertensive crisis - no glucagon should be used for the same reasons - IV contrast itself can precipitate crisis especially **_when hypertension is uncontrolled_**

Answer 99

- doesn't need IV contrast or use radiation - used in pregnancy and childhood For CT and MRI - sensitive for adrenal tumors \>0.5cm - less sensitive for recurrent tumors, mets and extra-adrenal paraganglionomas - if no tumor: C/A/P performed

Answer 100

I-MIBG can localise tumors but less sensitive for MEN2A/B disease or mets. Used when CT cannot locate a phaeo, making a paraganglionoma more likely. In-labelled octreotide scanning is sensitive for extra-adrenal disease and locating tumours missed by I-MIBG FDG-PET similarly may find missed tumours and when combined with non-con CT, is highly sensitive.

Answer 101

- surgical removal of phaeo or paraganglionomas is the treatment of choice. - alpha blockers are given prior to surgery - BP must be maintained 4-7 days prior to surgery or until ECG changes have normalised (may be months) - **_must_** give alpha or calcium blockers first as starting b-blockers first results in unopposed alpha-adrenergic action --\> hypertensive crisis. Labetalol has alpha blocking activity but can still cause paradoxical hypertension.

Answer 102

Tachyarrthymia intraop - atenolol Hypertension intra-op - short acting CCB or nitroprusside Post-op hypotension (caused by desentisisation of alpha receptors) --\> preop auto-transfusion of 1-2 units of PRBCs 12 hours prior can help prevent Post-op shock --\> IV saline and IV norad. Post-op hypoglycaemia prevention --\> IV 5% dex

Answer 103

Histopath does **not** reliably determine if tumour is malignant Recheck plasma metanephrines 2-4 weeks postop and when minimal pain MIBG scan 3 months post-op - undetected mets may reveal themselves BP and symptom monitoring for life Plasma metanephrines 6 monthly for 5 years EBRTx for osteolytic bone mets

Answer 104

If sufficient uptake on diagnostic I-MIBG, then can have therapy with high-activity I-MIBG

Answer 105

- impaired renal tubular phosphate reabsorption - normal serum Ca+, low phos, elevated ALP - high dose Vit-D and oral phos is tx - presence as failure to thrive in infancy, X-linked dominant

Answer 106

cerebellar haemangiomas retinal haemangiomas: vitreous haemorrhage renal cysts (premalignant) phaeochromocytoma extra-renal cysts: epididymal, pancreatic, hepatic endolymphatic sac tumours

Answer 107

Elevated TSH in primary hypothyroidism Low FT4 Delayed deep tendon reflexes, bradycardia, and dry skin Fatigue, cold, constipated, fat, hoarse and depressed

Answer 108

TSH - most sensitive for primary hypo and hyperthyroidism Free Thyroxine (Free T4)

Answer 109

Serum TSH - high in primary and low in secondary hypothyroidism Anti-thyroglobulin and anti-thyroperoxidase antibodies - both elevated in Hashimoto thyroiditis

Answer 110

Serum TSH - suppressed unless pituitary TSHoma/hyperplasia (rare) T3 or FT3 - elevated Antithyroglobulin and antimicrosomal (TPO) antibodies - elevated Anti-TSHr (TRab) antibodies - 65% positive in Graves disease 123-I uptake and scan - diffuse increased uptake (as opposed to 'hot' area)

Answer 111

FNA - best method for thyroid cancer 123-I uptake and scan - cancer usually 'cold 99m Tc scan - vascular vs avascular U/S - assists FNA bx, assesses malignancy risk (multinodular goitre or pure cysts are less likely to be malignant. Monitors nodules and patients post-op for carcinoma.

Answer 112

Interstitial accumulation of hydrophilic mucopolysaccharides --\> lymphoedema

Answer 113

Impaired renal NA+-K+-ATPase activity --\> reduced renal tubular reabsorption of sodium

Answer 114

Hashimoto thyroiditis

Answer 115

Sunitinib - used to treat GIST

Answer 116

Pre-existing auto-immune thyroiditis who are not iodine deficient. Elevated TSH w/ low or normal T4 Given just enough thyroxine to relieve symptoms

Answer 117

Hepatitis-C Risk of dysfunction even high when treated with either IFN-a or IFN-b

Answer 118

Menorrhagia

Answer 119

Cardiac enlargement 'myxedema heart' Pericardial effusion

Answer 120

_Coeliac disease_ Also - Addison, hypoPTH, DM, pernicious anaemia, Sjogren, vitiligo, and PBC.

Answer 121

Vitamin K - easy bruising Vitamin A - hyperkeratosis & night blindness Vitamin D - bone pain Vitamin E - neuropathy/ataxia (also B12)

Answer 122

Increased LDL, TGL, lipoprotein-a Increased liver enzymes and CK Increased prolactin Hyponatraemia Hypoglycaemia Anaemia Elevated ANA (but not indicative of lupus)

Answer 123

Serum TSH in upper range of normal with normal T4 levels Usually asymptomatic or subtle signs (fatigue, depression, hyperlipidemia) No need to replace if asymptomatic - associated with familial longevity Monitor - may become hypothyroid later

Answer 124

Not usually necessary. May get enlargement of pituitary gland due to hyperplasia which could be mistaken for pituitary adenoma as often have concomitant hyperprolactinaemia. May get thymic enlargement in autoimmune thyroiditis.

Answer 125

Third-most common iodothyronine the thyroid gland releases into the bloodstream T4 constitutes 90% and T3 is 9%. However, 95% of rT3 in human blood is made elsewhere in the body, as enzymes remove a particular iodine atom from T4.

Answer 126

The most common hormone pattern in sick euthyroid syndrome is a low total and unbound T3 levels with normal T4 and TSH levels. Affected patients may have normal, low, or slightly elevated TSH depending on the spectrum of illness. Total T4 and T3 levels may be altered by binding protein abnormalities, and medications. Reverse T3 levels are generally increased signifying inhibition of normal Type 1 enzyme or reduced clearance of reverse T3. Generally the levels of Free T3 will be lowered, followed by the lowering of Free T4 in relation to severity of the disease. Low serum T4 (very low = poor prognosis), low levels of free T4 Accelerated metabolism of T4 to rT3 Increased levels of rT3 due to stable production and decreased clearance May have normal or low TSH Critically ill patients have a circulating inhibitor to thyroxine binding globulin resulting in computed levels of protein-bound T3 and T4 to be low.

Answer 127

A low serum T4 with no elevation in TSH may also be due to pituitary insufficiency however without a prior brain lesion or hypopituitarism, it's unlikely to suddenly develop it. If suspected hypopituituarism, DI or CNS endocrine lesion, can give T4 empirically. Some antiseizure medications will call low serum FT4 by accelerating hepatic conversion of T4 to T3 and will also have normal TSH levels Dopamine may suppress TSH in prolonged dopamine infusion.

Answer 128

- bacterial pneumonia

Answer 129

_Severe life threatening hypothyroidism_ Impaired cognition to coma Seizures Severe hypothermia & hypoventilation _Hyponatraemia_, hypoglycaemia and hypotension Rhabdo and AKI Hyponatraemia may be severe and refractory Myxedema coma - elderly women who have had a stroke or stopped taking their meds Also if underlying illness Unusually sensitive to opioids - regular dosing may cause death.

Answer 130

Adrenal insufficiency and angina as these must be treated first.

Answer 131

Aim to keep between 0.4 and 2.0 and maintain clinical response Pregnant women After an overnight fast as food interferes a little with absorption

Answer 132

Smaller initial doses If known IHD, should have angio or bypass first.

Answer 133

High dose IV levothyroxine since myxedema interferes with intestinal absorption of PO Hypothermia - warming blankets only as faster can precipitate cardiovascular collapse. Hydrocort if concomitant adrenal insufficiency

Answer 134

Usually indicates the need for higher levo dose. Serum T3. Normal serum TSH and FT4 levels do not determine euthyroid status.

Answer 135

Anticonvulsants: Carbamazepine, phenytoin Antibiotics: Rifampicin TKIs: Sunitinib and Glivec

Answer 136

Iron (beware multivitamins!) Calcium Mag Aluminium Sevelamer Fibre Raloxifene Cholestyramine PPIs by reducing gastric acidity

Answer 137

Pregnancy or on oral estrogen therapy Requirements decrease after delivery and menopause

Answer 138

Fetus is partly dependent on maternal T4 for CNS development especially in the third trimester with requirement starting very early in pregnancy. Levo should be increased by approx 30 as soon as pregnancy is confirmed. This increases to nearly 50% by mid pregnancy.

Answer 139

1. Rising estrogen --\> increases thyroxine binding globulin concentration --\> free T4 reduced 2. Placental deiodinase promotes turnover of T4 3. Prenatal multivitamins (containing iron and Ca) binds to oral T4 and reduces intestinal absorption

Answer 140

Probably due to high levels of HCG (structurally homologous to TSH) stimulating thyroid hormone production. Low TSH patients in first trimester are euthyroid.

Answer 141

Medium chain triglyceride oil

Answer 142

- psych illness or recovery from a nonthyroidal illness - autoimmune disease can interfere with an assay - thyrotropin secreting tumors - increased by phenothiazines and atypical antipsychotics

Answer 143

Suboptimal T3 - may need to increase levo dose

Answer 144

0.4-4 is low \<0.03 is suppressed

Answer 145

Hypopituitarism or severe nonthyroidal illness Medications: NSAIDS, opioids, nifedipine, verapamil and short term high dose steroids

Answer 146

Adrenal insufficiency Hypogonadism Anaemia Coeliac disease depression Serum T3

Answer 147

Pregnancy and in women receiving oral oestrogens

Answer 148

No long term increased risk of cardiovascular disease, dysrhythmia or fractures. Suppressed - increased risk of all of the above - need monitoring for atrial arrhythmias and osteoporosis

Answer 149

20-50% Untreated hypothyroidism progresses to this

Answer 150

Palpitations, anxiety, weight loss, loose stools, heat intolerance, fatigue, menstrual irregularity

Answer 151

Tachycardia, warm moist skin, stare and tremor. In Graves: Goiter with bruit, opthalmopathy

Answer 152

Suppressed TSH in primary hyperthyroidism'; increased T4, FT4, T3, and FT3

Answer 153

Basedown disease

Answer 154

Autoantibodies bind TSH receptor in thyroid cell membranes and stimulate the gland to hyperfunction --\> increase in synthesis and release of thyroid hormones Thymus gland is typically enlarged and serum ANA are usually elevated

Answer 155

Infiltrative opthalmopathy (Graves exopthalmos) Less commonly - infiltrative dermopathy (pretibial myxoedema)

Answer 156

Familial tendency HLA-B8 and HLA-DR3 association

Answer 157

Dietary iodine supplementation Potassium iodide reatment Amiodarone

Answer 158

Sjogren syndrome Perncious anaemia Addison disease Alopecia Vitiligo Coeliac disease DM Type 1 Hypopth Myasthenia gravis Cardiomyopathy

Answer 159

Iodine-induced hyperthyroidism May occur in large multinodular goiters after large intake of dietary iodine, IV contrast, amiodarone Not associated with opthalmolpathy or dermopathy

Answer 160

- enlarged tender thyroid and hyperthyroidism - due to a viral infection - followed by hypothyroidism

Answer 161

- hyperthyroidism due to autonomously secreting thyroid tissue - found in 3% of ovarian dermoid tumours and teratomas - may secrete in concert with toxic nodule, MNG, or Graves

Answer 162

- elevated or normal serum TSH in the presence of true thyrotoxicosis - diminished feedback effect of T4 on the pituitary - rare

Answer 163

Hashimotos will cause transient hyperthyroidism during the initial destructive phase IFN-A, IFN-B, interleukin-2 Postpartum thyroiditis = Hashimoto's within first 6 months of delivery

Answer 164

Increased neonatal risk of IUGR, prematurity and transient thyrotoxicosis from transplacental transfer of thyrotropin receptor antibody (TRab) - very high serum levels of HCG may cause sufficient receptor activation to cause thyrotoxicosis in spite of their low affinity for the thyroid receptor

Answer 165

First 4 months of pregnancy Due to very high HCG levels

Answer 166

If they have high serum levels of asialo-HCG, a subfraction of HCG with greater affinity for TSH receptors

Answer 167

Induces a destructive subacute thyroiditis that may be painful and similar to type 2 amiodarone-induced thyrotoxicosis

Answer 168

4 months to 3 years after initiation

Answer 169

- may cause toxic MNG in setting of iodine deficiency w/ autonomous thyroid nodules - excess free iodine can trigger immunologic attack on thyroid resulting in Graves disease - diffuse thyroid enlargement and antithyroid peroxidase antibodies (70%)

Answer 170

Type 1 - diffuse enlargement, color flow doppler --\> increased vascularity and blood flow velocity. Thyroidal radioiodine uptake can be low/normal/increased Type 2 - no enlargement, no increase in vascularity, and very low thyroidal radioiodine uptake

Answer 171

- Due to destructive thyroiditis - Stored thyroid hormone released from damage cells - Can last 1-3 months and may be followed by hypothyroidism

Answer 172

Osteoporosis Clubbing Swelling of the fingers (acropachy)

Answer 173

- Tachycardia - AF w/ RVR - reversible pulmonary hypertension (mainly PaH)

Answer 174

Upper eyelid retraction (Dalrymple sign) Lid lag with downward gaze (von Graefe sign) Staring appearance (Kocher sign)

Answer 175

- opthalmopathy - conjunctival oedema (chemosis) - conjunctivitis - mild exopthalmos (proptosis)

Answer 176

- increased retro-orbital and eye muscles that have been thickened by lymphocytic infiltration - diplopia from extraocular muscle entrapment - weakness of upward gaze (Stellwag sign) - optic nerve compression --\> progressive loss of colour vision, fields, and acuity

Answer 177

It doesn't - some patients with Graves opthalmopathy are clinically euthyroid

Answer 178

Exopthalmometry Document degree of exopthalmos and detect progression of orbitopathy

Answer 179

Coexistent ocular myasthenia gravis More common in Graves Usually mild with selective eye involvement ACHr Abs only elevated in 40% Thymoma in 9%

Answer 180

- more common with high levels of TSH-stiulating Ig and in severe Graves opthalmopathy - glycosaminoglycan accumulation and lymphoid infiltration occurs in infected skin which becomes erythematous with a thickened rough texture

Answer 181

- extreme and rare - digital clubbing, swelling of fingers and toes and periosteal reaction of extremity bones - most patients are smokers - indicates severity of autoimmunity - high titres of thyroid-stimulating Ig

Answer 182

- rare - due to incresaed renal excretion of magnesium - severe depletion causes hypoparathyroidism that results in hypocalcaemia

Answer 183

- Increased risk of thyroid storm, eclampsia, CCS, prem, abruption - TSHrAb crosses the placenter - if maternal serum TSHrab levels \>500% in third tri --\> risk of transient neonatal graves

Answer 184

- Hypokalemic periodic paralysis - Asians and Native American men - symmetric flaccid paralysis often after oral carbs, vigorous exercise or IV dextrose - attacks last 7-72 hours

Answer 185

- asymptomatic individual - low serum TSH w/ normal FT4 and T3 - risk of progression higher with MNG

Answer 186

Hypercalcaemia Increased ALP Anaemia Agranulocytosis Thyrotoxic periodic paralyisis: Hypokalemia and hypophosphataemia

Answer 187

Detectable TSHRabs (65%) Antithyroglobulin or anti TPO can be elevated by not specific Elevated ANA/dsDNA w/o evidence of lupus or collagen-vascular disease

Answer 188

Increased ESR No anti-thyroid antibodies TSHRaBs are negative

Answer 189

Undetectable TSHrAbs No anti TPO antibodies Elevated urinary iodine concentration

Answer 190

Serum thyroglobulin levels will be low

Answer 191

Elevated FT4 Suppressed TSH - although failure to suppress may be due to misidentification of HCG T3 resin uptake is low because of high TBG concentration In Graves - _beneficial_ effect, decreasing antibody tires and decreasing FT4 as pregnancy progresses

Answer 192

Suppressed TSH - patients taking amiodarone will have high T4 and FT4 levels regardless of whether or not they're hyperthyroid.

Answer 193

Proptosis and TSH Ig

Answer 194

Graves Toxic nodular goitre

Answer 195

Type 1 amiodarone-induced thyrotoxicosis - usually detectable but low

Answer 196

Subacute thyroiditis Iodine induced hyperthyroidism Type 2 amiodarone induced thyrotoxicosis

Answer 197

- determine the cause of hyperthyroidism - not necessary if obvious Graves (TSHrabs or associated Graves opthalmopathy) - never in pregnant women

Answer 198

Screen for concomitant struma ovarii in women with Graves

Answer 199

Hyperthyroid patients particularly with palpable nodules

Answer 200

Distinguish between type-1 amiodarone induced thyrotoxicosis (increased blood flow velocity and vascularity) and type 2 (reduced vascularity)

Answer 201

MRI or CT visualises Graves opthalmopathy affecting the extraocular muscles Required in severe or unilateral cases, or in euthyroid exopthalmos that must be distinguished from orbital pseudotumor, tumors, and other lesions

Answer 202

- hypermetabolic states ie anaemia, leukaemia, polycythaemia dn cancer - Pheo - Acromegaly - cardiac disease suggests possibility of 'apathetic' hyperthyroidism - other causes of opthalmoplegia ie MG and exopthalmos ie tumor - must consider thyrotoxicosis in ddx of muscle weakness and thyrotoxicosis - may have concomitant DM or Addison disease

Answer 203

Hypercalcaemia Osteoporosis Nephrocalcinosis Decreased libidio, gynecomastia , erectile dysfunction and sperm motility Dysrhythmia Thyrotoxic hypokalemic periodic paralysis

Answer 204

- symptomatic relief of tachycardia, tremor, sweats anxiety - initial treatment of choice for thyroid storm - treatment for periodic paralysis

Answer 205

- methimazole/carbimazole or PTU - young patients with mild thyrotoxicosis, small goiters or fear of isotopes - elderly respond well - presurgical preparation - no permanent thyroid damage, assoc w/ lower chance of posttreatment hypothyroidism (c/w surgery or RAI) - _contraindicated in breastfeeding_

Answer 206

- better likelihood if: 1. small goiter or mild hyperthyroidism 2. requiring small doses of thiourea 3. high tpo and tg antibodies 2 years after therapy only have a 10% relapse rate

Answer 207

Agranulocytosis Genetic link Reversible Not improved by G-CSF Also: pruritus

Answer 208

No - because they're too similar

Answer 209

1st line for thyrotoxicosis - induction of permanent remission, prethyroidectomy, before and after radioactive iodine - less likely to cause fulminant hepatic necrosis and I¹³¹ treatment failure - risk of fetal anomalies, switch to PTU

Answer 210

Drug of choice for breastfeeding Favored in pregnancy Complications: Arthritis, lupus, aplastic anaemia, thrombocytopaenia, hypoprothrombinaemia In pregnancy: can be switched to carbimazole in second tri

Answer 211

- effective temporary treatment for thyrotoxicosis of any cause - Graves: blocked with carbimazole then replaced with iodinated agent - useful for symptomatic thyrotoxicosis - option for T4 overdose, subacute thyroiditis, amiodarone-induced thyrotoxicosis, intolerance to thiorureas and newborns with thyrotoxicosis secondary to maternal Graves

Answer 212

- destruction of overactive thyroid tissue (diffue or toxic nodular goiter) - no increased risk of subsequent thyroid cancer, leukaemia or other malignancy - normal rates of congenital abn - _should not be given to pregnant women_ due to fetal radiation being harmful

Answer 213

- Graves + a thiourea of any sort - can improve effectiveness if discontinue at least 4 days prior and if I¹³¹dose is adjusted up

Answer 214

Grave opthalmopathy - much more likely if patient a smoker. Pre-existent opthalmopathy worsens unless you give prophylactic prednisone 2 months prior esp if severe orbital involvement. Smoking decreases effectiveness of pred

Answer 215

FT4 levels may drop within 2 months then go up to thyrotoxic levels during which time RAI uptake is low - due to release of stored thyroid hormone from injured cells, not treatment failure --\> FT4 will eventually fall abruptly to hypothyroid levels

Answer 216

- increased lifetime risk of hyperparathyroidism particularly if radioidine given in childhood/adolescence - need lifetime followup with serum TSH, FT4 and calcium

Answer 217

Pregnant women with thyrotoxicosis not controlled with low doses of thioureeas Women who want to get pregnant in vvery near future Option for nodular goiters when there is a suspicion of malignancy

Answer 218

Hartley-Dunhill - treatment of choice for Graves having surgery - total resection of one lobe and a subtotal resection of the other lobe - subtotal thyroidectomy of both lobes - but 9% recurrence rate - total thyrodectomy - increased risk of hypoparathyroidism and damage to the recurrent laryngeal nerves

Answer 219

- rendered euthyroid preop with a thiourea - propranolol is given until euthyroid - may given iodine to reduce vascularity - if thyrotoxic during surgery --\> needs higher doses of propranolol

Answer 220

- recurrent laryngeal nerve palsy and vocal cord paralysis - if both damages --\> airway obstruction --\> intubation --\> trache

Answer 221

Usually benign if no surgery --\> FNA Symptomatic: Propranolol ER and carbi/PTU as for Graves - keep TSH slightly suppressed so stimulated growth of the nodule is reduced - under 40: surgery - over 40/poor health: I¹³¹, keeping TSH suppressed prior in order to reduce I¹³¹ uptake by the normal thyroid

Answer 222

- propranolol and carbi but 95% recurrence rate if stopped - definitive: surgery - either to release pressure or cosmetic - I¹³¹ - must stop carbimazole 4 days prior and follow low iodine diet to enhance RAI uptake

Answer 223

Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole _prevents the thyroid peroxidase enzyme_ from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4 (thyroxine).

Answer 224

Central - inhibits thyroperoxidase whichhelps iodine addition onto thyroglobulin - an essential step in T4 production Peripheral: PTU also acts by inhibiting the enzyme 5'-deiodinase (tetraiodothyronine 5' deiodinase), which converts T4 to the active form T3. (This is in contrast to methimazole, which shares propylthiouracil's central mechanism, but not its peripheral one.)

Answer 225

May induce Graves and Graves eye disease.

Answer 226

Propranolol for symptom relief if thyrotoxic NSAID or aspirin for pain Pred if severe Thioureas and RAI are unhelpful as thyroid production is actually low May have hypothyroidism afterward, need to monitor

Answer 227

- PTU in first tri then switch to lower risk of foetal abnormalities - both cross the placenta and can induce fetal hypothyroidism and TSH hypersecretion - T3 and T4 do not cross the placenta but fetal hypothyroidism is rare if mothers hyperthyroidism is controlled with small doses of thioureas

Answer 228

First tri - lower TSH - higher FT3 - normal FT4 Second tri - TSH should return to normal, may not - higher FT3 - lower later Third tri - as for second - higher FT3 - lower FT4

Answer 229

Propranolol for sx Prednisone May be able to continue amiodarone Carbimazole is ineffective

Answer 230

Propranolol 1 month trial of carbimazole Pred if severe or when carbi fails to correct Amiodarone is discontinued if possible

Answer 231

Higher risk of fulminant hepatic necrosis

Answer 232

Thiazolidinediones (glitazones)

Answer 233

IV methyl pred (superior to oral) Doesn't work as well for smokers Can also give retrorobulbar radiation with oral pred - although response less good if chronic proptosis and orbital muscle restriction. - orbital decompression if severe and may save vision but diplopia often persists

Answer 234

Slows RVR Need larger than normal doses due to increased clearence and increased number of cardiac sodium pumps needing inhibition Dose reduces as AF does B-blockers second line as negative inotropic effect may precipitate CHF

Answer 235

- LA enlargement on TTE - global LV dysfunction - recent CHF - hypertension - recurrent AF - hx prev VTE - smaller doses of Warfarin needed because there is an accelerated clearance of vitamin-K dependent clotting factors

Answer 236

- angina pectoris - reverse hyperthyroidism and reverse angina, thus avoiding the need for angioplasty

Answer 237

- triggered by stress, surg or RAI admin - severe delirium, tachy, vomiting, high fever - high mortality rate - Give hydrocort - avoid aspirin - delay definitive treatment until euthyroid

Answer 238

Displaces T4 from TBG raising FT4 levels.

Answer 239

Propranalol during hyperthyroid phase, levo during hypothyroid phase

Answer 240

- topical corticosteroid with nocturnal plastic occlusive dressings

Answer 241

Propranolol - normalise potassium and phosphate, reverses paralysis within 2-3 hours Avoid IV dextrose and oral CHO - aggravates Treat underlying hyperthyroidism No potassium or phosphate replacement usually required

Answer 242

Increased long-term risk of death from thyroid disease, cardiovascular disease, stroke, and fracture of the femur. Post-treatment hypothyroidism is common

Answer 243

30% chance of spontaneous remission before the third tri

Answer 244

- most don't have accelerated bone loss but if there is osteopenia, need to do regular followup BMDs.

Answer 245

People with very low TSH are closely monitored but are not treated unless AF or other manifestations of hyperthyroidism appear

Answer 246

- most common - b-lymphocytic invasian - Anti-TPO and antithyroglobulin antibodies

Answer 247

Familial Women 6x Childhood/occ exposure to head/neck external beam radiation

Answer 248

smokers High serum thyroid peroxidase levels

Answer 249

Polyglandular autoimmunity Celiac disease Turner Syndrome Hep-C

Answer 250

- occurs soon after delivery - may be due to accumulation of fetal cells in the maternal thyroid during pregnancy (microchimerism) - 70% chance of recurrence in subsequent pregnancies - occurs mostly if high levels of anti-TPO antibodies in first tri, or immediately after delivery

Answer 251

- also known as subacute, granulomatous or giant cell thyroiditis - usually post viral URTI - incidence peaks in summer - young and middle aged women

Answer 252

Riedel or fibrous thyroiditis. Usually found in elderly women as a manifestation of systemic fibrosis.

Answer 253

- diffusely enlarged, firm, and finely nodular thyroid, sometimes with lobular assymmetry - absence of pain - may be assoc w/ mild myasthenia gravis affecting extraocular muscles with low detectable AChR Ab or thymic disease

Answer 254

- hyperthyroidism 1-6 months after delivery - persists for 1-2 months - hypothyroidism develops 4-8 months after delivery

Answer 255

Acute and painful enlarged thyroid gland Low grade fever and fatigue Thyrotoxicosis in 50% and lasts several weeks followed by hypothyroidism that lasts 4-6 months

Answer 256

Increased anti-TPO antibodies Increased anti-thyroglobulin antibodies No need to monitor once diagnosed Antibodies decline during pregnancy and are undetectable by third tri.

Answer 257

Coeliac workup: Serum IgA endomysial aB or TTG Serum IgA Must not be on a gluten-free diet at thet ime

Answer 258

Markedly elevated ESR Low antithyroid antibody titres (Leuks elevated in suppurative thyroiditis)

Answer 259

Thyroiditis - serum FT4 levels proportinally higher than T3 since the hyperthyroidism is due to passive release of stored thyroid hormone (predominantly T4). Graves/toxic NG --\> T3 is relatively more elevated and hyperthyroidism more severe as T3 more active

Answer 260

U/S - diffuse hetergenous density and hypogenecity - distuingishes thyroiditis from MNG or suss nodules, guides FNA Color flow doppler - distuingishes from Graves (hypervascular) as normal or reduced vascularity RAI - very low in subacute thyroiditis but otherwise unhelpful in making dx of Hashimoto

Answer 261

Do it if they have a thyroid nodule RIsk of papillary cancer about 8% Not required for deQuervain (subacute) thyroiditis)

Answer 262

Higher relative risk of depression if high serum anti-TPO antibodies

Answer 263

Sensitive but not specific (If negative you've ruled it out, if positive it could be other stuff) Also positive in MNG, malignancy and concurrent Graves

Answer 264

- levo if hypothyroid - if large goitre --\> lots of levo to drive down TSH and shrink the goiter - if euthyroid - monitor, may become hypothyroid years later - simvastatin and selenium may have a role but no long term data

Answer 265

Aspirin - relieves pain and inflammation Propranolol if thyrotoxic and symptomatic Iodinated contrast causes prompt fall in serum T3 and thyrotoxic symptoms

Answer 266

Excellent - even if they become hypothyroid, it's easily treated

Answer 267

80% return to normal 50% develop permanent hypothyroidism within 7 years More common if multiparous or spontaneous abortion Papillary cancer plus Hashimoto has a good prognosis

Answer 268

Common and mostly benign Same cancer risk if multiple compared with one Higher risk if hx head-neck radiation, total body radiation for bone marrow transplant/exp to fallout, FHx, hx malignancy

Answer 269

Cosmetic embarassment If retrosternal --\> dyspnoea due to tracheal compression Large substernal --\> SVC syndrome

Answer 270

If abnormal TSH --\> need imaging to determine if hyperfunctioning (and if so, they are rarely malignant) Antibody tests --\> very high if Hashimoto If thyroiditis must check for malignancy as often coexists

Answer 271

Serum calcitonin

Answer 272

U/S - do to see if palpable nodule is part of MNG RAI - limited usefulness - only to determine if 'hot' or 'cold' but can't differentiate malignancy CT - larger nodules, degree of tracheal compression and mediastinal extension

Answer 273

- irregular or distinct margins - heterogenous nodule echogenecity - intranodular vascularity - microcalcifications - diameter \>1cm

Answer 274

FNA - best method Can be done on anticoagulation/aspirin Four largest (\>1cm) in MNG should be biopsied so you don't miss it

Answer 275

- \>5mm with suspicious appearance - assoc w/ abnormal lymph nodes - \>1cm and solid or have microcalcifications - mixed cystic-solid nodules \>1.5cm in diameter with any suspicious features on U/s - \>2cm and benign on U/S - spongiform and 2cm

Answer 276

Observe - pure cystic nodules are benign and don't need biopsy.

Answer 277

- about 20-25% - higher if much younger or older than age 50 - bloody aspirate higher chance of malignancy - surgery usually indicated on suspicious cytology

Answer 278

Toxic MNG!

Answer 279

- replaced if elevated TSH - suppression most therapy in iodine deficient ares of the world - long term tx keeps nodules from enlarging and may reduce emergence of new nodules

Answer 280

Cardiac disease - increases risk for angina and AF Also causes a small lose in BMD in post-menopausal women if serum TSH is suppressed Low baseline TSH because that means there is autonomous thyroid secretion, meaning levo won't work and will cause thyrotoxicosis instead

Answer 281

Shrinks benign cysts quite well as if you suck out the fluid it just comes back. Needs to be repeated but has 80% success rate.

Answer 282

Option for hyperthyroid patients with toxic adenoma, MNG or Graves Can be used to shrink benign nontoxic nodules May be used for MNG but may induce Graves Risk of hypothyroidism years after therapy

Answer 283

90% will increase in size over 5 years, cystic ones remain fairly stable MNGs persist or grow slowly Small incidentalomas require u/s followup ever 1-2 years but low risk

Answer 284

Painless swelling Normal thyroid function tests Past history of irradiation to head and neck Positive thyroid needle aspiration

Answer 285

Papillary carcinoma

Answer 286

Usually from a single nodule but can come out of an MNG - commonly multifocal within the gland Slow growing, may be more aggressive in older patients with local invasion and spread to the lungs Hx of head and neck irradiation, medical, Chernobyl etc.

Answer 287

- activating mutation of ras oncogene can cause benign adenoma or nodular goiter - _additional_ activation mutation in BRAF or TRK genes can lead to papillary carcinoma - 45% caused by overexpression of RET oncogene (medical radiation - retPTC-1, nuclear fallout retPTC-3)

Answer 288

Additional loss of p53 tumor suppressor gene in presence of activation mutation of ret oncogene and BRAF/TRK mutations

Answer 289

Autosomal dominant familial syndromes - familial thyroid ca - familial polyposis - Gardner & Turcot syndromes

Answer 290

Papillary carcinoma - 80% have microscopic mets but no increased mortality rate - if lymph nodes, only the risk of local recurrence increases

Answer 291

Follicular thyroid ca and it's variants (i.e. Hurthle cell ca) Generally more aggressive than papillary

Answer 292

- avidly absorb iodine so v treatable - mets to nodes, bones and lungs - high risk of poorly differentiated or Hurthle cell variants (both don't take up RAI)

Answer 293

- aberrant DNA methylation - ras oncogene - MEN1 gene

Answer 294

- 3% of thyroid cancer - 1/3 sporadic, 1/3 familial, 1/3 MEN2 - ret oncogene mutation on chromosome 10

Answer 295

Genetic analysis of peripheral white blood cells for the germline mutation of ret oncogene in exon 16. If positive - related family members must be tested for that gene defect. If no mutation, can still identify gene carriers with family linkage analysis, or if no defect at all, 6 monthly thyroid surveillance is required.

Answer 296

- arise from parafollicular thyroid cells that secrete calcitonin, prostaglandins, serotonin, ACTH, CRH and more - can be used as tumor markers - metastasises and does not concentrate iodine

Answer 297

Rarest Older patients with rapidly enlarging mass in a MNG Most aggressive and metastasizes early Does not concentrate iodine

Answer 298

Flushing and persistent diarrhoea - may be the initial clinical features Cushing syndrome in about 5% due to secretion of ACTH or CRH

Answer 299

- high in most papillary and follicular tumours making it a marker for recurrent or metastatic disease - MUST measure antithyroglobulin antibodies as elevation of these can affect the test - may be misleadingly elevated in thyroiditis which can coexist with Ca - some assays falsely report elevated levels after total thyroidectomy and tumor resection causing unneeded concern about mets.

Answer 300

- may also be elevated in thyroiditis, pregnancy, azotemia, hypercalcemia and other malignancies - measure with CEA pre-op, then postop every 4 months for 5 years, then every 6 months for life - if extensive mets, need to do it with serial dilutions - the **best** indication for recurrence is a _rising_ level of calcitonin, not simply a high one as may remain elevated.

Answer 301

Thyroid and whole body used post thyroidectomy for surveillance along with U/s

Answer 302

CT - particularly good for localising and monitoring lung mets but not good for neck mets MRI - particularly useful for bone mets. Medullary ca calcified in thyroid, nodes and liver but lung mets rarely do.

Answer 303

- mets that don't have good iodine uptake on RAI - enhanced if hypothyroid or on thyrotropin which increases metabolic activity of differentiated thyroid ca - low SUV = better prognosis

Answer 304

1/3 of medullary secrete serotonin and prostaglandins --\> flushing and diarrhoea and have coexistent phaeo or hyperparathyroidism - risks of radical neck surgery inc hypoPTH, vocal cord palsy - permanent hypothyroidism is expected post-op and should be treated

Answer 305

Surgical removal with preop neck u/s for LN involvement as may need neck dissection (esp if \>1cm diameter)

Answer 306

Thyroid lobectomy if \<4cm progressing to complete if malignancy detected Bilateral thyroidectomy as initial surg if \>4cm

Answer 307

Ppillary thyroid ca \>1cm in diameter under age 45 who have no hx of irradiation or mets.

Answer 308

- biopsy proven lateral cervical lymphadenopathy - muscle resection is usually avoided

Answer 309

Surgically - radiation or RAI doesn't work.

Answer 310

Happens in 20%, permanent in 2% Incidence reduced if accidentally resected parathyroids are immediately autotransplanted into neck muscles. Watch for tetany

Answer 311

- delay surg until after delivery unless fast growing then after 24 weeks - no difference in recurrence or survival if done during or after pregnancy - higher risk comes from thyroid surg, not cancer

Answer 312

Suppress to \< 0.1 with stage II disease Suppress to \<0.05 for higher stages Risk is lower bone density but relatively minor if euthyroid

Answer 313

Sorafenib and sunitib have partial response.

Answer 314

1- thyroid remnant ablation 2- tx of known or suspected thyroid ca

Answer 315

- iodised salt, fish and seaweed, commercial bread, dairy, processed meats, canned/dried fruit and juice, black tea, instant coffee, red dye # 3 and MVs. 2 weeks before I¹³¹ so the radioactive form gets taken up instead Must also avoid amiodarone and iodinated contrast

Answer 316

Improves survival and reduces recurrence rates in Stage III-IV and in II with gross extension or a distant met

Answer 317

Patients with a ret protooncogene mutation should have a prophylactic total thyroidectomy, ideally by age 6 years (MEN 2A) or at age 6 months (MEN 2B).

Answer 318

Thyrogen (rTSH) is given to increase the sensitive of serum thyroglobulin for residual ca and increase uptake of I¹³¹into remant tissue or cancer. - should NOT Be given to patients with an intact thyroid gland as will cause swelling and hyperthyroidism - and can cause this in patients with significant mets or residual normal thyroid - Nausea and headache are SEs, can cause neurologic deterioration in CNS mets

Answer 319

- anaplastic thyroid ca - brain mets with gamma knife radiosurgery

Answer 320

Serum T3 or FT3 level

Answer 321

Only after total or near-total thyroidectomy or I¹³¹ablation and particularly when there are no serum anti-thyroglobulin antibodies. - Detectable != recurrence - baseline is NOT helpful, stimulated measurements should be used and always w/ neck U/S

Answer 322

Supplements palpation Perform pre-op 3 months post-op Then as followup Better than CT or MRI for local LN mets.

Answer 323

High risk Persistant antithyrglobulin antibodies that make serum thyroglobulin determination unreliable Must be used \<2 weeks before scheduled I¹³¹treatment to avoid stunning the mets (or can use I123 as does not stun tumors and better for SPECT) Performed 2-4 months post op in differentiated disease May not need repeat scanning if clear post op and low serum thyroglobulin, but continue ultrasounds

Answer 324

No additional therapy, especially if serum thyroglobulin is very low

Answer 325

- useful for detecting mets when high serum thyroglobulin who have a normal whole-body RAI scan and unrevealing neck-ultrasound - avoid sweets and in diabetics, BSL \<20 - better sensitivity if done as a fusion scan with CT - poor specificity

Answer 326

Benign hepatic tumours Sarcoidosis Radiation therapy Suture granulomas Reactive LNs Inflammation Muscles Brown fat

Answer 327

Predicts survival better than standard staging - number, location and SUV of mets are all factors.

Answer 328

- few mets, low SUV on PET = better - under 40 even with mets = good - over 45, male, bone or brain mets, \>1cm, pulmonary mets or lack I131 = bad

Answer 329

tall cell columnar cell diffuse sclerosing brain mets reduce survival to 12 months but improves with resection

Answer 330

- tumor \>1cm and only limited thyroid surgery (subtotal or lobectomy) - no I131 ablation - higher in men - multifocal tumors

Answer 331

- 90% 10 year survival when confined to the thyroid, drops to 20% with distant mets - if LN involvement, modified radical neck dissection helps - MEN2A associated less agressive, also women under 40 - more aggressive in MEN2B, younger in age, M918T mutation

Answer 332

Myelomonocytic antigen M-1 Heavy immunoperoxidase stain for calcitonin

Answer 333

1 year survival of about 10% 5 year survival of 5% Fully localised tumor on MRI has a better prognosis

Answer 334

100% at 5 years Outside the thyroid, 63% Better if MALT Stridor, pain, palsy, mediastinal extension = worse

Answer 335

- low iodine diet - high rate of congenital hypothyroidism and cretinism - goiters may become multinodular and enlarge - most are euthyroid

Answer 336

Increased risk of miscarriage and stillbirth Congenital hypothyroidism --\> deafness, short stature, lower IQ Full blown cretinism

Answer 337

Sorghum/millet/maize/cassava Selenium, iron Water pollution Smoking Pregnancy

Answer 338

Normal serum T4 and TSH If TSH falls and hyperthyroidism --\> MNG has become autonomous in presence of sufficient amounts of iodine - Thyroid RAI uptake usually elevated but may be normal if iodine intake has improved - antithyroid antibodies either undetectable or low - eleavted serum thyroglobulin

Answer 339

- iodised table salt reduces prevalence but doesn't shrink goiter - Concurrent vitamin A and iodine deficiency increases risk of endemic goiter, concurrent repletion reduces - large multinodular goiter --\> thyroidectomy for cosmesis, compressive sx or thyrotoxicosis - high recurrence rate if subtotal + iodine deficient area, total is preferred

Answer 340

Iodine supplementation increases risk of autoimmune transformation Excess supplementation increases risk of goiter particularly if autonomonous MNG - avoid thyroxine suppression if low TSH Rarely - Graves post I131 in MNG

Answer 341

- diminished libido and erections - low serum or free testosterone - LH and FSH low/normal in hypogonadotropic hypogonadism - increased in testicular failure (hypergonadotropic hypogonadism)

Answer 342

- insufficient gonadotropin secretion by the pituitary (hypogonadotropic) - pathology in the testes (hypergonadotropic) - both

Answer 343

- FSH and LH deficiency due to pituitary failure, either in isolation or with other hormone deficiencies - can be primary - main causes are functional; obesity, poor health, normal aging - spermatogenesis preserved

Answer 344

After age 40, declines by 1-2% per year Free testosterone levels decline even faster due to increasing SHBG with age No concomitant increase in LH until after age 70, at which point it starts to rise, suggesting primary gonadal dysfunction with age

Answer 345

Low serum testosterone At least 3 of the following 6: Erectile dysfunction Poor morning erection Low libido Depression Fatgiue Inability to perform vigorous activity These men are most likely to benefit from testosterone replacement

Answer 346

- failure of testicular secretion of testosterone - can be caused by viruses (i.e. mumps), irradiation, ca, autoimmunity, myotonic dystrophy, genetics, andropause, single testicle failure, 17-hydroxylase deficiency, 17-ketosteroid reductase deficiency

Answer 347

47, XXY Most common male chromosomal abnormality Gynecomastia and tall stature Dx on karyotype of RNA for X-inactive-specific transcriptase on peripheral leukocyte PCR Azoospermia (although some produce sperm)

Answer 348

- failure of normal testicular development - mutation in SRY gene - no testosterone --\> sex reversal - external female genitalia w/o uterus, have intra-abdominal gonads - raised as girls, upon puberty, amenorrhea - resect intrabdominal testes, risk of malignancy - considered women, give estrogen

Answer 349

Delayed puberty if congenital or acquired during childhood Decreased libido Decreased man hair (after years) Low muscle mass Weight gain

Answer 350

Morning serum or free testosterone (declines throughout day) will be low - free testosterone esp important in elderly men due to high SHBG - should be confirmed with repeat assay and low LH and FSH - check for hyperprolactinaemia - mild anaemia as testosterone stimulates RBC production - BMD if longstanding as may have osteoporosis

Answer 351

- serum PRL may be elevated - normal/low LH/FSH - if gynecomastia, screen for partial 17-ketosteroid reducatse deficiency plus androstenedione and estrone which are elevated in this condition. - serum estradiol may be elevated if cirrhotic and if rare estrogen secreting tumour

Answer 352

Screen for hemochromatosis and MRI the pituitary and hypothalamus looking for a lesion

Answer 353

- low serum testosterone with high FSH and LH - karyotype or PCR leukocyte XIST for Klinefelters - testicular bx in young guys if no cause found

Answer 354

- boys who have not start puberty by age 14 - men with hypergonadtropic hypogonadism or severe hypogonadtropic hypogonadsim - hypogonadic symptoms (at least 3), with low serum or free testosterone

Answer 355

Active prostate or breast ca Erythrocytosis Need DRE and PSA prior to commencing Untreated OSA CHF

Answer 356

Must improve cardiac risk factors and give low-dose aspirin If on Warfarin --\> can increase INR and risk of bleeding Will increase cyclosporine and tac levels Hypoglycaemia in diabetic men on insulin or oral hypoglycaemics

Answer 357

Topical administration is best - more stable sterum testosterone Skin acts as reservoir of slow release - 10% gets into the blood, steady state in 1-3 days Transdermal is inconvenient and expensive Avoid breast or genitals Oral forms can cause liver tumors or peliosis hepatis

Answer 358

Low serum testosterone and at least 3 manifestations of hypogonadism

Answer 359

- increases risk of cardiovascular events in age over 65 with risk factors or pre-existing angina - may be due to decrease in HDL associated with testosterone therapy - aggravates BPH but not voiding sx - erythrocytosis with IM but no increased risk of thromboembolic events - aggravates sleep apnoea - acne - gynecomastia that resolves spontaneously, better with gel

Answer 360

60% of pubertal boys - spontaneously resolves, common in tall oor overweight Half of athletes who abuse HIV on HAART - esp efavirenz of didanosine - spontaneously resolves

Answer 361

- asymmetry - location not immediately below the areola - unusual firmness - nipple retraction, bleeding or discharge

Answer 362

PRL B-subunit of HCG suggest a testicular tumor (germ cell or Sertoli) or other malignancy (lung or liver) - low serum free testosterone and high LH --\> primary hypogonadism - high testosterone plus high LH --\> partial androgen resistance - estradiol increased from testicular tumours, increased B-HCG, liver disease and obesity

Answer 363

CXR for metastatic or bronchogenic ca

Answer 364

Works for lumpy 'glandular' gynecomastia rather than diffuse fatty kind. Give raloxifene

Answer 365

If persistent or severe

Answer 366

Turner's syndrome is a chromosomal disorder affecting around 1 in 2,500 females. It is caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes. Turner's syndrome is denoted as 45,XO or 45,X

Answer 367

short stature shield chest, widely spaced nipples webbed neck bicuspid aortic valve (15%), coarctation of the aorta (5-10%) primary amenorrhoea cystic hygroma (often diagnosed prenatally) high-arched palate short fourth metacarpal multiple pigmented naevi lymphoedema in neonates (especially feet) There is also an increased incidence of autoimmune disease (especially autoimmune thyroiditis) and Crohn's disease

Answer 368

G cells in antrum of the stomach Distension of stomach, vagus nerves (mediated by gastrin-releasing peptide), luminal peptides/amino acids Inhibited by: low antral pH, somatostatin Increase HCL, pepsinogen and IF secretion, increases gastric motility, stimulates parietal cell maturation

Answer 369

I cells in upper small intestine Partially digested proteins and triglycerides Increases secretion of enzyme-rich fluid from pancreas, contraction of gallbladder and relaxation of sphincter of Oddi, decreases gastric emptying, trophic effect on pancreatic acinar cells, induces satiety

Answer 370

S cells in upper small intestine Acidic chyme, fatty acids Increases secretion of bicarbonate-rich fluid from pancreas and hepatic duct cells, decreases gastric acid secretion, trophic effect on pancreatic acinar cells

Answer 371

Small intestine, pancreas Neural Stimulates secretion by pancreas and intestines, inhibits acid secretion

Answer 372

D cells in the pancreas & stomach Fat, bile salts and glucose in the intestinal lumen Decreases acid and pepsin secretion, decreases gastrin secretion, decreases pancreatic enzyme secretion, decreases insulin and glucagon secretion inhibits trophic effects of gastrin, stimulates gastric mucous production

Answer 373

Adrenal cortex (mnemonic GFR - ACD) zona glomerulosa (on outside): mineralocorticoids, mainly aldosterone zona fasciculata (middle): glucocorticoids, mainly cortisol zona reticularis (on inside): androgens, mainly dehydroepiandrosterone (DHEA)

Answer 374

PTH acts to increase the concentration of calcium in the blood by acting upon the parathyroid hormone 1 receptor (high levels in bone and kidney) and the parathyroid hormone 2 receptor (high levels in the central nervous system, pancreas, testis, and placenta).

Answer 375

Secretion of parathyroid hormone is controlled chiefly by serum [Ca2+] through negative feedback. Calcium-sensing receptors located on parathyroid cells are activated when [Ca2+] is elevated. In the parathyroid gland, high concentrations of extracellular calcium result in activation of the Gq G-protein coupled cascade through the action of phospholipase C. Hypermagnesemia also results in inhibition of PTH secretion. While low levels of magnesium stimulate parathyroid hormone secretion, very low serum concentrations induce a paradoxical block.

Answer 376

Stimulators Decreased serum [Ca2+]. Mild decreases in serum [Mg2+]. An increase in serum phosphate (increased phosphate causes it to complex with serum calcium, forming calcium phosphate, which reduces stimulation of Ca-sensitive receptors (CaSr) that do not sense calcium phosphate, triggering an increase in PTH). Inhibitors Increased serum [Ca2+]. Severe decreases in serum [Mg2+], which also produces symptoms of hypoparathyroidism (such as hypocalcemia).[13] Calcitriol

Answer 377

Activating TSH receptor mutations Activating mutations in either the TSH-R or the Gs subunit genes are identified in \>90% of patients with solitary hyperfunctioning nodules Thyrotoxicosis is usually mild Disorder is suggested by the presence of the thyroid nodule and by the absence of clinical features suggestive of Graves' disease or other causes of thyrotoxicosis A thyroid scan provides a definitive diagnostic test, demonstrating focal uptake in the hyperfunctioning nodule and diminished uptake in the remainder of the gland, as activity of the normal thyroid is suppressed

Answer 378

Decrease TGL Decrease VLDL Decrease total chol Increase HDL

Answer 379

Stimulate lipoprotein lipase by inducing PPAR-alpha receptors which induce the transcription of genes that facilitate lipid metabolism ApoCIII (a VLDL protein) is decreased as a result which increases LPL activity VLDL catabolism is enhanced which generates surface remnants, these are then taken up by HDL, helped by PPAR driven transcription of APoA1 and ApoA2 End result is increased HDL-mediated reverse chol transport, reduction in hepatic VLDL secretion, increased size and removal of LDL partiles, and reduced plasminogen activator inhibitor type 1 levels.

Answer 380

Chylomicrons carry diet-derived lipids to body cells VLDLs carry lipids synthesized by the liver to body cells LDLs carry cholesterol around the body HDLs carry cholesterol from the body back to the liver for breakdown and excretion.

Answer 381

1. ApoB (VLDL) secreted by liver 2. Connects to muscle and liver via surface APO-CIII which activates lipoprotein lipase 3. Core TGLs hydrolysed to FAs and cross capillary membrane, VLDL now ILDL (APO-B100) 4. ApO-B100 further freed of FAs by hepatic lipaseand becomes LDL (stil APO-B100) which expresses Apo CIII 5. ILDL and LDL shed APO-E and APOCIII remnants as they shrink, which get taken up by HDL 6. LDL or remnants reuptaken by LDLr or LRP OR - the remnants or chylomicron remnants get taken up by peripheral cells for cholesterol content or by capillary macrophages which have LDLr's --\> foam cells --\> atheroma.

Answer 382

1. Poorly lipidated APoA1 secreted by liver and intestine into the plasma 2. Cholesterol filled cell (inc macrophages) upregulate the ABCA transporter which converts cholesterol ester to free cholesterol from the lipid pool and delivers it to the cell membrane. 3. APOA1 collects this cholesterol and forms _nascent HDL_. ABCA keeps shuttling. 4. Lecithin cholesterol athyltransferase (LCAT) esterifies cholesterol on nascet HDL surface --\> chol ester moves to lipoprotein core --\> _HDL3_ is formed. 5. HDL collects more cholesterol from cell membranes via the FRB receptor, becomes _HDL2_. 6. HDL2 via cholesterol ester transfer protein (CETP) exchanges cholesterol for triglycerides with TGL-rich lipoproteins (VLDL and LDL) 7. HDL2 can then have it's TGLs hydrolysed by hepatic lipase and then become HDL3 again OR return to the liver where scavenger receptor SRB1 extracts cholesterol --\> HDL3, or HDL2 gets catabolised by the liver.

Answer 383

Remember - _excess calcitriol *(aka D3)*_ - hyperparathyroidism --\> upregulated 1-alpha hydroxylase in the kidney - Tumor production of calcitriol: * Predominant cause of hypercalcemia in _Hodgkin’s disease_ and in 1/3 of patients with NHL * Sarcoidosis and sarcoma * Usually responds to corticosteroid administration

Answer 384

Increased prolactin --\> amenorrhea, galactorrhoea, non peurpeural mastitis Granuloma's secrete 1-alpha hydroxylase --\> increased 1,25OHD --\> hypervitaminosis D --\> hypercalcemia

Answer 385

PTH-rP is the leading cause of hypercalcemia in malignancy (80% of cancer pt.’s with hypercalcemia have PTH-rP-related hypercalcemia). Hypercalcemia in malignancy occurs abruptly, is se vere, and portends a very poor prognosis (median survival only six weeks).

Answer 386

Breast, lung, and multiple myeloma

Answer 387

PTHrp Osteolytic mets Tumor production of calcitriol

Answer 388

PTH-rP is the leading cause of hypercalcemia in malignancy (80% of cancer pt.’s with hypercalcemia have PTH-rP-related hypercalcemia). * Also known as HHM (humoral hypercalcemia of malignancy) * PTH-rP is produced by a number of cells (neuro endocrine, epithelial, mesoderm-derived tissues) • Can be associated with any solid tumor (_most commonly breast cancer_) and occasionally humoral malignancy.

Answer 389

Remember the pneumonic BLT with a Kosher Pickle, Mustard & Mayo : Breast,Lung,Lymphoma,Thyroid, Kidney, Prostate, Multiple Myeloma • Most commonly caused by breast cancer and NSCLC

Answer 390

Beginning of menstrual cycle Hypothalamus releases GNRH Pituitary releases FSH FSH stimulates follicle (1 egg, oestrogen secretion) growth and maturation Follicle releases oestrogen Uterine endometrium proliferates via oestrogen Increasing GnRH results in LH secretion --\> luteal phase

Answer 391

Midpoint of cycle Ever increasing GnRH acts on pituitary to spike LH secretion Egg is released from follicle - takes 5-6 days to travel to uterus Follicle becomes _corpus luteum_ which secretes _progesterone_ Progesterone acts on endometrium to become secretory (favorable for egg) Continues to secrete progesterone No fertilisation --\> corpus luteum dies and in presence of both falling oestrogen and progesterone --\> sheds, period Fertilisation --\> corpus luteum keeps secreting progesterone for first 12 weeks of pregnancy.

Answer 392

Hypothalamus releases GnRH Ant pituitary releases LH & FSH LH goes to the _Leydig Cells_ in the _interstitial space_ _Leydig cells secrete testosterone_ Testosterone and dihydroxytestosterone negatively feedback on the anterior pituitary to reduce LH release and drop testosterone production.

Answer 393

Hypothalamus releases GnRH GnRH stimulates LH & FSH release LH --\> Leydig cells (interstitium) --\> testosterone _FSH --\> Sertoli cells (seminiferous tubules) --\> ABP_ (androgen binding protein) release _Testosterone binds ABP_ --\> stimulates sperm growth (spermiogenesis and spermatogenesis) Sertoli cells secrete inhibin --\> negative feedback to pituitary --\> reduced production of FSH.

Answer 394

- approx 3 degrees cooler than body (for sperm) - can drop away from body via spermatic cord if body gets too hot - _tunica albuginea_ protects teste, and extends inside to form septa --\> dividing teste into lobules containing _interstitium_ and _seminiferous tubules_

Answer 395

Seminferous tubule form sperm Interstitial cells form male hormones (androgens)

Answer 396

FSH --\> Spermatogonium undergo mitosis forming a daughter spermatogonium (for later) and a primary spermatocyte with 46 chromosomes. Primary Spermatocyte undergoes _meiosis 1_ Secondary spermatocyte is generated in which the DNA is not replicated beforehand, leaving it with only 23 chromosomes. Secondary spermatocyte undergoes _meiosis 2_, generating 4 spermatids each with 23 chromosomes. Spermatids then differentiate to form their own heads and tails --\> mature spermatozoa In summary: spermatogenesis forms 4 x spermatozoa (sperm cells) each with only 23 chromsomes from one primary spermatocyte (46 chromosomes). Female ova supply the other 23 chromosomes.

Answer 397

Head --\> contains nucleus and chromsomes. Tip (acrosome) contains penetrative enzymes Body --\> mitochondria for ATP and swimming energy Tail --\> flagellum Lives for hours to 3 days.

Answer 398

Seminefrous tubule Epididymus (coiled tube) --\> mature on way through here Emptied into vas deferens then passes through the inguinal canal, loops over then down the side of the bladder to the seminal vesicle Seminal vesicle supplies nutrition and most of the ejaculatory fluid and joins with the vas deferens to become the ejaculatory duct which passes through the prostate. Prostate - contracts and provides the alkaline fluid to neutralise vaginal acidity, supplies more of the ejaculatory fluid Sperm then travels through the bulbourethral glands which also provide alkali fluid to counteract urethral acidity and lubrication. Sperm then exits the urethra.

Answer 399

Anterior - corpus cavernosa (does the erection) Posterior - corpus spongiosum (has the urethra and forms the glans) Distal end - glans Foreskin - prepuce

Answer 400

GH is stimulated in response to stress, exercise, malnutrition and anorexia during the day (i.e. in _response to a catabolic state_ - hypoglycacemia, low FFAs and high circulating amino acid concentrations).

Answer 401

B. C, D, E are all potentially catabolic states which will increase circulating growth hormone concentration. At baseline physiology, growth hormone release is highest in sleep stage III and IV (deep sleep). B is the only option

Answer 402

Also known as 'somatotropin'. 'Stress hormone' that stimulates lipolysis, gluconeogenesis and also increases protein synthesis. Normally pulsatile secretion, highest during sleep stages III and IV, lowest in early morning Peaks in teenage years and declines after that, diminished further in heart failure patients. Stimulated by slow wave sleep, ghrelin, the 'hunger' hormone released by the stomach and a catabolic state (hypoglycaemia, stress, exercise).

Answer 403

Stress hormone Hepatic IGF-1 release (growth promoter) Gluconeogenesis Lipolysis --\> FFA release Protein synthesis Increases T4 to T3 deoiodination Cakcium retention and mineralisaton of bone Stimulates internal organ growth Homeostasis

Answer 404

Growth factor released by the liver in response to growh hormone. Responsible for human growth in general, and growth-effects of human growth hormone. Receptor number is regulated by GH and thyroxine.

Answer 405

Somatostatin TRH --\> somatostatin release (which suppresses TSH, in turn, hypothyroidism suppresses somastostatin) B-agonists --\> somatostatin release Exogenous glucocorticoids (at hypothalamus) High circulating FFAs Leptin (released by fat cells when there's lots of fat) Hyperglycaemia

Answer 406

Also known as GHIH - it's an inhibitory system In the anterior pituitary (secreted by hypothalamus): - inhibits GH (opposes GHRH) - inhibits TSH - inhibits prolactin release - always paracrine (not in blood) In the GI system (secreted by stomach, intestine and pancreatic delta cells) - suppresses all the GI hormones (gastrin, CCK, secretin, VIP, GIP, secretin, motilin) - decreases gastric emptying and reduces sm contractions in the intestine - suppresses pancreatic hormone (endocrine and exocrine) release inc insulin and glucagon.

Answer 407

IGF-1 most sensitive, so good screening test. If positive - GH suppression testing following oral glucose load - specific. Failure of suppression = acromegaly) Single GH value NOT useful.

Answer 408

Arthritis and carpal tunnel Myocardial hypertrophy DM due to insulin resistance Hypertension Heart and renal failure Colorectal ca

Answer 409

Hyponatraemia - in true diapetes insipidus, the patients are dehydrated from excessive water loss

Answer 410

Psychogenic: Concentrated urine both before and after desmopressin Central DI: Dilute urine before DDAVP, concentrated after Nephrogenic: Dilute urine before and after DDAVP

Answer 411

Man made vasopressin or ADH with little effect on BP as compared with vasopressin Used to treat central DI (bind renal collecting duct V2 receptors --\> aquoporin channels to apical membrane of duct) Promotes release of vWF (also on V2 receptor) and increases factor VIII survival thanks to this --\> used in VW disease, mild hemophilia A, and thrombocytopaenia. Can also be used with uremic induced platelet dysfunction. Not for haemophilia B or severe haemophilia A.

Answer 412

Primary hyperaldosteronism (also known as Conn’s syndrome): high aldosterone, normal cortisol, low renin Secondary hyperaldosteronism: high aldosterone, normal cortisol, high renin Addison’s disease (also known as adrenal insufficiency): low aldosterone, low cortisol, high renin Cushing’s syndrome: low-normal aldosterone, high cortisol, low renin

Answer 413

Diuretics including spironolactone which raises plasma renin levels, thereby reducing the ratio. Hypokalemia should be corrected before testing as low potassium suppresses aldosterone secretion.

Answer 414

Decreased tissue and hepatic LDL receptors Hyperlipidaemia of LDL origin - even in _subclinical hypothyroidism_

Answer 415

Hypertriglyceridaemia (as well as increase in total chol and LDL) Mainly Ritonavir

Answer 416

High triglycerides Low HDL Increased small dense LDL cholesterol

Answer 417

Elevated small dense LDL Low HDL Increased TGL

Answer 418

Raises TGLs Raises HDL Minimal effect on LDL - not recommended for prevention of coronary disease! ;)

Answer 419

Delayed oesophageal emptying eg stricture, achalasia; (they can cause serious oesophageal erosions) inability to stand, sit upright for greater than or equal to 30 min; hypocalcaemia renal impairment (mainly w/ IV therapy) (Zoledronate) recent uveitis incl bisphosphonate assoc history; pregnancy, lactation

Answer 420

Exogenous and cortisol producing-adrenal adenoma (both are forms of primary hypercortisolism) --\> ACTH suppressed (negative feedback depends on cortisol) Pseudo Cushings - cortisol and ACTH normal Cushing's disease (pituitary dependent) - normal/somewhat elevated (not in hundreds) ACTH (pituitary source) and high cortisol suppressed by high dexamethasone doses (tumour still sensitive somewhat) Ectopic Cushing's syndrome (pituitary independent) - high ACTH as it is ectopic production of ACTH driving the hypercortisolaemia, wouldn't matter if pituitary productions was suppressed - elevated in hundreds. Cortisol not suppressed at all by dex suppression test. Look in adrenals or lungs.

Answer 421

Both: Hypotension / collapse Coma Hypothermia or hyperthermia Hypoglycaemia (unless diabetic!) Low T4 _Adrenal only_ Hyperkalemia and hyponatraemia (these are ok in hypopituitarism because renin is not affected - only production of aldosterone by the adrenals)

Answer 422

Severe lethargy Convulsions Fever Hyperkalemia (elevated potassium level in the blood) Hypercalcemia (elevated calcium level in the blood): the etiology of hypercalcemia is a combination of increased calcium input into the extracellular space and reduced calcium removal by the kidney, this last caused by decreased glomerular filtration and increased tubular calcium reabsorption. Both renal factors are secondary to volume depletion and, in fact, improve rapidly during rehydration with saline infusion.[3] Hypoglycemia (reduced level of blood glucose) Hyponatremia (low sodium level in the blood) Hypotension (low blood pressure) Hypothyroid (low T4 level) Severe vomiting and diarrhea, resulting in dehydration

Answer 423

_Due to inadequate mineralocorticoids:_ vomiting due to salt-wasting leading to dehydration and death _Due to excess androgens:_ functional and average sized penis in cases involving extreme virilization (but no sperm) ambiguous genitalia, in some females, such that it can be initially difficult to identify external genitalia as "male" or "female". early pubic hair and rapid growth in childhood precocious puberty or failure of puberty to occur (sexual infantilism: absent or delayed puberty) excessive facial hair, virilization, and/or menstrual irregularity in adolescence infertility due to anovulation enlarged clitoris and shallow vagina

Answer 424

Approximately three-quarters of patients with PCOS (by the diagnostic criteria of NIH/NICHD 1990) have evidence of hyperandrogenism, with free testosterone being the single most predictive marker with ~60% of patients demonstrating supranormal levels

Answer 425

HCG - peaks in first tri then drops until birth Progesterone and oestrogen climb consistently into third tri.

Answer 426

Excessive ADH secretion and inappropriate water reabsoprtion Caused by: Ectopic - SCLC Drugs - sulfonylurea Lesion of baroreceptor pathway

Answer 427

Water retention and increased ANP leading to euvolaemic hyponatraemia Urine osmolarity greater than plasma osmolarity Elevated urinary sodium

Answer 428

ADH activity effectively dilutes the blood (decreasing the concentrations of solutes such as sodium), causing hyponatremia; this is compounded by the fact the body responds to water retention by decreasing aldosterone, thus allowing even more sodium wasting. For this reason, a high urinary sodium excretion will be seen.

Answer 429

Diuretics Diarrhoea Vomiting

Answer 430

SIADH - brain, lung ca, pain, psych meds Pseudo SIADH - hypothyroidism, hypoaldosteronism Thiazides Characterised by high urine osmolality

Answer 431

CHF Cirrhosis

Answer 432

Essential hypertension tends to have no electrolyte derangement, can have a bruit. Hyperaldosteronism seen in Conn's and renal artery stenosis will predispose to hypokalemia and alkalosis Phaeo tends to present young to mid age and can be paroxysmal with tachycardias.

Answer 433

When it's over 4cm or there's evidence of hormonal overactivation

Answer 434

ACEIs In renal artery stenosis, the afferent pressure is reduced by the narrowed vessel, hence autoregulation is almost exclusively dependent on changes in post-glomerular arteriolar tone. Because ACE inhibitors interfere with the production of angiotensin II, autoregulation is impaired, glomerular perfusion falls, renal ischaemic nephropathy develops and renal failure ensues. Angiotensin II forms part of the renal autoregulation of glomerular perfusion mechanism. The preglomerular arteriolar tone is reduced when renal perfusion falls, increasing glomerular blood flow and maintaining glomerular filtration. If this response is inadequate, renin is released, activating the RAAS cascade, leading to angiotensin II mediated constriction of the post-glomerular arteriole. Pressure within the glomerulus is therefore increased and filtration restored.

Answer 435

• Suspected white-coat hypertension (including in pregnancy) • Suspected masked hypertension (untreated subject with normal clinic BP and elevated ABP) * Suspected nocturnal hypertension or no night time reduction in BP (dipping) * Hypertension despite appropriate treatment * Patients with a high risk of future cardiovascular events (even if clinic BP is normal) * Suspected episodic hypertension. Ambulatory BP monitoring may also be useful for: * titrating antihypertensive therapy * borderline hypertension * hypertension detected early in pregnancy * suspected or confirmed sleep apnoea * syncope or other symptoms suggesting orthostatic hypotension, where this cannot be demonstrated in the clinic.

Answer 436

The common tumours secrete growth hormone (15%), prolactin (30%), ACTH (15%), gonatroophic (10% - asymptomatic) mixed secretions or no secretion at all.

Answer 437

Hypopituitarism

Answer 438

The aim of the basal aspect of insulin administration is to provide a constant level of insulin between meals without increasing the risk of hypoglycaemia, _particularly at night_ (nocturnal hypoglycaemia).

Answer 439

NPH activity peaks 3–5 hours after administration; its duration of action is only 14 ± 3 hours and hence it has to be injected twice daily. With NPH administered at bedtime, peak insulin activity is reached while the glucose levels are low, which increases the risk of nocturnal hypoglycaemia. Nocturnal hypoglycaemia is accepted to be an important barrier to the achievement of optimal glucose control, as users tend to lower the insulin dose to prevent hypoglycaemia.

Answer 440

The normal 24-hour urine osmolality is, on average, 500-800 mOsm/kg of water. Random urine osmolality should average 300-900 mOsm/kg of water. After 12-14 hours of fluid intake restriction, the urine osmolality should exceed 850 mOsm/kg of water.

Answer 441

The reference range for urine sodium is 40-220 mEq/L/24 hours

Answer 442

Diabetes insipidus Excess fluid intake Acute renal insufficiency Glomerulonephritis

Answer 443

Dehydration Syndrome Inappropriate ADH secretion (SIADH) Adrenal insufficiency Glycosuria Hypernatremia High protein diet

Answer 444

Insulinoma --\> high c-peptide and high fasting insulin Exogenous --\> high fasting insulin, low c-peptide

Answer 445

the A cells (20%) secrete glucagon, the B cells (70%) secrete insulin the D cells (5%) secrete somatostatin or gastrin. F cells secrete "pancreatic polypeptide."

Answer 446

Insulinomas are usually benign (about 90%) and secrete excessive amounts of insulin that causes hypoglyce- mia. Insulinomas also produce proinsulin and C-peptide. Insulinomas are solitary in 95% of sporadic cases but are multiple in about 90% of cases arising in MEN 1.

Answer 447

Gastrinomas secrete excessive quantities of the hor- mone gastrin (as well as "big" gastrin), which stimulates the stomach to hypersecrete acid, thereby causing hyper- plastic gastric rugae and peptic ulceration (Zollinger– Ellison syndrome). About 50% of gastrinomas are malignant and metastasize to the liver. Gastrinomas are typically found in the duodenum (49%), pancreas (24%), or lymph nodes (11%). Sporadic Zollinger–Ellison syn- drome is rarely suspected at the onset of symptoms; typi- cally, there is a 5-year delay in diagnosis. About 22% of patients have MEN 1. In patients with MEN 1, gastrinomas usually present at a younger age; hyperparathyroidism may occur from 14 years preceding the Zollinger–Ellison diag- nosis to 38 years afterward.

Answer 448

Carcinoid pancreatic neuroendocrine tumors secrete serotonin and can produce an atypical carcinoid syndrome manifested by pain, diarrhea, and weight loss; skin flushing occurs in 39% of patients. typi- cally indolent but usually metastasize to local and distant sites, particularly to other endocrine organs.

Answer 449

VIPomas are rare pancreatic neuroendocrine tumors that produce vasoactive intestinal polypeptide (VIP), a substance that causes profuse watery diarrhea and pro- found hypokalemia (Verner-Morrison syndrome).

Answer 450

MEn 1: tumors of the parathyroid glands, endocrine pancreas and duodenum, pituitary, adrenal, thyroid; lipomas and facial angiofibromas. MEn 2a: medullary thyroid cancers, pheochromo- cytomas, Hirschsprung disease. MEn 2B: medullary thyroid cancers, pheochromo- cytomas, Marfan-like habitus, mucosal neuromas, intestinal ganglioneuroma, delayed puberty.

Answer 451

Smooth muscle relaxation (LES, stomach, GB) Stimulates water and electrolyte secretion into pancreatic juice and bile Inhibits gastric acid secretion and absorption Stimulats enteric smooth muscle contraction Overall --\> increased motility Stimulates pepsinogen secretion by chief cells

Answer 452

During the hyperthyroid phase, iodine uptake is suppressed, while during the hypothyroid phase, uptake is increased. This situation contrasts greatly with the elevated iodine uptake found in patients with Graves' disease

Answer 453

Diabetic neuropathy

Answer 454

Diabetic autonomic neuropathy manifests first in longer nerves. The vagus nerve (the longest of the ANS nerves) accounts for ~75% of all parasympathetic activity; as such, even early affects of diabetic autonomic neuropathy are widespread.

Answer 455

a) there may be autonomic neuropathy Since epinephrine release is a function of the autonomic nervous system, the presence of autonomic neuropathy (i.e., a damaged autonomic nervous system) will cause the epinephrine release in response to hypoglycemia to be lost or blunted. b) the brain may have become desensitized to hypoglycemia. If a person has frequent episodes of hypoglycemia (even mild ones), the brain becomes "used to" the low glucose and no longer signals for epinephrine to be released during such times. More specifically, there are glucose transporters located in the brain cells (neurons). These transporters increase in number in response to repeated hypoglycemia (this permits the brain to receive a steady supply of glucose even during hypoglycemia). As a result, what was once the hypoglycemic threshold for the brain to signal epinephrine release becomes lower. Epinephrine is not released, if at all, until the blood glucose level has dropped to even lower levels. Clinically, the result is hypoglycemic unawareness. c) the person may be using medicines which mask the hypoglycemic symptoms - i.e. beta blockers

Answer 456

\>1cm is a concerning feature Start with a serum TSH - if it is a hyperfunctioning nodule it is less likely to be malignant so if TSH is suppressed and it's hot on imaging, less need to worry. If TSH is normal, then an ultrasound to see if it's cystic or has other concerning features should be considered.

Answer 457

When hypogammaglobulinemia is observed without a coincident paraprotein in the serum, the MLT should investigate the cause of hypogammaglobulinemia. If there is no known cause (immune disorder, chemotherapy, etc) for the patient's lack of antibody production, the lab should request the collection of a urine sample. It is possible that the patient has an overproduction of free light chains that is reducing the production of normal antibodies. The free light chains may be filtering through the kidneys and therefore, only observed in the patient's urine. The presence of free light chains is a clinically significant finding.

Answer 458

It is widely used (though off-label in many countries) in the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) when fluid restriction alone has been ineffective.[3] Physiologically, this works by reducing the responsiveness of the collecting tubule cells to ADH.

Answer 459

Dopamine agonist - usually bromocriptine or cabergoline (however long T1/2, may cause difficulties if low BP as hypotension is an SE) Dopamine antagonises prolactin and shrinks the tumor in 80% of cases. Surgery if refractory

Answer 460

The symptoms due to a prolactinoma are broadly divided into those that are caused by increased prolactin levels or mass effect. Those that are caused by increased prolactin levels are:[3] Amenorrhea Galactorrhea (infrequent in men) Loss of axillary and pubic hair Hypogonadism, gynecomastia, erectile dysfunction (in males) Those that are caused by mass effect are: Bitemporal hemianopsia (due to pressure on optic chiasm) Vertigo Nausea, vomiting

Answer 461

Renovascular hypertension

Answer 462

Over 99% of people affected by coeliac disease have the HLA DQ2, HLA DQ8, or parts of these genes. Therefore, a negative test for these genes effectively rules out coeliac disease. The gene test on its own cannot diagnose coeliac disease – only 1 in 30 people who have HLA DQ2 or HLA DQ8 will develop coeliac disease. A gluten free diet should only be started after confirmation of coeliac disease by small bowel biopsy.

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