Endocrine Diagnosis And Management Flashcards

Question

retinopathy overview

Answer 1

Divided into two forms Nonproliferative Proliferative (abnormal new blood vessels (neuvascularisation) Proliferative retinopathy leads to retinal detachment due to neuovascularisation producing fragile vessels, leading to haemorrhage etc. Most pts are asymptomatic until too late (often untreatable) stage Diabetes is most common cause of blindness in people over 65

Answer 2

Poorly controlled diabetes impairs polymorphonuclear leukocyte functions Increases infection risk Particularly UTI and skin (cellulitis, boils, abscesses) TB and candidiasis also more common in DM Infections can lead to loss of glycaemic control (common cause of DKA) In infections DT1 may need to increase insulin dosage Same with DT2

Answer 3

Condition causing weakness in bones of the foot; occurs in pts with significant nerve damage (peripheral neuropathy) ischaemia causing tissue necrosis Neuropathy: high foot arc, pressure sore and infection leads to diabetic foot As pt walks small bones of foot fracture and become deformed Presents with inflammation, erythema, warmth, neuropathy, bounding pedal pulses and possible deformities. Treatment is offloading weight from feet and surgical opinion in severe cases

Answer 4

12-17 years annual assessment should include diabetic foot assessment. If problem suspected then refer to appropriate specialist When diagnosed: should be assessed at least annually or if anymore problems arise or any hospital admission or any change is status while in hospital. Stratify by risk: low risk (no RFs present but callus alone), mod (deformity, neuropathy or non-critical limb ischaemia), high risk (previous ulceration, previous amputation, renal replacement therapy, neuropathy and non-critical limb ischaemia together or neuropathy in combo with callus or deformity or non-critical limb ischaemia in combo with callus or deformity), active diabetic foot problem (ulceration, spreading infection, critical iscaemia or gangrene or suspicion of acute Charcot arthropathy or unexplained hot, red, swollen foot with or without pain.

Answer 5

Principles of foot care: well-fitting shoes, regular chiropody, avoid trauma, daily inspection of feet and seek advice if damaged, avoid heat sources like radiators and hot water (for everyone) Low risk: annual foot checks Moderate risk: refer within 6-8 wks to foot protection service, assess feet and provide skin and nail care, specialist footwear if needed, vascular status of lower limbs etc. every 3-6 months High risk: refer within 2-4 wks to foot protection service, assess feet and provide skin and nail care, specialist footwear if needed, vascular status of lower limbs etc. every 1-2 months

Answer 6

Seen in unwell pts with DT2 Triggers include; MI, drugs, sepsis, bowel infarct History of deterioration is longer than DKA roughly 1 week Signs of marked dehydration, hypovolaemia, high osmolarity and glucose >30mmol/L Small amount of insulin means they don’t switch to DKA, instead have high osmolarity >320mosmol/kg

Answer 7

``` dehydration stupor or coma unconscious profound dehydration hypotension (later) tachycardia glucose >30mmol/L osmolarity >320 ```

Answer 8

treat dehydration with fluids (2 large bore cannulae) insulin therapy to correct hyperglycemia electrolyte replacement monitor throughout treatment for deterioration and improvements Intensive monitoring (including calculating osmolarity regularly) High dependency unit admission (CV catheter insertion) Saline 0.9% IV fluids to replace Na, Cl and K loss and correct hypovolemia Insulin started if significant ketonaemia is present but if not do not start insulin (CORRECT HYPOVOLAEMIA FIRST as insulin administration before correction can result in CV COLLAPSE) Once BG has stopped falling as result of fluid resuscitation; then insulin may be started; aim for BG fall of 5mmol/L per hour Monitor K+ and offer correction if needed Anticoagulation for pts with increased thromboembolism risk

Answer 9

Most common endocrine emergency Most common complication of insulin treatment Triggers: high activity, missed meal, insulin overdose Glucose <3mmol/L (normal fasting range 4-6; 2hrs post meal up to 7.8)

Answer 10

``` In seemingly unwell pts: Drugs: insulin, sulfonylureas, pentamidine, propranolol Non-pancreatic tumour eg sarcoma or hepatoma Addison’s disease Fulminant liver failure End stage kidney disease Excess alcohol Gastric surgery ``` ``` Seemingly well pts: Factitious hypoglycemia (surreptitious self-administration of insulin often in non-DM Functional beta cell disorders Autoimmune hypoglycaemia Islet cell tumour (insulinoma) ```

Answer 11

``` Sympathetic overactivity: Sweating Hunger Anxiety Tremor Palpitations Pallor Dizziness Neuroglycopenia: Confusion Drowsiness Visual trouble Personality changes Seizures Hemiparesis Coma Brain damage Death ```

Answer 12

``` Whipple's triad: diagnosis: Symptoms of hypoglycemia Low plasma glucose Glucose delivery resolves symptoms Investigations: In unwell pts: Plasma glucose Medication review Hepatic, renal and cardiac function tests Adrenocortical function Nonislet cell tumors Seemingly well pts: Observe during episode or after fast of up to 72 hours or after mixed meal Measure glucose Insulin C-peptide Pro-insulin Beta-hydroxy butyrate ```

Answer 13

Hyperglycaemia within 24 hrs fasting Increased plasma insulin, C-peptide and proinsulin Decreased plasma glucose <3mmol/L These are rare and mostly benign Needs CT scan imaging to isolate mass and begin treatment

Answer 14

``` Retinopathy Kidney complications Nerve problems Heart conditions Foot complications (peripheral neuropathy) Brain conditions; stroke, dementia MI, infections etc. ```

Answer 15

Pineal gland - melatonin Pituitary Hypothalamus - neural and hormonal functions Thyroid and parathyroid glands Thymus - thymosins and training T cells Adrenal Pancreas - both hormones and exocrine products Ovary - both hormones and exocrine products Testis - both hormones and exocrine products Other organs with endocrine glands: Heart Kidneys Stomach Small intestine

Answer 16

A line between the CNS and endocrine system Regulates thirst, appetite, sleep cycles, menstrual cycle, stress/mood etc. Hypothalamus releases factors which reach the anterior pituitary gland via the portal system (pituitary stalk) These factors stimulate or inhibit hormone production from the anterior pituitary (queen of the endocrine system) Vasopressin and oxytocin are produced in the hypothalamus and stored and released from the posterior pituitary

Answer 17

Negative feedback - response to hormone synthesis stops production Counter-regulation - hormones working against the action of another hormone such as insulin raising BG levels and glucagon and adrenaline released in response to decrease BG levels Positive feedback - rare; hormones secreted in response to hormone to increase it’s effect/action making it more potent e.g. oxytocin in labour is released to cause uterus contraction; more oxytocin is released in response and so on until delivery

Answer 18

Tyrosine derived: T3 and 4 from thyroid. Can pass through cell membrane and cytoplasm and reach nucleus of cell (nucleic receptors). Affect cells all over the body, very widespread effects. Steroid hormones: from adrenal or gonadal glands. Do not need receptor on cell surface membrane to enter as are lipophilic so can diffuse through. Bind to receptors in either the cytoplasm or nucleus of the target cell to form active receptor-hormone complex and produce response. Examples: oestrogen, progesterone, testosterone. Peptide hormones: part of proteins; includes all other hormones other than the two types above. Hydrophilic and lipophobic; cannot freely cross plasma memb. Bind to receptors in cell surface to activate series of complex secondary messengers to initiate cell response. Examples: insulin, glucagon, leptin, ADH, oxytocin.

Answer 19

AKA The pituitary gland Centre of the endocrine system, under control the hypothalamus, which in turn is under control of the upper CNS centres Endocrine gland around the size of a pea weighing roughly 0.5G Rests on the hypophyseal fossa of the sphenoid bone Surrounded by small bony cavity (sella turcica) covered by dural fold (diaphragma sellae) Below and behind the optic chiasma = pituitary mass = visual problem! Located just behind upper sphenoid sinus (preferred surgical route of approach) Helps to control blood pressure, energy management, gonadal organs, thyroid glands, metabolism and some aspects of pregnancy, birth and breastfeeding, water/salt concentration, temperature and pain relief! The anterior pituitary (or adenohypophysis) is a lobe of the gland that regulates several physiological processes (including stress, growth, reproduction, and lactation). [LH,FSH, GH, TSH, ACTH, PRL] The intermediate lobe synthesizes and secretes melanocyte-stimulating hormone [MSH]. The posterior pituitary (or neurohypophysis) is a lobe of the gland that is functionally connected to the hypothalamus by the median eminence via a small tube called the pituitary stalk (also called the infundibular stalk or the infundibulum). [ADH/Vasopressin, Oxytocin]

Answer 20

Most common form of pituitary disease Some are silent while others cause symptoms due to: Inadequate hormone production (hypopituitarism) Excess hormone secretion (hyperpituitarism) Local effects of tumour (such as progressive visual impairment from mass pressing into sella turcica)

Answer 21

``` Types: Reduced ADH secretion from post. Pituitary (cranial DI, CDI) Impaired response of kidney to ADH (nephrogenic DI, NDI) Causes: Improper hormone production Injury to hypothalamus Tumour or head surgery Kidney disorders Infections Genes ```

Answer 22

Results in Impaired water reabsorption by kidney Causes passing of large volumes of water (>3L/day) of dilute urine Also causes nocturia and compensatory polydipsia (excessive thirst/drinking) This is due to lack of ADH causing dehydration and hyperatremia (hyperosmolar blood)

Answer 23

Clinical history of classic symptoms (polyuria, nocturia, polydipsia) Tests for diabetes type 1 and 2 to rule these out Water deprivation test: not drinking liquid for several hours and measure urine output (will continue to pee lots) Blood test for ADH concentration, Ca and K concentration Urine tests for same (very dilute low conc of substances) Vasopressin test: injection of ADH to test reaction (decreased urine output = CDI, still continue to wee = NDI) MRI scan: assess for CDI damage to hypothalamus or pituitary glands/abnormalities

Answer 24

``` Traumatic brain injury Atherosclerosis Pituitary abnormalities Autoimmune diseases Family history Genetic mutations ``` complications: dehydration and electrolyte imbalance

Answer 25

not always needed in mild cases Increase water intake - mild CDI Desmopressin (ADH analog) - mod/severe CDI Low solute diet (mostly low sodium and low protein to help increase Na retention etc.) - mild NDI Thiazide like diuretics - mod/severe NDI NSAIDs - Mod/severe NDI Classifications and management: Mild CDI - 3-4 L urine over 24 hours; advise to drink 2.5L water everyday to compensate Mod/Severe CDI - more than 4 L urine output over 24 hours; first line desmopressin Mild NDI - reducing salt and protein in diet to increase kidney Na retention Mod/Severe NDI - unlikely to respond to desmopressin due to kidney malfunction. Instead recommend thiazide diuretics to reduce kidney filter rate. NSAIDs like ibuprofen to further help reduce urine volume in combo with diuretics.

Answer 26

Pituitary gland releases GH under control of GHRH (stimulates) and somatostain (inhibits) from the hypothalamus GH stimulates bone and soft tissue growth via increasing insulin -like growth factor-1 (IGF-1), made in the liver and other tissues Excessive GH production in children (before long bone fusion of epiphyses) causes GIGANTISM Excessive production in adults causes ACROMEGALY (acro-extremity; causes more effects in distal limbs) Rare condition caused by benign pituitary GH producing adenoma in almost all cases Gender doesn't influence Incidence highest in middle age

Answer 27

``` Hand growth (spade like), jaw and feet Coarsening face (large hands and face, but not strong); wide nose, big tongue Wide spaced teeth ``` ``` Puffy lips, eyelids Oily and large pores in skin Scalp folds Skin darkening Laryngeal dyspnoea (fixed cords) Obstructive sleep aponea Goitre (increase thyroid vascularity) Proximal weakness and arthropathy Carpal tunnel syndrome (50% cases) Cardiomegaly Hepatomegaly Nephromegaly Skin tags Splenomegaly ``` Signs of pituitary mass: Hypopituitarism in other hormones Reduced vision; hemianopia Fits

Answer 28

in some cases; DM or CHF can be first signs of presentation so always check hormone levels when screening these pts. Diabetes (impaired glucose tolerance; GH is stress hormone increase glucose secretion) IHD ischaemic heart disease HTN Stroke (GH increases fibrinogen and decreases protein S; inhibits clot formation increasing IHD) CHF (could be first presentation of acromegaly) Increased risk of colon cancer

Answer 29

Released from anterior pituitary Suppressed by secretion of dopamine from hypothalamus Has wide fluctuation level in blood Many major tranquilisers, antipsychotics etc. are essentially anti-dopaminergic and so increase prolactin secretion

Answer 30

Most common hormonal disturbance in pituitary Cause: Physiological: mild hyperprolactinemia is usually asymptomatic; occurs during pregnancy, breastfeeding, stress, post-orgasm Pathological: prolactinoma, microprolactinoma - macroprolactinoma Most common pituitary tumour and cause of severe hyperprolactinaemia Also caused by drugs such as: metodopramide, phenothiazides, oestrogens, cimetidine Other causes: primary hyperthyroidism (high TSH levels stimulate prolactin) PCOS Acromegaly (co-secretion of prolactin with GH by tumour)

Answer 31

Amenorrhea-galactorrhea syndrome PRL increase causes galactorrhea (spontaneous milk flow not associated with childbirth or breast feeding) Inhibits GnRH; decreasing LH/FSH and testosterone causing Oligo-/amenorrhoea (women), erectile dysfuntion (men), decreased libido, subfertility, osteoporosis (in both but specifically women) Pituitary tumour: headache, visual field defects

Answer 32

Treat the underlying cause if feasible. Asymptomatic patients with hyperprolactinaemia +/- a prolactinoma may not need treatment; 90-95% of of prolactinomas never increase in size. Indications for treatment are: Adverse effects of tumour size. Adverse effects of hyperprolactinaemia. Treat with dopamine agonists: cabergoline, bromocriptine or quinagolide. If DAs are ineffective: Surgery - to reduce tumour size. Radiotherapy - rarely used due to significant adverse effects and lack of effectiveness. Women with hypogonadism and microprolactinomas who do not wish to become pregnant may be treated for their hypogonadism with oestrogen-containing contraception, as long as their prolactin levels (checked annually) do not increase substantially and there is no evidence of tumour enlargement.

Answer 33

Small risk of tumour enlargement, particularly with macroadenomas (one third will enlarge). Refer urgently if there are headaches or visual disturbance. Patients should be under an endocrinologist (ideally for pre-conception counselling too). Depending on the individual situation, management may be: Omitting DAs for the duration of pregnancy and during lactation. If treatment is required, bromocriptine and cabergoline appear to be safe during pregnancy - bromocriptine is the most 'tried and tested' in this scenario.

Answer 34

This may be treated by withdrawing the drug (if feasible), with oestrogen/testosterone replacement, or with a cautious trial of a DA.

Answer 35

This condition usually requires no treatment and does not generally cause infertility

Answer 36

These will depend on the underlying cause, endocrine function and the tumour size (if due to a pituitary tumour). Possible complications are: Complications of hypogonadism Osteoporosis: Bone loss occurs in about 25% of women with hyperprolactinaemia and doesn't necessarily improve when prolactin levels return to normal A small retrospective study of men with prolactinoma demonstrated significant bone loss whether treatment was with surgery or medical therapy. The authors suggest that a prolactinoma, even when adequately treated, increases the risk of osteoporosis in men by about 5 times Reduced fertility. Erectile dysfunction, and infertility. Complications relating to tumour size: Visual loss. Headache. Pituitary apoplexy: This is the sudden onset of neurological symptoms (headache, visual symptoms, altered mental status, meningism) and hormonal dysfunction due to acute haemorrhage or infarction of a pituitary gland. It is uncommon. More likely in larger lesions. May develop in patients with giant prolactinomas if their tumours do not reduce in size substantially with a chosen form of therapy. CSF rhinorrhoea may occur with rapid size reductions in large prolactinomas that are highly sensitive to DA therapy. Very rarely, prolactinomas may be malignant.

Answer 37

This depends on the underlying cause. In women microprolactinomas spontaneously resolve in around a third, especially after the menopause or pregnancy. Treatment should be discontinued intermittently to see if it is still needed. The treatment dose may be decreased slowly over time. It is reasonable to attempt DA withdrawal in all patients who have been treated for three years, if prolactin levels are normal and the tumour volume has markedly reduced Five-year recurrence rates depend on the presence or absence of visible adenoma on MRI: Macroprolactinoma: Without visible remnant 33%. With visible remnant 78%. Microprolactinoma: Without visible remnant 26%. With visible remnant 42%. Follow-up to detect recurrence of hyperprolactinaemia and tumour enlargement is essential.

Answer 38

Follicles: small groupings of cells surrounding core of colloid cells (produce thyroid-precursor proteins called thyroglobulin) Follicular cells: follicle core surrounded by single layer of follicular cells. When stimulated by TSH from hypophysis they metabolise thyroglobulin in the colloid to secrete T3 and 4 Parafollicular cells: scattered among follicular cells. Secrete calcitonin (called C cells). Has no important endocrine role in humans

Answer 39

80-90% T4 secreted (inactive form of T3) 10-20% T3 (active hormone) T3/4 is protein bound eg to thyroid binding globulin (TBG) is inactive Free unbound is active hormone Regulation of thyroid hormone usually based on T3 T3 is 5 times more active than T4 T4 transformed to T3 in peripheral tissues Thyroid hormone abnormalities usually due to the gland itself Rarely caused by hypothalamus or pituitary Act on nearly every cell in body to regulate basal metabolic rate Affect protein synthesis, long bone growth, neural maturation, increase sensitivity to catecholamines (adrenaline), essential in cell development and differentiation, heat generation Hormone regulation: Primarily regulated by TSH from anterior hypophysis (stimulated by TRH from hypothalamus) TSH stimulates secretion Negative feedback from high conc of hormone stops secretion of regulatory molecules TRH and TSH production and release suppressed by high conc

Answer 40

Serum hormone levels (TSH, T4, T3, fT4, fT3) Iodine or technetium uptake scans Ultrasound scans Anti-thyroid antibodies TRH test Measure TSH Total hormone = bound + free Scan the gland to analyse the shape – is there a tumour or cyst Fine needle aspiration - for solid nodules Isotope scan for suspicious thyroid nodule: can detect HOT/COLD or neutral nodules based on uptake of isotope and comparing to remaining thyroid. Increased uptake is hot (metabolically active), decreased is cold (metabolically inactive) and the same is neutral. Few neutral and almost no hot nodules are malignant. 20% cold nodules are malignant. THR test: administer THR and look for TSH response. Normal = goes up after 20 mins then returns to normal level. Secondary hypothyroidism or thyrotoxicosis indicated if lack of TSH response or TSH response is too high/no return to normal levels.

Answer 41

Four small endocrine glands behind each lobe of thyroid yellow/brownish flat ovoid shaped resembles a lentil seed 6mm long, 3-4 mm wide Share similar blood supply, venous and lymphatic drainage to thyroid glands Produce parathyroid hormone PTH Regulated by negative feedback from Ca levels Act to increase Ca levels by: - increasing osteoclast activity releasing Ca and PO4 from bones - increase Ca and decrease PO4 reabsorption in kidney - increase production of vit D active form from precursor vit D3 Overall increases Ca and decreases PO4

Answer 42

Two small glands above the kidney Each has a cortex and medulla Cortex secretes steroid hormones, mineralocorticoids, glucocorticoids and androgens Medulla secretes catecholamines: adrenaline a noradrenaline Mineralocorticoids: aldosterone regulates BP, electrolytes balance Glucocorticoids: cortisol and corticosterone regulate carbohydrates, lipids and proteins metabolism Androgens: DHEA, no overall effect in males; converted to testosterone and DHT or to oestrogens in relevant gonads

Answer 43

``` Cushing’s syndrome Weight gain, moon face, increased appetite Skin atrophy, purple striae, acne Brittle vessels, easy-bruising Muscle wasting Gynecomastia Immunocompromised - increased infection chance Osteoporosis HTN DM Glaucoma, cataracts Rapid mood changes, irritable and anxious Depression Sleep disorders Growth retardation in children ```

Answer 44

Clinical presentations of chronic glucocorticoids excess Loss of normal feedback in HPA axis ie is not suppressed by DEXA administration Loss of circadian rhythm of cortisol secretion Causes: generally divided into two groups: ACTH dependent causes (high ACTH) such as pituitary adenoma (cushings DI) most common cause 80% ACTH independent causes : low ACTH chief cause of cushing syndrome in general is oral steroids (iatrogenic)

Answer 45

Hyperthyroidism – hyperfunction of the thyroid gland, too much Thyrotoxicosis – exposure to high levels of thyroid hormones, not because gland is hyperfunctioning e.g. took too much medication (thyroxine) Graves’ Disease - autoimmune Toxic nodules – overactive regions of thyroid gland Toxic adenoma – hormone producing tumour Thyroiditis – e.g. viral infection Iodine containing drugs – amiodarone (drug for heart?) Excessive T3 and T4 ingestion – replacement therapy, supplement Treatment – suppress hormone production eg carbimazole, surgery/radiotherapy to remove hyperfunctioning nodules Viral infections damage the gland, the gland releases too much hormone. Hypothyroidism can occur when the gland recovers before returning to normal Drugs containing iodine can cause a predisposition to thyroid hyperfunction Supplement demand of patients will change throughout their life so should be monitored and medication reviewed.

Answer 46

``` Excessive thyroid hormone, usually caused by thyroid hyperfunction Hyper acute F:M 4:1 ratio Thyrotoxicosis: excessive hormone Hyperthyroidism: excessive hormone due to thyroid hyperactivity Triggers in unprepared pt: recent thyroid surgery, radioiodine, infection, MI, trauma, stress Causes: Graves disease Toxic multinodular goitre TMG Toxic adenoma Ectopic thyroid tissue Exogenous iodine excess ```

Answer 47

``` Severe hyperthyroidism Agitation Confusion Coma Goitre Tachycardia Palpitations AF HF Acute abdomen syndrome Diarrhoea Weight loss Increased appetite Irritability Excessive sweating Heat intolerance Oligomenorrhea +/- infertility Fast and irregular pulse ```

Answer 48

``` HF Angina AF Osteoporosis Ophthalmopathy Gynaecomastia Thyroid storm ```

Answer 49

Bloods: TSH, FT3/4, FBC, autoantibodies: low TSH with high T3/4. may show mild normocytic anaemia, mild neutropenia, increased autoantibodies Isotope scan: if cause unclear or to detect nodular disease or subacute thyroiditis Visual tests: if ophthalmopathy present test visual fields, acuity and eye movements

Answer 50

Drugs: Beta blockers (propranolol 40mg/6h) rapid symptom control Antithyroid meds: titration eg carbimazole 20-40mg/24h PO 4wks then reduce according to TFTs every 1-2mnths. Block replace eg carbimazole and levothyroxine simultaneously (less risk of iatrogenic hypothyroidism) Radioiodine: Most become hypothyroid post treatment In active hyperthyroidism there is risk of thyroid storm Pregnancy and lactation Thyroidectomy: Risk of damage to recurrent laryngeal nerve (hoarse voice) and hypoparathyroidism Patients will become hypothyroid so will need a levothyroxine hormone replacement post. surgery

Answer 51

Gland with at least two autonomous nodules Seen in elderly and in iodine deficient areas Nodules secrete thyroid hormones Develops from endemic goitre becomes multinodular goitre and some nodules become autonomous (hot nodules); pt becomes hyperthyroid - TMG Surgery indicated for compressive symptoms from enlarged thyroid (dysphagia or dyspnoea)

Answer 52

Solitary nodule producing T3/4 | Isotope scan shows hot nodule and rest of gland is suppressed

Answer 53

Metastatic follicular thyroid cancer | Struma Ovarii: ovarian teratoma with thyroid tissue

Answer 54

Autonomous and produce sufficient hormone to suppress TSH secretion and contralateral lobe of thyroid gland Usually >3cm before symptoms arise Linked to activating mutations in TSH receptor or signalling

Answer 55

Amiodarone is main cause Type 1: caused by iodine in pts with underlying toxic multinodular goitre Type 2: inflammatory effect due to toxic effect of iodine on thyroid follicular cells

Answer 56

rare life threatening condition with rapid deterioration of thyrotoxicosis with hyperpyrexia, tachycardia and extreme restlessness. Eventually delirium, coma and death. Diagnosis if strong suspicious urgent treatment needed (don’t wait for tests).

Answer 57

``` Florid hyperthyroidism (graves disease; goitre, exophalamos, infiltrative dermopathy. Thyroiditis. Multinodular goitre) Fever Marked weakness and muscle wasting Extreme restlessness Wide emotional swings Confusion Psychosis Coma: particularly elderly Nausea Vomiting Diahrrhoea Hepatomegaly with mild jaundice Tachycardia AF Cardio collapse and shock ```

Answer 58

TSH, free T4/3 confirm technetium uptake (radioiodine scan if possible).

Answer 59

large doses of carbimazole (20mg 8hr orally) to block thyroid hormone synthesis. Propranolol (80mg 12hr orally to block orme effects. Lugol’s solution (K iodine 15mg 6 hr orally blocks release of hormone from gland acutely). Hydrocortisone (100mg IV 6hrly inhibits peripheral conversion of T4 to T3)

Answer 60

Prevalence 0.5% of population roughly ⅔ of hyperthyroidism cases F:M ratio 9:1 Typical onset 40-60 years Triggers: stress, infection, childbirth Associated with other diseases such as T1DM, Addison’s etc. Cause: Circulating IgG autoantibodies binding and activating thyroid receptors causing smooth thyroid enlargement (goitre) and high thyroid hormone production/secretion (esp. T3) Reacts with orbital autoantigens causing Graves eye signs

Answer 61

Diffuse goitre Thyroid bruit due to hyperfunctioning and hyperperfusion of thyroid Thyroid acropachy: clubbing, painful finger/toe swelling, periosteal reaction in limb bones Ophthalmopathy: exophthalmos, ophthalmoplegia Pretibial myxoedema: oedematous swelling above lateral malleoli

Answer 62

Autoantibodies TSH and FT3/4 Clinical exam if goitre present

Answer 63

Initially either regimen of antithyroid medication (carbimazole +/- levothyroxine for 12-18 months then withdraw 50% relapse then need radioiodine or surgery

Answer 64

Clinical effect of lack of thyroid hormone Common (4 in 1000/year) Many times is insidious If treated has good prognosis but very poor if untreated (heart disease, dementia) Etiology: Primary autoimmune hypothyroidism: primary atrophic and Hashimoto’s thyroiditis Iodine deficiency Post thyroidectomy of after radioiodine treatment Drug induced anti-arrhythmics, amiodarone, lithium, iodine Subacute thyroiditis Seonary - due to hypopituitarism: lack of TSH (rare)

Answer 65

``` non specific especially in women in 40s: Fatigue Lethargic Low mood Avoids the cold Weight gain Constipation Menorrhagia Hoarse voice Reduced memory/cognition Dementia Myalgia Cramps Weakness Bradycardia Neuropathy Myopathy Goitre Ataxia (lack of balance) Dry thin skin/hair Ascites +/- pitting oedema Round puffy face CHF ```

Answer 66

TFTs: high TSH, low T4 Cholesterol and triglyceride profile - high FBC - larger RBC high MCV Have low threshold for abnormality with suspicious or vague symptoms or in middle ages women are they on any drugs like amiodarone or OTC supplements? (vit D)

Answer 67

Levothyroxine 25-50mcg/24hr PO Review at 12 wks Aim to keep TSH >0.5mU/L In elderly or IHD pts; levothyroxine, L-thyroxine (T4) has risk of angina or MI so start with lower dose/be cautious

Answer 68

TSH - 0.4-4mU/l FT4 - 9-25pmol/l FT3 - 3.5-7.8pmol/l Ranges differ during pregnancy, children and infants, also vary from lab to lab so always look up guideline* Key points of interpretation guidelines: Acute illness ‘sick euthyroid’: Not recommended to perform TFTs in secondary care due to acute illness/treatments skewing results and interpretations leading to false diagnoses. Ethnicity; black ppl have lower TSH levels Age: mild TSH elevation 4-7mU/L may be normal with ageing Pregnancy: physiological TSH suppression in first trimester Medications: dopamine, high dose glucocorticoids, amphetamines, octreotide and bromocriptine suppress TSH levels Medications: containing iodine like lithium, amiodarone produce low TSH and high T4 can produce hyperthyroidism! Oestrogens: birth control pills cause high total T3/4 Biotin: OTC supplement causes abnormal result; check with pts and ensure they don’t take for at least few days before any TFTs

Answer 69

Must be symptomatic TSH levels must be outside of normal range (for non-physiological states) Start pts on levothyroxine (synthetic T4 hormone) There is no evidence that T3 treatment is effective (leothyronine) any treatment with this needs specialist endocrinologist opinion to see if it gains benefit or not. TSH >10 is over-hypothyroidism; indication to start treatment (NICE) Starting dose 25-50mcg levothyroxine, increase if no effect

Answer 70

Subclinical hypothyroidism is an early, mild form of hypothyroidism, a condition in which the body doesn't produce enough thyroid hormones. It's called subclinical because only the serum level of thyroid-stimulating hormone from the front of the pituitary gland is a little bit above normal Asymptomatic pts with raised TSH but still <10 with normal FT3/4 levels. Treatment: Monitor pt regularly, start with repeating tests within 3 months to see if anomaly or real change Until then no further treatment needed as no symptoms and is subclinical two repeated readings <10 can start treatment Start on 6 month trial after discussing with endocrinologist Always start on lowest dose; especially in elderly or those with cautions such as heart problems Subclinical hypothyroidism is likely an incidental finding as doesn’t actually present with symptoms Usually not a problem unless TSH keeps increasing with monitoring; there is under-lying problem, like above.

Answer 71

Inflammatory condition - autoimmune, infectious and toxic resulting in apoptotic pathways and follicle cell death Disruption of follicles results in thyroid hormone release and hyperthyroidism followed by mild hypothyroidism then recovery Presents first as hyperthyroidism followed by hypothyroidism Two conditions cause this presentation: Hashimoto’s and Postpartum thyroidosis Other inflammatory diseases of thyroid: subacute thyroiditis, acute thyroiditis, silent thyroiditis, riedel’s thyroiditis, palpation thyroiditis (traumatic injury)

Answer 72

hypothyroid condition Affects around 1% population More common in women (x6) More common after age 60 Goitre and autoimmune destruction of gland Autoimmune disorder where gland is infiltrated by lymphocyte B cels Anti-microsomal and anti-thyroid peroxidase Abs found in 95% cases Anti thyroglobulin Abs in 60% cases

Answer 73

Gland can’t produce hormones anymore No -ve feedback on TSH so rises significantly while T3/4 decrease Initially presents with hyperthyroidism Then a period of hypothyroidism Patients diagnosed are hypothyroid or euthyroid Rarely diagnosed in initial hyperthyroid period (hasi-toxicosis) Also more common in pts with T1DM, pernicious anaemia, addison’s disease etc.

Answer 74

Immunoassay for anti thyroid peroxidase antibodies most sensitive test Elevated TSH

Answer 75

In females following childbirth Glands become inflamed Initially presents with period of hyperthyroidism followed by hypothyroidism Usually function returns to normal after period of time (several months) Characterised by painless goitre Antibodies against thyroid peroxidase found in testing Usually doesn’t require treatment although thyroid hormone replacement may be needed during hypothyroid period for symptomatic relief

Answer 76

URTI causes thyrotoxicosis followed by hypothyroidism Uncommon Affects all ages, sexes but is most common in 40-50’s SYMPTOMS: URTI sudden and painful thyromegaly, neck pain, dysphagia, fever Diagnosed by blood tests Resolution is spontaneous with no treatment needed 5-10% develop permanent hypothyroidism and need thyroid hormone replacement

Answer 77

``` Thyromegaly Etiology: Diffuse: Physiological e.g. pregnancy Graves’ disease Hashimoto's thyroiditis Subacute thyroiditis Nodular: Multinodular goitre (MNG) Adenoma Carcinoma *Around 10% nodules are malignant. Lymphadenopathy strongly suggests may be malignant ```

Answer 78

Cause: MNG, fibrotic goitre Solitary thyroid nodule cause: cyst, adenoma, discrete nodule in MNG, malignant (10%) Investigations: TFTs: FT3/4, TSH USS: solid/cystic USS guided FNA - cytology benign or malignant (can’t differentiate between follicular adenoma and follicular carcinoma) Autoantibodies if suspicious of hashimoto's/graves Radionuclide scans (cold hot nodules): 10% cold nodules malignant, 90% other. Hot nodule: toxic adenoma. CXR large goitres located low in the neck; lung metastases in thyroid cancer

Answer 79

Often asymptomatic thyroid nodule presentation Uncommon Red flags!! Progressive in size, hard and irregular nodule, presence of enlarged neck lymph nodes Types: Papillary 60% well differentiated good prognosis Follicular 25% well diff. Good prognosis Medullary 5% Thyroid 5% Anaplastic carcinoma: rare, undifferentiated, poorest prognosis Risk factors: Low dose neck radiation in childhood - papillary carcinoma Positive family history of thyroid cancer

Answer 80

In younger pts Spread via lymph nodes into lungs - papilli grow slowly spreading towards nodes Risk factor: neck RT in childhood, exposure to ionising radiation Management is total thyroidectomy +/- node excision and radioiodine ablation with T4 suppression Post op radioiodine ablation removes possible necrosis of remaining thyroid tissue/metastases Post op levothyroxine needed to replace thyroid hormones and suppress TSH

Answer 81

Well differentiated AKA follicular adenocarcinomas In middle aged pts Spread via the blood to the bone and lungs; grows until it breaks through thyroid capsule into blood vessels FNA can’t differentiate between follicular adenoma and carcinoma Management: total thyroidectomy + radioiodine ablation and T4 suppression

Answer 82

Origin in C cells of thyroid; do not concentrate iodine so radioiodine scan or ablation does not work !! C cells more concentrated in upper 1/3rd of gland May produce calcitonin which can be used as tumour marker in post op follow ups (should decrease post op). May also release serotonin and vasoactive intestinal peptide increasing gastrointestinal mobility: ask about toilet habits changing? Sporadic mutation in 80% cases but can be familial; associated as part of MEN multiple endocrine neoplasia syndrome 20% cases For all cases need to screen for pheochromocytoma before operation; measure catecholamine metabolites in urine (if +ve in men screen for PCC 1st) Management: thyroidectomy and node excision

Answer 83

Lymphoma: Treatment chemo/radiotherapy Angioplasty carcinoma: Aggressive, no response to treatment, poor prognosis but radiotherapy may help Very rare, altered cells Grows beyond fibrous capsule and invade nearby structures Derived from existing papillary or follicular cancer

Answer 84

Solitary painless nodule Hard and immovable nodules more likely tumors Larynx : hoarse voice Oesophagus : dysphagia Usually no signs of hyper or hypothyroidism In medullary - diarrhoea and skin flushing (serotonin)

Answer 85

``` Thyroid ultrasound Calcitonin levels elevated - medullary carcinoma Radioiodine scan FNA: identify tumour type Treatment overview: Depends on type and how it spreads Partial or total thyroidectomy T4 suppression Radioiodine ablation ```

Answer 86

``` Causes: 80% solitary adenoma 20% hyperplasia of all glands Rarely parathyroid cancer Presentation: Asymptomatic often High Ca on routine tests picked up incidentally Tired Weak feeling Depressed Thirsty Dehydrated but polyuric renal stones Abdominal pain Pancreatitis Duodenal ulcers Bone pain, fracturing, osteropenia/osteoporosis High BP MEN-1 syndrome: adenoma/hyperplasia can present as part of multiple endocrine neoplasia type 1 ```

Answer 87

Bloods: high Ca, high PTH, low PO4 High ALP (bone activity) High 24hr urinary Ca CXR: subperiosteal erosions, cysts, brown tumours of phalanges, acro-osteolysis, pepper-pot skull, osteritis fibrosa cystica (severe reabsorption - rare) DEXA scan for bone densitometry: osteoporosis

Answer 88

Mild: high fluid intake to prevent stone, avoid thiazides, avoid high Ca and Vit D intake Follow ups every 6 months for bloods check Severe: excision of adenoma or all four hyperplastic glands. If high serum or urinary Ca, bone disease, peptic ulcers, osteoporosis, renal calculi, low renal function, age >50 Pre-op USS and sestamibi (liquid radioactive material injected into body and absorbed by overactive parathyroid but not healthy parathyroid) may localse adenoma Intra-op blood PTH sampling to confirm removal of correct parathyroid

Answer 89

Low Ca and high PTH Causes: Low vit D intake Chronic renal failure

Answer 90

``` Correct cause Phosphate binders Vitamin D Cinacalet if PTH is very high. Is a calcimimetic - increases sensitivity of parathyroids to Ca causing increase in -ve feedback so reduced PTH secretion Parathyoidectomy ```

Answer 91

High Ca and very high PTH Causes: Chronic renal failure, prolonged secondary hyperparathyroidism or hyperplastic or adenomatous parathyroid Glands act autonomously (no Ca -ve feedback) resulting in very high PTH and hypercalcemia Treatment: endocrinologist and other expert referrals

Answer 92

type 1: 3 P's; pituitary adenoma, parathyroid hyperplasia, pancreatic tumors type 2: PPM; parathyroid hyperplasia, medullary thyroid carcinoma, pheochromocytoma type 3: MMMP; mucosal neuromas, marfanoid body habitus, medullary thyroid carcinoma, pheochromocytoma

Answer 93

PTH secretion is low due to gland failure Caused by autoimmune diseases (DiGeorge syndrome) thymus aplasia and T cell immunity failure Signs and symptoms: hypocalcaemia (cramps, corpopedal spasm, bronchospasm, dysphagia, laryngospasm with co-morbidities like addison’s, pernicious anaemia, alopecia etc.) Investigations: PTH low, Ca low, PO4 high or neutral, ALP neutral Management: Ca supplements, calcitriol, synthetic PTH

Answer 94

``` Deletion syndrome of small segment from C.22 Causes cardiac abnormality Abnormal faeces Thymic aplasia Cleft palate hypocalcaemia/hypoparathyroidism ```

Answer 95

Radiation Surgery on thyroid or parathyroids Hypomagnesaemia (Mg needed for PTH secretion) Investigations: Ca low PTH low PO4 high or neutral

Answer 96

Failure of target cell response to PTH Cause is genetic Signs: short metacarpals (esp. 4+5th), round face, short stature, calcified basal ganglia Investigations: Ca low, PTH high, ALP neutral or high Management: Ca supplements, calcitriol, synthetic PTH

Answer 97

morphological features of pseudohypoparathyroidism but with normal biochemistry. Caused by genetics also.

Answer 98

*Subclinical hyperthyroidism needs referral if TSH is <0.1mU/L for at least 3 months and there is evidence of thyroid disease* *pre-pregnancy counselling needed for all women with overt or subclinical hyperthyroidism planning pregnancy. Advised to seek medical advice if pregnancy suspected or confirmed Arrange urgent specialist referral for all pregnant women with current or previous overt or subclinical hyperthyroid disease Check TFTs postpartum depending on specialist advice

Answer 99

Mild: Eating and drinking 15-20g fast acting carbohydrate such as glucose tablets, sweets, fizzy drinks or fruit juice May also need 15-20g slower acting carbohydrate if not due next meal soon Regularly test blood glucose Moderate-severe: If unconscious; glucagon injection/glucogel/dextrogel/rapilose gel, if they wake up within 10 minutes then encourage carbohydrate fluid or food to help correct hypoglycemia. If not; can repeat gel up to 3 times in total or if in hospital give IV glucose 10% as this is a medical emergency. Long acting carbohydrates given ASAP when conscious and BG >4mmol/L again. If seizures: time duration and frequency: if very aggressive stop IV glucose 10% and treat with glucogel up to 3 times and go back to IV if no response If not responding within 30-45 minutes of glucose gel; treat with IM glucagon or glucose 10% IV In alcoholic patients, thiamine supplementation should be given with, or following, the administration of intravenous glucose to minimise the risk of Wernicke's encephalopathy. If Insulin injection is due do NOT omit giving this; consider reviewing regimen however Hypoglycaemia caused by a sulfonylurea or long-acting insulin, may persist for up to 24–36 hours following the last dose, especially if there is concurrent renal impairment. Blood-glucose monitoring should be continued for at least 24–48 hours.

Answer 100

random plasma GH is unreliable so cannot use to detect disease: Oral glucose tolerance test (OGTT): high glucose fails to suppress GH levels MRI: of pituitary fossa to look for adenoma Visual fields and acuity ECG; Echo: cardiomegaly Biochem tests: assessing pituitary hormone secretion Old photos if possible to compare progression of signs in person

Answer 101

``` Trans-sphenoidal surgery (first line) Somatostain analogues (SSA) such as octreotide or lanreotide and/or radiotherapy GH antagonist (Pegvisomant); for those resistant to SSA; suppresses IGF-1 production by liver reducing metabolic effects ```

Answer 102

Syndrome: excess ACTH in the body Disease: excess ACTH caused specifically by adneomas/cancers

Answer 103

Clinical presentations of chronic glucocorticoids excess Loss of normal feedback in HPA axis ie is not suppressed by DEXA administration Loss of circadian rhythm of cortisol secretion Causes: generally divided into two groups: ACTH dependent causes (high ACTH) such as pituitary microadenoma (cushings DI) most common cause 80%; ectopic ACTH such as SCLC or carcinoid secretion ACTH independent causes : low ACTH chief cause of cushing syndrome in general is oral steroids (iatrogenic); adrenal adenoma or nodular hyperplasia causing high cortisol secretion *paraneoplastic Cushing’s is excess ACTH secretion from cancer; can be ectopic or not*

Answer 104

``` Obesity, moon face, buffalo hump Easy bruising, atrophic skin, purple striae, hirsutism Poor wound healing Susceptibility to infections Proximal myopathy High BP DM Menstrual irregularity/gynecomastia in males Osteoporosis Subtle mood changes Growth retardation in children peptic ulcer disease in GI ```

Answer 105

High chance of heart problems due to increase BP and increased fat storage High chance of DM from increased BG and increased fat storage (affect beta cells) Low immunity: prone to infection

Answer 106

Bilateral adrenal hyperplasia from ACTH secreting pituitary microadenoma Occurs equally in males and females peak incidence between 30-50years Specific features of ectopic ACTH: Pigmentation (ACTH stimulates melanocyte stimulating hormone MSH Hypokalaemic metabolic alkalosis Weight loss Hyperglycemia (DM)

Answer 107

Iatrogenic: pharma steroids; most common cause of Cushing’s Adrenal adenoma/cancer: tumor is autonomous so high dose DST fails to suppress cortisol production. Pts may also present with abdominal pain +/- virilisation in women Adrenal nodular hyperplasia: autonomous so high dose DST fails to suppress cortisol also

Answer 108

Low dose dexamethasone suppression test (1mg): If cortisol levels/ACTH/CRH do not decrease = Cushing’s disease; if abnormal; perform next step to differentiate between underlying causes. Normal response is decrease in hormone secretion from all glands. High dose dexamethasone suppression test (8mg): suppresses cortisol in cases of pituitary adenoma (still shows some negative feedback). In cases of ectopic ACTH (e.g. SCLC or adrenal adenomas) neither cortisol or ACTH will be suppressed as ACTH production is independent of the hypothalamus so no negative feedback is taking place 24 hr urinary free cortisol can be used as alternative to DST’s to diagnosis Cushing’s; but does not indicate underlying cause - high cortisol over 24 hrs = Cushing’s Bloods: FBC: raised WCC and electrolytes (potassium may be low if aldosterone also secreted by adrenal adenoma); plasma ACTH (low=adrenal adenoma/cancer, need CT/MRI; high = non adrenal cause indicates DST or CRH test; IV CRH increases cortisol in pituitary adenoma but not in ectopic) MRI: pituitary adenoma; detects only 70% microadenomas in Cushing’s Chest CT: SCLC Abdominal CT: adrenal tumours

Answer 109

Start low dose (1mg) test: results show low cortisol = normal axis function high/normal range cortisol= Cushings syndrome ``` High DST (8mg): Low cortisol = Cushings disease from pituitary adenoma High/normal cortisol = check ACTH levels high ACTH levels = Ectopic ACTH secretion from SCLC Low ACTH levels = Adrenal Cushing's (adrenal adenoma) ```

Answer 110

If iatrogenic: taper medications if possible Trans-sphenoidal removal of pituitary adenoma Surgical removal of adrenal tumour Surgical removal of tumour producing ectopic ACTH If surgical removal of the cause is not possible: may remove both adrenal glands and give pt steroidal replacements for life +/- radiotherapy + mitotane (direct selective cytotoxic effect on adrenal cortex causing adrenal atrophy) For ectopic ACTH (SCLC-carcinoid) that is inoperable or unlocatable; metyrapone, ketoconazole, fluconazole to decrease cortisol secretion

Answer 111

Adrenal insufficiency syndrome Primary: addison’s disease (rare; fatal) shows high pigmentation Secondary: iatrogenic: abrupt cessation of long term steroid therapy (common; fatal) does NOT show high pigmentation tertiary: caused from over secretion of CRH from hypothalamus (rare!) usually from long term steroid use axis suppression Addisonian crisis: shock and death Destruction of the adrenal cortex causing glucocorticoid and mineralocorticoid deficiency Can be associated with other autoimmune diseases like Graves, pernicious anaemia, T1DM etc. CAUSE: Autoimmune disease in 80% cases UK TB is most common cause in the world

Answer 112

``` in both addison’s disease and steroid withdrawal: Lean, tanned (pigmentation in palmar creases and buccal mucosa), vitiligo Tired, anorexia, tearful +/- weakness Dizzy, faint, postural Hypotension Flu-like myalgias Depression, psychosis Nausea, vomiting Abdominal pain diarrhoea/constipation ``` *pigmentation only in addison’s disease NOT steroid withdrawal* Difficult to diagnose symptoms are all over the place - think of Addisons always in unexplained abdominal pain or vomiting with any other findings!

Answer 113

Hydrocortisone (20mg on waking and 10mg evening to mimic normal diurnal rhythm) to correct glucocorticoid stress Mineralocorticoids (fludrocortisone 50-200mcg daily) to correct postural hypotension, hyponatraemia and hyperkalaemia Medic alert bracelet or necklace: carry steroid card: keep ampoule of hydrocortisone at home During any stress (infection, trauma, surgery) increase normal doses to compensate for increase demand of hormones

Answer 114

``` Acute presentation of severe Addisons, where the absence of steroid hormones leads to a life threatening presentation. Present with: Reduced consciousness/confusion Hypotension Oligura Profound weakness Hypoglycaemia, Hyponatraemia, Hyperkaemia Patients can be very unwell, similar to shock ```

Answer 115

can be the first presentation of Addison's Disease or triggered by infection, trauma, MI, asthma, alcohol intake, pregnancy, exogenous steroid withdrawal or reduction or other acute illness in someone with established Addisons. Or just forgot to take tablets. Most common cause is steroid withdrawal: always look for medic alert bracelet to indicate pt on steroids

Answer 116

Do not wait to perform investigations and establish a definitive diagnosis before treating someone with suspected Addisonian Crisis as this is life threatening and they need immediate treatment. Take bloods for plasma cortisol and ACTH before treatment but dont wait for results! Ask for FBC, urea, electrolytes, BG, serum Ca and blood cultures Hydrocortisone 100mg IV 0.9% saline 1L over 30-60mins 50mL 50% dextrose for hypoglycaemia Find cause/trigger eg infection Hydrocortisone then given IM 6 hourly until BP stable and vomiting ceased saline 2-4L IV in 12-24hrs; monitor JVP and CVP Expect recovery of BP, BG and Na within 12-24hrs When stable, convert to oral maintenance for life

Answer 117

Never stop therapies abruptly, always taper off to prevent inducing Addisons disease Steroid card: all prescribing Drs/dentists/surgeons must be informed of steroid use Whenever acutely unwell: go to GPs to increase steroid dose Pt should be aware of the side effects of steroid therapy; Peptic ulcer disease, HTN, osteoporosis, Cushingoid syndrome Receive regular check ups

Answer 118

2(Na) + 2(K) + Glucose + urea (Can calculate +/- potassium also. not sure it matterrrrs

Answer 119

OPQRST: Onset: “When did you first begin to gain weight?” “Have you struggled with your weight since childhood?” “What did you weigh in high school, college, early 20s, 30s, 40s?” “Did the weight gain begin when you started taking a certain medication?” Precipitating factors: “What life events may have led to your weight gain—such as college, work stress, marriage, divorce, financial loss, a period of depression, onset of an illness?” “How much weight did you gain with pregnancy?” “How much weight did you gain when you stopped smoking?” “How much additional weight did you gain when you started insulin, steroid ?” “Do you recall specific challenges or barriers to maintaining weight loss that led to regaining weight?” Quality of life: What do they struggle to do because of this? Does it impact their daily life at all? How do they feel and function; assess sleep (sleep apnea) Remedy: What have you tried in the past? Diets; supplements; Exercise; medications; what worked/didn’t. What did you find difficult about each? What worked best? Setting: What was going on in your life around this time? Stress factors; social support network Temporal pattern: Any patterns of weight gain? Seasonal? Over time? Over short periods? Triggers; stresses; What is their lightest and heaviest weight?

Answer 120

Weight (kg) / Height (m2) ``` Underweight - <18.5 Healthy weight - 18.5-24.9 Overweight - 25-29.9 Obese - 30-34.9 Severely obese - 35 - 39.9 Morbidly obese - 40+ ```

Answer 121

Combination of Obesity; diabetes and HTN: to diagnose need 3 or more of the following: Waist circumference of 94cm or more in European men, or 90cm or more in South Asian men Waist circumference of 80cm or more in European and South Asian women High triglyceride levels (fat in the blood) and low levels of HDL (the "good" cholesterol) in your blood, which can lead to atherosclerosis High blood pressure that's consistently 140/90mmHg or higher Inability to control blood sugar levels (insulin resistance)

Answer 122

From diet K+ rich foods: white beans, potatoes, parsnips, spinach, bananas, oranges, pineapples, apricots, leafy greens, lean meats, avocados, yogurt, coconut, water, beans and nuts Important for cell function, digestion, heart rhythm, pH, nerve impulses, maintaining water balance and muscle contractions Mostly intracellular stored in large reservoirs for cells to gain quickly Extra K+ not needed is removed from blood via the kidneys

Answer 123

Mild: 5.5-5.9mmol/L Moderate: 6-6.4mmol/L Severe: 6.5+ mmol/L

Answer 124

➤PSEUDOHYPERKALEMIA: haemolysis, prolonged transit time to lab or poor storage conditions, difficult venepuncture, marked leukocytosis ➤RENAL IMPAIRMENT: AKI/ CKD ➤ACIDOSIS ➤ADDISON’S DISEASE ➤ENDOGENOUS CAUSES: Tumour lysis syndrome, trauma, burns, rhabdomyolysis ➤DRUGS: Potassium sparing diuretics: Aldosterone antagonists: spironolactone ACE inhibitors and angiotensin II receptor blockers Potassium containing laxatives e.g. macrogol, fybogel

Answer 125

``` Muscle cramps, paralysis, weakness Numbness, tingling SoB Nausea, vomiting Chest pain Palpitations Hypo-or a reflexia Irritability ECG changes ```

Answer 126

always take ECG for all severities!! Peaked T waves (5.5+ mild/moderate hyperkalaemia) Progressive paralysis of atria: P waves wide and flattens; PR prolonged; P waves eventually hidden (6.5+severe hyperkalaemia) Conduction abnormalities and bradycardia: wide QRS bizarre morphology; conduction blocks; sinus bradycardia; slow AF; sine wave (7+ severe) Cardiac arrest: asystoles; VF; Pulseless electrical activity (PEA) with bizarre wide complex rhythm (9+ life threatening)

Answer 127

Five key steps: Protect the heart: Calcium gluconate/Calcium chloride Shift K+ into cells: Insulin and glucose infusion and nebulised salbutamol Remove K+ from body: Calcium resonium/haemodialysis Monitor K+ and glucose: Serum levels using VBG Prevent recurrence: Regular BP; prescribing and risk factors assessments and moitoring

Answer 128

calcium gluconate/ calcium chloride Reduced cardiomyocyte excitability to reduce chance of cardiac arrhythmia including VF 10 ml 10% calcium chloride (6.8 mmol Ca2+) IV over 5 - 10 minutes OR 30 ml 10% calcium gluconate (6.8 mmol Ca2+) IV over 15 minutes Dose can be repeated after 5 - 10 minutes if hyperkalaemic ECG changes persist and repeated later as required for recurrence of ECG changes. Calcium salts are irritant to veins – monitor injection site closely. Use large peripheral vein if a central venous access device is unavailable

Answer 129

insulin and glucose infusion AND nebulised salbutamol: Facilitates glucose uptake into cell which also results in K+ doing the same Give 10units soluble insulin (eg actrapid) in 50ml glucose 50% over 15 mins with regular capillary blood glucose checks Effective within 15-30mins Duration of action 4-6hrs NEBULISED SALBUTAMOL: Increases shift of extracellular potassium into intracellular space Nebulised salbutamol (10 - 20mg) should only be used as an adjuvant therapy in severe hyperkalemia (K+ ≥ 6.5 mmol/L). It should be used with caution in patients with cardiovascular disease. The effect of salbutamol is dose-dependent. A further dose may be given if necessary. Effective within: 30 - 60 minutes; max. effect should be seen 90 minutes after dose. Duration of action: 4 - 6 hours

Answer 130

calcium resonium/hemodialysis: Not recommended in emergency treatment of severe hyperkalaemia (onset action within 4hrs) Should be considered in pts with mild-mod hyperkalaemia. Use restricted to max 2 days and stopped once K+ normalalised Oral: 15 g every 6 - 8 hours in a suspension of water or syrup in the ratio of 3 - 4 ml/ g of resin. Rectal: Add 30 g to 150 ml water or 10% dextrose. Enema should be retained for at least 9 hours then colon irrigated to remove resin Co-prescribe lactulose with oral resin to avoid constipation and the formation of bezoars which could perforate the gut. Haemodialysis may be required to remove potassium in resistant cases, particularly in patients with acute kidney injury (AKI) or pre-existing chronic kidney disease.

Answer 131

Measure serum K+ at least 1, 2, 4, 6 and 24 hrs after treatment Look for rebound hyperkalaemia after initial response VBG used for monitoring BG should be monitored at 0, 15, 30, 60, 90, 120, 180, 240, 300 and 360 mins for minimum of 6hrs after administration to check for hypo/hyperglycemia etc.

Answer 132

Regular blood monitoring for pts with CKD Careful drug prescribing Assess risk factors e.g. current medications and make new follow up plan for pt treatment

Answer 133

Risk of re-entrant arrhythmias Often associated with hypomagnesia; increases risk of malignant ventricular arrhythmias Should always check Mg with K+ in any arrhythmia pt Top up Mg to >1mmol/L and K+ to 4-4.5mmol/L to stabilise myocardium and protect against arrhythmias Mild: 3.1-3.5mmol/L Moderate: 2.6-3mmol/L Severe: <2.5mmol/L

Answer 134

Drugs: diuretics (particularly loop, thiazides and thiazide like such as indapamine and metolazone), mineralcorticoids (esp. fludrocortisone), B adrenergic mimetics, insulin, Drugs primarily causing hypomagnesaemia, including aminoglycosides, cisplatin, amphotercin B, Abusive use of laxatives Nutritional status (anorexia nervosa, chronic alcoholism, vomiting/diarrhoea) DKA Urinary loss (Conn’s Syndrome, heart/liver failure, Cushing’s Syndrome) Ectopic ACTH production

Answer 135

``` Weakness Fatigue Muscle cramps Constipation Palpitations ECG changes: K+ <2.7mmol/L: increased P wave amp and width; PR prolongation; T wave flattening/inversion; ST depression; prominent U waves in precordial leads; long QT interval (due to fusion of T and U waves) ```

Answer 136

always look at local guidelines: Mild: give one or the other: Sando-K dispersible tablets (contain 12mmols K+); 2 tablets OD. Kay-Cee-L liquid (1mmol/ml K+) 20ml OD. Moderate: ORAL: SandoK: 2-3 tablets 3xdailys Kay-Cee-L syrup 20ml 3xdaily IV: 20-40mmol K+ replacement over 6-8hrs Severe: 20-40mmol K+ IV max rate 20mmol/hr Cardiac monitoring Solutions with more than 30mmol K+ given via large vein Infusion site should be checked every 4hrs for thrombophlebitis Recheck K+ at regular intervals to prevent hyperkalaemia

Answer 137

Mostly located in blood and fluid around cells Helps maintain fluid balance Plays key role in normal nerve and muscle function Obtained via diet and lost primarily in sweat and urine Healthy kidneys maintain Na level via excretion

Answer 138

dehydration/fluid loss Decreased thirst: with age thirst sensitivity decreases so aren’t as hydrated as needed Changes to kidney: aging kidney may be less able to reabsorb water and electrolytes from urine resulting in greater water excretion Less fluid in the body: in elderly the body contains less fluid. Only 45% body weight is fluid compared to 60% in younger people. This means a smaller fluid change in elderly can have more serious consequences than younger Inability to obtain water: some elderly physical problems prevent them getting something to drink when thirsty such as dementia pts who depend on other people to give them water and remind them to drink etc. Drugs: high BP drugs, DM or heart disorder drugs can increase excretion and magnify ill effects of fluid loss

Answer 139

➤ Serum Na >146mmol/L can be caused by reduced water intake (dehydration), or where water losses are greater than sodium losses (e.g. watery diarrhoea). ➤ There are no specific clinical features of hypernatraemia. It is usually diagnosed incidentally on serum testing. Also check other biochemical indices such as renal failure, hyperglycaemia and hypercalcaemia. ➤ Identify underlying cause of hypernatraemia. Consider measuring urine osmolality. ➤ Urine osmolality < plasma osmolality – look for diabetes insipidus ➤ Urine osmolality > plasma osmolality – look for osmotic diuresis / heatstroke, etc. ➤ If patient is also hypovolaemic, then monitor urinary output and renal function.

Answer 140

Replace missing water with oral water Address underlying cause where possible e.g. gastro fluid loss, control pyrexia, correct hypergycemia, withhold lactulose and diuretics which may be sufficient to reverse hypernatraemia. Where active correction is needed; fluids administered orally or enterally with IV as last resort Regular monitoring of serum Na and water then adjusting hypotonic infusion accordingly

Answer 141

Mild: 130-134mmol/L Moderate: 125-129 Severe: <125mmol/L

Answer 142

Pulmonary cancers (SCLC; mesothelioma) Gastrointestinal cancer (duodenum, pancreas and colon) Other cancers (brain tumours; carcinoid tumours; ewing sarcoma; leukaemia; thyroma etc.) Drugs (adenine arabinoside; cyclophosphamide; ifosfamide; methotrexate; antidepressants; antipsychotics; NSAIDs; anti-epileptics) Iarogenic volume depleted +/- NBM with inappropriate hypotonic fluid Hypovolaemic (hypotension, tachycardia, dry mucus membrane: GI loss; renal Na loss; hypoadrenalism; loop diuretics +/- ACEi; thiazide diuretics (elderly may be esp sensitive); cerebral salt wasting (e.g. after subarachnoid) hypothyroidism Hypervolaemia - CCF, advanced liver disease, renal failure Euvolaemia (SIADH)

Answer 143

``` Weakness, fatigue, anorexia, lethargy Nausea, vomiting Muscle cramps Headache Worsening mental status Irritability, agitation, confusion, disorientation Hallucinations Poor balance Seizures Coma ```

Answer 144

➤ Urea and electrolytes ➤ Serum osmolality: Readily differentiates between true hyponatraemia and pseudohyponatraemia (secondary to hyperlipidaemia or hyperproteinaemia) or may be hypertonic hyponatraemia associated with elevated glucose, mannitol, glycine (posturologic or postgynaecologic procedure), sucrose. ➤ Urine osmolality: Helps differentiate between impaired free-water excretion and primary polydipsia. In SIADH, >100mOsm/kg (submaximally dilute) indicates impaired ability of the kidneys to dilute the urine. ➤ Urine sodium In SIADH the urine sodium >20–40mEq/L. With hypovolaemia <25mEq/L ➤ TSH, serum cortisol - if hypothyroidism or hypoadrenalism is suspected ➤ LFTs and Lipids - high levels of hyperproteinaemia and hyperlipidaemia can cause pseudohyponatraemia ➤ CXR - ?underlying pulmonary cause of SIADH ➤ CT Head - cerebral oedema, R/O other causes of neurological status of pt

Answer 145

Developing within 48hrs has high risk of permanent neurological sequelae as result of cerebral oedema unless plasma Na corrected Pts with chronic hyponat. At risk of cerebral osmotic demyelination if correction is excessive or too rapid

Answer 146

Acute hyponatremia: moderate symptoms: Aim to raise Na by 1mmol/L each hr until symptoms resolve or serum Na >130mmol/L DO NOT raise by more than 12mmol/L in first 12hrs Consider giving furosemide to enhance free water loss If pt has severe neurological symptoms; consider hypertonic (3%) NaCl as IV infusion at 1-2mL/kg/hr Close monitoring esp for IV infusion preferably in HDU

Answer 147

Chronic hyponatraemia: Water restriction to 1L/day if volume repleted Investigate underlying cause Demeclocycline may be useful for patients with SIADH secondary to malignancy. This drug takes 1–2 weeks to have an effect Vasopressin-2 receptor antagonists – Tolvaptan (titrate starting at 15mg OD to 60mg OD, PO) Can also be used after Demeclocycline, if no improvement. *Pts to be treated with fluid restriction often require education regarding free water content of foods and explanation of need to limit intake of liquids to predetermined level*

Answer 148

The syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) is defined by the hyponatraemia and hypo-osmolality resulting from inappropriate, continued secretion or action of the hormone despite normal or increased plasma volume, which results in impaired water excretion

Answer 149

Primary brain injury (e.g. meningitis. subarachnoid haemorrhage) Malignancy (e.g. small-cell lung cancer) Drugs (e.g. carbamazepine, SSRIs, amitriptyline) Infectious (e.g. atypical pneumonia, cerebral abscess) Hypothyroidism

Answer 150

vary depending on severity and rate of development: mild cases may cause significant symptoms if it develops acutely (fast) whereas chronic cases may be completely asymptomatic. This is thought to be from cerebral adaptation (compensatory process) where metabolism adapts to consistently lowered Na levels Mild hyponatraemia: nausea, vomiting, headache, anorexia and lethargy. Moderate hyponatraemia: muscle cramps, weakness, confusion and ataxia. Severe hyponatraemia: drowsiness, seizures and coma.

Answer 151

Fluid status Bloods: serum Na low; reduced plasma osmolarity; TFTs (potential hypothyroidism); serum cortisol to rule out Addison’s U+Es: osmolarity; Na CXR/chest CT to rule out SCLC etc.

Answer 152

Hyponatraemia with corresponding hypo-osmolality (plasma osmolality <280mosmol/kg • Urine less than maximally dilute (greater than 100mOsm/kg, generally greater than 400–500mOsm/kg with normal renal function) • Continued renal excretion of sodium (>40mmol/l) • Absence of clinical evidence of volume depletion • Absence of other causes of hyponatraemia • Correction of hyponatraemia by fluid restriction

Answer 153

Carries electric charge when dissolved in body fluids Majority is bound to proteins stored in bones so does not carry charge Bone contains around 50% body’s Mg; blood contains very little Mg needed for bone and teeth formation; nerve and muscle function; enzyme function; also related to metabolism of Ca2+ and K+ Level in blood depends largely on how Mg is obtained from foods and excreted in urine and stool and less to do with total body stores

Answer 154

Under-diagnosed problem particularly as Mg is not routine biochem testing Common in oncology pts receiving treatment as can be caused by no. of chemotherapies Can also be caused by malabsorption, malnutrition, chronic alcoholism, uncontrolled DM, acute renal failure, diarrhea or fistulae and secondary to other electrolyte abnormalities (hyper/hypocalcaemia, hypokalaemia/TPN) Often accompanied by low Ca and K levels so must check these along with renal function If cause unclear order 24hr urinary Mg test

Answer 155

``` grade 1: Lower limit normal - 0.5mmol/L grade 2: 0.5-0.4 grade 3: 0.4-0.3 grade 4: <0.3 grade 5: Death ```

Answer 156

CV: ventricular arrhythmias; SVTs: HTN: Digoxin toxicity ECG changes: ST depression; altered T waves; reduced voltage; Prolonged PR interval and wide QRS complexes Neuromuscular: Tetany; muscle cramps; convulsion; muscle fasciculation; carpopedal spasm; peripheral paraesthesia; weakness Neurological: Confusion; psychosis; depression; agitation; ataxia; spasticity; Tremor; Delirium Other: Nausea; vomiting; diarrhoea

Answer 157

(per stage): Grade 1: No replacement needed; pts usually asymptomatic Grade 2: 5g (20mmol) Mg sulfate (MgSO4) in 500ml normal saline over 6-8hrs. Oral Mg supplements may be tried (not well tolerated usually causes diarrhoea) Mg glycerophosphate 4-8mmol up to qds. Grade 3 OR 4: risk of cardiac arrhythmias so also consider cardiac monitoring in severe cases. 5g (20mmol) MgSO4 in 1L normal saline over 8–10 hours. Repeat daily for up to 3–5 days until serum magnesium normal. If renal impairment: reduce dose to 2.5g (10mmol) MgSO4 over 24 hours. If hypocalcaemic, correct magnesium level until calcium in normal range. If hypokalaemic, Replace 40mmol potassium chloride (KCl) and 1.25mg (5mmol) MgSO4 in 500ml normal saline over 6 hours and repeat for up to 24 hours, checking potassium and Mg levels regularly.

Answer 158

Severe hypomagnesaemia with cardiac arrhythmias e.g. VT : * 2g MgSO4 IV over 15 minutes (max rate 0.6mmol/minute). * Followed by infusion of 5g (20mmol) MgSO4 in 1 normal saline for 3–5 days (see above). * Rapid IV Mg therapy can cause hypocalcaemia, hypotension: this should only be undertaken in an emergency, with adequate acute medical support. * Patients must be on a cardiac monitor and have regular assessment of all electrolytes.

Answer 159

99% Ca stored in bones but cells (esp. muscle) and blood also contain Ca Essential for bone and teeth formation; muscle contraction; normal enzyme; blood clotting and heart rhythm function Body precisely controls Ca in cells and blood Moves Ca out of bones into blood as needed to maintain steady Ca levels If not enough dietary Ca consumed then too much Ca is mobilised frombones wekneing them which can result in osteoporosis Need to consume around 1,000-1,500 milligrams Ca per day to prevent this weakening Regulated by PTH and calcitonin mainly

Answer 160

Hypercalcaemia can be a presenting feature of serious disease, including malignancy; even when calcium is not raised to acutely dangerous levels, it is important to define the cause. Mild: 2.65-3 (non-emergency) Mod: 3-3.5 (possible emergency) Severe: >3.5mmol/L (med emergency)

Answer 161

``` More than 90% cases are due to: ➤Primary hyperparathyroidism ➤Renal disease – tertiary hyperparathyroidism, treatment with vitamin D analogues. ➤Malignancy Less common causes of hypercalcaemia ➤Sarcoidosis ➤Vitamin D toxicity Other causes, including drugs e.g. lithium, thiazide ```

Answer 162

➤Ensure dehydration is corrected with IV sodium chloride 0.9% ➤Withhold or discontinue all medications that may promote hypercalcaemia E.g. thiazides, vitamin D compounds, lithium ➤Do not give infusion fluids containing calcium (such as Hartman’s) ➤First-line treatment is with disodium pamidronate; see BNF/ guidelines ➤In all cases, infusion rate must not exceed 1 mg/minute and concentration must not exceed 30 mg/125 mls. ➤The maximum treatment course in all patients is 90 mg. Higher doses do not improve clinical response. ➤A significant decrease in serum calcium is generally observed 24 to 48 hours after administration of pamidronate disodium, and normalisation is usually achieved within 3 to 7 days. ➤If normocalcaemia is not achieved within this time, a further dose may be given. The duration of the response may vary from patient to patient, and treatment can be repeated whenever hypercalcaemia recurs. ➤Clinical experience to date suggests that pamidronate disodium may become less effective as the number of treatments increases.

Answer 163

Renal function: check serum creatine before each dose of pamidronate (Bisphosphonates have been associated with renal toxicity manifested as deterioration of renal function and potential renal failure. Renal deterioration, progression to renal failure and dialysis have been reported in patients after the initial dose or a single dose) Serum calcium, phosphate and magnesium as hypocalcaemia, hypophosphataemia and hypomagnesaemia can occur. Monitor blood pressure

Answer 164

➤ Mild hypocalcaemia is usually asymptomatic. ➤ Symptoms of hypocalcaemia generally correlate with the rate and magnitude of calcium depletion. It has been suggested that patients are less likely to be symptomatic if the serum calcium concentration has declined slowly. ➤ Treatment regimen MUST NOT rely on serum calcium level alone.

Answer 165

``` ➤Septic shock ➤Rhabdomyolysis ➤Hypomagnesaemia ➤Pseudohypoparathyroidism ➤Malignant disease ➤Calcium malabsorption ➤Severe acute pancreatitis ➤Chronic renal insufficiency ➤Hypoparathyroidism ➤Post parathyroidectomy ➤Inadequate dietary calcium intake ➤Vitamin D deficiency ➤Massive blood transfusion ➤Drug-induced: including some anticonvulsants, bisphosphonates, calcitonin, phosphate, colchicine overdose, foscarnet, citrated blood transfusions, radio contrast dye, ketoconazole and some antineoplastic agents ```

Answer 166

ORAL: asymptomatic; mild cases usually oral Ca supplement given at dose of 10-50mmol daily adjusted to pt needs. IV replacement not thought to be any added benefit in mild cases Prescribe 2.2 to 4.5 mmol calcium gluconate as a slow intravenous injection over 5 to 10 minutes with ECG monitoring throughout the injection -THEN 22.5 mmol calcium (as gluconate) in 1 litre sodium chloride 0.9% administered at a rate of 50ml/hour 10ml/kg of the above described preparation is estimated to increase serum calcium concentrations by 0.3 - 0.5 mmol/L **always need ECG monitoring**

Answer 167

Monitoring: U+Es PTH and vit D before treatment Mg: if hypocalaemia secondary to hypoMg; correction of Mg may lead to spontaneous normalisation of Ca after lag of 2 days ECG monitoring Infusion site monitored regularly to ensure extravasation has not occurred Points to think about: There is a risk of cardiac arrhythmias if the calcium is administered too quickly. Some prefer calcium chloride to calcium gluconate for parenteral Administration, because retention of calcium from the chloride salt is thought to be greater than from the gluconate salt, and results in a more predictable increase in extracellular ionised calcium concentration. Calcium chloride is considered to be the most irritant of the calcium salts. Available preparations: - calcium gluconate 10% in 10ml injection (equivalent to 2.25mmol Ca2+)

Answer 168

Recommended intake for adults is 1.5-2.5L Indications for fluids: patients whose needs cannot be met by oral or enteral routes. Where possible oral fluid intake should be maximised and IV fluid only used to supplement the deficit.

Answer 169

``` Resuscitation Routine maintenance Replacement Redistribution Reassessment ```

Answer 170

Bloods Crystalloids: solutions of small molecules in water (e.g. sodium chloride, Hartmann’s, dextrose) Colloids: solutions of larger organic molecules (e.g. albumin, Gelofusine) Colloids are used less often than crystalloid solutions as they carry a risk of anaphylaxis and research has shown that crystalloids are superior in initial fluid resuscitation K+ cannot exceed around 10-20ml fast delivery must be set via pump to accurately measure delivery rate to avoid harmful arrhythmias/effects on heart

Answer 171

Administer initial 500ml fluid bolus of crystalloid solution (eg saline or hartmans) over <15mins Reassess pt status using ABCDE Give further 250-500ml bolus if needed the reassess again Can repeat process if ongoing clinical evidence suggests need to do so until up to 2000ml given total Seek expert help if fluids still needed Pts with comorbidities such as heart or renal failure should be much more cautions about giving fluids If pt if normovolaemic but has signs of shock seek expert help immediately

Answer 172

25-30 ml/kg/day of water and approximately 1 mmol/kg/day of potassium, sodium and chloride and approximately 50-100 g/day of glucose to limit starvation ketosis (however note this will not address the patient’s nutritional needs) Weight-based potassium prescriptions should be rounded to the nearest common fluids available. Potassium should NOT be manually added to fluids as this is dangerous. *Obese, elderly, HF, renal impaired, malnourished pts: adjust prescription to ideal body weight (lower range for volume per kg) as pts rarely need more than 3 L fluid per day* Patients with existing fluid or electrolyte abnormalities require a more tailored approach to fluid prescribing (see basic examples below): Dehydration – will require more fluid than routine maintenance Fluid overload – will require less fluid than routine maintenance Hyperkalaemia – will require less potassium Hypokalaemia – will require more potassium Estimate any fluid or electrolyte deficits/excesses: Add or subtract these estimates from the standard routine maintenance fluid regime discussed in the last section to provide a more tailored fluid prescription.

Answer 173

confusion or memory loss. numbness and tingling in the hands, feet, and face. depression. hallucinations. weak and brittle nails. easy fracturing of the bones. Chvostek sign: contraction of facial muscles in response to facial nerve stimulation via tapping lightly anterior to the ear on zygomatic arch; indicates nerve hyperexcitability Trousseau sign: caropopedal spasm caused by inflating BP cuff to level above systolic pressure for 3 mins. Hand curls inwards towards the body. Carpopedal spasm: frequent and involuntary muscle contractions in hands and feet. Can cause a lot of pain Seizures Tetany: spasms in hands and feet; cramps; overactive neurological reflexes. Generally specific to low blood Ca

Answer 174

HF AKI Higher risk in elderly and those with cardiac/renal impairment, sepsis, major injury/surgery Increased ADH secretion Excretion of excess Na and water is more difficult for injured or surgical pts (physiological response i injury and surgery affect renal function and therefore fluid balance

Answer 175

Primary adrenal insufficiency due to: CAH—certain types, most commonly 21-hydroxylase deficiency, are associated with MC deficiency. Congenital lipoid adrenal hyperplasia (CLAH) caused by mutations in the genes encoding steroidogenic acute regulatory protein (StAR), responsible for rapid import of cholesterol into the mitochondrion, and the side chain cleavage protein (CYP11A1), responsible for the conversion of cholesterol to pregnenolone, i.e. the first step of steroidogenesis. Adrenal hypoplasia congenita (AHC) caused by mutations in the genes encoding the transcription factors SF-1 (NR5A1) and DAX-1 (NR0B1) that play a crucial role in adrenal development. Adrenoleukodystrophy affecting 1/20,000 ♂; very long chain fatty acids (VLCFA) cannot be oxidized in peroxisomes and accumulate in tissues and the circulation. CNS symptoms may be absent initially, in particular, in the milder form adrenomyeloneuropathy, but progressive demyelination can lead to hypertonic tetraparesis, dementia, epilepsy, coma, or death (in particular, in the early childhood onset variant adrenoleukodystrophy). Rare inherited disorders of aldosterone biosynthesis. Pseudohypoaldosteronism—inherited resistance to the action of aldosterone. Autosomal dominant and recessive forms are described. Usually presents in infancy. Treated with sodium chloride.

Answer 176

All forms of non-congenital primary adrenal insufficiency the RAA system remains intact as the adrenal glands are anatomically intact Drugs—heparin (heparin for >5 days may cause severe hyperkalaemia due to a toxic effect on the zona glomerulosa); ciclosporin. Hyporeninaemic hypoaldosteronism—interference with the renin-angiotensin system leads to mineralocorticoid deficiency and hyperkalaemic acidosis (type IV renal tubular acidosis), e.g. diabetic nephropathy. Treatment is fludrocortisone and potassium restriction. ACEI may produce a similar biochemical picture, but here the PRA will be elevated, as there is no angiotensin II feedback on renin.

Answer 177

Hypervolemia Too much fluid in the blood; excess fluid (mostly Na and water) builds in the body resulting in weight gain Leading cause if from CHF Or caused by acute kidney injury Can be iatrogenic from fluid administration

Answer 178

Limb swelling (peripheral oedema) Ascites (fluid in abdomen) Extreme generalised oedema/skin swelling (anasarca) Pleural effusion

Answer 179

``` Diagnosed via exclusion of other conditions such as: Lung conditions; blood clots; infections; asthma Heart problems; pericarditis Venous circulation or lymphatic circulation problems Hypoproteinaemia Liver disease Thyroid disease Investigations: ECG CXR Bloods: infection; BNP (CHF) Urine output and drink intake ```

Answer 180

Diuretics (loop and thiazide) Mineralocorticoids/aldosterone receptor antagonists MRAs (spironolactone and eplerenone Dialysis may be needed for future Prognosis depends on the underlying condition and how progressed this condition was before fluid overload occurred

Answer 181

Tumour develops in chromaffin cells in centre of adrenal gland These cells are responsible for release of adrenaline and noradrenaline so help control HR, BP and blood sugar Extra-adrenal tumours (paragangliomas) are more rare and often found by aortic bifurcation

Answer 182

``` 10% rule 10% >> extra-adrenal 10% >> bilateral 10% >> malignant 10% >> in children 10% >> familial 10% >> is part of MEN-2 10% >> makes Stroke 10% >> is discovered incidentally 10% >> is not associated with HTN ```

Answer 183

``` Presentation: Classic triad: headache, sweating, tachycardia BP can be abnormally high or low Malignant HTN Multisystemic signs ``` ``` Triggers: Straining Exercise Stress Abdominal pressure Surgery Beta blockers Tricyclics IV contrast agents ```

Answer 184

Often vague ``` Cardiovascular: Tachycardia Palpitations Dyspnea Syncope Angina ``` ``` CNS: Headache Visual disorders Dizziness Tremor Numbness ``` Psychological: Anxiety Confusion Episodic psychosis Gut: D+V Abdominal pain over tumor sites ``` Other: sweats/flushes Heat intolerance Pallor Backache ```

Answer 185

Investigations: 24 hr urine samples for metanephrines/metadrenaline Abdominal CT/MRI MIBG scan Treatment: Surgery

Answer 186

excess aldosterone production independent of RAA system causing increase Na and water retention and decreased renin release from kidneys. Consider if HTN, hypokalaemia, alkalosis in pt not on diuretics. Na tends to be raised mildly or normal

Answer 187

Secondary: due to high renin from decreased renal perfusion eg renal artery stenosis, accelerated HTN, diuretics, CHF or hepatic failure

Answer 188

major cause of congenital (autosomal recessive) salt wasting. Na and Cl leak out of loop of henle via channel transporter mutations. Presents in childhood as failure to thrive, polyuria, polydipsia, volume depletion from Na loss, increased renin and aldosterone production leading to hypokalaemia and metabolic acidosis. Treated by replacing K+, NSAIDs to inhibit prostaglandins and ACEi

Answer 189

Present in at least ⅓ rd of men in course of their lifetime 60-90% neonates 50-60% adolescents 70% men aged 50-69 Breast cancer only detected in 1% of cases of male breast enlargement Pathophysiology: Oestrogen stimulates breast tissue growth while androgens inhibit growth The ratio of androgens to oestrogens determines overall growth Oestrogen levels can be enhanced by testosterone reduction of production/action Once this ratio falls, breast tissue growth is stimulated, leading to proliferation of breast ducts and fibroblastic stroma. If this stimulus continues then ducts and fibroblastic stroma replaced by fibrosis and gynaecomastia becomes well established and irreversible PSEUDOGYNAECOMASTIA: build up of adipose tissue not breast tissue

Answer 190

Conditions lowered testosterone: such as congenital absence of testes causing severe gynaecomastia. Androgen resistance. Klinefleter’s syndrome (XXY) associated with 80% cases (show increased risk of breast cancer), viral orchitis, trauma, castration or renal disease and dialysis Conditions increasing oestrogen: testicular tumours (secreting oestradiol); hermaphroditism; neoplasms producing hCG increasing oestradiol secretion; adrenal tumours; liver disease or cirrhosis (increased aromatisation); malnourishment and re-feeding syndrome; hyperthyroidism; obesity; extreme stress; aromatase excess syndrome Conditions affectsing sex hormone binding globulin (SHBG); liver disease and cirrhosis cause rise in SHBG Conditions causing androgen resistance Conditions causing increased conversion of testosterone to oestrogen (aromatase is one of the P450 enzymes involved in aromatisation of androgens to oestrogens. Found in many tissues such as adipose; enhanced adipose tissue in obesity increases this enzyme level and hence oestrogen production leading to gynaecomastia NEWBORNS: result of maternal oestrogens and will resolve after few weeks ADOLESCENCE: common around age 14; may be unilateral and tender. Resolves spontaneously within 1-2 years; may be due to relatively delayed testosterone surge with relation to oestrogen at puberty or temporary increase in aromatase activity INCREASING AGE: associated with low testosterone levels Medication accounts for up to 25% all cases in adult males: herbal remedies and cosmetics containing oestrogen; DIGOXIN (enhanced if liver derangement also exists); GnRH agonists; testosterone inhibitors; excessive testosterone replacement therapy; antiretrovirals; CCB; ACEi etc. IDIOPATHIC

Answer 191

Commonly asymptomatic Breast enlargement Tenderness of breast Sexual dysfunction Lack of testosterone: Hairless; shiny skin; testicular size; masses; tenor of voice Signs of cushing’s or hyperthyroidism Check medical history for drugs or abuse of drugs such as anabolic steroids, alcohol, heroin and marijuana Past medical history and family history

Answer 192

Clinical exam to determine if breast tissue is enlarged: pinch breast tissue between finger and thumb: true breast tissue proliferation felt as distinct ‘disc’ of tissue under skin; if not is probably psuedogynaecomastia Ultrasound or mammography to confirm if unsure Assess size and asymmetry LFTs; renal function tests; TFTs; hormone profile (oestradiol, testosterone, prolactin, beta-hCG, alpha fetoprotein AFP, LH) high LG and low testosterone indicated testicular failure, low LH and testosterone = increased oestrogens, high LH and testosterone = androgen resistance or neoplasms secreting GnRH Chromosomal karyotyping: XXY syndromes Ultrasounds Mammography CXR suspected lung lesions Needle core biopsy for definitive diagnosis

Answer 193

``` Unilateral enlargement hard/ irregular breast tissue Rapid enlargement Recent onset Fixed mass Nipple or skin abnormalities Painful >5cm large Axillary lymphadenopathy ```

Answer 194

Management: Refer if any red flag symptoms are present Treat underlying cause if found; medication alterations etc. Reassurance and pt. Education Tamoxifen for pain relief and side effects (anti-oestrogen) Prophylactic breast irradiation in cases of prostatic carcinoma as gynaecomastia is common reason for poor treatment adherence Prognosis: Mostly benign Complete resolution can occur if underlying cause identified and treated before fibrosis occurs

Answer 195

More common in women than men at reproductive age Can occur in nulliparous, menopausal woman and men Can be physiological in women but only pathological in men Cause: Most commonly from hyperprolactinaemia

Answer 196

Physiological: pregnancy and post-lactation: women may lactate from second trimester and continue until up to two years after stopping breastfeeding; fluctuating hormonal levels during menopause may cause this; neonatal (exposure to maternal hormones in-utero can produce gynaecomastia and galactorrhea in newborn; will resolve spontaneously); nipple stimulation or suckling Pathological: Idiopathic hyperprolactinaemia Prolactinomas Addison’s disease Acromegaly Cushing’s Metastatic tumours TB and other infections Sarcoidosis Histiocytosis Drugs increasing PRL: antipsychotics; antidepressants; antihypertensives; contraceptives (combined pill and depot contraceptives); elicit drugs (cannabis, opiates and amfetamines); DIGOXIN Chronic kidney disease; liver failure; hypothyroidism; epileptic seizures Breast surgery; burns; herpes zoster; spinal cord injury; trauma

Answer 197

Lactation: ask about duration, nature, colour, amount of fluid Unilateral or bilateral discharge (uni suggests local pathology and needs breast clinic referral) Spontaneous or expressed? Check medications; prescribed; OTC; elicit? Acne; menstrual irregularity; reduced libido; erectile dysfunction; infertility? Thyroid and endocrine symptoms Headaches; visual symptoms and cranial nerve symptoms (pituitary symptoms)

Answer 198

Clinical exam: thyroid exam, neurological exam; abdo exam for pregnancy; breast examination (discharge; previous breast surgery; palpate lumps and nodes) Bloods: PRL levels, TFTs, renal and LFTs; pregnancy test if needed Visual field tests MRI

Answer 199

Exclude serious pathologies Identify cause and treat if possible Complications depend on underlying cause

Answer 200

Result of enzyme lactase deficiency Lactose allergy is Ig-E mediated reaction Lactose is found exclusively in milk and it’s absorption is dependent on enzyme lactase Essential enzyme in babies but level of enzyme tends to decrease after age 2 although symptoms of intolerance rarely occur before age 6 It’s argued that the enzyme only persists to adulthood because of our habit of drinking other species milk Symptoms arise from reduced absorption of lactose which is broken down by intestinal bacteria leading to gas and short chain fatty acids

Answer 201

Primary: autosomal recessive condition develops with age aka lactase nonpersistence Secondary: follows damage to intestinal mucosa eg bacterial or viral gastroenteritis. Resolves when the disease process is over. More common in children esp. In developing countries Congenital: extremely rare autosomal recessive disorder associated with minimal or complete absence of lactase activity Developmental: occurs in premature babies and improves as intestines mature

Answer 202

``` Bloating Flatulence Abdominal discomfort Loose watery stool; diarrhoea Perianal itching (acidic stool)] Occur 1-several hrs post eating ```

Answer 203

Clinical features: cut out then re-introduce lactose and observe reactions Strict 2 week no lactose diet if symptoms resolve but recur on re-introduction then diagnosis made Lactose intolerance test Breath hydrogen test Genetics test Intestinal mucosal biopsy

Answer 204

``` IBS Milk protein allergy Infantile colic Diverticular disease Ulcerative colitis Coeliac disease CF ```

Answer 205

Avoid milk and dairy products Ca supplements PRN Primary: can often tolerate certain dairy’s Secondary may need fluid resuscitation, should avoid antibiotics Developmental: tube feeding containing reduced lactose milk or breast milk (lactase enzymes present) Congenital: diet full of essential nutrients excluding lactose; lactose free formula milk (NOT BREAST); wean on lactose free foods

Answer 206

Cholesterol carried in blood via lipoproteins LDL = bad cholesterol increase fatty deposits in arteries leading to athlerosclerotic plaque formation HDL = good cholesterol increase removal of these deposits and reduce atherosclerosis formation Total cholesterol normal value 5mmol/L or less LDL <3mmol/L HDL >1.2mmol/L Total cholesterol/HDL ratio 4.5 or less Severe hypertriglyceridemia TGs = >10mmol/L

Answer 207

``` Hypothyroidism Obstructive jaundice Cushing’s syndrome Anorexia nervosa Nephrotic syndrome CKD Familial dyslipidaemias Familial hypercholesterolaemia Apoprotein disorders Pregnancy Obesity Alcohol abuse Medications: thiazides, steroids, cyclosporin (after organ transplants), antiviral therapy, beta blockers, combined oral contraceptive pill etc. ```

Answer 208

``` Family history Smoking Lack of physical activity Obesity Poor diet high in LDLs; excessive salt Excess alcohol HTN High triglycerides Diabetes Kidney function diseases Male Early menopause Increasing age Ethnicity: indian, pakistan, bangladesh or Sri lanka ```

Answer 209

Usually discovered during routine bloods screening when assessing QRISK Fasting blood test (12hrs) Premature arcus senilis (white/grey ring in front of eyes) Tendon xanthomata (hard nodules on tendons of knuckles and achilles Xanthelasma (fatty deposits in eye)

Answer 210

Total lipid profile, TGs, LDL, HDL, total lipid/HDL ratio Fasting blood glucose Familial history: DNA testing TFTs; renal function tests; LFTs; pregnancy tests to exclude secondary causes QRISK

Answer 211

Lifestyle advice and changes: smoking cessation, healthy diet, increased exercise Medications: statins Referrals: If need confirmation of familial diagnosis (DNA testing) Diagnosed with familial hypercholesterolaemia with LDL-C conc >13mmol/L or possible signs of CHD (urgent referral unless life threatening in which case refer as emergency) If signs of failure of therapy Severe cases Tchol >10 or TGs >10mmol/L

Answer 212

Arterial pH <7.35 with plasma bicarbonate <22 Respiratory compensation normally takes effect immediately unless there is a respiratory pathology Calculate expected pCO2 compensation: pCO2 = (1.5 x [HCO3-])+8+/-2

Answer 213

Lactic acidosis (HF, drugs, toxins, inborn errors of metabolism DKA Starvation Excessive alcohol Substance poisoning Impaired acid excretion: renal failure; hyperaldosteronism; impaired H+ excretion Excessive renal bicarb loss: carbonic anhydrase inhibitors Excessive loss of GI bicarb: diarrhoea; faitulae of pancreas, biliary tree or intestine; urinary-GI diversion surgery; cholestyramine

Answer 214

``` Nausea Vomiting Anorexia Increased respiratory rate; tachyponea Dyspnoea Varying non-specific symptoms: lethargy Hypotension Signs of underlying cause ```

Answer 215

``` ABGs U+Es: anion gap; ketones LFTs ECG CXR for infection/cardiac failure Specific Ix for specific cause eg toxicity tests ```

Answer 216

Transfer to HDU for monitoring ECG, O2 sats, BP and HR Intubation or ventilation PRN Large bore IV access for rehydration Treat underlying cause (drug toxicity etc) Only use bicarb infusion in cases of drug poisoning (can be fatal!)

Answer 217

Lungs cannot remove enough CO2 from the body pH <7.35 Typically caused by underlying disease or condition (COPD, asthma, pneumonia, sleep apnea, obesity, scoliosis) Acute and chronic forms Acute: occurs quickly and is medical emergency; can be life threatening if untreated Chronic: develops over time. Does not cause symptoms and body adapts to acidity (metabolic compensation from kidneys producing more bicarb to maintain blood pH) can be exacerbated to cause acute acidosis

Answer 218

``` Headache Anxiety Blurred vision Restlessness Confusion Fatigue Lethargy Delirium or confusion SoB Coma Sleep disturbances Personality changes Memory loss ```

Answer 219

``` ABGs Electrolytes Lung FTs: underlying conditions CXR Management: Acute and chronic both mainly require treatment of underlying conditions causing this ```

Answer 220

pH >7.45 Caused by increased bicarb ions or too few H+ ions Two kinds: chloride responsive alkalosis (loss of H+ ions usually vomiting or dehydration) and chloride resistant (too many bicarb ions or when H+ shift into cells from blood) Respiratory acidosis takes effect quickly to partially or fully compensate while kidneys try to correct metabolic alkalosis

Answer 221

Loss of stomach acids: vomiting, suction Excess antacids: if weak or failing kidneys Diuretics: increase H+ excretion Hypokalaemia Reduced blood volume; liver cirrhosis or weakened heart Genetic causes: Bartter’s syndrome

Answer 222

``` Vomiting Peripheral oedema Fatigue Diarrhea Agitation Disorientation or confusion Seizures Coma ```

Answer 223

``` ABGs Medical history (of vomiting etc.) U+Es Vitals: sats; HR; BP Can also present with hypochloremia which can cause pt to go into shock; however is also treated with saline IV** ```

Answer 224

Chloride responsive: adjust diet to increase salt (NaCl) to increase blood acidity IV saline NaCl solution Chlorine resistant: depleted K+ levels; take potassium chloride pills 2-4xdaily to increase K+ K+ given by IV PRN

Answer 225

``` Too little CO2 within the lung Occurs with hyperventilation (blowing off CO2) pH >7.45 Causes: Heart attack Anxiety Pain Drug use Fever COPD Infection PE Pregnancy ```

Answer 226

``` Dizzy Bloating Numbness and muscle spasms in hands and feet Chest discomfort Dry mouth Tingling arms Heart palpitations SoB Confusion ```

Answer 227

ABGs Medical history Clinical presentation

Answer 228

Depends on underlying cause: find and treat Panic and anxiety related causes: breathing into paper bag increases inhalation of CO2 and should correct CO2 levels. Can also breathe in via pursed lips to restrict oxygen intake

Answer 229

thyrotoxicosis - TSH low; high T3/4 Primary hypothyroidism: High TSH with low T3/4 Secondary hypothyroidism: Low TSH with low T3/4 Subclinical hypothyroidism: TSH slightly raised but below 10; normal T3/4 Hyperthyroidism: low TSH high T3/4 T3 toxicosis: Low TSH; normal T4 and high T3

Answer 230

``` bones, stones, groans and moans High serum Ca Bone pain Kidney stones more likely Abdominal pain Psychiatric symptoms: mood changes etc. ```

Answer 231

measure 3-6 monthly: - adults using diet and lifestyle or on ONE drug (not associated with hypoglycaemia eg metformin) target 48mmol adults on drug associated with hypoglycaemia (gliclazide) target is 53mmol do not use aggressive techniques in elderly or frail BP guide 130/80 cholesterol - total <3 (QRISK >10% start atorvastatin 20mg)

Answer 232

Start with standard release, can switch to modified release if patient has side effects can use modified release Review renal profile; eGFR must be >30 use with caution if around this level Start with 500mg WITH BREAKFAST and increase on weekly basis by 500mg until max dose 2g reached or max tolerated dose Make sure patient takes food with it to minimise side effects Pros: - effective - cheap - does not cause hypo Cons: - large tablets difficult to swallow - common to cause GI upset - wind, blasting, diarrhoea (severe and sudden very often)

Answer 233

DPP4: - no hypo - modest effects on hba1c - not as much long term data - well tolerated - stigagliptin 100mg OD SU: - hypo risk - effective - causes weight gain - can induce beta cell failure at faster rate - used for many years - initially 40mg OD increased to max 160mg - educate pt on home testing

Answer 234

**When educating patients on hypoglycaemia as side effects of drugs - warn to always TEST BG before assuming hypo as might just be them adjusting to normal BG levels as a result of medications instead!! Warn it may take some time for them to adjust, to new levels of BG but not necessarily a hypo attack**

Answer 235

Failure of pancreatic Islet of Langerhans cells to produce enough insulin Either produce too little or none at all Leads to failure of glucose uptake into cells (mostly into storage of the liver - glycogen) Increased blood glucose levels leads to long term complications with eyes, kidneys, neuropathy, risk of stroke and MI etc. Short term complication is patient is likely to enter starvation state due to lack of cellular energy, can enter DKA and deteriorate rapidly

Endocrine Diagnosis And Management Flashcards

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