endocrine Flashcards

Question

what is grave's disease

Answer 1

Thyroid-stimulating immunoglobulins recognize and bind to the thyrotropin receptor (TSH receptor). It mimics the TSH to that receptor and activates the secretion of thyroxine (T4) and triiodothyronine (T3), and the actual TSH level will decrease in the blood plasma. The TSH levels fall because the hypothalamus-pituitary-thyroid negative feedback loop is working. The result is very high levels of circulating thyroid hormones and the negative feedback regulation will not work for the thyroid gland

Answer 2

``` grave's disease Toxic Multinodular Goitre = Plummer’s Disease Toxic Adenoma Thyrotoxic Phase of Thyroiditis Drugs ```

Answer 3

Toxic Multinodular Goitre = Plummer’s Disease Autonomous nodule develops on background multinodular goitre. Elderly and iodine-deficient areas Iodine scan shows hot nodules Anti-thyroid drugs Total or subtotal thyroidectomy.

Answer 4

Toxic Multinodular Goitre = Plummer’s Disease Autonomous nodule develops on background multinodular goitre. Elderly and iodine-deficient areas Iodine scan shows hot nodules

Answer 5

Toxic Adenoma Solitary hot nodule ± producing T3/T4 Most nodules are non-functional

Answer 6

Follicular adenoma Single thyroid nodule ± thyrotoxicosis (majority are cold) May get pressure symptoms benign, well circumscribed Hemithyroidectomy

Answer 7

Thyrotoxic Phase of Thyroiditis: Hashimoto’s de Quervain’s Subacute lymphocytic

Answer 8

Rx Medical Symptomatic: beta-B (e.g. propranolol 40mg/6h) - assess fluids and NG tube. bloods - t3, t4, culture if suspected infection. - hydrocortisone or dexamethasone to prevent peripheral conversion of T4 to T3. deca 4mg/8hr/ Anti-thyroid: carbimazole (inhibits TPO) Titrate according to TFTs or block and replace In Graves’ Rx for 12-18mo then withdraw ~50% relapse so then surgery or radioiodine SE: agranulocytosis Radiological: Radio-iodine Most become hypothyroid CI: pregnancy, lactation Surgical: Thyroidectomy Recurrent laryngeal N. damage causes hoarseness Hypoparathyroidism Hypothyroidism

Answer 9

Thyroid storm or thyrotoxic crisis is a rare but severe and potentially life-threatening complication of hyperthyroidism

Answer 10

``` Features raised temp Agitation, confusion, coma Tachycardia, AF Acute abdomen Heart failure ``` ``` Precipitants Recent thyroid surgery or radio-iodine Infection MI Trauma ```

Answer 11

Rx 1. Fluid resuscitation + NGT 2. Bloods: TFTs + cultures if infection suspected 3. Propranolol PO/IV 4. Digoxin may be needed 5. Carbimazole then Lugol’s Iodine 4h later to inhibit thyroid 6. Hydrocortisone 7. Rx cause

Answer 12

``` Symptoms: Lethargy Cold intolerance low appetite but increased wt. Constipation Menorrhagia low mood ``` ``` Signs: Cold hands Bradycardic Slow-relaxing reflexes Dry hair and skin Puffy face Goitre Myopathy, neuropathy Ascites Myxoedema - SC tissue swelling in severe hypothyroidism - Typically around eyes and dorsum of hand ```

Answer 13

``` Causes Primary Atrophic thyroiditis (commonest UK) Hashimoto’s thyroiditis Subacute thyroiditis (e.g. post-partum) Post De Quervain’s thyroiditis Iodine deficiency (commonest worldwide) ``` Drugs: carbimazole, amiodarone, lithium Congenital: thyroid agenesis Post-surgical Thyroidectomy Radioiodine Secondary Hypopituitarism (v. rare cause)

Answer 14

Atrophic Thyroiditis Thyroid antibodies +ve: anti-TPO, anti-TSH Lymphocytic infiltrate causes atrophy (no goitre) Associations Pernicious anaemia Vitiligo Endocrinopathies

Answer 15

Hashimoto’s Thyoiditis Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is attacked by a variety of cell- and antibody-mediated immune processes, causing primary hypothyroidism. It was the first disease to be recognized as an autoimmune disease. TPO +ve (an antibody vs thyroid peroxidase) Atrophy + regeneration causes goitre May go through initial thyrotoxicosis phase May be euthyroid or hypothyoid

Answer 16

``` Ix up TSH, down T3/T4 up MCV ± normochromic anaemia up triglyceride + up cholesterol Hyponatraemia (SIADH) up CK if assoc. myopathy Abs: TPO, TSH ```

Answer 17

Rx Levothyroxine Titrate to normalise TSH Enzyme inducers raise thyroxine metabolism Clinical improvement takes ~2wks Check for other AI disease: e.g. Addison’s, PA Key points initial starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease. The BNF recommends that for patients with cardiac disease, severe hypothyroidism or patients over 50 years the initial starting dose should be 25mcg od with dose slowly titrated. Other patients should be started on a dose of 50-100mcg od following a change in thyroxine dose thyroid function tests should be checked after 8-12 weeks the therapeutic goal is 'normalisation' of the thyroid stimulating hormone (TSH) level. As the majority of unaffected people have a TSH value 0.5-2.5 mU/l it is now thought preferable to aim for a TSH in this range women with established hypothyroidism who become pregnant should have their dose increased 'by at least 25-50 micrograms levothyroxine'* due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value there is no evidence to support combination therapy with levothyroxine and liothyronine ``` Side-effects of thyroxine therapy hyperthyroidism: due to over treatment reduced bone mineral density worsening of angina atrial fibrillation ``` Interactions iron: absorption of levothyroxine reduced, give at least 2 hours apart

Answer 18

Myxoedema coma is the extreme manifestation of (usually untreated) hypothyroidism. It is one of a relatively small number of endocrine emergencies, and it is a rare, but potentially fatal disorder. ``` Features Looks hypothyroid Hypothermia Hypoglycaemia Heart failure: bradycardia and low BP Coma and seizures ``` ``` Precipitants Radioiodine Thyroidectomy Pituitary surgery Infection, trauma, MI, stroke ``` Mx get them on ICU Bloods: TFTs, FBC, U+E, glucose, cortisol Correct any hypoglycaemia T3/T4 IV slowly (may ppt. myocardial ischaemia) Hydrocortisone 100mg IV Rx hypothermia and heart failure - may need fluid and inotropes.

Answer 19

``` Simple goitre Multinodular goitre Plummer’s/Toxic multinodular goitre Graves’ Hashimoto’s thyroiditis de Quervain’s Subacute lymphocytic Riedel’s thyoiditis Follicular adenoma Thyroid cysts ```

Answer 20

Thyroid cysts Solitary thyroid nodule Asympto or pressure symptoms Can lead to localised pain due to cyst bleed Aspiration or excision

Answer 21

Follicular adenoma Single thyroid nodule ± thyrotoxicosis (majority are cold) May get pressure symptoms Hemithyroidectomy

Answer 22

Riedel’s thyoiditis Hard fixed thyroid mass Mass effects Assoc. c¯ retroperitoneal fibrosis Autoimmune fibrosis Conservative rx

Answer 23

Early | Reactionary haemorrhage causes haematoma (

Answer 24

Subacute lymphocytic Diffuse painless goitre May occur post-partum Thyrotoxicosis then hypo then eu Autoimmune Self-limiting

Answer 25

Subacute thyroiditis (also known as De Quervain's thyroiditis) is thought to occur following viral infection and typically presents with hyperthyroidism ``` Diffuse painful goitre Preceding viral URTI common Thyrotoxicosis then hypo then eu decrease iodine uptake raised ESR ``` Viral: Coxsackie common Autoimmune Management usually self-limiting - most patients do not require treatment thyroid pain may respond to aspirin or other NSAIDs in more severe cases steroids are used, particularly if hypothyroidism develops

Answer 26

``` Diffuse painless goitre Mass effects: - dysphagia - stridor - SVC obstruction ``` Usually euthyroid, may then go to hypothyroid Endemic - iodine deficiency Sporadic - autoimmune - goitrogens (e.g. sulphonylureas) - hereditary (dyshormogenic) Thyroxine Total or subtotal thyroidectomy if pressure symptoms.

Answer 27

Multinodular goitre Evolves from long-standing simple goitre. Mass effects. Euthyroid (or subclinical hyperthyroid) causes same as for simple goitre: Endemic - iodine deficiency Sporadic - autoimmune - goitrogens (e.g. sulphonylureas) - hereditary (dyshormogenic) management: Thyroxine Total or subtotal thyroidectomy if pressure symptoms.

Answer 28

``` carcinomas: Papillary Follicular Medullary Anaplastic Lymphoma ```

Answer 29

Early: | Reactionary haemorrhage leads to haematoma (

Answer 30

``` Papillary = 80% Follicular = 10% Medullary= 5% Anaplastic = Rare, awful prognosis. Lymphoma = 5% ```

Answer 31

Early: | Reactionary haemorrhage leads to haematoma (

Answer 32

In exams primary hyperparathyroidism is stereotypically seen in elderly females with an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level. It is most commonly due to a solitary adenoma Primary Hyperparathyroidism ``` Causes of primary hyperparathyroidism 80%: solitary adenoma 15%: hyperplasia 4%: multiple adenoma 1%: carcinoma ``` Investigations raised calcium, low phosphate PTH may be raised or normal technetium-MIBI subtraction scan Bilateral hand radiographs in a middle-aged woman demonstrating generalised osteopenia, erosion of the terminal phalyngeal tufts (acro-osteolysis) and sub-periosteal resorption of bone particularly the radial aspects of the 2nd and 3rd middle phalanges. These changes are consistent with a diagnosis of hyperparathyroidism. Treatment total parathyroidectomy

Answer 33

Physiology PTH secreted in response to decreased Ca2+ increased osteoclast activity increased Ca2+ and decreased PO4 reabsorption in kidney increased 1alpha-hydroxylation of 25OH-Vit D3

Answer 34

Presentation: raised Ca2+ Stones Renal stones Polyuria and polydipsia (nephrogenic DI) Nephrocalcinosis Bones Bone pain Pathological #s Moans: depression ``` Groans Abdo pain n/v and constipation Pancreatitis PUD (increased gastrin secretion) ``` ``` Other: raised BP (check Ca2+ in all with HTN) ```

Answer 35

Primary Hyperparathyroidism Causes Solitary adenoma: 80% Hyperplasia: 20% Pathyroid Ca:

Answer 36

Secondary Hyperparathyroidism Causes Vitamin D deficiency Chronic renal failure Ix up PTH, down Ca, up PO4, up ALP, down vit D Rx Correct causes Phosphate binders With Ca: calcichew W/o Ca: sevelamer, lanthanum Vit D: calcitriol (active), cholecalciferol (innactive) Cinacalcet: up parathyroid Ca-sensitivity

Answer 37

Tertiary Hyperparathyroidism Prolonged secondary HPT causes autonomous PTH secretion up Ca2+, up PTH, down PO4, upALP

Answer 38

down PTH due to gland failure

Answer 39

Presentation: down Ca causes SPASMODIC Spasms (carpopedal = Trousseau’s sign) Perioral paraesthesia Anxious, irritable Seizures Muscle tone increase causes colic, wheeze, dysphagia Orientation impaired (confusion) Dermatitis Impetigo herpetiformis (decreased Ca + pustules in pregnancy) Chovsteks, cardiomyopathy (increased QTc causes TdP

Answer 40

Causes Autoimmune ``` Congenital: DiGeorge Cardiac abnormality: Fallot’s Abnormal facies Thymic aplasia Cleft palate Hypocalcaemia Chr 22 ``` Iatrogenic Surgery Radiation

Answer 41

Ix decreased Ca, increased PO4, decreased PTH, normal ALP Rx Ca supplements Calcitriol

Answer 42

``` Pseudohypoparathyroidism Failure of target organ response to PTH Symptoms of hypocalcaemia Short 4th and 5th metacarpals, short stature Ix: decrease Ca, raised PTH Rx: Ca + calcitriol ```

Answer 43

``` Pseudopseudohypoparathyroidism Normal (maternal) receptor in kidney causes normal biochem ``` Abnormal (paternal) receptors in body causes pseudohypoparathyroidsm phenotype

Answer 44

Clinical state produced by chronic glucocorticoid excess Features weight gain might be presentation. ``` Catabolic Effects Proximal myopathy Striae Bruising Osteoporosis ``` Glucocorticoid Effects DM Obesity poor healing Mineralocorticoid Effects HTN Hypokalaemia ``` Appearance Moon face Acne and hirsutism Interscapular and supraclavicular fat pads Centripetal obesity Striae Thin limbs Bruising Thin skin ```

Answer 45

Primary Hyperaldosteronism Excess aldosterone, independent of RAS ``` Features Hypokalaemia: weakness, hypotonia, hyporeflexia, cramps Paraesthesia raised BP alkalosis ``` Causes Bilateral adrenal hyperplasia (70%) Adrenocortical adenoma (30%): Conn’s syndrome Ix U+E: Care c¯ diuretics, hypotensives, laxatives, steroids Aldosterone:renin ratio: up c¯ primary ECG: flat / inverted T waves, U waves, depressed ST segments, prolonged PR and QT intervals Adrenal CT/MRI Rx (adrenal adenoma) Conn’s: laparoscopic adrenelectomy bilateral adrenocortical hyperplasia: aldosterone antagonist: spironolactone, eplerenone or amiloride

Answer 46

ACTH-Independent dexameth test causes drop in ACTH due to –ve FB but no suppression c¯ any dose of dex. serum ACTH might be very low on drum test due to the negative feedback loop. Causes Iatrogenic steroids: commonest cause Adrenal adenoma / Ca: carcinoma often causes virilisation Adrenal nodular hyperplasia Carney complex: LAME Syndrome McCune-Albright

Answer 47

ACTH-Dependent high cortisol due to increased ACTH. Causes Cushing’s disease: Bilat adrenal hyperplasia from ACTH-secreting pituitary tumour (basophilic microadenoma) Cortisol suppression c¯ high-dose dex test, or may cause no suppression at all. ``` Ectopic-ACTH: SCLC Carcinoid tumour Skin pigmentation, metabolic alkalosis, wt. loss, hyperglycaemia No suppression c¯ any dose of dex ```

Answer 48

``` Ix 1st: 24h urinary free cortisol Late night serum or salivary cortisol Highest @ AM, lowest @ midnight Dexamethasone suppression tests ACTH (but ACTH degrades v. quick after venepuncture) Localisation: CT, MRI DEXA scan ``` The two most commonly used tests are: overnight dexamethasone suppression test (most sensitive) - dexamethasone 1mg PO at midnight, measure serum cortisol at 8am. should be suppressed, no suppression in cushion's syndrome. 24 hr urinary free cortisol is an alternative. Rx: Treat Causes Cushing’s disease: trans-sphenoidal excision Adrenal adenoma / Ca: adrenelectomy Ectopic ACTH: tumour excision, metyrapone (inhibits cortisol synthesis)

Answer 49

Primary Hyperaldosteronism Excess aldosterone, independent of RAS Features Hypokalaemia: weakness, hypotonia, hyporeflexia, cramps Paraesthesia raised BP Causes Bilateral adrenal hyperplasia (70%) Adrenocortical adenoma (30%): Conn’s syndrome Ix U+E: up/normal Na, down K, alkalosis Care c¯ diuretics, hypotensives, laxatives, steroids Aldosterone:renin ratio: up c¯ primary ECG: flat / inverted T waves, U waves, depressed ST segments, prolonged PR and QT intervals Adrenal CT/MRI Rx Conn’s: laparoscopic adrenelectomy Hyperplasia: spironolactone, eplerenone or amiloride

Answer 50

Secondary Hyperaldosteronism Due to increased renin from low renal perfusion ``` Causes RAS Diuretics CCF Hepatic failure Nephrotic syndrome ``` Ix Aldosterone:renin ratio: normal Secondary hyperaldosteronism - adrenal response to increased levels of reninangiotensin – Causes • Renal ischaemia • Chronic oedema (Nephrotic syndrome, ascites)

Answer 51

Bartter’s Syndrome Autosommal recesive Blockage of NaCl reabsorption in loop of Henle (as if taking frusemide) Congenital salt wasting causes RAS activation which causes hypokalaemia and metabolic alkalosis Normal BP

Answer 52

In a patient with suspected Addison's disease the definite investigation is a ACTH stimulation test (short Synacthen test). Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated ``` Associated electrolyte abnormalities hyperkalaemia hyponatraemia hypoglycaemia metabolic acidosis ``` ``` Other 21-hydroxylase Abs: +ve in 80% of AI disease Plasma renin and aldosterone CXR: evidence of TB AXR: adrenal calcification ``` Rx Replace Hydrocortisone Fludrocortisone Advice Don’t stop steroids suddenly increase steroids during intercurrent illness, injury Wear a medic-alert bracelet F/up Watch for autoimmune disease

Answer 53

Primary Adrenal Insufficiency: Addison’s Destruction of adrenal cortex causes glucocorticoid and mineralocorticoid deficiency ``` Causes Autoimmune destruction: 80% in the UK TB: commonest worldwide Metastasis: lung, breast, kidneys Haemorrhage: Waterhouse-Friedrichson Congenital: CAH ``` ``` Symptoms Wt. loss + anorexia n/v, abdo pain, diarrhoea/constipation Lethargy, depression Hyperpigmentation: buccal mucosa, palmer creases Postural hypotension causes dizziness, faints Hypoglycaemia Vitiligo Addisonian crisis ```

Answer 54

``` Ix Bloods down Na/up K down glucose down Ca Anaemia ``` Differential Short synACTHen test Cortisol before and after tetracosactide Exclude Addison’s if raised cortisol raised 9am ACTH (usually low) ``` Other 21-hydroxylase Abs: +ve in 80% of AI disease Plasma renin and aldosterone CXR: evidence of TB AXR: adrenal calcification ``` Rx Replace Hydrocortisone Fludrocortisone Advice Don’t stop steroids suddenly increase steroids during intercurrent illness, injury Wear a medic-alert bracelet F/up Watch for autoimmune disease

Answer 55

Secondary Adrenal Insufficiency i.e. hypothalamo or pituitary failure Causes Chronic steroid use causes suppression of HPA axis Pituitary apoplexy / Sheehan’s Pituitary microadenoma Features Normal mineralocorticoid production No pigmentation (ACTH down)

Answer 56

Addisonian Crisis Presentation Shocked: increase HR, postural drop, oliguria, confused Hypoglycaemia Usually known Addisonian or chronic steroid user Precipitants Trauma Surgery Stopping long-term steroids sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison's, Hypopituitarism) adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia) Mx Bloods: cortisol, ACTH, U+E, cultures Check CBG: glucose may be needed Hydrocortisone 100mg IV 6hrly, continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action (ask an expert though), oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days. 1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic Septic screen Treat underlying cause

Answer 57

Pathology Catecholamine-producing tumours arising from sympathetic paraganglia Usually found in adrenal medulla Extra-adrenal phaeo’s found by aortic bifurcation ``` Rule of 10s 10% malignant 10% extra-adrenal 10% bilateral 10% part of hereditary syndromes ``` ``` Associations 10% part of herediatary syndromes MEN2a and 2b Neurofibrimatosis Von Hippel-Lindau: RCC + cerebellar signs ```

Answer 58

Presentation Triad: episodic headache, sweating and tachycardia many stimuli, even abdo palpation can cause acute hypertensive crises. ``` Other adrenergic features: increase BP, palpitations Headache, tremor, dizziness Anxiety d/v, abdo pain Heat intolerance, flushes ``` May have precipitant Straining, abdo palpation Exercise, stress beta-B, IV contrast, TCAs, GA

Answer 59

get help and take to ICU ``` Ix Plasma + urine metadrenaline Also vanillylmandelic acid Abdo CT/MRI MIBG (mete-iodobenzylguanidine) scan ``` Rx Medical If malignant Chemo or radiolabelled MIGB Surgery: adrenelectomy alpha-blocker first, then beta-blockade pre-op, Avoids unopposed alpha-adrenergic stimulation which can worsen hypertension. first = short acting = phentolamine 2-5mg IV then: Phenoxybenzamine = alpha-blocker longer acting. increase the dose until BP is controlled. beta 1 blocker to control tachyarrhy. Monitor BP post-op for massive drop in BP. surgery is done electively after 4 weeks to allow full effect of alpha blockade and volume expansion.

Answer 60

``` Features Pallor Pulsating headache Feeling of impending doom massive rise in BP increase ST and cardiogenic shock ``` Rx Phentolamine 2-5mg IV (alpha-blocker) or labetalol 50mg IV Repeat to safe BP (e.g. 110 diastolic) Phenoxybenzaime 10mg/d PO when BP controlled Elective surgery after 4-6wks to allow full alpha-blockade and volume expansion

Answer 61

Multiple Endocrine Neoplasia Definition Functioning hormone tumours in multiple organs All autosomal dominant MEN1 Pituitary adenoma: prolactin or GH Parathyroid adenoma / hyperplasia Pancreatic tumours: gastrinoma or insulinoma ``` MEN2 Thyroid medullary carcinoma Adrenal phaeochromocytoma A) Hyperthyroidism B) Marfanoid habitus ```

Answer 62

Carney Complex / LAME Syndrome ``` LAME S: Lentigenes: spotty skin pigmentation - Differential: Peutz-Jehgers Atrial Myxoma Endocrine tumours: pituitary, adrenal hyperplasia Schwannomas ``` Carney complex and its subsets LAMB syndrome[1] and NAME syndrome[1] are autosomal dominant conditions comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity.[2][3] It is distinct from Carney's triad. Approximately 7% of all cardiac myxomas are associated with Carney complex.

Answer 63

Peutz-Jeghers Mucocutaneous freckles on lips, oral mucosa and palms /soles GI hamartomas: obstruction, bleeds Pancreatic endocrine tumours increase risk of cancer: CRC, pancreas, liver, lungs, breast Peutz-Jeghers syndrome, also known as hereditary intestinal polyposis syndrome, is an autosomal dominant genetic disease characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa (melanosis)

Answer 64

``` Von Hippel-Lindau disease Renal cysts Bilateral renal cell carcinoma Haemangioblastomas Often in cerebellum leads to cerebellar signs Phaeochromocytoma Pancreatic endocrine tumours ``` Von Hippel–Lindau disease (VHL) disease results from a mutation in the von Hippel–Lindau tumor suppressor gene on chromosome 3p25.3

Answer 65

Autoimmune Polyendocrine Syndromes ``` Type 1 Autosomal recessive Addison’s Candidiasis Hypoparathyroidism ``` Type 2: Schmidt’s Syndrome Polygenic Addison’s Thyroid disease: hypothyroidism or Graves’ T1DM In medicine, autoimmune polyendocrine syndromes, also called polyglandular autoimmune syndrome (PGAS),[1] are a heterogeneous group[2] of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. There are three "autoimmune polyendocrine syndromes", and a number of other diseases which have endocrine autoimmunity as one of their features.

Answer 66

``` Causes Hypothalamic: Kallmann’s (anosmia + GnRH deficiency) Tumour Inflam, infection, ischaemia ``` Pituitary Stalk: Trauma Surgery Tumour (e.g. craniopharyngioma) ``` Pituitary: Irradiation Tumour Ischaemia: apoplexy, Sheehan’s Infiltration: HH, amyloid ``` Commonest causes of panhypopituitarism: Surgery Tumour Irradiation Features Hormone Deficiency: GH: central obesity, atherosclerosis, decrease CO, strength LH/FSH: M: decrease libido, ED, decrease hair F: decrease libido, amenorrhoea, breast atrophy TSH: hypothyroidism ACTH: secondary adrenal failure Cause Mass effects Other hormones: e.g. prolactin excess

Answer 67

``` Symptoms Polyuria Polydipsia Dehydration Hypernatraemia: lethargy, thirst, confusion, coma ``` ``` Causes Cranial Idiopathic: 50% Congenital: DIDMOAD / Wolfram Syndrome Tumours Trauma Vascular: haemorrhage (Sheehan’s syn.) Infection: meningoencephalitis Infiltration: sarcoidosis ``` ``` Nephrogenic Congenital Metabolic: decrease K, increase Ca Drugs: Li, demecleocycline, vaptans Post-obstructive uropathy ``` Diabetes insipidus (ADH deficiency) is caused by destructive lesions of the posterior pituitary which may also affect the anterior pituitary (neoplasms, trauma, surgery). Inappropriate ADH secretion occurs usually as a result of ectopic secretion of ADH by a lung neoplasm.

Answer 68

Prolactin is secreted by the anterior pituitary gland with release being controlled by a wide variety of physiological factors. Dopamine acts as the primary prolactin releasing inhibitory factor and hence dopamine agonists such as bromocriptine may be used to control galactorrhoea. It is important to differentiate the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia Causes Excess pituitary production Pregnancy, breastfeeding Prolactinoma (PRL >5000) primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release) Disinhibition by compression of pituitary stalk Pituitary adenoma Craniopharyngioma Dopamine antagonsists (commonest cause) Antiemetics: metoclopramide, domperidone Antipsychotics: risperidone, haldol Features of excess prolactin men: impotence, loss of libido, galactorrhoea women: amenorrhoea, galactorrhoea

Answer 69

Ix Basal hormone tests = TFTs, ACTH, glucose, pit fossa ct/mri Dynamic pituitary function test Insulin causes increase cortisol + increase in GH GnRH causes increase in LH/FSH TRH causes increase in T4 + increase in PRL MRI brain Rx waiting for lab confirmation can be fatal if in coma. hydrocortisone 100mg/6hr IV. liothyronine. Hormone replacement Treat underlying cause

Answer 70

Classification Size Microadenoma: 1cm Pathology Many are non-secretory ~50% produce PRL Others produce GH or ACTH Features Mass Effects Headache Visual field defect: bitemporal hemianopia CN palsies: 3, 4, 5, 6 (pressure on cavernous sinus) Diabetes insipidus CSF rhinorrhoea Hormone Effects PRL causes galactorrhoea, decreased libido, amenorrhoea, ED increase PRL causes decrease GnRH causes decrease LH/FSH GH causes acromegaly ACTH causes Cushing’s Disease

Answer 71

``` Ix MRI Visual field tests Hormones: PRL, IGF, ACTH, cortisol, TFTs, LF/FSH Suppression tests ``` Rx Medical Replace hormones Treat hormone excess Surgical: Trans-sphenoidal excision Pre-op hydrocortisone Post-op dynamic pituitary tests Radiotherapy: sterotactic

Answer 72

Pituitary Apoplexy Rapid pituitary enlargement due to bleed into a tumour Mass effects Headache, meningism, decrease GCS Bitemporal hemianopia Cardiovascular collapse due to acute hypopituitarism Rx: urgent hydrocortisone 100mg IV

Answer 73

Growth hormone (GH) levels vary during the day and are therefore not diagnostic. The definitive test is the oral glucose tolerance (OGTT) with serial GH measurements. Serum IGF-1 may also be used as a screening test and is sometimes used to monitor disease Oral glucose tolerance test in normal patients GH is suppressed to less than 2 mu/L with hyperglycaemia in acromegaly there is no suppression of GH may also demonstrate impaired glucose tolerance which is associated with acromegaly A pituitary MRI may demonstrate a pituitary tumour

Answer 74

``` Craniopharyngeoma: Originates from Rathke’s pouch Commonest childhood intracranial tumour causes growth failure Calcification seen on CT/MRI ``` Craniopharyngioma is a type of brain tumor derived from pituitary gland embryonic tissue,[1] that occurs most commonly in children but also in men and women in their 50s and 60s.[2] Patients may present with bitemporal inferior quadrantanopia leading to bitemporal hemianopia, as the tumor may compress the optic chiasm.

Answer 75

``` Causes Excess pituitary production Pregnancy, breastfeeding Prolactinoma (PRL >5000) Hypothyroidism (increaseTRH) Disinhibition by compression of pituitary stalk Pituitary adenoma Craniopharyngioma Dopamine antagonsists (commonest cause) Antiemetics: metoclopramide Antipsychotics: risperidone, haldol ``` ``` Symptoms Amenorrhoea Infertility Galactorrhoea decrease libido ED Mass effects from prolactinoma ```

Answer 76

Ix Basal PRL: >5000 = prolactinoma Pregnancy test, TFTs MRI Rx 1st line: Cabergoline or bromocroptine Da agonist decrease PRL secretion and decrease tumour size SE: nausea, postural hypotension, fibrosis (lung and heart) 2nd line: Trans-sphenoidal excision If visual or pressure symptoms don’t response to medical Rx

Answer 77

Causes Pituitary acidophil adenoma in 99% Hyperplasia from GHRH secreting carcinoid tumour GH stimulates bone and soft tissue growth through increase IGF1 ``` Symptoms Acroparaesthesia Amenorrhoea, decrease libido Headache Snoring Sweating Arthralgia, back ache Carpal tunnel (50%) ``` ``` Signs Hands Spade-like Thenar wasting Boggy sweaty palms (if active) increase skin fold thickness Carpal tunnel: decrease sensation + thenar wasting ``` ``` Face Prominent supraorbital ridges Scalp folds: cutis verticis gyrata Coarse face, wide nose and big ears Prognathism: look from side Macroglossia Widely-spaced teeth Goitre ``` Other Puffy, oily, darkened skin skin Proximal weakness + arthropathy Pituitary mass effects: bitemporal hemianopia ``` Complications Endocrine Impaired glucose tolerance (40%) DM (15%) Cardiovascular increase BP LVH Cardiomyopathy increase IHD and increase stroke Neoplasia increase risk of CRC ```

Answer 78

Ix increase IGF1 increase glucose, increase Ca, increase PO4 Glucose tolerance test - GH fails to suppress c¯ glucose in acromegaly Visual fields and acuity MRI brain ``` Rx 1st line: trans-sphenoidal excision 2nd line: somatostatin analogues – octreotide 3rd line: GH antagonist – pegvisomant 4th line: radiotherapy ```

Answer 79

``` Symptoms Polyuria Polydipsia Dehydration Hypernatraemia: lethargy, thirst, confusion, coma ``` ``` Causes Cranial Idiopathic: 50% Congenital: DIDMOAD / Wolfram Syndrome Tumours Trauma Vascular: haemorrhage (Sheehan’s syn.) Infection: meningoencephalitis Infiltration: sarcoidosis ``` ``` Nephrogenic Congenital Metabolic: decrease K, increase Ca Drugs: Li, demecleocycline, vaptans Post-obstructive uropathy ```

Answer 80

Ix Bloods: U+E, Ca, glucose Urine and plasma osmolality Exclude DI if U:P osmolality >2 Dx Water deprivation test c¯ desmopressin trial Differential DM Diuretics or Lithium Primary polydipsia Rx Cranial Find cause: MRI brain Desmopressin PO Nephrogenic Treat cause

Answer 81

``` PCOS Features secondary oligo-/amenorrhoea causes infertility Obesity Acene, hirsutism ``` US: bilateral polycystic ovaries Hormones: increase testosterone, decrease SHBG, increase LH:FSH ratio Mx Metformin COCP Clomifene for infertility

Answer 82

Gynaecomastia Abnormal amount of breast tissue in men May occur in normal puberty ``` Causes Cirrhosis Hypogonadism Hyperthyroidism Oestrogen- or HCG-producing tumours: e.g. testicular Drugs: spiro, digoxin, oestrogen ```

Answer 83

Hirsutism Causes Familial Idiopathic increase androgens: Ovary: PCOS Adrenals: Cushing’s, adrenal Ca Drugs: steroids

Answer 84

Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus. These cells release the peptides Growth hormone-releasing hormone (GHRH or somatocrinin) and Growth hormone-inhibiting hormone (GHIH or somatostatin) into the hypophyseal portal venous blood surrounding the pituitary. GH release in the pituitary is primarily determined by the balance of these two peptides, which in turn is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion.[12] Somatotropic cells in the anterior pituitary gland then synthesize and secrete GH in a pulsatile manner, in response to these stimuli by the hypothalamus.

Answer 85

Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up). Like most other protein hormones, GH acts by interacting with a specific receptor on the surface of cells. Increased height during childhood is the most widely known effect of GH. Height appears to be stimulated by at least two mechanisms: Because polypeptide hormones are not fat-soluble, they cannot penetrate cell membranes. Thus, GH exerts some of its effects by binding to receptors on target cells, where it activates the MAPK/ERK pathway.[35] Through this mechanism GH directly stimulates division and multiplication of chondrocytes of cartilage. GH also stimulates, through the JAK-STAT signaling pathway,[35] the production of insulin-like growth factor 1 (IGF-1, formerly known as somatomedin C), a hormone homologous to proinsulin.[36] The liver is a major target organ of GH for this process and is the principal site of IGF-1 production. IGF-1 has growth-stimulating effects on a wide variety of tissues. Additional IGF-1 is generated within target tissues, making it what appears to be both an endocrine and an autocrine/paracrine hormone. IGF-1 also has stimulatory effects on osteoblast and chondrocyte activity to promote bone growth. In addition to increasing height in children and adolescents, growth hormone has many other effects on the body

Answer 86

Deficiency Children growth retardation Excess Acromegaly (adults), Gigantism (Children) Static testing Random GH has a limited value IGF1 - a summary of GH status

Answer 87

oral glucose TT

Answer 88

``` amenorrhoea/oligomenorrhoea infertility loss of libido/erectile dysfunction gynaecomastia galactorrhoea ```

Answer 89

FSH Simulates spermatogenesis in testis Stimulates the follicle in the ovary & hence oestradiol

Answer 90

LH ``` Pulsatile secretion Continuous secretion is abnormal resulting in gonadal suppression Stimulates Testo in testis Causes ovulation & hence progesterone to ‘activate uterus’ ```

Answer 91

``` Hormone Target Organ Action GH (growth hormone) Liver Others somatomedin synthesis metabolic regulation ``` Prolactin Breast lactation ACTH (adrenocorticotrophic hormone) Adrenal cortex glucocorticoid synthesis/release pigmentation TSH (thyroid-stimulating hormone) Thyroid thyroid hormone synthesis/release ``` FSH (follicle-stimulating hormone) Ovary Testis oestrogen synthesis, oogenesis spermatogenesis ``` LH (luteinizing hormone) Ovary Testis ovulation, progesterone production testosterone synthesis

Answer 92

ADH / AVP (vasopressin) Renal collecting ducts Water reabsorption, urine concentration Oxytocin Breast / Uterus Milk release / Uterine contractility

Answer 93

Deficiency Children growth retardation Excess Acromegaly (adults), Gigantism (Children) Static testing Random GH has a limited value IGF1 - a summary of GH status Dynamic Testing • GH secretion is stimulated in several ways. Sleep or a protein meal are stimulants but are difficult to standardise. Glucagon or hypoglycaemia induced by insulin are easier to standardise, but the tests are hazardous, and use of the protocols requires training and is contraindicated in neurological patients because of the risk of seizures. • GH secretion is inhibited by glucose. In gigantism/acromegaly, GH secretion is persistent (as opposed to the normal pulsatile), and is not suppressed by glucose. The oral glucose tolerance test is easily extended to test GH during the procedure.

Answer 94

LH • Is secreted in pulses. Continuous LH secretion is abnormal and results in gonadal suppression • Stimulates testosterone production in the testis • Causes ovulation in the ovary, and hence progesterone

Answer 95

Prolactin • Controlled by hypothalamic dopamine, acting as an inhibitory release factor. • A prolactinoma, by growing and compressing other pituitary cells, may cause deficiency of other pituitary hormones e.g. gonadotrophins. • A visual field defect is a common presentation as suprasellar extension causes compression upon the optic chiasm

Answer 96

Static Testing This is usually all that is required. There are many cause of raised prolactin: • Prolactinoma. • Hypothyroidism. • Drugs: phenothiazines, haloperidol, oestrogens. • Lactation, pregnancy. Before assigning a raised level to prolactinoma, the analytical artefact of macroprolactin should be considered. Imaging the pituitary is also required before any surgery. Macroprolactin is the binding of prolactin to an immunoglobulin, reducing its clearance and so leaving more in the circulation at any one time. The problem of macro hormones is also found with macro enzymes: clinical confusion is caused by incorrect interpretation of raised levels.

Answer 97

Static testing Dexamethasone suppression tests are the investigation of choice in Cushing’s disease and syndrome plus appropriate imaging.

Answer 98

The Menopause • Pre-puberty there is a stock of potential follicles. • In each cycle, one follicle develops, and many others are lost completely. • From a state of continuous ovulatory cycles, individual cycles may be non-ovulatory. • The proportion of non-ovulatory cycles increases. • Eventually there is no ovulation and no cycles. • The menopause is a result of running out of follicles. From this description, it is apparent that the menopause is a lengthy process and not something which can be diagnosed by chemical tests. Age alone is the main predictor. Menopause at an unusually early age,

Answer 99

Antidiuretic hormone; Vasopressin • Deficiency of ADH (cranial diabetes insipidus) or insensitivity (nephrogenic diabetes insipidus) to its action leads to polyuria, nocturia, thirst and thus polydipsia. • Diagnosis is via a water deprivation test; careful patient monitoring is essential.

Answer 100

• Composed of three zones: – Zona glomerulosa • Outermost zone comprising 10% of the cortex and synthesising the mineralocorticoid aldosterone (regulated by plasma K+ and renin-angiotensin) – Zona fasciculata • Middle zone comprising 80% of the cortex and containing large amounts of relatively inactive cholesterol, on stimulation forms cells resembling the reticularis – Zona reticularis • Innermost zone which, with the zona fasciculata, synthesises glucocoticoids including cortisol and corticosterone, and androgens (underACTH control)

Answer 101

Excessive secretion of any one of the three basic types of corticosteroids gives rise to a distinct clinical syndrome: 1. Aldosterone – hyperaldosteronism (Conn’s syndrome) 2. Cortisol – Cushing’s syndrome 3. Androgens – adrenogenital syndromes

Answer 102

Primary hyperaldosteronism – excess aldosterone secretion which is independent of the renin-angiotensin system (Conn’s syndrome) – Causes: • Aldosterone secreting adenoma • Bilateral hyperplasia of the cortex • Rarely carcinoma – Clinical features: • Hypertension, hypokalaemia, sodium retention, muscle weakness, paraesthesia, ECG changes, cardiac decompensation

Answer 103

• Congenital adrenal hyperplasia – a small group of congenital metabolic errors, each characterized by a deficiency or lack of a particular enzyme involved in the synthesis of cortical steroids • Steroidogenesis is then channeled into other pathways, leading to increased production of androgens resulting in virilisation • The deficiency of cortisol leads to increasedACTH secretion and thus adrenal hyperplasia • Certain enzyme defects impair aldosterone secretion resulting in salt-wasting • The most common defects are 21-hydroxylase deficiency (95%) and 11 hydroxylase deficiency (3%)

Answer 104

21-hydroxylase deficiency may be mild or total and three syndromes are possible: ``` Salt-wasting adrenogenitalism – total deficiency => salt wasting, down Na, up K, acidosis, cardiovascular collapse, virilisation of female, precocious puberty in male. ``` ``` Simple virilizing adrenogenital syndrome – subtotal deficiency => reduced level of aldosterone but still sufficient for salt resorption; levels of glucocorticoid insufficient to inhibit ACTH, therefore up ACTH (and adrenal hyperplasia). ``` ``` Nonclassic adrenal virilism – mild deficiency => may be asymptomatic and only be diagnosed by genetic studies and demonstration of defects of steroidogenesis ```

Answer 105

Glucagon-like peptide-1 (GLP-1) or Incretin Naturally occurring peptide Increases insulin secretion Reduces glucagon secretion (enhances liver storage of glycogen, reduced gluconeogenesis) Slows gastric emptying and reduces appetite Third-line options in Ty 2 DM, usually in addition to first line treatment GLP-1 receptor agonists (Incretin analogues) Exenatide and Liraglutide Given by s/c injection, x2daily, before meals Prevent weight gain +/- weight loss NICE like patients to have achieved a 1% reduction in HbA1c and 3% weight loss after 6 months to justify the ongoing prescription of GLP-1 mimetics. The major adverse effect of GLP-1 mimetics is nausea and vomiting. The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide, reporting that is has been linked to severe pancreatitis in some patients Dipeptidyl peptidase-4 (DPP-4) inhibitors Breaks down native GLP-1 Sitagliptin, Vildagliptin and Saxagliptin Oral, less potent Key points oral preparation trials to date show that the drugs are relatively well tolerated with no increased incidence of hypoglycaemia do not cause weight gain NICE guidelines on DPP-4 inhibitors continue DPP-4 inhibitor only if there is a reduction of > 0.5 percentage points in HBA1c in 6 months NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedione

Answer 106

• Composed of three zones: – Zona glomerulosa • Outermost zone comprising 10% of the cortex and synthesising the mineralocorticoid aldosterone (regulated by plasma K+ and renin-angiotensin) – Zona fasciculata • Middle zone comprising 80% of the cortex and containing large amounts of relatively inactive cholesterol, on stimulation forms cells resembling the reticularis – Zona reticularis • Innermost zone which, with the zona fasciculata, synthesises glucocoticoids including cortisol and corticosterone, and androgens (underACTH control)

Answer 107

21-hydroxylase deficiency may be mild or total and three syndromes are possible: ``` Salt-wasting adrenogenitalism – total deficiency => salt wasting, down Na, up K, acidosis, cardiovascular collapse, virilisation of female, precocious puberty in male. ``` ``` Simple virilizing adrenogenital syndrome – subtotal deficiency => reduced level of aldosterone but still sufficient for salt resorption; levels of glucocorticoid insufficient to inhibit ACTH, therefore up ACTH (and adrenal hyperplasia). ``` ``` Nonclassic adrenal virilism – mild deficiency => may be asymptomatic and only be diagnosed by genetic studies and demonstration of defects of steroidogenesis ```

Answer 108

• Clinical features – Hypotension, hyponatraemia, collapse • Causes – Rapid withdrawal of long term steroid therapy – Sepsis/stress in patients with chronic adrenal dysfunction – Massive destruction of the adrenals * Perinatal haemorrhagic necrosis * Adrenal haemorrhage – heparin/warfarin, DIC * Post partum infarction • Adrenal haemorrhage complicating bacteraemia (eg meningococcal) =Waterhouse-Friderichson syndrome – trauma

Answer 109

MEN type II- Medullary thyroid carcinomas and C cell hyperplasias, parathyroid hyperplasia, adrenal medullary hyperplasia and phaeos. MEN type III- Medullary thyroid carcinomas and C cell hyperplasias, adrenal medullary hyperplasia and phaeos, mucosal neuromas and Marfanoid features. von-Hippel lindau- Renal, hepatic, pancreatic and epididymal cysts, Renal cell carcinomas, Phaeos, Angiomatosis and cerebellar haemangioblastomas. von Recklinghausen- neurofibromatosis, café au lait skin spots, schwannomas, meningiomas, gliomas and phaeos. Sturge-Weber – cavernous haemangiomas and phaeos.

Answer 110

Complications of Thyroid Surgery Early Reactionary haemorrhage causing haematoma (less than 1% of cases) Can cause airway obstruction. Call anaesthetist and remove wound clips, Evacuate haematoma and re-explore wound Laryngeal oedema Damage during intubation or surgical Manipulation Can cause airway obstruction Recurrent laryngeal nerve palsy (0.5%) Right RLN more common (oblique ascent), Damage to one causes hoarse voice, Damage to both causes obstruction needing trachyostomy Hypoparathyroidism (2.5%) causes decreased Ca2+ which causes Chvostek’s and Trousseau’s Thyroid storm Severe hyperthyroidism Rx: propranolol, antithyroid drugs, Lugol’s iodine and hydrocortisone sodium succinate Late Hypothyroidism Recurrent hyperthyroidism Keloid scar

Answer 111

Rapid or ‘soluble insulin’ is unaltered human insulin Intermediate insulin is formed by adding protamine to the insulin which increases its duration of action – Also termed ‘Isophane’ and ‘NPH’: Neutral Protamine Hagedorn Analogues are genetically altered to either increase or decrease duration of action Mixed insulin contain fast and acting elements e.g. Humalog Mix 25: 25% rapid, 75% long-acting

Answer 112

Block Potassium channels on the B-islet cells which results in the release of stored insulin A first-line option in Ty 2 DM (where there is residual Bcell activity). On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells. Examples: Gliclazide, Glipizide, Glibenclamide (Differences are mainly duration of action) Given x1/x2 daily with meals (tablets) Major side effects are similar to Insulin i.e. weight gain and hypoglycaemia Common adverse effects hypoglycaemic episodes (more common with long acting preparations such as chlorpropamide) weight gain ``` Rarer adverse effects syndrome of inappropriate ADH secretion bone marrow suppression liver damage (cholestatic) photosensitivity peripheral neuropathy ``` Sulfonylureas should be avoided in breast feeding and pregnancy

Answer 113

Glucagon-like peptide-1 (GLP-1) or Incretin Naturally occurring peptide Increases insulin secretion Reduces glucagon secretion (enhances liver storage of glycogen, reduced gluconeogenesis) Slows gastric emptying and reduces appetite Third-line options in Ty 2 DM, usually in addition to first line treatment GLP-1 receptor agonists (Incretin analogues) Exenatide and Liraglutide Given by s/c injection, x2daily, before meals Prevent weight gain +/- weight loss Dipeptidyl peptidase-4 (DPP-4) inhibitors Breaks down native GLP-1 Sitagliptin, Vildagliptin and Saxagliptin Oral, less potent

Answer 114

Stimulates the PPARƳ receptor Modulates transcription of genes involved in glucose and lipid metabolism Pioglitazone only one available – Rosiglitazone taken off the market due to concerns about CV safety Should not be used in patients with heart failure The PPAR-gamma receptor is an intracellular nuclear receptor. Its natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function. Adverse effects weight gain liver impairment: monitor LFTs fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin recent studies have indicated an increased risk of fractures bladder cancer: recent studies have showed an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64) NICE guidance on thiazolidinediones only continue if there is a reduction of > 0.5 percentage points in HbA1c in 6 months

Answer 115

The Only Biguanide in use Discovered in 1920s but (because of interest in Insulin) first trial was not until 1957. Now most widely prescribed antidiabetic drug in the world! (First choice in overweight pts) Increases peripheral insulin sensitivity Reduces hepatic glucose production Given x1-3 daily Can rarely cause lactic acidosis The other biguanides (buformin and phenformin) were withdrawn because of this, and concern over it delayed the introduction of Metformin in the USA. Should be avoided in renal, heart and liver failure Acts on the AMPK system (adenosine monophosphate- activated protein kinase) ``` Usually started in obese patients with type2 DM, also PCOS Side effects: lactic acidosis – more likely in liver, renal or heart failure (therefore contraindicated in these conditions) ```

Answer 116

5 – Reduce Glucose GI absorption Acarbose – alpha-glucosidase inhibitor, slows breakdown of complex CH – reduces postprandial G rose, poorly tolerated due to GI disturbance

Answer 117

diagnose diet and weight reduction if poor control it then depends on whether you're obese or not. obese = metformin non obese = sulfonylurea then next step is Metformin+sulphonylurea regardless. then you look at Insulin Glitazones Exenatide/Gliptins

Answer 118

Fluid Correct hypovolaemia – BUT more slowly (over ~24 hours) Use saline (0.9%) Insulin Only start after rehydration has commenced & glucose not falling fixed rate (0.05 units/kg/hour) – ie half the dose of DKA Aim max drop in glucose of 5mmol/h Anticoagulation HHS takes days to develop (unlike DKA, which is usually hours) Higher mortality than DKA Large, quick changes in fluid/glucose/electrolyes(esp Na) may precipitate cerebral oedema Fluid alone in HHS will drop the blood glucose level

Answer 119

• Composed of three zones: – Zona glomerulosa • Outermost zone comprising 10% of the cortex and synthesising the mineralocorticoid aldosterone (regulated by plasma K+ and renin-angiotensin) – Zona fasciculata • Middle zone comprising 80% of the cortex and containing large amounts of relatively inactive cholesterol, on stimulation forms cells resembling the reticularis – Zona reticularis • Innermost zone which, with the zona fasciculata, synthesises glucocoticoids including cortisol and corticosterone, and androgens (underACTH control)

Answer 120

Neuroblastoma is one of the most common neoplasms in childhood. The prognosis depends on age. Congenital neoplasms may regress spontaneously. Those in children over 1yr have the worst prognosis, and this correlates with cytogenetic abnormalities and oncogene expression. The neoplasm is made of sheets of small dark cells resembling lymphocytes (embryonic nerve cells, neuroblasts). Differentiation to varying levels is found in most neuroblastomas. If the neoplasm is completely differentiated it is composed of a fibrous background in which ganglion cells are scattered (ganglioneuroma).

Answer 121

Goitre = enlargement of thyroid Goitre most commonly develops secondary to relative lack of thyroid hormones leading to increased TSH production and hyperplasia of the thyroid follicles. The hyperplasia sometimes takes the form of multiple nodules, so-called multinodular goitre. Sometimes the follicles are enlarged and contain abundant colloid, so-called colloid goitre. The most common cause of goitre is iodine deficiency due to decreased intake of iodine. This form is usually endemic in areas with low levels of environmental iodine. Other reasons include inherited enzyme defects of thyroid hormone production and drugs such as carbimazole

Answer 122

Hyperpituitarism - usually a functioning adenoma of the anterior lobe; one cell type secreting one hormone. Functioning adenomas tend to be smaller at presentation than nonfunctioning ones, and may be confined to the sella turcica. ``` Prolactinomas - 20-30% ACTH - 10-15% Gonadotrophins 10-15% Growth hormone 5% Growth hormone + prolactin 5% Thyrothrophin 1% More than one hormone 20% ``` The 3 cell types in the pituitary are classified according to their staining affinity (chromophobe, basophil, acidophil), but immunostaining for specific hormones reveals 5 types. Non-functioning adenomas present as space-occupying lesions or hypopituitarism. The optic chiasm may be involved early, resulting in visual field defects. Morphology of pituitary adenomas. Encapsulated, well circumscribed. Necrosis and haemorrhage in larger lesions. Upward expansion beyond the sella turcica compresses the optic chiasm and cranial nerves. Later the sella and anterior clinoid processes are eroded, with extension into the cavernous sinus. More extensive invasion (seen in 30%) is called invasive adenoma. Cells are uniform polygonal shape, mitoses are rare. The functional status cannot be reliably predicted from the staining patter

Answer 123

Hypopituitarism: Causes of hypopituitarism: non-functioning pituitary adenoma, other lesions (metastases, cysts), surgery and radiation, pituitary apoplexy (haemorrhage into an adenoma), ischaemic necrosis (e.g. post-partum in Sheehan's syndrome). Rarely a congenital syndrome. Rarely secondary to hypothalamic disease (craniopharyngioma, tuberculous meningitis).

Answer 124

Diabetic complications Nephropathy - glomerulosclerosis The biochemical abnormalities caused by AGEs lead to alterations of the basement membrane and the mesangium and accumulation of mesangial matrix. This could diffusely involve all of the glomerular basal membrane or could be focal/nodular. Accordingly, the changes are described as diffuse or nodular glomerulosclerosis. Diffuse thickening of glomerular capillary basement membranes and increased amount of mesangial matrix with mesangial cell proliferation. The affected glomeruli develop diabetic glomerulosclerosis. These changes are seen in at about 40% of diabetic patients after 10 to 20 years. Nodular Glomerosclerosis (Kimmelstiel-Wilson disease or intercapillary glomerulosclerosis) More conspicuous focal accumulations of mesangial matrix, producing mesangial nodules located in the periphery of the affected glomerulus. The nodules contain lipids and fibrin. The nodules expand obliterating the glomerulus. Macroscopic appearance of end stage diabetic nephropathy. External surface is granular reflecting extensive sclerosis of cortical glomeruli (Left). Cut surface shows destruction of the renal papillae and scarring consistent with previous attacks of pyelonephritis (Right).

Answer 125

Diabetic microangiopathy affects the retinal vessels in 60% of the patients, ultimately causing blindness. - Capillary basal membranes are thickened - Microaneurysms - Haemorrhages and occlusion of the vessels by thrombi. These changes lead to ischaemia which stimulates neovascularisation, further impairing the vision. Other ocular complications include cataracts and glaucoma. Fundoscopic view of diabetic retina. There are so-called cotton-wool spots (fluffy-yellow areas) caused by haemorrhage, exudation and neovascularisation is seen.

Answer 126

unclear pathogenesis Decreased sensation and loss of reflexes occurs first in the toes bilaterally, then extends upward. It is usually described as glove-stocking distribution of numbness, sensory loss, dysesthesia and night time pain. The pain can feel like burning, pricking sensation, achy or dull. Pins and needles sensation is common. Loss of proprioception, the sense of where a limb is in space, is affected early. These patients cannot feel when they are stepping on a foreign body, like a splinter, or when they are developing a callous from an illfitting shoe Consequently, they are at risk for developing ulcers and infections on the feet and legs, which can lead to amputation. Similarly, these patients can get multiple fractures of the knee, ankle or foot, and develop a Charcot joint (neurogenic arthropathy).

Answer 127

TRH is produced by the hypothalamus in medial neurons of the paraventricular nucleus. Following secretion, TRH travels across the median eminence to the anterior pituitary gland via the hypophyseal portal system where it stimulates the release of thyroid-stimulating hormone from cells called thyrotropes. TSH (with a half life of about an hour) stimulates the thyroid gland to secrete the hormone thyroxine (T4), which has only a slight effect on metabolism. T4 is converted to triiodothyronine (T3), which is the active hormone that stimulates metabolism. About 80% of this conversion is in the liver and other organs, and 20% in the thyroid itself negative feedback loops

Answer 128

The Chvostek sign (/ˈkvɒstɨk/) is a clinical sign of existing nerve hyperexcitability (tetany) seen in hypocalcemia.[1] It refers to an abnormal reaction to the stimulation of the facial nerve. When the facial nerve is tapped at the angle of the jaw (i.e. masseter muscle), the facial muscles on the same side of the face will contract momentarily (typically a twitch of the nose or lips) because of hypocalcemia (i.e. from hypoparathyroidism, pseudohypoparathyroidism, hypovitaminosis D) with resultant hyperexcitability of nerves. Though classically described in hypocalcemia, this sign may also be encountered in respiratory alkalosis, such as that seen in hyperventilation, which actually causes decreased serum Ca2+ with a normal calcium level due to a shift of Ca2+ from the blood to albumin which has become more negative in the alkalotic state.

Answer 129

Trousseau sign of latent tetany is a medical sign observed in patients with low calcium.[1] This sign may become positive before other gross manifestations of hypocalcemia such as hyperreflexia and tetany, as such it is generally believed to be more sensitive (94%) than the Chvostek sign (29%) for hypocalcemia.[2][3] To elicit the sign, a blood pressure cuff is placed around the arm and inflated to a pressure greater than the systolic blood pressure and held in place for 3 minutes. This will occlude the brachial artery. In the absence of blood flow, the patient's hypocalcemia and subsequent neuromuscular irritability will induce spasm of the muscles of the hand and forearm. The wrist and metacarpophalangeal joints flex, the DIP and PIP joints extend, and the fingers adduct. The sign is also known as main d'accoucheur (French for "hand of the obstetrician") because it supposedly resembles the position of an obstetrician's hand in delivering a baby.

Answer 130

Complications of Thyroid Surgery Early Reactionary haemorrhage causing haematoma (less than 1% of cases) Can cause airway obstruction. Call anaesthetist and remove wound clips, Evacuate haematoma and re-explore wound Laryngeal oedema Damage during intubation or surgical Manipulation Can cause airway obstruction Recurrent laryngeal nerve palsy (0.5%) Right RLN more common (oblique ascent), Damage to one causes hoarse voice, Damage to both causes obstruction needing trachyostomy Hypoparathyroidism (2.5%) causes decreased Ca2+ which causes Chvostek’s and Trousseau’s Thyroid storm Severe hyperthyroidism Rx: propranolol, antithyroid drugs, Lugol’s iodine and hydrocortisone sodium succinate Late Hypothyroidism Recurrent hyperthyroidism Keloid scar

Answer 131

Because the thyroid gland is a hormone secreting organ, it is highly vascularized. It receives its blood supply from the superior and inferior thyroid arteries. These arteries lie between the fibrous capsule and the pretracheal layer of deep cervical fascia. The superior thyroid artery is the first branch of the external carotid artery and supplies the top half of the thyroid gland. It divides into anterior and posterior branches supplying respective sides of the thyroid. On the anterior side, the right and left branches anastomose with each other. On the posterior side, the right and left branches anastomose with their respective inferior thyroid arteries. The inferior thyroid artery supplies the lower half of the thyroid and is the major branch of the thyrocervical trunk, which comes off the subclavian artery. It too divides into several branches, supplying the inferior portion of the thyroid and anastomosing posteriorly with the superior thyroid branches. There are three main veins that drain the venous plexus on the anterior surface of the thyroid. They include the superior, middle, and inferior thyroid veins, and each drains its respective portion of the thyroid. The superior and middle thyroid veins drain into the internal jugular veins, whereas the inferior thyroid vein drains into the brachiocephalic veins, behind the manubrium of the sternum. Lymphatic drainage of the thyroid gland is quite extensive and flows multidirectionally. Immediate drainage flows first to the periglandular nodes, then to the prelaryngeal (Delphian), pretracheal, and paratracheal nodes along the recurrent laryngeal nerve, and then to mediastinal lymph nodes. The principal innervation of the thyroid gland is derived from the superior, middle, and inferior cervical sympathetic ganglia of the autonomic nervous system and parasympathetic fibers from the vagus nerves. These nerves reach the thyroid gland by coursing with the blood vessels (superior and inferior thyroid periarterial plexuses).

Answer 132

NICE updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2009. Key points are listed below: Dietary advice encourage high fibre, low glycaemic index sources of carbohydrates include low-fat dairy products and oily fish control the intake of foods containing saturated fats and trans fatty acids limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake discourage use of foods marketed specifically at people with diabetes initial target weight loss in an overweight person is 5-10% HbA1c the general target for patients is 48 mmol/mol (DCCT = 6.5%). HbA1c levels below 48 mmol/mol (DCCT = 6.5%) should not be pursued however, individual targets should be agreed with patients to encourage motivation HbA1c should be checked every 2-6 months until stable, then 6 monthly Blood pressure target is 48 mmol/mol (DCCT = 6.5%) if the patient is at risk from hypoglycaemia (or the consequences of) then a DPP-4 inhibitor or thiazolidinedione should be considered rather than a sulfonylurea meglitinides (insulin secretagogues) should be considered for patients with an erratic lifestyle if HbA1c > 58 mmol/mol (DCCT = 7.5%) then consider human insulin metformin treatment should be continued after starting insulin exenatide should be used only when insulin would otherwise be started, obesity is a problem (BMI > 35 kg/m^2) and the need for high dose insulin is likely. Continue only if beneficial response occurs and is maintained (> 1.0 percentage point HbA1c reduction and weight loss > 3% at 6 months) Starting insulin usually commenced if HbA1c > HbA1c > 58 mmol/mol (DCCT = 7.5%) NICE recommend starting with human NPH insulin (isophane, intermediate acting) taken at bed-time or twice daily according to need Other risk factor modification current NICE guidelines suggest giving aspirin to all patients > 50 years and to younger patients with other significant risk factors. However, recent evidence does not support this approach. The 2010 SIGN guidelines do not advocate the use of aspirin for primary prevention in diabetics following the 2014 NICE lipid modification guidelines only patients with a 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin. The first-line statin of choice is atorvastatin 20mg on

Answer 133

A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG) Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l Diabetes UK suggests: 'People with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn't have diabetes but does have IGT.'

Answer 134

1. How is the patient? 2. Is the patient hypoxaemic? the Pa02 on air should be >10 kPa 3. Is the patient acidaemic (pH 7.45) 4. Respiratory component: What has happened to the PaCO2? PaCO2 > 6.0 kPa suggests a respiratory acidosis (or respiratory compensation for a metabolic alkalosis) PaCO2 26 mmol/l (or a base excess > + 2mmol/l) suggests a metabolic alkalosis (or renal compensation for a respiratory acidosis)

Answer 135

Maturity-onset diabetes of the young (MODY) is characterised by the development of type 2 diabetes mellitus in patients

Answer 136

Prediabetes is a term which is increasingly used where there is impaired glucose levels which are above the normal range but not high enough for a diagnosis of diabetes mellitus. The term includes patients who have been labelled as having either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Diabetes UK estimate that around 1 in 7 adults in the UK have prediabetes. Many individuals with prediabetes will progress on to developing type 2 diabetes mellitus (T2DM) and they are therefore at greater risk of microvascular and macrovascular complications. Terminology Diabetes UK currently recommend using the term prediabetes when talking to patients and impaired glucose regulation when talking to other healthcare professionals research has shown that the term 'prediabetes' has the most impact and is most easily understood

Answer 137

Identification of patients with prediabetes NICE recommend using a validated computer based risk assessment tool for all adults aged 40 and over, people of South Asian and Chinese descent aged 25-39, and adults with conditions that increase the risk of type 2 diabetes patients identified at high risk should have a blood sample taken a fasting plasma glucose of 5.5-6.9 mmol/l or an HbA1c level of 42-47 mmol/mol (6.0-6.4%) indicates high risk Management lifestyle modification: weight loss, increased exercise, change in diet at least yearly follow-up with blood tests is recommended NICE recommend metformin for adults at high risk 'whose blood glucose measure (fasting plasma glucose or HbA1c) shows they are still progressing towards type 2 diabetes, despite their participation in an intensive lifestyle-change programme'

Answer 138

There are two main types of IGR: impaired fasting glucose (IFG) - due to hepatic insulin resistance impaired glucose tolerance (IGT) - due to muscle insulin resistance patients with IGT are more likely to develop T2DM and cardiovascular disease than patients with IFG Definitions a fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG) impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l people with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn't have diabetes but does have IGT

Answer 139

NICE updated it's guidance on the management of neuropathic pain in 2013. Diabetic neuropathy is now managed in the same way as other forms of neuropathic pain: first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin if the first-line drug treatment does not work try one of the other 3 drugs tramadol may be used as 'rescue therapy' for exacerbations of neuropathic pain topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia) pain management clinics may be useful in patients with resistant problems

Answer 140

Gastroparesis symptoms include erratic blood glucose control, bloating and vomiting management options include metoclopramide, domperidone or erythromycin (prokinetic agents)

Answer 141

Thyrotoxicosis (e.g. Graves' disease) Low TSH High T4 | In T3 thyrotoxicosis the free T4 will be normal

Answer 142

Primary hypothyroidism (primary atrophic hypothyroidism)

Answer 143

Secondary hypothyroidism:Replacement steroid therapy is required prior to thyroxine or Sick euthyroid syndrome*(*now referred to as non-thyroidal illness) - Common in hospital inpatients, T3 is particularly low in these patients, TSH may be normal in some cases

Answer 144

Subclinical hypothyroidism or Poor compliance with thyroxine

Answer 145

Steroid therapy

Answer 146

A number of new drugs to treat diabetes mellitus have become available in recent years. Much research has focused around the role of glucagon-like peptide-1 (GLP-1), a hormone released by the small intestine in response to an oral glucose load Whilst it is well known that insulin resistance and insufficient B-cell compensation occur other effects are also seen in type 2 diabetes mellitus (T2DM). In normal physiology an oral glucose load results in a greater release of insulin than if the same load is given intravenously - this known as the incretin effect. This effect is largely mediated by GLP-1 and is known to be decreased in T2DM. Increasing GLP-1 levels, either by the administration of an analogue (glucagon-like peptide-1, GLP-1 mimetics, e.g. exenatide) or inhibiting its breakdown (dipeptidyl peptidase-4 ,DPP-4 inhibitors - the gliptins), is therefore the target of two recent classes of drug. Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide) Exenatide is an example of a glucagon-like peptide-1 (GLP-1) mimetic. These drugs increase insulin secretion and inhibit glucagon secretion. One of the major advances of GLP-1 mimetics is that they typically result in weight loss, in contrast to many medications such as insulin, sulfonylureas and thiazolidinediones. Exenatide must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal. Liraglutide is the other GLP-1 mimetic currently available. One the main advantages of liraglutide over exenatide is that it only needs to be given once a day. Both exenatide and liraglutide may be combined with metformin and a sulfonylurea. Standard release exenatide is also licensed to be used with basal insulin alone or with metformin. Please see the BNF for a more complete list of licensed indications.

Answer 147

In 2011 WHO released supplementary guidance on the use of HbA1c on the diagnosis of diabetes: a HbA1c of greater than or equal to 6.5% (48 mmol/mol) is diagnostic of diabetes mellitus a HbAlc value of less than 6.5% does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes) in patients without symptoms, the test must be repeated to confirm the diagnosis it should be remembered that misleading HbA1c results can be caused by increased red cell turnover (see below) ``` Conditions where HbA1c may not be used for diagnosis: haemoglobinopathies haemolytic anaemia untreated iron deficiency anaemia suspected gestational diabetes children HIV chronic kidney disease ```

Answer 148

NICE recommend the following blood pressure targets for type 2 diabetics: if end-organ damage (e.g. renal disease, retinopathy) less than 130/80 mmHg otherwise less than 140/80 mmHg A 2013 Cochrane review casted doubt on the wisdom of lower blood pressure targets for patients with diabetes. It compared patients who had tight blood pressure control (targets less than 130/85 mmHg) with more relaxed control (less than 140-160/90-100 mmHg). Patients who were more tightly controlled had a slightly reduced rate of stroke but otherwise outcomes were not significantly different. Because ACE-inhibitors have a renoprotective effect in diabetes they are the first-line antihypertensives recommended for NICE. Patients of African or Caribbean family origin should be offered an ACE-inhibitor plus either a thiazide diuretic or calcium channel blocker. Further management then reverts to that of non-diabetic patients, as discussed earlier in the module. Remember than autonomic neuropathy may result in more postural symptoms in patients taking antihypertensive therapy. The routine use of beta-blockers in uncomplicated hypertension should be avoided, particularly when given in combination with thiazides, as they may cause insulin resistance, impair insulin secretion and alter the autonomic response to hypoglycaemia.

Answer 149

fluid retention | hypertension

Answer 150

fluid retention | hypertension

Answer 151

Minimal glucocorticoid activity, very high mineralocorticoid activity,

Answer 152

some? Glucocorticoid activity, high mineralocorticoid activity,

Answer 153

Predominant glucocorticoid activity, low mineralocorticoid activity

Answer 154

Very high glucocorticoid activity, minimal mineralocorticoid activity

Answer 155

Very high glucocorticoid activity, minimal mineralocorticoid activity

Answer 156

Calcium 2.1-2.6 mmol/l | Phosphate 0.8-1.4 mmol/l

Answer 157

The benefits of tight glycaemic control following a myocardial infarction were initially established by the DIGAMI study. These findings were not repeated in the later DIGAMI 2 study. However modern clinical practice is still that type 2 diabetics are converted to intravenous insulin in the immediate period following a myocardial infarction. NICE in 2011 recommended the following: 'Manage hyperglycaemia in patients admitted to hospital for an acute coronary syndrome (ACS) by keeping blood glucose levels below 11.0 mmol/litre while avoiding hypoglycaemia. In the first instance, consider a dose-adjusted insulin infusion with regular monitoring of blood glucose levels.'

Answer 158

Amiodarone-induced hypothyroidism The pathophysiology of amiodarone-induced hypothyroidism (AIH) is thought to be due to the high iodine content of amiodarone causing a Wolff-Chaikoff effect (*an autoregulatory phenomenon where thyroxine formation is inhibited due to high levels of circulating iodide) Amiodarone may be continued if this is desirable Amiodarone-induced thyrotoxicosis Amiodarone-induced thyrotoxicosis (AIT) may be divided into two types: AIT type 1 AIT type 2 in type 1 you get - Excess iodine-induced thyroid hormone synthesis, goitre and treat it with Carbimazole or potassium perchlorate in type 2 you get - Amiodarone-related destructive thyroiditis, no goitre and you treat with Corticosteroids Unlike in AIH, amiodarone should be stopped if possible in patients who develop AIT

Answer 159

Whilst Grave's disease is the most common cause of thyrotoxicosis it would not cause a tender goitre. In the context of thyrotoxicosis this finding is only really seen in De Quervain's thyroiditis. Hashimoto's thyroiditis is an autoimmune disorder of the thyroid gland. It is typically associated with hypothyroidism although there may be a transient thyrotoxicosis in the acute phase. The goitre is non-tender in Hashimoto's.

Answer 160

Goserelin is a gonadorelin analogue used in the treatment of advanced prostate cancer and can cause gynaecomastia. Tamoxifen may be used to treat gynaecomastia.

Answer 161

anyone on long term steroids can suppress their pituitary-adrenal axis, or who has overwhelming sepsis, or has metastatic cancer can suddenly develop adrenal insufficiency with deadly hypovolaemic shock. it is rare - 0.8/100,000 but can be fatal. consider in all with unexplained abdo pain or vomiting. look for the crease pigmentation.

Answer 162

somewhere between 4 and 7 mmol/l. below 3 = hypoglycaemia = treat.

Answer 163

Prediabetes is a term which is increasingly used where there is impaired glucose levels which are above the normal range but not high enough for a diagnosis of diabetes mellitus. The term includes patients who have been labelled as having either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Diabetes UK estimate that around 1 in 7 adults in the UK have prediabetes. Many individuals with prediabetes will progress on to developing type 2 diabetes mellitus (T2DM) and they are therefore at greater risk of microvascular and macrovascular complications. Terminology Diabetes UK currently recommend using the term prediabetes when talking to patients and impaired glucose regulation when talking to other healthcare professionals research has shown that the term 'prediabetes' has the most impact and is most easily understood Identification of patients with prediabetes NICE recommend using a validated computer based risk assessment tool for all adults aged 40 and over, people of South Asian and Chinese descent aged 25-39, and adults with conditions that increase the risk of type 2 diabetes patients identified at high risk should have a blood sample taken a fasting plasma glucose of 5.5-6.9 mmol/l or an HbA1c level of 42-47 mmol/mol (6.0-6.4%) indicates high risk Management lifestyle modification: weight loss, increased exercise, change in diet at least yearly follow-up with blood tests is recommended NICE recommend metformin for adults at high risk 'whose blood glucose measure (fasting plasma glucose or HbA1c) shows they are still progressing towards type 2 diabetes, despite their participation in an intensive lifestyle-change programme'

Answer 164

ACTH dependent causes Cushing's disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia ectopic ACTH production (5-10%): e.g. small cell lung cancer ACTH independent causes iatrogenic: steroids adrenal adenoma (5-10%) adrenal carcinoma (rare) Carney complex: syndrome including cardiac myxoma micronodular adrenal dysplasia (very rare) Pseudo-Cushing's mimics Cushing's often due to alcohol excess or severe depression causes false positive dexamethasone suppression test or 24 hr urinary free cortisol insulin stress test may be used to differentiate

Answer 165

There are three main types of altitude related disorders: acute mountain sickness (AMS), which may progress to high altitude pulmonary edema (HAPE) or high altitude cerebral edema (HACE). All three conditions are due to the chronic hypobaric hypoxia which develops at high altitudes Acute mountain sickness is generally a self-limiting condition. Features of AMS start to occur above 2,500 - 3,000m, developing gradually over 6-12 hours and potentially last a number of days: headache nausea fatigue Prevention and treatment of AMS the risk of AMS may actually be positively correlated to physical fitness gain altitude at no more than 500 m per day acetazolamide (a carbonic anhydrase inhibitor) is widely used to prevent AMS and has a supporting evidence base treatment: descent A minority of people above 4,000m go onto develop high altitude pulmonary oedema (HAPE) or high altitude cerebral oedema (HACE), potentially fatal conditions HAPE presents with classical pulmonary oedema features HACE presents with headache, ataxia, papilloedema Management of HACE descent dexamethasone Management of HAPE descent nifedipine, dexamethasone, acetazolamide, phosphodiesterase type V inhibitors* oxygen if available *the relative merits of these different treatments has only been studied in small trials. All seem to work by reducing systolic pulmonary artery pressure

Answer 166

This patient has hypothyroidism. The vast majority of cases are primary hypothyroidism with a high TSH and low T4. The common causes are: Autoimmune (Hashimoto's disease, atrophic) Iodine deficiency Thyroiditis (post-viral, post-partum) Iatrogenic (thyroidectomy, radioiodine, drugs) Secondary hypothyroidism is very rare and results in a low TSH and low T4. In these cases pituitary insufficiency is most likely and therefore an MRI of the gland should be performed.

Answer 167

Most common tumour causing bone metastases (in descending order) prostate breast lung

Answer 168

somatostatin inhibits growth hormone release | dopamine inhibits prolactin release

Answer 169

Background Retinopathy dots and blots hard exudates 6 cw spots ophthalmology referral ? PRPC (Panretinal photcoagulation) Proliferative new vessels PRPC Maculopathy oedema hard exudates macular grid laser

Answer 170

Definition: albuminuria (AER>300mg /24h) in a diabetic with retinopathy in the absence of another cause for renal disease 30% of type I diabetics 25-50% of type II diabetics Progresses to end-stage renal failure and the need for dialysis Preceded by microalbuminuria (AER=30-300mg/24h) Management: Microalbuminuria Macroalbuminuria tight glycaemic control (HbA1c insulin should replace all hypoglycaemic agents when CrCl

Answer 171

90% due to neuropathy leading to undetected injury and secondary infection additional effects of small vessel disease and peripheral vascular disease in prevented by regular checks, well fitting shoes nail and callous care 1 superficial - callus removal, swabs, oral antibiotics 2 deep with cellulitis - as above 3 foot ulceration + osteomyelitis - as above + admission and iv antibiotics 4 local gangrene as for 3 + vascular assessment, debridement + revasc. 5 gangrene of whole foot - as for 3 + amputation

Answer 172

``` Very rapid 15-30min peak 1h duration 5-6h Humalog/Novorapid ``` ``` Soluble insulin 30 min peak 1-2h duration 6-8h Actrapid ``` ``` Intermediate 2h peak 4-6h duration 8-12h Insulatard(Isophane) ``` ``` Long acting 4h peak 6-24h duration >24h Lantus/levemir ``` Intermediate Human Insulin (such as Insulatard) is termed Isophane or NPH (Neutral Protamine Hagedorn) is formed by adding protamine to the Insulin which increases its duration if action. Mixed Insulin (E.g Humalog, Novomix), contain fast and long acting elements. E.g: Humalog Mix 25 – 25% rapid, 75% long acting

Answer 173

``` 5 I's: Infection Ischaemia (cardiac, mesenteric) Infarction Ignorance (poor control) Intoxication (alcohol) ```

Answer 174

``` ABCDEF: Arthralgia/ Arthritis Blood pressure raised Carpal tunnel syndrome Diabetes Enlargemed organs Field defect ```

Answer 175

``` MD PIMPS ME: Malignancy Diuretics (thiazide the main culprit) Parathyroid (hyperparathyroidism) Immobilization/ Idiopathic Megadoses of vitamins A,D Paget's disease Sarcoidosis Milk alkali syndrome Endocrine (Addison's disease, thyrotoxicosis) ```

Answer 176

SIADH: Surgery Intracranial: infection, head injury, CVA Alveolar: Ca, pus Drugs: opiates,antiepileptics, cytotoxics, anti-psychotics Hormonal: hypothyroid, low corticosteroid level

Answer 177

``` THYROIDISM: Tremor Heart rate up Yawning [fatigability] Restlessness Oligomenorrhea & amenorrhea Intolerance to heat Diarrhea Irritability Sweating Musle wasting & weight loss ```

Answer 178

CUSHING: Central obesity/ Cervical fat pads/ Collagen fiber weakness/ Comedones (acne) Urinary free corisol and glucose increase Striae/ Suppressed immunity Hypercortisolism/ Hypertension/ Hyperglycemia/ Hirsutism Iatrogenic (Increased administration of corticosteroids) Noniatrogenic (Neoplasms) Glucose intolerance/ Growth retardation

Answer 179

``` "Protein LEAC": Proteinuria Lipid up Edema Albumin down Cholesterol up In nephrotic, the proteins leak out. ```

Answer 180

first symptomatic control e.g. with propranolol 40mg PO OD then reduce circulating levels of thyroid hormones e.g. with carbimazole 40mg PO OD and replace the reduced thyroxine to prevent iatrogenic hypothyroidism with levothyroxine 125 micrograms PO OD if resistant after a period of medical therapy then radio iodine therapy can be used.

Answer 181

also known as soft exudates. yellow-whitish discolourations of the retina. they are local infarcts of the surface of the retina that occur to impairment of blood supply. along with haemorrhages and venous beading they are signs of retinal ishcaemia

Answer 182

also known as hard exudates and are seen in background retinopathy.

Answer 183

proliferative retinopathy has begun which requires urgent referral.

Answer 184

give tetracosactide and check cortisol before and after. this is the sort synacthen test which uses exogenous ACTH to try and stimulate the adrenal gland to release cortisol.

Answer 185

a good initial test to screen for hyperaldosteroneism

Answer 186

to look for free catecholamine that would signify a phaechromocytoma. can also do this to look for cortisol to investigate suspected cushion's but this is a bit outdated and a dexamethasone suppression test is done now instead where you give dexamethasone and check cortisol before and after.

Answer 187

weight loss, lethargy, polydipsia leading to acute dehydration. the inability to use glucose means it act as an osmotic diuretic. untreated this leads to confusion, coma and death. DKA.

Answer 188

a punched out area over an area of hard callus. usually pain free and they will have reduced sensation in a glove and stocking distribution.

Answer 189

no, its how they relate the the oestrogen levels. the oestrogen:androgen ratio needs to rise. a range of drugs can cause this and some cancers can secrete oestrogens such as testicular.

Answer 190

pancreatic.

Answer 191

hypothyroidism

Answer 192

hypoglycaemia. also look for shaking and a precipitant such as infection or irregular eating or poor medication compliance.

Answer 193

metformin, particularly if they have a BMI over 25. sulphonylureas if they are not overweight, fail to tolerate metformin or it is CI. or if a quick response is needed due to hyperglycaemic symptoms. sulphonylureas can also be added as a second line treatment if sugar control remains suboptimal on metformin alone. thiazolidinediones eg pioglitazone can be added as a third line agent if control still needs improvement. they can also be considered as second line in place of a sulphonylurea if there are concerns over hypoglycaemic episodes. the glistens such as sitagliptin can be used second line if either sulphonylureas or metformin are CI or not tolerated. they can also be added as triple therapy in preference to thiazolidinediones or insulin.

Answer 194

if multi nodular then its called a multi nodular goitre and this will tend to cause thyrotoxicosis. single nodule goitres can represent cysts, adenomas or very rarely - cancers.

Answer 195

it runs through the cavernous sinus which is lateral and beneath the pituitary fossa, so a tumour in the pituitary fossa can invade or put pressure on the abducens nerve, causing a loss of lateral gaze.

Answer 196

these fragile new vessels form in ischaemic areas and represent worsening diabetic retinopathy and imply suboptimal glucose control. these are dangerous as they can leak fluid, bleed, cause scarring, and even detach the retina. the PT needs to be seen by an eye specialist for consideration of laser treatment of the new vessels and it must be stressed that they need to strive for better glucose control or risk losing their eyesight permanently.

Answer 197

the ability to understand, believe, retain and weigh up the necessary information in order to make a decision. it doesn't matter if the decision appears irrational to the doctor or may jeopardise their health, they are at liberty to do so. capacity is also fluid, and can be reassessed at any point, is decision dependent, i.e. they can have capacity for one decision but not another, and a doctor should always strive to facilitate they greatest level of capacity possible for a patient.

Answer 198

to treat under common law without the patients consent a doctor has to prove that they lack capacity to make the decision and then prove that the decision the doctor wants to make is in the PTs best interests. the only other exception of treating without consent is in an emergency where the doctor feels that the PT is in immediate danger, or they are at risk of harming others , or to prevent a crime.

Answer 199

if it is over 11.1mmol/L and accompanied by symptoms of hyperglycaemia. if they are asymptomtic then repeat the test.

Answer 200

if the fasting reading is over 7mmol/L and they have symptoms, or if it remains high once repeated.

Answer 201

for people with a fasting reading of 6.1-6.9mmol/l. it is the only means of identifying people with impaired glucose tolerance.

Answer 202

decreased sensation especially vibration in a glove and stocking distribution with reduced ankle reflexes and resulting deformities of the feet - e.g. calluses that can lead to ulcers and chariot's joints.

Answer 203

haemosiderin is an iron storage complex that is released from erythrocytes as they extravasate into the skin in venous ulcer disease. it stimulates melanin production thus turning the skin brown.

Answer 204

tenderness of the veins on the back of the calf is indicative of phlebitis and is common in venous disease.

Answer 205

the antiemetic prochlorperazine, metoclopramide and the antipsychotic haloperidol, along with other DA antagonist drugs.

Answer 206

0.5-5.7 for TSH 9-22 for free T4 nb don't confuse with total T4 which is 70-140. this is subclinical hypothyroidism, with the symptomatic presentation they should be commenced on a trial of levothyroxine to see whether there is an improvement in symptoms. it is common and does not need replacement treatment if asymptomatic. if TPO antibodies are present they are at risk of an autoimmune thyroiditis and thus should be monitored with an annual TSH test, earlier if symptoms.

Answer 207

common in acute illness, with a low - to normal TSh and a low/high T4/T3

Answer 208

hypocalcaemia. needs to be corrected or can lead to arrhythmias due to prologed QT and subsequent collapse. check the PTH and calcium

Answer 209

Features of excess prolactin men: impotence, loss of libido, galactorrhoea women: amenorrhoea, galactorrhoea ``` Causes of raised prolactin prolactinoma pregnancy oestrogens physiological: stress, exercise, sleep acromegaly: 1/3 of patients polycystic ovarian syndrome primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release) ``` ``` Drug causes of raised prolactin metoclopramide, domperidone phenothiazines haloperidol very rare: SSRIs, opioids ```

Answer 210

Hyperacute acute rejection (minutes to hours) due to pre-existent antibodies against donor HLA type 1 antigens (a type II hypersensitivity reaction) rarely seen due to HLA matching

Answer 211

Acute graft failure (

Answer 212

Causes of chronic graft failure (> 6 months) both antibody and cell mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy) recurrence of original renal disease (MCGN > IgA > FSGS)

Answer 213

The presence of worsening renal function, together with muddy brown casts is strongly suggestive of acute tubular necrosis

Answer 214

eGFR calculations such as the Cockcroft and Gault equation are less reliable in populations with high GFR's

Answer 215

Causes sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison's, Hypopituitarism) adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia) steroid withdrawal Management hydrocortisone 100 mg im or iv 1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days

Answer 216

commonly now the MDRD equation that requires a calculator (can be online), but up until recently the Cockcroft-Gault (CG) formula was used. this is viewed as a bit less accurate and doesn't take into account the impact of race (black men have higher serum creatine on average due to higher muscle mass on average) unlike the MDRD, its benefit however is that its simpler and can be calculated much more simply. the CG equation estimates creatinine clearance Crcl = [(140-age)xMass (kg) x 0.85 (if female)]/ (72x serum creatinine (mg/dl)) or Crcl = [(140-age)xMass (kg) x constant]/ (serum creatinine (micro moles/L)) where the constant is 1.23 for men and 1.04 for women. be familiar with these

Answer 217

Serum Osmolality = (2 x (Na + K)) + (urea in mmol/l) + (glucose in mmol/l)

Answer 218

with hepatitis in children and neuropsych symptoms in young adults. low serum caeruloplasmin and copper.

Answer 219

confusion and drowsiness on a background of polyuria and polydipsia in a young shocked patient should be treated as DKA until proven otherwise. fluid, insulin, potassium, education. BNF says 1 - normal saline fluid challenges to get systolic bp over 90. then infuse at a rate to replace losses and to provide maintenance 2 - add K CL based on plasma K, serial measure each hour. 3 - IV insulin infusion. 0.1units/kg/hour at conc of 1unit/ml in saline. 4 - continue established long acting SC insulin. 5 - monitor ketones and glucose hourly. adjust insulin accordingly. see BNF for target correction rates. 6 - once glucose below 14 infuse glucose 10% at 125ml/hr as well.

Answer 220

an alpha1 sympathomimetic used in the Rx of orthostatic hypotension.

Answer 221

cortisol is falsely high after dexamethasone suppression test due to metabolism of dexamethasone, sometimes due to the action of a hepatic enzyme inducer e.g. phenytoin Some frequently occurring illnesses can induce a phenotype that largely overlaps with Cushing syndrome and is accompanied by hypercorticolism.[1] These illnesses include the following: ``` Depression Obesity Physical stress Malnutrition Eating disorders Polycystic ovarian syndrome (PCOS) Uncontrolled diabetes Obstructive sleep apnea (OSA) Chronic alcoholism ``` In these instances, this phenotype is called a pseudo-Cushing syndrome (PCS).[2] Particular type of hypercortisolism caused by the above conditions, named functional hypercortisolism, is caused by chronic activation of hypothalamic-pituitary-adrenal (HPA) axis. It is usually mild and disappears when the underlying disorder is resolved.[1] PCS initially was described by Smalls et al, in 1976; the investigators reported 3 cases of alcoholic patients who had the physical and biochemical abnormalities of Cushing syndrome.[3] Most of the abnormalities disappeared after 1-3 weeks of alcohol abstinence. Drugs such as phenytoin, phenobarbitone, carbamezepine, and rifampicin will induce hepatic enzymatic clearance of dexamethasone, thereby reducing the plasma dexamethasone concentration (73, 74) and resulting in false positive responses to dexamethasone testing. Estrogens increase the cortisol-binding globulin concentration in the circulation; since RIAs measure total cortisol, false positive rates are seen in 50% of women on the oral contraceptive pill (75). It is our routine practice, where possible, and particularly in mild cases, to stop such estrogen-containing drugs and delay investigation for 6 weeks to allow the cortisol-binding globulin to return to baseline

Answer 222

must maintain a minimum calorific intake each hour (even if just a can of coca-cola or a pot of yoghurt), and extra rapid acting insulin depending on extent of ketonuria. needs very clear safety net advice as to when to retained A and E if they want to go home and not be admitted.

Answer 223

thiazolidinediones eg pioglitazone so CI in heart failure.